Vikas Dudeja

Bio: Vikas Dudeja is an academic researcher from University of Miami. The author has contributed to research in topics: Pancreatic cancer & Triptolide. The author has an hindex of 39, co-authored 143 publications receiving 4733 citations. Previous affiliations of Vikas Dudeja include Memorial Sloan Kettering Cancer Center & University of Minnesota.

BMI does not accurately predict overweight in Asian Indians in northern India

Abstract: Asian Indians are at high risk for the development of atherosclerosis and related complications, possibly initiated by higher body fat (BF). The present study attempted to establish appropriate cut-off levels of the BMI for defining overweight, considering percentage BF in healthy Asian Indians in northern India as the standard. A total of 123 healthy volunteers (eighty-six males aged 18--75 years and thirty-seven females aged 20--69 years) participated in the study. Clinical examination and anthropometric measurements were performed, and percentage BF was calculated. BMI for males was 21.4 (sd 3.7) kg/m(2) and for females was 23.3 (sd 5.5) kg/m(2). Percentage BF was 21.3 (sd 7.6) in males and 35.4 (sd 5.0) in females. A comparison of BF data among Caucasians, Blacks, Polynesians and Asian ethnic groups (e.g. immigrant Chinese) revealed conspicuous differences. Receiver operating characteristic (ROC) curve analysis showed a low sensitivity and negative predictive value of the conventional cut-off value of the BMI (25 kg/m(2)) in identifying subjects with overweight as compared to the cut-off value based on percentage BF (males >25, females >30). This observation is particularly obvious in females, resulting in substantial misclassification. Based on the ROC curve, a lower cut-off value of the BMI (21.5 kg/m(2) for males and 19.0 kg/m(2) for females) displayed the optimal sensitivity and specificity, and less misclassification in identification of subjects with high percentage BF. Furthermore, a novel obesity variable, BF:BMI, was tested and should prove useful for interethnic comparison of body composition. In the northern Indian population, the conventional cut-off level of the BMI underestimates overweight and obesity when percentage BF is used as the standard to define overweight. These preliminary findings, if confirmed in a larger number of subjects and with the use of instruments having a higher accuracy of BF assessment, would be crucial for planning and the prevention and treatment of various obesity-related metabolic diseases in the Asian Indian population.

Triptolide Induces Pancreatic Cancer Cell Death via Inhibition of Heat Shock Protein 70

Abstract: Pancreatic cancer is highly resistant to current chemotherapy agents. We therefore examined the effects of triptolide (a diterpenoid triepoxide) on pancreatic cancer growth and local-regional tumor spread using an orthotopic model of pancreatic cancer. We have recently shown that an increased level of HSP70 in pancreatic cancer cells confers resistance to apoptosis and that inhibiting HSP70 induces apoptosis in these cells. In addition, triptolide was recently identified as part of a small molecule screen, as a regulator of the human heat shock response. Therefore, our aims were to examine the effects of triptolide on (a) pancreatic cancer cells by assessing viability and apoptosis, (b) pancreatic cancer growth and local invasion in vivo, and (c) HSP70 levels in pancreatic cancer cells. Incubation of PANC-1 and MiaPaCa-2 cells with triptolide (50-200 nmol/L) significantly reduced cell viability, but had no effect on the viability of normal pancreatic ductal cells. Triptolide induced apoptosis (assessed by Annexin V, caspase-3, and terminal nucleotidyl transferase-mediated nick end labeling) and decreased HSP70 mRNA and protein levels in both cell lines. Triptolide (0.2 mg/kg/d for 60 days) administered in vivo decreased pancreatic cancer growth and significantly decreased local-regional tumor spread. The control group of mice had extensive local invasion into adjacent organs, including the spleen, liver, kidney, and small intestine. Triptolide causes pancreatic cancer cell death in vitro and in vivo by induction of apoptosis and its mechanism of action is mediated via the inhibition of HSP70. Triptolide is a potential therapeutic agent that can be used to prevent the progression and metastases of pancreatic cancer.

Heat shock protein 70 increases tumorigenicity and inhibits apoptosis in pancreatic adenocarcinoma.

Abstract: Pancreatic carcinoma is a malignant disease that responds poorly to chemotherapy because of its resistance to apoptosis. Heat shock proteins (Hsp) are not only cytoprotective but also interfere with the apoptotic cascade. Here, we investigated the role of Hsp70 in regulating apoptosis in pancreatic cancer cells. Hsp70 expression was increased in pancreatic cancer cells compared with normal pancreatic ductal cells. This was confirmed by increased mRNA levels for Hsp70 in human pancreatic cancer tissue compared with neighboring normal tissue from the same patient. Depletion of Hsp70 by quercetin decreased cell viability and induced apoptosis in cancer cells but not in normal pancreatic ductal cells. To show that this is a specific effect of Hsp70 on apoptosis, levels of Hsp70 were knocked down by short interfering RNA treatment, which also induced apoptosis in cancer cells as indicated by Annexin V staining and caspase activation. Daily administration of quercetin to nude mice decreased tumor size as well as Hsp70 levels in tumor tissue. These findings indicate that Hsp70 plays an important role in apoptosis and that selective Hsp70 knockdown can be used to induce apoptosis in pancreatic cancer cells.

Management of Helicobacter pylori infection—the Maastricht V/Florence Consensus Report

Abstract: Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.

SF-010-4 Distant metastasis occurs late during the genetic evolution of pancreatic cancer

Abstract: Metastasis, the dissemination and growth of neoplastic cells in an organ distinct from that in which they originated, is the most common cause of death in cancer patients. This is particularly true for pancreatic cancers, where most patients are diagnosed with metastatic disease and few show a sustained response to chemotherapy or radiation therapy. Whether the dismal prognosis of patients with pancreatic cancer compared to patients with other types of cancer is a result of late diagnosis or early dissemination of disease to distant organs is not known. Here we rely on data generated by sequencing the genomes of seven pancreatic cancer metastases to evaluate the clonal relationships among primary and metastatic cancers. We find that clonal populations that give rise to distant metastases are represented within the primary carcinoma, but these clones are genetically evolved from the original parental, non-metastatic clone. Thus, genetic heterogeneity of metastases reflects that within the primary carcinoma. A quantitative analysis of the timing of the genetic evolution of pancreatic cancer was performed, indicating at least a decade between the occurrence of the initiating mutation and the birth of the parental, non-metastatic founder cell. At least five more years are required for the acquisition of metastatic ability and patients die an average of two years thereafter. These data provide novel insights into the genetic features underlying pancreatic cancer progression and define a broad time window of opportunity for early detection to prevent deaths from metastatic disease.

Heat shock factors: integrators of cell stress, development and lifespan

Abstract: Heat shock factors (HSFs) are essential for all organisms to survive exposures to acute stress. They are best known as inducible transcriptional regulators of genes encoding molecular chaperones and other stress proteins. Four members of the HSF family are also important for normal development and lifespan-enhancing pathways, and the repertoire of HSF targets has thus expanded well beyond the heat shock genes. These unexpected observations have uncovered complex layers of post-translational regulation of HSFs that integrate the metabolic state of the cell with stress biology, and in doing so control fundamental aspects of the health of the proteome and ageing.