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Awards & Distinctions ?

American Urological Association
American College of Surgeons

Affiliations ?

Dr. Sehgal is affiliated with 1 hospitals.

Hospital Affiliations

  • Philadelphia Veterans Affairs Medical Center
    3900 Woodland Ave, Philadelphia, PA 19104
  • Publications & Research

    Dr. Sehgal has contributed to 11 publications.
    Title Gossypol, a Phytochemical with Bh3-mimetic Property, Sensitizes Cultured Thoracic Cancer Cells to Apo2 Ligand/tumor Necrosis Factor-related Apoptosis-inducing Ligand.
    Date January 2007
    Journal The Journal of Thoracic and Cardiovascular Surgery

    OBJECTIVES: Chemotherapeutic agents sensitize cancer cells to Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) via recruitment of the mitochondria-dependent activation of caspase and induction of apoptosis. This study was designed to evaluate whether gossypol, a phytochemical compound with BH3-mimetic property that functions as an inhibitor of Bcl2/BclXL, would sensitize cultured thoracic cancer cells to this death-inducing ligand. METHODS: Cancer cell lines from the lung (H460, H322), the esophagus (TE2, TE12), and the pleura (H290, H211) or primary normal cells were treated with gossypol+Apo2L/TRAIL combinations. Cell viability and apoptosis were evaluated by (4,5-dimethylthiazo-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) assays, respectively. Caspase 9 and 3 specific proteolytic activity in combination-treated cells was determined by fluorometric enzymatic assay. RESULTS: Gossypol, selectively cytotoxic to cancer cells and not primary normal cells, significantly sensitized thoracic cancer cells to Apo2L/TRAIL as indicated by 1.5- to more than 10-fold reduction of Apo2L/TRAIL 50% inhibitory concentration values in cells treated with gossypol+Apo2L/TRAIL combinations. Whereas less than 20% of cancer cells exposed to either gossypol (5 micromol/L) or Apo2L/TRAIL (20 ng/mL) were dead, more than 90% of cells treated with the drug combinations were apoptotic. Combination-induced cytotoxicity and apoptosis was completely abrogated either by overexpression of Bcl2 or by the selective caspase 9 inhibitor. This combination was not toxic to normal cells. CONCLUSION: Gossypol profoundly sensitizes thoracic cancer cells to the cytotoxic effect of Apo2L/TRAIL via activation of the mitochondria-dependent death signaling pathway. This study provides evidence for the profound anticancer activity of this drug combination and should be further evaluated as a novel targeted molecular therapeutic for thoracic cancers.

    Title Suppression of Pro-metastasis Phenotypes Expression in Malignant Pleural Mesothelioma by the Pi3k Inhibitor Ly294002 or the Mek Inhibitor Uo126.
    Date May 2006
    Journal Anticancer Research

    BACKGROUND: This study aimed to evaluate the impact of selective abrogation of either the MEK/ERK1/2 (UO126 or PD98059) or the PI3K/AKT (LY294002) signaling cascade on cell proliferation, motility and invasion and production of VEGF (collectively termed pro-metastasis phenotypes) in cultured malignant pleural mesothelioma (MPM) cells. MATERIALS AND METHODS: Treatment-induced cytotoxicity was evaluated by MTT or Annexin V assays. Cell motility was assessed by wound healing and Matrigel invasion assays. VEGF in conditioned media of cancer cells was measured by ELISA. RESULTS: LY294002 and UO126 significantly inhibited cell proliferation and clonogenicity of MPM cells in vitro. A substantial reduction of cell motility, Matrigel invasion as well as inhibition of basal or EGF-induced VEGF production were observed in drug-treated cells. CONCLUSION: The selective MEK or PI3K kinase inhibitors are equally effective in down-regulating the expression of pro-metastasis phenotypes, suggesting that MEK or PI3K are appropriate targets for the development of molecular therapeutics for malignant pleural mesothelioma.

    Title Use of Mycelial Suspension and Metabolites of Paecilomyces Lilacinus (fungi: Hyphomycetes) in Control of Aedes Aegypti Larvae.
    Date August 2000
    Journal The Journal of Communicable Diseases

    Mycelial suspension of possible was assessed to examine its Paecilomyces lilanicus, a fungus, detrimental effects on fourth instar larvae of Aedes aegypti. The immature stages suffered 64-68% mortality with 0.5-1% mycelial suspension. There was 12-16% adult emergence which was statistically significant (P < 001). Czapeckdox and PYG media metabolites were used against the third instar larvae in various concentrations. The effects were evaluated on several parameters like mortality, mean survival time and time taken for adult emergence. The results indicate that the fungus does not producae any toxic metabolites.

    Title Bioactivity of Ethanol Extract of Karanja (pongamia Glabra Vent) Seed Coat Against Mosquitoes.
    Date June 2000
    Journal The Journal of Communicable Diseases

    Laboratory evaluation revealed that the treatment of larvae of Aedes aegypti and Culex quinquefasciatus with ethanol extract of karanja seed coat (ALKSC) significantly increased the larval mortality and developmental period proportianately with increase in the extract concentrations. Aedes proved more sensitive to the effect of extract in terms of mortality than Culex. At a high concentration (8 ppm), 100% Aedes larvae died in the first instar within two days whereas, 16 pmm was required for achieving the same level of mortality in Culex. Culex was also found more sensitive than Aedes regarding IGR effect. In emerging Culex pupae several abnormalities were observed while Aedes pupae did not exhibit any abnormalities. However larvae which pupated successfully resulted in adults with several structural abnormalities in both the species.

    Title Effects of Aqueous Extract of Deoiled Neem (azadirachta Indica A. Juss) Seed Kernel and Karanja (pongamia Glabra Vent) Seed Kernel Against Culex Quinquefasciatus.
    Date April 1997
    Journal The Journal of Communicable Diseases

    Aqueous extract obtained from deoiled neem and karanja seed kernels (ADNSD and ADKSK) were assessed for their toxic and growth regulating activities against Cx quinquefaciatus treated as first instar larvae. ADNSK at various concentrations was effective on the growth regulating mechanism, inducing prolonged larval stages. However, 100% larval mortality was observed, especially during the first and the second instars at all the tested concentrations. ADKSK caused 100% mortality in the fourth instar larvae and prepupae at the concentration of 100 ppm with no significant effect on the developmental period. The adults emerging from treated (50 ppm) larvae were smaller in size and malformed. We found ADNSK to be more effective than ADKSK.

    Title Modified Bovine Surfactant (survanta) Versus a Protein-free Surfactant (exosurf) in the Treatment of Respiratory Distress Syndrome in Preterm Infants: a Pilot Study.
    Date May 1994
    Journal Journal of the National Medical Association

    We undertook a prospective, randomized, non-blinded pilot study to determine whether infants with respiratory distress syndrome (RDS) who were treated with protein-containing bovine surfactant (Survanta, Ross/Abbott Laboratories, Columbus, Ohio) had earlier and larger responses in gas exchange when compared with similar infants treated with a synthetic surfactant (Exosurf, Burroughs Wellcome, Research Triangle Park, North Carolina). Forty-one infants weighing between 600 g and 1750 g at birth with RDS of sufficient severity to require assisted ventilation with an FiO2 > 0.39 were enrolled in the study and treated with surfactant from 1 to 8 hours after birth. Infants were randomly selected to receive treatment with either Exosurf or Survanta. Despite randomization, the Survanta group was overrepresented with factors associated with greater severity of RDS (lower birthweight, more males, and fewer African Americans). No statistically significant difference was found in the primary outcome measure (arterial/alveolar PaO2 > 0.3 at 24 hours) by univariate or multivariate analysis. The percentage of responders in the Survanta-treated group was significantly increased 24 hours after treatment in two of four secondary measures of oxygenation when analyzed by univariate tests using one-tailed P values. Based on these results, we anticipate that acute outcomes after Survanta or Exosurf will approximate those found in this trial and that differences in measures of oxygenation between treatment groups will approximate 30% to 50% 24 hours after initial treatment.

    Title Reduction of Neonatal Mortality After Multiple Doses of Bovine Surfactant in Low Birth Weight Neonates with Respiratory Distress Syndrome.
    Date July 1991
    Journal Pediatrics

    To determine if outcomes of low birth weight neonates with respiratory distress syndrome can be improved by the administration of multiple doses of bovine surfactant, we conducted two identical multicenter, controlled trials, and the results were combined for analysis. Seven hundred and ninety-eight neonates weighing 600 to 1750 g at birth who had developed respiratory distress syndrome within 6 hours of birth were assigned randomly to receive either 100 mg of phospholipid/kg of Survanta, a modified bovine surfactant (n = 402), or a sham dosing procedure (n = 396). Neonates whose respiratory distress persisted could be given up to three more doses, with all doses to be given in the first 48 hours after birth. Dosing was performed by investigators not involved in the clinical care of the neonates; nursery staff were kept blinded as to the treatment assignment. Fewer Survanta-treated neonates died of any cause (18.4% vs 27.3%, P = .002), died of respiratory distress syndrome (9.0% vs 20.3%, P less than .001), and either died or developed bronchopulmonary dysplasia due to respiratory distress syndrome (51.2% vs 64.6%, P less than .001). Neonates who received Survanta also had greater improvement in their oxygenation and ventilatory status from baseline to 72 hours than did control neonates. Survanta-treated neonates were at lowered risk for developing pulmonary interstitial emphysema (18.6% vs 39.3%, P less than .001) and other pulmonary air leaks (11.5% vs 25.9%, P less than .001). We conclude that multiple doses of Survanta given after diagnosis of respiratory distress syndrome reduce mortality and morbidity.

    Title Gamma Irradiation Effect on Oogenesis in Culex Quinquefasciatus Say Exposed As Pupa.
    Date April 1989
    Journal The Journal of Communicable Diseases
    Title Microanalysis of the Reaction Product in Karnovsky and Roots Histochemical Localization of Acetylcholinesterase.
    Date July 1982
    Journal The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society

    X-ray energy dispersive microanalysis of the reaction product in Karnovsky and Roots histochemical localization of acetylcholinesterase indicated the presence of sulfur, iodine, copper, and iron. The reaction was run in vitro using purified acetylcholinesterase from the electric eel to confirm our previous results on similarly treated neuromuscular junction in situ.

    Title Thiocholine Methods for the Demonstration of Acetylcholinesterase in Neuromuscular Junctions.
    Date November 1981
    Journal Cytobios

    The extensor digitorum longus muscles of rat were stained for the localization of acetylcholinesterase activity at the neuromuscular junctions. The modified methods of Koelle-Friedenwald and Karnovsky-Roots were used with acetylthiocholine iodide as the substrate. The merits and demerits of both these methods are discussed. TEM and SEM X-ray dispersive analyses of the muscle fibres treated histochemically by both the methods were also made in order to elucidate further the nature of the reaction products. Denervated muscles were subjected to similar treatment.

    Title Preliminary Studies on the Chemical Nature of Mosquito-breeding Waters in Delhi.
    Date September 1970
    Journal Bulletin of the World Health Organization

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