DSpace community: 附設醫院腫瘤醫學部

Epstein-Barr Virus-Containing T-Cell Lymphoma Presents with Hemophago Cytic Syndrome Mimicking Malignant Histiocytosis

Tue, 13 Oct 2009 15:23:25 GMT

title: Epstein-Barr Virus-Containing T-Cell Lymphoma Presents with Hemophago Cytic Syndrome Mimicking Malignant Histiocytosis abstract: BACKGROUND. The previously designated malignant histiocytosis (MH) may include lymphoid neoplasms of T-cell lineage as well as patients with benign virus-associated hemophagocytic syndrome (VAHS). In this study, the association of Epstein-Barr virus (EBV) with T cell lymphomas which present with clinicopathologic features indistinguishable from malignant histiocytosis (MH) was investigated further. METHODS. Four adult patients, three women and one man, were admitted because of fever, cutaneous lesions, hepatosplenomegaly, and jaundice. Laboratory examinations revealed pancytopenia, abnormal liver functions and coagulopathy. All patients ran a fulminant course terminating in a hemophagocytic syndrome within 1 month. Immunophenotypic study, Southern blot analysis, and in situ hybridization were performed on the specimens obtained from the four patients. RESULTS. The biopsy-necropsy specimens from skin, liver, spleen, and bone marrow showed infiltration of atypical large cells with reactive histiocytosis and florid hemophagocytosis activity. Based on the clinical and histologic findings, these cases would have been designated as MH by previous criteria. Immunophenotypic, Southern blot, and in situ hybridization studies, however, showed clonotypic proliferation of EBV genomes in the nuclei of the large atypical cells that expressed T-cell antigens. Therefore, these patients should be diagnosed as a recently described EBV-associated peripheral T-cell lymphoma (EBV-PTCL). CONCLUSIONS. EBV-PTCL may present with a fulminant hemophagocytic syndrome indistinguishable from the previously designated MH. This finding represents a step forward in our changing concept regarding MH, some of which only recently has been suggested to be of T-cell lymphoma origin. Differentiation from benign VAHS is clinically important. Features useful in this distinction are tabulated and discussed.

Gefitinib Treatment for Non-Small Cell Lung Cancer-a Study Including Patients with Poor Performance Status

Tue, 13 Oct 2009 15:21:13 GMT

title: Gefitinib Treatment for Non-Small Cell Lung Cancer-a Study Including Patients with Poor Performance Status abstract: Background and Purpose: Gefitinib is effective in the treatment of advanced non small tell lung cancer (NSCLC) However, most studies have only investigated patients who have good performance status or are, evaluable. This study evaluated the efficacy of gefitinib in a consecutive series of patients with NSCLC. Methods: The treatment response of all gefitinib-trated NSCLC patients from November 2001 to September 2003 at a single medical institute was retrospectively evaluated All patients receiving at least 1 dose of gefitinib during the study period were included. Results: A total of 66 NSCLC patients were treated including 22 patients with Eastern Clinical Oncology Group performance status 3 or 4 No prior chemotherapy had been given in 14 patients because of their personal preference or poor general condition The duration of treatment ranged from 1 day to 19.3 months (median 2.5 months) The partial remission rate was 15.2% and the stable disease rate was 25. 8%. The median survival for all patients was 5.9 months and the 1 year survival rate was 27.9% Symptom improvement and response correlated well to survival Female gender non smoking status and performance status of 0-2 were associated with better survival The disease control rate was 22.7% in patients with performance Status of 3-4. Conclusions: Gefitinib can be recommended for the treatment of advanced NSCLC in patients for whom standard chemotherapy is not an option. Further study is required to determin the optimal selection criteria of patients and the timing of starting therapy.

Interleukin-6 in Cervical Cancer: The Relationship with Vascular Endothelial Growth Factor

Tue, 13 Oct 2009 15:19:43 GMT

title: Interleukin-6 in Cervical Cancer: The Relationship with Vascular Endothelial Growth Factor abstract: Objective. Interleukin-6 (IL-6), a central proinflammatory cytokine, has been implicated in cervical cancer, though its role remains elusive, This study was an attempt to elucidate the role of IL-6 in the pathogenesis of cervical cancer, with particular emphasis on tumor angiogenesis, Methods. Cytosolic IL-6, vascular endothelial growth factor( VEGF), and platelet- derived growth factor (PDGF) levels were determined via enzyme immunoassay in 60 FIGO stage IB- IIA cervical cancer patients, Immunohistochemical staining in tissue sections was performed to analyze the distributions of IL-6 and IL-6 receptors, Meanwhile, human papillomavirus (HPV) DNA was detected by polymerase chain reaction-based survey. In vitro studies of two cervical cancer cell lines, C33A and SiHa, for the interaction between IL-6 and VEGF were also performed, Results. Consistently higher expression of IL-6 and VEGF was evident in cancerous tissues than in adjacent noncancer tissues in early-stage cervical cancer patients (P < 0. 01). After recombinant human IL-6 was added, VEGF was induced in a time- and dose-dependent manner in cervical cancer cell line C33 A, Correspondingly, interrupting the IL-6 autocrine machinery with either anti- IL-6 or anti-IL-6 receptor antibody markedly reduced the expression of VEGF at the transcriptional level in SiHa cells. Significantly higher levels of IL-6 in cancer tissues were observed in patients older than 45 ( P < 0.01), patients with tumors 22 cm (P < 0. 01), patients with oncogenic HPV-16 or -18 infections (P < 0.01), and patients with squamous cell carcinoma (P = 0.02). Patients with a deeper stromal invasion, vaginal invasion, lymphovascular emboli, or lymph node metastasis appeared to have higher intratumoral IL-6 levels, although the differences were statistically insignificant. Conclusions. Substantially high microenvironmental IL-6 levels promote tumor angiogenesis and the development of cervical cancer. Thus, inhibition of the biological activity of IL-6 may be potentially beneficial. (C) 2001 Academic Press.

The Anti-Apoptotic Role of Interleukin-6 in Human Cervical Cancer Is Mediated by up-Regulation of Mcl-1 through a Pi3-K/Akt Pathway

Tue, 13 Oct 2009 15:17:29 GMT

title: The Anti-Apoptotic Role of Interleukin-6 in Human Cervical Cancer Is Mediated by up-Regulation of Mcl-1 through a Pi3-K/Akt Pathway abstract: Interleukin-6 (IL-6), a multifunctional cytokine, has recently been implicated in human cervical cancer, though the mechanism remains elusive. This study demonstrates that the anti-apoptotic protein Mcl-1 and IL-6 was concomitantly expressed in human cervical cancer tissues and cell lines, but not in normal cervix tissues. Upon IL-6 treatment, Mcl-1 , but not other Bcl-2 family members, was rapidly up- regulated peaking at 4-8 h in human cervical cancer C33A cells. Supporting this observation, using anti-IL-6 or anti- IL-6 receptor antibody to interrupt the IL-6 autocrine loop in SiHa cells significantly reduced cellular level of Mcl-1 . This study hypothesizes that the expression of Mcl-1 in cervical cancer cells is regulated by IL-6. The matter of which signaling pathways transduced by IL-6 is responsible for the Mcl-1 up-regulation is further investigated herein. Blocking the STAT3 or MAPK pathway with dominant-negative mutant STAT3F or the MEK inhibitor PD98059 failed to inhibit IL-6-mediated Mcl-1 expression. Meanwhile, the IL-6-induced Mcl-1 up-regulation was effectively abolished by treatment with PI 3-K inhibitors, LY294002. Additionally, overexpression of dominant-negative (dn) Akt in C33A cells could inhibit the IL-6-induced increase of Mcl-1. Finally, overexpression of IL-6 in C33A cells caused a markable resistance to apoptosis induced by doxorubicin or cisplatin. Transient transfection of IL-6-overexpressed cells with a mcl-1 antisense vector, leading to the attenuation of their apoptosis-resistant activity. In conclusion, the data herein suggest that IL-6 regulated the mcl-1 expression via a PI 3 -K/Akt-dependent pathway that may facilitate the oncogenesis of human cervical cancer by modulating the apoptosis threshold.