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Non Selective Inhibition of COX Activity Reversed Inflammation and Reactive Oxygen Radicals Mediated Prostate Cancer Risk and Decreased Disease Progression in Preclinical Model

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Journal of Cancer Therapy 2016年第1期7卷 41-49页

作者： maxwell omabe Kenneth Nwobini omabe Clement Ademola Famurewa Alberta Egwu Okorocha Grace maxwell omabe Tumor Immunology Group Division of Oncology Cancer Research Division Department of Pathology and Laboratory Medicine University of Saskatchewan Saskatoon Canada Molecular Pathology and Cancer Biology Research Group Chemical Pathology Division Department of Medical Laboratory Sciences Faculty of Health Science Ebonyi State University Ebonyi Nigeria Department of Biochemistry and Molecular Biology Faculty of Natural Sciences Federal University Ndufu Alike Ikwo Nigeria Department of Medical Biochemistry Faculty of Basic Medical Sciences Federal University Ndufu Alike Ikwo Nigeria Department of Physiology Faculty of Basic Medical Sciences Ebonyi State University Ebonyi Nigeria

Prostate cancer (PCa) represents the most frequent urologic diagnosis in elderly males. We have previously shown that exposure of prostate to lipopolysaccharide (LPS) promotes cancer risk. We investigated the effect of non-selective cyclooxygenase (COX) inhibition on prostate inflammation-mediated cancer risk in vivo. The prostates of male rats were inoculated with E. coli as sources of inflammatory molecules (LPS) and were treated with COX inhibitor, aspirin 2 mg/Kg orally for 14 days or PBS. Oxidative stress was induced with two 2 mls of hydrogen peroxide orally twice daily or PBS for 14 days;they were either treated with COX inhibitor or PBS for another 14 days. Blood was collected and analyzed for acid phosphatase and PSA. Data showed presences of LPS in the prostate of the rats resulted in gradual increase in PSA when compared to control (P 2O2 had 2.5 fold increase in acid phosphatase (ACP) compared control (P < 0.0001), and by inhiting COX activity, a statistically significant reduction in ACP from 11.2 IU/L ± 0.67 to 5.7 IU/L ± 0.347 (P < 0.0034) was observed. Thus since increased in PSA was associated to cancer risk, our data suggested that inflammation mediated prostate cancer risk was reversible by Inhibition of COX Activity in rats.

关键词： Inflammation Prostate Cancer Reactive Oxygen Species

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Xenobiotics-Induced Liver Damage Is Biochemically Abrogated by Treatment with Lipophilic Extracts of <i>Moringa oleifera in Vivo</i>

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Health 2018年第3期10卷 313-325页

作者： maxwell omabe Kenneth Nwobini omabe David Igwe Ogbonnaya Chukwu John Samuel Kalu Uchenna Sunday Elom Department of Oncology Cancer Research Division Immunology Group University of Saskatchewan Saskatoon Canada Diagnostic Molecular Biology Research Group Molecular Pathology and Immunology Division Chemical Pathology & Histopathology Unit Department of Medical Laboratory Sciences School of Biomedical Science Faculty of Health Science Ebonyi State University Abakaliki Nigeria Department of Molecular Biology Faculty of Natural Sciences Federal University Abakaliki Nigeria Department of Trauma and Orthopaedic Rotherham NHS Trust Rotherham UK Department of Medical Biochemistry Faculty of Basic Medical Sciences Federal University Abakaliki Nigeria

Context Drug-induced hepatotoxicity represents a significant proportion of liver disease cases. Currently, there is no effective treatment. To date efforts to identify treatment regimen that can reverse progressive damage have not been successful. We have previously shown that extract from Moringa (M) oleifera possesses clinically relevant antidiabetic and electrolyte modulators. Objective The aim of the current studies is to create experimental model of xenobiotic induced liver damage and investigate if treatment with lipophilic extract of M. oleifera could biochemically reverse progressive liver damage. Materials and Method For two groups of healthy rats, 7 in each group received 200 mg of extract or vehicle twice daily for 14 days. Acute toxicity, hepatotoxicity and hematologic/endothelial toxicity were monitored. Then 30 rats weighing 130 - 200 g received repeated dose of acetaminophen (xenobiotics) (640 mg/kg) for 5 days. Hepatotoxicity was confirmed biochemically by an established protocol. Treatment with M. oleifera extract resulted in mean weight of 132.2 ± 5.05 compared to the control with 134.1 ± 5.08 (P > 0.8115) among the healthy rats. Their LDH levels were 170.7 ± 13.02 and 133.8 ± 7.17 (P > 0.0698) for controls group, while the mean serum (ALT) level was 12.4 ± 1.2 or 25.6 ± 5.644 (P M. oleifera resulted in 100% biochemical recovery from hepatitis compared to the control group (P M. oleifera could effectively and biochemically abrogate xenobiotics induced liver damage in animal model.

关键词： Phytopharmaceuticals Phytomedicine Drug Discovery Inflammation Alanine-Aminotransferase Haematological Toxicity Lactate Dehydrogenase Hepatitis

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HER2-Specific Vaccines for HER2-Positive Breast Cancer Immunotherapy

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World Journal of Vaccines 2015年第2期5卷 106-128页

作者： maxwell omabe Shahid Ahmed Amer Sami Yufeng Xie Min Tao Jim Xiang Cancer Research Cluster Saskatchewan Cancer Agency Saskatoon Canada Department of Oncology University of Saskatchewan Saskatoon Canada Department of Oncology The first Affiliated Hospital Soo-Chow University Suzhou China

Anti-human epidermal growth factor receptor-2 (HER2) immunization can be elicited by vaccination with DNA encoding the extra- or intra-cellular domain (ECD or ICD) of HER2, naked or encap-sulated in viral vectors. HER2-peptides derived from ECD or ICD of HER2, and HER2-pulsed dendritic cells (DCs) or engineered DCs expressing HER2, respectively. We performed a computer- based literature search which includes but is not limited to the following keywords: breast cancer, immunotherapy, HER2-peptide vaccine, HER2-DNA vaccine, HER-DC vaccine, HER2 vaccine, and HER2/neu, in PubMed, Medline, EMBO and Google Scholar;data from recently reported clinical trials were also included. Drawing upon this synthesis of literature, this work summarizes the de-velopment and current trend in experimental and clinical investigations in HER2-positive breast cancer using HER2-specific vaccine and immunotherapy, focusing especially on: (i) DNA-;(ii) peptide-;and (iii) DC-based vaccines. It addresses interventions that have been applied to overcome immunotolerance thereby to improve treatment outcomes. These include blocking the inhibitory cytotoxic T lymphocyte-associated protein-4 (CTLA-4), which is expressed at high levels by regulatory T (Treg) cells, or complete Treg depletion to improve T-cell activation. Moreover, modulatory interventions can provide further improvement in the efficacy of HER2-specific vaccine. The interventions include the use of immunogenic adjuvants such as cytokines interleukin-12 (IL-12), tumor necrosis factor (TNF)-α and granulocyte-macrophage colony-stimulating factor (GM-CSF), the use of Toll-like receptor (TLR) ligands and tetanus toxin’s universal epitopes such as the CD4+ help T (Th)-epitope P30, and the use of either chimeric or heterogenous xenogeneic HER2. Combining active HER2-vaccination with adoptive trastuzumab antibody immunotherapy is likely to increase the effectiveness of each approach alone. The development of effective HER2-vaccines for breast

关键词： HER2 Breast Cancer DNA Peptide Dendritic Cell Vaccine

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Gene Expression Profile, Androgen Independence and Prostate Cancer

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Journal of Cancer Therapy 2012年第5期3卷 637-644页

作者： maxwell omabe Joel C. Onyeanusi Nworie Amos Martin Ezeani Simon Imakwu Okekpa Histopathology Unitt Department of Medical Laboratory Sciences School of Biomedical Science Faculty of Health Science Ebonyi State University Abakaliki Nigeria Medical Microbiology Unit Department of Medical Laboratory Science Faculty of Health Science Ebonyi State University Abakaliki Nigeria Molecular Pathology Division Chemical Pathology and Immunology Unit Department of Medical Laboratory Sciences School of Biomedical Science Faculty of Health Science Ebonyi State University Nigeria Ebonyi Nigeria

It is now generally accepted that the burden of disease due to prostate cancer has tremendously increased globally. Current data indicates that prostate cancer is the most common form of cancer in men in the United State of America, and the second leading cause of death due to cancer in men. Progression to androgen independence and subsequent therapeutic resistance and death is a common fate of patients with prostate cancer. This review highlights the gene expression profile of androgen independent prostate cancer and the possible mechanisms that results in transformation to such treatment resistant state.

关键词： Prostate Cancer Androgen Ablation Gene Expression Microarrays

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