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The Impact Of Post-Mastectomy Radiation Therapy On Male Breast Cancer Patients--A Case Series, Edward Yu, Hiromichi Suzuki, Jawaid Younus, Tarek Elfiki, Larry Stitt, Gary Yau, Olga Vujovic, Francisco Perera, Michael Lock, Patricia Tai Nov 2012

The Impact Of Post-Mastectomy Radiation Therapy On Male Breast Cancer Patients--A Case Series, Edward Yu, Hiromichi Suzuki, Jawaid Younus, Tarek Elfiki, Larry Stitt, Gary Yau, Olga Vujovic, Francisco Perera, Michael Lock, Patricia Tai

Michael Lock

OBJECTIVE: To assess the impact of radiation management on male breast cancer (MBC) at London Regional Cancer Program (LRCP).

METHODS AND MATERIALS: Men with a diagnosis of breast cancer referred to LRCP were reviewed. The seventh American Joint Committee on Cancer staging system was used. Patients treated with and without post-mastectomy radiation therapy (PMRT) were analyzed. Disease-free survival (DFS) was defined as time duration from diagnosis to first recurrence. Overall survival (OS) was defined as time duration from pathologic diagnosis to death or last follow-up with any death defined as an event. Survival estimates were obtained using Kaplan-Meier methodology.

RESULTS: …


Prediction Of Radiation Pneumonitis By Dose-Volume Histogram Parameters In Lung Cancer--A Systematic Review, George Rodrigues, Michael Lock, David D'Souza, Edward Yu, Jake Van Dyk Nov 2012

Prediction Of Radiation Pneumonitis By Dose-Volume Histogram Parameters In Lung Cancer--A Systematic Review, George Rodrigues, Michael Lock, David D'Souza, Edward Yu, Jake Van Dyk

Michael Lock

BACKGROUND AND PURPOSE: To perform a systematic review of the predictive ability of various dose-volume histogram (DVH) parameters (V(dose), mean lung dose (MLD), and normal tissue complication probability (NTCP)) in the incidence of radiation pneumonitis (RP) caused by external-beam radiation therapy.

METHODS AND MATERIALS: Studies assessing the relationship between CT-based DVH reduction parameters and RP rate in radically treated lung cancer were eligible for the review. Synonyms for RP, lung cancer, DVH and its associated parameters (NTCP, V(20), V(30), MLD) were combined in a search strategy involving electronic databases, secondary reference searching, and consultation with experts. Individual or group data …


Technology Assessment Of Automated Atlas Based Segmentation In Prostate Bed Contouring, Jeremiah Hwee, Alexander Louie, Stewart Gaede, Glenn Bauman, David D'Souza, Tracy Sexton, Michael Lock, Belal Ahmad, George Rodrigues Nov 2012

Technology Assessment Of Automated Atlas Based Segmentation In Prostate Bed Contouring, Jeremiah Hwee, Alexander Louie, Stewart Gaede, Glenn Bauman, David D'Souza, Tracy Sexton, Michael Lock, Belal Ahmad, George Rodrigues

Michael Lock

BACKGROUND: Prostate bed (PB) contouring is time consuming and associated with inter-observer variability. We evaluated an automated atlas-based segmentation (AABS) engine in its potential to reduce contouring time and inter-observer variability.

METHODS: An atlas builder (AB) manually contoured the prostate bed, rectum, left femoral head (LFH), right femoral head (RFH), bladder, and penile bulb of 75 post-prostatectomy cases to create an atlas according to the recent RTOG guidelines. 5 other Radiation Oncologists (RO) and the AABS contoured 5 new cases. A STAPLE contour for each of the 5 patients was generated. All contours were anonymized and sent back to the …


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 Oct 2012

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 Oct 2012

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 Oct 2012

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 …


Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana Akinsete, Gabriela Ion, Theodore Witte, W. Hardman Oct 2012

Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana Akinsete, Gabriela Ion, Theodore Witte, W. Hardman

Gabriela Ion

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to …


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 Oct 2012

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 Oct 2012

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 Oct 2012

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 Oct 2012

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 Sep 2012

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 Sep 2012

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 Sep 2012

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 …


Global Analysis Of Gene Expression Changes During Retinoic Acid-Induced Growth Arrest And Differentiation Of Melanoma: Comparison To Differentially Expressed Genes In Melanocytes Vs Melanoma, Mary Estler, Goran Boskovic, James Denvir, Sarah Miles, Donald Primerano, Richard Niles Sep 2012

Global Analysis Of Gene Expression Changes During Retinoic Acid-Induced Growth Arrest And Differentiation Of Melanoma: Comparison To Differentially Expressed Genes In Melanocytes Vs Melanoma, Mary Estler, Goran Boskovic, James Denvir, Sarah Miles, Donald Primerano, Richard Niles

James Denvir

BACKGROUND: The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-trans-retinoic acid (RA). The molecular changes responsible for the biological activity of RA in melanoma are not well understood. RESULTS: In an analysis of sequential global gene expression changes during a 4-48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment) between non-malignant melan-a mouse melanocytes and …


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 Sep 2012

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 Sep 2012

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 Aug 2012

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 …


Rapid Selection And Proliferation Of Cd133(+) Cells From Cancer Cell Lines: Chemotherapeutic Implications, Sarah Kelly, Altomare Benedetto, Adelaide Greco, Candace Howard, Vincent Sollars, Donald Primerano, Jagan Valluri, Pier Claudio Aug 2012

Rapid Selection And Proliferation Of Cd133(+) Cells From Cancer Cell Lines: Chemotherapeutic Implications, Sarah Kelly, Altomare Benedetto, Adelaide Greco, Candace Howard, Vincent Sollars, Donald Primerano, Jagan Valluri, Pier Claudio

Pier P. Claudio

Cancer stem cells (CSCs) are considered a subset of the bulk tumor responsible for initiating and maintaining the disease. Several surface cellular markers have been recently used to identify CSCs. Among those is CD133, which is expressed by hematopoietic progenitor cells as well as embryonic stem cells and various cancers. We have recently isolated and cultured CD133 positive [CD133(+)] cells from various cancer cell lines using a NASA developed Hydrodynamic Focusing Bioreactor (HFB) (Celdyne, Houston, TX). For comparison, another bioreactor, the rotary cell culture system (RCCS) manufactured by Synthecon (Houston, TX) was used. Both the HFB and the RCCS bioreactors …


Endothelial Cell Pseudopods And Angiogenesis Of Breast Cancer Tumors, Ivan Cameron, Nicholas Short, Luzhe Sun, W. Hardman Aug 2012

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 …


Omega-3 Fatty Acids To Augment Cancer Therapy, W. Hardman Aug 2012

Omega-3 Fatty Acids To Augment Cancer Therapy, W. Hardman

Elaine Hardman Ph.D.

The results of animal studies have demonstrated that the consumption of omega-3 fatty acids can slow the growth of cancer xenografts, increase the efficacy of chemotherapy and reduce the side effects of the chemotherapy or of the cancer. Molecular mechanisms postulated to contribute to the multiple benefits of omega-3 fatty acids include 1) suppressing the expression of cyclooxygenase-2 in tumors, thus decreasing proliferation of cancer cells and reducing angiogenesis in the tumor; 2) decreasing the expression of AP-1 and ras, two oncogenes implicated in tumor promotion; 3) inducing differentiation of cancer cells; 4) suppressing nuclear factor--kB activation and bcl-2 expression, …


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 Aug 2012

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 Aug 2012

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 …


Dietary Walnut Suppressed Mammary Gland Tumorigenesis In The C(3)1 Tag Mouse, W. Hardman Aug 2012

Dietary Walnut Suppressed Mammary Gland Tumorigenesis In The C(3)1 Tag Mouse, W. Hardman

Elaine Hardman Ph.D.

Walnuts contain multiple ingredients that, individually, have been shown to slow cancer growth, including omega-3 fatty acids, antioxidants, and phytosterols. In previous research, consumption of walnuts has slowed the growth of implanted breast cancers. We wanted to determine whether regular walnut consumption might reduce the risk for developing cancer. Homozygous male C(3)1 TAg mice were bred with female SV129 mice consuming either the control AIN-76 diet or the walnut-containing diet. At weaning, the female hemizygous pups were randomized to control or walnut-containing diets and followed for tumor development. Compared to a diet without walnuts, consumption of walnuts significantly reduced tumor …


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 Aug 2012

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 …


Rapid Selection And Proliferation Of Cd133(+) Cells From Cancer Cell Lines: Chemotherapeutic Implications, Sarah Kelly, Altomare Benedetto, Adelaide Greco, Candace Howard, Vincent Sollars, Donald Primerano, Jagan Valluri, Pier Claudio Aug 2012

Rapid Selection And Proliferation Of Cd133(+) Cells From Cancer Cell Lines: Chemotherapeutic Implications, Sarah Kelly, Altomare Benedetto, Adelaide Greco, Candace Howard, Vincent Sollars, Donald Primerano, Jagan Valluri, Pier Claudio

Vincent E Sollars

Cancer stem cells (CSCs) are considered a subset of the bulk tumor responsible for initiating and maintaining the disease. Several surface cellular markers have been recently used to identify CSCs. Among those is CD133, which is expressed by hematopoietic progenitor cells as well as embryonic stem cells and various cancers. We have recently isolated and cultured CD133 positive [CD133(+)] cells from various cancer cell lines using a NASA developed Hydrodynamic Focusing Bioreactor (HFB) (Celdyne, Houston, TX). For comparison, another bioreactor, the rotary cell culture system (RCCS) manufactured by Synthecon (Houston, TX) was used. Both the HFB and the RCCS bioreactors …


Ybx1 Expression And Function In Early Hematopoiesis And Leukemic Cells, Jasjeet Bhullar, Vincent Sollars Aug 2012

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 Aug 2012

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 …


Rapid Selection And Proliferation Of Cd133(+) Cells From Cancer Cell Lines: Chemotherapeutic Implications, Sarah Kelly, Altomare Benedetto, Adelaide Greco, Candace Howard, Vincent Sollars, Donald Primerano, Jagan Valluri, Pier Claudio Aug 2012

Rapid Selection And Proliferation Of Cd133(+) Cells From Cancer Cell Lines: Chemotherapeutic Implications, Sarah Kelly, Altomare Benedetto, Adelaide Greco, Candace Howard, Vincent Sollars, Donald Primerano, Jagan Valluri, Pier Claudio

Donald A Primerano

Cancer stem cells (CSCs) are considered a subset of the bulk tumor responsible for initiating and maintaining the disease. Several surface cellular markers have been recently used to identify CSCs. Among those is CD133, which is expressed by hematopoietic progenitor cells as well as embryonic stem cells and various cancers. We have recently isolated and cultured CD133 positive [CD133(+)] cells from various cancer cell lines using a NASA developed Hydrodynamic Focusing Bioreactor (HFB) (Celdyne, Houston, TX). For comparison, another bioreactor, the rotary cell culture system (RCCS) manufactured by Synthecon (Houston, TX) was used. Both the HFB and the RCCS bioreactors …


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 Aug 2012

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 …