Oncology Commons^™

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

Yulia Dementieva

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 …

Vitamin A (Retinoids) Regulation Of Mouse Melanoma Growth And Differentiation, Richard Niles

Richard M Niles

The incidence of melanoma is rapidly increasing in the U.S. population. At the present, there is no effective chemotherapy against invasive melanoma. At our laboratory, we have been studying retinoic acid (RA)-induced growth arrest and differentiation in the B16 murine melanoma cell model. Several immediate-early gene targets of RA were identified by gene arrays. In one of these genes, T-box binding protein-2 (Tbx-2), an RA response element, was identified in the promoter region that mediates the RA responsiveness of this gene. RA also induces a sixfold to eightfold increase in protein kinase C (PKC)α RNA and protein. This gene is …

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

Nancy A. Proper

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 …

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

Jamie K. Lau

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 …

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

Carla R. Cook

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, Jun Fan, Linda Eastham, Melinda Varney, Adam Hall, Nicolas Adkins, Vincent Sollars, Philippe Georgel, Richard Niles

Linda L. Eastham

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 …

Pparα/Γ Expression And Activity In Mouse And Human Melanocytes And Melanoma Cells, Linda Eastham, Caroline Mills, Richard Niles

Linda L. Eastham

Purpose. We examined the expression of PPARs and the effects of PPARα and PPARγ agonists on growth of mouse and human melanocytes and melanoma cells.

Methods. PPARα,β, and PPARγ mRNA qualitative expression in melan-a mouse melanocytes, B16 mouse melanoma, human melanocytes, and A375 and SK-mel28 human melanoma cells was determined by RT-PCR, while quantitative PPARα mRNA levels were determined by QuantiGene assay. PPARα and PPARγ protein was assessed by Western blotting. The effect of natural and synthetic PPAR ligands on cell growth was determined by either hemocytometer counting or crystal violet assay. PPAR transcriptional activity was determined by a PPRE-reporter …

Expression And Function Of Cd9 In Melanoma Cells, Jun Fan, Guo-Zhang Zhu, Richard Niles

Jun Fan

CD9, a member of the tetraspanin family, functions as an organizer in “tetraspanin webs,” through interacting with other cell adhesion molecules. It plays a role in differentiation, fertilization, and cell migration. We investigated the expression and function of CD9 in melanoma. CD9 protein expression in B16 mouse melanoma and six human melanoma cell lines was decreased compared to normal melanocytes. B16F1 clones stably overexpressing CD9 had reduced ability to form colonies in soft agar; however, paradoxically these overexpressing clones had increased ability to invade Matrigel. Similarly, transient overexpression of CD9 in the human metastatic melanoma cell line WM9 dramatically decreased …

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

Jun Fan

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 …

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

Elsa I. Mangiarua

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 …

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 …

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 …

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, 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 …

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, 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, 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, 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 …

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 …

Ybx1 Expression And Function In Early Hematopoiesis And Leukemic Cells, Jasjeet Bhullar, Vincent Sollars

Vincent E Sollars

Hematopoietic transcription factors play a critical role in directing the commitment and differentiation of hematopoietic stem cells along a particular lineage. Y-box protein (YBX1) is a transcription factor which is widely expressed throughout development and is involved in erythroid cell development; however, its role in early hematopoietic differentiation is not known. This study aims to investigate the role of YBX1 expression in early hematopoietic differentiation and leukemia. Here, we show that YBX1 is highly expressed in mouse erythroid myeloid lymphoid-clone 1 (EML), a hematopoietic precursor cell line, but is down-regulated in myeloid progenitors and GM-CSF-treated EML cells during the course …

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

Vincent E Sollars

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 …

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

Richard M Niles

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 …

Expression And Function Of Cd9 In Melanoma Cells, Jun Fan, Guo-Zhang Zhu, Richard Niles

Richard M Niles

CD9, a member of the tetraspanin family, functions as an organizer in “tetraspanin webs,” through interacting with other cell adhesion molecules. It plays a role in differentiation, fertilization, and cell migration. We investigated the expression and function of CD9 in melanoma. CD9 protein expression in B16 mouse melanoma and six human melanoma cell lines was decreased compared to normal melanocytes. B16F1 clones stably overexpressing CD9 had reduced ability to form colonies in soft agar; however, paradoxically these overexpressing clones had increased ability to invade Matrigel. Similarly, transient overexpression of CD9 in the human metastatic melanoma cell line WM9 dramatically decreased …

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

Richard M Niles

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 …

Pparα/Γ Expression And Activity In Mouse And Human Melanocytes And Melanoma Cells, Linda Eastham, Caroline Mills, Richard Niles

Richard M Niles

Purpose. We examined the expression of PPARs and the effects of PPARα and PPARγ agonists on growth of mouse and human melanocytes and melanoma cells.

Methods. PPARα,β, and PPARγ mRNA qualitative expression in melan-a mouse melanocytes, B16 mouse melanoma, human melanocytes, and A375 and SK-mel28 human melanoma cells was determined by RT-PCR, while quantitative PPARα mRNA levels were determined by QuantiGene assay. PPARα and PPARγ protein was assessed by Western blotting. The effect of natural and synthetic PPAR ligands on cell growth was determined by either hemocytometer counting or crystal violet assay. PPAR transcriptional activity was determined by a PPRE-reporter …