tbuckley/cabot-search huggingface dataset:
Rural appalachia: Disparities within disparities.
Authors: Nengliang Yao
Journal: Journal of Clinical Oncology (2015)

Article Tools Cancer Prevention, Genetics, and Epidemiology Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/jco.2015.33.15_suppl.e12632 Journal of Clinical Oncology - published online before print May 20, 2015 Rural appalachia: Disparities within disparities. Nengliang YaoxNengliang YaoSearch for articles by this author Show More Virginia Commonwealth Univ School of Medcn, Richmond, VA Abstract Disclosures https://doi.org/10.1200/jco.2015.33.15_suppl.e12632 Abstract Abstract e12632 Background: Lyndon Johnson had declared a "war on poverty" in 1964 when he finished a tour in Appalachia. In 1992, the National Cancer Institute has created a public health program in response to the disproportionately high cancer burden in Appalachia. This paper provides an updated overview of disparities in cancer incidence, stage at diagnosis, mortality, and survival and the time trends in rural Appalachia. Methods: Mortality data of all United States from 1969 to 2011 were obtained from the National Center for Health Statistics (NCHS) using SEER*Stat. Incidence and survival data of about 28% US population from 2000 to 2011 were acquired from the Surveillance, Epidemiology, and End Results (SEER) 18 Program. Two Appalachian states, Kentucky and Georgia, are included in the SEER 18 program. Results: Rural Appalachians had the lowest cancer mortality rates in the country in the 1970s, but the disparity had reversed direction and they had the highest rates after 1995. The progress of mortality reduction has been most rapid for urban non-Appalachians, among whom death rates have declined by approximately 21%, but only 13% and 10% decline were found in urban and rural Appalachians. If rural Appalachian had equal mortality rates as most Americans, about 16,000 lives could be saved during 2007-2011. The risk of getting cancer decreased by 9% between 2000 and 2011 in urban non-Appalachians, 7% in rural non-Appalachians and 6% in urban Appalachians, but the age adjusted incidence rates increasedby 6% in rural Appalachians. In 2007-2011, about 83% of all staged breast cancer patients living in urban non-Appalachian areas were diagnosed at stage 0-II, while 79% of rural Appalachian patients were diagnosed at early stages. In contrast, the percentage of early stage colorectal cancer patients were about the same in two subgroups. Both 3- and 5-year survival rates for breast, colorectal, and prostate cancer were lower in rural Appalachian than most Americans, even if they are diagnosed at early stages. Conclusions: Rural Appalachians suffer from disproportionately high burden of cancer across the continuum of cancer prevention and control. Progress of mortality reduction has been rapid for most Americans including African Americans, but it has been slow in rural Appalachia. © 2015 by American Society of Clinical Oncology
A gender-specific association between a novel A5495G variant inthe endothelial nitrix oxide synthase gene (NOS3) andrespiratory allergy in the Czech population
Authors: Lydie Izakovičová Hollá, Andrea Stejskalová, Dana Bučková, Marcel Schüller, Vladimír Znojil
Journal: European Respiratory Journal (2003)

Several studies suggest that abnormalities in nitrix oxide (NO)
synthesis may contribute to the development of pulmonary
diseases. We recently identified a novel variant within intron
4 of the NOS3 gene: A to G conversion at nucleotide position
5495. We have, therefore, performed a case-control study to
investigate a plausible association between this polymorphism
in the NOS3 gene and respiratory allergic diseases.
Complete Revascularization in ST-Elevation Myocardial Infarction?
Authors: Lars Køber
Journal: New England Journal of Medicine (2017)

Between 40 and 50% of patients who present with acute ST-elevation myocardial infarction (STEMI) have multivessel coronary artery disease.1,2 Joint guidelines from the American College of Cardiology, the American Heart Association, and the European Society of Cardiology recommend treatment of the culprit vessel only, but data from a few trials of intermediate size favor complete revascularization, mainly on the basis of reductions in the need for repeat revascularizations.37 The severity of nonculprit vessel lesions has generally been assessed by means of angiography; in one trial, fractional flow reserve (FFR) was used.7 Important questions therefore remain: among patients presenting . . .
PULMONARY-SYSTEMIC PULSE PRESSURE RATIO IS ASSOCIATED WITH ADVERSE CLINICAL OUTCOMES IN GROUP 1 PULMNONARY HYPERTENSION
Authors: Sula Mazimba, Jamie Kennedy, Manu Mysore, Jeremy Mazurek, Andrew Mihalek, Lavone Smith, Eliany Mejia-Lopez, Timothy Welch, William C. Harding, Kenneth Bilchick
Journal: Journal of the American College of Cardiology (2017)
EARLY MORTALITY IN PATIENTS WITH NEW ONSET ATRIAL FIBRILLATION: RESULTS FROM THE GARFIELD-AF REGISTRY
Authors: Samuel Z. Goldhaber, A. John Camm, Gabriele Accetta, Jean-Pierre Bassand, David Fitzmaurice, Shinya Goto, Sylvia Haas, Werner Hacke, Gloria Kayani, Frank Misselwitz, Lorenzo Mantovani, Alexander Turpie, Martin van Eickels, Freek Verheugt, Ajay Kakkar
Journal: Journal of the American College of Cardiology (2017)
Molecular signatures generated with RNA isolated from formalin-fixed paraffin-embedded tumor specimens differentiate metastatic and non-metastatic primary colorectal cancer
Authors: D. Shimizu, H. Kuramochi, K. Tanaka, J. Cooc, Y. Xiong, M. William, R. Li, K. D. Danenberg, P. V. Danenberg, H. J. Lenz
Journal: Journal of Clinical Oncology (2006)

3615 Background: Colorectal cancer (CRC) can be either non-metastatic (locally-advanced) or metastatic, with the latter having a considerably worse prognosis. Because tissue from patients is generally available only as FFPE specimens, we investigated whether distinct molecular signatures could be obtained for these CRC types using RNA isolated from archival FFPE specimen blocks in gene expression arrays. Methods: FFPE specimens were available from 12 non-metastatic tumors and 9 primary tumors along with their matching metastases. Up to 5 10-micron sections of each were microdissected to isolate areas of tumor tissue. RNA was extracted using a proprietary procedure of Response Genetics, Inc. and was then amplified and labeled. The resulting cRNA was hybridized to the U133 plus 2.0 GeneChip. Unsupervised PCA analysis of the samples resulted in the first principal component separating 2 distinct groups, which consisted of the non-metastatic and metastatic tumors. A differentially expressed gene list between metastatic and non-metastatic CRC was determined. These data were also analyzed for differential canonical pathways using Ingenuity Pathway Analysis. Results: Hierarchical clustering analysis segregated locally advanced primary tumors and metastatic primary tumors into two clusters with distinct gene signatures. A T-test with unequal variance assumption identified 609 differentially expressed probe sets with FDR (false discovery rate) = 0.05. Comparison of primary tumors with their liver metastases using a paired T-test showed only 2 differentially expressed genes at FDR = 0.05 but 526 genes with significance p value &lt; 0.005. Pathway analysis showed significant deregulation of VEGF, hypoxia, B Cell receptor, PI3K/AKT, ERK/MAPK and G-protein coupled receptor signaling between locally advanced and metastatic tumors. Pathway analysis of primary tumors and metastases showed deregulated TGF-b, integrin and chemokine signaling pathways. Conclusion: We have demonstrated the feasibility of identifying metastatic and non-metastatic tumors by microarray analysis using FFPE CRC tissue. This result is currently being validated in a separate larger cohort of patients. [Table: see text]
LONG-TERM VASCULAR RESPONSE TO PERMANENT POLYMER EVEROLIMUS-ELUTING STENT COMPARED WITH BIODEGRADABLE POLYMER BIOLIMUS-ELUTING STENT: FIVE-YEAR FOLLOW-UP OPTICAL COHERENCE TOMOGRAPHY STUDY
Authors: Shoichi Kuramitsu, Shinjo Sonoda, Hiroyuki Jinnouchi, Yoshitaka Muraoka, Takenori Domei, Makoto Hyodo, Shinichi Shirai, Kenji Ando
Journal: Journal of the American College of Cardiology (2017)
Preclinical antitumor and antiangiogenic activity of a metronomic schedule of cisplatin against human transitional cell carcinoma (TCC)
Authors: W. Jian, J. M. Levitt, S. P. Lerner, G. Sonpavde
Journal: Journal of Clinical Oncology (2009)

e16018 Background: Conventional cisplatin every 3 weeks is frequently precluded in patients with TCC due to renal dysfunction. A metronomic schedule of other chemotherapeutic agents demonstrates anti-angiogenic and anti-tumor activity coupled with better tolerability. A rationale can be made to preclinically evaluate the activity of a metronomic (weekly or 3 days a week) schedule of cisplatin in a preclinical system of TCC. Methods: The activity of cisplatin was assessed in vitro against HUVECs (human umbilical vein endothelial cells). MTT, flow cytometry with Annexin-FITC and scratch assays were employed to assess proliferation, apoptosis and migration, respectively. The activity of cisplatin was evaluated in vivo in murine xenograft models of TCC. The subcutaneous xenografts included 5 × 10 6 RT4 or 5637 human TCC cells injected into 6- to 8-week-old female athymic BALB/c nu/nu mice. Cisplatin was administered 4 mg/kg IP (intraperitoneal) weekly for up to 6 weeks and compared with untreated mice. Then, 3 groups of tumor-bearing mice received either no therapy, cisplatin 6 mg/kg weekly or cisplatin 2 mg/kg for 3 days a week for up to 6 weeks. Tumor size is measured twice a week. Nephrotoxicity is assessed by serum creatinine and kidney histopathological examination. IHC (immunohistochemistry) of xenografts is performed to measure proliferation (ki-67), apoptosis (cleaved caspase-3) and angiogenesis (CD31). Results: Cisplatin demonstrated significant anti-proliferative, anti-migration and pro-apoptotic activity against HUVECs in vitro. Cisplatin 4 mg/kg weekly inhibited tumor growth, induced higher apoptosis and down-regulated angiogenesis and proliferation in vivo compared to controls. Results from the experiment comparing cisplatin 6 mg/kg weekly with 2 mg/kg 3 days a week (i.e. more metronomic, with potentially more anti-angiogenic and anti-tumor activity and less nephrotoxic) will be presented. Conclusions: A metronomic schedule of cisplatin inhibits tumor growth and demonstrates anti-angiogenic activity in a preclinical model of human TCC. The clinical evaluation of a metronomic schedule of cisplatin may be warranted. No significant financial relationships to disclose.
DNA hypermethylation of <i>SHISA3</i> as a mechanism of gene inactivation and as a novel prognostic biomarker in colorectal cancer.
Authors: Chun-Chieh Chen, Ming-Hong Tsai, Wen-Chi Chen, Sung-Liang Yu, Tzu-Ming Jao, Chi-Yan Huang, Sheng-Tai Tzeng, Sou-Jhy Yen, Ya-Chien Yang
Journal: Journal of Clinical Oncology (2015)

e14532 Background: Shisa3, a newly identified tumor suppressor, inhibits tumorigenesis and metastasis via counter-regulation of β-catenin in non-small cell lung cancer. However, its tumor suppressor role in other human cancers and the mechanism of gene inactivation still remain unknown. Methods: We validated the expression of SHISA3 gene by qRT-PCR. Then, we treated CRC cell lines with 5-aza-2’-deoxycytidine (5-Aza-CdR) and carried out bisulfate sequencing PCR and pyrosequencing in paired colorectal tumor and normal mucosa tissues to assess the DNA methylation status of SHISA3 gene. Results: We found that SHISA3 expression was significantly down-regulated in 34 (65.4%) of 52 colorectal carcinomas compared with corresponding normal mucosae by qRT-PCR. To explore the epigenetic silencing of SHISA3 gene, CRC cells were treated with DNA methylation inhibitor 5-Aza-CdR, and SHISA3 expression was obviously induced in four (66.7%) of six cell lines. CpG islands spanning SHISA3 gene were predicted via MethPrimer program. Tumor-specific methylation of five CpG sites in the first intron of SHISA3 was identified in CRC cell lines and primary tumors by bisulfite sequencing, and then their methylation levels were further quantified in 127 pairs of primary CRC tissues by bisulfite pyrosequencing. The SHISA3 methylation levels in tumors were noticeably higher than that in matched normal mucosae, and were inversely correlated with gene expression. In addition, SHISA3 hypermethylation was significantly associated with an increased risk of disease recurrence in patients with Dukes’ B and C (P = 0.007), as well as was an independent predictor of poor overall survival (P = 0.002) and disease free survival (P= 0.003) of CRC patients. Conclusions: This study shows for the first time that SHISA3gene is epigenetically inactivated in a substantial fraction of CRC, and its hypermethylation is of prognostic significance in predicting clinical outcome. In addition, the quantitative bisulfite pyrosequencing assay established could be a cost-effective tool for providing a potential biomarker of adverse prognosis in CRC, and would have extensive clinical and research implications.
CHRONIC ALPHA BLOCKER USE AND OUTCOMES IN OLDER MALE MEDICARE BENEFICIARIES HOSPITALIZED FOR HEART FAILURE
Authors: Daniel Dooley, Phillip Lam, Meenakshi Tomer, Cherinne Arundel, Jacqueline Gannuscio, Essraa Bayoumi, Jonathan Segal, Marc Blackman, Gregg Fonarow, Prakash C. Deedwania, Michel White, Javed Butler, Wilbert Aronow, Richard Allman, Ali Ahmed
Journal: Journal of the American College of Cardiology (2017)
Thyroid transcription factor 1 (TTF-1) and overall survival in wild type EGFR patients treated with erlotinib.
Authors: Mary J. Fidler, Sanjib Basu, Thomas A. Hensing, Lela Buckingham, Mark Pool, Brett Mahon, Marta Batus, Kelly Kaiser Walters, Philip D. Bonomi
Journal: Journal of Clinical Oncology (2013)

e19113 Background: TTF-1 is a transcription factor involved in regulating epithelial to mesenchymal transition. TTF-1 has a favorable prognosis in early stage lung adenocarcinoma, although it’s prognostic value in erlotinib treated patients remains unknown (Somaiah ASCO 2011). The goal of this study was to validate the relationship between TTF-1 expression and clinical outcomes in wild-type (WT) stage IV non-small cell lung cancer (NSCLC) patients (pts) treated with erlotinib. Methods: Pts that received erlotinib were retrospectively analyzed by IHC for TTF-1 expression (positive = greater than 5% of tumor cells with moderate (2+) or strong (3+) nuclear staining). Pts’ tumors were considered WT if no mutations were detected in Exon 19 or L858R (Exon 21) using single-strand conformation polymorphism and sequence-specific polymerase chain reaction (PCR). Log Rank was used to correlate TTF-1 positivity with outcomes. Results: 216 pts were analyzed. EGFR activating gene mutations were found in 11.6% of cases. TTF-1 positivity was strongly correlated with the presence of an activating EGFR mutation (p=.0006, negative predictive value=97.7%). Of WT pts: median age was 65, 61% female, 15% never smokers. TTF-1 was positive in 8% of squamous cell and 71% of adenocarcinoma pts. In EGFR WT pts, the median progression free survival (PFS) in TTF-1 positive and negative pts was 2.1 vs. 1.6 months respectively, p=.255. TTF-1 strongly correlated with prolonged overall survival (OS) on erlotinib therapy in WT pts (6.2 vs. 3.2 months, log rank p=.004). After excluding for squamous cell histology, in TTF-1 positive EGFR WT pts there was still a highly significant correlation with prolonged OS on erlotinib (6.2 vs. 2.8 months, p=.001) and a trend toward prolonged PFS (2.2 vs. 1.4 months, p=.05). Conclusions: TTF-1 is related to the presence of exon 19 and 21 EGFR mutations in this group of NSCLC pts, and, similar to early stage lung cancer, TTF-1 appears to be at least a prognostic indicator for OS in stage IV WT EGFR NSCLC pts treated with erlotinib. Exploration of the potential predictive value of this readily available marker should be considered in pts with EGFR WT tumors treated with erlotinib.
Non Interventional Prospective Clinical Study on Peripheral Blood Stem Cell Mobilization in Patients with Relapsed Lymphomas
Authors: Gwendolyn van Gorkom, Herve Finel, Sebastian Giebel, David Pohlreich, Avichai Shimoni, Mark Ringhoffer, Gulsan Ayhan Sucak, Nicolaas PM Schaap, Peter Dreger, Anna Sureda, Harry C Schouten
Journal: Blood (2014)
INTER-STUDY REPRODUCIBILITY OF MITRAL REGURGITATION QUANTITATION USING CARDIAC MAGNETIC RESONANCE IMAGING
Authors: Nickalaus L. Gramze, Mohammad Khan, Eric Yang, Kyle Autry, Jeremy Hinojosa, Corinne Bontiff, Farzan Hassan, Michael Reardon, Stephen Little, William Zoghbi, Faisal Nabi, Dipan Shah
Journal: Journal of the American College of Cardiology (2017)
Canadian National Breast Screening Study (CNBSS): Mortality (MOR), survival (SUR), and mammographic screening (MS).
Authors: Lori H Pai, Rachel J. Buchsbaum, Gary M. Strauss
Journal: Journal of Clinical Oncology (2015)

e12614 Background: Among randomized trials on MS for breast cancer (BC), CNBSS is most controversial. Original CNBBS publications (CMAJ, 1992) suggest that MS may be detrimental to women age 40-49 and 50-59 yrs. Notwithstanding, CNBSS investigators interpret results in a recent paper (BMJ, 2014) as supporting that MS leads to BC overdiagnosis (OD). Objective here is to investigate the hypothesis that randomization (RAN) failure confounded interpretation of CNBSS. Methods: CNBSS1 compared annual MS and clinical breast examination (CBE) to a single CBE in women 40-49 yrs. CNBSS2 compared MS+CBE to CBE in women 50-59 yrs. We performed statistical analyses on published CNBSS data. Results: In CNBSS1, after 7 yrs, there were more invasive BCs in experimental group (EG) (RR = 1.2; p = 0.02). There were also more BCs with > 4+ nodes on prevalence screen (RR = 3.4; p = 0.01) & after 7 yrs (RR = 2.0; p = 0.004). While BC MOR was higher in EG (RR = 1.4; p = 0.3), higher MOR relates to higher incidence (INC) of poor prognosis BCs in EG. In CNBSS2, randomization failure appears to have contributed to negative results; eg BC INC (RR = 1.8; p = 0.001) and MOR (RR = 2.1; p = 0.047) were significantly higher in EG in prevalence screen. In their 2014 report, CNBSS investigators pool results of both studies. Among BCs detected during 5-yr experimental period, INC was 27% higher in EG (666 vs. 524, p < 0.0001). After 25 yrs, there were 180 vs. 171 BC deaths among these cases (RR = 1.1; p = 0.7). While MOR slightly favors controls, SUR was significantly superior in EG: 25-yr SUR was 71% in EG vs 63% in CG (RR = 0.8; p = 0.02). Among EG women whose cancer was detected by MS, 25-yr SUR was 80%. CNBSS investigators conclude that OD accounts for SUR/MOR discrepancy. Conclusions: OD does not account for SUR/MOR discrepancy in CNBSS. Higher rates of poor prognosis BCs in EG support that RAN failed to provide comparison groups with an equal probability of BC MOR. MOR comparisons do not provide an accurate measure of MS efficacy in CNBSS. Problems with RAN more plausibly account for these findings. The 2014 CNBSS report provides little evidence about MS effectiveness. Nonetheless, superior long-term SUV in EG supports that MS improved outcome for those randomized to MS in CNBSS.
Major changes in breast cancer incidence in the United States over the period 2002 to 2004
Authors: P. Ravdin, K. A. Cronin, N. Howlader, C. D. Berg, E. J. Feuer, D. A. Berry
Journal: Journal of Clinical Oncology (2007)

1533 Background: We have recently reported that a steep decrease in the incidence of breast cancer occurred in the United States in 2003 relative to 2002 (BCRT 100: S5, 2006). This decrease was most evident in patients older than 50, and largely occurred because of a decrease in the incidence of estrogen receptor positive breast cancer. This decrease occurred after the report in 2002 of the results of first of the Women s Health Initiative trials of postmenopausal hormone therapy (HT). This publication showed that use of a combined estrogen/progestin combination was associated with increased risk of breast cancer and heart disease and led to an immediate and substantial decrease in the use of HT in the US. Dramatic shifts in breast cancer incidence are unusual, and provide unique opportunities to test models that have been developed to explain trends in breast cancer incidence and mortality. We have been engaged in modeling trends in breast cancer incidence and mortality, in collaborative effects such as the Cancer Intervention and Surveillance Modeling Network (CISNET), to understand these and other processes (NEJM 353:1784–1792,2005). These models have practical implications for understanding the impact of changes in risk factors, use of prevention strategies, screening, and treatment of breast cancer. Methods: SEER public use incidence data from 1990 to the end of 2003 will be updated with information from the release in the spring of 2007 of incidence data for 2004. We will analyze the full data set through 2004 and report on the trends in incidence of breast cancer in the population as a whole and by subsets (such as age, estrogen receptor status, stage etc). We will also use the most recent and detailed data about HT use and screening mammography during this period as part of modeling. Results: We are awaiting SEER data from 2004 which will be released by April of 2007. Conclusions: Our first SEER based multi-year analysis of breast cancer incidence following the change in HT use in the US will be presented. Modeling of these trends in incidence will be discussed in the context of understanding the role of various contributors to the change in breast cancer incidence and what insights on the evolution of preclinical disease might be possible. No significant financial relationships to disclose.
INCREMENTAL RISK OF ISCHEMIC STROKE OVER TIME IN NEWLY DIAGNOSED HEART FAILURE PATIENTS WITHOUT ATRIAL FIBRILLATION
Authors: Jeffrey S. Berger, Eric Peterson, François Laliberté, Guillaume Germain, Dominique Lejeune, Jeffrey Schein, Patrick Lefebvre, Qi Zhao, Matthew Weir
Journal: Journal of the American College of Cardiology (2017)
INDEPENDENT ASSOCIATION OF SYMPTOMATIC PERIPHERAL ARTERIAL DISEASE FOR ADVERSE OUTCOMES, POOR GRAFT SURVIVAL AND LENGTH OF HOSPITAL STAY FOLLOWING HEART TRANSPLANTATION: AN ANALYSIS OF 22,820 HEART TRANSPLANTS FROM THE UNOS DATABASE
Authors: Prasad C. Gunasekaran, Trenton Bickel, Deepak Parashara, Buddhadeb Dawn
Journal: Journal of the American College of Cardiology (2017)