Biomedical subjects

Shalini Jain

Publications and source records attributed to Shalini Jain.

8 recordsLinked to original sources

PubMed2007

Osteopontin: an emerging therapeutic target for anticancer therapy.

Distant migration of malignant cells or metastasis is considered one of the hallmarks of tumour progression and makes cancer a most deadly disease. The elevated expression of osteopontin (OPN), a metastasis-associated small integrin-binding ligand N-linked glycoprotein family member has been observed in several cancers and, thus, this protein is considered as a potent prognostic marker during tumour progression. OPN regulates a series of signalling cascades and augments the expression of several oncogenic molecules. Therefore, understanding the molecular mechanism and the signalling pathways by which OPN promotes tumorigenesis may be helpful in designing a novel anticancer therapy. At present, the role of OPN in regulating cancer progression is the subject of intense investigation and targeting OPN might be an appropriate therapeutic strategy for the treatment of cancer. This review is focused on OPN-based anticancer therapy, which may provide a new dimension for the successful treatment of cancer.

Animals↗

PubMed2006

Antidiabetic effect of probiotic dahi containing Lactobacillus acidophilus and Lactobacillus casei in high fructose fed rats.

OBJECTIVE: We investigated the effect of low-fat (2.5%) dahi containing probiotic Lactobacillus acidophilus and Lactobacillus casei on progression of high fructose-induced type 2 diabetes in rats. METHODS: Diabetes was induced in male albino Wistar rats by feeding 21% fructose in water. The body weight, food and water intakes, fasting blood glucose, glycosylated hemoglobin, oral glucose tolerance test, plasma insulin, liver glycogen content, and blood lipid profile were recorded. The oxidative status in terms of thiobarbituric acid-reactive substances and reduced glutathione contents in liver and pancreatic tissues were also measured. RESULTS: Values for blood glucose, glycosylated hemoglobin, glucose intolerance, plasma insulin, liver glycogen, plasma total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and blood free fatty acids were increased significantly after 8 wk of high fructose feeding; however, the dahi-supplemented diet restricted the elevation of these parameters in comparison with the high fructose-fed control group. In contrast, high-density lipoprotein cholesterol decreased slightly and was retained in the dahi-fed group. The dahi-fed group also exhibited lower values of thiobarbituric acid-reactive substances and higher values of reduced glutathione in liver and pancreatic tissues compared with the high fructose-fed control group. CONCLUSION: The probiotic dahi-supplemented diet significantly delayed the onset of glucose intolerance, hyperglycemia, hyperinsulinemia, dyslipidemia, and oxidative stress in high fructose-induced diabetic rats, indicating a lower risk of diabetes and its complications.

Animals↗

PubMed2006

The crucial role of cyclooxygenase-2 in osteopontin-induced protein kinase C alpha/c-Src/IkappaB kinase alpha/beta-dependent prostate tumor progression and angiogenesis.

The regulation of tumor progression towards its malignancy needs the interplay among several cytokines, growth factors, and enzymes, which are controlled in the tumor microenvironment. Here, we report that osteopontin, a small integrin-binding ligand N-linked glycoprotein family of calcified extracellular matrix-associated protein, regulates prostate tumor growth by regulating the expression of cyclooxygenase-2 (COX-2). We have shown that osteopontin stimulates the activation of protein kinase C alpha/nuclear factor-inducing kinase/nuclear factor-kappaB-dependent signaling cascades that induces COX-2 expression, which in turn regulates the prostaglandin E(2) production, matrix metalloproteinase-2 activation, and tumor progression and angiogenesis. We have revealed that suppression of osteopontin-induced COX-2 expression by the nonsteroidal anti-inflammatory drug celecoxib or blocking the EP2 receptor by its blocking antibody resulted in significant inhibition of cell motility and tumor growth and angiogenesis. The data also showed that osteopontin-induced mice PC-3 xenograft exhibits higher tumor load, increased tumor cell infiltration, nuclear polymorphism, and neovascularization. Interestingly, use of celecoxib or anti-EP2 blocking antibody drastically suppressed osteopontin-induced tumor growth that further indicated that suppression of COX-2 or its metabolites could significantly inhibit osteopontin-induced tumor growth. Human clinical prostate cancer specimen analysis also supports our in vitro and animal model studies. Our findings suggest that blockage of osteopontin and/or COX-2 is a promising therapeutic approach for the inhibition of prostate tumor progression and angiogenesis.

Animals↗

PubMed2006

Hypoxia regulates cross-talk between Syk and Lck leading to breast cancer progression and angiogenesis.

Hypoxia is a key parameter that controls tumor angiogenesis and malignant progression by regulating the expression of several oncogenic molecules. The nonreceptor protein-tyrosine kinases Syk and Lck play crucial roles in the signaling mechanism of various cellular processes. The enhanced expression of Syk in normal breast tissue but not in malignant breast carcinoma has prompted us to investigate its potential role in mammary carcinogenesis. Accordingly, we hypothesized that hypoxia/reoxygenation (H/R) may play an important role in regulating Syk activation, and Lck may be involved in this process. In this study, we have demonstrated that H/R differentially regulates Syk phosphorylation and its subsequent interaction and cross-talk with Lck in MCF-7 cells. Moreover, Syk and Lck play differential roles in regulating Sp1 activation and expressions of melanoma cell adhesion molecule (MelCAM), urokinase-type plasminogen activator (uPA), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor (VEGF) in response to H/R. Overexpression of wild type Syk inhibited the H/R-induced uPA, MMP-9, and VEGF expression but up-regulated MelCAM expression. Our data also indicated that MelCAM acts as a tumor suppressor by negatively regulating H/R-induced uPA secretion and MMP-9 activation. The mice xenograft study showed the cross-talk between Syk and Lck regulated H/R-induced breast tumor progression and further correlated with the expressions of MelCAM, uPA, MMP-9, and VEGF. Human clinical specimen analysis supported the in vitro and in vivo findings. To our knowledge, this is first report that the cross-talk between Syk and Lck regulates H/R-induced breast cancer progression and further suggests that Syk may act as potential therapeutic target for the treatment of breast cancer.

Animals↗

PubMed2006

Effect of skim milk and dahi (yogurt) on blood glucose, insulin, and lipid profile in rats fed with high fructose diet.

In the present study, the effect of skim milk and the fermented milk product named dahi (yogurt) on plasma glucose, insulin, and lipid levels as well as on liver glycogen and lipid contents in rats fed with high fructose diet has been investigated. Rats were fed with high fructose diet (21%) supplemented with skim milk, dahi (10 g/day each), or no milk product (control group) for 6 weeks. After 6 weeks of high fructose diet administration, the plasma glucose became significantly higher in control animals (246 mg/dL), whereas it was lower in skim milk (178 mg/dL)- and dahi (143 mg/dL)-fed rats. The glucose tolerance became impaired at the third week of feeding of high fructose diet in control animals, whereas in skim milk- and dahi-fed animals achievement of glucose intolerance was delayed until the fourth and fifth week, respectively. Blood glycosylated hemoglobin and plasma insulin were significantly lower in skim milk (10% and 34%, respectively)- and dahi (17%, and 48%, respectively)-fed animals than those of the control group. Plasma total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and very-low-density lipoprotein-cholesterol and blood free fatty acids were significantly lower in skim milk (13%, 14%, 14%, 19%, and 14%, respectively)- and dahi (22%, 33%, 30%, 33%, and 29%, respectively)-fed animals as compared with control animals. Moreover, the total cholesterol, triglyceride, and glycogen contents in liver tissues were also lower in skim milk (55%, 50%, and 36%, respectively)- and dahi (64%, 27%, and 4%, respectively)-fed animals as compared with control animals. In contrast, high-density lipoprotein-cholesterol in plasma was higher in skim milk (14%)- and dahi (29%)-fed animals as compared with control animals. These results indicate that skim milk and its fermented milk product, dahi, delay the progression of fructose-induced diabetes and dyslipidemia in rats and that these may be useful as antidiabetic food supplements that can be included in daily meals of the diabetic as well as normal population.

Animals↗

PubMed2006

Effect of Dahi containing Lactococcus lactis on the progression of diabetes induced by a high-fructose diet in rats.

The antidiabetic effect of dahi was observed on high-fructose-induced diabetic rats. The fasting blood glucose, glycosylated haemoglobin, insulin, free fatty acids and triglyceride levels of the dahi fed group animals were significantly lower than those of the control group (p<0.05). The imparity of the glucose tolerance test was also delayed by one week in the dahi-fed animals.

Animals↗

PubMed2006

The multifaceted roles of osteopontin in cell signaling, tumor progression and angiogenesis.

Osteopontin (OPN) is a chemokine like phosphorylated glycoprotein that plays important role in cancer progression. Extensive research from various laboratories has demonstrated the likely role of OPN in regulating the cell signaling that ultimately controls tumor growth and metastasis. Several earlier reports indicated that OPN is associated with various cancers; but its functional role in carcinogenesis is still not well defined. Besides the role of OPN in tumor biology, several studies have demonstrated the pathophysiological role of OPN in diverse biological events. This review will focus on recent advances in understanding the molecular mechanism by which OPN regulates a series of signaling cascades through activation of various kinases and transcription factors that ultimately control the expression of downstream effector genes, which contribute to tumor progression and angiogenesis in vitro and animal models. We will also provide evidences that suggest the enhanced expression of OPN is not only associated with several tumor types, but its level of expression is directly correlated to various stages of the clinical specimens of breast and prostate cancers. These studies may be useful for identifying novel OPN-based therapeutic approach for the treatment of cancer.

Animals↗

PubMed2005

Internet resources for diabetes.

Internet is transforming lives of many people in the world. Nowadays Internet has become one of the most common media to extract information of interest to researchers. The Internet is composed of a large number of smaller interconnected networks called Intranets. These Intranets connect thousands computers enabling them to share information with each other and to share various resources such as powerful super computers, software and databases of information. It has made it possible for people all over the world to effectively and inexpensively communicate with each other. The Internet has become world's biggest library where retrieval of scientific resources is only a mouse click away. The geometric growth in Internet usage is mainly due to the great success of "World Wide Web". Various useful databases on diabetes are already on 'the Net' and many more being added regularly. The present article is an attempt to provide a review of several sites that may be of great significance to the diabetes researchers before execution for new assignment/project.

Diabetes Mellitus↗