Manipal University

About: Manipal University is a education organization based out in Manipal, Karnataka, India. It is known for research contribution in the topics: Population & Medicine. The organization has 9525 authors who have published 11207 publications receiving 110687 citations.

A novel Gln358Glu mutation in ectodysplasin A associated with X-linked dominant incisor hypodontia.

Abstract: Patrick Tarpey, Trevor J. Pemberton, David W. Stockton, Parimal Das, Vasiliki Ninis, Sarah Edkins, P. Andrew Futreal, Richard Wooster, Sushanth Kamath, Rabindra Nayak, Michael R. Stratton, and Pragna I. Patel* Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK Institute for Genetic Medicine, University of Southern California, Los Angeles, California Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, California Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas Department of Internal Medicine, Baylor College of Medicine, Houston, Texas Department of Ophthalmology, Baylor College of Medicine, Houston, Texas Department of Neurology, Baylor College of Medicine, Houston, Texas Kasturba Medical College, Mangalore, India Ambedkar Medical College, Kadugondanahalli, Bangalore, India Departments of Pediatrics and Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan

Evaluation of the radioprotective effect of Ageratum conyzoides Linn. extract in mice exposed to different doses of gamma radiation.

Abstract: The effect of various doses (0, 25, 50, 75, 100, 125, 150, 300, 600 and 900 mg kg(-1)) of the alcoholic extract of the plant Ageratum conyzoides Linn. (ACE), on the alteration of radiation-induced mortality in mice exposed to 10 Gy of gamma radiation was studied. The acute toxicity studies showed that the drug was non-toxic up to a dose of 3000 mg kg(-1), the highest dose that could be tested for acute toxicity. Administration of ACE resulted in a dose-dependent decline in radiation-induced mortality up to a dose of 75 mg kg(-1), the dose at which the highest number of survivors (70.83%) was observed. Thereafter, the number of survivors declined with increasing doses of ACE and a nadir was reached at 900 mg kg(-1) ACE. Since the number of survivors was highest for 75 mg kg(-1) ACE, this was considered the optimum dose for radioprotection and used in further studies in which mice were treated with 75 mg kg(-1) ACE before exposure to 6, 7, 8, 9, 10 and 11 Gy of gamma radiation. The treatment of mice with 75 mg kg(-1) ACE reduced the severity of symptoms of radiation sickness and mortality at all exposure doses, and a significant increase in survival was observed compared with the non-treated irradiated group. The ACE treatment effectively protected mice against the gastrointestinal as well as bone marrow related death, as revealed by the increased number of survivors at all irradiation doses. The dose reduction factor was found to be 1.3. To understand the mechanism of action, various doses of ACE were evaluated for their in-vitro scavenging action on 1,1-diphenyl-2-picrylhydrazyl (DPPH), a chemically stable free radical. ACE was found to scavenge DPPH radicals in a concentration-dependent manner, indicating that the radioprotection afforded by ACE may be in part due to the scavenging of reactive oxygen species induced by ionizing radiation.

TAMing pancreatic cancer: combat with a double edged sword

Abstract: Among all the deadly cancers, pancreatic cancer ranks seventh in mortality. The absence of any grave symptoms coupled with the unavailability of early prognostic and diagnostic markers make the disease incurable in most of the cases. This leads to a late diagnosis, where the disease would have aggravated and thus, incurable. Only around 20% of the cases present the early disease diagnosis. Surgical resection is the prime option available for curative local disease but in the case of advanced cancer, chemotherapy is the standard treatment modality although the patients end up with drug resistance and severe side effects. Desmoplasia plays a very important role in chemoresistance associated with pancreatic cancer and consists of a thick scar tissue around the tumor comprised of different cell populations. The interplay between this heterogenous population in the tumor microenvironment results in sustained tumor growth and metastasis. Accumulating evidences expose the crucial role played by the tumor-associated macrophages in pancreatic cancer and this review briefly presents the origin from their parent lineage and the importance in maintaining tumor hallmarks. Finally we have tried to address their role in imparting chemoresistance and the therapeutic interventions leading to reduced tumor burden.

Genistein Induces Alterations of Epigenetic Modulatory Signatures in Human Cervical Cancer Cells.

Abstract: Introduction Epidemiological studies indicate that diet rich in fruits and vegetables is associated with decreased cancer risk thereby indicating that dietary polyphenols can be potential chemo-preventive agents. The reversible nature of epigenetic modifications makes them a favorable target for cancer prevention. Polyphenols have been shown to reverse aberrant epigenetic patterns by targeting the regulatory enzymes, DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). In vitro and in silico studies of DNMTs and HDACs were planned to examine genistein's role as a natural epigenetic modifier in human cervical cancer cells, HeLa. Methods Expression of the tumour suppressor genes (TSGs) [MGMT, RARβ, p21, E-cadherin, DAPK1] as well the methylation status of their promoters were examined alongwith the activity levels of DNMT and HDAC enzymes after treatment with genistein. Expression of DNMTs and HDACs was also studied. In-silico studies were performed to determine the interaction of genistein with DNMTs and HDACs. Results Genistein treatment significantly reduced the expression and enzymatic activity of both DNMTs and HDACs in a time-dependent way. Molecular modeling data suggest that genistein can interact with various members of DNMT and HDAC families and support genistein mediated inhibition of their activity. Timedependent exposure of genistein reversed the promoter region methylation of the TSGs and re-established their expression. Conclusions In this study, we find that genistein is able to reinstate the expression of the TSGs studied by inhibiting the action of DNMTs and HDACs. This shows that genistein could be an important arsenal in the development of epigenetic based cancer therapy.