bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B84: NADPH oxidase 1 (NOX1) and related NOX isoforms as key mediators of NFκB signaling in colon cancer
Authors: Wang Rong , Dashwood Wan-Mohaiza , Nian Hui , Tsuchiya Naoto , Nakagama Hitoshi , Dashwood Roderick 
Published: May 2012

Abstract
B84
NADPH oxidase/dual-oxidase (Nox/Duox) family members have been implicated in nuclear factor kappa-B (NFκB)-mediated inflammation and inflammation-associated pathologies. In rats given 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) alternating with a high-fat diet, Nox1, Nox4 and Duo2, but not Nox2, were over-expressed in colon tumors at 1 year, as shown by quantitative RT-PCR and immunoblotting. Over-expression of Nox/duox isoforms coincided with increased nuclear NFκB protein, and elevated levels of downstream targets IL-1β, IL6, TNF-α and TNFR1. Over-expression of Nox1 and activation of NFκB also occurred at early stages of colon carcinogenesis, prior to tumor development. Nox/Duox isoforms were over-expressed in primary human colon cancers and in several human colorectal cancer cell lines. In HT29 cells, silencing of Nox1 inhibited nuclear translocation and DNA binding activity of NFκB, attenuated downstream targets IL1β, c-myc, and cyclin D1, and blocked lipopolysaccharide-induced phosphorylation of IκB kinaseα/β, resulting in G1 arrest. We conclude that the Nox1-NFκB pathway is important in colon tumorigenesis, and that Nox1 may provide a target for novel therapeutic strategies against colon cancer development.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):B84.
Abstract CN05-03: Modulating ER stress-induced autophagy to cancer control
Authors: Yin Xiao-Ming 
Published: May 2012

Abstract
CN05-03
Two major protein degradation systems are present in the cell, the ubiquitin proteasome system and the autophagy machinery. Inhibition of proteasome can activates autophagy, suggesting that the two systems are functionally coupled. Autophagy plays a compensatory role as suppression of autophagy promotes the accumulation of polyubiquitinated protein aggregates. Autophagy is likely activated in response to endoplasmic reticulum stress caused by misfolded proteins during proteasome inhibition. Indeed, direct disturbing ER environment with chemicals such as A23187, tunicamycin, thapsigargin and brefeldin A, can induce autophagy. Suppression of a major unfolded protein response pathway mediated by IRE1 by either gene deletion or RNAi dramatically suppresses the activation of autophagy by proteasome inhibitors or ER stress inducers. Interestingly, JNK but not XBP-1, both of which are the known downstream targets of IRE1, seems to participate in autophagy induction by proteasome inhibitors. Autophagy induced under these conditions is important for controlling endoplasmic reticulum stress and for reducing cell death in cancer cells. Thus a combined use of proteasome inhibitors and autophagy inhibitors enhances tumor cell death both in vitro and in vivo. Notably, this enhanced toxicity was not observed in non-transformed normal cells, suggesting that the impact of autophagy on cell survival during endoplasmic reticulum stress is likely contingent on the oncogenic status of cells. These findings indicate that blocking both autophagic and proteasomal degradation systems could be a novel and selective strategy for cancer control via the regulation of ER stress.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):CN05-03.
Abstract ED02-03: The integration of new in vivo and in vitro diagnostic technologies with new therapeutics to accelerate the development and approval of new cancer therapeutics
Authors: Heath James 
Published: May 2012

Abstract
ED02-03
The Nanosystems Biology Cancer Center (NSBCC) was founded three years ago by the NCI to accelerate the translation of systems biology models of cancer into clinical tool for cancer diagnosis and treatment. Over the past three years we have demonstrated that we can go, within a period of 1 to 1.5 years, from a concept on paper to Phase I trials or demonstrations in humans for three major cancer technologies: in vivo PET molecular imaging probes of cancer, siRNA-based cancer therapeutics, and highly multiplexed in vitro diagnostic assays. These advances represent major cost reductions and efficiency increases in three major aspects of cancer clinical care. However, the goal of achieving the same level of cost reductions and efficiency improvements in pushing a new therapeutic from a Phase I trial to an FDA-approved drug remains a daunting challenge. In this talk, I will discuss how the integration of in vivo and in vitro diagnostic tools with drug trials can be done to achieve this goal, and I will give examples of how we are beginning to push in this direction.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):ED02-03.
Abstract PR-14: Regression of rectal polyps in familial adenomatous polyposis patients with freeze-dried black raspberries
Authors: Stoner Gary , Hasson Henrietta , Sardo Christine , Wang Li-Shu , Pearl Dennis , Buchta Anthony , Burke Carol 
Published: May 2012

Abstract
PR-14
Familial adenomatous polyposis (FAP) is a dominantly inherited disease characterized by the early onset of colonic polyposis and a risk of colon cancer of nearly 100% by the age of 40. The traditional management of FAP is colectomy followed by lifelong endoscopic surveillance of the rectum and removal of rectal polyps. Our laboratory has reported on the ability of freeze-dried black raspberry (BRB) powder to prevent chemically-induced cancer in the rodent colon. Administration of BRB powder at 2.5, 5 and 10% in a synthetic diet to rats treated with the carcinogen, azoxymethane, reduced the development of colonic adenocarcinomas by 50 - 80%. BRBs prevent cancer in rodents by reducing cell proliferation, inflammation and angiogenesis, and by stimulating apoptosis and differentiation. We also showed in a Phase I clinical trial that BRB powder is well tolerated by humans when administered in a slurry of water at 45g/day for 7 days. Based upon these results, we undertook the present study to determine if BRB might regress rectal polyps in FAP patients. Fourteen FAP patients who had undergone a colectomy were treated with BRB daily for a period of nine months. Seven patients received BRB powder (20g/3x/day) orally in a slurry of water plus two suppositories (each composed of 700 mg BRB) that patients inserted into the rectum one hour before bedtime. The other seven patients were randomized to receive an oral placebo plus the two rectal suppositories. Rectal polyp counts were taken at time zero and after nine months of BRB treatment. The number of rectal polyps was reduced by a median of 43% at nine months overall including a median reduction of 59% in patients treated by both routes and 36% in patients treated with the suppositories only. Polyps and aberrant crypt foci were collected both before and after berry treatment, and molecular studies are underway to determine the mechanism(s) for BRB-induced rectal polyp regression in FAP patients.
(Supported by NCI grant CA103180 and USDA grant 38903-03560).
Citation Information: Cancer Prev Res 2008;1(7 Suppl):PR-14.
Abstract A102: Genetic reduction of circulating IGF-1 decreases growth of pancreatic tumors in an orthotopic transplant model
Authors: Lashinger Laura M. , Malone Lauren , Perkins Susan N. , Colby Jennifer K.L. , Fischer Sue M. , Hursting Stephen D. 
Published: May 2012

Abstract
Pancreatic cancer is the 4th deadliest cancer in the U.S. Obesity has emerged as a significant and modifiable risk factor for pancreatic cancer. Calorie restriction (CR) is an anti-obesity intervention that has been shown in many model systems to have potent anticancer effects. Levels of bioavailable insulin-like growth factor (IGF)-1, an established mitogen in a variety of cancer cell lines, increase in response to positive energy balance and decrease with CR. We hypothesized that the genetic reduction of circulating IGF-1 levels seen in liver-specific IGF-1-deficient (LID) mice would diminish the tumor burden of orthotopically transplanted pancreatic cancer cells, similar to CR, while administration of exogenous IGF-1 would restore the tumor burden. To test this hypothesis, mouse pancreatic cancer cells (JC101, derived from our BK5-COX-2 transgenic mouse model of spontaneous pancreatic cancer) were orthotopically transplanted in LID and littermate control (LC) mice. LID mice were also randomized to receive Alzet miniature osmotic pumps (implanted subcutaneously) continuously infusing either vehicle (n=8) or 1 µg/hr of recombinant human IGF-1 (Increlex®, Tercica, Inc., Brisbane, CA; n=8). LC mice were infused with vehicle (n=8). Mice were killed 28 days after injection, blood was collected by cardiac puncture and serum samples were stored at −80°C, and tumors were weighed and fixed in 10% normal buffered formalin for histological and immunohistochemical (IHC) analysis. IHC staining was performed on paraffin-embedded tissues using antibodies against Ki67 and cyclin D1 to assess proliferation. LID mice exhibited significantly smaller tumors (0.20 ± 0.02 g) than LC mice (0.45 ± 0.11 g, p&lt;0.05) or LID + IGF-1 mice (0.57 ± 0.14 g, p&lt;0.01). Serum IGF-1 levels were reduced approximately 60% in the LID mice relative to the LC mice (p&lt;0.01), while infusion of human IGF-1 resulted in total serum IGF-1 levels (murine plus human IGF-1) exceeding either LC or LID mice (p&lt;0.01). In contrast, insulin and leptin levels in LID mice were significantly higher than those seen in LC (p&lt;0.05) or LID+IGF-1 (p&lt;0.01) mice. Consistent with tumor burden data, LID tumors, relative to LC and LID + IGF-1, displayed less expression of proliferative markers. These findings suggest that genetic reduction of circulating IGF-1 levels decreases transplanted pancreatic tumor growth despite increased levels of insulin and leptin, underscoring the importance of the IGF-1 pathway as a pancreatic cancer prevention target.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A102.
Abstract A112: Flavonol intake may modify the association between interleukin genetic polymorphisms and colorectal adenoma recurrence in the polyp prevention trial
Authors: Bobe Gerd , Murphy Gwen , Albert Paul S. , Sansbury Leah B. , Lanza Elaine , Schatzkin Arthur , Colburn Nancy H. , Cross Amanda J. 
Published: May 2012

Abstract
Background: Interleukin (IL) 1β, 6, and 8 are pro-inflammatory cytokines that may promote colorectal carcinogenesis, whereas IL-10 is an anti#x2010;inflammatory cytokine with pro- and anti-carcinogenic effects. Single nucleotide polymorphisms (SNPs) in the promoter regions of these cytokine genes may alter inflammation and consequently colorectal carcinogenesis. Flavonols, found in fruits and vegetables, have anti-inflammatory and chemopreventive properties and they may modify the effect of SNPs in IL-encoding genes on colorectal carcinogenesis.
Aims: To determine whether SNPs in IL-1β, 6, 8, and 10 were associated with their corresponding serum concentrations and adenoma recurrence and whether flavonol consumption modified these associations.
Methods: Using logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for SNPs in IL-encoding genes, flavonol intake, and risk of adenoma recurrence in 1,687 participants of the Polyp Prevention Trial, a 4-year trial of a low-fat, high-fiber, high-fruit & -vegetable, flavonol-rich diet.
Results: Overall, SNPs in genes encoding IL-1s, IL-6, IL-8, IL-10 were not associated with their corresponding serum concentrations or adenoma recurrence. However, statistically significant interactions were observed between flavonol intake and IL-8 -251 T &gt; A genotype for any (P = 0.04) and advanced adenoma recurrence (P = 0.01). Individuals consuming above the median level of flavonol intake and had IL-8 -251 AA (vs. TT) had an increased risk of any (OR = 1.54, 95% CI: 1.00–2.39) and advanced adenoma recurrence (OR = 4.44, 95% CI: 1.32–15.0).
Conclusion: Our results suggest that flavonol consumption may modify the association between IL-8 SNPs and colorectal adenoma recurrence.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A112.
Abstract A116: Carotenoid intakes and risk of breast cancer by estrogen receptor status: A pooled analysis of 16 prospective cohort studies
Authors: Zhang Xuehong , Smith-Warner Stephanie A. 
Published: May 2012

Abstract
Associations between dietary carotenoid intakes and breast cancer risk by estrogen receptor (ER) status remain unclear. We prospectively investigated these associations using a pooled analysis of the primary data from 16 cohort studies. During follow-up of 996,735 women ranging from 6 to 22 years, 34,524 breast cancer cases (4,552 ER-/19,722 ER+) were identified. We used Cox proportional hazards models to estimate study-specific relative risks (RRs) and 95% confidence intervals (CIs) and pooled the estimates using a random-effects model. In the preliminary analyses, comparing the highest and lowest quintiles of intake, beta-carotene intake was associated with a 10% lower risk of ER- breast cancer (pooled multivariate RR = 0.89 (95% CI: 0.81–0.99), Ptrend = 0.07) but not with risk of ER+ breast cancer (pooled multivariate RR = 1.02 (95% CI: 0.97–1.08), Ptrend = 0.76, Ptest for common effects by ER status = 0.02). Similarly, lutein/zeaxanthin intake was associated with a 13% reduced risk of ER- breast cancer (pooled multivariate RR = 0.87 (95%CI: 0.79–0.96), P trend = 0.04) but not with risk of ER+ breast cancer (pooled multivariate RR = 0.99 (95%CI: 0.93–1.06), Ptrend = 0.33, Ptest for common effects by ER status = 0.03). Alpha-carotene, beta-cryptoxanthin and lycopene intakes were not associated with breast cancer risk regardless of ER status. We observed similar associations when we categorized carotenoid consumption using identical absolute intake cutpoints or modeled intakes as continuous variables. The associations between carotenoid intake and risk of ER- and ER+ breast cancer did not differ by alcohol consumption, smoking habits, or menopausal status (Ptest for interaction &gt; 0.05). Beta-carotene and lutein/zeaxanthin intakes appeared to be associated with a lower risk of ER-breast cancer but not with risk of ER+ breast cancer.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A116.
Abstract A120: Physical activity, body mass index, and vitamin D metabolite concentrations
Authors: Cisneroz Martin , Martinez Maria Elena , Thompson Patricia A. , Jacobs Elizabeth T. 
Published: May 2012

Abstract
Serum 25(OH)D concentrations have been demonstrated to be inversely related to several cancers. Because vitamin D can be obtained from both dietary sources and endogenous synthesis, the best strategy for improving vitamin D status is unclear, though abbreviated sun exposure, supplementation, and fortification have been suggested. Both physical activity and body mass index (BMI) have been shown to be correlated with 25(OH)D concentrations and themselves have been linked to colorectal neoplasia. We sought to investigate the types of physical activity that contribute most to circulating concentrations of vitamin D metabolites in a study population in southern Arizona, and to further evaluate the relative contributions BMI and type of physical activity to 25(OH)D concentrations. Individuals in the highest category of recreational physical activity were significantly more likely to have 25(OH)D concentrations of &gt;=30 ng/ml as compared to those who were less active (p=0.007). After adjustment for BMI, age, race, sex, and season of blood draw, recreational physical activity remained statistically significantly associated with serum concentrations of 25(OH)D (p= 0.002), while household and sedentary physical activity were not related in either crude or adjusted models. For those participants with a normal BMI (18 &lt; BMI &lt;25), recreational physical activity had no influence on circulating concentrations of 25(OH)D (p=0.28); however, for those who were overweight (25&lt;BMI&lt;30) or obese (BMI &gt;=30), recreational physical activity was directly associated with 25(OH)D levels (p=0.002 and p=0.009, respectively). For example, among obese participants, those in the lowest tertile of physical activity had a mean (+sd) 25(OH)D concentration of 22.4 + 7.8, while those in the highest tertile had levels of 27.0 + 7.2 (p-trend=0.009), possibly due to increased sun exposure. These results suggest that overweight individuals may be able to improve vitamin D status via recreational physical activity, which may in turn reduce the risk of several cancers.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A120.
Abstract A121: Genetic variation in CYP7A1, bile acids, and risk of adenoma in the proximal colon
Authors: Wertheim Betsy C. , Martinez Maria Elena , Alberts David S. , Jacobs Elizabeth T. , Lance Peter , Thompson Patricia A. 
Published: May 2012

Abstract
Background: Secondary bile acids, specifically deoxycholic acid (DCA), are probable carcinogens of colorectal cancer, particularly for lesions arising in the proximal colon. Cholesterol 7α-hydroxylase (CYP7A1) is the rate-limiting enzyme in the conversion of cholesterol to primary bile acids in the liver. Genetic variation in CYP7A1 has been reported to modify risk of colorectal neopolasia arising in the proximal colon.
Methods: Using the placebo arm of our ursodeoxycholic acid chemoprevention trial, we studied the relationships between baseline fecal bile acid concentrations, six allelic variants in CYP7A1, and risk of proximal adenomas after three years of follow-up (n = 253). Because bile acid levels are strongly influenced by sex, we considered gender as a potential effect modifier. After testing four possible modes of inheritance for associations between genetic polymorphisms and proximal adenoma, we present results generated under log-additive models.
Results: The relationship between fecal DCA levels and development of proximal adenoma was strongly modified by gender (pinteraction &lt; 0.001). Compared with the lowest quintile, higher levels of DCA were associated with significantly increased odds of proximal adenoma in men (OR = 7.14; 95% CI = 2.07 to 24.6) but non-significantly decreased odds in women (OR = 0.39, 95% CI = 0.13 to 1.20). These associations were slightly attenuated for men (OR = 5.82; 95% CI = 1.65 to 20.5) and women (OR = 0.44, 95% CI = 0.14 to 0.43) after adjusting for age and body mass index. In addition, analyses of two linked CYP7A1 SNPs (D′ = 0.75 and r2 = 0.5) showed that carriage of the minor allele for rs8192871 and rs13251096 lowered the odds of proximal adenoma by 45% (OR = 0.55; 95% CI = 0.36 to 0.85) and 41% (OR = 0.59, 95% CI = 0.40 to 0.89), respectively. Furthermore, these two SNPs were associated with DCA, such that carriers of two minor alleles had significantly lower fecal DCA levels (Kruskal-Wallis p = 0.003 for both SNPs). None of the other four CYP7A1 SNPs showed any association with proximal adenoma or fecal bile acid levels.
Conclusions: In this study population, CYP7A1 polymorphisms are significantly associated with risk of adenoma in the proximal colon, likely through their effects on bile acid levels. Sex, age, body mass index, and other factors that influence bile acid levels may further affect this risk.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A121.
Abstract A125: Genetic variation in nicotinic acetylcholine receptor region on chromosome 15q25 and lung cancer risk
Authors: Wei Chongjuan , Frazier Marsha , Wun Issac , Amos Chris 
Published: May 2012

Abstract
Lung cancer is the leading cause of cancer death in the U.S and is approximately 30% higher in African-Americans than in Caucasians. Recently, several groups including ours, using genome-wide association study, identified and replicated a region of chromosome 15q24–25.1 that had a highly reliable and significant association with lung cancer risk. Analysis of SNPs in this region identified association with variability in expression of exons 3–5 of CHRNA5. To identify additional variation that may be associated with lung cancer risk we started to re-sequence all of the exons and surrounding intron/exon boundaries for the genes in the region including CHRNA3, CHRNA5, PSMA4 and LOC123688, in 46 lung cancer cases and 46 control. Among these 4 genes, the first two are nicotinic acetylcholine receptor. Results of sequencing identified many new variants, and there were significantly more rare variants in cases than controls for CHRNA5. We evaluated 6 of these rare variants, located within the region of exon3–5 of CHRNA5 that were identified by resequencing, in a case controls study of African America population. However none of these 6 novel variants we identified were significantly more common in 467 cases than in 388 controls. In addition to these rare variants, we identified insertion/deletion variations in the promoters region of CHRNA5 and we will evaluate the association of these insertion/deletion variations with lung cancer in a large sample size of African America population. Taken together, the finding provides additional information on the association of nicotinic acetylcholine receptor region on chromosome 15q25 and lung cancer risk.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A125.
Abstract A128: Racial and ethnic disparities in lung cancer incidence, United States 1998–2005
Authors: Underwood Jon M. , Fairley Temeika , Townsend Julie , Tai Eric , Stewart Sherri 
Published: May 2012

Abstract
Background: Lung cancer is the second most commonly diagnosed cancer in men and women and the leading cause of cancer related death in the United States. Racial disparities in lung cancer incidence, treatment, mortality and survival have been documented. Advances in cancer surveillance, such as expansions in geographic coverage, allow for a more complete description of lung cancer incidence. This population-based study examines racial and ethnic disparities in incidence of lung cancer for the United States by demographic, geographic, and tumor characteristics.
Methods: We analyzed lung cancer incidence data obtained from cancer registries affiliated with Center for Disease Control's National Program of Cancer Registries and the National Cancer Institute's Surveillance, Epidemiology, and End Results program. The combined data collected on new cases diagnosed during 1998–2005 cover approximately 81% of the U.S. population. We calculated age-adjusted (2000 US standard) incidence rates, rate ratios, and 95% confidence intervals by demographic and tumor characteristics such as age, sex, race, ethnicity, U.S. Census Region, tumor grade, stage and histology.
Results: A total of 1,296,933 lung and bronchial cancer cases were diagnosed in the U.S. from 1998 until 2005. The overall incidence rate was (69.2/100,000 persons). Rates were higher among men (88.5) than women (55.1). Among men, incidence rates were highest for blacks (111.1) followed by whites (87.7), Asian/Pacific Islanders (API) (53.4) and American Indians/Alaska Natives (AI/AN) (53.3). Among women, whites (56.3) had the highest incidence rates followed by blacks (53.1), API (37.4), and AI/AN (27.3). Compared to non-Hispanics (71.8), Hispanics (37.5) had lower lung cancer incidence rates. More blacks were diagnosed at younger ages (40–59 years) compared to all other groups. At time of diagnosis, blacks have a higher percentage of distant disease (17%), and a higher percentage of poorly differentiated tumors (14%) compared to whites. Incidence rates differed amongst U.S. Census regions by race. Among whites, the highest lung cancer incidence rate was in the South (76.8) whereas rates among blacks (88.6), American Indians/Alaska Natives (61.5) & Hispanics (41.1) were highest in the Midwest.
Conclusion: This report updates previous findings from population-based studies describing U.S. disparities in lung cancer incidence. Differences in stage at diagnosis by race were also noted. We describe regional differences in incidence rates for certain racial and ethnic groups. These differences may reflect differences in tobacco use behaviors, early detection, treatment, or other unknown factors. Further investigation into the source of differences is warranted.
Citation Information: Cancer Prev Res 2010;3(1 Suppl):A128.