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Thymoma Database V
Publication Date from 2005/01/01 to 2005/12/31
updated:2006.2.2

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1: Immunol Lett. 2006 Mar 15;103(2):108-14. Epub 2005 Oct 24. Related Articles, Links: Inhibition of interleukin-4 production in activated T cells via down-regulation of NF-AT DNA binding activity by apigenin, a flavonoid present in dietary plants.

Park J, Kim SH, Kim TS.

School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.

Apigenin, a flavonoid present in many dietary plants, exhibits anti-allergic activity and inhibits IL-4 production by basophils and mast cells. However, the mechanism by which apigenin suppresses IL-4 production especially in T cells remains unclear. In this study, the effect of apigenin and its underlying mechanism on IL-4 production were investigated in activated T cells. Apigenin significantly inhibited IL-4 production in both EL4 T thymoma cells and primary lymph node cells. Apigenin also inhibited IL-4 gene promoter activity in EL4 cells transiently transfected with IL-4 gene promoter constructs, but this inhibitory effect was impaired in EL4 cells transfected with an IL-4 promoter construct deleted of NF-AT binding sites. In addition, apigenin inhibited NF-AT DNA binding activities, indicating that apigenin may inhibit IL-4 production in T cells via down-regulation of NF-AT DNA binding activity.

PMID: 16280168 [PubMed - in process]

2: Biol Reprod. 2006 Feb;74(2):375-82. Epub 2005 Oct 26. Related Articles, Links: Exogenous Nitric Oxide Stimulates Cell Proliferation via Activation of a Mitogen-Activated Protein Kinase Pathway in Ovine Fetoplacental Artery Endothelial Cells.

Zheng J, Wen Y, Austin JL, Chen DB.

Department of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin, Madison, Wisconsin 53715.

Sodium nitroprusside (SNP), a nitric oxide (NO) donor and a nitrovasodilator drug used for patients with hypertensive crisis, has been shown to promote angiogenesis. However, direct evidence showing the involvement of NO in the SNP-induced angiogenesis is not available. Accordingly, we assessed whether NO generated from SNP-stimulated ovine fetoplacental artery endothelial (OFPAE) cell proliferation via activation of mitogen-activated protein kinase 3/1 (MAPK3/1, also termed ERK1/2). We observed that SNP dose dependently stimulated (P < 0.05) cell proliferation with a maximal effect at 1 muM and that SNP rapidly (</=15 min) phosphorylated (P < 0.05) MAPK3/1 but not v-akt murine thymoma viral oncogene homolog 1 (AKT1). Treatment of cells with SNP caused a rapid increase in NO levels in media. These increased NO levels were inhibited (P < 0.05) by 2-phenyl-4,4,5,5 tetramethylimidazoline-1-oxyl 3-oxide (PTIO), a NO scavenger. The SNP-induced cell proliferation and MAPK3/1 phosphorylation were attenuated (P < 0.05) by both PTIO and PD98059, a specific mitogen-activated protein kinase kinase 1 and 2 (MAP2K1/2, also termed MEK1/2) inhibitor. Using a semiquantitative RT-PCR analysis, we also showed that up to 12 h of treatment, SNP and N(G)-monomethyl-l-arginine (l-NMMA, a NOS inhibitor) did not alter mRNA expression of VEGF, FGF2, and their major receptors in OFPAE cells. The SNP's stimulatory effects on OFPAE cell proliferation and MAPK3/1 activation were confirmed in a human placental artery endothelial (HPAE) cell line. These data indicate that exogenous NO generated from SNP is able to stimulate fetoplacental artery endothelial cell proliferation at least partly via activation of the MAP2K1/2/MAPK3/1 cascade. These data also suggest that SNP could potentially be used to modulate placental angiogenesis.

PMID: 16251502 [PubMed - in process]

3: Lung Cancer. 2006 Feb;51(2):251-5. Epub 2005 Dec 13. Related Articles, Links: A case of recurrent non-small-cell lung carcinoma and paraneoplastic Cushing's syndrome.

Noorlander I, Elte JW, Manintveld OC, Tournoy KG, Praet MM, van Meerbeeck JP, Aerts JG.

Sint Franciscus Gasthuis, Department of Respiratory Diseases, Kleiweg 500, 3045 PM Rotterdam, The Netherlands.

Secretion of ectopic adrenocorticotropic hormone (ACTH) with consequently Cushing's syndrome is a rare paraneoplastic phenomenon. It has been described in a variety of malignancies, like bronchial carcinoids, small-cell lung carcinoma, thymoma, pancreatic carcinoma and other. In many cases of suspected ectopic ACTH secretion, it is difficult to histologically or cytochemically confirm the diagnosis. We present a 63-year-old woman with a recurrent poorly differentiated squamous cell lung carcinoma with clinical and biochemical features consistent with ectopic Cushing's syndrome. Immunocytochemical staining confirmed the secretion of ACTH by tumour cells.

PMID: 16352372 [PubMed - in process]

4: Neurobiol Dis. 2006 Jan;21(1):127-37. Epub 2005 Aug 8. Related Articles, Links: Amygdaloid kindled seizures can induce functional and pathological changes in thymus of rat: role of the sympathetic nervous system.

Bhatt R, Bhatt S, Hameed M, Rameshwar P, Siegel A.

Department of Neurology and Neurosciences, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.

The present study sought to determine the effects of long-term kindled seizures of the basal amygdala upon immune function in rat, utilizing the thymus, as a principal target for study. Histopathology from kindled Sprague-Dawley rats revealed the presence of epithelial cell thymoma in 70% of these rats. The results revealed an increased rate of apoptosis and proliferation in thymic epithelial cells. Analysis of thymocytes indicated a decrease in the ratio of CD4 to CD8 positive T cells and reduced proliferative response to T-cell mitogens. To determine whether these effects were mediated through the sympathetic nervous system, animals were treated with guanethidine, which blocked the development of epithelial cell thymomas, while mifepristone treatment, employed to determine the possible role of the hypothalamic-pituitary axis, was ineffective in attenuating thymoma development. Thus, the present study demonstrated that functional and pathological changes in the thymus during kindled seizures are mediated through the sympathetic nervous system.

PMID: 16084731 [PubMed - in process]

5: J Neuroimmunol. 2005 Dec 30;170(1-2):172-8. Epub 2005 Oct 7. Related Articles, Links: Altered expression of chemokine receptor CXCR5 on T cells of myasthenia gravis patients.

Saito R, Onodera H, Tago H, Suzuki Y, Shimizu M, Matsumura Y, Kondo T, Itoyama Y.

Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryo-Machi, Aobaku, Sendai 980-8574, Japan.

Myasthenia gravis (MG) is characterized by the T cell-dependent production of anti-acetylcholine receptor (AChR) antibodies. The chemokine receptor CXCR5 regulates lymphocyte migration and is expressed on a subset of CD4+ T cells named follicular helper T cells (T(FH)), the key modulators of antibody production by B cells. We studied the frequency of CXCR5-positive lymphocytes in the peripheral blood of MG patients before and after therapy (thymectomy plus glucocorticoid). Before therapy, the MG patients showed a significantly higher frequency of CXCR5+ CD4+ T cells in the peripheral blood compared with the control group, while no significant difference in the percentages of CXCR5+ CD4+ T cells was observed between the patients of the hyperplasia group and those of the thymoma group. The CXCR5+ CD4+ T cell frequency correlated with the disease severity. The CXCR5+ CD4+ T cell frequency of MG patients positive for other autoantibodies together with anti-AChR antibodies was significantly higher than in those having only anti-AChR antibodies. After therapy, the CXCR5+ CD4+ T cell percentage decreased gradually to the control level with a significant inverse correlation between the CXCR5+ CD4+ T cell frequency and duration after the initiation of MG therapy. The CXCR5+ CD4+ T cell populations in the hyperplastic thymuses and thymomas were not significantly different from those in the control thymuses. These results suggest that CXCR5+ CD4+ T cells play an important role in the disease activity of MG and that some MG patients have a systemic abnormality in T cell-dependent antibody production.

PMID: 16214223 [PubMed - in process]

6: J Neuroimmunol. 2005 Dec 30;170(1-2):141-9. Epub 2005 Sep 22. Related Articles, Links: Novel autoantibodies to a voltage-gated potassium channel Kv1.4 in a severe form of myasthenia gravis.

Suzuki S, Satoh T, Yasuoka H, Hamaguchi Y, Tanaka K, Kawakami Y, Suzuki N, Kuwana M.

Department of Neurology, Keio University School of Medicine, 35 Shinanomachi, Tokyo 160-8582, Japan.

Sera from patients with myasthenia gravis (MG) were screened for autoantibodies to skeletal muscle-specific antigens by immunoprecipitation assay, using rhabdomyosarcoma and leukemia cell lines. Eleven of 61 MG sera immunoprecipitated a rhabdomyosarcoma-specific 70-kDa protein, which was identified as the voltage-gated K+ channel 1.4 (Kv1.4). This antibody specificity was not detected in 30 patients with polymyositis/dermatomyositis, 9 with thymoma alone, or 30 healthy controls. Clinical features associated with anti-Kv1.4 antibody included bulbar involvement, myasthenic crisis, thymoma, myocarditis, and QT prolongation on electrocardiogram. These findings suggest that anti-Kv1.4 antibody is a novel autoantibody associated with a severe MG subset and thymoma.

PMID: 16182377 [PubMed - in process]

7: Hum Gene Ther. 2005 Dec 28; [Epub ahead of print] Related Articles, Links: In Vitro Functional Correction of the Mutation Responsible for Murine Severe Combined Immune Deficiency by Small Fragment Homologous Replacement.

Zayed H, McIvor RS, Wiest DL, Blazar BR.

University of Minnesota Cancer Center, and Department of Pediatrics, Division of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455.

A homologous recombination (HR) approach for site-specific correction of mutations would be highly desirable for the treatment of genetic disorders if recombination efficiencies were sufficiently high as to permit a biological effect. Using a T cell thymoma line derived from severe combined immunodeficient (SCID) mice with a point mutation in the gene encoding the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), we have shown that short DNA fragments (SDFs; 621 bases) can provide genotypic and functional correction of these cells. Double-stranded SDFs (dsSDFs) or single-stranded SDFs (ssSDFs) were designed to span the wild-type sequence of exon 85 in the DNA-PKcs gene and part of the 3' and 5' flanking intron regions. SCID cells were nucleofected with both single- and double-stranded wild-type SDF sequences. Corrected cells were selected on the basis of protection from radiation hypersensitivity that occurs as a consequence of the SCID mutation. Correction was mediated by both SDF forms (double and single stranded). These results indicate that SDFs can correct point mutations by HR with the possibility of harnessing ionizing radiation (IR) as a selection method to eliminate noncorrected cells and enrich for corrected SCID radioresistant cells.

PMID: 16384524 [PubMed - as supplied by publisher]

8: Presse Med. 2005 Dec 17;34(22 Pt 1):1741. Related Articles, Links

[Mediastinal thymolipoma]

[Article in French]

Chateil JF, Pietrera P.

Imagerie pediatrique, Groupe hospitalier Pellegrin-Enfants, Place Amelie Raba-Leon, 33076 Bordeaux Cedex. jean-francois.chateil@chu-bordeaux.fr

Publication Types:

Case Reports

PMID: 16374399 [PubMed - indexed for MEDLINE]

9: Ann Thorac Cardiovasc Surg. 2005 Dec;11(6):367-73. Related Articles, Links: Clinical usefulness of the WHO histological classification of thymoma.

Sonobe S, Miyamoto H, Izumi H, Nobukawa B, Futagawa T, Yamazaki A, Oh T, Uekusa T, Abe H, Suda K.

Department of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, and Department of Clinical Laboratory, Labor Welfare Corporation Kanto Rosai Hospital, Kanagawa, Japan.

PURPOSE: Rosai et al. published the World Health Organization (WHO) classification of thymic epithelial tumors in 1999, and its clinical usefulness seems to be established. It is our purpose to find the clinically relevant diagnostic points in the WHO Histological Classification of Thymoma. METHODS: Thymomas surgically removed from 100 consecutive patients at Juntendo University Hospital between October 1983 and February 2002 were classified according to the WHO histological classification. We assessed overall survival and recurrence-free rate calculated for each tumor type in the WHO classification compared with those of tumors classified by the Masaoka system. RESULTS: The thymic epithelial tumors in this series comprised 10 type A, 15 type AB, 18 type B1, 21 type B2, 33 type B3, and 3 type C tumors according to the WHO classification. Based on the Masaoka system, the disease was stage I in 53 patients, stage II in 30, stage III in 15, and stage IV in 2. The 15-year recurrence-free rate was 100% for type A, AB and B1, while the rates for types B2 and B3 were 66.7% and 54.5%, respectively. The 10-year recurrence-free rate was 66.7% for type C. The 15-year recurrence-free rate of the 64 patients with type A, AB, B1, and B2 thymomas was significantly higher from that of the 33 patients with type B3 thymoma (p=0.0026). CONCLUSION: When using the WHO classification, it is critical to distinguish type B3 thymoma from other tumor types.

PMID: 16401984 [PubMed - in process]

10: Ann Thorac Surg. 2005 Dec;80(6):2000-1. Related Articles, Links

Comment on:

Ann Thorac Surg. 2005 Dec;80(6):1994-2000.

Invited commentary.

Kondo K.

Department of Oncological and Regenerative Surgery, University of Tokushima Graduate School, Tokushima, 770-8503, Japan. kondo@clin.med.tokushima-u.ac.jp

Publication Types:

Comment

PMID: 16305832 [PubMed - indexed for MEDLINE]

11: Cancer Res. 2005 Dec 1;65(23):11156-63. Related Articles, Links: Tumor immunotherapy targeting fibroblast activation protein, a product expressed in tumor-associated fibroblasts.

Lee J, Fassnacht M, Nair S, Boczkowski D, Gilboa E.

Center for Translational Research, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.

Murine studies have shown that immunologic targeting of the tumor vasculature, a key element of the tumor stroma, can lead to protective immunity in the absence of significant pathology. In the current study, we expand the scope of stroma-targeted immunotherapy to antigens expressed in tumor-associated fibroblasts, the predominant component of the stroma in most types of cancer. Mice were immunized against fibroblast activation protein (FAP), a product up-regulated in tumor-associated fibroblasts, using dendritic cells transfected with FAP mRNA. Using melanoma, carcinoma, and lymphoma models, we show that tumor growth was inhibited in tumor-bearing mice vaccinated against FAP and that the magnitude of the antitumor response was comparable to that of vaccination against tumor cell-expressed antigens. Both s.c. implanted tumors and lung metastases were susceptible to anti-FAP immunotherapy. The antitumor response could be further enhanced by augmenting the CD4+ T-cell arm of the anti-FAP immune response, achieved by using a lysosomal targeting sequence to redirect the translated FAP product into the class II presentation pathway, or by covaccination against FAP and a tumor cell-expressed antigen, tyrosinase-related protein 2. No morbidity or mortality was associated with anti-FAP vaccination except for a small delay in wound healing. The study suggests that FAP, a product which is preferentially expressed in tumor-associated fibroblasts, could function as a tumor rejection antigen in a broad range of cancers.

PMID: 16322266 [PubMed - indexed for MEDLINE]

12: Exp Mol Pathol. 2005 Dec;79(3):249-58. Epub 2005 Sep 15. Related Articles, Links: Adenosine-induced apoptosis in EL-4 thymoma cells is caspase-independent and mediated through a non-classical adenosine receptor.

El-Darahali A, Fawcett H, Mader JS, Conrad DM, Hoskin DW.

Department of Microbiology and Immunology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.

Cell death caused by the accumulation of extracellular adenosine is believed to contribute to the profound loss of T lymphocytes in patients with severe combined immunodeficiency disease due to adenosine deaminase deficiency. Although adenosine is known to trigger apoptosis in thymocytes and peripheral T cells, the molecular basis of this effect is not understood. In this study, we show that adenosine-induced apoptosis in mouse EL-4 thymoma cells was associated with the generation of reactive oxygen species and a reduction in mitochondrial transmembrane potential. In addition, cell death was by a caspase-independent mechanism because caspase inhibitors did not protect EL-4 cells from adenosine-induced cytotoxicity. Although reverse transcriptase polymerase chain reaction revealed that EL-4 cells expressed A2b and A3 adenosine receptor subtypes, blockade of A2b and A3 adenosine receptors with receptor-selective antagonists did not attenuate adenosine-induced cell death. Nevertheless, the failure of nucleoside transport inhibitors to prevent adenosine cytotoxicity suggested that adenosine was acting through a cell-surface receptor. In addition, adenosine-induced apoptosis was not due to an accumulation of intracellular cyclic adenosine monophosphate (cAMP) since neither forskolin nor 8-Br-cAMP was cytotoxic for EL-4 cells. Adenosine therefore acts through a non-classical receptor at the cell surface to trigger caspase-independent apoptosis in mouse thymoma cells.

PMID: 16168410 [PubMed - indexed for MEDLINE]

13: FASEB J. 2005 Dec;19(14):2072-4. Epub 2005 Oct 3. Related Articles, Links: PGC-1alpha gene expression is down-regulated by Akt- mediated phosphorylation and nuclear exclusion of FoxO1 in insulin-stimulated skeletal muscle.

Southgate RJ, Bruce CR, Carey AL, Steinberg GR, Walder K, Monks R, Watt MJ, Hawley JA, Birnbaum MJ, Febbraio MA.

Cellular and Molecular Metabolism Laboratory, RMIT University, Bundoora, Victoria, Australia.

There are multiple binding domains on the promoter region of the peroxisome proliferator activator receptor gamma coactivator-1 alpha (PGC-1alpha) gene, including a trio of insulin responsive elements that are activated by the forkhead box class-O (FoxO1) winged helix transcription factor, which is known to be regulated by acute transforming retrovirus thymoma (Akt). Here we show that in skeletal muscle biopsy specimens from healthy humans and cultured human skeletal myotubes, insulin phosphorylates Akt (Ser473) and FoxO1 (Thr24, Ser256), leading to reduced nuclear abundance of FoxO1 total protein. This is associated with an insulin-mediated repression of the mRNA expression PGC-1alpha and downstream genes associated with oxidative phosphorylation. In contrast, in muscle taken from insulin resistant humans or in palmitate-treated insulin resistant myotubes, neither Akt nor FoxO1 was phosphorylated by insulin, resulting in a failure for nuclear exclusion of FoxO1 total protein, and an inability for insulin to repress the mRNA expression of PGC-1alpha and down-stream genes. To determine whether the regulation of FoxO1 was Akt dependent, we next treated Akt2 -/- and wild-type mice with or without insulin. Insulin phosphorylated Akt and FoxO1 (Thr24, Ser256) resulting in a reduced nuclear expression of FoxO1 total protein in wild-type but not Akt2 -/- skeletal muscle. We conclude that insulin decreases the expression of genes involved in oxidative metabolism in healthy but not insulin resistant muscle, due to a decrease in FoxO1 phosphorylation and nuclear exclusion secondary to reduced Akt activity.

PMID: 16203862 [PubMed - in process]

14: Mol Cell Biol. 2005 Dec;25(24):10675-83. Related Articles, Links: Runx1 binds positive transcription elongation factor b and represses transcriptional elongation by RNA polymerase II: possible mechanism of CD4 silencing.

Jiang H, Zhang F, Kurosu T, Peterlin BM.

Department of Medicine, Microbiology and Immunology, Rosalind Russell Medical Research Center, University of California at San Francisco, 94143-0703, USA.

Runx1 binds the silencer and represses CD4 transcription in immature thymocytes. In this study, we found that Runx1 inhibits P-TEFb, which contains CycT1, CycT2, or CycK and Cdk9 and stimulates transcriptional elongation by RNA polymerase II (RNAPII) in eukaryotic cells. Indeed, its inhibitory domain, spanning positions 371 to 411, not only bound CycT1 but was required for silencing CD4 transcription in vivo. Our chromatin immunoprecipitation assays revealed that Runx1 inhibits the elongation but not initiation of transcription and that RNAPII is engaged at the CD4 promoter but is unable to elongate in CD4(-) CD8(+) thymoma cells. These results suggest that active repression by Runx1 occurs by blocking the elongation by RNAPII, which may contribute to CD4 silencing during T-cell development.

PMID: 16314494 [PubMed - indexed for MEDLINE]

15: Oncol Rep. 2005 Dec;14(6):1621-4. Related Articles, Links: Aberrant methylation: common in thymic carcinomas, rare in thymomas.

Suzuki M, Chen H, Shigematsu H, Ando S, Iida T, Nakajima T, Fujisawa T, Kimura H.

Department of Thoracic Surgery, Graduate School of Medicine, 1-8-1 Inohana, Chuoh-ku, Chiba 260-8677, Japan. smakoto@faculty.chiba-u.jp

Thymic carcinoma, which is a rare epithelial neoplasm of the thymus gland, is different from thymoma in its clinical and pathological features. To clarify the mechanism underlying the aggressive behavior of thymic carcinoma, we examined the clinicopathologic features, aberrant methylation patterns of the tumor suppressor genes, and epidermal growth factor receptor (EGFRs) mutation in both thymic carcinomas and thymomas. Clinical data of 11 thymic cancers and 13 thymomas were reviewed. Resected samples of 5 thymic cancers and 6 thymomas selected from 24 cases were used for methylation and mutation studies. Positive tumor markers were more frequent in thymic cancers than in thymomas (p=0.0233), and the methylation index, which reflects the overall methylation pattern, was significantly higher in thymic carcinomas (p=0.0053). No tumors showed a mutation of EGFR, KRAS, and HER2. Thymic carcinoma is distinct from thymoma not only with respect to clinicopathological features, but also aberrant methylation patterns of the tumor suppressor genes.

PMID: 16273266 [PubMed - indexed for MEDLINE]

16: Rev Med Interne. 2005 Dec;26(12):924-30. Epub 2005 Sep 29. Related Articles, Links: [Myasthenia in elderly patients: a series of 23 cases]

[Article in French]

Durand F, Camdessanche JP, Jomir L, Antoine JC, Cathebras P.

Service de medecine interne, hopital Nord, CHU de Saint-Etienne, 42055 Saint-Etienne cedex 02, France.

PURPOSE: There is evidence that myasthenia gravis is substantially underdiagnosed in older people, for which diagnosis and treatment may be difficult. METHOD: We report on a series of 23 cases of myasthenia gravis diagnosed after the age of 65. Diagnosis was ascertained by compatible symptoms, associated with electrophysiological evidence and/or presence of antibodies to the acetylcholine receptor (AchRAb) and/or positive prostigmine test. RESULTS: Twelve female and 11 male patients were identified, with a mean age of 77 (range: 66-89). Initial symptoms were ocular in 8 cases (35%), bulbar and ocular in 9 cases (39%), generalized in 6 cases (26%). Diagnosis was delayed in many patients (mean delay 31+/-47 months). Prostigmine test was positive in 16 cases (100%), AchRAb were positive in 19/23 cases (83%). Only one thymoma was found. Other diagnoses than myasthenia gravis, mainly stroke, were often considered. Treatment with anticholinesterase drugs, prescribed in all cases, has been able to control symptoms in only 3 cases. Corticosteroids were used in 10 cases, azathioprine or mycophenolate mofetil in 14 cases, intravenous immunoglobulins in 8 cases, and plasma exchanges in 2 cases. Thymectomy was performed on one patient with thymoma. Three patients were hospitalized in intensive care units for several weeks, and 3 patients died from their myasthenia. CONCLUSION: Diagnosis of myasthenia gravis is often missed or delayed in the elderly, because of a broad differential diagnosis in older people, and because the high incidence of the disease in middle and old age is often overlooked. The outcome of myasthenia gravis in older people is far from simple, and immunomodulation proves to be necessary in most cases. However, quality of life of surviving patients appears good.

PMID: 16229927 [PubMed - indexed for MEDLINE]

17: Rev Neurol (Paris). 2005 Dec;161(12 Pt 1):1260-6. Related Articles, Links: [Cramp-fasciculation syndrome]

[Article in French]

Lagueny A.

Service de Neurologie, USN Hopital du Haut-Leveque, Pessac. alain.lagueny@chu-bordeaux.fr

The cramp-fasciculation syndrome is a rare clinical entity in comparison with the frequency of cramps and isolated fasciculations in the general population. It is recognized as a benign syndrome without weakness and atrophy, however a few reports suggest that it may precede the occurrence of a motor neuron disease. Most often, the cramp-fasciculation syndrome is idiopathic and may be a component of a hyperexcitable peripheral nerve syndrome including other activities such as myokymia and neuromyotonia where antibodies to voltage-gated potassium channels (VGKCs) appear to be one of the effector mechanisms. The most complete form of this hyperexcitable peripheral nerve syndrome is Isaacs' syndrome. The central nervous system is also concerned with anti-VGKC antibodies found in Morvan's disease and limbic encephalitis which is often a paraneoplastic condition. These findings extend the spectrum of the anti-VGKC syndrome that may be associated with other auto-immune diseases, chiefly myasthenia gravis with thymoma. Carbamazepine and phenytoin cause reduction of the clinical and electrophysiological signs of the nerve hyperexcitability, and plasmapheresis and (or) immunosuppressors are useful when an auto-immune origin is considered.

PMID: 16340924 [PubMed - in process]

18: Schweiz Arch Tierheilkd. 2005 Dec;147(12):546-8, 551-3. Related Articles, Links: [Thorax examination by computed tomography: general aspects and case report]

[Article in French]

Huber D.

Centre veterinaire Les Grillieres, Montcherand/Orbe.

This article describes the application of the helicoidal tomography for the study of mediastinal and pulmonal affections by small animals. The global presentation is completed by clinical cases that show the interest in this technic. A thymoma, a chronic pleuresia due to thorns and a mediastinal cranio-dorsal neoplasia provoking only lameness signs will be presentated in details.

PMID: 16398193 [PubMed - in process]

19: Int J Cancer. 2005 Nov 20;117(4):574-86. Related Articles, Links: Increased rejection of primary tumors in mice lacking B cells: inhibition of anti-tumor CTL and TH1 cytokine responses by B cells.

Shah S, Divekar AA, Hilchey SP, Cho HM, Newman CL, Shin SU, Nechustan H, Challita-Eid PM, Segal BM, Yi KH, Rosenblatt JD.

Sylvester Comprehensive Cancer Center, University of Miami School of Medicine, FL 33136, USA.

We investigated the role of B cells in tumor immunity by studying immune responses of mice genetically lacking B cells to primary tumors. IgM(-/-) B cell-deficient mice (BCDM) exhibited enhanced resistance to 3 histologically diverse syngeneic tumors as compared to the wild-type (WT) mice. EL4 thymoma and MC38 colon carcinoma grew progressively in WT mice, but regressed spontaneously in BCDM whereas growth of B16 melanoma was slowed significantly in BCDM as compared to the WT mice. BCDM exhibited increased T cell infiltration of tumors, higher T(H)1 cytokine response and, in the case of MC38, a higher anti-tumor CTL response. The increased tumor resistance of BCDM did not seem to result from intrinsic changes in their non-B immunocytes because adoptive transfer of WT splenic B cells to BCDM abrogated tumor rejection and resulted in diminished anti-tumor T(H)1 cytokine and CTL responses. Studies involving BCR-transgenic mice indicated that B cells may inhibit anti-tumor T cell responses by antigen-nonspecific mechanisms since neither tumor-specific antibodies nor cognate T:B interactions were necessary for inhibition of tumor immunity by B cells. IFN-gamma secretion in splenocyte:tumor co-cultures of tumor-challenged BCDM was inhibited by WT but not CD40(-/-) B cells indicating that B cells may inhibit anti-tumor T(H)1 cytokine responses in a CD40-dependent manner. Adoptive transfer of CD40(-/-) B cells into BCDM resulted in restored growth of MC38 suggesting additional factors other than CD40 are involved in dampening anti-tumor responses. The effects of B cells on anti-tumor response warrant further study. Copyright 2005 Wiley-Liss, Inc.

PMID: 15912532 [PubMed - indexed for MEDLINE]

20: Cancer. 2005 Nov 15;104(10):2063-71. Related Articles, Links: Long-term disease-free survival of patients with radically resected thymomas: relevance of cell-cycle protein expression.

Mineo TC, Ambrogi V, Mineo D, Baldi A.

Department of Thoracic Surgery, Tor Vergata University, Rome, Italy.

BACKGROUND: Despite radical surgical resection, thymomas often recur. The objective of the current retrospective study was to investigate the prognostic relevance of the expression of cell-cycle proteins in these neoplasms to formulate a possible therapeutic surveillance strategy for the prevention of recurrence. METHODS: The authors retrospectively reviewed the main clinicopathologic factors, including the World Health Organization (WHO) classification, of patients with thymoma who had undergone radical surgical resection. Specimens were studied using immunohistochemistry and the expression of cell-cycle proteins (i.e., p21, p27, and p53) was assessed. Univariate and multivariate analysis of predicting survival prognostic factors were performed. RESULTS: The authors analyzed 88 patients with thymoma who underwent radical surgical resection at the study institution. According to the Masaoka staging system, 41 patients had Stage I disease, 31 patients had Stage II disease, and 16 patients had Stage III disease. There were 24 tumor recurrences (27.3%), 4 of which were local, 16 of which were distant intrathoracic, and 4 of which were extrathoracic. The second radical resection provided a disease-free survival rate that was similar to the first. Only Masaoka stage (P = 0.001), WHO classification (P=0.001), high expression of p53 (P=0.03), and low expression of p21 (P=0.02) and p27 (P=0.001) were found to be correlated with a reduced disease-free survival. Low p27 expression was found to be the most significant predictive factor of a short disease-free survival (P=0.001), especially when associated with low p21 expression and high p53 expression (P=0.0001). CONCLUSIONS: Long-term disease-free survival in thymoma patients treated with radical surgical resection was found to be correlated with Masaoka stage, WHO classification, and expression of cell-cycle proteins, with the latter found to be the most significant predictive factor. Functional cooperation between cell-cycle proteins might constitute another level of regulation in tumor growth. More careful surveillance should be adopted whenever there is negative cell-cycle protein expression. Copyright 2005 American Cancer Society

PMID: 16206298 [PubMed - indexed for MEDLINE]

21: Nippon Naika Gakkai Zasshi. 2005 Nov 10;94(11):2385-7. Related Articles, Links: [32 year old male case of paraneoplastic non-herpetic limbic encephalitis with thymoma]

[Article in Japanese]

Kuga A, Uesaka Y, Kunimoto M, Nagasaka S, Itami J, Iwamura A, Yuasa T.

Department of Neurology, International Medical Center of Japan, Tokyo.

PMID: 16363744 [PubMed - in process]

22: Anticancer Res. 2005 Nov-Dec;25(6A):3697-701. Related Articles, Links: Immunohistochemical staining of hedgehog pathway-related proteins in human thymomas.

Tasaki A, Akiyoshi T, Koga K, Nakashima H, Yamanaka N, Kubo M, Matsumoto K, Kojima M, Tanaka M, Nakamura M, Katano M.

Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

The thymus plays an essential role in the maturing of progenitor cells to functional T cells. Recent studies suggest that the Hedgehog (Hh) signaling pathway contributes to this differentiation process. However, there is limited information concerning the expression of Hh pathway-related proteins (Hh proteins) in the human thymus. The staining of Hh proteins in the thymic epithelium of 26 surgically resected thymoma tissues was examined by immunohistochemistry. The staining of sonic Hh (Shh) correlated relatively well with the World Health Organization histological classification of thymoma. The higher the grade, the fainter the staining. However, no significant difference in Shh staining was found between normal and neoplastic epithelia. Interestingly, Gli1 staining in thymomas was significantly greater than that in normal thymus (p < 0.0001). Thus, some members of the Hh signaling pathway may contribute to the development of thymoma.

PMID: 16302728 [PubMed - indexed for MEDLINE]

23: Cancer Cell. 2005 Nov;8(5):349-50. Related Articles, Links

Comment on:

Cancer Cell. 2005 Nov;8(5):369-80.

The dual adverse effects of TGF-beta secretion on tumor progression.

Trapani JA.

Cancer Immunology Program, Peter MacCallum Cancer Centre, St. Andrew's Place, East Melbourne, 3002, Australia. joe.trapani@petermac.org

When a cancer escapes the growth-inhibitory effects of TGF-beta secreted by cancer cells themselves or by cells in the local stroma, a further adverse outcome for the host is the associated TGF-beta-induced suppression of anticancer T cell immunity. In addition to the previously described dampening of T cell activation and proliferation, TGF-beta markedly and directly suppresses the transcription of genes encoding multiple key proteins of the "cytotoxic program" of CD8+ CTL, such as perforin and granzymes, cytotoxins that act through the granule exocytosis pathway. The findings described below suggest that TGF-beta and its signaling pathways will be major targets for novel cancer therapeutics.

Publication Types:

Comment

PMID: 16286241 [PubMed - indexed for MEDLINE]

24: Cancer Radiother. 2005 Nov;9(6-7):351-7. Epub 2005 Sep 15. Related Articles, Links

[Thymic tumors]

[Article in French]

Le Pechoux C, Mahe M, Bretel JJ, Roberti E, Ruffie P.

Departement de radiotherapie, institut Gustave-Roussy, 39, rue Camille-Desmoulins, 94000 Villejuif, France. lepechoux@igr.fr

Thymomas and thymic carcinomas are rare and slow-growing tumors, which develop within the anterior mediastinum. Thymomas are often associated with autoimmune disorders and most particularly myasthenia gravis. The treatment of choice remains a complete surgical resection. Postoperative radiotherapy is often combined in case of invasive thymoma invading into adjacent organs. Postoperative radiotherapy in stage II with invasion into capsule has been more controversial lately. In inoperable locally advanced, or metastatic thymic tumors, neoadjuvant cisplatin-based followed by surgery and radiotherapy has given interesting results in the past years.

Publication Types:

Review

PMID: 16168694 [PubMed - indexed for MEDLINE]

25: Cytometry A. 2005 Nov;68(1):36-44. Related Articles, Links: DPSS yellow-green 561-nm lasers for improved fluorochrome detection by flow cytometry.

Telford W, Murga M, Hawley T, Hawley R, Packard B, Komoriya A, Haas F, Hubert C.

Experimental Transplantation and Immunology Branch, Center for Cancer Research, NCI-NIH, Bethesda, Maryland 20892, USA. telfordw@mail.nih.gov

INTRODUCTION: Blue-green 488-nm laser sources are widespread in flow cytometry but suffer some drawbacks for cell analysis, including their excitation of endogenous proteins (resulting in high cellular autofluorescence) and their less-than-optimal coincidence with the excitation maxima of commonly used fluorochromes, including the phycoerythrins (PE). Longer wavelength lasers such as green helium-neons and, more recently, diode-pumped solid state (DPSS) 532-nm sources have previously been employed to overcome these difficulties and improve overall sensitivity for PE. In this study, we evaluate an even longer wavelength DPSS 561-nm for its ability to improve PE and DsRed fluorescent protein detection sensitivity. METHODS: A DPSS 561-nm laser emitting at 10 mW was mounted onto a BD LSR II. Mouse thymoma cells labeled with cell surface marker antibodies conjugated to the R- and B-forms of PE were analyzed and compared with conventional 488-nm excitation using the same bandpass filters and signal travel distances. A similar analysis was carried out with cell lines expressing the red fluorescent protein DsRed, several green-yellow excited low molecular weight fluorochromes, and a rhodamine-based caspase substrate. Additionally, cells labeled with PE and co-labeled with fluorescein or simultaneously expressing green fluorescent protein (GFP) were analyzed to determine if PE excitation at 561 nm with simultaneous fluorescein/GFP detection was feasible. RESULTS: The DPSS 561-nm laser gave a several-fold improvement in the fluorochrome to autofluorescence ratios between PE-labeled cells and unlabeled controls. Analysis of cells expressing the fluorescent protein DsRed with the DPSS 561-nm source gave a 6-7-fold improvement in sensitivity over 488-nm excitation, and gave excellent excitation of yellow-green excited fluorochromes and rhodamine-based physiological probes. Yellow-green laser light also caused virtually no impingement on the spatially separated fluorescein/GFP detector, a significant problem with green laser sources, and also allowed simultaneous analysis of GFP and PE with virtually no signal overlap or requirement for color compensation. CONCLUSIONS: DPSS 561-nm laser excitation gave significantly improved sensitivity for both PE-labeled and DsRed expressing cells, with little contamination of a typical fluorescein/GFP detector.

PMID: 16163703 [PubMed - in process]

26: Eur J Intern Med. 2005 Nov;16(7):523-4. Related Articles, Links: Malignant thymoma complicated by amegakaryocytic thrombocytopenic purpura.

Maslovsky I, Gefel D, Uriev L, Ben Dor D, Lugassy G.

Department of Internal Medicine, Barzilai Medical Centre, Ashkelon 78306, Israel. igorgn@012.net.il

We report the case of a 41-year-old man with malignant thymoma complicated by amegakaryocytic thrombocytopenia 10 years after diagnosis of myasthenia gravis. A bone marrow aspirate showed an absence of megakaryocytes with normal maturation and differentiation of myeloid precursors. Three months later, severe neutropenia occurred, and a bone marrow examination confirmed the diagnosis of severe aplastic anemia. Associations between thymoma and myasthenia gravis, between thymoma and pure red cell aplasia, and between thymoma and aplastic anemia are well documented. Amegakaryocytic thrombocytopenia is not a recognized paraneoplastic syndrome complicating thymoma. Amegakaryocytic thrombocytopenia complicating thymoma may be a very early presentation of impending aplastic anemia.

PMID: 16275552 [PubMed]

27: Gastrointest Endosc. 2005 Nov;62(5):768-74. Related Articles, Links: EUS-guided fine needle tissue acquisition by using high negative pressure suction for the evaluation of solid masses: a pilot study.

Larghi A, Noffsinger A, Dye CE, Hart J, Waxman I.

Section of Endoscopy and Therapeutics, The University of Chicago, Chicago, Illinois 60637, USA.

BACKGROUND: The capability of obtaining tissue samples for histologic examination during EUS has theoretical advantages over cytology alone. The objective was to evaluate the feasibility and the yield of EUS-guided FNA tissue acquisition (EUS-FNTA) by using high negative pressure suction. METHODS: The study design is a prospective, observational pilot study set at a tertiary referral center. Twenty-seven patients with a solid mass amenable to sampling with EUS were included in the study. FNA with a 22-gauge needle was used for a total of 5 passes. An additional pass with the same needle was performed by applying continuous high negative pressure suction using the Alliance II inflation system. The main outcome measurements were the rate of tissue acquisition and the diagnostic accuracy of EUS-FNTA. OBSERVATIONS: Tissue samples were obtained in 26 of the 27 patients (96%). Malignancy was detected in 20 of the 26 biopsy specimens obtained by FNTA and in 20 of the 27 FNA specimens. In 3 patients, EUS-FNTA failed to disclose malignancy, which in two of the patients was diagnosed by FNA. Conversely, EUS-FNTA diagnosed a recurrent malignant thymoma and a schwannoma in two FNA-negative patients. In 3 patients with both FNTA and FNA negative for malignancy, a definitive diagnosis could not be established. Overall, diagnostic accuracy was 76.9% for both EUS-FNTA and EUS-FNA. When combined, a correct diagnosis was achieved in 84.6% of the patients. Immunostaining of the retrieved tissue allowed characterization of the primary tumor in 5 cases and the diagnosis of a schwannoma and two neuroendocrine tumors. Limitations of the study were small sample size and a pilot study. CONCLUSIONS: EUS-FNTA has a high yield for the retrieval of core tissue samples. Further studies in which EUS-FNTA is performed before FNA and with variable number of passes are needed to better define its diagnostic role and performance characteristics.

PMID: 16246694 [PubMed - in process]

28: Int J Colorectal Dis. 2005 Nov;20(6):485-93. Epub 2005 Apr 6. Related Articles, Links: Characterization of gene expression profiles of T cells during anti-tumor response.

Stremmel C, Siebenhaar R, Croner R, Reingruber B, Slavin AJ, Hohenberger W.

Department of Surgery, University of Erlangen-Nuremberg, Krankenhausstrasse 12, 91054, Erlangen, Germany.

BACKGROUND AND AIMS: T cells of tumor-bearing mice or cancer patients exhibit an immune dysfunction, enabling the tumor to escape immune surveillance. METHODS: The experiments are based on EL4 thymoma cells that were transfected with costimulatory ligands B7-1, B7-2, or both at the same time. We used oligonucleotide-based DNA chip microarrays to characterize the genomic expression profile of peripheral T cells according to their anti-tumor immune response in vivo. These murine T cells were also characterized by ELISA, FACS analysis, and co-stimulatory assays. RESULTS: Using commonly established methods, such as FACS analysis or the analysis of the cytokine profile by ELISA, it was not possible to determine functional differences in the in vivo activity of T lymphocytes against tumor cells. EL4 tumor cells induced multiple anti-tumor immune responses in vivo depending on their B7 expression. We successfully used microarray analysis to identify genes that were differentially expressed in the dysfunctional T cells, which were unable to reject tumors in vivo. Although Th1 and Th2 cytokine expression was not affected, we observed differential expression of genes involved in the regulation of an innate immune response. CONCLUSION: Our results provide evidence that the anti-tumor response can be identified by the "gene profile" of T cells. Genomic scale analysis offers the opportunity to identify subtle changes in gene expression in T cells reflecting a distinct biological behavior in vivo.

PMID: 15812645 [PubMed - in process]

29: J Clin Neurosci. 2005 Nov;12(8):954-7. Related Articles, Links: Symptomatic pituitary metastasis of malignant thymoma.

Kanayama S, Matsuno A, Nagashima T, Ishida Y.

Department of Neurosurgery.

Pituitary metastases from malignant thymoma are extremely rare. We report an 86 year-old-man with pituitary metastasis of malignant thymoma who complained of visual impairment and right ptosis. A pituitary lesion, which was partially removed by trans-sphenoidal surgery, was pathologically similar to the primary lesion and was diagnosed as pituitary metastasis of malignant thymoma. One autopsied case of pituitary metastasis of malignant thymoma has been found in the literature, and one case of this condition has been previously described in life. The present paper is the second report of symptomatic pituitary metastasis of malignant thymoma. Surgical removal of the pituitary lesion is a reasonable choice for the relief of progressive visual symptoms and for good quality of life in these patients.

PMID: 16326276 [PubMed - in process]

30: J Thorac Cardiovasc Surg. 2005 Nov;130(5):1413-21. Epub 2005 Oct 13. Related Articles, Links: Predictors of recurrence in thymic tumors: importance of invasion, World Health Organization histology, and size.

Wright CD, Wain JC, Wong DR, Donahue DM, Gaissert HA, Grillo HC, Mathisen DJ.

Division of General Thoracic Surgery, Massachusetts General Hospital, Department of Surgery, Harvard Medical School, Boston, Mass 02114, USA. wright.Cameron@mgh.harvard.edu

OBJECTIVE: This study sought to define predictors of recurrence after resection of thymic tumors. METHODS: A single-institution retrospective study was performed of 179 patients who underwent resection of a thymic tumor from 1972 through 2003. RESULTS: Resection was complete in 90% (161/179) of patients. After a median follow-up of 115 months, the recurrence rate was 11% (20/179), the tumor-related death rate was 7.8% (14/179), and the overall death rate was 36.3% (65/179). Tumor recurrence correlated with advanced stage and histology (P < .0001). The difference in recurrence between Masaoka stage I (0) and II (1.7% [1/59]) was insignificant. Recurrence rates correlated with World Health Organization tumor type: A and AB, 0%; B1 and B2, 8% (4/51); B3, 27% (14/51); and C, 50% (2/4; P < .0001). Tumor size separation into quintiles demonstrated a step-up of recurrence at 8 cm (<8 cm, 1.8% [2/113]; > or =8 cm, 28% [18/64]; P < .003). Multivariate Cox modeling demonstrated that Masaoka stage (odds ratio, 5.70; P < .001), World Health Organization histology (odds ratio, 5.77; P = .003), and size (odds ratio, 1.16; P = .001) were independent predictors of recurrence. CONCLUSION: The Masaoka staging system could be collapsed to 3 degrees of invasion by combining stages I and II. The World Health Organization histologic type can be simplified for clinical use into A (A, AB), early B (B1, B2), advanced B (B3), and C tumors. Size of 8 cm or larger is an independent risk factor, even when patients with Masaoka stage III tumors are considered alone, and might identify candidates for preoperative therapy.

PMID: 16256797 [PubMed - indexed for MEDLINE]

31: J Vet Intern Med. 2005 Nov-Dec;19(6):855-9. Related Articles, Links: Differentiating benign and malignant causes of lymphocytosis in feline bone marrow.

Weiss DJ.

Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, 1971 Commonwealth Avenue, St. Paul, MN 55108, USA. weiss005@umn.edu

Differentiation of benign and malignant causes of lymphocytosis in blood or bone marrow can be problematic. In the present study, reports of examinations of bone marrow from cats, submitted over an 8-year period, were reviewed to identify cats with increased numbers of small lymphocytes. Of 203 reports reviewed, 12 (5.9%) indicated increased numbers of small lymphocytes. Diagnoses for these cats included chronic lymphocytic leukemia (CLL; n = 2), pure red cell aplasia (PRCA; n = 4), immune-mediated hemolytic anemia (IMHA; n = 3), thymoma (n = 1), cholangiohepatitis (n = 1), and fever of unknown origin (n = 1). Several factors were identified that could be used to differentiate reactive lymphocytosis from CLL. Cats with CLL tended to be older, and lymphocytes were slightly larger and had cleaved or lobulated nuclei. Reactive lymphocytosis was associated with immune-mediated anemias and inflammatory diseases. In reactive lymphocytosis, the proliferating lymphocytes were organized into lymphoid aggregates in bone marrow and were predominately B cells. Alternatively, in CLL and thymoma, the proliferating lymphocytes were diffusely distributed and were predominately T cells. Therefore, differentiation of the causes of lymphocytosis should include evaluation of signalment, concurrent disease conditions, lymphocyte morphology, lymphocyte distribution in bone marrow, and immunophenotype. Cat age, presence of severe anemia, and evidence of inflammatory disease also should be considered.

PMID: 16355680 [PubMed - indexed for MEDLINE]

32: Kyobu Geka. 2005 Nov;58(12):1023-9; discussion 1029-31. Related Articles, Links

[Surgery for the thymoma combined with pure red cell aplasia and myasthenia gravis]

[Article in Japanese]

Ayabe T, Matsuzaki Y, Edagawa M, Shimizu T, Hara M, Tomita M, Akiyama Y, Onitsuka T.

Department of Second Surgery, Miyazaki Medical College, University of Miyazaki, Miyazaki, Japan.

Pure red cell aplasia (PRCA) and myasthenia gravis (MG) are respectively combined with thymoma, however, these 3 complications are extremely rare coexisted as a clinical triad. A 73-year-old female with mediastinal tumor found in 2000 was pointed out anemia in June 2002. As PRCA was diagnosed by the bone marrow examination, blood transfusion had been performed. By a chest computed tomography (CT), a thymoma in size of 7 x 5 cm in diameter was recognized in the anterior mediastinum. The serum level of anti-acetylcholine receptor antibody was elevated to be 35 nmol/l. MG was simultaneously diagnosed with a decreased power of neck muscle. The extended thymectomy was performed in August 2002, and pathological diagnosis disclosed a 'type AB' by World Health Organization (WHO) classification. After the operation, the decreased power of neck muscle had been improved, however, PRCA had not been remitted in the early-postoperative term. Blood transfusion had been required (2-4 units/1-2 weeks) for the postoperative 7 months' term. A cyclosporin (250 mg/day) as an adjuvant therapy was administered in April 2003. One month later, the patient's serum level of Hb had been over 10 g/dl without blood transfusion. The patient has been followed up with reducing the dose of cyclosporin. Conclusions: Surgery for a thymoma combined with PRCA and MG was effective for MG but not for PRCA in an early-postoperative term, however, a multimodality therapy with immunosuppressant as a postoperative adjuvant should bring a favorable outcome to patient's clinical data, and the postoperative long-observation must be critical in this case.

Publication Types:

PMID: 16281850 [PubMed - indexed for MEDLINE]

33: Mol Ther. 2005 Nov;12(5):892-9. Epub 2005 Jul 11. Related Articles, Links: Transduction of CpG DNA-stimulated primary human B cells with bicistronic lentivectors.

Kvell K, Nguyen TH, Salmon P, Glauser F, Werner-Favre C, Barnet M, Schneider P, Trono D, Zubler RH.

Division of Hematology, Department of Internal Medicine, University Hospitals, 1211 Geneva-14, Switzerland.

Recently, using HIV-1-derived lentivectors, we obtained efficient transduction of primary human B lymphocytes cocultured with murine EL-4 B5 thymoma cells, but not of isolated B cells activated by CD40 ligation. Coculture with a cell line is problematic for gene therapy applications or study of gene functions. We have now found that transduction of B cells in a system using CpG DNA was comparable to that in the EL-4 B5 system. A monocistronic vector with a CMV promoter gave 32 +/- 4.7% green fluorescent protein (GFP)+ cells. A bicistronic vector, encoding IL-4 and GFP in the first and second cistrons, respectively, gave 14.2 +/- 2.1% GFP+ cells and IL-4 secretion of 1.3 +/- 0.2 ng/10(5) B cells/24 h. This was similar to results obtained in CD34+ cells using the elongation factor-1alpha promoter. Activated memory and naive B cells were transducible. After transduction with a bicistronic vector encoding a viral FLIP molecule, vFLIP was detectable by FACS or Western blot in GFP+, but not in GFP-, B cells, and 57% of sorted GFP+ B cells were protected against Fas ligand-induced cell death. This system should be useful for gene function research in primary B cells and development of gene therapies.

PMID: 16005685 [PubMed - indexed for MEDLINE]

34: J Neurol Sci. 2005 Oct 15;237(1-2):39-43. Related Articles, Links: Extrathymic malignancies in patients with myasthenia gravis.

Levin N, Abramsky O, Lossos A, Karussis D, Siegal T, Argov Z, Ben Hur T.

Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah-Hebrew University Hospital, Jerusalem 91120, Israel.

INTRODUCTION: Myasthenia gravis (MG) is considered a paraneoplastic phenomenon of thymomas in 15% of patients. Co-existence of MG with extrathymic malignancies, and an increased risk of second malignancy in patients with thymoma have been reported. Data on clinical characteristics of MG patients with extrathymic malignancies and the role of concomitant diseases and their treatment are lacking. METHODS: The clinical records of 188 consecutive MG patients were studied retrospectively. We examined whether gender, age, generalized disease, seropositivity for acetyl-choline receptor antibodies, occurrence of thymoma, immunosuppressive therapy and occurrence of other autoimmune diseases determined an increased risk for development of extrathymic malignancy. RESULTS: This group followed the typical epidemiological characteristics of MG. Thirty-three patients (17.6%) had a thymoma. Twenty-nine patients (15.4%) had 30 extrathymic malignant tumors of various origins. Only four patients with extrathymic tumors had an associated thymoma. Tumors were diagnosed between 20 years prior to and 35 years after the appearance of MG. Older age of MG onset was the only risk factor identified for development of malignancy in MG. DISCUSSION: Extrathymic malignancies are common in MG patients, especially in the older age group. There are no specific clinical features of the subgroup of MG patients with cancer. Although MG is not a paraneoplastic phenomenon of extrathymic malignancy, the association between MG and malignancy may be due to a common background of immune dysregulation.

PMID: 15990114 [PubMed - indexed for MEDLINE]

35: Am J Med Sci. 2005 Oct;330(4):172-5. Related Articles, Links: Stage IV thymic carcinoma: a study of 20 patients.

Lin JT, Wei-Shu W, Yen CC, Liu JH, Chen PM, Chiou TJ.

Division of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan. ljtmi@yahoo.com

BACKGROUND: This study was performed to investigate the clinical factors, tumor characteristics, treatment approach, and prognosis of patients with Stage IV thymic carcinoma (WHO type C). METHODS: The records of 20 patients with histologically confirmed thymic carcinoma treated between 1988 and 2002 at the Division of Oncology at Taipei Veterans General Hospital were reviewed. RESULTS: Therapy consisted of surgical debulking, adjuvant radiotherapy, and chemotherapy in six patients (30%), surgical debulking with adjuvant chemotherapy in two patients (10%), surgical debulking with adjuvant radiotherapy in one patient (5%), radiotherapy with adjuvant chemotherapy in eight patients (40%), and chemotherapy alone in three patients (15%). After a median follow-up of 22 months (range, 5-72 months), three patients (15%) were alive. Eighteen patients (90%) experienced disease recurrence after a median of 9 months (range, 2-41 months); 12 (66%) of these patients initially had stage IVa disease, and 6 (33%) had stage IV b disease. Five patients had an undifferentiated type of histology. The median time to progression was 5 months. However, none of these patients was able to receive salvage therapy due to their poor performance status. For those patients with a lymphoepithelioma-like histology, the median survival was 36 months; there was tumor recurrence in five patients and they all received salvage chemotherapy. The median survival time for these five patients was 51 months. For patients with squamous cell type, the median time to progression was 10 months. Five patients received salvage chemotherapy and the median survival was 28 months. There was a significant difference (P < 0.0001) in the median survival between those who received chemotherapy (18 months) after tumor relapse and those who did not (1 month). CONCLUSIONS: Our results indicate that multidisciplinary treatment, including surgery, radiotherapy, and chemotherapy, is beneficial in treating primary thymic carcinoma. Chemotherapy plays an important role in both primary and relapsed stage IV thymic carcinoma in terms of prolonging the disease-free survival and median survival of patients with lymphoepithelioma-like or squamous cell histology types. For patients with an undifferentiated histology, multidisciplinary treatment or chemotherapy might not be helpful in either primary or relapsed stage IV thymic carcinoma.

PMID: 16234609 [PubMed - indexed for MEDLINE]

36: Ann Neurol. 2005 Oct;58(4):644-8. Related Articles, Links: A CTLA4high genotype is associated with myasthenia gravis in thymoma patients.

Chuang WY, Strobel P, Gold R, Nix W, Schalke B, Kiefer R, Opitz A, Klinker E, Muller-Hermelink HK, Marx A.

Institute of Pathology, University of Wurzburg, Wurzburg, Germany.

Myasthenia gravis (MG) in thymoma patients depends critically on intratumorous generation and export of mature autoreactive CD4+ T cells. Why non-MG thymomas fail to produce CD4+ T cells is unknown. We studied three single-nucleotide polymorphisms of the cytotoxic T-lymphocyte-associated antigen 4(CTLA4) gene in thymoma patients, nonthymoma early-onset MG patients, and control subjects. Surprisingly, the CTLA4high genotype +49A/A, which is protective against several autoimmune diseases, exerted a prominent predisposing effect to paraneoplastic MG in thymoma patients. The unusual disease association with a CTLA4high genotype implies a unique pathogenesis of paraneoplastic MG, with high CTLA4 levels possibly supporting the nontolerogenic selection of CD4+ T cells in MG-associated thymomas.

PMID: 16178018 [PubMed - indexed for MEDLINE]

37: Anticancer Drugs. 2005 Oct;16(9):997-1002. Related Articles, Links

A phase I and pharmacokinetic study of the selective, non-peptidic inhibitor of matrix metalloproteinase BAY 12-9566 in combination with etoposide and carboplatin.

Molina JR, Reid JM, Erlichman C, Sloan JA, Furth A, Safgren SL, Lathia CD, Alberts SR.

Department of Oncology, Mayo Clinic, Rochester, Minnesota 55905, USA.

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that degrade the extracellular matrix during the processes of invasion, metastasis and angiogenesis. BAY 12-9566 (BAY) is a selective, non-peptidic biphenyl inhibitor of MMPs, with nanomolar inhibitory activity against MMP-2, -3 and -9, and anti-invasive, anti-metastatic and anti-angiogenic activity in a variety of tumor models. This phase I study of oral BAY was conducted to evaluate the safety and pharmacokinetics of BAY when administered in combination with etoposide (VP-16) or in combination with VP-16 and carboplatin (CBDCA) in subjects with advanced cancer. The first cohort of patients (n=8) received a cycle of VP-16, 60 mg/m, followed 1 week later by a fixed daily oral dose of BAY, 800 mg b.i.d., to which three potential possible doses of VP-16 (low dose: 60 mg/m; mid dose: 90 mg/m; high dose: 120 mg/m) were added every 3 weeks as tolerated. The second cohort (n=5) received VP-16 (120 mg/m) and CBDCA (AUC=5) followed 1 week later by a fixed daily oral dose of BAY (800 mg) b.i.d., to which VP-16 (120 mg/m) and CBDCA (AUC=5) were added. Dose-limiting toxicity (DLT) was defined as toxicity grade 3 or above. Maximum tolerated dose was declared if two or more patients experienced DLT. A performance status of 0-2 and acceptable organ function were required for eligibility. Plasma concentrations of BAY and VP-16 were measured to investigate pharmacokinetic interactions. Eight eligible patients with a variety of tumor types (median age 64 years, range 44-76) were enrolled in the first cohort, six of who whom completed all three levels of VP-16. Progressive disease occurred in five of the eight patients; three patients continued on study with treatment. Drug level and pharmacokinetics analysis of BAY and VP-16 were also determined. The combination of BAY and VP-16 was tolerable in the first cohort, permitting enrollment of the second cohort. In the second cohort (n=5), the combination of BAY, VP-16 and CDBCA was intolerable at the doses used due to excessive hematologic toxicity in the first five patients enrolled. Pharmacokinetics and toxicity analysis was performed for this group of patients. Only Level 1 of treatment was completed for Cohort II. At this point the study was halted due to toxicity and the results of an interim analysis that failed to demonstrate sufficient clinical activity of this compound in other clinical trials. We conclude that the combination of BAY and VP-16 was well tolerated. However, the combination of BAY, VP-16 and CDBCA produces significant hematologic toxicity. Findings from this study may help to direct further studies with other inhibitors of MMPs.

Publication Types:

PMID: 16162976 [PubMed - indexed for MEDLINE]

38: Chest. 2005 Oct;128(4):3010-2. Related Articles, Links: Videothoracoscopic resection of stage II thymoma: prospective comparison of the results between thoracoscopy and open methods.

Cheng YJ, Kao EL, Chou SH.

Division of Thoracic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, 100 Shih-Chuan First Rd, Kaohsiung 80708, Taiwan. yujen.cheng@msa.hinet.net

STUDY OBJECTIVES: Although videothoracoscopic (VTS) resection of Masaoka stage I thymoma has been reported to be a less invasive method than open thoracotomy and to achieve a comparable surgical outcome, the usefulness of this method in the treatment of stage II thymoma has not yet been prospectively evaluated. We therefore compared the VTS and open (median sternotomy) methods to see whether VTS resection could be used as successfully to treat stage II thymoma disease. DESIGN, SETTING, AND PATIENTS: Patients (11 women and 11 men) with stage II thymoma were prospectively enrolled between November 1999 and September 2004. Of these, 12 patients (the VTS group) underwent tumor resection using a three-port endoscopic technique, and 10 patients (the open group) underwent tumor excision using a standard sternotomy approach. The diagnosis of all resected thymoma lesions and their stage were confirmed by histopathogic examination. MEASUREMENTS AND RESULTS: Neither group experienced mortality or any major morbidity. The difference in mean age (+/- SD) between the VTS and open groups (40.2 +/- 16.3 years and 47.7 +/- 8.5 years, p = 0.202); mean operation time (193.3 +/- 79.6 min and 207.5 +/- 85.8 min, p = 0.692); mean duration of pleural drainage (4.2 +/- 2.1 days and 4.6 +/- 2.1 days, p = 0.702); and mean duration of postoperative hospital stay (6.8 +/- 2.3 days and 8.9 +/- 4.4 days, respectively; p = 0.157) were not statistically significant. However, mean intraoperative blood loss amounts were statistically different (119.2 +/- 70.6 mL and 238.5 +/- 110.2 mL, respectively; p = 0.006). During the mean follow-up period of 33.9 +/- 19.7 months, all patients survived without sign of recurrence, and the mean survival time was not statistically significant (32.3 +/- 22.0 months and 35.8 +/- 17.5 months, respectively; p = 0.686). CONCLUSION: Using careful and skillful technique, the VTS method is an effective treatment of stage II thymoma.

PMID: 16236980 [PubMed - indexed for MEDLINE]

39: Chest. 2005 Oct;128(4):2893-909. Related Articles, Links

Tumors of the mediastinum.

Duwe BV, Sterman DH, Musani AI.

Department of Internal Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.

Tumors of the mediastinum represent a wide diversity of disease states. The location and composition of a mass is critical to narrowing the differential diagnosis. The most common causes of an anterior mediastinal mass include the following: thymoma; teratoma; thyroid disease; and lymphoma. Masses of the middle mediastinum are typically congenital cysts, including foregut and pericardial cysts, while those that arise in the posterior mediastinum are often neurogenic tumors. The clinical sequelae of mediastinal masses can range from being asymptomatic to producing symptoms of cough, chest pain, and dyspnea. This article will review the anatomy of the mediastinum as well as the different clinical, radiographic, and prognostic features, and therapeutic options of the most commonly encountered masses.

Publication Types:

Review

PMID: 16236967 [PubMed - indexed for MEDLINE]

40: Curr Opin Neurol. 2005 Oct;18(5):598-603. Related Articles, Links: Paraneoplastic syndromes of the peripheral nerves.

Rudnicki SA, Dalmau J.

Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.

PURPOSE OF REVIEW: To describe the paraneoplastic disorders of the motor and sensory nerves and neurons, and their immunologic associations. RECENT FINDINGS: Recently proposed diagnostic criteria for paraneoplastic disorders may assist in determining the likelihood a given neuropathy or neuronopathy is related to an underlying malignancy. Of this group of disorders, paraneoplastic sensory neuronopathies are the most frequent; many of these patients have anti-Hu antibodies and small-cell lung cancer. There is often motor, autonomic, or central nervous system involvement, and electrophysiological studies may demonstrate not only sensory changes, but also motor abnormalities. While cancer has been found more frequently than expected in patients with Guillain-Barre syndrome, this association is extremely rare. A limited number of reports have described chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy with conduction block, vasculitic neuropathies, and motor neuron disease as paraneoplastic disorders. Anti-CV2 antibodies are frequently associated with a paraneoplastic sensorimotor axonal neuropathy and small-cell lung cancer. Peripheral nerve hyperexcitability may occur with or without a cancer association, and in both instances patients often have antibodies to voltage-gated potassium channels; thymoma and small-cell lung cancer are the most common underlying tumors. Plasma cell proliferative disorders are frequently associated with neuropathies, particularly demyelinating ones. SUMMARY: There is increasing recognition of an extensive variety of paraneoplastic disorders of the peripheral nerves. In many of these disorders onconeuronal antibodies are absent. Whole body fluorodeoxyglucose positron emission tomography scanning helps uncover the associated tumor, and recently proposed criteria may assist in the diagnosis. In many instances, prompt treatment of the tumor and immunotherapy result in symptom stabilization or neurologic improvement.

PMID: 16155447 [PubMed - in process]

41: Eur J Cardiothorac Surg. 2005 Oct;28(4):611-6. Related Articles, Links: Expression of neurotrophin receptors in surgically resected thymic epithelial tumors.

Kim DJ, Yang WI, Kim SH, Park IK, Chung KY.

Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, CPO Box 8044, Seoul 120-752, South Korea.

OBJECTIVE: Neurotrophins are known to exert a variety of pleiotropic responses in different target tissues, but little is known about their effect on thymic epithelial tumors. Therefore, we analyzed the expression of neurotrophin receptors in surgically resected thymic epithelial tumors and evaluated their clinical relevance. METHODS: The expression of neurotrophin receptors (Trk-A, Trk-B, Trk-C and p75(NTR)) in thymic epithelial tumors was evaluated in 99 consecutive patients based on immunohistochemical staining. The pattern of expression was analyzed according to the WHO classification, and survival outcomes were estimated. RESULTS: Thymic tumors were classified as type A (n=6), AB (n=21), B1 (n=15), B2 (n=24), B3 (n=22) or C (n=11). All tumors, except one type C thymoma, demonstrated cytoplasmic Trk-A immunostaining, and no thymic tumors showed Trk-B or Trk-C immunoreactivity. p75(NTR) immunostaining demonstrated characteristic patterns according to the WHO subtypes of thymomas. All type A and type AB thymomas showed p75(NTR) immunoreactivity, except one type A tumor. The expression of p75(NTR) was negative in 6 patients (40%) with type B1 thymomas, 19 patients (79.2%) with type B2 thymomas, 17 patients (77.3%) with type B3 thymomas and 10 patients (90.9%) with type C thymomas. Tumor-related survival at 5 and 10 years was 95.5 and 89.5%, respectively, in p75(NTR)-positive thymomas and 82.8 and 77.2%, respectively, in p75(NTR)-negative thymomas; however, the differences were not statistically significant (P=0.14). CONCLUSIONS: Among the neurotrophin receptors examined, the pattern of p75(NTR) expression closely correlated with the WHO subtypes of thymomas. Further study of p75(NTR) expression may aid in understanding the biology of thymic epithelial tumors.

PMID: 16125946 [PubMed - in process]

42: Genes Chromosomes Cancer. 2005 Oct;44(2):154-60. Related Articles, Links: Familial occurrence of thymoma and autoimmune diseases with the constitutional translocation t(14;20)(q24.1;p12.3).

Nicodeme F, Geffroy S, Conti M, Delobel B, Soenen V, Grardel N, Porte H, Copin MC, Lai JL, Andrieux J.

Laboratoire de Genetique Medicale, Hopital Jeanne de Flandre, CHRU, Lille, France.

Thymomas are low-grade epithelial cancers of the thymus whose prevalence varies between 0.1/100,000 and 0.4/100,000. Familial occurrence of thymoma is very rare. We studied a family bearing the constitutional chromosome translocation t(14;20)(q24;p12), 3 of whose members had a thymoma. In this family, among 27 patients, 11 had the translocation: 3 had thymoma and 4 others had 5 different autoimmune diseases: type 1 diabetes mellitus, Graves' disease, pernicious anemia, primitive Sjogren disease, and autoimmune pancytopenia. FISH studies allowed us to be more specific about the translocation breakpoints. The 14q24 breakpoint was in intron 5 of RAD51L1, and the 20p12 breakpoint was 100 kb telomeric to BMP2. RAD51L1 is a tumor-suppressor gene belonging to the RAD51 family, already implicated in many tumors (uterine leiomyomas, pseudo-Meigs syndromes, pulmonary chondroid hamartomas) and involved in recombinational repair of DNA double-strand breaks. BMP2 belongs to the TGFbeta superfamily, and the BMP2-BMP4 genes are involved in thymocyte differentiation by blocking progression from CD4-CD8- to CD4+CD8+ while maintaining a sufficient pool of immature precursors. Dysregulation of RAD51L1 and/or BMP2 may explain this familial occurrence of thymomas and autoimmune diseases. Using QRT-PCR, we studied the expression of BMP2 in 20 sporadic thymomas and found various levels of expression that may be associated with autoimmune diseases.

PMID: 15942943 [PubMed - indexed for MEDLINE]

43: Gynecol Oncol. 2005 Oct;99(1):228-31. Related Articles, Links

Malignant thymoma metastatic to the pelvis: a rare case and considerations for management.

Elliott KS, Borowsky ME, Bakdounes K, Huang J, Abulafia O, Lee YC.

Department of Obstetrics and Gynecology, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Box #24, Brooklyn, NY 11203, USA. Kevinselliott@aol.com

BACKGROUND: Thymoma is the most common tumor of the anterior mediastinum. Due to its relative rarity, its inconsistent clinical course and its frequent proximity to vital thoracic structures, management of this generally indolent tumor varies considerably. We present an unusual case of recurrent thymoma metastatic to the pelvis and review treatment experience employing surgical, radiotherapeutic and medical modalities. CASE REPORT: The present case is that of a 46-year-old woman with recurrent thymoma metastatic to a distal pelvic lymph node. Resection of the pelvic recurrence followed many years of local and systemic treatment for her thoracic primary tumor. Her case is unique for its involvement of pelvic anatomy and her clinical course marked by treatment-related congestive heart failure. CONCLUSION: While the indolent clinical course of thyomoma frequently necessitates re-treatment and multi-modality therapy in patients suffering recurrences, treatment selection must take into account potential long-term morbidity and attendant quality of life. When anatomically and technically feasible, resection of recurrent disease should be considered in attempts to avoid potential cumulative and long-term toxicity resultant from radiotherapy and chemotherapy.

Publication Types:

Case Reports

PMID: 16055177 [PubMed - indexed for MEDLINE]

44: Head Neck. 2005 Oct;27(10):927-33. Related Articles, Links

Extrathyroid carcinoma showing thymus-like differentiation (CASTLE) tumor--a new case report and review of literature.

Luo CM, Hsueh C, Chen TM.

Department of Otolaryngology, Chang Gung Memorial Hospital, 5F, No. 222, Mai-Chin Rd., Keelung, 204 Taiwan.

BACKGROUND: We report a case of extrathyroid carcinoma showing thymus-like differentiation (CASTLE) tumor. METHODS: A 47-year-old man had a left neck mass that gradually enlarged over approximately 3 months. Sonography and CT scans showed a soft tissue mass located at the left parapharyngeal space with displacement of left carotid artery and submandibular gland. RESULTS: After total excision, the pathologic diagnosis was CASTLE tumor. The patient then received radiotherapy with a total dosage of 6600 cGy. After 21 months of postoperative follow up, there was no evidence of recurrence. CONCLUSION: Generally, the treatment of choice is surgical excision with or without radiotherapy. Because CASTLE tumors have been reported to be radiosensitive, however, and because local recurrence is common, surgical excision with postoperative radiotherapy is suggested. (c) 2005 Wiley Periodicals, Inc.

Publication Types:

PMID: 15952197 [PubMed - indexed for MEDLINE]

45: J Neuroimmunol. 2005 Oct;167(1-2):186-9. Related Articles, Links

Altered populations of natural killer cell and natural killer T cell subclasses in myasthenia gravis.

Suzuki Y, Onodera H, Tago H, Saito R, Ohuchi M, Shimizu M, Itoyama Y.

Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryo-Machi, Aobaku, Sendai 980-8574, Japan.

Since the innate immune system can influence the disease activity of myasthenia gravis (MG), such as during infection, the frequencies of natural killer (NK) cells and NKT cells were analyzed in the blood and thymus. Before therapy (thymectomy plus glucocorticoid), the MG patients with thymic hyperplasia, but not those with thymoma, showed increased frequencies of mature NKT cells (CD3(+)TCRV(alpha)24(+)CD161(bright)) in the blood, while the frequency of immature NKT cells was unaltered. In the blood of the patients with thymoma, but not those with hyperplasia, the frequency of cytotoxic subclass of NK cells (CD3(-)CD16(+)CD56(dim)) was lower than that of the control. These alterations returned to normal after therapy. The thymic frequencies of NKT cells and NK cells in MG thymuses were unaltered. These results suggest the involvement of both innate and acquired immunity in the disease activity of MG.

Publication Types:

Clinical Trial

PMID: 16040133 [PubMed - indexed for MEDLINE]

46: J Neurol. 2005 Oct;252(10):1262-6. Epub 2005 Oct 5. Related Articles, Links: Thymectomy in myasthenia gravis: comparison of outcome in Santiago, Cuba and Nottingham, UK.

Shahrizaila N, Pacheco OA, Vidal DG, Miyares FR, Wills AJ.

Dept. of Neurology, Queen's Medical Centre, Nottingham NG7 2 UH, UK.

OBJECTIVES: We compared the outcome of thymectomy for myasthenia gravis (MG) in two healthcare systems. In Nottingham, UK, thymectomy is performed for thymic enlargement and considered in acetylcholine receptor (AchR) antibody positive patients. In Santiago, Cuba, thymectomy is considered in all generalised MG patients irrespective of their radiological findings or AchR antibodies. METHOD: 22 MG patients in Nottingham and 75 in Santiago who had a thymectomy were identified and their notes reviewed. We compared the median age, stage of disease, thymic histology and clinical outcome at two years post-thymectomy. RESULTS: The median ages for the Cuban and Nottingham patients were 25 and 35 years respectively. The median stage of disease was IIa by Osserman's classification in both. In Nottingham, 59% (13/22) showed an improvement compared with 88 % (66/75) in Santiago (p < 0.01). There were significantly more cases of thymoma in Nottingham whereas thymic hyperplasia and atrophy were a more frequent finding in Cuban patients. The majority of cases who improved post-thymectomy had thymic hyperplasia on histology in both Nottingham (46%) and Cuban (61%) patients. CONCLUSION: Selecting MG patients based on thymic enlargement alone or AchR antibody positivity may be inadequate and thymectomy should perhaps be considered in all patients with generalised myasthenia.

PMID: 16200466 [PubMed - in process]

47: Lung Cancer. 2005 Oct;50(1):59-66. Related Articles, Links: World Health Organization histologic classification: an independent prognostic factor in resected thymomas.

Rena O, Papalia E, Maggi G, Oliaro A, Ruffini E, Filosso P, Mancuso M, Novero D, Casadio C.

Thoracic Surgery Department, University of Eastern Piedmont, Maggiore della Carita General Hospital, via Mazzini 18, Novara 28100, Italy. ottaviorena@libero.it

The histologic classification of thymoma remained controversial since 1999, when the World Health Organization (WHO) Consensus Committee published a histologic typing system for tumours of thymus. Clinical features, postoperative relapsing rates, and survival of patients with thymoma were evaluated with reference to the WHO histologic classification, based on a series of 178 patients, submitted to surgery between 1988 and 2000.There were 21 type A, 49 type AB, 45 type B1, 50 type B2 and 13 type B3 tumours. The invasiveness of tumours was 23.8%, 51%, 73.3%, 82% and 100% for types A, AB, B1, B2 and B3 tumours, respectively. The frequency of invasion of the great vessels increased according to the tumour type in the order A (0%), AB (4%), B1 (6.6%), B2 (22%), and B3 (23%). The 10-year disease-free survival was 95%, 90%, 85%, 71% and 40% for types A, AB, B1, B2 and B3, respectively. According to the Masaoka staging system, the disease-free survival rates were 94%, 88% and 66% for stages I, II and III, respectively, at 10 years. No stage IVA thymomas reached 10 years follow-up. Overall survival at 10 years were 88% and 25% when complete and incomplete resection were considered. By multivariate analysis, Masaoka staging system, WHO histologic classification and complete resection were significant independent prognostic factors, whereas age- and sex-associated myasthenia gravis were not. The present study demonstrated the World Health Organization histologic classification a good prognostic factor, such as completeness of surgical resection and Masaoka staging system.

PMID: 16009453 [PubMed - indexed for MEDLINE]

48: Zhonghua Jie He He Hu Xi Za Zhi. 2005 Oct;28(10):717-9. Related Articles, Links: [Advance in diagnosis and management for thymoma]

[Article in Chinese]

Wang JH, Zhang SC.

PMID: 16255960 [PubMed - in process]

49: Cancer Res. 2005 Sep 15;65(18):8479-86. Related Articles, Links: Distinct and overlapping roles of interleukin-10 and CD25+ regulatory T cells in the inhibition of antitumor CD8 T-cell responses.

Dercamp C, Chemin K, Caux C, Trinchieri G, Vicari AP.

Laboratory for Immunological Research, Schering-Plough Research Institute, Dardilly, France. dercamp@cervi-lyon.inserm.fr

Lack of antitumor immunity is often related to impaired CD8 T-cell responses that could result from a poor priming capacity by tumor-infiltrating dendritic cells (TIDC) and/or further inhibition by regulatory T cells (T(reg)). Interleukin-10 (IL-10) has been implicated in the inhibition of TIDC as well as in the generation and functions of T(reg). Here, we address some of the respective and possibly overlapping roles of IL-10 and CD25+ T(reg) in CD8 antitumor immunity. Whereas tumor antigen-specific CD8 T cells proliferated in vivo in the presence of IL-10 or T(reg), optimal effector functions were observed in mice lacking both IL-10 and T(reg). Indeed, tumors grown in normal but not in IL-10-deficient or CD25-depleted mice induced tumor antigen-specific CD8 suppressor T cells. Suppression involved transforming growth factor-beta. Similarly, both IL-10 and T(reg) were responsible for impaired CD8 T cell priming by TIDCs, but IL-12 production by TIDCs was prevented only by T(reg)-independent IL-10. Subsequently, IL-10 defect and T(reg) depletion were required to achieve optimal induction of CD8 T-cell effectors by TIDC following CpG activation. Our results point out major redundant and nonredundant roles for IL-10 and T(reg) in the inhibition of TIDC-mediated generation of antitumor CD8 T-cell response.

PMID: 16166328 [PubMed - indexed for MEDLINE]

50: Clin Cancer Res. 2005 Sep 15;11(18):6495-504. Related Articles, Links: Estrogen inhibits cell proliferation through in situ production in human thymoma.

Ishibashi H, Suzuki T, Suzuki S, Moriya T, Kaneko C, Nakata T, Sunamori M, Handa M, Kondo T, Sasano H.

Department of Pathology, Tohoku University School of Medicine, Japan. hishiba@kf6.so-net.ne.jp

PURPOSE: We showed previously estrogen receptor (ER) alpha as an independent prognostic marker in human thymoma. Estrogen sulfotransferase (EST), steroid sulfatase (STS), 17beta-hydroxysteroid dehydrogenase (17beta-HSD), and aromatase are considered to play important roles in hormone metabolism of estrogen-dependent tumors. EXPERIMENTAL DESIGN: We examined estrogen production using primary cultures of human thymoma epithelial cells (TEC), intratumoral estradiol (E(2)) concentrations, and status of these enzymes above using immunohistochemistry or semiquantitative reverse transcription-PCR. We then correlated these findings with clinicopathologic variables and/or clinical outcome in 132 patients. RESULTS: E(2) inhibited cell proliferation via ERalpha in TEC, which synthesized estrone and E(2). Intratumoral E(2) concentrations were inversely correlated with EST, positively correlated with STS or 17beta-HSD type 1, and significantly higher in lower-grade or early-stage thymoma. EST status was positively correlated with tumor size, clinical stage, histologic differentiation, and Ki-67 labeling index and significantly associated with adverse clinical outcome and turned out to be a potent independent prognostic factor. STS and/or 17beta-HSD type 1 status was inversely correlated with Ki-67 labeling index and associated with lower histologic grade or early clinical stages. CONCLUSIONS: E(2) inhibits proliferation of TEC through ERalpha, which suggests that E(2) may be effective in treatment of thymoma, especially inoperable tumor, possibly through suppressing its cell proliferation activity. EST status is a potent prognostic factor in thymoma through inactivating estrogens. In situ estrogen synthesis through intracrine mechanism therefore may play important roles in tumorigenesis and/or development of thymoma through regulation of cell proliferation in an intracrine manner.

PMID: 16166425 [PubMed - indexed for MEDLINE]

51: Neurology. 2005 Sep 13;65(5):782-3; author reply 782-3. Related Articles, Links

Comment on:

Neurology. 2005 Feb 8;64(3):536-8.

Thymus changes in anti-MuSK-positive and -negative myasthenia gravis.

Saka E, Topcuoglu MA, Akkaya B, Galati A, Onal MZ, Vincent A.

Publication Types:

PMID: 16157930 [PubMed - indexed for MEDLINE]

52: Neurology. 2005 Sep 13;65(5):770-2. Related Articles, Links: Perivascular infiltrate of memory lymphocytes and mature dendritic cells in MG thymomas.

Nagane Y, Utsugisawa K, Akutsu H, Sato Y, Terayama Y.

Department of Neurology, Iwate Medical University, 19-1 Uchimaru, Morioka, 020-8505, Japan.

In thymomas associated with myasthenia gravis (MG), the authors found that perivascular infiltrates of memory lymphocytes and mature dendritic cells (DCs) were more frequent in patients with early improvement after thymectomy than in patients without response to thymectomy. Although these findings may be limited to particular types of thymoma, thymectomy may interrupt the recruitment of mature DCs in thymus and export of activated T cells to extra-thymic tissues, thereby improving the disease.

PMID: 16157920 [PubMed - indexed for MEDLINE]

53: Am J Surg Pathol. 2005 Sep;29(9):1208-13. Related Articles, Links

Thymoma arising within cardiac myxoma.

Miller DV, Tazelaar HD, Handy JR, Young DA, Hernandez JC.

Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, USA.

Hematopoietic, glandular, and mesenchymal elements can be found within cardiac myxomas; ectopic endocrine tissues and "thymic rests" have also rarely been described. Atrial tumors (one right and one left) from 2 patients (a 69-year-old man and a 77-year-old woman) were encountered among the atrial myxoma cases in one of the author's consultation files. Both tumors were comprised of classic cardiac myxoma (with characteristic rings and syncytial chains of myxoma cells in a loose myxoid matrix) and cellular thymoma-like elements (characterized by a lobulated sheet-like growth of epithelioid spindle cells admixed with small lymphocytes punctuated by vessels with prominent perivascular spaces). Neither patient had evidence of thymoma elsewhere. Immunophenotypically, the thymoma-like component reacted strongly with antibodies to keratins (AE1/AE3, Cam 5.2, wide spectrum, CK19, CK7) and CD57 and weakly with antibodies to CD31, CD34, and calretinin. This intermediate phenotypic expression of both epithelial and vascular antigens likely reflects the multipotential nature of the cells comprising this lesion. The most likely explanation for this extremely unusual finding is neoplastic transformation of thymic rests within a myxoma.

Publication Types:

Case Reports

PMID: 16096411 [PubMed - indexed for MEDLINE]

54: Br J Dermatol. 2005 Sep;153(3):558-64. Related Articles, Links

Autoantibody production from a thymoma and a follicular dendritic cell sarcoma associated with paraneoplastic pemphigus.

Wang J, Bu DF, Li T, Zheng R, Zhang BX, Chen XX, Zhu XJ.

Department of Dermatology, Peking University First Hospital, 8 Xishiku St, Beijing 100034, China.

BACKGROUND: Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease. We previously reported that B cells in a Castleman tumour associated with PNP produced autoantibodies. However, it is uncertain whether the production of autoantibodies from the associated tumour is a common mechanism in PNP. OBJECTIVES: To investigate autoantibody production in a thymoma and a follicular dendritic cell sarcoma that were excised from two patients with PNP. METHODS: Tumour cells were cultured, and their surface markers were identified. Indirect immunofluorescence, immunoblotting and enzyme-linked immunosorbent assay (ELISA) using culture media from the tumours were used to detect PNP autoantibodies. RESULTS: B cells with markers (CD22+, surface membrane IgG+ and surface membrane IgM+) of mature B lymphocytes constituted a proportion of cultured tumour cells in both tumours. Western blot showed that the medium from both the thymoma and the follicular dendritic cell sarcoma cells recognized 190-kDa periplakin and 210-kDa envoplakin bands of human epithelial proteins as well as recombinant linker regions of periplakin, envoplakin, desmoplakin and bullous pemphigoid antigen 1. ELISA was positive for antidesmoglein 3 antibody. CONCLUSIONS: The presence and localization in tumours of B-lymphocyte clones against proteins of the plakin family and desmoglein 3 in skin may not be confined to PNP with Castleman disease, but is possibly a common mechanism in PNP associated with various tumours.

Publication Types:

PMID: 16120143 [PubMed - indexed for MEDLINE]

55: Histopathology. 2005 Sep;47(3):292-302. Related Articles, Links: Glia maturation factor-beta is produced by thymoma and may promote intratumoral T-cell differentiation.

Yamazaki H, Tateyama H, Asai K, Fukai I, Fujii Y, Tada T, Eimoto T.

Department of Pathology, Nagoya University Medical School, Nagoya, Japan.

AIMS: To investigate whether Glia maturation factor-beta (GMFB) is expressed in thymomas and is associated with T-cell development. METHODS AND RESULTS: We investigated the expression of GMFB by immunohistochemistry in 86 cases of thymoma classified into five type A, 35 type AB, 11 type B1, 26 type B2, and nine type B3 thymomas according to the World Health Organization classification system. Immunoblotting and in situ hybridization (ISH) studies were also performed in selected cases. The results of the immunoblot analysis were in accordance with those of immunohistochemical scoring. The ISH study ascertained the tumour cells producing the protein. Immunohistochemically, GMFB expression was observed in one (20%) of type A, 32 (80%) of type AB, all (100%) of type B1 and B2, and eight (89%) of type B3 thymoma with statistically significant differences between type A and type AB, type B1, or type B2 thymoma, and between type B3 and type AB or type B2 thymoma. There was a significant correlation between GMFB expression and the amount of accompanying non-neoplastic T cells. GMFB promoted T-cell differentiation into CD4-/CD8+ cells when analysed by two-colour flow cytometry. CONCLUSIONS: The present study suggests that T-cell development in thymoma may be maintained partly by GMFB produced by the tumour cells.

PMID: 16115230 [PubMed - indexed for MEDLINE]

56: Immunology. 2005 Sep;116(1):134-41. Related Articles, Links: Circulating and thymic CD4 CD25 T regulatory cells in myasthenia gravis: effect of immunosuppressive treatment.

Fattorossi A, Battaglia A, Buzzonetti A, Ciaraffa F, Scambia G, Evoli A.

Department of Oncological Gynaecology, Catholic Univeristy, Rome, Italy.

Accumulating evidence indicates an immunosuppressive role of the thymus-derived CD4+ T-cell population constitutively expressing high level of CD25, T regulatory (Treg) cells, in autoimmune diseases. Here we show that the number of Treg cells in the blood is significantly lower in untreated myasthenia gravis patients than in age-matched healthy subjects, whereas it is normal or elevated in patients on immunosuppressive therapy (prednisone frequently associated with azathioprine). Therapeutic thymectomy (Tx) for either the thymoma or non-neoplastic thymic alterations that are often associated with myasthenia gravis provided unique material for studying intrathymic Treg cells and correlating them with their peripheral counterparts. We observed that Tx prevents the increase of Treg cells in the circulation that follows immunosuppressive therapy (particularly evident if the thymus is not neoplastic), indicating that the thymus contributes to Treg-cell normalization. However, thymic Treg cells are not modulated by immunosuppressive therapy and even in thymectomized patients Treg-cell numbers in the blood eventually recover. The present findings suggest that a deficiency in Treg cells favours the development of myasthenia gravis and that their normalization is an important clinical benefit of immunosuppressive therapy. Treg normalization appears to be largely thymus independent and possibly reflects the reported capacity of corticosteroids to promote Treg-cell development.

PMID: 16108825 [PubMed - indexed for MEDLINE]

57: J Clin Endocrinol Metab. 2005 Sep;90(9):5270-8. Epub 2005 Jul 5. Related Articles, Links: Osteopontin is overexpressed in human papillary thyroid carcinomas and enhances thyroid carcinoma cell invasiveness.

Guarino V, Faviana P, Salvatore G, Castellone MD, Cirafici AM, De Falco V, Celetti A, Giannini R, Basolo F, Melillo RM, Santoro M.

Dipartimento di Biologia e Patologia Cellulare e Molecolare, Facolta di Medicina e Chirurgia, Universita di Napoli Federico II, via S. Pansini 5, 80131 Naples, Italy.

The transmembrane glycoprotein CD44v6 is overexpressed in most papillary thyroid carcinomas (PTC). We previously reported that osteopontin (OPN), a secreted glycoprotein that functions as a ligand for CD44v6, is overexpressed in thyrocytes transformed by the RET/PTC oncogene. OBJECTIVE: In this study we asked whether OPN is overexpressed in human PTC samples, and whether its expression correlates with clinical and histological features of the tumors. Furthermore, we wanted to establish the functional role of the CD44-OPN axis in thyroid tumorigenesis. DESIGN: Thyroid samples from 117 patients who had undergone surgical resection of the thyroid gland for benign or malignant lesions were collected. OPN and CD44 expressions were evaluated by immunohistochemistry with specific monoclonal antibodies. OPN expression was correlated with different PTC histological variants, lymph node metastasis, and PTC size. RESULTS: In this study we show that OPN is overexpressed in human PTCs with respect to normal thyroid tissue, follicular adenomas, and multinodular goiters (P < 0.05). The prevalence and intensity of OPN staining were significantly correlated with the presence of lymph node metastases (P = 0.0091) and tumor size (P = 0.0001). We also show that treatment of human PTC cells with recombinant exogenous OPN stimulated Matrigel invasion and activated the ERK and V-AKT murine thymoma viral oncogene homolog 1/protein kinase B; signaling pathways. Blockage of anti-CD44 antibodies prevented these effects. CONCLUSIONS: Given its prevalence and its correlation with aggressive features of human PTCs, we suggest that OPN might be used as a diagnostic and prognostic marker for these tumors. Furthermore, given the role of the OPN-CD44v6 axis in PTC cells, we suggest that CD44 and/or OPN may be molecular targets for therapeutic intervention in aggressive PTCs.

PMID: 15998773 [PubMed - indexed for MEDLINE]

58: J Clin Neurosci. 2005 Sep;12(7):824-7. Related Articles, Links: Thymoma metastatic to the extradural spine.

Farin A, Aryan HE, Abshire BB.

Department of Neurosurgery, University of Southern California, Los Angeles.

BACKGROUND: Spinal epidural metastases are the most common spinal tumor, occurring in 10% of cancer patients. Malignant thymoma is a mediastinal tumor, with extrathoracic metastases occurring in 15% of patients to liver, kidney, and bone. Spinal metastasis is exceptionally rare. We present a case of thymoma with extradural metastasis and discuss the relevant literature. CASE REPORT: We describe a 45-year old man presenting with back pain and hypoesthesia twelve years after a diagnosis of thymoma. A review of the literature reveals few cases of thymoma metastatic to the extradural spine. We describe a novel surgical approach allowing ventral spinal cord decompression through a posterior incision. CONCLUSION: Spinal epidural metastases should be suspected in all cancer patients with back pain. Early detection of epidural metastases may enable improved pain control and preservation of spinal stability, ambulation and sphincter control.

PMID: 16198922 [PubMed - in process]

59: J Pathol. 2005 Sep;207(1):72-82. Related Articles, Links: Micronodular thymoma: an epithelial tumour with abnormal chemokine expression setting the stage for lymphoma development.

Strobel P, Marino M, Feuchtenberger M, Rouziere AS, Tony HP, Wulbrand U, Forster R, Zettl A, Lee Harris N, Kreipe H, Laeng RH, Muller-Hermelink HK, Marx A.

Institute of Pathology, University of Wurzburg, Germany. philipp.stroebel@mail.uni-wuerzburg.de

The aetiology of primary B-cell lymphomas of the thymus is enigmatic. Although thymic follicular lymphoid hyperplasia (TFH) is commonly associated with myasthenia gravis (MG), lymphoma is not a complication of this condition. The present paper reports a high frequency of monoclonal B-cell populations (6 of 18 cases; 33%) in micronodular thymoma (MNT), a peculiar thymic epithelial neoplasm with a B-cell-rich stroma, while B cells were consistently polyclonal in TFH (25 cases) and other types of thymomas (15 cases) (p < 0.001). An intratumoural lymphoma could be identified in three of the six monoclonal MNTs. Sequencing of the monoclonal IgH chain revealed partially overlapping VDJ gene usage in MNT and thymic mucosa-associated lymphoid tissue (MALT) lymphomas. The neoplastic epithelium of MNTs, but not of TFH and other types of thymoma, expressed high levels of dendritic cell, T-cell, and B-cell chemoattractants, such as CCL18, CCR6, and CCL20. It is concluded that abnormal chemokine expression in an epithelial tumour, MNT, can promote the recruitment of MALT, the emergence of monoclonal B cells, and, eventually, the subsequent development of mediastinal lymphomas. More generally, the concept that expression of a 'high-risk' spectrum of chemokines due to local or genetic factors may interfere with B-cell homeostasis and may contribute to MALT lymphoma development in chronic inflammatory states is proposed. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

PMID: 15965907 [PubMed - indexed for MEDLINE]

60: J Thorac Cardiovasc Surg. 2005 Sep;130(3):918-9. Related Articles, Links

Mediastinitis and pseudoaneurysm of brachiocephalic artery long after the resection of invasive thymoma and postoperative irradiation.

Okubo K, Isobe J, Kitamura J, Ueno Y.

General Thoracic Surgery and Cardiac Surgery, National Hospital Organization, Nagara Medical Center, Gifu, Japan. okubo@nagara-lan.hosp.go.jp

Publication Types:

Case Reports

PMID: 16153964 [PubMed - indexed for MEDLINE]

61: Kyobu Geka. 2005 Sep;58(10):887-92. Related Articles, Links

[Imaging aid for thoracoscopic thymectomy; thymic vein visualization]

[Article in Japanese]

Okuda I, Kokubo T, Kohno T, Yamase H, Shibuya K.

Department of Diagnostic Radiology, Toranomon Hospital, Tokyo, Japan.

The spread and progress of thoracoscopic surgery has been remarkable. There are many important organs and blood vessels in the mediastinal space, thus, as inadvertent injury invites serious consequences, it is necessary to understand the anatomical position of existing structures. When enucleating the thymoma under a thoracoscope, one of the blood vessels to be careful about is the thymic vein. Therefore, we examined whether the thymic vein could be confirmed using a multidetector-row computed tomography (MD CT). We believed we could understand the anatomical position of the thymic vein by analyzing the high resolution slice data provided in MD CT using a work station. The diameter of the thymic is from a little less than 1 mm to 3 mm, and there were individual variations in position and the number of the vein. The thymic vein flowed into the left brachiocephalic vein in many cases. In some cases, the thymic vein flowed into the right internal thoracic vein or superior vena cava. It appears that visualization of the thymic vein could provide useful data when performing thoracoscopic thymectomy.

Publication Types:

Case Reports

PMID: 16167815 [PubMed - indexed for MEDLINE]

62: Rev Clin Esp. 2005 Sep;205(9):457-8. Related Articles, Links

[Patient with pleuritic pain and mediastinic mass]

[Article in Spanish]

Rodriguez Suarez PM, Santana Rodriguez N, Camacho Galan R, Freixinet Gilart J.

Servicio de Cirugia Toracica, Hospital Universitario de Gran Canaria Dr. Negrin, Las Palmas de Gran Canaria.

Publication Types:

Case Reports

PMID: 16194482 [PubMed - indexed for MEDLINE]

63: Toxicol Appl Pharmacol. 2005 Sep 1;207(2 Suppl):133-41. Related Articles, Links: "Fluorescent Cell Chip" for immunotoxicity testing: Development of the c-fos expression reporter cell lines.

Trzaska D, Zembek P, Olszewski M, Adamczewska V, Ulleras E, Dastych J.

International Institute of Molecular and Cell Biology, Warsaw, Poland.

The Fluorescent Cell Chip for in vitro immunotoxicity testing employs cell lines derived from lymphocytes, mast cells, and monocytes-macrophages transfected with various EGFP cytokine reporter gene constructs. While cytokine expression is a valid endpoint for in vitro immunotoxicity screening, additional marker for the immediate-early response gene expression level could be of interest for further development and refinement of the Fluorescent Cell Chip. We have used BW.5147.3 murine thymoma transfected with c-fos reporter constructs to obtain reporter cell lines expressing ECFP under the control of murine c-fos promoter. These cells upon serum withdrawal and readdition and incubation with heavy metal compounds showed paralleled induction of c-Fos expression as evidenced by Real-Time PCR and ECFP fluorescence as evidenced by computer-supported fluorescence microscopy. In conclusion, we developed fluorescent reporter cell lines that could be employed in a simple and time-efficient screening assay for possible action of chemicals on c-Fos expression in lymphocytes. The evaluation of usefulness of these cells for the Fluorescent Cell Chip-based detection of immunotoxicity will require additional testing with a larger number of chemicals.

PMID: 16023160 [PubMed - in process]

64: Wien Klin Wochenschr. 2005 Sep;117(18):620-7. Related Articles, Links: [Thymoma]

[Article in German]

Gripp S, Bolke E, Orth K.

Klinik fur Strahlentherapie, Universitatsklinikum Dusseldorf, Dusseldorf, Deutschland. gripp@uni-duesseldorf.de

Thymoma is a rare epithelial tumor of the thymus, but the most common malignancy in the anterior mediastinum. A unique feature is its association with paraneoplastic syndromes, in particular myasthenia gravis. According to the WHO classification 6 histologic types of thymic epithelial tumors can be discriminated. Tumor stage according to MASAOKA is the most important prognostic factor. Non-invasive tumors (stage I) are usually completely resected and no further therapy is warranted. For incompletely resected tumors and locally advanced invasive thymomas (stage Ill-IV) postoperative radiotherapy with 50-60 Gy is advisable. Chemotherapy, preferably with Cisplatinum, is indicated with inoperable thymomas or metastatic disease. In general thymomas have a fair prognosis even in advanced stage. Long term follow-up is mandatory up to 10 years.

PMID: 16416343 [PubMed - in process]

65: Acta Neurol Scand. 2005 Aug;112(2):108-14. Related Articles, Links: Factors influencing the outcome of transsternal thymectomy for myasthenia gravis.

Huang CS, Hsu HS, Huang BS, Lee HC, Kao KP, Hsu WH, Huang MH.

Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan.

BACKGROUND: Thymectomy is one of the current treatment strategies for patients with myasthenia gravis (MG); however, the selection criteria for surgery remain controversial. METHODS: The demographic data and the surgical results of 168 patients with MG who underwent transsternal thymectomy from June 1986 to December 2000 were retrospectively reviewed. Follow-up information was obtained by review of the hospital records or telephone contact. The postoperative status of MG was assessed at the interval of 1, 3 and 6 months and then annually. The complete remission rate (CRR) between groups was compared. RESULTS: A total of 168 patients, including 69 male patients and 99 female patients, with a mean age of 38.3 years (range 13-80 years), were analyzed. The symptom duration before operations was from 1 to 312 months with a mean of 33.8 months. Complete follow-up information was obtained on 154 patients (91.6%) with a mean follow-up duration of 98.9 months. Complete remission was achieved in 89 of 154 patients (57.8%) and marked clinical improvement in 47 patients (30.5%). Total improvement rate was 88.3%. Seventeen of 24 patients (70.8%) with ocular MG and 18 of 35 patients (51.4%) with thymoma had reached complete remission during the follow-up period. The CRR increased with each consecutive year and reached the plateau in the fourth postoperative year. There was no surgical mortality. The complication rate was 16.6%. Univariate analysis demonstrated that age <35 years old (P = 0.0001), symptom duration before operation <24 months (P = 0.01) and absence of preoperative steroid treatment (P = 0.04) were favorable prognostic factors. Multivariate Cox regression analysis revealed age <35 years old (odds ratio = 3.645, P = 0.001), symptom duration before operation <24 months (2.311, P = 0.041) were favorable prognostic factors for patients having transsternal thymectomy. CONCLUSIONS: Transsternal thymectomy is feasible in the management of patients with MG at all stages with high improvement rate and low surgical morbidity. Those patients aged 35 years or less at operation, with symptoms developed <24 months before operation, may benefit more from thymectomy. MG patients with thymoma did as well as patients without thymoma, and 18 of 35 patients with thymoma had reached complete remission during the follow-up period. Thymectomy seems to be beneficial also for ocular MG.

PMID: 16008537 [PubMed - indexed for MEDLINE]

66: Ann Rheum Dis. 2005 Aug;64(8):1238-40. Related Articles, Links

An unusual presentation of Wegener's granulomatosis mimicking thymoma.

Wang CR, Chang JM, Shen WL, Lin WJ, Lee JY, Liu MF.

Publication Types:

PMID: 16014689 [PubMed - indexed for MEDLINE]

67: Ann Thorac Surg. 2005 Aug;80(2):741-2. Related Articles, Links: Papillary carcinoma of the thymus gland.

Yoshino M, Hiroshima K, Motohashi S, Shibuya K, Iyoda A, Sekine Y, Fujisawa T.

Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.

In 1999, the World Health Organization introduced a new classification of a rare thymic cancer called papillary adenocarcinoma of the thymus gland. In this study we report on a case of papillary thymic carcinoma in a 29-year-old woman. Histologically, the tumor consisted of a papillary component admixed with a solid component, a component that is commonly found in type A thymoma.

PMID: 16039252 [PubMed - in process]

68: Ann Thorac Surg. 2005 Aug;80(2):739-41. Related Articles, Links: Stiff man syndrome with thymoma.

Tanaka H, Matsumura A, Okumura M, Kitaguchi M, Yamamoto S, Iuchi K.

Department of Surgery, National Kinki Central Hospital for Chest Diseases, Osaka, Japan. h-tanaka@kch.hosp.go.jp

Paraneoplastic stiff man syndrome with a thymoma is rare disease. We treated a 57-year-old woman with a type B1 thymoma, based on the World Health Organization classification, who had stiff man syndrome. Her symptoms were alleviated after a thymectomy. Herein we report a case of stiff man syndrome with a thymoma and also review three cases reported previously.

PMID: 16039251 [PubMed - in process]

69: Brain. 2005 Aug;128(Pt 8):1764-77. Epub 2005 May 11. Related Articles, Links

Comment in:

Brain. 2005 Aug;128(Pt 8):1745-6.

Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates.

Ances BM, Vitaliani R, Taylor RA, Liebeskind DS, Voloschin A, Houghton DJ, Galetta SL, Dichter M, Alavi A, Rosenfeld MR, Dalmau J.

Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.

We report seven patients, six from a single institution, who developed subacute limbic encephalitis initially considered of uncertain aetiology. Four patients presented with symptoms of hippocampal dysfunction (i.e. severe short-term memory loss) and three with extensive limbic dysfunction (i.e. confusion, seizures and suspected psychosis). Brain MRI and [(18)F]fluorodeoxyglucose (FDG)-PET complemented each other but did not overlap in 50% of the patients. Combining both tests, all patients had temporal lobe abnormalities, five with additional areas involved. In one patient, FDG hyperactivity in the brainstem that was normal on MRI correlated with central hypoventilation; in another case, hyperactivity in the cerebellum anticipated ataxia. All patients had abnormal CSF: six pleocytosis, six had increased protein concentration, and three of five examined had oligoclonal bands. A tumour was identified and removed in four patients (mediastinal teratoma, thymoma, thymic carcinoma and thyroid cancer) and not treated in one (ovarian teratoma). An immunohistochemical technique that facilitates the detection of antibodies to cell surface or synaptic proteins demonstrated that six patients had antibodies to the neuropil of hippocampus or cerebellum, and one to intraneuronal antigens. Only one of the neuropil antibodies corresponded to voltage-gated potassium channel (VGKC) antibodies; the other five (two with identical specificity) reacted with antigens concentrated in areas of high dendritic density or synaptic-enriched regions of the hippocampus or cerebellum. Preliminary characterization of these antigens indicates that they are diverse and expressed on the neuronal cell membrane and dendrites; they do not co-localize with VGKCs, but partially co-localize with spinophilin. A target autoantigen in one of the patients co-localizes with a cell surface protein involved in hippocampal dendritic development. All patients except the one with antibodies to intracellular antigens had dramatic clinical and neuroimaging responses to immunotherapy or tumour resection; two patients had neurological relapse and improved with immunotherapy. Overall, the phenotype associated with the novel neuropil antibodies includes dominant behavioural and psychiatric symptoms and seizures that often interfere with the evaluation of cognition and memory, and brain MRI or FDG-PET abnormalities less frequently restricted to the medial temporal lobes than in patients with classical paraneoplastic or VGKC antibodies. When compared with patients with VGKC antibodies, patients with these novel antibodies are more likely to have CSF inflammatory abnormalities and systemic tumours (teratoma and thymoma), and they do not develop SIADH-like hyponatraemia. Although most autoantigens await characterization, all share intense expression by the neuropil of hippocampus, with patterns of immunolabelling characteristic enough to suggest the diagnosis of these disorders and predict response to treatment.

PMID: 15888538 [PubMed - indexed for MEDLINE]

70: Cell Signal. 2005 Aug;17(8):961-73. Epub 2004 Dec 24. Related Articles, Links: CD44v6 promotes proliferation by persisting activation of MAP kinases.

Marhaba R, Bourouba M, Zoller M.

Department of Tumor Progression and Tumor Defense, German Cancer Research Center, Heidelberg.

CD44v6 is transiently expressed during T cell activation, and constitutively CD44v4-v7 expressing transgenic T cells show accelerated responses towards nominal antigens. The underlying mechanism is unknown. The mouse thymoma EL4 was transfected with CD44 standard isoform (CD44s) or CD44v6 cDNA (EL4-s, EL4-v6). Only EL4-v6 cells proliferated at an over 10-fold higher rate than untransfected cells, displayed up-regulated expression of CD69, CD25, and IL-2, and were protected from apoptosis by CD44v6 cross-linking. In the absence of any stimulus, ERK1/2 was partly phosphorylated, and phosphorylation was significantly increased by CD44v6 cross-linking. The same accounted for JNK, c-jun, and IkappaBalpha. Moreover, NF-kappaB was partly translocated into the nucleus. Instead, CD44s cross-linking induced ERK1/2, JNK, c-jun, and IkappaBalpha phosphorylation only in the context of TCR engagement. No selectively CD44v6 associated transmembrane proteins were uncovered in EL4 cells. However, CD44v6, as opposed to CD44s, did not colocalise with the TCR/CD3 complex after CD3 cross-linking. Furthermore, a CD44-associated 85-kDa protein became hypophosphorylated only after CD44v6 cross-linking. Threonine hypophosphorylation of this protein coincided with the activation of MAP and SAP kinases, which was prohibited in the presence of a phosphatase inhibitor. Thus, CD44v6, distinct to CD44s, stimulates autonomously growth and IL-2 secretion of a thymoma line and rescues cells from apoptosis.

PMID: 15894169 [PubMed - indexed for MEDLINE]

71: J Immunol. 2005 Aug 1;175(3):1694-705. Related Articles, Links

Erratum in:

J Immunol. 2005 Nov 1;175(9):6238.

Runx3 regulates integrin alpha E/CD103 and CD4 expression during development of CD4-/CD8+ T cells.

Grueter B, Petter M, Egawa T, Laule-Kilian K, Aldrian CJ, Wuerch A, Ludwig Y, Fukuyama H, Wardemann H, Waldschuetz R, Moroy T, Taniuchi I, Steimle V, Littman DR, Ehlers M.

Institute of Molecular Biology (Cancer Research), University of Essen, Medical School, Essen, Germany.

During thymic T cell development, immature CD4+CD8+ double-positive (DP) thymocytes develop either into CD4+CD8- Th cells or CD4-CD8+ CTLs. Differentially expressed primary factors inducing the fate of these cell types are still poorly described. The transcription factor Runx3/AML-2 Runx, runt [corrected] dominant factor; AML, acute myeloid leukemia is expressed specifically during the development of CD8 single-positive (SP) thymocytes, where it silences CD4 expression. Deletion of murine Runx3 results in a reduction of CD8 SP T cells and concomitant accumulation of CD4+CD8+ T cells, which cannot down-regulate CD4 expression in the thymus and periphery. In this study we have investigated the role of Runx3 during thymocyte development and CD4 silencing and have identified integrin alpha(E)/CD103 on CD8 SP T cells as a new potential target gene of Runx3. We demonstrate that Runx3 is necessary not only to repress CD4, but also to induce CD103 expression during development of CD8 SP T cells. In addition, transgenic overexpression of Runx3 reduced CD4 expression during development of DP thymocytes, leading to a reduced number of CD4 SP thymocytes and an increased number of CD8 SP thymocytes. This reversal is not caused by redirection of specific MHC class II-restricted cells to the CD8 lineage. Overexpression of Runx3 also up-regulated CD103 expression on a subpopulation of CD4 SP T cells with characteristics of regulatory T cells. Thus, Runx3 is a main regulator of CD4 silencing and CD103 induction and thus contributes to the phenotype of CD8 SP T cells during thymocyte development.

PMID: 16034110 [PubMed - indexed for MEDLINE]

72: J Nutr. 2005 Aug;135(8):1859-64. Related Articles, Links: Curcumin blocks interleukin-1 (IL-1) signaling by inhibiting the recruitment of the IL-1 receptor-associated kinase IRAK in murine thymoma EL-4 cells.

Jurrmann N, Brigelius-Flohe R, Bol GF.

German Institute of Human Nutrition, Potsdam-Rehbruecke, Biochemistry of Micronutrients, Nuthetal.

Curcumin is a dietary compound with diverse anti-inflammatory and anticarcinogenic effects in several experimental models. A mechanism by which curcumin exerts these actions might be the direct modification of protein thiols, thereby altering the activity of the affected proteins. An early event in inflammatory signaling cascades is the recruitment of the interleukin-1 (IL-1) receptor-associated kinase (IRAK) to the IL-1 receptor (IL-1RI) upon stimulation with IL-1. IRAK recruitment was shown recently to be inhibited by agents that modify thiols of IRAK. We asked, therefore, whether IRAK is also a target for curcumin. Curcumin indeed blocked IRAK thiols in a murine T-cell line stably overexpressing IRAK (EL-4(IRAK)), which resulted in the inhibition of IRAK recruitment to the IL-1RI and phosphorylation of IRAK and IL-1RI-associated proteins. Inhibitory effects were not reversible by thiol-reducing agents. Thus, modification by curcumin did not occur by oxidation but rather by alkylation, as is typical for electrophilic compounds reacting as Michael addition acceptors. The block in one of the earliest events in the IL-1 signaling cascade can explain the often observed inhibition of IL-1-mediated signaling steps by curcumin further downstream. Hence, thiol modification might be a crucial step in the anti-inflammatory functions of curcumin.

PMID: 16046709 [PubMed - indexed for MEDLINE]

73: J Otolaryngol. 2005 Aug;34(4):223-6. Related Articles, Links

Ectopic cervical thymoma in the submandibular region.

Bakshi J, Ghosh S, Pragache G, Vaiphei K, Gupta N.

Department of Otolaryngology, Head and Neck Surgery, Institute for Medical Education and Research, Chandigarh, India. drjayabakshi@yahoo.com

Publication Types:

PMID: 16048688 [PubMed - indexed for MEDLINE]

74: J Small Anim Pract. 2005 Aug;46(8):393-7. Related Articles, Links

Comment in:

J Small Anim Pract. 2005 Aug;46(8):369-70.

Recurrent bilateral exophthalmos associated with metastatic thymic carcinoma in a pet rabbit.

Wagner F, Beinecke A, Fehr M, Brunkhorst N, Mischke R, Gruber AD.

Department of Small Animal Medicine and Surgery, School of Veterinary Medicine Hannover, Bischofsholer Damm 15, 30173 Hannover, Germany.

A five-year-old, castrated, male chinchilla rabbit was presented for evaluation of recurrent bilateral exophthalmos. Besides a transient and stress-related exophthalmos with protrusion of both third eyelids, the ophthalmological examination was unremarkable. Plain radiography of the thorax revealed a large precardial mass of soft tissue density. Cytological preparations from the thoracic mass were dominated by small, mature lymphocytes with approximately 10 to 20 per cent lymphoblasts. Computed tomography of the head showed a symmetrical laterodorsal deviation of both eyes without evidence of retrobulbar masses. On necropsy a large cystic mass was present in the cranial thorax associated with severe hydrothorax, hydropericardium and ascites. Histology identified the precardial mass as thymic carcinoma with metastases in the kidneys. This case illustrates the difficulty of diagnosing thymic tumours based on cytological or histological features of the primary tumour alone. To the authors' knowledge, this is the first case of recurrent bilateral exophthalmos associated with a metastatic thymic carcinoma in a pet rabbit.

Publication Types:

Case Reports

PMID: 16119059 [PubMed - indexed for MEDLINE]

75: Lancet Oncol. 2005 Aug;6(8):626-8. Related Articles, Links

Non-myeloablative allogeneic haemopoietic stem-cell transplantation for treatment of metastatic invasive thymoma.

Numata A, Yasuda K, Fukuda T, Baba E, Yamasaki S, Takase K, Miyamoto T, Nagafuji K, Nakano S, Harada M.

First Department of Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.

Publication Types:

Case Reports

PMID: 16054574 [PubMed - indexed for MEDLINE]

76: South Med J. 2005 Aug;98(8):836-8. Related Articles, Links

Thymoma-associated hypocalcemic crisis.

McHayleh W, Kressel B, Nylen ES.

Department of Medicine and Endocrinology, George Washington University Medical Center, Washington, DC, USA.

A previously healthy male was diagnosed with a malignant thymoma. During the workup, he had syncope, which was due to severe unrecognized hypocalcemia. Additional workup was suggestive of parathyroid failure. In particular, there was no evidence of autoimmune parathyroid failure due to antibodies against the calcium-sensing receptor. Literature review reveals one additional thymoma case with these clinical features of chronic hypoparathyroidism of unknown cause.

Publication Types:

PMID: 16144186 [PubMed - indexed for MEDLINE]

77: Vet Dermatol. 2005 Aug;16(4):281-4. Related Articles, Links

Thymoma-associated exfoliative dermatitis in a rabbit.

Florizoone K.

Small Animal Practice Het Binnenhof, Bisschopslaan 68, B-2340 Beerse, Belgium. koenraadflorizoone@hotmail.com

A 5-year-old rabbit with generalized scaling is presented. Multiple skin scrapings and acetate tape impressions were negative for mites and Malassezia. Culture for dermatophytes was also negative. Skin biopsies showed similarities with sebaceous adenitis described in rabbits (absence of sebaceous glands, perifollicular lymphocytic infiltrate at the level of the absent sebaceous glands, lymphocytic mural folliculitis, interface dermatitis). The owners refused any treatment and 2 months later the rabbit was euthanized due to anorexia. At necropsy a mass was found in the anterior mediastinum. Histopathology confirmed a diagnosis of thymoma. A possible paraneoplastic skin disease was suspected, based on similarities with thymoma-associated exfoliative dermatitis in cats.

Publication Types:

Case Reports

PMID: 16101800 [PubMed - indexed for MEDLINE]

78: J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Jul 25;821(2):181-7. Related Articles, Links: Determination of intracellular concentrations of the TRPM2 agonist ADP-ribose by reversed-phase HPLC.

Gasser A, Guse AH.

University Medical Center Hamburg-Eppendorf, Center of Experimental Medicine, Institute of Biochemistry and Molecular Biology I: Cellular Signal Transduction, Martinistr. 52, 20246 Hamburg, Germany.

Since the NAD metabolite ADP-ribose (ADPR) has recently gained attention as a putative messenger, a method was established for the quantification of intracellular ADPR by reversed-phase HPLC. Cellular nucleotides were extracted with trichloroacetic acid, and crude cell extracts purified by solid phase extraction using a strong anion exchange matrix. After optimization of the extraction procedure, cellular ADPR levels were determined using two different reversed-phase columns (C18 versus C12), operated in ion pair mode. Intracellular ADPR concentrations in human Jurkat T-lymphocytes and murine BW5147 thymocytes were determined to be 44+/-11 microM and 73+/-11 microM, respectively.

PMID: 15921966 [PubMed - indexed for MEDLINE]

79: Nippon Hoshasen Gijutsu Gakkai Zasshi. 2005 Jul 20;61(7):942-50. Related Articles, Links

[A key to thorax MR imaging]

[Article in Japanese]

Fujita I.

Publication Types:

Review

PMID: 16049401 [PubMed - indexed for MEDLINE]

80: Clin Cancer Res. 2005 Jul 15;11(14):5078-83. Related Articles, Links: Analysis of cell cycle regulator proteins in encapsulated thymomas.

Baldi A, Ambrogi V, Mineo D, Mellone P, Campioni M, Citro G, Mineo TC.

Department of Thoracic Surgery, Tor Vergata University, Rome, Italy. alfonsobaldi@tiscali.it

PURPOSE: Although survival of encapsulated thymomas is usually good, some patients present a higher incidence rate of recurrence and a shorter long-term survival. Abnormalities in the components of cell cycle checkpoints are extremely common among virtually all neoplasms. In this study, three components of the cell cycle machinery (i.e., p21, p27 and p53) were examined in a series of well-characterized encapsulated thymoma specimens to analyze coregulation and influence on recurrence and survival. EXPERIMENTAL DESIGN: Sixty-eight consecutive patients with thymoma were operated in our center from 1987 to 2000. Expression of p53, p21, and p27 was studied in specimens from 25 encapsulated thymomas using immunohistochemistry. Generic factors and gene expression influencing the probability of recurrence were studied. Positive expression was dichotomized defining positive when present in more than 5% of tumor cells. Mean follow up was 85.9 months; clinical data about recurrence were recorded. RESULTS: Univariate analysis suggests that positive p53 (P < 0.05), negative p21 (P = 0.01), and especially negative p27 expressions (P = 0.001) significantly correlate with poor prognosis for disease-free survival. Multivariate Cox regression analysis suggests that negative p27 immunohistology is the only significant variable for poor prognosis (P = 0.03; odds ratio, 0.08; 95% confidence interval, 0.01-0.88). CONCLUSIONS: These results show that loss of control of cell cycle checkpoints is a common occurrence in thymomas and support the idea that functional cooperation between different cell cycle inhibitor proteins constitutes another level of regulation in cell growth control and tumor suppression.

PMID: 16033820 [PubMed - indexed for MEDLINE]

81: Clin Rheumatol. 2005 Jul 12; [Epub ahead of print] Related Articles, Links: Malignant thymoma associated with mixed connective tissue disease: a case report.

Lin YC, Wu CC, Ou TT, Yen JH, Liu HW, Tsai WC.

Department of Internal Medicine, Rheumatology Unit, Kaohsiung Medical University Hospital, Kaohsiung City 807, Taiwan (R.O.C.), d10153@ms14.hinet.net.

Many autoimmune diseases have been reported to be associated with malignancy. Mixed connective tissue disease (MCTD), however, has rarely been associated with malignancy. Thymoma is one of the neoplasms often reported to be related to various immunological disorders. Among the types of thymoma defined by WHO, malignant thymoma (thymoma type C) is the one least reported to be associated with autoimmune disease. Here, we report a case of malignant thymoma with concurrent MCTD, which manifested with acrosclerosis, Raynaud's phenomenon, arthritis (synovitis), and a high titer of anti-ribonucleoprotein antibody.

PMID: 16010443 [PubMed - as supplied by publisher]

82: Acta Cytol. 2005 Jul-Aug;49(4):424-6. Related Articles, Links

Malignant melanoma of mediastinum misdiagnosed as a spindle cell thymoma in a fine needle aspirate: a case report.

Bavi P, Shet T, Gujral S.

Department of Pathology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India.

BACKGROUND: Malignant melanomas in the medastinum are extremely rare. Both primary melanomas and metastatic lesions from a primary elsewhere can occur in the mediastinum. Aspiration biopsy of a melanoma at this unusual site may pose problems in diagnosis. CASE: A 35-year-old woman presented with an anterior mediastinal mass. Cytologic smears were hemorrhaghic and revealed a loosely dispersed population of spindle cells with prominent nucleoli. In view of the location, the possibility of spindle cell thymoma was suggested on cytology. Subsequent histology revealed a malignant melanoma. CONCLUSION: This case stresses that the cytopathologist should keep in mind the remote differential diagnosis of a malignant melanoma while evaluating spindle cell neoplasms of the mediastinum, especially in tumors with prominent cell dispersal and with cells that have prominent nucleoli even without melanin pigment. Accurate diagnosis helps in evaluating patients and avoids unnecessary surgery when the lesion represents a metastasis to the mediastinum from a primary elsewhere.

Publication Types:

Case Reports

PMID: 16124173 [PubMed - indexed for MEDLINE]

83: Am J Pathol. 2005 Jul;167(1):129-39. Related Articles, Links: Increased toll-like receptor 4 expression in thymus of myasthenic patients with thymitis and thymic involution.

Bernasconi P, Barberis M, Baggi F, Passerini L, Cannone M, Arnoldi E, Novellino L, Cornelio F, Mantegazza R.

Department of Neurology IV, Istituto Nazionale Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy. pbernasconi@istituto-besta.it

Thymic abnormalities are present in approximately 80% of myasthenia gravis (MG) patients, and the thymus seems to be the main site of autosensitization to the acetylcholine receptor. In view of findings that the innate immune system can generate an autoimmune response, we studied the expression of Toll-like receptors (TLRs) 2 to 5, key components of innate immunity signaling pathways, in 37 thymuses from patients with autoimmune MG. TLR4 mRNA levels were significantly greater in thymitis (hyperplasia with diffuse B-cell infiltration) and involuted thymus than in germinal center hyperplasia and thymoma. By immunohistochemistry and confocal microscopy, cells positive for TLR4 protein were rarely detected in thymoma. However, in thymitis TLR4 protein was mostly found on epitheliomorphic (cytokeratin-positive) cells located in close association with clusters of acetylcholine receptor-positive myoid cells in thymic medulla and also at the borders between cortical and medullary areas. B cells were never TLR4-positive. TLR4 protein was also present in remnant tissue of involuted thymus. This is the first finding of a possible link between innate immunity and MG. We speculate that in a subgroup of MG patients, an exogenous or endogenous danger signal may activate the innate immune system and give rise to TLR4-mediated mechanisms contributing to autoimmunity.

PMID: 15972959 [PubMed - indexed for MEDLINE]

84: Carcinogenesis. 2005 Jul;26(7):1224-32. Epub 2005 Mar 10. Related Articles, Links: Effect of common B-RAF and N-RAS mutations on global gene expression in melanoma cell lines.

Bloethner S, Chen B, Hemminki K, Muller-Berghaus J, Ugurel S, Schadendorf D, Kumar R.

Division of Molecular Genetic Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.

We studied global gene expression in three melanoma cell lines with the most common and potent V600E mutation in the B-RAF gene-four cell lines with a common Q61R mutation in the N-RAS gene and three cell lines with no mutations using human HG-U133A 2.0 micro-arrays with 22 277 transcripts. Data analysis using stringent criteria revealed several upregulated and downregulated genes in cell lines with B-RAF and N-RAS mutations compared with cell lines without mutations. We found 29 genes specifically upregulated and 32 genes downregulated in cell lines with B-RAF mutations, whereas 70 genes were upregulated and 39 downregulated in cell lines with N-RAS mutations; 11 genes showed overlapping upregulation and 45 downregulation. The micro-array data for nine selected genes were validated by the real-time PCR technique. Expression of a large number of genes, that encode members or regulators of the RAS/RAF/MEK/ERK pathways or are involved in metastasis or invasion, was affected in cell lines with mutations in B-RAF and N-RAS. Upregulated genes in cell lines with mutations included dual-specificity phosphatase 6 (DUSP6), sprouty 2 (SPRY2), v-akt murine thymoma viral oncogene homolog 3 (AKT3) and matrix metalloproteinase 14 (MMP14); downregulated genes included interleukin 18 (IL18), Kruppel-like factor 5 (KLF5) and inhibitor of DNA binding 2 (ID2). Our results, though carried on cell lines, provide a novel insight into the effect of mutations in the B-RAF and N-RAS genes on global gene expression in melanoma and highlight the complexity of mechanisms involved in tumour initiation and maintenance.

PMID: 15760917 [PubMed - indexed for MEDLINE]

85: Chest. 2005 Jul;128(1):140-4. Related Articles, Links: Immunohistochemical KIT (CD117) expression in thymic epithelial tumors.

Nakagawa K, Matsuno Y, Kunitoh H, Maeshima A, Asamura H, Tsuchiya R.

Department of Pathology, National Cancer Center Hospital, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.

STUDY OBJECTIVES: It is sometimes very difficult both clinically and pathologically to distinguish thymic epithelial tumors from primary lung carcinoma with massive anterior mediastinal involvement. The expression of KIT (CD117) in thymic epithelial tumors was investigated in order to evaluate its usefulness as a marker supporting differential diagnosis and choice of therapy. METHODS: We examined the immunohistochemical expression of KIT in 70 resected thymic epithelial tumors (thymomas, 50; thymic carcinomas, 20) that had been reclassified on the basis of the World Health Organization histologic classification system. We also compared the expression of KIT and CD5 in 20 thymic carcinomas with their expression in 20 resected pulmonary squamous cell carcinomas that were spreading directly into the mediastinum. RESULTS: Of the 50 thymomas, only 2 (4%) showed positive immunoreactivity for KIT (type A thymoma, 1; type B3 thymoma, 1), whereas 16 of the 20 thymic carcinomas (80%) showed positive immunoreactivity. Testing was positive for CD5 in 14 of the 20 thymic carcinomas (70%). In the pulmonary squamous cell carcinomas, in contrast, the immunohistochemical expression of KIT and CD5 was found in only 4 of 20 carcinomas (20%) and 3 of 20 carcinomas (15%), respectively. Furthermore, of the 40 specimens examined (either thymic or lung carcinoma) all 13 that were positive for both KIT and CD5 were thymic carcinomas, and 13 of the 16 that were negative for both were lung carcinomas. CONCLUSION: KIT expression is a useful immunohistochemical marker for the diagnosis of thymic carcinoma, and its examination in combination with CD5 immunohistochemistry would greatly help in the differential diagnosis of primary thymic carcinoma from pulmonary squamous cell carcinoma. Further investigations at a genetic level should be encouraged, not only to define the role of KIT in the oncogenesis of thymic epithelial tumors, but also to establish target-based therapy.

PMID: 16002927 [PubMed - indexed for MEDLINE]

86: Eur J Cardiothorac Surg. 2005 Jul;28(1):22-5. Related Articles, Links

Myasthenia gravis appearing after thymectomy for thymoma.

Kondo K, Monden Y.

Department of Oncological and Regenerative Surgery, Institute of Health Biosciences, University of Tokushima Graduate School, Kuramoto-cho, Tokushima 770-8503, Japan. kondo@clin.med.tokushima-u.ac.jp

OBJECTIVE: A few thymoma patients without myasthenia gravis (MG) have been observed to develop MG after total removal of the thymoma (postoperative MG). However, the cause of this is not yet known because of the rarity of postoperative MG patients. This study evaluated the clinical characteristics of the 8 postoperative MG patients. METHODS: We compiled 1089 thymoma patients treated between 1990 and 1994 in 115 institutes in Japan, and found 8 cases of postoperative MG. RESULTS: Postoperative MG was found in 8 (0.97%) of 827 thymoma patients without preoperative MG. The postoperative MG patients included 1 male and 7 females, with a mean age of 50.5+/-15.0 years. The thymoma was completely resected in all cases. The surgical method used was extended thymectomy in 2 cases and thymothymectomy in 6 cases. There were 2 cases (0.7%) of postoperative MG in the extended thymectomy group (n = 275), 6 (1.9%) in the thymothymectomy group (n = 321), and none in the tumor resection group (n = 137). The interval between thymectomy and the onset of postoperative MG varied (6 days-45 months, 19.3+/-16.5 months). The type of MG was ocular in 2 cases and general in 5 cases, according to the modified Osserman classification. The postoperative MG was responsive to anti-cholinesterase compounds and/or steroids. The improvement rate was 86%. CONCLUSIONS: Postoperative MG was present in about 1% of the patients who underwent total thymoma resection. Resection of the thymus gland does not prevent postoperative MG.

Publication Types:

Multicenter Study

PMID: 15935686 [PubMed - indexed for MEDLINE]

87: Eur J Neurol. 2005 Jul;12(7):566-70. Related Articles, Links: Myasthenia gravis accompanied by alopecia areata: clinical and immunogenetic aspects.

Suzuki S, Shimoda M, Kawamura M, Sato H, Nogawa S, Tanaka K, Suzuki N, Kuwana M.

Department of Neurology, Keio University School of Medicine, Shinanomachi, Tokyo, Japan.

The purpose of this study was to evaluate the clinical characteristics of patients who had both myasthenia gravis (MG) and alopecia areata (AA). Clinical information was retrospectively collected for 159 Japanese patients with MG. Human leukocyte antigen (HLA)-DQB1 and DRB1 alleles were determined by genotyping. Of 159 MG patients, six (3.7%) developed AA after the onset of MG and thymectomy. The prevalence of AA in MG patients was higher than that reported in Caucasians. The frequencies of bulbar involvement, myasthenic crisis, and thymoma were significantly higher in MG patients with AA than in those without (P = 0.007, 0.004, and 0.006, respectively). All but one patient with AA had advanced stage thymoma. Three patients with a severe form of AA (alopecia totalis) had additional autoimmune diseases: myocarditis, myositis, and pure red cell aplasia. DRB1*0901 and DQB1*0303 tended to be more frequently detected in the six MG patients with AA than in the 82 patients without it. In conclusion, a subset of MG patients who have severe neuromuscular symptoms and thymoma develop AA several years after thymectomy.

PMID: 15958099 [PubMed - indexed for MEDLINE]

88: Eur Surg Res. 2005 Jul-Aug;37(4):199-203. Related Articles, Links: Bilateral video-assisted thoracoscopic thymectomy vs. extended transsternal thymectomy in myasthenia gravis: a prospective study.

Chang PC, Chou SH, Kao EL, Cheng YJ, Chuang HY, Liu CK, Lai CL, Huang MF.

Department of Surgery, Kaohsiung Medical University, Kaohsiung, Taiwan.

The optimal approach to thymectomy remains controversial. This study is designed to prospectively compare the results between bilateral video-assisted thoracoscopic thymectomy (BVTx) and extended transsternal thymectomy (ETTx) in patients with myasthenia gravis (MG) without thymoma. Fifteen patients who had undergone BVTx and 16 patients who had undergone ETTx were compared for age, gender, severity of disease, preoperative duration of disease, operative time, intraoperative blood loss, postoperative complications, hospital stay, duration of chest tube drainage, thymic histopathology, pain perception by visual analog scale (VAS), remission and improvement rate, period of follow-up, and activities of daily living (ADL). Fisher's exact test, t test and paired t test were used for statistical analysis. BVTx had longer operative time and less intraoperative blood loss than that of the ETTx. Their remission rates and their degree of postoperative ADL improvement were not significantly different. However, the lowering of VAS was significantly greater in the sternotomy group at 3 months. All other parameters were not significantly different. No mortality was noted in the series. We consider BVTx as an effective alternative procedure to the transsternal approach for patients with nonthymomatous MG. As more and more people care about cosmetics, BVTx could become the future trend. Copyright (c) 2005 S. Karger AG, Basel.

PMID: 16260868 [PubMed - in process]

89: Int J Radiat Oncol Biol Phys. 2005 Jul 1;62(3):942. Related Articles, Links

Comment on:

Int J Radiat Oncol Biol Phys. 2004 Nov 15;60(4):1113-9.

Treatment of thymoma and prognostic factors: In regard to Zhu et al. (Int J Radiat Oncol Biol Phys 2004;60:1113-1119).

Altundag K, Morandi P, Altundag O, Yigitbasi OG.

Publication Types:

PMID: 15936584 [PubMed - indexed for MEDLINE]

90: J La State Med Soc. 2005 Jul-Aug;157(4):183-6. Related Articles, Links

A middle-aged woman with an anterior mediastinal mass and respiratory failure.

Saavedra MC, Culotta R, Kamboj S, Chaney S, Lopez FA.

Louisiana State University School of Medicine, New Orleans, USA.

The discovery of an anterior mediastinal mass presents a challenge to the physician. In addition to distinguishing between benign and malignant conditions, it is important to recognize the potential for associated paraneoplastic phenomena. We present a case of a malignant thymoma associated with myasthenia gravis.

Publication Types:

Case Reports

PMID: 16250367 [PubMed - indexed for MEDLINE]

91: J Neuroimmunol. 2005 Jul;164(1-2):124-8. Related Articles, Links: Decreased frequency of intrathymic regulatory T cells in patients with myasthenia-associated thymoma.

Luther C, Poeschel S, Varga M, Melms A, Tolosa E.

Department of General Neurology, Hertie Institute for Clinical Brain Research, Tuebingen University Hospital, Otfried-Muller-Strasse 27, D-72076 Tuebingen, Germany.

Naturally occurring CD4+CD25+ regulatory T cells (Treg) are essential for the control of unwanted autoimmune responses. In this study, we analysed their frequency in peripheral blood and in the thymus/thymomas of patients with myasthenia gravis (MG). We found a marked decrease in the number of CD4+CD25+ thymocytes in MG-associated thymomas, but no differences in the peripheral compartment, suggesting that the thymic development of Treg might be impaired in these patients.

PMID: 15923045 [PubMed - indexed for MEDLINE]

92: J Nucl Cardiol. 2005 Jul-Aug;12(4):473-5. Related Articles, Links

Pathologic extracardiac uptake of Tc-99m tetrofosmin identified in the chest during myocardial perfusion imaging.

Vijayakumar V, Gupta R, Rahman A.

Nuclear Medicine Section, Department of Radiology, University of Texas Medical Branch, Clinical Science Building, 301 University Boulevard, Galveston, TX 77555, USA. vavijaya@utmb.edu

Publication Types:

Case Reports

PMID: 16084437 [PubMed - indexed for MEDLINE]

93: Kyobu Geka. 2005 Jul;58(8 Suppl):739-44. Related Articles, Links

[Thymoma in elderly patients]

[Article in Japanese]

Yano M, Fujii Y.

Department of Oncology, Immunology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

One hundred and twenty-three cases with primary thymoma have undergone an operation from 1972. Sixteen elderly patients (over 70 years old) were compared with 107 young patients in clinical appearance, pathological findings and outcome. There were no differences in Masaoka's classification, World Health Organization (WHO) pathological classification and frequency of complications as myasthenia gravis in both groups. In elderly patients different kinds of neoplasms often occurred during follow-up periods compared to in young patients. In both groups, basically policy of treatment is same. In the case of stage I or II, (extended) thymothymomectomy is performed. In the case of stage IIl, partial resection of invaded surrounding organs is added. We often perform preoperative corticosteroid therapy to shrink the tumor. In the case of stage IV a with pleural dissemination, thymothymomectomy with resection of all dissemination lesions is performed. The case with widespread invasion to pericardium and pericardial dissemination are considered as inoperable and undergo chemoradiotherapy. Postoperatively radiotherapy is added in the case of stage III and IV. In elderly patients 5 and 10 year survival rates were 60.2 and 48.1%. These were significantly worse compared to young patients. It depended on postoperative complications as sternomyelitis and different kinds of critical complications.

Publication Types:

Review

PMID: 16097629 [PubMed - indexed for MEDLINE]

94: Lab Invest. 2005 Jul;85(7):851-61. Related Articles, Links: Malignant transformation of thymoma in recipient rats by heterotopic thymus transplantation from HTLV-I transgenic rats.

Tsuji T, Ikeda H, Tsuchikawa T, Kikuchi K, Baba T, Ishizu A, Yoshiki T.

Department of Pathology/Pathophysiology, Division of Pathophysiological Science, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.

Transgenic rats expressing the pX gene of human T lymphocyte virus type-I (HTLV-I) under control of the rat lymphocyte-specific protein tyrosine kinase type-I promoter (lck-pX rats) developed benign epithelial thymomas. When the thymuses of newborn lck-pX rats were transplanted into the subcapsular space of the kidney in other thymectomized lck-pX rats, similar tumors developed in the transplanted thymuses. Following the tumor growth, dissemination in the abdominal cavity and distant metastasis occurred. The tumors were histopathologically similar to the original thymomas, but prominent nuclear atypia and high mitotic activity were present. The Ki-67 index was twice as high as that in the originals. The tumors were transplantable into the subcutis of lck-pX rats, although transplantation of the originals never succeeded. All evidence indicated that malignant transformation of thymoma was induced by the heterotopic transplantation. Expression of the pX transgene in the transformed tumors were significantly reduced. Among host genes, the expression of p16ink4a/ARF, which was significantly upregulated in the originals, was never detected in the transformed tumors. Genomic Southern blots and PCR suggest that homozygous deletion of the p16ink4a/ARF gene may play important roles in malignant transformation in this model. Our model described here is a useful unique model for in vivo malignant transformation.

PMID: 15924152 [PubMed - indexed for MEDLINE]

95: Pediatr Surg Int. 2005 Jul;21(7):548-51. Epub 2005 May 31. Related Articles, Links

Thymoma in a child: case report and review of the literature.

Rothstein DH, Voss SD, Isakoff M, Puder M.

Department of Surgery, Children's Hospital and the Harvard Medical School, NRB 11213, Boston, MA 02115, USA.

Thymic lesions comprise approximately 2-3% of all pediatric mediastinal tumors and include thymic cysts, hyperplasia, carcinoma, and thymomas. Thymomas, which represent less than 1% of all mediastinal tumors, are rare mediastinal tumors in the pediatric population. Fewer than 30 cases in children have been described in the literature. These tumors are typically aggressive, with poor outcomes. We report a thymoma in a 14-year-old girl and review the available literature on thymomas and their treatment.

Publication Types:

PMID: 15926048 [PubMed - indexed for MEDLINE]

96: Tumori. 2005 Jul-Aug;91(4):361-3. Related Articles, Links

Fatal immunodeficiency in a patient with thymoma and Good's syndrome.

Montella L, Merkabaoui G, Vitiello L, Bulgarelli G, Sinagra G, Masci AM, Racioppi L, Palmieri G.

Medical Oncology Unit, "S Giovanni di Dio" Hospital, Frattaminore, Naples, Italy. limontel@libero.it

Thymoma is a rare tumor characterized by an association with autoimmune diseases. Immunological abnormalities are increasingly being recognized in thymoma patients and are the cause of a peculiar susceptibility to infections. The authors present the clinical history of a thymoma patient affected by fatal immunodeficiency.

Publication Types:

Case Reports

PMID: 16277106 [PubMed - indexed for MEDLINE]

97: Zhonghua Bing Li Xue Za Zhi. 2005 Jul;34(7):397-401. Related Articles, Links: [Ectopic hamartomatous thymoma: a clinicopathological and immunohistochemical study of two cases]

[Article in Chinese]

Wang J, Zhang RY.

Department of Pathology, Cancer Hospital, Fudan University, Shanghai 200032, China.

OBJECTIVE: To study the clinicopathological and immunohistochemical features of ectopic hamartomatous thymoma (EHT), and to discuss its histogenesis. METHODS: The clinical and pathologic features of two EHT cases of were evaluated. Immunohistochemical study was performed by LSAB method using a panel of antibodies including AE1/AE3, CK5, CK7, CK8, CK20, EMA, vimentin, CD5, CD10, alpha-SMA, calponin, desmin, CD34, S-100 protein, CD57, GFAP, TTF-1 and CD99. RESULTS: Both cases occurred in males aged 20 years and 40 years respectively. Each patient presented with a solitary mass, one located in the suprasternal fossa and the other in the left supraclavicular region for a period of 6 months and 2 months respectively. Grossly, the masses were well-circumscribed with spherical and ovoid appearance, measuring 5 cm and 3 cm in maximum diameter respectively. On cut section, they were gray-white in color and of soft consistency. Histologically, both tumors were composed of a mixture of spindle cells, epithelial cells and mature adipose tissue. The spindle cells element accounted 85% and 70% each in the two cases. They resembled fibroblasts in morphology and were arranged frequently in fascicular, woven or storiform patterns. Epithelial cells element represented nearly 10% in both cases. Most of the epithelial cells had a non-keratinization squamous appearance. They formed small solid islands and adamantinoma-like "nastomosing cords", or appeared as lining cells in large cystic spaces. In focal areas, glandular differentiation presented as small glands. A transition between the spindle cell and epithelium components could be also identified in some areas. Mature adipose tissue was irregularly distributed in the two tumors, about < 5% and 20% respectively. Immunohistochemically, the epithelial element expressed AE1/AE3, CK5, CK7, CK8 and EMA, whereas the spindle component expressed AE1/AE3, CK5, CK7, CK8, vimentin, CD10, CD34, alpha-SMA, MSA, and calponin. Both elements were negative for CK20, TTF-1, desmin, S-100 protein, CD57, GFAP and CD99. CONCLUSIONS: EHT is a benign tumor that occurs predominantly in the lower neck region of young to middle-aged males. Immunohistochemical study revealed myoepithelial differentiation of the spindle cells, suggesting EHT is a mixed tumor composed of epithelial and myoepithelial cells. EHT possibly originates from the remnants of cervical sinus of His, and therefore, may be renamed as branchial anlage mixed tumor.

PMID: 16251042 [PubMed - in process]

98: Biochem Biophys Res Commun. 2005 Jun 24;332(1):279-87. Related Articles, Links: Cellular trafficking of the IL-1RI-associated kinase-1 requires intact kinase activity.

Bol GF, Jurrmann N, Brigelius-Flohe R.

German Institute of Human Nutrition Potsdam-Rehbruecke, Biochemistry of Micronutrients, 14558 Nuthetal, Germany. boel@mail.dife.de

Upon stimulation of cells with interleukin-1 (IL-1) the IL-1 receptor type I (IL-1RI) associated kinase-1 (IRAK-1) transiently associates to and dissociates from the IL-1RI and thereafter translocates into the nucleus. Here we show that nuclear translocation of IRAK-1 depends on its kinase activity since translocation was not observed in EL-4 cells overexpressing a kinase negative IRAK-1 mutant (EL-4(IRAK-1-K239S)). IRAK-1 itself, an endogenous substrate with an apparent molecular weight of 24kDa (p24), and exogenous substrates like histone and myelin basic protein are phosphorylated by nuclear located IRAK-1. Phosphorylation of p24 cannot be detected in EL-4(IRAK-1-K239S) cells. IL-1-dependent recruitment of IRAK-1 to the IL-1RI and subsequent phosphorylation of IRAK-1 is a prerequisite for nuclear translocation of IRAK-1. It is therefore concluded that intracellular localization of IRAK-1 depends on its kinase activity and that IRAK-1 may also function as a kinase in the nucleus as shown by a new putative endogenous substrate.

PMID: 15896328 [PubMed - indexed for MEDLINE]

99: Ann Pathol. 2005 Jun;25(3):245-6. Related Articles, Links

[A rare but distinctive soft tissue tumour]

[Article in French]

Wilt M, Rodier JF, Ghnassia JP.

Service d'Anatomie Pathologique, Centre Paul Strauss, Strasbourg. MWilt@strasbourg.fnclcc.fr

Publication Types:

Case Reports

PMID: 16230953 [PubMed - indexed for MEDLINE]

100: Ann Thorac Surg. 2005 Jun;79(6):1834-9. Related Articles, Links: Adjuvant radiation of stage III thymoma: is it necessary?

Mangi AA, Wain JC, Donahue DM, Grillo HC, Mathisen DJ, Wright CD.

Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.

BACKGROUND: The criteria for administration of adjuvant radiation therapy after thymoma resection remains controversial, and it is unclear whether patients with Masaoka stage III thymoma benefit from adjuvant radiation. The goal of this report was to determine whether or not this group benefits from radiation therapy in disease-specific survival and disease-free survival. METHODS: Case records of the Massachusetts General Hospital were retrospectively reviewed from 1972 to 2004. One hundred and seventy-nine patients underwent resection for thymoma, of which 45 had stage III disease. RESULTS: Forty-five stage III patients underwent resection and in 36 it was complete. Thirty-eight stage III patients received radiation therapy. Baseline prognostic factors between radiated and nonradiated groups were similar. The addition of adjuvant radiotherapy did not alter local or distant recurrence rates in patients with stage III thymoma. Disease-specific survival at 10 years in stage III patients who did not receive radiation was 75% (95% confidence interval, 32% to 100%) and in patients who did receive radiation therapy it was 79% (95% confidence interval, 64% to 94%) (p = 0.21). The most common site of relapse was the pleura. CONCLUSIONS: Most patients who have stage III thymoma undergo complete resection. Some patients enjoy prolonged disease-free survival without adjuvant radiation after resection of stage III thymoma. Radiation does not seem to prevent pleural recurrences when given after resection of stage III thymomas. The use of routine adjuvant radiation after a complete resection of stage III thymoma needs to be re-addressed. There may be a role for the use of chemotherapy to reduce pleural recurrences.

PMID: 15919266 [PubMed - in process]

101: Arch Mal Coeur Vaiss. 2005 Jun;98(6):680-3. Related Articles, Links

[Lympho-epithelial thymoma revealed by a cardiac tamponade]

[Article in French]

Genee O, Dumont P, Champagne De Labriolle A, Pacouret G, Lemarie E, Charbonnier B.

Unite de soins cardiaques intensifs, service de cardiologie A. o.genee@free.fr

The authors report the case of a 62 year old patient admitted for a tamponade, revealing a mixed lympho-epithelial thymoma with invasion of the pericardium, the aorta and of the pulmonary arteria. The histological diagnosis was confirmed by a surgical biopsy performed after emergency pericardiocentesis. A neoadjuvant chemotherapy was administered followed by incomplete surgical resection and then a post operative radiotherapy. A local relapse was diagnosed at one year follow up by CT scan and a second line chemotherapy was administered. No further relapse occurred and patient was alive at four years.

Publication Types:

Case Reports

PMID: 16007825 [PubMed - indexed for MEDLINE]

102: Asian Cardiovasc Thorac Ann. 2005 Jun;13(2):149-52. Related Articles, Links: Rearrangement of T-cell receptor beta and gamma genes in thymoma.

Nakajima J, Matsumoto J, Takeuchi E, Fukami T, Takamoto S.

Department of Cardiothoracic Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan. nakajima-tho@h.u-tokyo.ac.jp

To investigate the differentiation stage of tumor-infiltrating lymphocytes in thymoma tissue, we performed Southern blot analysis of T-cell receptor beta and gamma genes in thymomas resected from 19 patients. At the same time, we conducted flow cytometric analysis of T-cell surface markers and examined the clinicopathological features of the thymomas. We found that the incidence of T-cell receptor gamma gene rearrangement was significantly higher in Masaoka stage I thymomas (11 of 12 cases) than in stage II or III invasive thymomas (3 of 7 cases). Moreover, gamma gene rearrangement was observed in all 10 type AB and B1 thymoma specimens and in 4 of 6 type B2 thymoma specimens. The 2 specimens of type B3 thymomas, which were classified as stage III, showed neither gamma nor beta gene arrangement and were single-positive for CD4 or CD8. Six thymoma specimens that showed beta gene rearrangement expressed both CD4 and CD8. In conclusion, thymomas have the capability of T-lineage cell differentiation, except for a subset of invasive thymomas with malignant characteristics.

PMID: 15905344 [PubMed - indexed for MEDLINE]

103: Autoimmun Rev. 2005 Jun;4(5):264-9. Epub 2004 Nov 13. Related Articles, Links

Intravenous immunoglobulins in autoimmune- or parvovirus B19-mediated pure red-cell aplasia.

Mouthon L, Guillevin L, Tellier Z.

Department of Internal Medicine, Hopital Cochin, Assistance Publique-Hopitaux de Paris and Universite Paris V, 27 rue du Faubourg Saint Jacques, 75679 Paris Cedex 14, France. luc.mouthon@cch.ap-hop-paris.fr

Pure red-cell aplasia (PRCA) is defined as the absence of mature erythroid precursors in a bone marrow that otherwise exhibit normal cellularity. Acquired PRCA may occur in association with neoplasms (such as lymphoproliferative disorders), thymoma, autoimmune disorders, pregnancy, or as a consequence of chronic human parvovirus B19 (B19) infection in an immunologically incompetent host. PRCA may also develop after exposure to drugs (erythropoietin or tacrolimus). PRCA of autoimmune origin was first treated successfully with intravenous immunoglobulins (IVIg) more than 20 years ago. Since then, B19-associated PRCA in solid-organ transplant recipients and in human immunodeficiency virus (HIV)-infected patients has also been successfully treated with IVIg. Routine maintenance therapy is probably not indicated in HIV-infected patients with CD4+ counts above 300/microL, whereas repeated infusions might be necessary if CD4+ count is below 80.

Publication Types:

Review

PMID: 15990072 [PubMed - indexed for MEDLINE]

104: Diagn Cytopathol. 2005 Jun;32(6):358-62. Related Articles, Links

Fine-needle aspiration biopsy of ectopic cervical spindle-cell thymoma: a case report.

Gerhard R, Kanashiro EH, Kliemann CM, Juliano AG, Chammas MC.

Department of Pathology, Hospital das Clinicas, University of Sao Paulo, Sao Paulo 05403-000, Brazil. regerhard@terra.com.br

In this report, we describe a case of ectopic cervical thymoma (medullary or type A thymoma, according to the WHO classification) located in the anterior cervical region (thyroid topography) that was submitted to ultrasound-guided fine-needle aspiration biopsy. The cytologic smears were moderately cellular to very cellular and were composed of numerous spindle-shaped cells placed predominantly in tissue fragments, with no specific arrangement. Isolated spindle-shaped cells were also present in a hemorrhagic background. The nuclei were elongated with finely granular chromatin and inconspicuous nucleoli. Mitosis, nuclear atypia, and necrosis were not detected. There was a scarce lymphoid population of small lymphocytes. The cytologic aspects, the correlation with histologic findings, and the differential cytologic diagnosis are reviewed.

Publication Types:

Case Reports

PMID: 15880711 [PubMed - indexed for MEDLINE]

105: Int Immunopharmacol. 2005 Jun;5(6):947-60. Epub 2005 Jan 25. Related Articles, Links: Systemic treatment with n-6 polyunsaturated fatty acids attenuates EL4 thymoma growth and metastasis through enhancing specific and non-specific anti-tumor cytolytic activities and production of TH1 cytokines.

Salem ML.

Department of Surgery, Section of Surgical Oncology, Holling Cancer Center R313, Medical University of South Carolina, Charleston, SC 29425, USA. salemm@musc.edu

Recently, there has been a great interest in the effects of different types of n-6 polyunsaturated acids (n-6 PUFAs) upon the immune system and cancer development. However, the effects of n-6 PUFAs are still controversial and as yet undefined. The present study aimed to investigate the anti-tumor effects of n-6 PUFAs against EL4 thymoma and the associated immune mechanisms. To this, sesame oil, a vegetable oil enriched with n-6 PUFAs, or free linoleic acid (LA) were administered intraperitoneally into C57BL/6 mice before and after challenge with EL4 lymphoma cells. Treatment with either sesame oil or LA attenuated the growth and metastasis of EL4 lymphoma. The anti-tumor effect of LA was superior to that of sesame oil, and associated with an increase in the survival rate of the tumor-bearing mice. In addition, both sesame oil and LA showed dose-dependent anti-lymphoma growth in vitro. Treatment with LA generated significant increases in the anti-lymphoma cytolytic and cytostatic activities of T cells and macrophages, respectively, and enhanced production of IL-2 and IFN-gamma while decreased production of IL-4, IL-6 and IL-10. In summation, the results suggest that n-6 PUFAs, represented by LA, can attenuate EL4 lymphoma growth and metastasis through enhancing the specific and non-specific anti-tumor cytolytic activities and production of TH1 cytokines. These findings might be of great importance for a proper design of systemic nourishment with PUFAs emulsions for cancer patients.

PMID: 15829411 [PubMed - indexed for MEDLINE]

106: Intern Med. 2005 Jun;44(6):572-7. Related Articles, Links

Increase in incidence of elderly-onset patients with myasthenia gravis in Nagano Prefecture, Japan.

Matsuda M, Dohi-Iijima N, Nakamura A, Sekijima Y, Morita H, Matsuzawa S, Sato S, Yahikozawa H, Tabata K, Yanagawa S, Ikeda S.

Third Department of Medicine, Shinshu University School of Medicine, Asahi, Matsumoto.

OBJECTIVES: In European countries and the United States the incidence of elderly-onset myasthenia gravis (MG) has recently been increasing. To investigate whether the incidence of the elderly-onset MG has increased in Nagano Prefecture of Japan, we divided the patients into young and elderly groups, and retrospectively examined their incidence. PATIENTS AND METHODS: On the basis of two-step questionnaires sent to hospitals and the patient list of the intractable disease registration system in Nagano Prefecture we studied 213 MG patients diagnosed between 1982 and 2001. This 20-year period was divided into 4 five-year terms, and the incidence of MG in young- (younger than 65) and elderly-onset (65 or older) groups was investigated separately for each term. RESULTS: The ratio of the elderly-onset group showed a significantly positive correlation with terms irrespective of associated thymoma (r=0.98, p<0.05). There was a significant difference in the mean onset age among the 4 terms (p<0.005). The standardized incidence of MG gradually increased in both young- and elderly-onset groups as well as in the whole age range. The elderly group showed a particularly high incidence in females (12.01/million/year) and in patients without thymoma (8.78/million/year) in the final five years. CONCLUSIONS: We confirmed that the incidence of elderly-onset MG has recently been increasing in the Nagano Prefecture. Since the change of the age distribution in this district is almost identical to that of the whole country, the incidence of MG might have been increasing in Japan as a whole, particularly in the elderly population.

Publication Types:

Multicenter Study

PMID: 16020882 [PubMed - indexed for MEDLINE]

107: J Microbiol Immunol Infect. 2005 Jun;38(3):218-20. Related Articles, Links

Thymoma and hypogammaglobulinemia (Good's syndrome): a case report.

Tsai YG, Lai JH, Kuo SY, Chen HC, Chang DM.

Department of Pediatrics, Christian Hospital, Institute of Medical Research, Chang Jung Christian University, Changhua, Taiwan.

Good's syndrome is extremely rare and refers to an acquired B and T cell immunodeficiency in thymoma patients. We report a 51-year-old female thymoma patient who presented with recurrent herpes zoster, pneumonia, diarrhea and opportunistic infections. She was found to have acquired hypogammaglobulinemia with absent B cells. Despite repeat intravenous immunoglobulin replacement and antibiotic therapy, she died of bacterial pneumonia-induced acute respiratory distress syndrome. Clinicians should look for evidence of immunologic dysfunction in thymoma patients presenting with recurrent infections.

Publication Types:

Case Reports

PMID: 15986073 [PubMed - indexed for MEDLINE]

108: J Radiol. 2005 Jun;86(6 Pt 1):693-4. Related Articles, Links

[Case #2: thoracic pathology: thymoma type A or medullary thymoma]

[Article in French]

Scherrer A.

Imagerie Medicale, CMC Foch, Suresnes.

Publication Types:

Case Reports

PMID: 16149200 [PubMed - indexed for MEDLINE]

109: J Surg Res. 2005 Jun 1;126(1):34-40. Related Articles, Links: Role of positive selection of thymoma-associated T cells in the pathogenesis of myasthenia gravis.

Inada K, Okumura M, Shiono H, Inoue M, Kadota Y, Ohta M, Matsuda H.

Department of Surgery, Division of General Thoracic Surgery, Osaka University Graduate School of Medicine, Suita-City, Osaka 565-0871, Japan.

BACKGROUND: A human thymoma is a thymic epithelial neoplasm and is characterized by its frequent association with myasthenia gravis. The histological characteristic of thymoma is coexistence of a large number of lymphocytes, including CD4(+)CD8(+) double positive T cells, phenotypes of the cortical thymocytes. To elucidate the role of these T lymphocytes in the pathogenesis of thymoma-associated myasthenia gravis, we examined the usage of alphabeta or gammadelta T cell receptor of the T lymphocytes in thymoma in conjunction with the positive selection event. MATERIALS AND METHODS: Thymomas were obtained from 28 patients. Nine patients were associated with myasthenia gravis. Lymphocytes were freshly isolated from the tumor tissue and were subjected to four-color flow cytometric analysis. RESULTS: The average proportion of TCRalphabeta(+) cells in thymomas associated with myasthenia gravis was 47.0% and was significantly higher (P = 0.0008) than that without myasthenia gravis (23.4%). Positive selection event was then examined in terms of CD69, a positive selection marker. The mean proportion of TCRalphabeta(+)CD69(+)CD4(+)CD8(-) cells in the myasthenic thymomas (8.22%) was significantly greater (P = 0.015) than the nonmyasthenic thymomas (2.99%). On the other hand, there was not a significant difference in the mean proportion of TCRalphabeta(+)CD69(+)CD4(-)CD8(+) cells between the myasthenic and the nonmyasthenic thymomas. CONCLUSIONS: The possible role of development of TCRalphabeta(+) T cells, especially the role of positive selection of TCRalphabeta(+)CD4(+)CD8(-) T cells in thymoma, was suggested in the pathogenesis of thymoma-associated myasthenia gravis.

PMID: 15916972 [PubMed - indexed for MEDLINE]

110: Nephrol Dial Transplant. 2005 Jun;20(6):1075-82. Epub 2005 Mar 23. Related Articles, Links

Renal and thymic pathology in thymoma-associated nephropathy: report of 21 cases and review of the literature.

Karras A, de Montpreville V, Fakhouri F, Grunfeld JP, Lesavre P; Groupe d'Etudes des Nephropathies Associees aux Thymomes.

Service de Nephrologie, Hopital Necker, Paris, France. a.karras@hopital-foch.org

BACKGROUND: Acquired thymic disease (malignant thymoma or thymic hyperplasia) is associated with various autoimmune diseases, such as myasthenia gravis (MG), pure red-cell aplasia (PRCA), pemphigus vulgaris or systemic lupus erythematosus (SLE). Renal disease has rarely been observed in association with thymoma. METHODS: This retrospective, multicentric study collected data on patients with thymic disease and biopsy-proven renal involvement. RESULTS: Twenty-one patients were studied (age: 49+/-14 years; male/female ratio: 8/13). Thymic pathology revealed mostly high-grade malignant thymoma (B2 and AB type); two cases were associated with non-malignant thymic hyperplasia. MG was found in nine out of 21 cases, SLE in three, PRCA in three and pemphigus in two. In 47% of these cases, nephropathy occurred after curative treatment of thymoma (108+/-83 months; range: 8-180 months), mainly based on surgical thymectomy associated with radiotherapy. Clinical and laboratory findings included nephrotic syndrome (75%), renal failure (50%), frequent presence of antinuclear antibodies and hypogammaglobulinaemia. Renal pathology showed minimal change disease in 14 patients and focal segmental glomerulosclerosis (FSGS) in one. Membranous nephropathy was observed in four cases, ANCA-associated glomerulonephritis in two and thrombotic microangiopathy in one. Most patients with minimal change disease or FSGS (11/13) were steroid-sensitive. Despite good response to steroids, 38% of patients died from thymoma and 17% developed end-stage renal failure. CONCLUSIONS: Glomerulopathy can be associated with thymoma or thymic hyperplasia. The present series shows that minimal change disease is the most frequent thymoma-associated glomerular lesion and that it may occur several years after thymectomy.

Publication Types:

PMID: 15788438 [PubMed - indexed for MEDLINE]

111: Oncol Rep. 2005 Jun;13(6):1127-31. Related Articles, Links: Multimodality therapy and significance of serum CYFRA21-1 for thymic carcinoma.

Suzuki M, Ando S, Iida T, Fujisawa T, Kimura H.

Division of Thoracic Diseases, Chiba Cancer Center, 666-2 Nitona-cho, Chuoh-ku, Chiba 260-8717, Japan. smakoto@chiba-cc.jp

Thymic carcinoma is a rare mediastinal neoplasm with a poor prognosis due to delayed diagnosis and highly malignant behavior. To evaluate 7 serum tumor markers and the outcome of treatment, 11 stage III-IVb thymic carcinomas undergoing multimodality treatment were reviewed. High levels of serum CYFRA21-1 were detected in 5 patients (45%) and correlated with the progression of disease. Of the patients, 6 underwent surgery. The median survival time was 38.4 months, and the 5-year survival rate was 15.6%. The metastatic stage (IVb) and treatment without resection were significantly associated with poorer overall survival (p=0.0034 and p=0.0041, respectively). Our data demonstrated that serum CYFRA21-1 may represent a potential new biomarker in thymic carcinoma. Stage may provide a basis for prognosis in stage III-IVb thymic carcinoma, and resection is one of the most important parts of multimodality treatment for advanced thymic carcinoma. Effective neoadjuvant treatment is therefore essential.

PMID: 15870932 [PubMed - indexed for MEDLINE]

112: Rev Mal Respir. 2005 Jun;22(3):485-6. Related Articles, Links

[A monstrous mediastinal mass]

[Article in French]

Daoud K, Aubert A, Lantuejoul S, Brichon PY, Diab S, Ferretti G, Moro-Sibilot D.

CHU Grenoble, DMAS, Oncologie thoracique BP 217 X, Grenoble, France.

Publication Types:

Case Reports

PMID: 16227936 [PubMed - indexed for MEDLINE]

113: World J Gastroenterol. 2005 May 28;11(20):3165-6. Related Articles, Links

Retrotracheal thymoma masquerading as esophageal submucosal tumor.

Ko SF, Tsai YH, Huang HY, Ng SH, Fang FM, Tang Y, Sung MT, Hsieh MJ.

Departments of Radiology, Chang Gung University, Chang Gung Memorial Hospital at Kaohsiung, Kaohsiung Hsien, Taiwan, China.

A 42-year-old man presented with a two-year history of progressive dysphagia and hoarseness. Esophagogram and endoscopy revealed submucosal mass effect on the upper esophagus. Computed tomography and magnetic resonance imaging revealed an elongated mass in the retrotracheal region of the lower neck with extension to the posterior mediastinum. Partial tumor resection and histopathological evaluation revealed a WHO type B2 thymoma. Adjuvant radiation and chemotherapy were subsequently administered resulting in complete tumor regression. To our knowledge, this is the first report of ectopic retrotracheal thymoma with clinical and imaging manifestations mimicking those for esophageal submucosal tumor.

Publication Types:

Case Reports

PMID: 15918212 [PubMed - indexed for MEDLINE]

114: FEBS Lett. 2005 May 23;579(13):2833-41. Epub 2005 Apr 25. Related Articles, Links: Immune cell-induced synthesis of NO and reactive oxygen species in lymphoma cells causes their death by apoptosis.

Hu DE, Brindle KM.

Department of Biochemistry, University of Cambridge, UK.

Induction of apoptosis in a lymphoma cell line using immune cell-conditioned medium, etoposide or an nitric oxide (NO) donor, resulted in the production of reactive oxygen species (ROS). Agents that inhibited NO production or scavenged ROS or species formed by reaction of NO with ROS, protected the cells from apoptosis. These data support the suggestion that immune rejection of an immunogenic derivative of this lymphoma in vivo involves the induced synthesis of both NO and ROS by the tumour cells.

PMID: 15907488 [PubMed - indexed for MEDLINE]

115: J Immunol. 2005 May 15;174(10):6184-94. Related Articles, Links: Enforced expression of Spi-B reverses T lineage commitment and blocks beta-selection.

Lefebvre JM, Haks MC, Carleton MO, Rhodes M, Sinnathamby G, Simon MC, Eisenlohr LC, Garrett-Sinha LA, Wiest DL.

Immunobiology Working Group, Division of Basic Sciences, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.

The molecular changes that restrict multipotent murine thymocytes to the T cell lineage and render them responsive to Ag receptor signals remain poorly understood. In this study, we report our analysis of the role of the Ets transcription factor, Spi-B, in this process. Spi-B expression is acutely induced coincident with T cell lineage commitment at the CD4(-)CD8(-)CD44(-)CD25(+) (DN3) stage of thymocyte development and is then down-regulated as thymocytes respond to pre-TCR signals and develop beyond the beta-selection checkpoint to the CD4(-)CD8(-)CD44(-)CD25(-) (DN4) stage. We found that dysregulation of Spi-B expression in DN3 thymocytes resulted in a dose-dependent perturbation of thymocyte development. Indeed, DN3 thymocytes expressing approximately five times the endogenous level of Spi-B were arrested at the beta-selection checkpoint, due to impaired induction of Egr proteins, which are important molecular effectors of the beta-selection checkpoint. T lineage-committed DN3 thymocytes expressing even higher levels of Spi-B were diverted to the dendritic cell lineage. Thus, we demonstrate that the prescribed modulation of Spi-B expression is important for T lineage commitment and differentiation beyond the beta-selection checkpoint; and we provide insight into the mechanism underlying perturbation of development when that expression pattern is disrupted.

PMID: 15879115 [PubMed - indexed for MEDLINE]

116: Acta Neuropathol (Berl). 2005 May;109(5):539-42. Epub 2005 Apr 20. Related Articles, Links

Involvement of mitochondria in myasthenia gravis complicated with dermatomyositis and rheumatoid arthritis: a case report.

Shichijo K, Mitsui T, Kunishige M, Kuroda Y, Masuda K, Matsumoto T.

Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, 3-18-15 Kuramoto-cho, 770-8503, Tokushima, Japan.

We report a 57-year-old male with myasthenia gravis complicated with dermatomyositis and rheumatoid arthritis without evidence of thymoma. He showed prominent muscle wasting and weakness in the four extremities and trunk in addition to swallowing disturbance. He showed intolerance to exercise on a bicycle ergometer, and muscle biopsy specimens demonstrated ragged-red fibers. An anti-acetylcholine receptor (AChR) antibody was detected in his serum but no anti-mitochondrial M2 component antibody was found. In contrast, results of immunohistochemical study indicated that his serum sample reacted to muscle mitochondria as well as AChR. These results indicate the presence of an unidentified anti-mitochondrial antibody that may be involved in the development of mitochondrial dysfunction in skeletal muscle of the present patient.

Publication Types:

Case Reports

PMID: 15843907 [PubMed - indexed for MEDLINE]

117: Ann Nucl Med. 2005 May;19(3):239-41. Related Articles, Links

Unexpected abnormal extra-cardiac mediastinal accumulation of technetium-99m-tetrofosmin in patient with acute pericarditis.

Yutaka K, Zen K, Sawada T, Azuma A, Matsubara H.

Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Japan.

A 58-year old woman had felt some chest pains on effort for several days. She was admitted to the emergency room with severe and refractory chest pain after exercise. Electrocardiogram showed marked ST-segment elevations in II, III, aVF and V1-6 electrodes. Echocardiogram revealed neither wall motion asynergy in the left ventricle nor abnormal pericardial effusion. Chest X-ray showed normal findings, and mild elevation of C-reactive protein was observed in the blood chemistry data. Her chest pain was relieved by nitroglycerin administration. Emergent technetium-99m-tetrofosmin myocardial imaging did not show any abnormal perfusion in the left ventricle. However, an abnormal extra-cardiac mediastinal accumulation was detected in the planar image. Contrast-enhanced chest CT scanning also demonstrated an inhomogeneously enhanced tumor in the anterior superior mediastinum. The tumor was surgically removed and was finally diagnosed as an invasive thymoma. Technetium-99m-tetrofosmin scintigraphy happened to provide useful information for diagnosing acute pericarditis with mediastinal tumor.

Publication Types:

Case Reports

PMID: 15981679 [PubMed - indexed for MEDLINE]

118: Ann Thorac Surg. 2005 May;79(5):e32-3. Related Articles, Links: Trans-arterial infusion chemotherapy for recurrence of pleural dissemination after thymectomy.

Terada Y, Kambayashi T, Okahashi S, Noguchi T, Kamakari K, Kubo S.

Department of Thoracic Surgery, Nagahama City Hospital, Nagahama, Japan. yaterada@ex.biwa.ne.jp

We present a report of trans-arterial infusion chemotherapy through the intercostal arteries and subphrenic artery for pleural dissemination of recurrent thymoma after thymectomy. The disseminated tumor did not enlarge for more than a year after this treatment, and there were no side effects. Trans-arterial infusion chemotherapy appears to be a preferable procedure for pleural dissemination of thymoma.

PMID: 15854916 [PubMed - in process]

119: Chirurgia (Bucur). 2005 May-Jun;100(3):215-22. Related Articles, Links: [Thoracoscopic thymectomy in the treatment of myasthenia gravis]

[Article in Romanian]

Tomulescu V, Ion V, Kosa A, Popescu I.

Centrul de Chirurgie Generala si Transplant Hepatic, Institutul Clinic Fundeni. victor.tomulescu@icfundeni.ro

A series of 151 thoracoscopic thymectomy performed in the Department of General Surgery and Liver Transplantation of the Fundeni Clinical Institute between April 1999 and April 2004 is analyzed. These were 89.34% from all the thymectomies performed in our department in this period. Thoracoscopic thymectomies were performed on 131 female patients (86.75%) and 20 male patients (23.25%), aged between 8 and 60 years. All patients were previously treated in the Neurological Department of the Fundeni Clinical Institute for at least 3 months. The thoracoscopic thymectomy was indicated for: myasthenia gravis without thymic neoplasia (141 cases), stage I Masaoka thymoma (8 cases), remnant postoperative thymic tissue (3 cases). We have used a left thoracoscopic approach in 73 cases and a right thoracoscopic approach in 76 cases. In 2 cases a mixed cervical and thoracoscopic approach was needed..No mortality and morbidity 6.62% (10 cases). From this 151 patients 100 have been constantly followed for more then one year. From the other 51, 32 are in the first postoperative year, and the other 19, 12.58% have been lost in surveillance. The one year evaluation regarding the Research Standards of Myasthenia Gravis Task Force Foundation shows: improvement--90% (complete stable remission--14%; pharmacological remission--20%; minimal manifestation--56%), unchanged--8%, worsened--2%. Our results with a complete stable remission of 14% at the end of the first year and 50% at 5 years are at least comparable with literature results with other open or thoracoscopic approaches.

PMID: 16106927 [PubMed - indexed for MEDLINE]

120: Dig Dis Sci. 2005 May;50(5):928-32. Related Articles, Links

Adult-onset autoimmune enteropathy in the setting of thymoma successfully treated with infliximab.

Elwing JE, Clouse RE.

Division of Gastroenterology, Washington University School of Medicine, St Louis, Missouri 63110, USA.

Publication Types:

PMID: 15906770 [PubMed - indexed for MEDLINE]

121: Dokl Biol Sci. 2005 May-Jun;402:224-9. Related Articles, Links: Accumulation of neutrophils in the spleen of mice immunized with cells of allogenic tumors.

Pobezinskii LA, Pobezinskaya EL, Zvezdova ES, Petrishchev VN, Grinenko TS, Baturina IA, Anfalova TV, Khromykh LM, Vasil'eva TV, Kazanskii DB.

Blokhin Oncological Research Center, Russian Academy of Medical Sciences, Kashirskoe sh. 24, Moscow, 115478 Russia.

PMID: 16121951 [PubMed - indexed for MEDLINE]

122: Histopathology. 2005 May;46(5):583-5. Related Articles, Links

Cervical ectopic thymoma: a diagnostic pitfall on frozen section.

Mourra N, Duron F, Parc R, Flejou JF.

Department of Pathology, Hopital Saint-Antoine, AP-HP, Paris, France.

Publication Types:

Case Reports

PMID: 15842641 [PubMed - indexed for MEDLINE]

123: J Cancer Res Clin Oncol. 2005 May;131(5):314-22. Epub 2005 Feb 10. Related Articles, Links: Glucocorticoids induce G1 cell cycle arrest in human neoplastic thymic epithelial cells.

Funakoshi Y, Shiono H, Inoue M, Kadota Y, Ohta M, Matsuda H, Okumura M, Eimoto T.

Division of General Thoracic Surgery, Department of Surgery (E1), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871 Osaka, Japan.

PURPOSE: Glucocorticoids exert anti-proliferative effects in various cell types and have long been known to induce apoptosis in thymocytes. Although a few reports have described the regression of human thymoma with glucocorticoid therapy, its effects on neoplastic thymic epithelial cells (TECs) have not been reported. In the present study, we investigated glucocorticoid receptor (GR) expression on neoplastic TECs and the effects of glucocorticoids in vitro on the cell cycle progression of tumor cells. PATIENTS AND METHODS: Thymoma specimens were obtained during surgery from 21 patients. Three of the specimens with glucocorticoid therapy were examined using the TdT-mediated dUTP-biotin nick-end labeling method. Primary tumor specimens from ten untreated thymomas were examined for GR expression by immunohistochemistry. Isolated neoplastic TECs from the remaining eight untreated thymomas were examined using immunohistochemistry, flow cytometric and cell cycle analysis. RESULTS: GR are expressed on neoplastic TECs as well as on non-neoplastic thymocytes in thymomas, regardless of WHO histological classification. Glucocorticoids caused an accumulation of TEC in G0/G1 phase in all cases examined (n = 6), and also induced apoptosis in the three with the lowest levels of Bcl-2 expression. CONCLUSIONS: Our results indicate that neoplastic TECs express GR and that glucocorticoids directly suppress their in vitro proliferation.

PMID: 15703942 [PubMed - indexed for MEDLINE]

124: J Card Surg. 2005 May-Jun;20(3):291-2. Related Articles, Links

Incidental locally infiltrating malignant thymoma and coronary artery bypass surgery-excision should always be considered.

Mirsadraee S, Shah SS, Kumar B, Kaul P.

Yorkshire Heart Centre, The General Infirmary at Leeds, Leeds, UK. niloogan@hotmail.com

The incidental finding of thymic tumors during thoracic surgery has been reported. Meticulous management planning is necessary if such tumor is found during a cardiac operation. We describe a rare case of asymptomatic invasive malignant thymoma discovered incidentally during routine elective coronary artery bypass grafting in a 48-year-old male. Total thymectomy and enbloc excision of tumor with adjacent involved pericardium, pleura, and phrenic nerve was performed. This was followed by quadruple coronary artery bypass grafting and adjuvant radiotherapy. The patient made an uneventful recovery and remains free from recurrence and angina 2 years following surgery. The different management options available for incidentally occurring malignant thymomas are discussed.

Publication Types:

Case Reports

PMID: 15854100 [PubMed - indexed for MEDLINE]

125: J Nucl Cardiol. 2005 May-Jun;12(3):359-61. Related Articles, Links

Focal uptake of radioactive tracer in the mediastinum during SPECT myocardial perfusion imaging.

Chadika S, Kokkirala AR, Giedd KN, Johnson LL, Giardina EG, Bokhari S.

New York Presbyterian Hospital, Columbia University, NY 10032, USA.

Publication Types:

Case Reports

PMID: 15944541 [PubMed - indexed for MEDLINE]

126: Nephrol Dial Transplant. 2005 May;20 Suppl 4:iv3-8. Related Articles, Links

Erratum in:

Nephrol Dial Transplant. 2005 Aug;20(8):1773.

What is antibody-mediated pure red cell aplasia (PRCA)?

Casadevall N.

Service d'Hematologie Biologique (AP-HP), Hotel-Dieu, 1 Parvis Notre Dame, 75181 Paris Cedex 04, France. nicole.casadevall@htd.ap-hop-paris.fr

Antibody (Ab)-mediated pure red cell aplasia (PRCA) is an immunological pathology associated with the production of neutralizing Abs that inhibit the erythropoietic activity of endogenous erythropoietin (EPO) and recombinant erythropoiesis-stimulating agents (ESAs). Although this disorder occurs very rarely, the number of reported cases has increased dramatically in recent years, predominantly in patients with chronic kidney disease (CKD)-associated anaemia receiving subcutaneous (s.c.) injections of one particular formulation of recombinant epoetin-alpha. This disorder is differentiated from classic forms of PRCA that are caused by chemical toxaemia (i.e. erythroblastopenia induced by chemical compounds), lymphoproliferative neoplasms, thymoma, human parvovirus B19 and certain autoimmune disorders. Patients with Ab-mediated PRCA develop resistance to EPO and severe anaemia that follows a period of successful erythropoietic response, and exhibit characteristic decreases in blood haemoglobin (Hb) level and in the number of circulating reticulocytes. However, it is not yet possible to predict which patients will develop PRCA or when in the course of their treatments PRCA may develop. Laboratory confirmation of Ab-mediated PRCA requires bone marrow examination demonstrating few or no erythroid precursors and the presence of serum anti-EPO Abs using a validated assay. These neutralizing anti-EPO Abs recognize the protein core of the EPO molecule; carbohydrate groups on EPO can affect the binding of Abs but are themselves not immunological determinants. Animal models are being developed to increase further our understanding of the immunological mechanisms underlying the onset and progression of Ab-mediated PRCA.

Publication Types:

Review

PMID: 15827056 [PubMed - indexed for MEDLINE]

127: Thorac Surg Clin. 2005 May;15(2):287-95. Related Articles, Links

Preoperative preparation of the patient with myasthenia gravis.

Kernstine KH.

Department of Thoracic Surgery, City of Hope National Medical Center, 1500 East Duarte Road, Suite 2001, Duarte, CA 91010-3000, USA. kkernstine@coh.org

All patients who are to undergo a thymectomy should be evaluated thoroughly by a neurologist--ideally one with special training and interest in the diagnosis and management of MG. Confirmatory tests to diagnose MG and other potential diseases should be reviewed. The antibody test seems to be most specific, but there are rare cases of other diseases that are ACh-R antibody positive. In 10% of MG patients, serology is negative, and other tests are necessary to confirm the diagnosis. All patients should undergo a contrast-enhanced high-resolution CT scan with 5- to 8-mm slices because thymoma or thymic carcinoma may be present. Pulmonary function tests, including vital capacity, forced expiratory volume, maximal expiratory force, arterial blood gas, and a flow-volume loop, should be performed. Exercise testing to evaluate for hypoxia and hypotension with exercise and ambulation also may be appropriate. A thorough assessment for cardiac dysfunction, including echocardiography, nuclear medicine studies, or a formal cardiology evaluation, may be beneficial. Because MG is a complex autoimmune disease, preoperative blood tests should include thyroid function testing, antinuclear antibody, and rheumatoid factor in addition to routine preoperative studies. Plasmapheresis or intravenous immunoglobulin should be considered for patients with advanced disease, bulbar symptoms, or poor pulmonary function. Given these guidelines, careful selection of candidates for surgery should optimize the long-term results for patients with MG.

Publication Types:

Review

PMID: 15999526 [PubMed - indexed for MEDLINE]

128: J Neurol Sci. 2005 Apr 15;231(1-2):85-8. Epub 2005 Jan 25. Related Articles, Links: Low-dose tacrolimus for two cases of myasthenia gravis with invasive thymoma that relapsed shortly after thymectomy.

Tsukaguchi M, Shimamura M, Ikeda K, Urai Y, Sasaki I, Deguchi K, Touge T, Takeuchi H, Kuriyama S.

Third Departement of Internal Medicine, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, 761-0793 Kagawa, Japan.

Two patients with myasthenia gravis (Ossermann IIb) involving invasive thymoma who underwent extensive thymectomy manifested myasthenic crisis shortly after the procedure; however, both patients were treated with intravenous immunoglobulin and recovered from myasthenic crisis that had been deteriorating for about 1 week. Subsequently, the patients were administered a low-dose of tacrolimus (3 mg/day) in addition to prednisolone. Several months later, tacrolimus continued to control fluctuations of myasthenic symptoms and maintained remission in these patients. The serum titer of anti-Ach-receptor antibodies decreased in parallel with clinical improvement due to tacrolimus, and we accordingly reduced the dosage of prednisolone. Tacrolimus is a new immunosuppressive agent acting through the selective inhibition of helper-T-cell activation that can be reduced dosage of steroids and can maintain remission of myasthenia gravis with invasiv