bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B39: Estrogen and cytochrome P450 1B1 contribute to early-stage head and neck carcinogenesis
Authors: Shatalova Ekaterina G. , Cukierman Edna , Clapper Margie L. 
Published: January 2011

Abstract
Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most common type of cancer in the U.S. Major risk factors for HNSCC include tobacco and alcohol use. Data from this group and others suggest that estrogens may also contribute to the development of HNSCCs. We demonstrated previously that various cell lines derived from both premalignant (MSK-Leuk1) and HNSCCs express estrogen metabolism genes, including cytochrome P450 1B1 (CYP1B1) and estrogen receptor β (ERβ). CYP1B1 is the major enzyme that catalyzes the formation of carcinogenic metabolites of both 17β-estradiol (E2) and constituents of tobacco smoke. The goal of the present study was to assess the impact of E2 exposure on CYP1B1 expression and evaluate the role of E2 and CYP1B1 in regulating motility, apoptosis and proliferation of epithelial cells of the head and neck. Cell lines established from a dysplastic leukoplakia of the oral cavity (MSK-Leuk1) and five human tongue SCCs were exposed to either vehicle (0.01% ethanol) or E2 (1 nM) for 24 hours and the level of CYP1B1 transcripts was analyzed by quantitative real-time PCR. Exposure to E2 induced CYP1B1 expression in MSK-Leuk1 cells (2.3-fold relative to vehicle-treated controls, P=0.0004) but not in HNSCC cells.
To further evaluate the contribution of CYP1B1 to early head and neck carcinogenesis, CYP1B1 was knocked down in MSK-Leuk1 cells by lentivirus encoded shRNA, and the effect of CYP1B1 depletion on cell motility, proliferation and apoptosis was analyzed. Cell motility was evaluated by monitoring the ability of vector and shRNA-expressing cells to close an evenly distributed gap in the cell monolayer over a 16-hour period. CYP1B1 knockdown inhibited the migration of MSK-Leuk1 cells by 57%. Proliferation and apoptosis were assessed in MSK-Leuk1 cells (expressing either vector or CYP1B1 shRNA) exposed to either vehicle or E2 (1 nM) for 3 days. CYP1B1 knockdown inhibited the proliferation of MSK-Leuk1 cells by 45%, relative to vector expressing cells, as measured by total DNA content. E2 inhibited apoptosis by 26%, as compared to vehicle-treated cells, as measured using a Nexin kit.
These data provide novel insight into the mechanisms underlying head and neck carcinogenesis and may facilitate the identification new targets for chemopreventive intervention.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B39.
Abstract B57: Modulation of prostaglandin E2 by statins in human bronchial epithelial cells harboring K-ras mutation: The potential advantage of combination therapy
Authors: Hazra Saswati , Lee Gina , Grant Jeanette , Walser Tonya , Prasad Sri , Larsen Jill E. , Minna John , Dubinett Steven M. 
Published: January 2011

Abstract
Statin drugs, such as lovastatin and simvastatin, block cholesterol synthesis by inhibiting the function of HMG-CoA reductase in the cellular cholesterol biosynthesis pathway. In a recent large case-control study, statins reduced the risk of lung cancer suggesting the utility of statins for lung cancer chemoprevention. In our studies, while both lovastatin and simvastatin dose-dependently decreased proliferation in both histologically normal and K-ras mutated human bronchial epithelial cells (HBECs), it also unexpectedly increased expression of PGE2 in mutated HBECs. The statin-mediated upregulation of PGE2 is most pronounced in K-ras mutated HBECs compared to P53 deleted or EGFR mutated HBECs. Treatment with the cholesterol precursor, mevalonic acid, inhibited statin mediated up-regulation of PGE2 indicating that the effect of the statins on PGE2 is sterol-dependent. We found that the suppression of proliferation by statins is also sterol dependent. Statins up-regulate the production of PGE2 by up-regulating mRNA and protein expression of COX-2. The addition of the MEK inhibitor (U0126) revealed the potential involvement of the ERK pathway for statin-mediated upregulation of PGE2 in HBECs. The combination of statins and a low dose of celecoxib (0.1 micro molar), a COX-2 inhibitor, suppressed the increased production of PGE2 by K-ras mutated HBECs. Studies are underway to determine the effect of statin-mediated upregulation of PGE2 on apoptosis resistance and invasion in K-ras mutated HBECs. Our studies suggest that the combination of statins with a low dose of celecoxib overcomes the upregulation of PGE2 induced by statins alone. Thus the combination represents a potentially effective lung cancer chemopreventative regimen worthy of further investigation.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B57.
Abstract B77: High-risk human papillomavirus genotypes among HIV-negative black women with or without cervical disease in South Africa
Authors: McDonald Alicia C. , Kuhn Louise , Denny Lynette , Wright Thomas C. 
Published: January 2011

Abstract
Objective: Persistent high-risk human papillomavirus (HPV) infections are associated with cervical pre-malignant lesions and cervical cancer. Women in sub-Saharan Africa are at high risk of advanced cervical disease as well as cervical cancer. We examined the prevalence and distribution of high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 66) among HIV-negative Black women enrolled in three cervical cancer screening studies in Cape Town, South Africa. Knowledge of the epidemiology of high-risk HPV types in this population will help target prevention interventions.
Methods: Black women, aged 17-65 years, were tested for high risk HPV DNA using the Hybrid Capture 2 (HC2) assay and positive samples were typed by PCR to determine the specific genotype. Cervical disease status was determined by colposcopy and cervical biopsy. The prevalence and distribution of high-risk HPV types as well as the frequency of multiple high-risk HPV types were examined by age and cervical disease.
Results: Among 8,073 HIV-negative women included in the study, 20.9% (n=1689) were HC2 HPV DNA positive; and, in 73.62% (n=1223/1661) of these positives, a specific high-risk HPV type was detected. Overall, the prevalence of high-risk types was 19.94%. The most common high-risk types across cervical disease status were HPV 16 and 35. Among women without cervical disease, younger women, aged 17-29 years, had the highest prevalence of high-risk types in comparison to older women. Among women with CIN 2 or CIN 3, a higher prevalence of HPV 16 and 45 was observed among older women, aged 40-65 years, than among younger women, aged 17-29 years; as for HPV 35, the prevalence was stable across age groups. The distribution of HPV 16, 35, and 33 were statistically significantly higher among HC2 DNA positive, high-risk HPV positive women with advanced cervical disease than women with no cervical disease or CIN 1 (p-values &lt; 0.02). Younger women, aged 17-29 years, had more multiple types overall and across all cervical disease status than older women, aged 40-65 years.
Conclusion: HPV 16 and 35 are the leading contributors of cervical disease among HIV-negative Black South African women. Therefore, the HPV vaccine has the capacity to result in significant reduction in HPV-related cervical disease in this population.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B77.
Abstract B80: Melanoma incidence rates among whites in the U.S. military
Authors: Zhou Jing , Enewold Lindsey , Zahm Shelia H. , Devesa Susan S. , Anderson William F. , Potter John F. , McGlynn Katherine A. , Zhu Kangmin 
Published: January 2011

Abstract
Melanoma incidence rates may differ between the U.S. active-duty military population and the U.S. general population due to potentially higher exposure to sunlight among military personnel and other risk factors for melanoma. However, few studies have compared melanoma incidence rates and trends over time between the military and the general population. The purpose of this study was to examine melanoma incidence rates from 1990 to 2004 among white active-duty military personnel and the general U.S. population, using data from the military's Automated Central Tumor Registry (ACTUR) and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program. Age-adjusted melanoma rates overall were significantly lower in the military than in the general population; the incidence rate ratio (IRR) was 0.75 for men and 0.56 for women. Age-specific rates, however, were significantly lower among younger individuals aged &lt;45 years but significantly higher among those aged 45 years or older (p-values&lt;0.05). Melanoma incidence rose from 1990-1994 to 2000-2004 in both populations, with the most rapid increase (40%) among younger men in the military. Melanoma incidence rates also varied by branch of military service with rates highest in the Air Force. These results suggest that melanoma incidence rate patterns differ between the two populations, and further studies of risk factors for melanoma in the military are needed to explain these findings.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B80.
Abstract B85: Childhood obesity and risk of adult squamous-cell carcinoma of the esophagus in a high risk area
Authors: Etemadi Arash , Golozar Asieh , Freedman Neal , Kamangar Farin , Shakeri Ramin , Islami Farhad , Boffetta Paolo , Brennan Paul , Abnet Christian , Dawsey Sanford , Malekzadeh Reza 
Published: January 2011

Abstract
Background: Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer worldwide and the first cause of cancer morbidity and mortality in parts of the world, including northeastern Iran. While obesity has been shown to be a risk factor for esophageal adenocarcinoma, little is known about the association between childhood obesity and ESCC.
Methods: As part of the Gastroesophageal Malignancies in Northern Iran (GEMINI) project, a case-control study was conducted between December 2003 and March 2007 in Golestan Province, in northeastern Iran. Newly-diagnosed histologically-proven cases of esophageal squamous cell carcinoma were recruited from the only GI specialty clinic in the region. Two neighborhood controls, matched by age and sex, were recruited for each case. We collected demographic and health-related information from participants using structured questionnaires. In addition, each individual was shown a standard pictogram validated for this population to report the body size at present and at age 15, starting with picture 1 (very slim) to 7 in men and 9 in women (very obese). We used conditional logistic regression (matched on age, sex and current place of residence) to analyze the association between cancer and body size at 15. The model was further adjusted for ethnicity, education, number of siblings, smoking, as well as childhood place of residence, use of piped water, physical activity, therapeutic opium use, early smoking age, and oral health.
Results: There were 300 cases and 571 age and sex-matched controls. Twenty-seven percent of cases and 26% of controls were urban residents, and 57% versus 55% were from Turkmen ethnicity, respectively. 10.4% of cases and 4.4% of controls had been very obese at the age of 15 (p&lt;0.001). In the adjusted model, women reporting the highest level of obesity at age 15 had an OR of 2.9 (95%CI: 1.3-6.6) for developing ESCC. In men, this was not significant (OR=1.3, 95% CI: 0.3-5.2) For all participants, body size at 15 showed a positive association with the risk of ESCC (OR=1.1 for each level of increase, 95% CI: 1.05-1.2). In addition, physical activity level during childhood was inversely associated with ESCC risk (OR=0.8, 95%CI: 0.7-0.9).
Conclusion: Children, especially girls, with higher weight and low physical activity may be at increased risk of developing squamous cell carcinoma of the esophagus as adults. This underlines the importance of lifestyle modifications much earlier than what is generally considered for ESCC prevention.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B85.
Abstract B94: An integrated database in colorectal cancer outcomes, prognosis, and epidemiology (The COPE database)
Authors: Liu Richard Z. , Fulton Ariel , Ge William , Shibata David , Eschrich Steven A. , Siegel Erin M. 
Published: January 2011

Abstract
Introduction: With the move towards a completely electronic medical record system in the United States, there is an opportunity to leverage these electronic data for longitudinal epidemiological studies. Capturing data electronically that would otherwise have been manually abstracted reduces errors and increases the possible number of data elements collected; however these integrated data systems are not readily available. Therefore, for the purposes of a longitudinal study of colorectal cancer patient prognosis, we constructed an Oracle database to integrate multiple data sources.
Experimental Procedures: A molecular epidemiology study was initiated to measure outcomes, epidemiology risk factors, obesity and inflammation-related molecular markers. An integrated Oracle database was constructed that combines several disparate data sources, including realtime messaging for clinic schedules (HL7), outcomes from a cancer registry and paper-based questionnaires into a single Oracle database. A web-based frontend was created to manage study activities.
Results: The IRB-approved cohort study involves the identification of colorectal cancer patients, study-specific consenting and tracking of follow-up questionnaires and blood draws. A web-based interface was created to assist study coordinators and physicians in identifying eligible patients based on a real-time feed of scheduling and admissions. Once a patient has consented to the study, basic demographic information from clinical systems is populated into the study database. A web-based calendar view allows for scheduling study participants’ follow-up visits at 3, 6 and 12 months for blood draws and questionnaires during normal clinic visits. Patient questionnaire data is currently filled out on paper, scanned into electronic form and loaded into the database. Additional data, including anthropometric measurements and blood draw information are manually entered in the system. Although currently entered manually, research tissue collection details will be automatically populated within the study database. The integration of tissue gene expression data and biomarker results is currently under development.
Conclusion: An integrated database system for patient accrual, consent status, patient information, questionnaires, anthropometric measurements and blood draws enables the successful collection of data for colorectal cancer prognosis cohort studies. This database serves as a prototype that can be customized for larger cohort studies that focus on cancer prognosis and survivorship.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B94.
Abstract B96: Stimulation of lung adenocarcinoma by social stress
Authors: Unger Hussein A. Al-Wadei, Benjamin , Brody Joel , Schuller Hildegard M. 
Published: January 2011

Abstract
Lung cancer is one of the most common cancers and the leading cause of cancer deaths.
Adenocarcinoma (AC) is the leading histological type of lung cancer in all investigated populations and shows a significantly lower association with smoking than other lung cancers. We have previously reported that the proliferation and migration of human AC cells in vitro is stimulated by beta-adrenergic receptors (β-ARs). Agonists for these receptors promoted the progression of AC in hamsters while a beta-blocker had strong cancer preventive effects. The stress neurotransmitters noradrenaline and adrenaline are the physiological agonists for β-ARs. They are released from nerve endings and the adrenal medulla in response to nicotinic acetylcholine receptor (nAChR) stimulation by acetylcholine. Our current study has therefore tested the hypothesis that social stress stimulates the growth of xenografts from human ACs and that nAChRs are involved in this response. Social stress was induced in accordance with published procedures in nude mice carrying xenografts from AC cell lines NCI-H322 and NCI-H441. The diameters of xenografts in mice expose to social stress versus unstressed mice were measured. Levels of noradrenaline and adrenaline, the stress hormone cortisol, the neurotransmitter γ-aminobutyric acid (GABA) in serum and xenograft tissues and levels of cAMP in the cellular fraction of blood and in xenograft tissue were assessed by immunoassays. The levels of GAD65, GAD67, nAChRs and signaling proteins downstream of β-ARs in the tumor tissue were determined by Western blotting. Our data show a significant stimulation of xenograft growth by social stress accompanied by elevated levels of stress neurotransmitters, cortisol and cAMP. In addition, protein expression of nAChR subunits α 3, α4, α5 and α7 as well as β-adrenergic signaling proteins were upregulated while GABA and both GAD enzymes were downregulated. Our data provide first experimental evidence for a significant role of social stress in the development and progression of AC.
Supported by Challenge grant 1RC1CA144640-01 with National Institutes of Health.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):B96.
Abstract CN02-04: Phase II study of genistein in men with prostate cancer
Authors: Bergan Raymond C. 
Published: January 2011

Abstract
Progression of cells to a metastatic phenotype begins in the primary organ and represents an important chemoprevention target. In preclinical studies, genistein induces reversion of human prostate cancer (PCa) cells to a less metastatic phenotype. In a phase II study, men with localized PCa were randomized between genistein treatment versus not prior to radical prostatectomy. Analysis of prostate epithelial cells within harvested organs revealed that genistein had the following effects: 1) it decreased matrix metalloproteinase 2 (MMP-2) expression; 2) it induced nuclear spreading; a surrogate marker of inhibition of cell detachment; and 3) gene expression profiling demonstrated selective modulation of genes associated with regulation of cell motility in other cell types. By engineering the expression of these genes in cell lines, we demonstrated that they were important regulators of human PCa cell invasion. Genistein increased the expression of genes that suppress invasion and decreased the expression of genes that enhance invasion. Together, this study demonstrates that genistein induces reversion of human prostate cells in man to a less metastatic phenotype. Importantly, this study demonstrates the proof-of-principal concept that the conduct of molecular screens in human chemoprevention trials has the ability to identify the mechanism of action of investigational agents.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):CN02-04.
Abstract CN07-03: Natural history of bronchial preneoplasia
Authors: Lam Stephen , Daniels Johannes M.A. , Sutedja Thomas , Thunnissen Eric , Shibuya Kiyoshi , Hoshino Hidehisa , Thiberville Luc , McWilliams Annette , leRiche Jean C. , Lockwood William , Lam Wan , Gazdar Adi 
Published: January 2011

Abstract
Preinvasive bronchial lesions defined as dysplasia and carcinoma in-situ (CIS) have been considered as precursors of squamous cell carcinoma of the lung. The risk and rate of progression of preinvasive lesions to invasive squamous cell carcinoma as well as the mechanism of progression or regression are incompletely understood. The evidence for the multistage, stepwise progression model is weak with relatively few documented lesions that progress through normal to hyperplasia, metaplasia and various grades of dysplasia to CIS and then to invasive carcinoma. Collective data from longitudinal studies using autofluorescence bronchoscopy directed sequential bronchial biopsies from the Netherlands, Canada, France, and Japan as well as published data suggest that the time to development of CIS or invasive squamous cell carcinoma from precursor lesions does not follow an anticipated trend from a stepwise progression model. Aside from severe dysplasia that has the shortest progression time, there is no pattern between the baseline pathology and the time of development of CIS or invasive cancer. The presence of dyspalsia or CIS is a field cancerization risk marker for lung cancer both in the central airways and peripheral lung. Specific genetic alterations and host factors such as the inflammatory load and levels of anti-inflammatory proteins in the lung likely influence the progression or regression of pre-invasive lesions. Recently, using integrative genomic approach, combining high-resolution comparative genomic hybridization and gene expression microarray profiles, the focal amplification of an oncogene -BRF2 in chromosome region 8p12 was found to be specific for development of lung squamous cell carcinoma through the increase of Pol III mediated transcription. BRF2 was frequently activated in carcinoma in situ and dysplasia (PLoS Med 7(7): e1000315. doi:10.1371/journal.pmed.1000315). Molecular analysis of rare lesions that progress from normal, hyperplasia, metaplasia or dysplasia to CIS or invasive cancer will shed further light on the key molecular determinants driving development to an invasive phenotype versus those associated with tobacco smoke damage.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):CN07-03.
Abstract CN07-05: Efficient designs for lung cancer prevention trials: Lessons learned and moving forward
Authors: Lee J. Jack 
Published: January 2011

Abstract
Despite intense efforts, there are few lung cancer prevention trials showing positive results in the past few decades. Smoking cessation remains an important yet challenging public health issue. Multiple chemopeventive agents have been tested but, to date, there is none ready for clinical use and some even showed harmful effects in subgroups of subjects. To make progress, we need to learn from our past experiences and incorporate efficient designs in future trials. A few key areas will be reviewed and discussed in the presentation including the followings: (1) The success rate for large, randomized, phase III trials based solely on epidemiology data or retrospective analysis is low. (2) It is important to identify high-risk populations to increase the study efficiency. (3) Although several lung cancer risk models for predicting individual's cancer risk have been proposed, validation studies are needed to confirm their clinical applicability. (4) Similarly, markers for predicting lung cancer risks have been proposed but required independent validation. (5) Surrogate endpoints such as biomarker modulation are often used in prevention trials because it is often not feasible to use cancer development as the primary endpoint. However, surrogate endpoints are valuable only if they are associated with clinically meaningful endpoints. (6) Identification of prognostic and predictive markers for prevention can increase the study efficiency by stratifying subjects and focusing on the subgroups who are more likely to benefit. (7) Construct efficient designs for evaluating multiple preventive agents by applying adaptive designs to allow early stopping due to futility, efficacy, or equivalence, adding/dropping arms based on interim data, adaptive randomization to assign more patients to the more effective arms, seamless phase II/III studies, etc. In addition, evaluate the use of multistage designs to efficiently evaluate the treatment effect, identify important markers, and study the interaction between treatments and markers. (8) Screen preventive agents by using windows of opportunity trials with short term intervention and endpoints. (9) Encourage more randomized phase II trials and discourage lunching definitive phase III trial prematurely. (10) Develop a platform and modular clinical trial design approach for the development of preventive agents.
Citation Information: Cancer Prev Res 2010;3(12 Suppl):CN07-05.