bluuebunny/crossref_metadata_2025_split huggingface dataset:
β-Blocker treatment during pregnancy and adverse pregnancy outcomes: a nationwide population-based cohort study
Authors: Meidahl Petersen Kasper , Jimenez-Solem Espen , Andersen Jon Traerup , Petersen Morten , Brødbæk Kasper , Køber Lars , Torp-Pedersen Christian , Poulsen Henrik Enghusen 
Published: July 2012

ObjectiveTo investigate the association between exposure to β-blockers during pregnancy and the risk of being born small for gestational age (SGA), preterm birth and perinatal mortality in a nationwide cohort.DesignA population-based retrospective cohort study, using the Danish Fertility Database. The authors identified all pregnant women redeeming a prescription for β-blockers using the National Prescription Registry. Multivariate logistic regression models were used to assess the association between exposure and our outcomes.SettingRegister-based survey.Participants911'685 births between 1995 and 2008 obtained from the Danish Fertility Database.Outcome measuresBeing born SGA was defined as having a birth weight below the 10th percentile for the corresponding gestational week. Preterm birth was defined as birth before the 37th gestational week. Perinatal mortality was defined as either death occurring within the first 28 days of life or stillbirth. Before 2004, fetal deaths were recorded as stillbirths if they occurred after 28 weeks of gestation, but since then stillbirth is recorded for deaths after 22 gestational weeks.ResultsThe authors identified 2459 pregnancies exposed to β-blockers. β-Blocker exposure during pregnancy was found to be associated with increased risk of SGA (adjusted OR 1.97, 95% CI 1.75 to 2.23), preterm birth (adjusted OR 2.26, 95% CI 2.03 to 2.52) and perinatal mortality (adjusted OR 1.89, 95% CI 1.25 to 2.84). Analyses were adjusted for socioeconomic and maternal variables. The authors found similar risk profiles for pregnancies exposed to labetalol and for pregnancies exposed to other β-blockers.ConclusionsThe authors found that exposure to β-blockers during pregnancy was associated with being born SGA, preterm birth and perinatal mortality. Our findings show that labetalol is not safer than other β-blockers during pregnancy.
Uroradiological screening for upper and lower urinary tract anomalies in patients with hypospadias: a systematic literature review
Authors: Chariatte Vincent , Ramseyer Pascal , Cachat François 
Published: July 2012

IntroductionHypospadias is associated with anomalies of the urinary tract, but the exact prevalence and significance of these anomalies are still controversial.ObjectivesTo assess the percentage of patients with hypospadias and associated urological anomalies, either requiring or not requiring medical or surgical attention.Material and methodsWe searched several databases using the following Mesh terms: hypospadias AND urination, ultrasonography, urinary tract/abnormalities, urinary bladder/radiography, ureteral obstruction, hydronephrosis or vesico-ureteral reflux. Type of uroradiological studies performed, type of urological anomalies, medical or surgical interventions, number of patients available, enrolled and undergoing uroradiological studies and number of patients with abnormal uroradiological exams were recorded.ResultsWe found 24 studies. Four studies included 100% of available patients. In the other ones, the percentage of patients undergoing uroradiological screening varied from 12 to 82%. Frequency of anomalies varied from 0 to 56%. The most common anomalies were kidney position anomalies, vesico-ureteral reflux and hydronephrosis.ConclusionsThe data published about screening patients with hypospadias for associated anomalies of their urinary tract are of poor quality. The clinical significance of the anomalies found is difficult to evaluate. We found no relationship between the severity of the hypospadias and associated anomalies of the upper or lower urinary tract.
Hedgehog Signaling Regulates Bladder Cancer Growth and Tumorigenicity
Authors: Fei Dennis Liang , Sanchez-Mejias Avencia , Wang Zhiqiang , Flaveny Colin , Long Jun , Singh Samer , Rodriguez-Blanco Jezabel , Tokhunts Robert , Giambelli Camilla , Briegel Karoline J. , Schulz Wolfgang A. , Gandolfi A. Jay , Karagas Margaret , Zimmers Teresa A. , Jorda Merce , Bejarano Pablo , Capobianco Anthony J. , Robbins David J. 
Published: July 2012

Abstract
The role of Hedgehog (HH) signaling in bladder cancer remains controversial. The gene encoding the HH receptor and negative regulator PATCHED1 (PTCH1) resides on a region of chromosome 9q, one copy of which is frequently lost in bladder cancer. Inconsistent with PTCH1 functioning as a classic tumor suppressor gene, loss-of-function mutations in the remaining copy of PTCH1 are not commonly found. Here, we provide direct evidence for a critical role of HH signaling in bladder carcinogenesis. We show that transformed human urothelial cells and many urothelial carcinoma cell lines exhibit constitutive HH signaling, which is required for their growth and tumorigenic properties. Surprisingly, rather than originating from loss of PTCH1, the constitutive HH activity observed in urothelial carcinoma cell lines was HH ligand dependent. Consistent with this finding, increased levels of HH and the HH target gene product GLI1 were found in resected human primary bladder tumors. Furthermore, on the basis of the difference in intrinsic HH dependence of urothelial carcinoma cell lines, a gene expression signature was identified that correlated with bladder cancer progression. Our findings therefore indicate that therapeutic targeting of the HH signaling pathway may be beneficial in the clinical management of bladder cancer. Cancer Res; 72(17); 4449–58. ©2012 AACR.
Ectopic ATP Synthase Blockade Suppresses Lung Adenocarcinoma Growth by Activating the Unfolded Protein Response
Authors: Chang Hsin-Yi , Huang Hsuan-Cheng , Huang Tsui-Chin , Yang Pan-Chyr , Wang Yi-Ching , Juan Hsueh-Fen 
Published: July 2012

Abstract
Ectopic expression of the mitochondrial F1F0-ATP synthase on the plasma membrane has been reported to occur in cancer, but whether it exerts a functional role in this setting remains unclear. Here we show that ectopic ATP synthase and the electron transfer chain exist on the plasma membrane in a punctuated distribution of lung adenocarcinoma cells, where it is critical to support cancer cell proliferation. Applying ATP synthase inhibitor citreoviridin induced cell cycle arrest and inhibited proliferation and anchorage-independent growth of lung cancer cells. Analysis of protein expression profiles after citreoviridin treatment suggested this compound induced the unfolded protein response (UPR) associated with phosphorylation the translation initiation factor 2α (eIF2α), triggering cell growth inhibition. Citreoviridin-enhanced eIF2α phosphorylation could be reversed by siRNA-mediated attenuation of the UPR kinase PKR-like endoplasmic reticulum kinase (PERK) combined with treatment with the antioxidant N-acetylcysteine, establishing that reactive oxygen species (ROS) boost UPR after citreoviridin treatment. Thus, a coordinate elevation of UPR and ROS initiates a positive feedback loop that convergently blocks cell proliferation. Our findings define a molecular function for ectopic ATP synthase at the plasma membrane in lung cancer cells and they prompt further study of its inhibition as a potential therapeutic approach. Cancer Res; 72(18); 4696–706. ©2012 AACR.
Oxidation-Mediated DNA Cross-Linking Contributes to the Toxicity of 6-Thioguanine in Human Cells
Authors: Brem Reto , Karran Peter 
Published: July 2012

Abstract
The thiopurines azathioprine and 6-mercaptopurine have been extensively prescribed as immunosuppressant and anticancer agents for several decades. A third member of the thiopurine family, 6-thioguanine (6-TG), has been used less widely. Although known to be partly dependent on DNA mismatch repair (MMR), the cytotoxicity of 6-TG remains incompletely understood. Here, we describe a novel MMR-independent pathway of 6-TG toxicity. Cell killing depended on two properties of 6-TG: its incorporation into DNA and its ability to act as a source of reactive oxygen species (ROS). ROS targeted DNA 6-TG to generate potentially lethal replication-arresting DNA lesions including interstrand cross-links. These triggered processing by the Fanconi anemia and homologous recombination DNA repair pathways. Allopurinol protected against 6-TG toxicity by acting as a ROS scavenger and preventing DNA damage. Together, our findings provide mechanistic evidence to support the proposed use of thiopurines to treat HR-defective tumors and for the coadministration of 6-TG and allopurinol as an immunomodulation strategy in inflammatory disorders. Cancer Res; 72(18); 4787–95. ©2012 AACR.
Abstract 1892: Folate intake and incident colorectal cancer by KRAS mutation status in a population-based cohort of older women
Authors: Razzak Anthony , Vierkant Robert A. , Wang Alice H. , Tillmans Lori S. , Lynch Charles F. , Anderson Kristin E. , Haile Robert W. , Harnack Lisa J. , Potter John D. , Slager Susan L. , Smyrk Thomas C. , Thibodeau Stephen N. , Cerhan James R. , Limburg Paul J. 
Published: July 2012

Abstract
Background: Folate intake (FI) appears to affect colorectal cancer (CRC) risk, but the molecular mechanism(s) involved are incompletely defined. In this study, we analyzed associations between FI and incident CRC, overall and by KRAS mutation status, in the population-based Iowa Women's Health Study (IWHS).
Methods: The IWHS recruited 41,836 randomly selected Iowa women, ages 55-69 years, with a valid driver's license at study entry (1986). FI and other exposure variables were assessed at baseline, by self-report. Incident CRC cases were ascertained by annual linkage with the Iowa Cancer Registry. Archived, paraffin-embedded tissue specimens were recently collected from 732 representative CRC cases diagnosed through 12/31/2002. FI (including supplements) was categorized by quartiles. KRAS mutation status (wildtype [wt] vs. mutated [mut]) was determined by direct sequence analysis of codons 12 and 13 (exon 2). Multivariate Cox regression models were fit to estimate relative risks (RRs) and 95% confidence intervals (CIs).
Results: Of the 732 available CRC cases, 470 (64%) had complete FI and KRAS data. FI was not associated with incident CRC overall (for quartile 4 vs. quartile 1, RR = 1.03; 95% CI = 0.82-1.28; p trend = 0.90), or with the KRAS-wt or KRAS-mut subtypes (see Table).
Conclusions: These data do not support an association between FI and incident CRC, overall or by KRAS-defined subtypes, among older, predominately white, non-Hispanic women.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1892. doi:10.1158/1538-7445.AM2011-1892
Abstract 1904: B vitamin intake and incidence of colorectal cancer by tumor site and stage: Results from the Women's Health Initiative cohort
Authors: Zschäbitz Stefanie , Cheng Ting-Yuan D. , Neuhouser Marian L. , Zheng Yingye , Ray Roberta M. , Miller Joshua W. , Song Xiaoling , Bailey Lynn B. , Maneval David R. , Beresford Shirley AA , Ulrich Cornelia M. 
Published: July 2012

Abstract
Introduction: The role of one-carbon metabolism related nutrients (folate, riboflavin (B2), B6, and B12) in colorectal carcinogenesis is still not fully understood. Folate and other B vitamins are essential for DNA methylation and repair and higher levels have been associated with a decreased risk for colorectal cancer (CRC) in some studies; however, non-linear relationships have been observed. We investigated the dietary intake of one-carbon nutrients and CRC risk in the WHI Observational Study, a large cohort of postmenopausal women.
Methods: Dietary intake of folate and other B vitamins was determined via a Food Frequency Questionnaire and supplement inventory in 88,045 healthy women (aged 50 – 79 years, recruited between 1994 – 1998). Multivariate Cox proportional hazards regression models was used to estimate associations between nutrient intake and CRC risk and to evaluate differences in the associations by tumor site and stage. Hazard ratios (HR) for the 4th vs. 1st quartile were estimated.
Results: In age-adjusted analyses significantly reduced risks for CRC were observed for the total (supplemental plus dietary) intake of folate (HR=0.82, 95%CI=0.68-0.97), vitamin B12 (HR=0.82, 0.69-0.99), vitamin B6 (HR=0.77, 0.65-0.92), and riboflavin (HR=0.75, 0.63-0.90). After multivariate adjustment (age, BMI, race, prior colonoscopy, smoking, physical activity, postmenopausal HT use) only the total intake of riboflavin (HR=0.80, 0.66-0.96) remained associated with a reduced risk for CRC. For the intake of vitamin B6 a borderline significance was observed (p=0.06, HR=0.85, 0.70-1.02). A site-specific observation was notable for supplemental and total riboflavin intake with a reduced risk for cancer of the distal colon (HRsupp=0.56, 0.33-0.96; HRtotal=0.69, 0.46-1.04) but not in proximal and rectal cancer. In regards to tumor stage, no significant difference was detected for localized and distant disease; the inverse association between the supplemental and total intake of riboflavin and vitamin B6 was limited to regionally spread disease (HRB2;supp=0.66, 0.45-0.96; HRB2;total=0.73, 0.54-0.99; HRB6;supp=0.69, 0.49-0.98; HRB6;total=0.72, 0.53-0.97).
Conclusion: Higher riboflavin and vitamin B6 intake was linked to decreased risk for colorectal cancer in a large cohort of postmenopausal women, with some suggestion for stage- and site-specific associations. Our study provides limited support for an association of other B vitamins with CRC risk. (NIH R01 CA120523, N01WH22110)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1904. doi:10.1158/1538-7445.AM2011-1904
Abstract 1905: The association between coffee and green tea intake and upper aerodigestive tract cancer in Japanese population
Authors: Oze Isao , Matsuo Keitaro , Hosono Satoyo , Ito Hidemi , Watanabe Miki , Tajima Kazuo , Tanaka Hideo 
Published: July 2012

Abstract
[Background] Coffee and tea are the most common beverages worldwide. Specifically, green tea is the most common tea in Japan. Coffee and green tea are potentially thought to have anticancer effect because of the antioxidative components such as chlorogenic acids in coffee and catechins in tea. On the other hand, coffee and green tea are often consumed with high temperature. Hot foods and beverages are considered as risk factor for esophageal cancer (e.g. yarba mate in Latin America). Thus, coffee and green tea might be carcinogenic. Then, we conducted a case-control study to elucidate the association between UAT cancer and coffee and green tea consumption.
[Method] Cases were 961 patients with histologically diagnosed as UAT cancer (head and neck cancer in 527 and esophageal cancer in 434) between January 2001 and December 2005 at Aichi Cancer Center Hospital. Controls were 2883 first-visit outpatients who were confirmed to have no cancer during the same period. Cases and Controls were matched by age and sex. Information on coffee and green tea consumption and other lifestyle factors were obtained via self-administered questionnaire. Associations between coffee and green tea consumption and UAT cancer were assessed by odds ratios (ORs) and 95% confidence intervals (CIs) by using conditional logistic regression models.
[Result] Both coffee and green tea consumption had significant association with UAT cancer overall (trend p=0.011 and 0.007, respectively). Those who had three or more cups of coffee a day showed significantly lower OR for UAT cancer (OR 0.71, 95% CI 0.55-0.93) than those with non-daily consumers. In contrast, three or more cups of green tea consumption had significant positive association with UAT cancer (OR 1.28, 95% CI 1.06-1.56). These trends were not clear for esophageal cancer. The inverse association between coffee consumption and UAT cancer was evident among current drinkers, while the positive association between green tea and UAT cancer was evident among never drinkers. Similar trends were observed in other categories.
[Conclusion] UAT cancer was inversely associated with coffee consumption, and positively associated with green tea consumption. Further epidemiologic studies are warranted.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1905. doi:10.1158/1538-7445.AM2011-1905
Abstract 1907: Pancreatic cancer risk update: Associations with meat-derived carcinogen intake in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) cohort
Authors: Anderson Kristin E. , Mongin Steven J. , Sinha Rashmi , Stolzenberg-Solomon Rachael , Gross Myron D. , Ziegler Regina G. , Mabie Jerome E. , Risch Adam , Kazin Sally S. , Church Timothy R. 
Published: July 2012

Abstract
Epidemiological studies report positive associations between high-temperature cooked meat intake and pancreatic cancer. We assessed the association between dietary intake of heterocyclic amines (HCAs) and benzo(a)pyrene (BaP)_mutagens formed in meat cooked at high temperatures_and incident exocrine pancreatic cancer in a prospective cohort. Methods: The 62,581 subjects randomized to screening in the multi-center Prostate, Lung, Colorectal and Ovarian Screening Trial (PLCO) who completed a dietary survey at study entry, which assessed meat intake, cooking methods, and doneness preferences defined the cohort. Subjects were surveyed annually for incident cancers through 2007; information was also obtained from physicians, next-of-kin, state registries, and national mortality data. A National Cancer Institute research database (CHARRED) was used to estimate intake of HCA, BaP, and mutagenic activity (Mutagenic Activity Index) from the dietary survey data. The proportional hazard ratios (HRs) for risk of pancreatic cancer were estimated from multivariate-adjusted survival analyses. Results: During follow-up (median: 10 yrs), 248 cases of exocrine pancreatic cancer were confirmed. Intake of well- and very-well done meat was generally associated with increased risks. For example, intake of very well done steak yielded an HR (95% confidence interval) of 1.43 (0.80, 2.56). Using estimated mutagen intake, significant elevations in the risk of pancreatic cancer were found in the upper quintiles of the Mutagenic Activity Index, with HRs of 1.81 (1.16, 2.83) and 1.87 (1.16, 3.02) for quintiles 4 and 5, respectively, relative to the lowest quintile. Significantly increased risks were also associated with exposure high levels of two specific mutagens: 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx). The HRs for DiMeIQx for quintiles 4 and 5 were 1.31 (0.86, 1.98) and 1.81 (1.20, 2.74), respectively, while those for MeIQx were 1.34 (0.87, 2.06) and 1.75 (1.11, 2.76). All three of these exposures exhibited significant positive trends in risk as their intake increased (P for linear trend: 0.01-0.03). Conclusion: Additional follow-up of this cohort has provided stronger evidence that consumption of well-done meat with elevated mutagen levels from high temperature cooking confers an increased risk of pancreatic cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1907. doi:10.1158/1538-7445.AM2011-1907
Abstract 2002: Prevention of gastric cancers induced by Helicobacter pylori infection with a DNA demethylating reagent, 5-aza-2′-deoxycytidine
Authors: Niwa Tohru , Toyoda Takeshi , Tsukamoto Tetsuya , Mori Akiko , Tatematsu Masae , Ushijima Toshikazu 
Published: July 2012

Abstract
Aberrant DNA methylation is deeply involved in carcinogenesis, and Helicobacter pylori infection, a Group-I carcinogen according to IARC classification, is known to induce aberrant methylation in gastric epithelial cells. Therefore, it is likely that methylation induction is the major mechanism by which H. pylori infection induces gastric cancers. In this study, using a Mongolian gerbil model, we aimed to clarify whether a DNA demethylating reagent, 5-aza-2′-deoxycytidine (5-aza-dC), can prevent H. pylori-induced gastric cancers. Administration of N-methyl-N-nitrosourea (20 p.p.m. by drinking water from 5 to 25 weeks of age) and H. pylori infection (∼108 CFU, at 5 weeks of age) induced gastric cancers in 55.2% of the gerbils at 55 weeks of age. By intraperitoneal infection of 5-aza-dC (0.125 mg/kg body weight, twice a week from 5 to 55 weeks of age), the incidence decreased significantly to 23.3% (P&lt;0.05). Methylation levels of two CpG islands in gastric epithelial cells decreased to 46-69% of those of the infected gerbils without 5-aza-dC treatment (P&lt;0.05). Also, the global methylation level decreased from 83.0% to 80.3% by 5-aza-dC as measured by luminometric methylation assay (P&lt;0.05). At the same time, 5-aza-dC treatment tended to reduce expression of inflammation-related genes (Il1b and Nos2) in the stomach, suggesting that 5-aza-dC treatment can also modulate inflammatory responses. These results showed that H. pylori infection-induced gastric cancers could be suppressed by 5-aza-dC, and suggested that inhibition of methylation induction and/or immunomodulation by 5-aza-dC were the mechanisms of the suppression. Suppression of epigenetic alterations is a promising target for cancer prevention.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2002. doi:10.1158/1538-7445.AM2011-2002