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Biomedical subjects

S K Mitra

Publications and source records attributed to S K Mitra.

At least 19 recordsLinked to original sources
PubMed2006

Intrinsic FAK activity and Y925 phosphorylation facilitate an angiogenic switch in tumors.

Elevated focal adhesion kinase (FAK) expression occurs in advanced cancers, yet a signaling role for FAK in tumor progression remains undefined. Here, we suppressed FAK activity in 4T1 breast carcinoma cells resulting in reduced FAK Y925 phosphorylation, Grb2 adaptor protein binding to FAK, and signaling to mitogen-activated protein (MAP) kinase (MAPK). Loss of a FAK-Grb2-MAPK linkage did not affect 4T1 cell proliferation or survival in culture, yet FAK inhibition reduced vascular endothelial growth factor (VEGF) expression and resulted in small avascular tumors in mice. This FAK-Grb2-MAPK linkage was essential in promoting angiogenesis as reconstitution experiments using Src-transformed FAK-null fibroblasts revealed that point mutations affecting FAK catalytic activity (R454) or Y925 phosphorylation (F925) disrupted the ability of FAK to promote MAPK- and VEGF-associated tumor growth. Notably, in both FAK-inhibited 4T1 and Src-transformed FAK-null cells, constitutively activated (CA) mitogen-activated protein kinase kinase 1 (MEK1) restored VEGF production and CA-MEK1 or added VEGF rescued tumor growth and angiogenesis. These studies provide the first biological support for Y925 FAK phosphorylation and define a novel role for FAK activity in promoting a MAPK-associated angiogenic switch during tumor progression.

Animals↗
PubMed2006

Intrinsic focal adhesion kinase activity controls orthotopic breast carcinoma metastasis via the regulation of urokinase plasminogen activator expression in a syngeneic tumor model.

Expression of focal adhesion kinase (FAK) is elevated in malignant breast cancer, yet the role of intrinsic FAK activity in promoting tumor progression remains undefined. Here, we have inhibited FAK activity or expression in murine 4T1 breast carcinoma cells via dominant-negative focal adhesion kinase-related non-kinase (FRNK) or anti-FAK short hairpin RNA (shRNA) expression, respectively. Neither FRNK nor FAK shRNA ( approximately 80% reduced FAK levels) affected 4T1 proliferation in culture, whereas reduced FAK activity or expression blocked 4T1 cell invasion through Matrigel and resulted in 2-3-fold lower urokinase plasminogen activator (uPA) expression. Control 4T1 cells implanted into mammary fat pads of BALB/c mice exhibited spontaneous metastasis to the lungs, to the peritoneal cavity, and resulted in 90% lethality within 21 days. Whereas FAK shRNA-expressing 4T1 cells formed tumors in mice with low levels of apoptosis, when mammary-injected, these cells did not exhibit lung metastasis after 21 days and caused only 40% lethality up to 60 days. Transient re-expression of wild-type but not kinase-dead FAK in 4T1 FAK shRNA cells promoted uPA production and mammary to lung metastasis within 7 days. In fact, stable human uPA overexpression in 4T1 FAK shRNA cells promoted Matrigel invasion and lung metastasis equal to 4T1 controls. Conversely, treatment with plasminogen activator inhibitor-1 or neutralizing antibody to uPA blocked Matrigel invasion of 4T1 control cells. These studies provide the first direct proof that FAK catalytic activity can facilitate metastatic breast cancer progression by regulating uPA expression.

Animals↗
PubMed2006

Induction and evaluation of atherosclerosis in New Zealand white rabbits.

Atherosclerosis was experimentally induced in New Zealand white rabbits by feeding a high cholesterol diet for 12 weeks for screening of drugs against atherosclerosis. After 12 weeks, blood was collected from ear vein for evaluation of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) levels, then the animals were sacrificed to collect the livers for estimation of cholesterol, and aorta for gross and histopathological evaluations. The elevated levels of serum and liver parameters accompanied by gross and histopathological changes like accumulation of foam cells, atheromatous plaque formation and replacement fibrosis supported the successful induction of atherosclerosis in New Zealand white rabbits.

Animals↗
PubMed2004

Posterior urethral valves: incidence and progress of vesicoureteric reflux after primary fulguration.

This is a prospective study of 20 cases of posterior urethral valves (PUV) presenting between the ages of 12 days and 5.5 years (median 15 months) in order to determine the incidence and progress of vesicoureteric reflux (VUR), hydronephrosis (HN), and renal functional status. The efficacy of fulguration as the sole modality of treatment for PUV was assessed in terms of improvement or disappearance of VUR over a 6-month follow-up period. VUR was present in 60% of the patients, being unilateral in 41.7%. Out of 19 renal units with VUR, reflux subsided in 31.5% by 3 months and 78.94% by 6 months. The blood urea and serum creatinine levels, which were raised in 50% of the patients at presentation, came down to normal by 6 months in all the cases. Improvement in glomerular filtration rates (GFR) was noted in all the children at each follow-up and was found to be statistically significant ( p<0.01). HN was present in all the patients at presentation and was bilateral in 90%. It decreased significantly during the follow-up period, though its complete disappearance was seen only in one case. Vesicoureteric reflux dysplasia syndrome (VURD) was present in two cases. Our study showed that VUR disappeared in a majority of the cases by 6 months once adequate urethral patency was restored, although hydronephrosis persisted.

Child, Preschool↗
PubMed2004

The role of research in a technical assistance agency: the case of the 'German Agency for Technical Co-operation'.

Technical assistance agencies have a sustainable impact on the health systems of the countries they are operating in. As well as policy-makers at the national level, technical assistance agencies see themselves confronted that their interventions should be based on evidence, usually meaning the results of research. This study has the aim to analyse role of research in the implementation of technical assistance. We sent a questionnaire to all health project managers of the 'German Agency for Technical Co-operation' and performed a qualitative case study in one of the health projects. Forty-seven of 80 (58.8%) of the questionnaires were completed and sent back. The managers considered publications of International Organisations (IOs), scientific articles and local research as most important for their work. The case study showed application problems in the daily work. Research use not only depends on the relevance of the data but also on analytical skills, linguistic barriers and technical access to research by the potential users. The role of knowledge and information management has to be clearly defined in an organisation of technical assistance. The specific needs at the different levels have to be analysed so that skills and resources can be allocated adequately.

Cooperative Behavior↗
PubMed2003

Downregulation of hepatitis B surface antigen expression in human hepatocellular carcinoma cell lines by HD-03, a polyherbal formulation.

Hepatitis B virus is associated with chronic or acute liver diseases and with hepatocellular carcinoma. In the present study, we examined the activity of HD-03, a polyherbal formulation, on two hepatitis B surface antigen (HBsAg) expressing human hepatocellular carcinoma cell lines, PLC/PRF/5 and HepG2/A2. We observed that HD-03 downregulates HBsAg expression from these cell lines. Our studies have also shown that this effect is neither due to cytotoxicity on the cell lines nor due to blockade of the release of the antigen from the cells nor due to binding of the substance with the antigen. The possible mode of its antiviral activity is explained.

Antineoplastic Agents↗
PubMed2003

Histological changes in intestine in semichronic diarrhoea induced by lactose enriched diet in rats: effect of Diarex-Vet.

Efficacy of Diarex-Vet (The Himalaya Drug Company, Makali, Bangalore, India) was evaluated histologically in semichronic diarrhoea induced by lactose enriched diet in rats. The rats in different groups were given lactose enriched diet alone for 2 days before starting the treatment with Diarex-Vet at a dose of 250, 500 and 750 mg/kg body weight along with lactose enriched diet for 5 days. Animals were euthanised at the end of 5 days of treatment and histological changes were observed in the ileum, caecum and colon. Semiquantitative analysis of goblet cells in intestines showed dose dependent response among the treated groups. The morphological changes were comparable to normal in the group given 750 mg/kg body wt Diarex-Vet. The effects observed were attributed to the lactase like analogous activity of Diarex-Vet or the inhibition of the osmotic processes in the intestinal lumen thereby reducing the morphological changes in the intestines.

Animals↗
PubMed2001

Inhibition of anchorage-independent cell growth, adhesion, and cyclin D1 gene expression by a dominant negative mutant of a tyrosine phosphatase.

PTP-S4/TC48 protein tyrosine phosphatase is localized in the nuclear and cytoplasmic membranes. To investigate the role of PTP-S4 in cell growth, adhesion, and transformation, normal and a catalytically inactive mutant form of this phosphatase were expressed in polyoma virus-transformed F111 fibroblast cell line, PyF. Expression of mutant PTP-S4 in PyF cells resulted in strong inhibition of anchorage-independent growth in soft agar but had no significant effect on growth in liquid culture. Tumor formation in nude mice was also reduced by mutant PTP-S4. Expression of normal PTP-S4 in PyF cells significantly increased anchorage-independent cell growth and tumor formation in nude mice. Overexpression of catalytically inactive mutant of PTP-S2/TC45 (a splice variant of PTP-S4 that is nuclear) did not inhibit anchorage-independent growth of PyF cells. Mutant PTP-S4-expressing cells were inhibited in adhesion and spreading on tissue culture plates compared to control cells. Expression of mutant PTP-S4 in PyF cells reduced the levels of cyclin D1 and cyclin A mRNA, whereas cyclin D2 mRNA level was not affected significantly. Expression of antisense cyclin D1 strongly inhibited anchorage-independent growth. Inhibition of anchorage-independent growth by mutant PTP-S4 was overcome to a large extent by coexpression of cyclin D1. These results suggest that mutant PTP-S4 inhibits anchorage-independent growth and adhesion of polyoma virus-transformed cells by interfering with the normal function of PTP-S4 upstream of cyclin D1 gene expression.

Animals↗
PubMed2001

The protective effect of HD-03 in CCl4-induced hepatic encephalopathy in rats.

The liver is a major parenchymal organ involved in many functional activities in the body. Hepatic encephalopathy is a syndrome characterized by increased blood ammonia level and is one of the major complications of cirrhosis. In the present study the protective effect of HD-03, a poly-herbal formulation, was evaluated against CCl4-induced hepatic encephalopathy in rats. Hepatic encephalopathy was induced in Wistar rats by administration of CCl4 at a dose of 1 mL/kg orally in liquid paraffin (1:1) twice a week for 90 days. The liver enzymes (SGPT and SGOT) and blood ammonia levels were significantly (p < 0.001) higher in the CCl4-intoxicated group compared with the untreated control group. Administration of HD-03 at a dose of 750 mg/kg orally as an aqueous suspension significantly prevented the elevation of SGPT, SGOT and blood ammonia levels. Histomorphometric evaluation of liver and brain showed a protective effect of the HD-03 treatment, thus correlating with the changes in biochemical profiles. The protective effect of HD-03 against CCl4-induced encephalopathy may be due to the improved hepatocellular function, which in turn helps in regulating the metabolism of ammonia. However, further studies are required to measure the activity of enzymes involved in the urea cycle and brain aromatic amino acids in order to elucidate the exact mechanism of action of HD-03.

Alanine Transaminase↗
PubMed2001

The beneficial effect of OST-6 (OsteoCare), a herbomineral formulation, in experimental osteoporosis.

OST-6 (OsteoCare), a herbomineral formulation, was evaluated for its inhibitory effect on the progress of bone loss induced by ovariectomy in rats. Ovariectomized (Ovx) rats were administered with OST-6 at 250 and 500 mg/kg b.wt., orally daily for 90 days. On 91st day, ovariectomized rats showed reduced bone mineral content and increased serum alkaline phosphatase levels, excretion of urinary calcium and pyridinium cross-links levels. Histologically, bone sections revealed narrowed and disappearance of trabeculae and widened medullary spaces. The total numbers of Tartrate-resistant acid phosphatase (TRAP) positive cells were significantly increased both in-vivo and in-vitro methods. OST-6, at a dose of 500 mg/kg, significantly improved bone mineral contents, serum alkaline phosphatase levels, reduced the elevated urinary calcium and pyridinium cross-links excretion, number of TRAP positive cells and reversal of the above mentioned histological features. These results indicate the usefulness of OST-6 in the management of osteoporosis in a natural way through herbal resources.

Amino Acids↗
PubMed2000

Bone mineralization by OST-6 (OsteoCare), a herbomineral preparation, in experimentally induced rickets in rats.

In the present study the efficacy of OST-6 (OsteoCare), a herbomineral preparation, on bone mineralization in experimental rickets has been evaluated. This was accomplished by feeding pregnant rats and subsequently their pups with vitamin D and calcium deficient (VDCD) with low phosphorus diet. The parameters such as serum and bone mineral contents (calcium and inorganic phosphorus), serum alkaline phosphatase, sex hormones and histology of bone were considered. VDCD resulted in a significant reduction in bone and serum calcium and inorganic phosphorus, increased serum alkaline phosphatase and decreased sex hormones (testosterone in males, progesterone and oestrogen in females). Histologically the bone showed osteodystrophic changes and disproportionate cartilaginous proliferations in the epiphyseal region. Incorporation of OST-6 into feed at 5% concentration resulted in a complete reversal of rickets, which was substantiated by biochemical and histological observations. It has been concluded that OST-6 is useful in the management of rickets in a natural way through herbal resources.

Animals↗
PubMed2000

Anti-inflammatory, antioxidant and antimicrobial activity of Ophthacare brand, an herbal eye drops.

In the present study, the herbal preparation of Ophthacare brand eye drops was investigated for its anti-inflammatory, antioxidant and antimicrobial activity, using in vivo and in vitro experimental models. Ophthacare brand eye drops exhibited significant anti-inflammatory activity in turpentine liniment-induced ocular inflammation in rabbits. The preparation dose-dependently inhibited ferric chloride-induced lipid peroxidation in vitro and also showed significant antibacterial activity against Escherichia coli and Staphylococcus aureus and antifungal activity against Candida albicans. All these findings suggest that Ophthacare brand eye drops can be used in the treatment of various ophthalmic disorders.

Animals↗
PubMed2000

Neonatal intestinal obstruction with isolated levocardia.

An unusual case of isolated levocardia, duodenal obstruction, and malrotation with volvulus is reported. Three cases of situs inversus abdominus with malrotation with volvulus have been reported to date. The current case is the fourth case and only the second survivor in the series. In cases of situs inversus abdominus, because of inversion of viscera, the volvulus may occur in an anticlockwise direction and, thus, should be derotated in a clockwise direction.

Humans↗
PubMed2000

Effect of HD-03--a herbal formulation in galactosamine-induced hepatopathy in rats.

The effect of HD-03 a herbal preparation was studied on galactosamine (400 mg/kg b.wt., i.p.) induced hepatotoxicity in rats. Animals were pre-treated for 14 days with HD-03 and compared against untreated group for SGPT, SGOT, serum bilirubin and liver glycogen. Histopathology of liver lobes was considered to evaluate the extent of hepatic injury induced by galactosamine. These were reversed by HD-03 pre-treatment. HD-03 provided convincing evidence of hepatoprotection against galactosamine induced hapatotoxicity.

Animals↗
PubMed2000

Stromal sarcoma of breast: a case report.

A 34 years unmarried female was admitted with an ulcerated foul smelling growth in her right breast. On examination the fungating mass measured 17.5 cm x 15 cm in central and lower part of right breast involving the nipple and areola. The ulcer was covered with slough and rest part of the breast appeared bosselated. Her Hb was 4 g/dl and incision biopsy from the margin of the tumour showed histology of sarcoma. The patient was infused 6 units of blood and right sided total mastectomy was done. Histopathological examination confirmed it was a case of stromal sarcoma of breast. Chemotherapy was started with vincristine, adriamycin and cylophosphamide. The patient was doing well in next follow-up.

Adult↗
PubMed2000

Inhibition of experimental cirrhosis in rats by HD-03.

AIM: To investigate the protective effect of HD-03 in experimental cirrhosis following chronic intoxication with thioacetamide (TAA). METHODS: The effect of HD-03 (750 mg/kg p.o.) was studied in rats following TAA-induced intoxication (50 mg/kg p.o.) for a period of 90 d. HD-03 was administered as an aqueous suspension. Levels of biochemical markers indicative of hepatotoxicity were assessed in serum and liver. Histopathological evaluation of liver was also carried out to find out the protective effect of HD-03 following TAA-induced chronic intoxication. RESULTS: Administration of TAA at a dose of 50 mg/kg p.o. for 90 d resulted in a significant derangement of serum [serum glutamic pyruvate transaminase (SGPT), serum glutamic oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), albumin and bilirubin] and hepatic (triglycerides, protein, hydroxyproline, collagen and glycogen) biochemical parameters. Histopathological evaluation of liver sections following TAA-intoxication showed necrosis and proliferative changes characteristic of cirrhosis. Simultaneous treatment of TAA-intoxicated rats with HD-03 at a dose of 750 mg/kg p.o. for the same duration significantly prevented the changes in both serum and hepatic biochemical parameters. The reversal of serum and hepatic biochemical parameters also correlated with the preservation of liver histoarchitecture in HD-03 treated rats. CONCLUSION: The responses such as membrane stabilization, hepatocellular regeneration, and inhibition of collagen formation are the contributing factors in the correction of TAA-induced cirrhosis by HD-03.

Alanine Transaminase↗