bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Genetic Variation in Genes Implicated in the β-Catenin Destruction Complex with Risk of Breast Cancer
Authors: Wang Xianshu , Goode Ellen L. , Fredericksen Zachary S. , Vierkant Robert A. , Pankratz V. Shane , Liu-Mares Wen , Rider David N. , Vachon Celine M. , Cerhan James R. , Olson Janet E. , Couch Fergus J. 
Published: August 2008

AbstractAberrant Wnt/β-catenin signaling leading to nuclear accumulation of the oncogene product β-catenin is observed in a wide spectrum of human malignancies. The destruction complex in the Wnt/β-catenin pathway is critical for regulating the level of β-catenin in the cytoplasm and in the nucleus. Here, we report a comprehensive study of the contribution of genetic variation in six genes encoding the β-catenin destruction complex (APC, AXIN1, AXIN2, CSNK1D, CSNK1E, and GSK3B) to breast cancer using a Mayo Clinic Breast Cancer Case-Control Study. A total of 79 candidate functional and tagging single nucleotide polymorphisms (SNP) were genotyped in 798 invasive cases and 843 unaffected controls. Of these, rs454886 in the APC tumor suppressor gene was associated with increased breast cancer risk (per allele odds ratio, 1.23; 95% confidence intervals, 1.05-1.43; Ptrend = 0.01). In addition, five SNPs in AXIN2 were associated with increased risk of breast cancer (Ptrend &lt; 0.05). Haplotype-based tests identified significant associations between specific haplotypes in APC and AXIN2 (P ≤ 0.03) and breast cancer risk. Further characterization of the APC and AXIN2 variants suggested that AXIN2 rs4791171 was significantly associated with risk in premenopausal (Ptrend = 0.0002) but not in postmenopausal women. The combination of our findings and numerous genetic and functional studies showing that APC and AXIN2 perform crucial tumor suppressor functions suggest that further investigation of the contribution of AXIN2 and APC SNPs to breast cancer risk are needed. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2101–8)
Cyclooxygenase-2 Inhibitors in Colorectal Cancer Prevention: Point
Authors: Arber Nadir 
Published: August 2008

Abstract
The limited success of current treatments for most advanced common malignancies highlights the importance of cancer prevention. Clinical trials on cyclooxygenase (COX) inhibitor drugs showed the potential of chemoprevention as a strategy for reducing cancer incidence, although not without associated side effects. The attractiveness of these drugs partly stems from an ability to engage multiple mechanisms of action by their potential to influence multiple components of the carcinogenesis pathway, from initiation to progression. There are two isoforms of the COX enzymes. COX-1 is constitutively expressed in normal tissues and serves as a “housekeeper” of mucosal integrity, whereas COX-2 is an immediate early response gene that is highly inducible by neoplastic and inflammatory stimuli. COX-2 is significantly overexpressed in colorectal neoplasms, making it an attractive therapeutic target. The drug market has been revolutionized by the development of preparations targeted selectively against COX-2, and a proof of concept has been achieved. Chemoprevention of colorectal cancer is already possible with celecoxib, but it is still not the ultimate drug of choice especially because of the cardiovascular risk associated with COX-2 inhibitors. Better patient selection and more effective and safer drugs are needed. Celecoxib is probably best used in a subset of individuals at moderate to high colorectal cancer risk and low risk of cardiovascular disease. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1852–7)
Cancer Screening for Underserved Women: The Breast and Cervical Cancer Intervention Study
Authors: Hiatt Robert A. , Pasick Rena J. , Stewart Susan , Bloom Joan , Davis Patricia , Gardiner Philip , Luce Judith 
Published: August 2008

Abstract
Objective: To report on the effect of the Breast and Cervical Cancer Intervention Study (BACCIS), a multicomponent intervention conducted in the San Francisco Bay Area between 1992 and 1997.
Methods: BACCIS targeted ∼25,000 multiethnic, underserved women in eight neighborhoods and the public health clinics that served them. An outreach intervention using lay health worker peers and clinic provider inreach intervention to improve breast and cervical cancer screening were evaluated in a quasi-experimental, controlled trial with pretest and posttest household surveys of 1,599 and 1,616 women, respectively. Surveys were conducted in English, Spanish, Mandarin, and Cantonese.
Results: Analyses of community survey results showed no significant improvement in reported screening behaviors. Reports of mammography in the intervention areas in the previous 2 years, or for Pap smear in the previous 3 years, did not differ significantly (73-71% and 84-87%, respectively, for pretest and posttest surveys).
Conclusion: High baseline screening rates, lack of sensitive measures of change at the population level, contamination of the control group, and an imbalance of predictive factors at baseline contributed to the difficulty of assessing the value of the intervention. Lessons learned from this inconclusive study may be of value to future community intervention studies of cancer screening and other health behaviors in multiethnic underserved urban populations. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1945–9)
Effect of Nonmotorized Wheel Running on Mammary Carcinogenesis: Circulating Biomarkers, Cellular Processes, and Molecular Mechanisms in Rats
Authors: Zhu Zongjian , Jiang Weiqin , Sells Jennifer L. , Neil Elizabeth S. , McGinley John N. , Thompson Henry J. 
Published: August 2008

Abstract
The objective of this experiment was to identify circulating growth factors, hormones, and cellular and molecular mechanisms that account for the effects of physical activity on mammary carcinogenesis. A total of 120 female Sprague-Dawley rats were injected with 1-methyl-1-nitrosourea (50 mg/kg) and 7 days thereafter were randomized to either a physically active or a sedentary control group. Individually housed rats were given free access to a nonmotorized, computer-controlled activity wheel and running behavior was reinforced by food reward. Rats self-determined their daily intensity and duration of running. Sedentary control rats received the same amount of food as the physically active rats to which they were paired. Physical activity reduced mammary cancer incidence (P = 0.015) and cancer multiplicity (P = 0.01). Physical activity induced changes in plasma insulin, insulin-like growth factor-I, and corticosterone, suggesting that mechanisms regulating glucose homeostasis were affected. Western blot analyses of mammary carcinomas revealed that proteins involved in cell proliferation were reduced (P &lt; 0.001) and those involved in apoptosis via the mitochondrial pathway were elevated (P &lt; 0.001) by physical activity. The hypothesis that these effects were mediated by activation of AMP-activated protein kinase, and down-regulation of protein kinase B, which collectively down-regulate the activity of the mammalian target of rapamycin, was evaluated. Evidence in support of this hypothesis was found in the Western blot analyses of mammary carcinomas, mammary gland, liver, and skeletal muscle. Collectively, these findings provide a rationale for additional studies of energy-sensing pathways in the elucidation of mechanisms that account for the inhibition of carcinogenesis by physical activity. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1920–9)
Prevalence of Genital Human Papilloma Virus Infection and Genotypes among Young Women in Sicily, South Italy
Authors: Ammatuna Pietro , Giovannelli Lucia , Matranga Domenica , Ciriminna Saverio , Perino Antonio 
Published: August 2008

Abstract
Infection with oncogenic human papilloma virus (HPV) types is a necessary cause of cervical cancer. This study assessed the prevalence of HPV infection and genotypes among 1,006 randomly selected women, ages 18 to 24 years, living in Sicily (south Italy). The overall HPV rate was 24.1% (95% confidence interval, 21.5-26.9). The most frequent types were HPV-16 (4.5%), HPV-53 (2.7%), and HPV-84 (2.6%). The prevalence of vaccine types HPV-6, HPV-11, and HPV-18 was 1.4%, 0.1%, and 1.3%, respectively. Cytologic abnormalities were uncommon (3.1%) and associated with HPV detection (P &lt; 0.0001). The only risk factor for HPV infection was the number of sexual partners (women with 2-3 partners versus women with 1 partner: odds ratio, 3.86; 95% confidence interval, 2.45-6.09). Genital HPV infection is relatively high in young Italian women. The high prevalence of viral types other than vaccine types should be taken into account to ensure accurate postvaccine surveillance and early detection of a possible genotype replacement. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2002–6)
Metastatic Gastrointestinal Stromal Tumors in the Era of Imatinib: Improved Survival and Elimination of Socioeconomic Survival Disparities
Authors: Artinyan Avo , Kim Joseph , Soriano Perry , Chow Warren , Bhatia Smita , Ellenhorn Joshua D.I. 
Published: August 2008

Abstract
Background: Imatinib was approved in 2002 for unresectable and metastatic gastrointestinal stromal tumors. Our objective was to determine if the introduction of imatinib coincided with improved survival from metastatic gastrointestinal stromal tumor in the U.S. population and in specific socioeconomic groups.
Methods: Query of the Surveillance, Epidemiology, and End Results registry identified 552 patients with metastatic gastrointestinal stromal tumor between 1995 and 2004. Year of diagnosis was categorized into two periods, 1995 to 2000 and 2001 to 2004, to account for the effect of imatinib. Kaplan-Meier and multivariate Cox regression analyses were used to examine differences in survival between periods and among socioeconomic groups.
Results: Median survival increased from 12 to 33 months from 1995 to 2000 to 2001 to 2004 (P &lt; 0.001); survival at 47 months increased from 21% to 41%, respectively (P &lt; 0.001). Median survival times for White, Black, Hispanic, and Asian or Pacific Islander, and for low-, middle-, and high-income groups increased significantly in the era of imatinib (all P &lt; 0.05). On multivariate analysis, Black race [hazard ratio, 1.96; 95% confidence interval (95% CI), 1.15-3.32; P = 0.013], Hispanic race (hazard ratio, 2.11; 95% CI, 1.14-3.88; P = 0.017), and low income (hazard ratio, 1.81; 95% CI, 1.13-2.89; P = 0.014) were associated with the poorest survival during the 1995 to 2000 period. During 2001 to 2004, these disparities in survival were no longer statistically apparent.
Conclusions: Survival from metastatic gastrointestinal stromal tumor has improved significantly in the era of imatinib. This improvement has been uniform across all socioeconomic groups, with concomitant elimination of socioeconomic survival disparities potentially due to an assistance program intended to provide universal access to imatinib therapy. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2194–201)
Circulating 2-Hydroxy- and 16α-Hydroxy Estrone Levels and Risk of Breast Cancer among Postmenopausal Women
Authors: Eliassen A. Heather , Missmer Stacey A. , Tworoger Shelley S. , Hankinson Susan E. 
Published: August 2008

Abstract
Circulating estrogens are associated with breast cancer risk in postmenopausal women. Given that estrogen metabolites are potentially both mitogenic and genotoxic, it is possible that plasma levels of estrogen metabolites are related to breast cancer risk. We conducted a prospective, nested case-control study within the Nurses' Health Study. Blood samples, collected in 1989 to 1990, were assayed for 2-OH and 16α-OH estrone among 340 cases and 677 matched controls not taking postmenopausal hormones. Multivariate relative risks (RR) and 95% confidence intervals (95% CI) were calculated by conditional logistic regression, adjusting for breast cancer risk factors. Neither 2-OH nor 16α-OH estrone concentrations were significantly associated with breast cancer risk overall (top versus bottom quartile: RR, 1.19; 95% CI, 0.80-1.79; Ptrend = 0.40 for 2-OH estrone and RR, 1.04; 95% CI, 0.71-1.53; Ptrend = 0.81 for 16α-OH estrone). The ratio between the two metabolites (2-OH:16α-OH estrone) was similarly unrelated to risk overall (1.30; 95% CI, 0.87-1.95; Ptrend = 0.35). Although no associations were detected among women with estrogen receptor (ER)–positive/progesterone receptor (PR)–positive tumors, significant positive associations were observed for 2-OH estrone and the 2-OH:16α-OH estrone ratio among women with ER-negative/PR-negative tumors (RR, 3.65; 95% CI, 1.23-10.81; Ptrend = 0.01; Pheterogeneity = 0.02 for 2-OH estrone; RR, 3.70; 95% CI, 1.24-11.09; Ptrend = 0.004; Pheterogeneity = 0.005 for 2-OH:16α-OH estrone). These data do not support the hypothesized inverse associations with 2-OH estrone and the 2-OH:16α-OH estrone ratio or the hypothesized positive association with 16α-OH estrone. The significant positive associations with 2-OH estrone and the 2-OH:16-OH estrone ratio among women with ER-negative/PR-negative tumors needs to be replicated in future studies. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2029–35)
No Acute and Persistent DNA Damage after an Ironman Triathlon
Authors: Reichhold Stefanie , Neubauer Oliver , Ehrlich Veronika , Knasmüller Siegfried , Wagner Karl-Heinz 
Published: August 2008

Abstract
During acute and strenuous exercise, the enhanced formation of reactive oxygen species can induce damage to lipids, proteins, and nucleic acids. The aim of this study was to investigate the effect of an Ironman triathlon (3.8 km swim, 180 km cycle, 42 km run), as a prototype of ultra-endurance exercise, on DNA stability. As biomarkers of genomic instability, the number of micronuclei, nucleoplasmic bridges, and nuclear buds were measured within the cytokinesis-block micronucleus cytome assay in once-divided peripheral lymphocytes of 20 male triathletes. Blood samples were taken 2 days before, within 20 min after the race, and 5 and 19 days post-race. Overall, the number of micronuclei decreased (P &lt; 0.05) after the race, remained at a low level until 5 days post-race, and declined further to 19 days post-race (P &lt; 0.01). The frequency of nucleoplasmic bridges and nuclear buds did not change immediately after the triathlon. The number of nucleoplasmic bridge declined from 2 days pre-race to 19 days post-exercise (P &lt; 0.05). The frequency of nuclear buds increased after the triathlon, peaking 5 days post-race (P &lt; 0.01) and decreased to basic levels 19 days after the race (P &lt; 0.01). The results suggest that an Ironman triathlon does not cause long-lasting DNA damage in well-trained athletes. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1913–9)
Hemoglobin Adducts of Benzene Oxide in Neonatal and Adult Dried Blood Spots
Authors: Funk William E. , Waidyanatha Suramya , Chaing Shu H. , Rappaport Stephen M. 
Published: August 2008

AbstractAdducts of reactive chemicals with hemoglobin (Hb) or human serum albumin can be used as biomarkers of internal doses of carcinogens. Because dried blood spots are easier to collect and store than conventional venous blood samples, they encourage applications of biomarkers of exposure in large epidemiologic studies. In addition, neonatal dried blood spot can be used to investigate chemical exposures in utero. Here, we report a simple method to isolate Hb from dried blood spot with high recovery and purity using the addition of ethanol to aqueous dried blood spot extracts. To prove the concept that dried blood spot–derived proteins can be used to assay for adducts, we measured Hb adducts of benzene oxide, a reactive metabolite of the ubiquitous air pollutant benzene in nine neonatal and nine adult dried blood spots (from volunteer subjects), using a gas chromatography–mass spectrometry method that we had previously developed. For comparison, benzene oxide–Hb adducts were measured in the same nine adult subjects using Hb that had been isolated and purified using our conventional method for venous blood. The geometric mean of benzene oxide–Hb levels in all dried blood spot samples ranged from 27.7 to 33.1 pmol/g globin. Neither of the comparisons of mean (logged) benzene oxide–Hb levels between sources (adult conventional versus adult dried blood spot and adult dried blood spot versus newborn dried blood spot) showed a significant difference. Based upon the estimated variance of the benzene oxide–Hb levels, we had 80% power to detect a 1.7-fold difference in geometric mean levels of benzene oxide–Hb in our sample of nine subjects. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1896–901)
The Role of the BRCA2 Gene in Susceptibility to Prostate Cancer Revisited
Authors: Ostrander Elaine A. , Udler Miriam S. 
Published: August 2008

Abstract
Prostate cancer is a genetically complex disease with multiple predisposing factors affecting presentation, progression, and outcome. Epidemiologic studies have long shown an aggregation of breast and prostate cancer in some families. More recently, studies have reported an apparent excess of prostate cancer cases among BRCA2 mutation–carrying families. Additionally, population-based screens of early-onset prostate cancer patients have suggested that the prevalence of deleterious BRCA2 mutations in this group is 1% to 2%, imparting a significantly increased risk of the disease compared with noncarrier cases. However, studies of high-risk prostate cancer families suggest that BRCA2 plays at most a minimal role in these individuals, highlighting the potential genetic heterogeneity of the disease. In this commentary, we review the current literature and hypotheses surrounding the relationship between BRCA2 mutations and susceptibility to prostate cancer and speculate on the potential for involvement of additional genes. (Cancer Epidemiol Biomarkers Prev 2008;17(8):1843–8)
Chemokine Decoy Receptor D6 Plays a Negative Role in Human Breast Cancer
Authors: Wu Feng-Ying , Ou Zhou-Luo , Feng Lan-Yun , Luo Jian-Min , Wang Lei-Ping , Shen Zhen-Zhou , Shao Zhi-Min 
Published: August 2008

Abstract
Chemokine binding protein D6 is a promiscuous decoy receptor that can inhibit inflammation in vivo; however, the role it plays in cancer is not well known yet. In this study, we showed for the first time that human breast cancer differentially expressed D6 and the expression could be regulated by some cytokines. More importantly, overexpression of D6 in human breast cancer cells inhibits proliferation and invasion in vitro and tumorigenesis and lung metastasis in vivo. This inhibition is associated with decreased chemokines (e.g., CCL2 and CCL5), vessel density, and tumor-associated macrophage infiltration. Furthermore, D6 expression is inversely correlated to lymph node metastasis as well as clinical stages, but positively correlated to disease-free survival rate in cancer patients. Therefore, D6 plays a negative role in the growth and metastasis of breast cancer. (Mol Cancer Res 2008;6(8):1276–88)
Effects of Palifermin on Antitumor Activity of Chemotherapeutic and Biological Agents in Human Head and Neck and Colorectal Carcinoma Xenograft Models
Authors: Brake Rachael , Starnes Charlie , Lu John , Chen Danlin , Yang Suijin , Radinsky Robert , Borges Luis 
Published: August 2008

Abstract
Damage to the gastrointestinal mucosa is a common dose-limiting toxicity of several anticancer therapies. Until recently, adequate control of oral mucositis was considered a significant unmet medical need, with most available treatments providing only palliative benefits without protecting the gastrointestinal epithelium from the damaging effects of cancer therapy. In 2005, palifermin [recombinant human keratinocyte growth factor (KGF)] was approved to decrease the incidence and duration of severe oral mucositis in patients with hematologic malignancies receiving myelotoxic therapy requiring hematopoietic stem cell support. Current trials are investigating the use of palifermin in solid tumor settings. The objective of this study was to determine whether combining palifermin with different chemotherapeutic or biological agents affected the antitumor activity of these agents in human head and neck (FaDu) and colorectal (HT29) carcinoma xenograft models. Nude CD1 mice were injected with 1 × 107 of either FaDu or HT29 cells, which express both KGF and epithelial growth factor receptors. Animals were treated with palifermin in various combinations with chemotherapeutic (5-fluorouracil and cisplatin) and/or biological (bevacizumab, cetuximab, and panitumumab) agents. Palifermin alone had no effect on either FaDu or HT29 tumor growth. Palifermin did not affect the therapeutic efficacy of 5-fluorouracil, cisplatin, cetuximab, bevacizumab, or panitumumab in any of the two- or three-way drug combinations tested in either model. The results of this study showed that palifermin did not promote the growth of two carcinoma cell lines that express functional KGF receptors and did not protect these tumor cells from the antitumor effects of several chemotherapeutic and biological agents. (Mol Cancer Res 2008;6(8):1337–46)
c-Jun Is Critical for the Progression of Osteosarcoma: Proof in an Orthotopic Spontaneously Metastasizing Model
Authors: Dass Crispin R. , Khachigian Levon M. , Choong Peter F.M. 
Published: August 2008

Abstract
The oncogene c-Jun has been found to be up-regulated in a variety of cancers including osteosarcoma. DNA enzymes (DNAzymes) are oligonucleotides capable of specific catalysis of target mRNA. A c-Jun DNAzyme inhibited the growth and metastasis of osteosarcoma in an orthotopic spontaneously metastasizing model of the disease. c-Jun down-regulation–mediated apoptosis in osteosarcoma cells involved caspase-1, caspase-2, and caspase-8, but not the Fas/FasL pathway. Clinically, knockdown of c-Jun with DNAzymes may proffer an improved treatment outcome for these tumors originating in bone. (Mol Cancer Res 2008;6(8):1289–92)
Cross-talk between Aryl Hydrocarbon Receptor and Mitogen-Activated Protein Kinase Signaling Pathway in Liver Cancer through c-raf Transcriptional Regulation
Authors: Borlak Jürgen , Jenke Hans Stephan 
Published: August 2008

Abstractc-raf is a serine-threonine kinase and a downstream effector of ras signaling. This kinase plays an essential role in cell proliferation, differentiation, and apoptosis. In the past, we reported induction of c-raf gene expression in rat liver cancer on treatment with a mixture of aryl hydrocarbon receptor (AhR) agonists. This prompted our interest in investigating the role of AhR in the transcriptional regulation of c-raf. Initially, we cloned the rat c-raf promoter and sequenced the genomic DNA and cDNA by Southern blotting and capillary electrophoresis. Then, a genetic algorithm was applied to search for putative AhR-binding sites. DNA-binding activity of AhR was confirmed by electromobility shift assay. We also studied c-raf gene expression in rat hepatoma cell lines with functional and/or devoid AhR and in primary human and rat hepatocyte cultures. Overall, we identified five and three AhR-binding sites in the human and rat c-raf gene, respectively. Treatment of hepatocyte cultures with the AhR antagonist resveratrol reduced DNA binding of AhR. Only rat hepatoma cells with functional AhR responded to 1 nmol/L 2,3,7,8-tetrachlorodibenzo-p-dioxin treatment with &gt;10-fold c-raf mRNA induction. Treatment of human and rat hepatocyte cultures with various AhR-activating chemicals resulted in induction of c-raf gene expression, albeit at different levels. Taken collectively, we show AhR to be a master regulator of c-raf and propose cross-talk between AhR and the mitogen-activated protein kinase signaling pathway in chemically induced hepatocarcinogenesis. (Mol Cancer Res 2008;6(8):1326–36)