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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 …


Resetting And Termination Of A Short Rp Tachycardia: What Is The Mechanism?, Anand Kenia Oct 2012

Resetting And Termination Of A Short Rp Tachycardia: What Is The Mechanism?, Anand Kenia

Anand S Kenia

No abstract provided.


Factors Associated With Inadequate Colorectal Cancer Screening With Flexible Sigmoidoscopy, Adeyinka Laiyemo, Chyke Doubeni, Paul Pinsky, V. Paul Doria-Rose, Andrew Sanderson, Robert Bresalier, Joel Weissfeld, Robert Schoen, Pamela Marcus, Phillip Prorok, Christine Berg Oct 2012

Factors Associated With Inadequate Colorectal Cancer Screening With Flexible Sigmoidoscopy, Adeyinka Laiyemo, Chyke Doubeni, Paul Pinsky, V. Paul Doria-Rose, Andrew Sanderson, Robert Bresalier, Joel Weissfeld, Robert Schoen, Pamela Marcus, Phillip Prorok, Christine Berg

Chyke A. Doubeni

BACKGROUND AND STUDY AIM: Inadequate colorectal cancer screening wastes limited endoscopic resources. We examined patients factors associated with inadequate flexible sigmoidoscopy (FSG) screening at baseline screening and repeat screening 3-5 years later in 10 geographically-dispersed screening centers participating in the ongoing Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial.

METHODS: A total of 64,554 participants (aged 55-74) completed baseline questionnaires and underwent FSG at baseline. Of these, 39,385 participants returned for repeat screening. We used logistic regression models to assess factors that are associated with inadequate FSG (defined as a study in which the depth of insertion of FSG was …


Contribution Of Behavioral Risk Factors And Obesity To Socioeconomic Differences In Colorectal Cancer Incidence, Chyke Doubeni, Jacqueline Major, Adeyinka Laiyemo, Mario Schootman, Ann Zauber, Albert Hollenbeck, Rashmi Sinha, Jeroan Allison Oct 2012

Contribution Of Behavioral Risk Factors And Obesity To Socioeconomic Differences In Colorectal Cancer Incidence, Chyke Doubeni, Jacqueline Major, Adeyinka Laiyemo, Mario Schootman, Ann Zauber, Albert Hollenbeck, Rashmi Sinha, Jeroan Allison

Chyke A. Doubeni

BACKGROUND:Health behaviors are known risk factors for colorectal cancer and are more common in low socioeconomic status (SES) populations. We evaluated the extent to which behavioral risk factors and body mass index (BMI) explain SES disparities in colorectal cancer incidence, overall and by tumor location.

METHODS: We analyzed prospective National Institutes of Health-AARP Diet and Health Study data on 506 488 participants who were recruited in 1995-1996 from six US states and two metropolitan areas and followed through 2006. Detailed baseline data on risk factors for colorectal cancer, including health behaviors, were obtained using questionnaires. SES was measured by self-reported …


Socioeconomic Status, Healthcare Density, And Risk Of Prostate Cancer Among African American And Caucasian Men In A Large Prospective Study, Jacqueline Major, M. Oliver, Chyke Doubeni, Albert Hollenbeck, Barry Graubard, Rashmi Sinha Oct 2012

Socioeconomic Status, Healthcare Density, And Risk Of Prostate Cancer Among African American And Caucasian Men In A Large Prospective Study, Jacqueline Major, M. Oliver, Chyke Doubeni, Albert Hollenbeck, Barry Graubard, Rashmi Sinha

Chyke A. Doubeni

OBJECTIVES: The purpose of this study was to separately examine the impact of neighborhood socioeconomic deprivation and availability of healthcare resources on prostate cancer risk among African American and Caucasian men. METHODS: In the large, prospective NIH-AARP Diet and Health Study, we analyzed baseline (1995-1996) data from adult men, aged 50-71 years. Incident prostate cancer cases (n = 22,523; 1,089 among African Americans) were identified through December 2006. Lifestyle and health risk information was ascertained by questionnaires administered at baseline. Area-level socioeconomic indicators were ascertained by linkage to the US Census and the Area Resource File. Multilevel Cox models were …


Variation Of Adenoma Prevalence By Age, Sex, Race, And Colon Location In A Large Population: Implications For Screening And Quality Programs, Douglas Corley, Christopher Jensen, Amy Marks, Wei Zhao, Jolanda De Boer, Theodore Levin, Chyke Doubeni, Bruce Fireman, Charles Quesenberry Oct 2012

Variation Of Adenoma Prevalence By Age, Sex, Race, And Colon Location In A Large Population: Implications For Screening And Quality Programs, Douglas Corley, Christopher Jensen, Amy Marks, Wei Zhao, Jolanda De Boer, Theodore Levin, Chyke Doubeni, Bruce Fireman, Charles Quesenberry

Chyke A. Doubeni

BACKGROUND and AIMS: Reliable community-based colorectal adenoma prevalence estimates are needed to inform colonoscopy quality standards and to estimate patient colorectal cancer risks; however, minimal data exist from populations with large numbers of diverse patients and examiners. METHODS: We evaluated the prevalence of adenomas detected by sex, age, race/ethnicity, and colon location among 20,792 Kaiser Permanente Northern California members >/=50 years of age who received a screening colonoscopy exam (102 gastroenterologists, years 2006-2008). RESULTS: Prevalence of detected adenomas increased more rapidly with age in the proximal colon (adjusted odds ratio [OR], 2.39; 95% confidence interval [CI], 2.05-2.80; 70-74 vs 50-54 …


Self-Reported Colorectal Cancer Screening Of Medicare Beneficiaries In Family Medicine Vs. Internal Medicine Practices In The United States: A Cross-Sectional Study, Angela Higgins, Anna Doubeni, Karon Phillips, Adeyinka Laiyemo, Becky Briesacher, Jennifer Tjia, Chyke Doubeni Oct 2012

Self-Reported Colorectal Cancer Screening Of Medicare Beneficiaries In Family Medicine Vs. Internal Medicine Practices In The United States: A Cross-Sectional Study, Angela Higgins, Anna Doubeni, Karon Phillips, Adeyinka Laiyemo, Becky Briesacher, Jennifer Tjia, Chyke Doubeni

Chyke A. Doubeni

BACKGROUND: The benefit of screening for decreasing the risk of death from colorectal cancer (CRC) has been shown, yet many patients in primary care are still not undergoing screening according to guidelines. There are known variations in delivery of preventive health care services among primary care physicians. This study compared self-reported CRC screening rates and patient awareness of the need for CRC screening of patients receiving care from family medicine (FPs) vs. internal medicine (internists) physicians. METHODS: Nationally representative sample of non-institutionalized beneficiaries who received medical care from FPs or internists in 2006 (using Medicare Current Beneficiary Survey). The main …


First-In-Class Small Molecule Inhibitors Of The Single-Strand Dna Cytosine Deaminase Apobec3g, Ming Li, Shivender Shandilya, Michael Carpenter, Anurag Rathore, William Brown, Angela Perkins, Daniel Harki, Jonathan Solberg, Derek Hook, Krishan Pandey, Michael Parniak, Jeffrey Johnson, Nevan Krogan, Mohan Somasundaran, Akbar Ali, Celia Schiffer, Reuben Harris Sep 2012

First-In-Class Small Molecule Inhibitors Of The Single-Strand Dna Cytosine Deaminase Apobec3g, Ming Li, Shivender Shandilya, Michael Carpenter, Anurag Rathore, William Brown, Angela Perkins, Daniel Harki, Jonathan Solberg, Derek Hook, Krishan Pandey, Michael Parniak, Jeffrey Johnson, Nevan Krogan, Mohan Somasundaran, Akbar Ali, Celia Schiffer, Reuben Harris

Celia A. Schiffer

APOBEC3G is a single-stranded DNA cytosine deaminase that comprises part of the innate immune response to viruses and transposons. Although APOBEC3G is the prototype for understanding the larger mammalian polynucleotide deaminase family, no specific chemical inhibitors exist to modulate its activity. High-throughput screening identified 34 compounds that inhibit APOBEC3G catalytic activity. Twenty of 34 small molecules contained catechol moieties, which are known to be sulfhydryl reactive following oxidation to the orthoquinone. Located proximal to the active site, C321 was identified as the binding site for the inhibitors by a combination of mutational screening, structural analysis, and mass spectrometry. Bulkier substitutions …


Long-Term Correction Of Very Long-Chain Acyl-Coa Dehydrogenase Deficiency In Mice Using Aav9 Gene Therapy, Allison Keeler, Thomas Conlon, Glenn Walter, Huadong Zeng, Scott Shaffer, Fu Dungtao, Kirsten Erger, Travis Cossette, Qiushi Tang, Christian Mueller, Terence Flotte Sep 2012

Long-Term Correction Of Very Long-Chain Acyl-Coa Dehydrogenase Deficiency In Mice Using Aav9 Gene Therapy, Allison Keeler, Thomas Conlon, Glenn Walter, Huadong Zeng, Scott Shaffer, Fu Dungtao, Kirsten Erger, Travis Cossette, Qiushi Tang, Christian Mueller, Terence Flotte

Christian Mueller

Very long-chain acyl-coA dehydrogenase (VLCAD) is the rate-limiting step in mitochondrial fatty acid oxidation. VLCAD-deficient mice and patients clinical symptoms stem from not only an energy deficiency but also long-chain metabolite accumulations. VLCAD-deficient mice were treated systemically with 1 x 10(12) vector genomes of recombinant adeno-associated virus 9 (rAAV9)-VLCAD. Biochemical correction was observed in vector-treated mice beginning 2 weeks postinjection, as characterized by a significant drop in long-chain fatty acyl accumulates in whole blood after an overnight fast. Changes persisted through the termination point around 20 weeks postinjection. Magnetic resonance spectroscopy (MRS) and tandem mass spectrometry (MS/MS) revealed normalization of …


Infection With Streptococcus Pneumoniae Moderately Resistant To Penicillin Does Not Alter Clinical Outcome, Todd Gress, Kevin Yingling, Ronald Stanek, Maurice Mufson Sep 2012

Infection With Streptococcus Pneumoniae Moderately Resistant To Penicillin Does Not Alter Clinical Outcome, Todd Gress, Kevin Yingling, Ronald Stanek, Maurice Mufson

Maurice A. Mufson

Increasingly, drug-resistant Streptococcus pneumoniae is an identified pathogen causing pneumonia, sepsis, and meningitis. Our study evaluated outcome variables of patients infected with strains of S. pneumoniae moderately resistant to penicillin. We retrospectively analyzed the data on 110 Huntington, West Virginia, community patients who had types 6, 9, 14, 19, and 23 pneumococcal infections between 1982 and 1994. These strains are most likely to demonstrate resistance. Comparing patients infected with sensitive vs. moderately resistant pneumococcal strains, we found no significant difference in days in the hospital (10.9 vs. 11.1, P =.96), days of fever (2.4 vs. 2.8, P =.74), or mortality …


Driving Assessment Results In Patients With A Diagnosis Of Dementia, Shirley Neitch, Guillermo Madero, Shawn Maynard Sep 2012

Driving Assessment Results In Patients With A Diagnosis Of Dementia, Shirley Neitch, Guillermo Madero, Shawn Maynard

Shirley M. Neitch

Primary care physicians are frequently involved in cases in which they must decide if a patient with dementia should stop driving. The decision is complex, and there are no firm clinical guidelines available. We examined the results of a number of patients who have undergone assessment in our Driving Assessment Clinic, to determine if any of our findings correlated with the diagnosis of dementia. If any associations exist, recommendations may be possible to assist PCPs in making the decision to have patients stop driving, even if full formal testing cannot be done.


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 …


Non-Helicobacter Pylori Related Duodenal Ulcer Disease In Children, Yoram Elitsur, Zandra Lawrence Sep 2012

Non-Helicobacter Pylori Related Duodenal Ulcer Disease In Children, Yoram Elitsur, Zandra Lawrence

Yoram Elitsur

Background. In spite of the worldwide distribution of Helicobacter pylori infection, recent data have reported an increased rate of non-H. pylori, non-NSAIDs-duodenal ulcer disease in adults. The estimated rate of these ulcers in children is unknown. We aimed to investigate the prevalence of non-H. pylori, non-NSAIDs-peptic ulcer disease in our pediatric patients who undergo upper endoscopic procedures. Methods. A retrospective analysis of 622 upper endoscopic reports was performed. Reports that documented mucosal ulcerations were included in our study. The demographic, clinical, endoscopic, and histological data were retrieved. The H. pylori-negative, duodenal/gastric ulcer-positive patients were compared with H. pylori-positive, duodenal/gastric ulcer-positive …


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 …


Neighborhood Socioeconomic Status And Use Of Colonoscopy In An Insured Population--A Retrospective Cohort Study, Chyke Doubeni, Guruprasad Jambaulikar, Hassan Fouayzi, Scott Robinson, Margaret Gunter, Terry Field, Douglas Roblin, Robert Fletcher Aug 2012

Neighborhood Socioeconomic Status And Use Of Colonoscopy In An Insured Population--A Retrospective Cohort Study, Chyke Doubeni, Guruprasad Jambaulikar, Hassan Fouayzi, Scott Robinson, Margaret Gunter, Terry Field, Douglas Roblin, Robert Fletcher

Chyke A. Doubeni

BACKGROUND: Low-socioeconomic status (SES) is associated with a higher colorectal cancer (CRC) incidence and mortality. Screening with colonoscopy, the most commonly used test in the US, has been shown to reduce the risk of death from CRC. This study examined if, among insured persons receiving care in integrated healthcare delivery systems, differences exist in colonoscopy use according to neighborhood SES. METHODS: We assembled a retrospective cohort of 100,566 men and women, 50-74 years old, who had been enrolled in one of three US health plans for >/=1 year on January 1, 2000. Subjects were followed until the date of first …


Developing And Testing An Intervention To Prevent Homelessness Among Individuals Discharged From Psychiatric Wards To Shelters And ‘No Fixed Address’, Cheryl Forchuk, S. Macclure, M. Van Beers, C. Smith, Rick Csiernik, J. Hoch, E. Jensen Aug 2012

Developing And Testing An Intervention To Prevent Homelessness Among Individuals Discharged From Psychiatric Wards To Shelters And ‘No Fixed Address’, Cheryl Forchuk, S. Macclure, M. Van Beers, C. Smith, Rick Csiernik, J. Hoch, E. Jensen

Rick Csiernik

Shelter data in a recent study revealed discharges from psychiatric facilities to shelters or the street occurred at least 194 times in 2002 in London, Ontario, Canada. This problem must be addressed to reduce the disastrous effects of such discharge, including re-hospitalization and prolonged homelessness. An intervention was developed and tested to prevent homelessness associated with discharge directly to no fixed address. A total of 14 participants at-risk of being discharged without housing were enrolled, with half randomized into the intervention group. The intervention group was provided with immediate assistance in accessing housing and assistance in paying their first and …


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 …