bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B43: The Vitamin D receptor and retinoid X receptor-alpha expression related to DNMT levels in a murine model of colitis
Authors: Knackstedt Rebecca , Moseley Vondina , Morris Jay , Wargovich Michael 
Published: June 2012

Abstract
Vitamin D3, whose functionality is controlled by signaling through the vitamin D receptor (VDR), plays a regulatory role in inflammation. To properly signal, VDR must heterodimerize with its signaling partner, Retinoid X Receptor (RXRα). When the signaling capability of Vitamin D3 goes awry, this mechanism of inflammation regulation is unchecked and cells are free to proliferate and release inflammatory signaling molecules. Inflammation and dysregulated Vitamin D3 signaling have been implicated in allowing the progression of colitis to cancer, but the mechanism by which this happens is poorly understood. Previous studies in our laboratory revealed that expression of RXRα is decreased in high-grade dysplasia in a mouse model of colon cancer. Whether RXRα or VDR are downregulated in human colitis remains to be clarified. The dextran sodium sulfate (DSS) model is a well-accepted animal model for human colitis, based on its histological similarity to human disease. Addition of azoxymethane (AOM), a carcinogen, is often utilized to encourage colon cancer development in mice with DSS-induced colitis.
As a first step, we examined the expression profiles of RXR and VDR in the DSS induced and the DSS/AOM induced mouse models of colitis. To achieve colitis with the DSS model, ten C57BL/6J mice were given 2% DSS for one week followed by a two week recovery period with water and five control mice received only water. This was repeated two times to simulate the remission and relapses evidenced in human colitis. Mice were sacrificed after the third cycle. For the AOM/DSS model, ten C57BL/6J mice were intraperitoneally (IP) injected with 10mg/kg of AOM (control mice were IP with saline) and allowed to recover for one week with water before being given the same DSS model as described above. Mice were killed after one cycle for the acute model or after three cycles for the chronic model. At sacrifice, colons were either swiss-rolled for IHC analysis of VDR, RXRα and PCNA or the mucosal layer was scraped for determination of VDR, RXRα and DNA methyltranferase (DNMT) expression and protein levels. We found that in both mouse colitis protocols VDR protein levels were decreased with altered levels of RXRα protein. In accord with these primary effects, we also found DNMT expression to be altered. We conclude that downregulation of key transcription factors by epigenetic mechanisms could play a role in murine colitis models. We are also investigating whether this find translates to one's risk for colon cancer
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B43.
Abstract B45: Inhibitory effects of fermented korean red ginseng on Helicobacter pylori-induced gastric inflammation and carcinogenesis
Authors: Kim Eun-Hee , Hong Kyung-Sook , Choi Ki-Seok , Ock Chan Young , Hong Hua , Han Young-Min , Paek Nam-Soo , Kim Sung-Soo , Hahm Ki Baik 
Published: June 2012

Abstract
Helicobacter pylori infection has been implicated in acute gastritis, chronic atrophic gastritis, peptic ulcers as well as gastric cancer. Since we have documented that anti-H. pylori, anti-inflammatory, anti-oxidative, and anti-mutagenic actions of Korean red ginseng and the enhancing anti-inflammatory activities and attenuating anti-inflammatory roles of Lactobacillus plantarum, in the current study, we investigated the effects of L. plantarum-fermented Korean red ginseng on subacute or chronic pathology in H. pylori-infected mouse model. 5-week-old interleukin-10 deficient mice were inoculated with H. pylori (Sidney strain 1), after which L. plantarum (Lp), Korean red ginseng (RG) and fermented Korean red ginseng (FRG) were administrated by drinking water for 14 or 24 weeks. After killing, in addition to gross and pathologic evaluations, the expressions of inflammatory enzymes or cytokines were analyzed by Western blot analysis or ELISA, respectively. H. pylori infection induced the expression of inflammatory enzymes, iNOS and COX-2, and cytokines such as IL-1β and IL-6 in subacute 14 weeks model. Moreover, H. pylori infection significantly provoked tumorigenesis in chronic 24 weeks model. Lp, RG and FRG inhibited the expression of inflammatory enzymes and cytokines in both subacute and chronic models. Among those, FRG showed the significant anti-inflammatory and anti-tumorigenic effects on H. pylori-infected gastric carcinogenesis reflected with decreased incidence of tumor formations. Probiotics fermented Korean red ginseng exerted significant protections against H. pylori infection through attenuating gastritis, rescuing from tumorigenesis and enhancing gastroprotection. We suppose that chronic intake of FRG can be an anticipating strategy in chemoprevention of H. pylori-associated gastric cancer.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B45.
Abstract B52: The role of p38 activation in nucleotide excision repair in human skin
Authors: Christian Perry , D'Orazio John 
Published: June 2012

Abstract
Keratinocyte-based skin malignancies are diagnosed over one million times a year in this country alone despite widespread knowledge about UV avoidance and sunscreen use. The majority bear evidence of UV-induced mutations in key cancer-related genes such as TP53, highlighting the importance of environmental sun and tanning bed exposure in their pathophysiology. Accumulation of UV-induced DNA mutations, and ultimately skin cancer risk, is determined not only by UV exposure but also by the ability of keratinocytes to repair mutagenic damage caused by UV radiation. Xeroderma pigmentosum patients, in whom DNA repair is defective due to homozygous loss of any one of at least eight enzymes in the nucleotide excision repair (NER) pathway, suffer exceptionally high incidences of UV-induced skin cancers, illustrating the importance of NER in resistance to skin cancer. There is little understanding of the factors that determine the efficiency of NER in the skin. We have found that NER can be modified exogenously by inducing a cAMP-based pathway in the skin. Specifically, topically-applied forskolin, an activator of adenylate cyclase reproducibly enhances clearance of UV-induced cyclobutane dimers in human skin explants and in human keratinocytes. Pharmacologic induction of cAMP via forskolin efficiently activates the protein kinase A (PKA) signaling cascade and leads to downstream phosphorylation of the cAMP responsive binding element (CREB) transcription factor. Intriguingly, we and others have found that UV radiation also results in robust CREB phosphorylation in human skin and human keratinocytes, but in a PKA-independent manner. Furthermore, UVB induced CREB phosphorylation displays similar kinetics to UVB induced p38 activation and is diminished upon p38 inhibition. Together, these data suggests the p38 damage response pathway, recruited by UV, directly phosphorylates CREB without involving the cAMP second messenger. Currently, we are determining the effects of p38 inhibition on NER activity. We hypothesize that inhibiting p38 will lead to decreased NER activity in human skin and this loss of NER can be overcome with the addition of forskolin. Our observations presented here suggest that the p38/CREB signaling axis may be a major determinant of NER efficiency in the skin and raise the exciting possibility of a novel skin cancer preventative approach outside of UV-avoidance.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B52.
Abstract B86: Indoor tanning use and incidence of skin cancer
Authors: Zhang Mingfeng , Qureshi Abrar A. , Geller Alan , Frazier Lindsay , Hunter David , Han Jiali 
Published: June 2012

Abstract
Tanning beds are used by 30 million Americans each year. The use of tanning beds has been shown to increase the risk of skin cancers in previous epidemiological studies. A 2007 meta-analysis by the International Agency for Research on Cancer (IARC) reported positive associations of ever-use of tanning beds with increased risks of melanoma and squamous cell carcinoma (SCC). In 2009, the IARC classified UV radiation from tanning beds as human carcinogen (group 1). However, risk effect of indoor tanning on basal cell carcinoma (BCC), the most prevalent skin cancer in Caucasians, has been inconclusive. Besides, evidence for a dose-response relationship with melanoma and SCC was inconsistent across previous studies. In this study, using a large and well-characterized cohort in the U.S., the Nurses' Health Study II, we followed up 73,494 female nurses for 20 years and investigated the frequency of tanning bed use during high school/college, at age 25–35, as well as the overall average usage during both periods in relation to three types of skin cancer (BCC, melanoma, and SCC). We used Cox proportional hazards models to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for each type of skin cancer. During follow-up, 5,526 BCC cases, 348 melanoma cases, and 400 SCC cases developed. We found highly significantly elevated risk of BCC among participants who used tanning beds either during high school/college or at ages 25–35 (p &lt; 0.001). The multivariable-adjusted HR for 1 time/year use was 1.10 (95% CI 1.08–1.12) with the use during high school/college and 1.06 (95% CI 1.04–1.07) with the use at ages 25–35. A dose-response effect was detected for all three types of skin cancers, with the multivariable-adjusted HRs for average 1 time/year use during both periods of 1.04 (95% CI, 1.03–1.05; p &lt; 0.001) for BCC, 1.03 (95% CI, 0.995 − 1.06; p = 0.09) for melanoma, and 1.05 (95% CI, 1.02–1.08; p = 0.002) for SCC. Compared to individuals who used tanning beds from ages 25–35, we found a significantly higher risk of BCC for those who used it during high school/college (p for heterogeneity = 0.002). Of note, for those with &gt; 6 times/year use, the multivariable-adjusted HR of BCC compared to non-users was 1.35 (95% CI, 1.23–1.49) at ages 25–35 and 1.82 (95% CI, 1.60–2.08) during high school/college (p for heterogeneity &lt; 0.001). Our data provide strong evidence for an association between tanning bed use and the risk of skin cancers with a dose-response effect, especially for BCC.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B86.
Abstract B88: Comorbidity and survival among black women and white women 35 to 64 years of age at diagnosis with invasive breast cancer
Authors: Lu Yani , Ma Huiyan , Sullivan-Halley Jane , Malone Kathleen E. 
Published: June 2012

Abstract
Introduction: The impact of comorbidity on overall survival among older women diagnosed with breast cancer has been studied extensively. However, less is known about its impact on overall survival among women diagnosed with breast cancer before age 65 years.
Methods: We followed 4516 (1605 black, 2911 white) women ages 35 to 64 years when diagnosed with incident invasive breast cancer between 1994 and 1998. The pre-diagnosis history of 11 comorbid conditions and whether they had been treated were collected shortly after breast cancer diagnosis. Multivariate Cox regression models were used to examine the impact of these comorbidities on overall survival.
Results: During a median of 8.2 years follow-up, 1052 (524 black, 528 white) women died. The prevalence of comorbidities diagnosed before breast cancer was higher among black women than among white women (61.3% vs. 44.7%). Compared to women without any comorbidities, women were at increased risk of death if they had any treated comorbidity except when gallbladder disease; peptic, stomach, gastric, or duodenal ulcer; or liver disease was the only comorbidity. The risk of death increased with increasing number of treated comorbidities (P-trend&lt;0.001; adjusted relative risk [RR] of death=1.21, 1.20 and 1.90 for women with 1, 2, and 3 or more comorbid conditions). However, when stratified by tumor stage, having more comorbid conditions was associated increasing mortality risk among women diagnosed with localized tumors (P-trend&lt;0.001), but not among women diagnosed with non-localized tumors (P-trend=0.29) (P for homogeneity of trend&lt;0.001). This risk pattern was consistent among black women and white women.
Conclusions: Among women ages 35 to 64 years when diagnosed with invasive breast cancer, having more comorbidities at breast cancer diagnosis has a greater impact on overall survival for women with localized tumors than for women with non-localized tumors.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B88.
Abstract B90: Diabetes and the risk of colorectal adenomas: Black Women's Health Study
Authors: Dash Chiranjeev , Palmer Julie R. , Rosenberg Lynn , Boggs Deborah A. , Adams-Campbell Lucile L. 
Published: June 2012

Abstract
Introduction: Metabolic abnormalities associated with diabetes mellitus (DM) are hypothesized as colorectal carcinogenesis mediators. Results from epidemiologic studies on the association of DM with colorectal cancer are inconclusive. However, limited data from small case-control studies suggests a stronger association of diabetes with colorectal adenoma. Given the relative lack of information on the risk of colorectal adenomas in African-American women, and the higher prevalence of diabetes in African Americans we investigated DM as a risk factor for colorectal adenomas in the Black Women's Health Study.
Methods: We conducted a nested case-control study among participants in the Black Women's Health Study - a cohort study of 59,000 women followed biennially since 1995. Cases were defined as women diagnosed with incident colorectal adenoma between 1997 and 2009. Only those adenoma cases verified by medical record review were included. Controls were participants who also underwent lower gastrointestinal endoscopy in the same period and in whom no adenoma or other polyp was found. DM and insulin use were self-reported by participants on each biennial questionnaire. Using logistic regression models, we obtained odds ratios (OR) for colorectal adenoma in relation to DM, adjusting for age, education, body mass index, physical activity, fruit and vegetable intake, family history of colorectal cancer, smoking, alcohol intake, energy intake, and aspirin use.
Results: There were 742 adenoma cases and 14,434 non-cases. After adjusting for multiple covariates, there was no association of DM with colorectal adenomas (OR: 1.02, 95% CI: 0.82–1.26) in this study of African-American women. Insulin therapy for DM was also not associated with adenoma risk. Compared to women without DM, the ORs (95% CI) for diabetic women using insulin, and those not using insulin were 1.14 (0.78–1.68) and 0.98 (0.78 − 1.25), respectively.
Conclusions: We did not find an association of DM with colorectal adenomas among African-American women. Our results support the findings from two recent cohort studies that showed no association of type 2 DM with colorectal cancer in women. Further research is needed to confirm these findings in African American women, and explore the association of DM and colorectal adenoma in African-American men.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):B90.
Abstract CN02-02: Ovarian cancer GWAS: Path from risk assessment to prevention?
Authors: Sellers Thomas A. 
Published: June 2012

Abstract
Ovarian cancer risk is known to be influenced by highly penetrant mutations in BRCA1 and BRCA2. However, these are rare in the population and collectively account for around 10% of cases. Since these genes account for less than 50% of the familial risk of ovarian cancer, other loci must surely exist. Genome wide association studies have contributed to the identification of at least six additional chromosomal regions harboring common genetic variants that are associated with modest levels of risk increase or decrease. The knowledge of Mendelian and oligogenic susceptibility genes lays the foundation for risk-appropriate preventive interventions. Several options have already been identified through epidemiologic research, ranging from relatively innocuous strategies such as use of oral contraceptives, to more invasive surgical approaches such as tubal ligation and oophorectomy, each with varying degrees of effectiveness as well as complication rates and side effects. The level of genetic risk should inform decisions and strategies as to the appropriate intervention. However, there is a need for less invasive prevention strategies, especially chemoprevention. Finally, more progress is needed in the translation and dissemination of risk assessment to risk reduction in the clinical practice and public health settings.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN02-02.
Abstract CN02-03: Prevention of human papillomavirus-related malignancy in the post-vaccine era
Authors: Goodman Marc T. 
Published: June 2012

Abstract
We are presently at a crossroads in clinical practice as new public health models for cervical cancer prevention and detection are being developed and tested. In the US, we are in the midst of redefining government policy and medical decision-making based on human papillomavirus (HPV) natural history studies, randomized trials, and prophylactic vaccine uptake. Novel diagnostic, progression and treatment approaches are emerging that are based on a paradigm that recognizes the central role of HPV persistence in anogenital cancer development. Gaps in epidemiological and clinical research will be examined including the role of immune markers in viral clearance, the transmission dynamics of anogenital HPV infection, novel screening modalities in high risk populations, and the implementation of population-based surveillance activities to determine the public health benefit and cost-effectiveness of the prophylactic HPV vaccine.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN02-03.
Abstract CN04-01: New drugs for the chemoprevention of experimental breast cancer
Authors: Liby Karen T. , Tran Kim , Kim Eun-Hee 
Published: June 2012

Abstract
Tamoxifen, raloxifene and exemestane are all effective for prevention of estrogen-receptor positive (ER+) breast cancer in women. Despite these significant advances, novel drugs are needed for the chemoprevention of estrogen-receptor negative (ER−) breast cancer, especially for women with hereditary breast cancers who frequently harbor BRCA (breast cancer-associated gene) mutations. Currently, “watchful waiting” or bilateral prophylactic mastectomy is offered to these patients, although these high risk women are ideal candidates for an effective, safe chemopreventive regimen. Two relevant mouse models were used to study drugs that are used to treat human breast cancer or drugs with known chemopreventive activity in other animal models. When conditional knockout (co) of BRCA1 is coupled with a mutation in p53, Brca1Co/Co;MMTV-Cre;p53+/− mice develop ER− mammary tumors within 6–10 months of age. In the PyMT mouse model, the polyomamiddle T oncoprotein drives carcinogenesis by inducing significant infiltration of tumor-associated macrophages (TAM). The efficacy of synthetic triterpenoids, rexinoids, histone deacetylase inhibitors, and PARP (Poly ADP ribose polymerase) inhibitors as well as potential biomarkers and mechanisms for these drugs will be discussed.
Supported by the Breast Cancer Research Foundation and Komen for the Cure
Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN04-01.
Abstract CN04-02: Tumor and genomic heterogeneity in breast cancer prevention
Authors: Ambrosone Christine B. 
Published: June 2012

Abstract
Prevention of breast cancer, first and foremost, requires an understanding of the etiology of the disease. Although epidemiological studies have identified a number of risk factors for breast cancer over the last several decades, there is still a sizeable proportion of variability in disease incidence that is unexplained. It is likely that heterogeneity, both in tumor biology and in inherent genomic make up, may blur potential associations. If we accept that breast cancer is more than one disease, as increasingly demonstrated by better understanding of breast tumor subtypes, then it stands to reason that risk factors may differ in etiologic pathways. For example, parity has long been considered to reduce risk of breast cancer. However, there is a growing body of evidence suggesting that having children does reduce risk of estrogen receptor (ER) positive or luminal A breast cancer, but actually increases risk of ER negative and/or basal-like breast cancer, which occurs more often in women of African ancestry. Further examination of risk factors by breast cancer subtypes may clarify some of the uncertainty regarding associations between other exposures and breast cancer risk.
In addition to tumor heterogeneity, the genetic make-up of at-risk populations is known to vary substantially. Common differences in genomic DNA, such as single nucleotide polymorphisms (SNPs), occur in genes that are involved in numerous pathways that could be related to breast cancer risk, including hormone metabolism, carcinogen activation and detoxification, DNA repair, and cell cycle control. Although there has been focused attention on the potential role of gene/environment interactions in breast cancer risk over the last decades, with some persuasive findings, the majority of these studies have not examined such associations in relation to breast tumor subtypes. In this presentation, the role of tumor and genomic heterogeneity in breast cancer risk will be presented, particularly in relation to breast cancer in African American women, and potential preventive strategies will be discussed.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):CN04-02.