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Biomedical subjects

R Pandita

Publications and source records attributed to R Pandita.

25 records · Page 2Linked to original sources

Induction of interleukin-2 receptor by tumor necrosis factor alpha on cultured ovarian tumor-associated lymphocytes.

We have recently reported that autologous tumor-specific cytotoxic T lymphocyte (CTL) lines and clones can be developed from lymphocytes infiltrating ovarian malignant ascites (TAL). In this study, we investigated the biological effects of tumor necrosis factor alpha (TNF alpha) in the induction, expansion, long-term proliferation and lytic function of CD8+ TAL. TNF alpha up-regulated the IL-2 receptor (IL-2R) alpha chain (Tac antigen) on the surface of CD3+ CD8+ CD4- TAL, enhanced the proliferation of autologous tumor-specific CTL, and potentiated their lytic function in long-term cultures. Furthermore, in the induction and expansion phase of CD8+ TAL, the presence of TNF alpha was associated with a selective increase in CD8+ IL-2R+ (Tac+) cells, and subsequent decrease in CD4+ IL-2R+ (Tac+) cells. These results suggest that the observed facilitation of the outgrowth of CD8+ cells in TAL cultures may be due, at least in part, to the up-regulation of IL-2R, and indicate the usefulness of TNF alpha in the analysis of signalling in autologous tumor-reactive CTL.

Antigens, Differentiation, T-Lymphocyte↗

HIV-1 tat gene induces tumor necrosis factor-beta (lymphotoxin) in a human B-lymphoblastoid cell line.

The tat protein from human immunodeficiency virus type 1 (HIV-1) activates viral gene expression and is essential for HIV replication in vitro. It has also been shown that the tat gene product specifically inhibits antigen-induced proliferation of human peripheral blood lymphocytes. In order to understand the growth and immunomodulatory roles of HIV-1 tat, we have examined the effect of the tat gene on the expression of tumor necrosis factors in a human B-lymphoblastoid cell line (Raji). We report here that the HIV-1 tat gene introduced into Raji cells by retroviral-mediated transformation induces production of tumor necrosis factor-beta (TNF-beta). The tat-mediated induction of TNF-beta seems to be both at the transcriptional and post-transcriptional levels because, concurrent with a 30-fold increase in the levels of TNF-beta protein, an approximate 8-fold increase in mRNA was observed in tat-transformed Raji cells. It is recently reported that tat protein of HIV-1 stimulates growth of cells derived from Kaposi's sarcoma lesions of AIDS patients (Ensoli, B., Barillari, G., Salahuddin, S.Z., Gallo, R.C., and Wong-Staal, F. (1990) Nature 345, 84-86). Since TNF has been shown to function as a growth factor for several cell types, our results showing induction of TNF-beta by tat indicate the possibility that a growth-stimulatory role of HIV-1 tat on Kaposi's sarcoma cells is mediated through TNF-beta.

B-Lymphocytes↗

All-transretinoic acid and chemotherapy in the treatment of acute promyelocytic leukemia.

BACKGROUND: All-transretinoic acid (ATRA) and chemotherapy has improved complete remission rates and disease free survival in acute promyelocytic leukemia (APL). There is scanty data from Middle East. AIM: To determine the efficacy of ATRA and multi-agent combination chemotherapy in treatment of APL in a single Centre in Kuwait. SET-UPS AND DESIGN: Tertiary cancer centre, retrospective study. METHODS AND MATERIAL: All newly diagnosed APL patients were treated with oral ATRA 45 mg/m2 daily until complete remission (CR), intravenous daunorubicin 50 mg/m2 on days 1,3 and 5, cytosine arabinoside 100 mg/m2 12 hrly on days 1 through 10 and etoposide 100 mg/m2 on days 1 through 5. Post remission three courses of intensive consolidation chemotherapy were administered. Since October 1999, maintenance chemotherapy consisting of oral 6 mercaptopurine 9 mg/m2 daily, methotrexate 15 mg/m2 weekly and ATRA 45 mg/m2 for 2 weeks every three months was added. Complete remission rates and duration, relapse rate and toxicity were studied. RESULTS: 22 of 24 evaluable patients (91.6%) achieved CR. The median duration of remission was 13 months (range 2-55 months). Three patients (12.5%) relapsed. Two patients (8.3%) developed retinoic acid syndrome and responded to dexamethasone. Five patients (20.8%) died one each of refractory disease, during remission induction and of relapse. Two patients died while in remission. CONCLUSION: ATRA and combination chemotherapy results in high complete remission rates and low relapse rate in newly diagnosed APL. Maintenance therapy may be useful in preventing relapses.

Adolescent↗