bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B87: A study of tobacco exposure and oxidative stress related biomarkers in oral cancer
Authors: Patel Jayendrakumar , Shukla Shilin , Shah Pankaj , Patel Prabhudas 
Published: May 2012

Abstract
B87

Objective
Oral cancer is the leading malignancy in India, with tobacco playing a major role in the etiology. The aims of the present study was (i) to assess tobacco exposure related biomarkers in controls, patients with oral precancers (OPC) and oral cancer patients, (ii) evaluate nitric oxide [as NO2+NO3] and antioxidant enzymes in the subjects and (iii) to evaluate correlation between tobacco exposure and oxidative stress related biomarkers in oral cancer patients.

Materials and Methods
Healthy individuals (n=90) were grouped into without habit of tobacco (NHT, n=30) and healthy individuals with habit of tobacco (WHT, n=60). Oral cancer patients with a tobacco habit were classified into abstinence (n=62) and non-abstinence (n=64) groups according to status of tobacco habits at the study time. Urinary nicotine and cotinine levels were analyzed by HPLC using a UV detector. Plasma NO2+NO3, superoxide dismutase (SOD) and catalase levels were estimated by spectrophotometry.

Results
The Odds Ratio (OR) analysis indicated positive associations of both smoking and chewing habits of tobacco with high risk of development of oral cancer. Urinary nicotine and cotinine were significantly elevated in WHT, patients with OPC and oral cancer patients as compared with the NHT group. Levels of urinary nicotine and cotinine were also higher in the non-abstinence group with oral cancers than abstinence group. Mean plasma NO2+NO3 levels were elevated in patients with OPC and oral cancer patients as compared to the controls. Erythrocyte SOD and catalase levels were higher in WHT and patients with OPC as compared to NHT. The erythrocyte SOD and catalase activities were lower in oral cancer patients than patients with OPC. Person’s correlation analysis revealed that the changes in erythrocyte SOD and catalase activities were positively associated with urinary nicotine values. The alterations in plasma NO2+NO3 levels were negatively associated with changes in erythrocyte SOD activities.

Conclusion
The results confirmed that (i) tobacco chewing and smoking habits are prominent risk factors for development of oral cancer in the western part of India (Gujarat). (ii)Urinary nicotine and cotinine levels can be helpful for screening programs for oral cancer. (iii) The alterations in antioxidant activities were associated with production of nitric oxide in oral cancer, which may have significant role in oral carcinogenesis.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B87.
Abstract B90: Genomic loss of a microRNA leads to overexpression of EZH2 in cancer
Authors: Cao Qi , Varambally Sooryanarayana , Mani Ram-Shankar , Shankar Sunita , Wang Xiaosong , Ateeq Bushra , Laxman Bharathi , Brenner J. Chad , Kim Jung , Cao Xuhong , Han Bo , Kumar-Sinha Chandan , Tan Patrick , Palanisamy Nallasivam , Lonigro Robert , Maher Christopher , Chinnaiyan Arul 
Published: May 2012

Abstract
B90
Enhancer of zeste homolog 2 (EZH2), is a histone methyltransferase involved in epigenetic silencing of target genes and plays a central role in regulating embryonic stem cells, metastasis, and cancer survival. EZH2 is overexpressed in aggressive solid tumors and has been shown to function as an oncogene, however, the mechanism of its elevation in cancer is unclear. Here, we identified that a microRNA is a tumor suppressor that inhibits EZH2 expression and function. In contrast to EZH2, this microRNA expression is decreased during prostate cancer progression. Importantly, the genomic loci of this microRNA are somatically lost in prostate cancer as well as in other cancers. Taken together, this suggests a model in which genomic loss of a microRNA in cancer leads to overexpression of EZH2 and concomitant dysregulation of epigenetic pathways resulting in cancer progression and metastasis.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B90.
Abstract CN01-01: Genetic and epigenetic changes in prostate cancer as targets for prevention
Authors: Nelson William , Haffner Michael , Speed Traci , Lee Byron , Yegnasubramanian Srinivasan 
Published: May 2012

Abstract
CN01-01
Prostate cancer cells are known to carry a variety of genetic defects, including gene translocations (eg. TMPRSS-ERG1), amplifications (eg. AR), mutations, and deletions. These changes are thought to endow the prostate cancer cells with new capabilities for dysregulated proliferation, inappropriate survival, tissue invasion and destruction, immune system evasion, and metastasis. In addition, cancer cells also carry epigenetic defects, manifest as changes in CpG dinucleotide methylation patterns and in chromatin structure and organization (eg. at GSTP1 and many others), which are equivalent to genetic changes in promoting malignant phenotypes. During the pathogenesis of prostate cancer, the somatic epigenetic alterations tend appear earlier during cancer development than genetic changes, as well as more commonly and consistently. For this presentation, new data concerning the mechanism(s) by which androgen action might promote translocations at AR target genes, and by which inflammatory processes might trigger CpG island hypermethylation, in prostate cells will be presented. These new insights into the formation of somatic genetic and epigenetic changes will provide new molecular biomarkers to aid in prostate cancer detection and diagnosis, and may lead to new opportunities for prostate cancer prevention and treatment.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):CN01-01.
Abstract CN02-03: Prospects for targeted reduction of ovarian cancer risk
Authors: Johnson Karen 
Published: May 2012

Abstract
CN02-03
The 5 year survival for patients diagnosed with Stage 3 and 4 epithelial ovarian cancer (EOC) is less than 40% in spite of overall benefit from primary treatment with debulking surgery and chemotherapy. For advanced EOC, even clinical complete responses are usually time-limited, a situation that supports a strategy for earlier intervention. Efforts to establish a screening program with ultrasound and CA-125 have been encumbered by false positive results. The absence of demonstrated benefit in a definitive trial precludes the implementation of widespread screening in the general population. For high risk women like those with BRCA or HNPCC mutations, prophylactic salpingo-oophorectomy is available for risk reduction. Otherwise, the identification of specific risk markers and precursor lesions in the general population remains a challenging goal for EOC prevention research. Because access to human tissues of interest is limited, many questions about the natural history of EOC remain to be answered, and translational efforts have focused on preclinical models and animal studies. In spite of the difficulties, there are promising leads and methodology that can be pursued to make ovarian cancer risk reduction a broader reality.
From epidemiologic studies, a major result in risk modification is the association of oral contraceptive use with EOC risk reduction. The literature is replete with studies that also link EOC with a variety of other hormonal and reproductive factors. These results have been used to support a number of etiologic hypotheses including risk related to 1) incessant ovulation, 2) gonadotropins, 3) hormones (estrogen/androgen/progesterone, and 4) inflammation. These hypotheses are interrelated and support a systems biology approach that integrates changes in the tumor microenvironment along with changes in the epithelium to identify targeted opportunities for preventive modulation. At this point, the translational research process may be well served by small clinical trials that are carefully designed to reconcile inconsistencies in existing data and to test mechanistic leads from preclinical studies as well as from investigations with therapeutics like bevacizumab and anti-Mullerian hormone. Pathways of interest include those related to aromatase and prostaglandins. With specific targets in mind, biomarker comparison in controls using placebo versus subjects using chemopreventive agents as mechanistic probes should allow an improved definition of risk and response.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):CN02-03.
Abstract CN04-03: Phase 1b sulindac study for women at high risk for breast cancer
Authors: Thompson Patricia , Vining Donna , May Melissa , Chew Wade , Green Sylvan , Stopeck Alison , Alberts David , Chow H-H. 
Published: May 2012

Abstract
CN04-03

Background
Regular use of non steroidal anti-inflammatory agents (NSAIDs) has been associated with reduced risk of breast cancer. The breast specific activity of each of the numerous NSAID agents and their relative potency to prevent breast cancer remains unknown. Sulindac, a non selective NSAID with pro apoptotic activity is a strong candidate for chemoprevention.

Objective and Methods
To assess concentrations of sulindac and its metabolites as well as their effects on known molecular markers in nipple aspirate fluid (NAF) in 15 subjects receiving 150 mg once daily and 15 subjects receiving 150 mg twice daily sulindac. NAF and serum samples were collected before and after 6 weeks of sulindac dosing.

Results
Sulindac and sulfide were detectable in 57.7% of NAF samples with sulfone detectable in 11.6%. There were no statistically significant differences between sulindac or sulfide levels in NAF by dose. There was a significant positive correlation between NAF sulindac and NAF sulfide levels. NAF 13,14-dihydro-15-keto prostaglandin A2 (PGEM), a stable derivative of prostaglandins, exhibited a non significant trend towards decreased levels (p =0.1). Serum levels of sulindac, but not NAF sulindac, was correlated with a decrease in NAF PGEM levels (p=0.03). The NSAID inducible protein, growth differentiation factor GDF-15, showed a borderline significant trend towards higher levels in NAF in the 300 mg daily group (p = 0.07). Serum CRP levels were decreased with sulindac exposure with the greatest decrease observed among those women with elevated CRP levels at baseline.

Conclusion
Sulindac and its sulfide metabolites partition to the breast and are detectable in NAF. Sulindac exposure was associated with a trend towards reduction in PGEM that was correlated with serum levels of sulindac. GDF-15 levels increased in the high dose group. NAF levels of PGEM and GDF-15 may prove useful as NSAID response biomarkers if for larger efficacy based intervention studies in breast cancer prevention.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):CN04-03.
Abstract CN06-01: Obesity, physical activity, and colon polyps: Black Women's Health Study
Authors: Adams-Campbell Lucile 
Published: May 2012

Abstract
CN06-01
Incidence and mortality rates of colorectal cancer are higher in African-American women than any other ethnic group in the United States and the disparity may be widening. The obesity epidemic in the United States has disproportionately affected African-American women, with obesity being nearly twice as prevalent in African-Americans as Whites. The causes of these increasing rates of obesity are not well understood, although it is hypothesized to be caused by dietary changes and decreased physical activity in the general population over time. An appreciable body of evidence suggests that leisure-time physical activity reduces the incidence of colon cancer. There is much less evidence on whether physical activity protects against colorectal adenomas, which are thought to be precursors to most colon cancers, although the evidence has been inconsistent. No findings have been reported on the relation of physical activity to the incidence of colorectal polyps in African-American women. We report here on the effect of obesity and physical activity on the incidence of colorectal polyps in the Black Women’s Health Study (BWHS), a large follow-up study of black women in the U.S.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):CN06-01.
Abstract CN06-03: Pediatric obesity research: a transdisciplinary approach
Authors: Spruijt-Metz Donna 
Published: May 2012

Abstract
CN06-03
Energy balance has been defined as the integrated effects of diet, physical activity, and genetics on growth and body weight over the life course, including links to cancer and other co-morbidities. Pediatric obesity is thus a complex field that involves interactions between psychosocial, environmental, neurobiological and metabolic pathways. To understand what drives obesity and related behaviors in minority at-risk adolescent populations, highly transdisciplinary approaches are therefore required. This talk will cover some approaches that have been successfully used to promote transdisciplinary research in pediatric obesity, some of the problems encountered to transdisciplinary work, and some possible solutions to those problems. Examples will be taken from series of increasingly transdisciplinary studies on pediatric obesity in minority youth. These studies draw from a wide range of disciplines including (but not limited to) biology, cancer and cancer biomarkers, metabolism, psychology, nutrition, exercise physiology, engineering, genetics, geography and entertainment, and represent first steps towards an integrated understanding of determinants and outcomes of pediatric obesity.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):CN06-03.
Abstract CN07-03: Discriminatory accuracy from Single Nucleotide Polymorphisms in models of absolute breast cancer risk
Authors: Gail Mitchell 
Published: May 2012

Abstract
CN07-03
One purpose for seeking single nucleotide polymorphisms (SNPs) that are associated with disease is to improve models for projecting individualized disease risk. Seven SNPs have recently been confirmed to be associated with breast cancer. I used published estimates of relative risks and allele frequencies to calculate how much these SNPs could improve discriminatory accuracy measured as the area under the receiver operating characteristic curve (AUC). A model with these seven SNPs (AUC = 0.574 ) and a hypothetical model with 14 such SNPs (AUC = 0.604) have less discriminatory accuracy than a model, the National Cancer Institute’s Breast Cancer Risk Assessment Tool (BCRAT), which is based on ages at menarche and at first live birth, family history of breast cancer, and history of breast biopsy examinations (AUC = 0.607). Adding the seven SNPs to BCRAT improved discriminatory accuracy to an AUC of 0.632, which was, however, less than the improvement from adding mammographic density. Thus, these seven SNPs improve the discriminatory accuracy of BCRAT only modestly. I used other criteria to compare BCRAT with a model that added the seven SNPs to BCRAT. These criteria included the proportion of cases in the portion of the population with the highest 90% of risk, the expected losses when using risk models to decide which women should be given a mammogram, and the expected losses when using a risk model to decide which women should take tamoxifen to prevent breast cancer. The seven SNPs provided very little improvement over BCRAT for any of these applications. Hundreds of SNPs would be required to achieve high discriminatory accuracy.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):CN07-03.
Abstract CN09-03: Current controversies in the viral etiology of cancer
Authors: Engels Eric 
Published: May 2012

Abstract
CN09-03
Viruses are among the proven causes of several cancers and suspected in the etiology of others. Highly sensitive molecular techniques (e.g., polymerase chain reaction [PCR]), which can detect minute amounts of viral nucleic acids in human tumors, are useful in suggesting possible causal associations. Detection of viral DNA or RNA in human tumors, on its face, supports the conclusion that the virus is present in the tumor and may therefore have been instrumental in its development. However, reliance on these methods in recent years has generated controversial results in several instances, and some proposed associations have not withstood the test of time.
There are several reasons why use of these sensitive molecular techniques is insufficient in establishing causal associations between viruses and cancer. First, PCR is widely available but poorly standardized, and the methods sometimes yield false-positive results when applied to tumor tissues. Along these lines, quantitative PCR methods are helpful in distinguishing low-level PCR contamination from biologically relevant infection; in the latter case, one would predict at least one PCR-quantifiable copy of virus per tumor cell. Second, additional laboratory techniques are required to localize viruses within tumor cells, demonstrate expression of key viral oncoproteins, and establish integration into host DNA and clonality of the virus_all of which add important supportive evidence that the virus is present in the tumor and driving proliferation. Third, epidemiologic evidence from population-based studies in humans is required to demonstrate that host infection precedes development of the cancer and that infection is associated with an increased risk of cancer during follow-up. A strong magnitude of association (i.e., a large relative risk relating infection to a sizably increased cancer risk) provides important supportive evidence. These epidemiologic studies require rigorous design and validated measurements of host infection (e.g., assays for systemic antibody production or viremia).
Controversy typically arises when evidence from molecular studies of tumor tissues is not supported by, or actually conflicts, with other lines of evidence. Further controversy can arise from inconsistencies in molecular results within or across laboratories. Several examples will be reviewed, including a recent controversy surrounding the possible role of simian virus 40 in development of several cancers in humans. Investigators must treat initial reports of possible associations between viruses and cancer with caution. Replication of initial findings by independent research groups, and evaluation of the proposed association using several complementary laboratory and epidemiologic approaches, is required to establish a causal relationship.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):CN09-03.
Abstract CN12-01: Clonal evolution over time in Barrett's Esophagus
Authors: Maley Carlo 
Published: May 2012

Abstract
CN12-01
Our current theory of neoplastic progression specifies that clones arise through genetic or epigenetic instability, and if they have a reproductive or survival advantage over other cells in the neoplasm, within their microenvironment, they will expand in the neoplasm in a selective sweep. Thus, we believe neoplastic progression is characterized by a series of selective sweeps. However, virtually all data on that process to date is cross-sectional, with observations of genetic diversity and large clonal expansions within neoplasms at a single time point. I will describe data that, for the first time, tracks the evolutionary dynamics of clones in a solid neoplasm over time. We have analyzed the frequency of large clonal expansions, the rate of those expansions and changes in clonal diversity over time in a cohort of 174 patients with Barrett’s esophagus. Barrett’s esophagus is a premalignant condition that predisposes to the evolution of esophageal adenocarcinoma. Unlike most other premalignant neoplasms, the Barrett’s tissue is not resected upon detection due to significant mortality and morbidity associated with esophagectomies. Instead, serial endoscopic surveillance for the early detection of cancer is the recommended management of the condition. This allows us to study neoplastic progression over both space and time in unprecedented detail. In the Seattle Barrett’s Esophagus Project, we also gather data on host and environmental factors that may impact progression, including use of non-steroidal anti-inflammatory drugs, which have been associated with a dramatic reduction of risk for progression to cancer. I will relate the factors associated with clonal expansions and genetic diversity to the parameters that determine the rate of evolution: mutation rate, population size, stem cell generation time and the fitness effects of mutations.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):CN12-01.
Abstract CN12-02: Evolution in carcinogenesis
Authors: Shibata Darryl 
Published: May 2012

Abstract
CN12-02
Histories are inherently recorded within genomes by errors that inevitably occur during replication. Essentially, the greater the number of genome replications, on average the greater the numbers of differences between two genomes (“molecular clock hypothesis”). Recent “cancer genome projects” have revealed how a genome changes during its evolution to colorectal cancer. Interesting findings are the relatively low numbers of somatic mutations (&lt;1 mutation per 100,000 bases), the infrequency of commonly mutated genes (many more “hills” than “mountains”), and marked heterogeneity of mutations between different cancers (overlap of mutated genes was minimal). There was an average of ~80 somatic mutations in genes per cancer, with relatively more “passenger” mutations than “driver” mutations. Greater than 80% of the mutated genes within a cancer genome are thought to be neutral passenger mutations. Relatively normal cell division and mutation rates can account for the numbers of changes in a cancer genome. By counting numbers of somatic changes (mutation and epigenetic changes), it may be possible to reconstruct the mode and tempo of cancer evolution starting from the zygote.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):CN12-02.
Abstract CN13-02: Breast tissue composition and risk of breast cancer
Authors: Boyd Norman , Martin Lisa , Menichouk Olga , Gunasekara Anoma , Selah Ahesha , Yaffe Martin , Chavez Sonia , Bronskill Michael 
Published: May 2012

Abstract
CN13-02

Background
Susceptibility to breast carcinogens is greatest before the age of 20 years. We have used magnetic resonance (MR) to measure the water content of the breast in young women, and have identified factors associated with variations in breast water. Breast water, like mammographic density, reflects fibro-glandular breast tissue, which is strongly associated with breast cancer risk in middle aged and older women.

Methods
We recruited 400 young women aged 15-30 years and their mothers, measured breast water and fat in daughters using (MR), and obtained anthropometric and other data. Mothers provided mammograms (n=365) and a random sample (n=100) also had breast MR.

Results
Percent water by MR in daughters (median=44.8%) was greater than in mothers (median=27.8%) (P&lt;0.0001), and was greater in daughters aged 15-19 years (n=199; median=49%) than in those aged 20-30 years (n=201; median=41%). Percent water in daughters was correlated with both breast water (n=100 pairs; r=0.28; p=0.005), and percent mammographic density in mothers (n=356 pairs; r=0.25, p&lt;0.0001). Percent water in daughters was independently associated with their age (p=0.04) and weight (p&lt;0.0001) (both inversely), and with their height (p&lt;0.0001) and percent density in their mothers’ mammogram (p&lt;0.0001) (both positively).

Conclusions
Percent breast water was greatest at ages when susceptibility to breast carcinogens is also greatest. The distribution of breast water according to age was consistent with a model in which mammographic density in mid-life is in part the result of genetic influences and growth and development in early life that determine initial breast tissue composition.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):CN13-02.