Mg624, An A7-Nachr Antagonist, Inhibits Angiogenesis Via The Egr-1/Fgf2 Pathway,
2012
Marshall University
Mg624, An A7-Nachr Antagonist, Inhibits Angiogenesis Via The Egr-1/Fgf2 Pathway, Kathleen Brown, Jamie Lau, Aaron Dom, Theodore Witte, Haitao Luo, Clayton Crabtree, Yashoni Shah, Brandon Shiflett, Aileen Marcelo, Nancy Proper, W. Hardman, Richard Egleton, Yi Chen, Elsa Mangiarua, Piyali Dasgupta
Richard D. Egleton
Small cell lung cancer (SCLC) demonstrates a strong etiological association with smoking. Although cigarette smoke is a mixture of about 4,000 compounds, nicotine is the addictive component of cigarette smoke. Several convergent studies have shown that nicotine promotes angiogenesis in lung cancers via the α7-nicotinic acetylcholine receptor (α7-nAChR) on endothelial cells. Therefore, we conjectured that α7-nAChR antagonists may attenuate nicotine-induced angiogenesis and be useful for the treatment of human SCLC. For the first time, our study explores the anti-angiogenic activity of MG624, a small-molecule α7-nAChR antagonist, in several experimental models of angiogenesis. We observed that MG624 potently suppressed the proliferation …
Capsaicin Displays Anti-Proliferative Activity Against Human Small Cell Lung Cancer In Cell Culture And Nude Mice Models Via The E2f Pathway,
2012
Marshall University
Capsaicin Displays Anti-Proliferative Activity Against Human Small Cell Lung Cancer In Cell Culture And Nude Mice Models Via The E2f Pathway, Kathleen C. Brown, Theodore R. Witte, W. Elaine Hardman, Haitao Luo, Yi C. Chen, A. Betts Carpenter, Jamie K. Lau, Piyali Dasgupta
Piyali Dasgupta
Background: Small cell lung cancer (SCLC) is characterized by rapid progression and low survival rates. Therefore, novel therapeutic agents are urgently needed for this disease. Capsaicin, the active ingredient of chilli peppers, displays antiproliferative activity in prostate and epidermoid cancer in vitro. However, the anti-proliferative activity of capsaicin has not been studied in human SCLCs. The present manuscript fills this void of knowledge and explores the anti-proliferative effect of capsaicin in SCLC in vitro and in vivo. Methodology/Principal Findings: BrdU assays and PCNA ELISAs showed that capsaicin displays robust anti-proliferative activity in four human SCLC cell lines. Furthermore, capsaicin potently …
Mg624, An A7-Nachr Antagonist, Inhibits Angiogenesis Via The Egr-1/Fgf2 Pathway,
2012
Marshall University
Mg624, An A7-Nachr Antagonist, Inhibits Angiogenesis Via The Egr-1/Fgf2 Pathway, Kathleen Brown, Jamie Lau, Aaron Dom, Theodore Witte, Haitao Luo, Clayton Crabtree, Yashoni Shah, Brandon Shiflett, Aileen Marcelo, Nancy Proper, W. Hardman, Richard Egleton, Yi Chen, Elsa Mangiarua, Piyali Dasgupta
Piyali Dasgupta
Small cell lung cancer (SCLC) demonstrates a strong etiological association with smoking. Although cigarette smoke is a mixture of about 4,000 compounds, nicotine is the addictive component of cigarette smoke. Several convergent studies have shown that nicotine promotes angiogenesis in lung cancers via the α7-nicotinic acetylcholine receptor (α7-nAChR) on endothelial cells. Therefore, we conjectured that α7-nAChR antagonists may attenuate nicotine-induced angiogenesis and be useful for the treatment of human SCLC. For the first time, our study explores the anti-angiogenic activity of MG624, a small-molecule α7-nAChR antagonist, in several experimental models of angiogenesis. We observed that MG624 potently suppressed the proliferation …
Emergence Of A Unique Penicillin-Resistant Streptococcus Pneumoniae Serogroup 35 Strain,
2012
Marshall University
Emergence Of A Unique Penicillin-Resistant Streptococcus Pneumoniae Serogroup 35 Strain, Ronald Stanek, Mary Maher, Nancy Norton, Maurice Mufson
Nancy B. Norton
We analyzed seven Streptococcus pneumoniae serogroup 35 isolates by pulsed-field gel electrophoresis of the genome and pbp2b gene nucleotide sequences. Three penicillin-susceptible strains and one penicillin-intermediate-resistant strain exhibited 100% identity to prototype R6. Two resistant strains and one other intermediate strain differed from them and contained a unique sequence.
Effect Of Dna Damage On Pcr Amplification Efficiency With The Relative Threshold Cycle Method,
2012
Marshall University
Effect Of Dna Damage On Pcr Amplification Efficiency With The Relative Threshold Cycle Method, Jan Sikorsky, Donald Primerano, Terry Fenger, James Denvir
James Denvir
Polymerase stop assays used to quantify DNA damage assume that single lesions are sufficient to block polymerase progression. To test the effect of specific lesions on PCR amplification efficiency, we amplified synthetic 90 base oligonucleotides containing normal or modified DNA bases using real-time PCR and determined the relative threshold cycle amplification efficiency of each template. We found that while the amplification efficiencies of templates containing a single 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) were not significantly perturbed, the presence of a single 8-oxo-7,8-dihydro-2′-deoxyadenosine, abasic site, or a cis–syn thymidine dimer dramatically reduced amplification efficiency. In addition, while templates containing two 8-oxodGs separated by 13 …
Resveratrol Is Rapidly Metabolized In Athymic (Nu/Nu) Mice And Does Not Inhibit Human Melanoma Xenograft Tumor Growth,
2012
Marshall University
Resveratrol Is Rapidly Metabolized In Athymic (Nu/Nu) Mice And Does Not Inhibit Human Melanoma Xenograft Tumor Growth, Richard Niles, Carla Cook, Gary Meadows, Ya-Min Fu, Jerry Mclaughlin, Gary Rankin
Gary O. Rankin
Resveratrol has been shown to have anticarcinogenic activity. We previously found that resveratrol inhibited growth and induced apoptosis in 2 human melanoma cell lines. In this study we determined whether resveratrol would inhibit human melanoma xenograft growth. Athymic mice received control diets or diets containing 110 μmol/L or 263 μmol/L resveratrol, 2 wk prior to subcutaneous injection of the tumor cells. Tumor growth was measured during a 3-wk period. Metabolism of resveratrol was assayed by bolus gavage of 75 mg/kg resveratrol in tumor-bearing and nontumor-bearing mice. Pellets containing 10–100 mg resveratrol were implanted into the mice, next to newly palpated …
Silencing And Re-Expression Of Retinoic Acid Receptor Beta2 In Human Melanoma,
2012
Marshall University
Silencing And Re-Expression Of Retinoic Acid Receptor Beta2 In Human Melanoma, Jun Fan, Linda Eastham, Melinda Varney, Adam Hall, Nicolas Adkins, Vincent Sollars, Philippe Georgel, Richard Niles
Philippe T. Georgel
Many melanoma cells are resistant to the anti-proliferative effect of all trans retinoic acid (ATRA). Retinoic Acid Receptor-β2 (RAR-β2) mediates the ATRA growth inhibition. We found a correlation between the anti-proliferative activity of ATRA and expression of RAR-β2. There was not a strict correlation between DNA methylation of RAR-β gene and its expression. There was no difference in global and RARβ specific nucleosome repeat length (NRL) in melanoma and melanocytes or between control and ATRA treated cells. Pan-acetylation of H3 and H4 within the RAR-β gene promoter was higher in cells expressing RAR-β2. All trans retinoic acid treatment of …
Effect Of Dna Damage On Pcr Amplification Efficiency With The Relative Threshold Cycle Method,
2012
Marshall University
Effect Of Dna Damage On Pcr Amplification Efficiency With The Relative Threshold Cycle Method, Jan Sikorsky, Donald Primerano, Terry Fenger, James Denvir
Terry W. Fenger
Polymerase stop assays used to quantify DNA damage assume that single lesions are sufficient to block polymerase progression. To test the effect of specific lesions on PCR amplification efficiency, we amplified synthetic 90 base oligonucleotides containing normal or modified DNA bases using real-time PCR and determined the relative threshold cycle amplification efficiency of each template. We found that while the amplification efficiencies of templates containing a single 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) were not significantly perturbed, the presence of a single 8-oxo-7,8-dihydro-2′-deoxyadenosine, abasic site, or a cis–syn thymidine dimer dramatically reduced amplification efficiency. In addition, while templates containing two 8-oxodGs separated by 13 …
Eradication Of Therapy-Resistant Human Prostate Tumors Using An Ultrasound-Guided Site-Specific Cancer Terminator Virus Delivery Approach,
2012
Marshall University
Eradication Of Therapy-Resistant Human Prostate Tumors Using An Ultrasound-Guided Site-Specific Cancer Terminator Virus Delivery Approach, Adelaide Greco, Altomare Benedetto, Candace Howard, Sarah Kelly, Rounak Nande, Yulia Dementieva, Michele Miranda, Arturo Brunetti, Marco Salvatore, Luigi Claudio, Devanand Sarkar, Paul Dent, David Curiel, Paul Fisher, Pier Claudio
Pier P. Claudio
Intratumoral injections of a replication-incompetent adenovirus (Ad) expressing melanoma differentiation– associated gene-7/interleukin-24 (Ad.mda-7), a secreted cytokine displaying cancer-selective, apoptosis-inducing properties, profoundly inhibits prostate cancer (PC) growth in immune-incompetent animals. In contrast, Ad.mda-7 is ineffective in PCs overexpressing antiapoptotic proteins such as Bcl-2 or Bcl-x L . However, intratumoral injections of a conditionally replication-competent Ad (CRCA) in which expression of the adenoviral E1A gene is driven by the cancer-specific promoter of progression-elevated gene-3 (PEG-3) and which simultaneously expresses mda-7/interleukin (IL)-24 in the E3 region of the Ad (Ad.PEG-E1A-mda-7), a cancer terminator virus (CTV), is highly active in these cells. A major …
Endothelial Cell Pseudopods And Angiogenesis Of Breast Cancer Tumors,
2012
Marshall University
Endothelial Cell Pseudopods And Angiogenesis Of Breast Cancer Tumors, Ivan Cameron, Nicholas Short, Luzhe Sun, W. Hardman
Elaine Hardman Ph.D.
Background A neoplastic tumor cannot grow beyond a millimeter or so in diameter without recruitment of endothelial cells and new blood vessels to supply nutrition and oxygen for tumor cell survival. This study was designed to investigate formation of new blood vessels within a human growing breast cancer tumor model (MDA MB231 in mammary fat pad of nude female mouse). Once the tumor grew to 35 mm3, it developed a well-vascularized capsule. Histological sections of tumors greater than 35 mm3were stained with PAS, with CD-31 antibody (an endothelial cell maker), or with hypoxia inducible factor 1α antibody (HIF). The extent …
Three Percent Dietary Fish Oil Concentrate Increased Efficacy Of Doxorubicin Against Mda-Mb 231 Breast Cancer Xenografts,
2012
Marshall University
Three Percent Dietary Fish Oil Concentrate Increased Efficacy Of Doxorubicin Against Mda-Mb 231 Breast Cancer Xenografts, W. Hardman, C. Reddy Avula, Gabriel Fernandes, Ivan Cameron
Elaine Hardman Ph.D.
Omega 3 polyunsaturated fatty acids (the type of fat found in fish oil) have been used to kill or slow the growth of cancer cells in culture and in animal models and to increase the effectiveness of cancer chemotherapeutic drugs. An AIN-76 diet containing 5% corn oil (CO) was modified to contain 3% w/w fish oil concentrate (FOC) and 2% CO to test whether a clinically applicable amount of FOC is beneficial during doxorubicin (DOX) treatment of cancer xenografts in mice. Compared with the diet containing 5% CO, consumption of FOC increased omega 3 polyunsaturated fatty acids and lipid peroxidation …
Mg624, An A7-Nachr Antagonist, Inhibits Angiogenesis Via The Egr-1/Fgf2 Pathway,
2012
Marshall University
Mg624, An A7-Nachr Antagonist, Inhibits Angiogenesis Via The Egr-1/Fgf2 Pathway, Kathleen Brown, Jamie Lau, Aaron Dom, Theodore Witte, Haitao Luo, Clayton Crabtree, Yashoni Shah, Brandon Shiflett, Aileen Marcelo, Nancy Proper, W. Hardman, Richard Egleton, Yi Chen, Elsa Mangiarua, Piyali Dasgupta
Elaine Hardman Ph.D.
Small cell lung cancer (SCLC) demonstrates a strong etiological association with smoking. Although cigarette smoke is a mixture of about 4,000 compounds, nicotine is the addictive component of cigarette smoke. Several convergent studies have shown that nicotine promotes angiogenesis in lung cancers via the α7-nicotinic acetylcholine receptor (α7-nAChR) on endothelial cells. Therefore, we conjectured that α7-nAChR antagonists may attenuate nicotine-induced angiogenesis and be useful for the treatment of human SCLC. For the first time, our study explores the anti-angiogenic activity of MG624, a small-molecule α7-nAChR antagonist, in several experimental models of angiogenesis. We observed that MG624 potently suppressed the proliferation …
Capsaicin Displays Anti-Proliferative Activity Against Human Small Cell Lung Cancer In Cell Culture And Nude Mice Models Via The E2f Pathway,
2012
Marshall University
Capsaicin Displays Anti-Proliferative Activity Against Human Small Cell Lung Cancer In Cell Culture And Nude Mice Models Via The E2f Pathway, Kathleen C. Brown, Theodore R. Witte, W. Elaine Hardman, Haitao Luo, Yi C. Chen, A. Betts Carpenter, Jamie K. Lau, Piyali Dasgupta
Elaine Hardman Ph.D.
Background: Small cell lung cancer (SCLC) is characterized by rapid progression and low survival rates. Therefore, novel therapeutic agents are urgently needed for this disease. Capsaicin, the active ingredient of chilli peppers, displays antiproliferative activity in prostate and epidermoid cancer in vitro. However, the anti-proliferative activity of capsaicin has not been studied in human SCLCs. The present manuscript fills this void of knowledge and explores the anti-proliferative effect of capsaicin in SCLC in vitro and in vivo. Methodology/Principal Findings: BrdU assays and PCNA ELISAs showed that capsaicin displays robust anti-proliferative activity in four human SCLC cell lines. Furthermore, capsaicin potently …
Therapeutic Electromagnetic Field (Temf) And Gamma Irradiation On Human Breast Cancer Xenograft Growth, Angiogenesis And Metastasis,
2012
Marshall University
Therapeutic Electromagnetic Field (Temf) And Gamma Irradiation On Human Breast Cancer Xenograft Growth, Angiogenesis And Metastasis, Ivan L. Cameron, Luzhe Sun, Nicholas Short, W. Elaine Hardman, C. Douglas Williams
Elaine Hardman Ph.D.
Background The effects of a rectified semi-sinewave signal (15 mT amplitude, 120 pulses per second, EMF Therapeutics, Inc.) (TEMF) alone and in combination with gamma irradiation (IR) therapy in nude mice bearing a human MDA MB231 breast cancer xenograft were tested. Green fluorescence protein transfected cancer cells were injected into the mammary fat pad of young female mice. Six weeks later, mice were randomly divided into four treatment groups: untreated controls; 10 minute daily TEMF; 200 cGy of IR every other day (total 800 cGy); IR plus daily TEMF. Some mice in each group were euthanized 24 hours after the …
High Dietary Level Of Synthetic Vitamin E On Lipid Peroxidation, Membrane Fatty Acid Composition And Cytotoxicity In Breast Cancer Xenograft And In Mouse Host Tissue,
2012
Marshall University
High Dietary Level Of Synthetic Vitamin E On Lipid Peroxidation, Membrane Fatty Acid Composition And Cytotoxicity In Breast Cancer Xenograft And In Mouse Host Tissue, Ivan L. Cameron, Jesus Munoz, Christopher J. Barnes, W. Elaine Hardman
Elaine Hardman Ph.D.
Background d-α-tocopherol is a naturally occurring form of vitamin E not previously known to have antitumor activity. Synthetic vitamin E (sE) is a commonly used dietary supplement consisting of a mixture of d-α-tocopherol and 7 equimolar stereoisomers. To test for antilipid peroxidation and for antitumor activity of sE supplementation, two groups of nude mice bearing a MDA-MB 231 human breast cancer tumor were fed an AIN-76 diet, one with and one without an additional 2000 IU/kg dry food (equivalent to 900 mg of all-rac-α-tocopherol or sE). This provided an intake of about 200 mg/kg body weight per day. The mice …
Rbc And Wbc Fatty Acid Composition Following Consumption Of An Omega 3 Supplement: Lessons For Future Clinical Trials,
2012
Marshall University
Rbc And Wbc Fatty Acid Composition Following Consumption Of An Omega 3 Supplement: Lessons For Future Clinical Trials, Theodore R. Witte, Alexander J. Salazar, Oscar F. Ballester, W. Elaine Hardman
Elaine Hardman Ph.D.
Background: Results from increasing numbers of in vitro and in vivo studies have demonstrated that omega 3 fatty acids incorporated in cell culture media or in the diet of the animals can suppress the growth of cancers. When human clinical trials are initiated to determine the ability of omega 3 fatty acids to alter growth or response to chemotherapeutic interventions of cancers, it will be essential to determine the omega 3 intake of individuals in the trial to determine compliance with consumption of the supplement and to correlate with endpoints of efficacy. We wondered if the fatty acid composition of …
Dietary Omega-3 Fatty Acids And Ionizing Irradiation On Human Breast Cancer Xenograft Growth And Angiogenesis,
2012
Marshall University
Dietary Omega-3 Fatty Acids And Ionizing Irradiation On Human Breast Cancer Xenograft Growth And Angiogenesis, W. Elaine Hardman, Luzhe Sun, Nicholas Short, Ivan L. Cameron
Elaine Hardman Ph.D.
Background The effects of an omega-3 (n-3) fatty acid enriched diet alone and in combination with gamma irradiation (IR) therapy in nude mice bearing a human MDA-MB231 breast cancer xenograft were tested. The cancer cells were injected into the mammary fat pad of young female mice. Six weeks later, mice were randomly divided into two diet groups: 1) mice with 10% corn oil (rich in omega 6 fatty acids) in their food, 2) mice consuming a 10% fat diet that was enriched in n-3 fatty acids. After two weeks on the diet, treatment with 200 cGy of IR every second …
Therapeutic Electromagnetic Field Effects On Angiogenesis And Tumor Growth,
2012
Marshall University
Therapeutic Electromagnetic Field Effects On Angiogenesis And Tumor Growth, C. Douglas Williams, Marko S. Markov, W. Elaine Hardman, Ivan L. Cameron
Elaine Hardman Ph.D.
Background: A new approach to cancer therapy based on the application of therapeutic electromagnetic fields (TEMF) has been developed by EMF Therapeutics, Inc., Chattanooga, TN, USA. This study was designed to assess the effect of TEMF on tumor vascularization and growth of murine 16/C mammmary adenocarcinoma cells in C3H/HeJ mice. Materials and Methods: Implanted tumors were allowed to grow for seven days until the tumor volume reached 100 mm3 before treatment was started. Mice (20 per control, 10 per EMF exposed group) received treatment (10 minutes per day with 0, 10 mT, 15 mT or 20 mT) with a 120 …
Consumption Of An Omega-3 Fatty Acids Product, Incell Aafa Tm , Reduced Side-Effects Of Cpt-11 (Irinotecan) In Mice,
2012
Marshall University
Consumption Of An Omega-3 Fatty Acids Product, Incell Aafa Tm , Reduced Side-Effects Of Cpt-11 (Irinotecan) In Mice, W. Hardman, M. Moyer, Ivan Cameron
Elaine Hardman Ph.D.
INCELL AAFA™, an omega-3 polyunsaturated fatty acid product containing a high concentration of long chain fatty acids, was tested for its ability to ameliorate the harmful side effects of CPT-11 chemotherapy including: leukopenia, anaemia, asthenia, weight loss and liver involvement. Four groups of mice were fed an AIN-76 diet modified to contain: 10% w/w corn oil (CO), 0% AAFA™; 9% CO, 1% AAFA™; 8% CO, 2% AAFA™; or 7% CO, 3% AAFA™. After 2 weeks on the diets, half of the mice received CPT-11 chemotherapy (60 mg kg-1 q 4 days, i.v.) the rest of the mice received vehicle for …
Differential Regulation Of Osteoblast Activity By Th Cell Subsets Mediated By Parathyroid Hormone And Ifn-,
2012
Marshall University
Differential Regulation Of Osteoblast Activity By Th Cell Subsets Mediated By Parathyroid Hormone And Ifn-, Nathan Young, Natallia Mikhalkevich, Ying Yan, Di Chen, Wei-Ping Zeng
Wei-ping Zeng
Bone loss is a typical pathological feature of chronic inflammatory bone diseases including rheumatoid arthritis, in which CD4 effector T cells play critical roles. We found that activated mouse Th2 and not Th1 cells produced the parathyroid hormone (PTH). Unlike in the parathyroid cells, PTH expression in Th2 cells was not regulated by the fluctuation of calcium level, but rather it required the full activation of the T cells. Although PTH was expressed in immature Th2 cells, and its receptor was transiently expressed during Th1 and Th2 cell differentiation, PTH did not significantly affect the outcome of the differentiation. In …
