bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5467: Green tea catechin intervention of human breast cell carcinogenesis chronically induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
Authors: Choudhary Shambhunath , Sood Shilpa , Rathore Kusum , Wang Hwa-Chain Robert 
Published: August 2012

Abstract
The purpose of our study was to investigate the mechanism by which dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces breast cell carcinogenesis. More than 85% of breast cancers are sporadic and attributable to long-term exposure to environmental factors, such as carcinogens in the diet, through a multi-step disease process progressing from non-cancerous to premalignant and malignant stages. The dietary carcinogen PhIP is one of the most abundant heterocyclic amines found in high-temperature cooked meats and is recognized as a mammary carcinogen. Here, we demonstrated, for the first time, that cumulative exposures to PhIP at physiologically-achievable, pico- to nano-molar concentrations effectively induced progressive carcinogenesis of human breast epithelial MCF10A cells from a non-cancerous stage to premalignant and malignant stages in a dose- and exposure-dependent manner. Progressive carcinogenesis was measured by increasingly-acquired, cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, acinar-conformational disruption, proliferation, migration, invasion, tumorigenicity with metastasis, and increased stem-like cell populations. These biological changes were accompanied by biochemical and molecular changes, including upregulated H-Ras gene expression, ERK pathway activation, Nox-1 expression and reactive oxygen species (ROS) elevation. The Ras-ERK-Nox-ROS pathway played an important role in not only initiation but also maintenance of cellular carcinogenesis induced by PhIP. Using biological, biochemical, and molecular changes as targeted endpoints, we identified that the green tea catechin components, at non-cytotoxic doses, were capable of suppressing PhIP-induced cellular carcinogenesis and tumorigenicity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5467. doi:1538-7445.AM2012-5467
Abstract 5481: Mitochondrial DNA copy number and lung cancer risk among Chinese female non-smokers
Authors: Mu Lina , Bonner Matthew , Irla Alyssa , Jin Jiahe , Olson James , Ellison Corie , Zhang Zuo-feng 
Published: August 2012

Abstract
Objectives It has been speculated that mitochondrial DNA copy number is involved in carcinogenesis of several cancers. The purpose of this pilot study was to explore the role of mitochondrial DNA copy number in the development of lung cancer among Chinese female non-smoker. Methods A subset of lung cancer cases (N=95) and healthy controls (N=96) were randomly selected from an original lung cancer case-control study conducted in Taiyuan City, China. mtDNA content was determined with Quantitative Real-time Polymerase Chain Reaction (qRT-PCR). Cases and controls were blindly assayed consecutively. Each sample was done in triplicate. Unconditional logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals after adjusting for age, education level and annual personal income. Spearman correlation coefficient was applied to determine correlation between mtDNA copy number and age or indoor air pollution index. Results Lung cancer cases had a significantly lower median mtDNA copy number of 4.5 as opposed to 7.2 in the controls (p&lt;0.0001). There was an inverse relationship seen between mtDNA copy number and risk of lung cancer. Risk of lung cancer decreased in a dose-response manner with mtDNA copy number (Ptrend=0.0409) in the crude analysis. Those women in the highest quartile of mtDNA have a seventy percent lower risk of lung cancer as opposed to those women in the lowest quartile (aOR=0.3, 95%CI: 0.1-0.7). A significant negative correlation was observed between mtDNA copy number and indoor air pollution index which was developed based on individual's exposure to passive smoking, solid fuel use for heating and cooking, frequency of opening windows and exhaust hood use in the kitchen (p=0.0026). There was not a significant correlation between mtDNA copy number and age (p=0.6672), however a significant inverse relationship seen between mtDNA copy number and risk of lung cancer in those women over the age of 57.1. Conclusion Although the exploratory study showed that mtDNA copy number was negatively associated with indoor air pollution exposure and risk of lung cancer, the small sample size of the study and random selection of the subset from original study has limited the power and generalization of pilot study. Further large sample size studies are needed to verify the findings.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5481. doi:1538-7445.AM2012-5481
Abstract 5488: The rate of vertical transmission of human papillomavirus from mothers to infants: Relationship between infection rate and mode of delivery
Authors: Kim Tae Jin , Lee Jae Ho , Jang Hyoung S. , Kim Jun S. , Lee In H. , Cho A R. , Kim Jae W. , Shim Jae W. , Lee Ki H. , Lim Kyung T. , Hong Sung R. 
Published: August 2012

Abstract
Objectives: To assess the prevalence of human papillomavirus(HPV) infection among pregnant women and to evaluate the rate of vertical transmission of HPVs to their infants. Methods: 491 pregnant women and their infants delivered at Cheil General Hospital & Women's Healthcare Center were prospectively recruited for this study between February 2010 and November 2011. Cervical swabs and blood samples were collected from the women at 32-36 weeks of gestation. Neonatal buccal swabs and cord blood were taken immediately after birth. HPV positive neonates were rechecked HPV DNA at 6 months postpartum. HPV genotyping with HPV DNA chip (MyGene Co., Seoul, Korea) was used to detect the HPV of mothers and neonates. Type specific PCR was performed to see HPV DNA in the maternal and cord blood in cases of mother and infant infected same types of HPV DNA. Results: HPV DNA was positive in 16%(80/500) of mothers and 3.5%(17/491) of neonates. The rate of vertical transmission of HPV to their infant was 21.3%(17/80). HPV DNA type-specific maternal/neonate concordance was 100%. 16 HPV positive infants were delivered vaginally and 1 HPV positive infant was delivered by cesarean section with labor. There is no HPV positive infants delivered from cesarean section without labor. All HPV positive neonates were converted HPV negative at 6 months after birth. There was no viremia in maternal and cord blood in cases of mother and infant infected same type of HPV DNA. Conclusions: Prevalence of HPV DNA in neonates born from HPV positive mothers was significantly high. However, these data suggest that neonatal HPV DNA positive is not true vertical infection but contamination during vaginal delivery. Key words: Human papillomavirus, vertical transmission
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5488. doi:1538-7445.AM2012-5488
Abstract 549: Role of the glucocorticoid receptor in skin carcinogenesis and stem cell maintenance: Implication for the use of selective GR activators (SEGRA) as anti-cancer drugs
Authors: Baida Gleb , Rundhaug Joyce , Bhalla Pankaj , Budunova Irina 
Published: August 2012

Abstract
Glucocorticoids are important physiological and pharmacological regulators of epidermal proliferation, differentiation and skin tumorigenesis. The glucocorticoid effects are mediated via the glucocorticoid receptor (GR), a transcription factor that regulates genes expression by DNA-binding dependent transactivation, and DNA-binding independent transrepression through negative interaction with other transcription factors. Our previous studies demonstrated that keratin5.GR transgenic animals are resistant to skin carcinogenesis. We also found that GR diminishes the number of follicular epithelial stem cells (SC), reduces their proliferative and survival potential and affects the expression of follicular SC “signature” genes. To further explore the tumor suppressor role of GR in skin carcinogenesis we generated skin-specific GR knockout animals by breeding of GRflox/flox animals with Keratin5.Cre recombinase animals in C57Bl genetic background. Skin-specific GR KO (Cre/GRfl/fl) mice do not have gross skin or hair phenotype. However, the detailed analysis of keratinocyte markers revealed decreased expression of some intermediate/late markers of differentiation including Keratin 10 and loricrin. We also found that Cre/GRfl/fl mice are more sensitive to the effects of UV irradiation and tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA). The ongoing DMBA/TPA skin carcinogenesis experiment showed that Cre/GRfl/fl mice are more prone to skin carcinogenesis: they have higher tumor incidence and tumor multiplicity compared to GRfl/fl littermates. The analysis of global effect of the GR overexpression and GR silencing on gene expression in follicular epithelial SC, basal keratinocytes, and mouse skin tumors 1) revealed important GR targets in keratinocytes including STAT3 and REDD1 - the major regulator of mTOR; 2) provided an unexpected evidence that gene transrepression by GR plays critical role in the maintenance of SC and in inhibition of skin carcinogenesis. It is well understood that therapeutic effects of glucocorticoids are mediated by GR transreprssion, while many adverse metabolic effects are mediated by GR transactivation. Thus, our findings are important in light of drug discovery programs focused on the development of selective GR acivators (SEGRA) that preferentially induce GR transrepression. Some of SEGRA entered preclinical studies or clinical trials as anti-inflammatory GR ligands with reduced side effects. Our results suggest that SEGRA could be also used for skin cancer prevention/treatment.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 549. doi:1538-7445.AM2012-549
Abstract 5494: The development and validation of risk predictive models for cervical low-grade and high-grade squamous intraepithelial lesions
Authors: Wu Ming-Tsang 
Published: August 2012

Abstract
Aim To develop and validate a risk predictive model for cervical high-grade squamous intraepithelial lesions (HGSIL; CIN2/CIN3). Materials and Methods Study women were from a community survey network for cervical cytological screening to evaluate and develop a simplified risk-score system (Jan., 2003-Feb., 2009, Kaohsiung county). Two other series of study participants obtained, respectively, from a follow-up of disease-free women in the community (followed from Apr., 2004-Feb., 2010) and from a hospital screening (Nov., 2008-Aug. 2011, KMUH) for cervical lesions were used to validate the risk-score system. Kaplan-Meier failure functions and the Cox proportional hazards model were used to evaluate the cervical precancerous risk for women with high-risk scores. Results Women who have a risk score of ≥5 obtained from the HGSIL model were defined as high risk subjects for the cervical lesion. The sensitivity and specificity of the risk-score system were 76.3% and 88.1%. The results of validation showed that the HGSIL model had high sensitivity and specificity (100% and 89.6%) for the community follow-up samples. We also evaluated the incidences of HGSIL among women with a high risk-score using the community follow-up cohort. The first and second-year cumulative incidences of HGSIL among women with the score of ≥5 were 1.05% and 3.63%, respectively. Conclusion With an acceptable accuracy, our data suggest that the HGSIL risk predictive model can be used to assist the screening of HGSIL.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5494. doi:1538-7445.AM2012-5494
Abstract 5495: Does KRAS testing in metastatic colorectal cancer impact overall survival: A comparative effectiveness study in a population-based sample
Authors: Feigelson Heather Spencer ,   The CERGEN Study Team
Published: August 2012

Abstract
The anti-epidermal growth factor (EGFR) monoclonal antibodies cetuximab and panitumumab are approved for the treatment of metastatic colorectal cancer (mCRC), but have been shown to be ineffective if the tumor has a mutation in KRAS codon 12 or 13. Comparative effectiveness research is intended to create evidence for decision making, and to find out “what works” in health care. This is especially important in scenarios like KRAS testing among patients with mCRC, since there is uncertainty around the significance of rarer mutations, and no proven alternative treatment for those who are found to harbor KRAS mutations in codons 12 or 13. We sought to determine whether recommendations for KRAS testing implemented in mid-2008 impacted survival in mCRC among 1203 mCRC patients from seven integrated health plans that are part of the Cancer Research Network. We included Stage IV cases diagnosed from 2006- 2009 and stage III cases initially diagnosed from 2004- 2008 who progressed to distant metastatic CRC (determined using chart review). We abstracted complete treatment data, pathology reports, survival data and KRAS testing results from electronic medical records. For cases that had not been previously tested for KRAS mutation status, we tested archived pathology specimens from the primary tumor. We used Kaplan-Meier plots and Cox proportional hazards models to examine whether overall survival differed among stage III and IV cases diagnosed before (n=751) and after (n=452) the implementation of KRAS testing. We included 918 stage IV cases and 285 stage III cases with progression. KRAS mutations (codon 12, 13, or 61) were found in 40% of tumors. Mutations were more common among tumors arising in the proximal compared to distal colon (46% mutated in ascending colon versus 33% in sigmoid colon). Median survival among stage III cases with progression was 589 days, compared to 437 days for stage IV cases (p=0.004). EGFR inhibitors were given to 26% of patients in the pre-recommendation period, and 13% of patients in the post-recommendation period. We found no survival differences by mutation status. We also found no statistically significant difference in survival time between the pre- and post- KRAS testing recommendations. Our data suggest that KRAS testing can be used to target anti-EGFR therapies without compromising overall survival time among mCRC patients in a usual care setting.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5495. doi:1538-7445.AM2012-5495
Abstract 5506: HPV genotyping of 15,307 Brazilian patients using a microarray based platform.
Authors: Stiepcich Monica M. , Silva Ismael D. , Scarpellini Bruno 
Published: August 2012

Abstract
Introduction: Human papillomavirus (HPV) is the leading cause of cervical cancer and genital lesions in women and men, representing an important global health problem. There are still few data about the prevalence and HPV co-infection in Brazilian patients. Objective: This study aims to describe type specific distribution and co-infection of HPV in patients of a private health clinic using HPV DNA testing. Material and Methods: From April 2010 to October 2011, 15,307 consecutive patients of a private health institution in Sao Paulo, Brazil, were tested using a DNA-array assay, which detects simultaneously 24 HPV types - 19 high risk (HR) and 5 low risk (LR) types (PapilloCheck®). Results: HPV infection was detected in 39% of 13,770 female and 65% of 1,537 male samples. The most common HR-HPV types in women were HPV16, 51, 53, 68, 56 (7.3; 7.2; 7.1; 7.1 and 6.7%) followed by types 39, 66, 52, 31 and 58 (4.7 to 3.9%), which accounted for approximately 56.2% of all detected HPV types. LR-HPV 42 (8.5%) and 44/45 (8.2%) were the most frequent LR types. In males, HR-HPV 16, 51, 56, 68, 53, 39 and 66 (7.8; 7.3; 5.3; 4.6; 4.4 and 4.2%) accounted for 38,7% of all types; HPV 6 (12,8%) and 42 (8%) were the most frequent LR types. HPV 18 accounted for only 1,8% and 2,3% of HPV DNA-positive women and men. Co-infection was observed in 16.3% of female and 36.4% of male samples. 7.1% of women and 22.8% of men showed co-infection with three or more types of HPV. Overall, 59.8% of women and 44% of men had only HR type-infections. 17,6% of women and 23,7% of men had only LR-HPV infections. Co-infection with HR and LR-HPV was observed in 22,6% of female and 32,3% of male samples. Conclusion: Our findings show a high HPV infection prevalence and a high proportion of co-infections in our population. These data can be useful to plan in a more efficient way screening programs and application of prophylactic HPV vaccines in Brazil.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5506. doi:1538-7445.AM2012-5506
Abstract 5507: Breast cancer in Jordan: A comprehensive epidemiological analysis 1996-2008
Authors: Salem Ahmed , Almousa Abdelatief , El-Tannir Dania , Salem Abdel-Fattah 
Published: August 2012

Abstract
Background: The epidemiology of breast cancer has been extensively studied in developed countries; however, epidemiological data is scarce in the Middle East. We present an epidemiological analysis of breast cancer in the Jordan in an attempt to aid continuously evolving strategies for cancer surveillance and control. Furthermore, we highlight the temporal changes of cancer care delivery over the period of this study. Material and methods: Data from the national cancer registry addressing the period from January 1996 to December 2008 were reviewed. The Jordanian national cancer registry was established in 1996 and utilizes a passive and active capture system. Tumor stage was classified into local, regional, distant or unknown. Crude incidence rates are expressed per 100,000. Results: Over the study years, 7,813 breast cancer cases were registered. The crude incidence rate of breast cancer ranged from 20 to 29.9 with 28.2% of cases occurring in 40-49, 26.4% of cases occuring in 50-59 and 18% of cases occuring in the 60-69 age groups. The median age was 51 (range, 16-100 years). Ductal carcinoma was found in 7,018 (89.8%), lobular adenocarcinoma in 478 (6.1%) and sarcoma in 139 (1.8%) patients. Overall; 1,412 (17.4%) cases harbored local, 1,504 (19.3%) harbored regional, 1,572 (18.3%) harbored metastatic disease while in 3,306 patients (45.2%) staging data was missing. Over the years; 2,361 (30.2%) cases were treated at academic/ comprehensive cancer centers while 4,760 (60.9%) cases were treated at a primary care/ community and/or private healthcare setting. In 692 (8.9%) patients, the location of healthcare delivery was unknown 1,652 (21.1%). We observed a trend towards referring more patients to academic/ comprehensive cancer centers over the years of the study; only 29 (6.5%) of a total of 449 patients presenting in 1996 were treated at such institutions as opposed to 406 (47.5%) of a total of 855 patients in 2008. Conclusions: This study represents the first comprehensive assessment of the epidemiological features of breast cancer in Jordan basing a framework for enhancing strategic health plans regarding cancer surveillance and control in Jordan and the Middle East.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5507. doi:1538-7445.AM2012-5507
Abstract 5518: Clinicopathologic associations with colorectal cancer molecular pathways in a cohort study of older women
Authors: Sammader N Jewel , Vierkant Robert A. , Tillmans Lori S. , Wang Alice H. , Weisenberger Daniel J. , Laird Peter W. , Lynch Charles F. , Anderson Kristin E. , French Amy J. , 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: August 2012

Abstract
Background: Colorectal cancer (CRC) is a molecularly heterogeneous disease. Three molecular pathways (traditional, serrated and alternate) have been recently proposed based on integrated combinations of microsatellite instability (MSI), CpG island methylation phenotype (CIMP), BRAF mutation, and KRAS mutation status (Gastroenterol 2010;138:2088-2100). To our knowledge, clinicopathologic associations with these CRC pathways have not been previously described. Methods: Data and tissue resources were obtained from the population-based Iowa Women's Health Study, which recruited 41,836 randomly selected women, ages 55-69 years, at study entry (1986). Incident CRC cases were ascertained by annual linkage with the Iowa Cancer Registry. Archived, paraffin-embedded tissue specimens were collected from 732 CRC cases diagnosed through 12/31/2002. Established laboratory methods were used to characterize CRC cases by MSI (MSS/MSI-L or MSI-H), CIMP (neg, low, or high), BRAF mutation (wt or mut), and KRAS mutation (wt or mut) status. Molecular pathways were defined as: traditional (MSS/MSI-L, CIMP-neg, BRAF wt, and KRAS wt); serrated (any MSI, CIMP-high, BRAF mut, and KRAS wt), alternate (MSS/MSI-L, CIMP-low, BRAF wt, and KRAS mut), or other pathway. Chi-square tests and analyses of variance were used to compare clinicopathologic features at CRC presentation (age, anatomic subsite, tumor grade, and SEER stage) across the molecular pathways. Results: Comlete and informative MSI, CIMP, BRAF and KRAS data were obtained for 491/732 (67%) CRC cases. Clinicopathologic associations are shown in the Table. Conclusions: These data suggest that distributions of age at diagnosis, subsite, and tumor grade, but not SEER stage, differ across the traditional, serrated, and alternate carcinogenic pathways, which may have implications for molecularly-targeted CRC prevention and/or therapy strategies.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5518. doi:1538-7445.AM2012-5518