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Biomedical subjects

J Subhashini

Publications and source records attributed to J Subhashini.

9 recordsLinked to original sources

Anti-proliferative and apoptotic effects of celecoxib on human chronic myeloid leukemia in vitro.

Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is the only non-steroidal anti-inflammatory drug so far which has been approved by the FDA for adjuvant treatment of patients with familial adenomatous polyposis. The molecular mechanism responsible for the anti-cancer effects of celecoxib is not fully understood. There is little data on the potential role of COX-2 in lymphoma pathogenesis. In view of the reported induction of apoptosis in cancer cells by cyclooxygenase-2 inhibitors, the present study is undertaken to test the effect of celecoxib on human chronic myeloid leukemia cell line, K562 and other hematopoietic cancer cell lines like Jurkat (human T lymphocytes), HL60 (human promyelocytic leukemia) and U937 (human macrophage). Treatment of these cells with celecoxib (10-100 microM) dose-dependently, reduced cell growth with arrest of the cell cycle at G0/G1 phase and induction of apoptosis. Further mechanism of apoptosis induction was elucidated in detail in K562 cell line. Apoptosis was mediated by release of cytochrome c into the cytoplasm and cleavage of poly (ADP-ribose) polymerase-1 (PARP-1). This was followed by DNA fragmentation. The level of anti-apoptotic protein Bcl-2 was decreased without any change in the pro-apoptotic Bax. Celecoxib also inhibited NF-kB activation. Celecoxib thus potentiates apoptosis as shown by MTT assay, cytochrome c leakage, PARP cleavage, DNA fragmentation, Bcl-2 downregulation and possibly by inhibiting NF-kB activation.

Apoptosis↗

Anti-inflammatory properties of BHUx, a polyherbal formulation to prevent atherosclerosis.

BHUx is a polyherbal formulation consisting of water-soluble fractions of five medicinal plants (Commiphora mukul, Terminalia arjuna, Boswellia serrata, Semecarpus anacardium and Strychnos nux vomica). The present study was undertaken to evaluate its antioxidant and antiinflammatory effects. BHUx, standardized by HPLC fingerprinting and filtered through 0.2 microm filter paper, was employed for different studies under in vivo and in vitro conditions. Under in vivo conditions, BHUx significantly reduced inflammation in the carrageenan-induced rat paw oedema model of inflammation, suggesting its anti-inflammatory properties. In order to test the mechanism of action of BHUx, further in vitro studies were undertaken on cumene-hydroperoxide-induced lipid peroxidation (CHP) in liver homogenate, LPS-induced NO production in peritoneal macrophages and on key enzymes of arachidonic acid cascade, involved in the mediation of inflammation. Under the conditions, BHUx showed concentration-dependent inhibition of CHP-induced lipid peroxidation in liver homogenate, suggesting its antioxidant properties. Similarly the potent anti-inflammatory effects of BHUx are evident by (a) preferential inhibition of COX-2 (IC50 for COX-2 = 80 microg/ml and IC50 for COX-1 = 169 microg/ml), (b) low ratios in the IC50 values of COX-2/COX-1 (0.47), (c) decreased production of NO in LPS-induced peritoneal macrophages and (d) inhibition of 5-LOX (IC50 = 795 microg/ml). BHUx also showed a preference for inhibiting 15-lipoxygenase (IC50 = 44 microg/ml), a key enzyme implicated in LDL oxidation. These studies suggest that BHUx is acting mainly at three levels, i.e., as a potent natural antioxidant, by reduction of key inflammatory mediators of arachidonic acid cascade and by preventing 15-LOX-mediated LDL oxidations, to prevent atherosclerosis.

Analgesics↗

C-Phycocyanin, a selective cyclooxygenase-2 inhibitor, induces apoptosis in lipopolysaccharide-stimulated RAW 264.7 macrophages.

C-Phycocyanin (C-PC) is one of the major biliproteins of Spirulina platensis, a blue green algae, with antioxidant and radical scavenging properties. It is also known to exhibit anti-inflammatory and anti-cancer properties. However, the mechanism of action of C-PC is not clearly understood. Previously, we have shown that C-PC selectively inhibits cyclooxygenase-2 (COX-2), an inducible isoform that is upregulated during inflammation and cancer. In view of the reported induction of apoptosis in cancer cells by cyclooxygenase-2 inhibitors, the present study is undertaken to test the effect of C-PC on LPS stimulated RAW 264.7 mouse macrophage cell line. These studies have shown a dose dependent reduction in the growth and multiplication of macrophage cell line by C-PC. This decrease in cell number appears to be mediated by C-PC induced apoptosis as evidenced by flow cytometric and confocal microscopic studies. Cells treated with 20 micro M C-PC showed typical nuclear condensation and 16.6% of cells in sub-G(o)/G(1) phase. These cells also showed DNA fragmentation in a dose dependent manner. The studies on poly(ADP ribose) polymerase (PARP) cleavage showed typical fragmentation pattern in C-PC treated cells. This C-PC induced apoptosis in RAW 264.7 cells appears to be mediated by the release of cytochrome c from mitochondria and independent of Bcl-2 expression. These effects of C-PC on RAW 264.7 cells may be due to reduced PGE(2) levels as a result of COX-2 inhibition.

Animals↗

Primary papillary carcinoma in a thyroglossal cyst.

Papillary carcinoma arising in a thyroglossal cyst is rare. There is controversy regarding optimum management. We report a case managed by Sistrunk's procedure and external radiotherapy and review the literature on the subject.

Adult↗

Hyperfractionation in advanced carcinoma of the uterine cervix: a preliminary report.

Experience with twice-a-day radiation therapy program for carcinoma of the uterine cervix (FIGO Stages IIB, IIIA & IIIB) is presented. The program consists of delivering 120 cGy per fraction, two fractions a day with 6 hours between fractions. A total of 6000 cGy was delivered in 50 fractions over 5 weeks. A control group was given conventional fractionation 5000 cGy in 25 fractions, 200 cGy per fraction over 5 weeks. This feasibility study enrolled 30 patients, 15 in each group. Normal tissue reactions in skin, mucosa and bowel were recorded. The acute normal tissue reactions were enhanced in the hyperfractionation group. This was significant with regard to the bowel complications. The tumor control rate did not show any significant difference between the two groups. A short follow-up period has revealed complete healing of all acute normal tissue reactions. This study shows that further dose escalation is feasible and a study with large sample size and longer follow-up is required to reach definite conclusions.

Carcinoma, Squamous Cell↗

Primary small intestinal lymphoma.

Gastro-intestinal tract is the most common site of extranodal presentation in non-Hodgkin's lymphoma. Among the subsites the small intestine predominates. This paper presents a review of 21 cases of primary gastro-intestinal lymphoma seen at the Department of Radiation Oncology, Christian Medical College, Vellore, during the period 1979-1986. All patients had laparotomy, and biopsy from the primary site. Histopathological subtypes were done in the International Working Formulation. Stage groupings were done applying the Crowther and Blackledge staging system. Post-laparotomy treatment decision was made depending on the patient's general condition, completeness of surgery and histological subtype. The overall survival rate was 31.5% at 5 years. Early stage disease and high-grade lymphomas have a better prognosis if treated adequately.

Female↗