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Full-Text Articles in Life Sciences

Co-Targeting Plk1 And Dnmt3a In Advanced Prostate Cancer, Zhuangzhuang Zhang, Lijun Cheng, Qiongsi Zhang, Yifan Kong, Daheng He, Kunyu Li, Matthew Rea, Jianlin Wang, Ruixin Wang, Jinghui Liu, Zhiguo Li, Chongli Yuan, Enze Liu, Yvonne N. Fondufe-Mittendorf, Lang Li, Tao Han, Chi Wang, Xiaoqi Liu May 2021

Co-Targeting Plk1 And Dnmt3a In Advanced Prostate Cancer, Zhuangzhuang Zhang, Lijun Cheng, Qiongsi Zhang, Yifan Kong, Daheng He, Kunyu Li, Matthew Rea, Jianlin Wang, Ruixin Wang, Jinghui Liu, Zhiguo Li, Chongli Yuan, Enze Liu, Yvonne N. Fondufe-Mittendorf, Lang Li, Tao Han, Chi Wang, Xiaoqi Liu

Toxicology and Cancer Biology Faculty Publications

Because there is no effective treatment for late-stage prostate cancer (PCa) at this moment, identifying novel targets for therapy of advanced PCa is urgently needed. A new network-based systems biology approach, XDeath, is developed to detect crosstalk of signaling pathways associated with PCa progression. This unique integrated network merges gene causal regulation networks and protein-protein interactions to identify novel co-targets for PCa treatment. The results show that polo-like kinase 1 (Plk1) and DNA methyltransferase 3A (DNMT3a)-related signaling pathways are robustly enhanced during PCa progression and together they regulate autophagy as a common death mode. Mechanistically, it is shown that Plk1 …


Binge Alcohol Exposure Causes Neurobehavioral Deficits And Gsk3Β Activation In The Hippocampus Of Adolescent Rats, Zhe Ji, Lin Yuan, Xiong Lu, Hanqing Ding, Jia Luo, Zun-Ji Ke Feb 2018

Binge Alcohol Exposure Causes Neurobehavioral Deficits And Gsk3Β Activation In The Hippocampus Of Adolescent Rats, Zhe Ji, Lin Yuan, Xiong Lu, Hanqing Ding, Jia Luo, Zun-Ji Ke

Pharmacology and Nutritional Sciences Faculty Publications

Heavy alcohol exposure causes profound damage to the adolescent brain, particularly the hippocampus, which underlie some behavioral deficits. However, the underlying molecular mechanisms remain inconclusive. The current study sought to determine whether binge alcohol exposure affects the hippocampus-related behaviors and key signaling proteins that may mediate alcohol neurotoxicity in adolescent rats. Alcohol exposure reduced the number of both NeuN-positive and doublecortin-positive cells in the hippocampus. Alcohol also induced neurodegeneration which was confirmed by ultrastructural analysis by electronic microscopy and was accompanied with the activation of microglia. Binge alcohol exposure impaired spatial learning and memory which was evaluated by the Morris …


Role Of The Calcium Plateau In The Neuronal Injury And Behavioral Morbidities Following Organophosphate Intoxication, Laxmikant S. Deshpande, Robert E. Blair, Kristin F. Phillips, Robert J. Delorenzo Jan 2016

Role Of The Calcium Plateau In The Neuronal Injury And Behavioral Morbidities Following Organophosphate Intoxication, Laxmikant S. Deshpande, Robert E. Blair, Kristin F. Phillips, Robert J. Delorenzo

Neurology Publications

Organophosphate (OP) chemicals include nerve agents and pesticides, and there is a growing concern of OP based chemical attacks against civilians. Current antidotes are essential in limiting immediate mortality associated with OP exposure. However, further research is needed to identify molecular mechanisms underlying long-term neurological deficits following survival of OP toxicity in order to develop effective therapeutics. We have developed rat survival models of OP induced status epilepticus (SE) that mimic chronic mortality and morbidity following OP intoxication. We have observed significant elevations in hippocampal calcium levels after OP SE that persisted for weeks following initial survival. Drugs inhibiting intracellular …


Pharmacological Blockade Of The Calcium Plateau Provides Neuroprotection Following Organophosphate Paraoxon Induced Status Epilepticus In Rats, Laxmikant S. Deshpande, Robert E. Blair, Beverly A. Huang, Kristin F. Phillips, Robert J. Delorenzo Jan 2016

Pharmacological Blockade Of The Calcium Plateau Provides Neuroprotection Following Organophosphate Paraoxon Induced Status Epilepticus In Rats, Laxmikant S. Deshpande, Robert E. Blair, Beverly A. Huang, Kristin F. Phillips, Robert J. Delorenzo

Neurology Publications

Organophosphate (OP) compounds which include nerve agents and pesticides are considered chemical threat agents. Currently approved antidotes are crucial in limiting OP mediated acute mortality. However, survivors of lethal OP exposure exhibit delayed neuronal injury and chronic behavioral morbidities. In this study, we investigated neuroprotective capabilities of dantrolene and carisbamate in a rat survival model of paraoxon (POX) induced status epilepticus (SE). Significant elevations in hippocampal calcium levels were observed 48-h post POX SE survival, and treatment with dantrolene (10 mg/kg, i.m.) and carisbamate (90 mg/kg, i.m.) lowered these protracted calcium elevations. POX SE induced delayed neuronal injury …


Mechanisms Of Cell Death Initiated In Herpes Simplex Virus Thymidine Kinase Expressing Colon Tumor Cells Treated With Ganciclovir And Ucn-01, Christina Elizabeth Ahn Apr 2005

Mechanisms Of Cell Death Initiated In Herpes Simplex Virus Thymidine Kinase Expressing Colon Tumor Cells Treated With Ganciclovir And Ucn-01, Christina Elizabeth Ahn

Theses and Dissertations in Biomedical Sciences

Metastatic colon carcinoma is the second leading cause of death from malignancy in the United States, and development of more effective treatments is essential. Heterologous expression of Herpes Simplex Virus Thymidine Kinase (HSVtk) in combination with the prodrug, ganciclovir (GCV), has shown great promise for the genetic therapy of many cancers, but most patients have had only a partial or minimal response to the therapy. After screening a panel of two drug combinations, our laboratory has shown that the combination of GCV and the protein kinase inhibitor UCN-01 (7-hydroxystaurosporine) enhances tumor cell death more effectively than either drug alone. However …


Cytolytic T Lymphocytes Specific For Tumors And Infected Cells From Mice With A Retrovirus-Induced Immunodeficiency Syndrome., Jennifer G. Erbe, Kathy A. Green, Karen M. Crassi, Herbert C. Morse, W R. Green May 1992

Cytolytic T Lymphocytes Specific For Tumors And Infected Cells From Mice With A Retrovirus-Induced Immunodeficiency Syndrome., Jennifer G. Erbe, Kathy A. Green, Karen M. Crassi, Herbert C. Morse, W R. Green

Dartmouth Scholarship

LP-BM5 retrovirus complex-infected C57BL/6 mice develop immunodeficiency, somewhat analogous to AIDS, termed murine AIDS (MAIDS). After secondary stimulation with syngeneic B-cell lymphomas from LP-BM5-infected mice, C57BL/6 mice produced vigorous CD8+ cytotoxic T lymphocytes specific for MAIDS-associated tumors. An anti-LP-BM5 specificity was suggested because spleen and lymph node cells from LP-BM5-infected mice served as target cells in competition assays, and cells from LP-BM5, but not ecotropic, virus-infected mice functioned as secondary in vitro stimulators to generate cytotoxic T lymphocytes to MAIDS tumors.