bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiometabolic Risk Factors in Patients with Erectile Dysfunction
Authors: Tanik Serhat , Sarikaya Savas , Zengin Kürşad , Albayrak Sebahattin , Yilmaz Yunus Keser , Akyol Lutfi 
Published: January 2014

Introduction. There is an increasing interest in the association between erectile dysfunction (ED) and cardiovascular risk factor. Epicardial adipose tissue (EAT) is associated with insulin resistance, increased cardiometabolic risk, and coronary artery disease. Our aim was to investigate relationships between epicardial fat thickness (EFT) as a cardiometabolic risk factor and erectile dysfunction.Method. We selected 30 erectile dysfunction patients without comorbidities and 30 healthy individuals. IIEF-5 score was applied to all patients, and IIEF-5 score below 22 was considered as erectile dysfunction. EFT was measured by echocardiography.Results. Body mass index (BMI) was higher in ED patients than those without ED (28.19 ± 4.45 kg/m2versus23.84±2.36 kg/m2,P = 0.001, resp.). Waist circumstance (WC) was higher in ED patients than those without ED (106.60±5.90versus87.86 ± 14.51,P = 0.001, resp.). EFT was higher in ED patients compared to non-ED patients (0.49 ± 0.09 cm versus0.45 ± 0.03 cm,P = 0.016, resp.). There was positive correlation among BMI, WC, and EFT. There was negative correlation between EFT and IIEF-5 score (r : -0.632,P = 0.001).Conclusion. EAT, BMI, and WC as cardiometabolic risk factors were higher in erectile dysfunction patients.
Prior Autoimmune Disease and Risk of Monoclonal Gammopathy of Undetermined Significance and Multiple Myeloma: A Systematic Review
Authors: McShane Charlene M. , Murray Liam J. , Landgren Ola , O'Rorke Michael A. , Korde Neha , Kunzmann Andrew T. , Ismail Mohammad Roshidi , Anderson Lesley A. 
Published: January 2014

Abstract
Background: Several observational studies have investigated autoimmune disease and subsequent risk of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. Findings have been largely inconsistent and hindered by the rarity and heterogeneity of the autoimmune disorders investigated. A systematic review of the literature was undertaken to evaluate the strength of the evidence linking prior autoimmune disease and risk of MGUS/multiple myeloma.
Methods: A broad search strategy using key terms for MGUS, multiple myeloma, and 50 autoimmune diseases was used to search four electronic databases (PubMed, Medline, Embase, and Web of Science) from inception through November 2011.
Results: A total of 52 studies met the inclusion criteria, of which 32 were suitably comparable to perform a meta-analysis. “Any autoimmune disorder” was associated with an increased risk of both MGUS [n = 760 patients; pooled relative risk (RR) 1.42; 95% confidence interval (CI), 1.14–1.75] and multiple myeloma (n&gt;2,530 patients; RR 1.13, 95% CI, 1.04–1.22). This risk was disease dependent with only pernicious anemia showing an increased risk of both MGUS (RR 1.67; 95% CI, 1.21–2.31) and multiple myeloma (RR 1.50; 95% CI, 1.25–1.80).
Conclusions: Our findings, based on the largest number of autoimmune disorders and patients with MGUS/multiple myeloma reported to date, suggest that autoimmune diseases and/or their treatment may be important in the etiology of MGUS/multiple myeloma. The strong associations observed for pernicious anemia suggest that anemia seen in plasma cell dyscrasias may be of autoimmune origin.
Impact: Underlying mechanisms of autoimmune diseases, general immune dysfunction, and/or treatment of autoimmune diseases may be important in the pathogenesis of MGUS/multiple myeloma. Cancer Epidemiol Biomarkers Prev; 23(2); 332–42. ©2014 AACR.
Improved Recurrence-Free Survival with ARCON for Anemic Patients with Laryngeal Cancer
Authors: Janssens Geert O. , Rademakers Saskia E. , Terhaard Chris H. , Doornaert Patricia A. , Bijl Hendrik P. , van den Ende Piet , Chin Alim , Takes Robert P. , de Bree Remco , Hoogsteen Ilse J. , Bussink Johan , Span Paul N. , Kaanders Johannes H. 
Published: January 2014

Abstract
Purpose: Anemia is associated with poor tumor control. It was previously observed that accelerated radiotherapy combined with carbogen breathing and nicotinamide (ARCON) can correct this adverse outcome in patients with head and neck cancer. The purpose of this study was to validate this observation based on data from a randomized trial.
Experimental Design: Of 345 patients with cT2-4 laryngeal cancer, 174 were randomly assigned to accelerated radiotherapy and 171 to ARCON. Hemoglobin levels, measured before treatment, were defined as low when &lt;7.5 mmol/L for women and &lt;8.5 mmol/L for men. The hypoxia marker pimonidazole was used to assess the oxygenation status in tumor biopsies. Data were analyzed 2 years after inclusion of the last patient.
Results: Pretreatment hemoglobin levels were available and below normal in 27 of 173 (16%) accelerated radiotherapy and 27 of 167 (16%) ARCON patients. In patients with normal pretreatment, hemoglobin levels treatment with ARCON had no significant effect on 5-year loco-regional control (LRC, 79% versus 75%; P = 0.44) and disease-free survival (DFS, 75% vs. 70%; P = 0.46) compared with accelerated radiotherapy. However, in patients with low pretreatment, hemoglobin levels ARCON significantly improved 5-year LRC (79% vs. 53%; P = 0.03) and DFS (68% vs. 45%; P = 0.04). In multivariate analysis including other prognostic factors, pretreatment hemoglobin remained prognostic for LRC and DFS in the accelerated radiotherapy treatment arm. No correlation between pretreatment hemoglobin levels and pimonidazole uptake was observed.
Conclusion: Results from the randomized phase III trial support previous observations that ARCON has the potential to correct the poor outcome of cancer patients with anemia (ClinicalTrials.gov number, NCT00147732). Clin Cancer Res; 20(5); 1345–54. ©2014 AACR.
FOXM1c Promotes Pancreatic Cancer Epithelial-to-Mesenchymal Transition and Metastasis via Upregulation of Expression of the Urokinase Plasminogen Activator System
Authors: Huang Chen , Xie Dacheng , Cui Jiujie , Li Qi , Gao Yong , Xie Keping 
Published: January 2014

Abstract
Purpose: The transcription factor Forkhead box M1 (FOXM1) plays important roles in the formation of several human tumors, including pancreatic cancer. However, the molecular mechanisms by which FOXM1 promotes pancreatic tumor epithelial-to-mesenchymal transition (EMT) and metastasis are unknown.
Experimental Design: The effect of altered expression of FOXM1 and urokinase-type plasminogen activator receptor (uPAR) on EMT and metastasis was examined using animal models of pancreatic cancer. Also, the underlying mechanisms of altered pancreatic cancer invasion and metastasis were analyzed using in vitro molecular biology assays. Finally, the clinical relevance of dysregulated FOXM1/uPAR signaling was investigated using pancreatic tumor and normal pancreatic tissue specimens.
Results: Pancreatic tumor specimens and cell lines predominantly overexpressed the FOXM1 isoform FOXM1c. FOXM1c overexpression promoted EMT in and migration, invasion, and metastasis of pancreatic cancer cells, whereas downregulation of FOXM1 expression inhibited these processes. The level of FOXM1 expression correlated directly with that of uPAR expression in pancreatic cancer cell lines and tumor specimens. Moreover, FOXM1c overexpression upregulated uPAR expression in pancreatic cancer cells, whereas inhibition of FOXM1 expression suppressed uPAR expression. Furthermore, transfection of FOXM1c into pancreatic cancer cells directly activated the uPAR promoter, whereas inhibition of FOXM1 expression by FOXM1 siRNA suppressed its activation in these cells. Finally, we identified an FOXM1-binding site in the uPAR promoter and demonstrated that FOXM1 protein bound directly to it. Deletion mutation of this site significantly attenuated uPAR promoter activity.
Conclusions: Our findings demonstrated that FOXM1c contributes to pancreatic cancer development and progression by enhancing uPAR gene transcription, and thus, tumor EMT and metastasis. Clin Cancer Res; 20(6); 1477–88. ©2014 AACR.
Insidious Changes in Stromal Matrix Fuel Cancer Progression
Authors: Miles Fayth L. , Sikes Robert A. 
Published: January 2014

Abstract
Reciprocal interactions between tumor and stromal cells propel cancer progression and metastasis. A complete understanding of the complex contributions of the tumor stroma to cancer progression necessitates a careful examination of the extracellular matrix (ECM), which is largely synthesized and modulated by cancer-associated fibroblasts. This structurally supportive meshwork serves as a signaling scaffold for a myriad of biologic processes and responses favoring tumor progression. The ECM is a repository for growth factors and cytokines that promote tumor growth, proliferation, and metastasis through diverse interactions with soluble and insoluble ECM components. Growth factors activated by proteases are involved in the initiation of cell signaling pathways essential to invasion and survival. Various transmembrane proteins produced by the cancer stroma bind the collagen and fibronectin-rich matrix to induce proliferation, adhesion, and migration of cancer cells, as well as protease activation. Integrins are critical liaisons between tumor cells and the surrounding stroma, and with their mechano-sensing ability, induce cell signaling pathways associated with contractility and migration. Proteoglycans also bind and interact with various matrix proteins in the tumor microenvironment to promote cancer progression. Together, these components function to mediate cross-talk between tumor cells and fibroblasts ultimately to promote tumor survival and metastasis. These stromal factors, which may be expressed differentially according to cancer stage, have prognostic utility and potential. This review examines changes in the ECM of cancer-associated fibroblasts induced through carcinogenesis, and the impact of these changes on cancer progression. The implication is that cancer progression, even in epithelial cancers, may be based in large part on changes in signaling from cancer-associated stromal cells. These changes may provide early prognostic indicators to further stratify patients during treatment or alter the timing of their follow-up visits and observations.
Visual Overview: http://mcr.aacrjournals.org/content/12/3/297/F1.large.jpg.
Mol Cancer Res; 12(3); 297–312. ©2014 AACR.
Abstract A106: Optimal strategies for selecting samples for sequencing families with a common cancer: The Genetic Epidemiology of Lung Cancer Consortium.
Authors: Amos Christopher , Bailey-Wilson Joan , Pinney Susan , Andrada Maria de , Gaba Colette , Mandal Diptasri , You Ming , Spitz Margaret , Anderson Marshall 
Published: January 2014

Abstract
In order to select samples that are optimally informative for sequence analysis, studies for the Genetic Epidemiology Consortium, we implemented three strategies for analysis, taking into account the known family histories of lung cancer. Susceptibility for lung cancer arises from a complex interplay between largely unknown genetic factors and smoking behavior. In order to optimize our ability to identify genetic factors for lung cancer we have recruited individuals with extensive family histories of lung cancer and also collected information about their smoking behaviors. For this study, we have modeled family history to identify individuals to select for sequencing using three approaches. First, we used an expert opinion approach in which multiple investigators evaluated pedigree structures with family history to reach a consensus priority in selecting individuals. Second we developed an approximation that assumes a low penetrance among noncarriers and uses known cancer status in first degree relatives. Third, we used the cancer, smoking behaviors and family information along with a likelihood that models penetrance according to genetic susceptibility and an interaction with smoking to estimate the probabilities individuals carry susceptibility factors. In this analysis we compare results among these methods. We evaluate effectiveness of these methods using simulation-based approaches.
Citation Format: Christopher Amos, Joan Bailey-Wilson, Susan Pinney, Maria de Andrada, Colette Gaba, Diptasri Mandal, Ming You, Margaret Spitz, Marshall Anderson. Optimal strategies for selecting samples for sequencing families with a common cancer: The Genetic Epidemiology of Lung Cancer Consortium. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A106.
Abstract A113: Regional variations in esophageal cancer incidence rates by census region in the United States, 1999-2008
Authors: Drahos Jennifer , Wu Manxia , Anderson William F. , Trivers Katrina F. , King Jessica , Rosenberg Philip S. , Eheman Christie R. , Cook Michael B. 
Published: January 2014

Abstract
Background: U.S. national cancer incidence estimates show a dramatic increase in esophageal adenocarcinoma (EA) and a simultaneous steady decrease in esophageal squamous cell carcinoma (ESCC). However, it is unknown whether substantial regional variations exist due to previous data limitations. Using the combined resource of NPCR and SEER, which covered 89% of the U.S. population, we assessed whether regional rates and trends significantly deviated from national estimates.
Methods: From NPCR-SEER, we extracted cancer case counts and populations for whites aged 45-84 years by calendar year, histology, sex, and census region for the period 1999-2008. We calculated age-standardized incidence rates (ASRs), annual percent changes (APCs), and male-to-female incidence rate ratios (MFIRRs).
Results: This analysis included 65,823 EAs and 27,094 ESCCs diagnosed during 778 million person-years. We observed significant geographic variability in EA and ESCC incidence rates and trends by census region, especially in men diagnosed with EA. The highest male ASRs for EA were observed in the Northeast (17.7 per 100,000) and Midwest (18.1 per 100,000), both of which were significantly higher (p&lt;0.001) than the national estimate (16.0 per 100,000). The APC for men with EA in the Northeast was 62% higher than the national estimate (3.19% vs. 1.97%, P&lt;0.001). The MFIRR for each histology remained fairly constant across calendar time, despite changes in incidence rates.
Conclusion: National estimates of esophageal cancer are not generalizable to specific census regions of the US. The stable MFIRRs may indicate predominant factors affecting esophageal cancer incidence rates are similar in men and women. These results underscore the importance of examining geographic and sex disparities in esophageal cancer.
Citation Format: Jennifer Drahos, Manxia Wu, William F. Anderson, Katrina F. Trivers, Jessica King, Philip S. Rosenberg, Christie R. Eheman, Michael B. Cook. Regional variations in esophageal cancer incidence rates by census region in the United States, 1999-2008. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A113.
Abstract A46: Role of the endocytic adaptor Epsin in cancer cell migration
Authors: Madhivanan Kayalvizhi , Aguilar R. Claudio 
Published: January 2014

Abstract
One of the most common links between cancer and endocytosis is defective internalization of Receptor Tyrosine Kinases, for example, linked to a deficit in endocytic proteins. This scenario leads to hypersignaling and in turn to malignant transformation. Nevertheless, there are also cases in which endocytic proteins, such as the epsin adaptors, are found upregulated in invasive cancers. Indeed, we demonstrated that overexpression of the epsins enhances cancer cell migration and invasion. Furthermore, depletion of epsins (by siRNA) led to impairment of cancer cell invasion. However, the different epsin paralogs varied in their capacity to enhance migration/invasion in the following order: epsin 3 &gt; epsin2 &gt;&gt; epsin1. The epsin paralogs have a highly conserved Epsin N-terminal Homology or the ENTH domain (N-terminus) and a C-terminus where the most divergent regions are housed. While our data shows that both the ENTH domain and the C-terminus are required for enhancing migration, we speculate that the differential ability of the paralogs to migrate/invade lies in their less conserved C-terminus region.
This study aims to uncover the mechanism by which epsin overexpression leads to enhanced migration/invasion and to identify the regions of the epsin C-terminus which gives the paralogs their differential ability to enhance migration/invasion. Here we describe a systematic combinatorial approach for mapping the epsin determinants involved in localizing epsin at endocytic sites and required for its effect on cancer cell migration/invasion. Our data clearly shows that Clathrin binding motifs (out of the 4 types of endocytic determinants) are the strongest localization determinants of epsin2, however are not sufficient. Infact, 2 types of endocytic determinants are required for proper epsin2 localization suggesting co-operativity and redundancy. We also found that mutation of any 2 types of endocytic determinants can also reduce the ability of epsin2 to migrate as compared to the wild-type protein. Expanding the results obtained from epsin2 to epsin3 will reveal the similarities and differences between the paralogs. Taking together our findings and the requirement of these proteins for cancer cell invasion, we envision epsin2 and epsin3 as targets for novel anti-cancer and anti-metastatic approaches.
Citation Format: Kayalvizhi Madhivanan, R. Claudio Aguilar. Role of the endocytic adaptor Epsin in cancer cell migration. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A46.
Abstract A52: Tyrosine kinase activity of c-Abl is essential for p53 dependent transactivation of p21Waf1/Cip1
Authors: Udden S. M. Nashir , Satake Masanobu , Ikawa Shuntaro 
Published: January 2014

Abstract
c-Abl non-receptor tyrosine kinase is a pivotal upstream positive modulator in cellular response to DNA damage, which attributes to the activation of p53 tumor suppressor protein, hence the expression of the p53 target proteins promoting growth arrest and apoptosis. Nevertheless, the comprehensive function of c-Abl in the activation of p53 mediated by phosphorylation and acetylation is still largely elusive. Thus, in an attempt to determine the significance of tyrosine kinase activity of c-Abl in p53 activation, we examined the extent of p53 activation by exposing cells to Adriamycin (ADR). Under the presence of Abl kinase inhibitor, STI571, p53 dependent transactivation of p21 and Ser15/20 phosphorylation of p53 were markedly impaired. Furthermore, overexpression of the wild type c-Abl in ADR treated cells led to marked increase in p21 expression, whereas that of tyrosine kinase deficient c-Abl led to striking decrease. When U2OS cells were treated with increasing (0, 5, 10 & 15 μM) concentration of STI571, p21 expression gradually diminished with increasing concentration of STI571. In response to DNA damage Atm activates c-Abl, which in turn tyrosine phosphorylates and activates Atm making a positive feedback loop between Atm and c-Abl. We speculate the kinase activity of c-Abl is prerequisite to potentiate Atm activity by this feedback loop resulting in the augmented activation of p53. Preliminary experiments revealed that c-Abl abrogated deacetylation of p53 and Histone protein at p53 target genes promoter mediated by Histone deacetylases (HDACs). Detailed descriptions and significance of these observations will be discussed at the meeting.
Citation Format: S. M. Nashir Udden, Masanobu Satake, Shuntaro Ikawa. Tyrosine kinase activity of c-Abl is essential for p53 dependent transactivation of p21Waf1/Cip1. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A52.
Abstract A58: High Throughput Search for a Combination Cancer Preventive Treatment
Authors: Uray Ivan P. , Brown Powel H. 
Published: January 2014

Abstract
Identification of safer chemopreventive drugs is essential for the future of cancer preventive treatment. Although the feasibility for chemoprevention of estrogen receptor (ER) -positive breast cancers has been exemplified by the use of selective estrogen response modifiers (SERMs), we are still lacking preventive options for many other disease types, including breast cancers not dependent on ER status. Rexinoids are a class of agents that effectively reduce the incidence of both ER-positive and -negative tumors in animal models of breast cancer and thus may be better cancer preventive drugs than the current standard SERMs. However, significant side-effects at the effective clinical dose, including hypertriglyceridemia and weight gain, limit its generalized use. A phase II biomarker trial of the synthetic rexinoid, bexarotene (Targretin, LGD1069) demonstrated that bexarotene reduces expression of the proliferation markers Ki67 and Cyclin D1 in normal breast epithelium of postmenopausal women, suggesting that the cancer preventive effects of bexarotene are associated with its ability to elicit cell cycle blockade and inhibit proliferation of premalignant mammary epithelial cells. Here we hypothesize that the combination of repurposed drugs and some small molecule compounds with low dose rexinoid will minimize toxicity and result in effective anti-proliferative in premalignant cells. Therefore, we designed an image-based in vitro assay system to conduct high throughput screens to identify existing drugs and drug-like small molecules which enhance the growth suppressive effect of cancer preventive rexinoids. We used an automated 96 well platform to test the NIH clinical collection of drugs and a library of structurally diverse compounds (MayBridge Hitfinder) alone or in combination with 100nM bexarotene. Through multiparametric determination of cell counts, DNA content and cellular toxicity, we identified combination treatments of premalignant breast cells that fit the above criteria and report on dose-response studies and secondary screens for optimal dose and cell health. Validation of some of the candidate agents and plans for in vivo testing of their chemopreventive activity will be discussed.
Citation Format: Ivan P. Uray, Powel H. Brown. High-throughput search for a combination cancer preventive treatment. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A58.