bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1856: A KRAS-variant as a putative biomarker of ovarian cancer risk
Authors: Weidhaas Joanne B. , Slack Frank 
Published: February 2011

Abstract
Purpose: Ovarian cancer is the single most deadly form of women's cancer, largely due to a lack of known risk factors or genetic markers. The KRAS oncogene and altered levels of the microRNA let-7 are associated with an increased risk of developing solid tumors. We investigated the association of a single nucleotide variant (rs61764370), referred to as the KRAS-variant, that disrupts a let-7 microRNA binding site in the KRAS oncogene 1, and ovarian cancer risk.
Methods: Specimens were obtained from non-selected ovarian cancer patients in three independent cohorts (n = 457) and two independent ovarian case-control studies. Specimens from ovarian cancer patients with hereditary breast and ovarian cancer (HBOC) syndrome (n = 58) and their family members were also collected.
Findings: The KRAS-variant is found in greater than 29% of non-selected ovarian cancer cases and is a marker for a significant increased risk of developing ovarian cancer by case control analysis (OR = 2.46, CI = 1.14-5.29, p = .020, n = 201). This was validated in a second independent ovarian case-control (n = 630). The KRAS-variant was also identified in 60% of HBOC patients without BRCA1 or BRCA2 mutations (n = 25, p &lt; 0.001), previously considered uninformative, as well as in their family members with cancer.
Interpretation: These findings support the hypothesis that the KRAS-variant is a genetic marker of an increased risk of developing ovarian cancer, and suggests that the KRAS-variant may be a new biomarker of risk for HBOC families without other known genetic abnormalities.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1856.
Abstract 1862: Inactivation of P53 by HPV 16/18 E6 proteins in lung cancer is correlated with P53 codon 72 genotypes
Authors: Hsu Nan-Yung , Chen Chih-Yi , Chou Ming-Chih , Cheng Ya-Wen 
Published: February 2011

Abstract
A polymorphism at codon 72 of the p53 tumor suppressor gene is as a possible determinant for cancer risk and particularly carcinomas associated with HPV infection. Our recent report has shown that high-risk HPV 16/18 E6 proteins were associated with p53 protein degradation in lung cancer. To address the relationship of the different p53 genotypes and HPV oncoprotein expression in p53 protein degradation of lung cancer, 141 primary lung cancer patients were included in this study. PCR-RFLP, nested-PCR and immunohistochemial analysis were used to detect the p53 codon 72 polymorphism, HPV 16/18 infection, HPV 16/18 E6 and p53 protein expression. Our data showed that HPV 16/18 E6 protein but not HPV 16/18 DNA were reversely correlated with p53 expression, which was further confirmed by tissue in situ immunostaining. Additionally, the frequency of p53 protein negative expression in HPV 16/18 E6-positive/Arg homozygosity lung cancer tumors is much higher than that in the other three categorizes. This correlation was not found in HPV DNA infection. In conclusion, HPV 16/18 E6 proteins involvement in p53 inactivation to contribute to HPV-infected lung tumorigenesis is correlated with p53 codon 72 genotypes.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1862.
Abstract 1863: MutL homolog 1 promoter polymorphism in prostate cancer and benign prostatic hyperplasia
Authors: Tanaka Yuichiro , Liu Jan , Zaman Mohd S. , Majid Shahana , Saini Sharanjot , Chen Yi , Kawakami Kazumori , Dahiya Angela V. , Khatri Gaurav , Deng Guoren 
Published: February 2011

Abstract
MutL homolog (MLH1) is one of several DNA mismatch repair genes of which defects can result in mutation and genomic instability, and ultimately may lead to cancer. Polymorphisms of MLH1 promoter have been shown to be a risk for several types of cancers and thus, we hypothesize that MLH1 promoter polymorphisms can be a risk factor for prostatic diseases. To test this hypothesis, the genetic distribution of MLH1 polymorphism of the promoter region at nucleotide positions prior to translation start site at −1913 (rs34013758), −593 (rs34566456), −93 (rs1800734) and recently identified −107 (base change C to G) were analyzed in 131 normal healthy subjects, 134 benign prostatic hyperplasia (BPH), and 177 sporadic prostate cancer samples in a Japanese population by sequence-specific PCR and sequencing. These experiments show that the variant G/G genotype at the −93 location is associated with prostate cancer when compared to normal controls. Odds ratio and 95% confidence interval for cancer were 1.93 and 1.01-3.69, respectively, for the variant G/G genotype when compared to wildtype (A/A). Likewise, the variant G allele was associated as a risk for prostate cancer (P=0.063). However, no differences were observed for the promoter −93 polymorphism between BPH and controls as well as between stages or grades of prostate cancer. Interestingly, when analyzing the promoter −93 site with the Ile219Val (A to G) polymorphic site, a significant linkage was observed among controls (D’=1). Haplotype analysis showed bases A-A reflecting the wildtype forms for −93 and Ile219Val sites, respectively, to be significantly reduced in cancer compared to controls (P=0.033). The promoter −107 site was extremely rare with C/G type observed in one cancerous patient whereas rs34013758 and rs34566456 were not observed in this Asian population. This is the first report that demonstrates an association for the MLH1 promoter polymorphism with prostate cancer and these results are important in understanding its role in this disease.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1863.
Abstract 1868: Evaluation of the nucleotide excision repair polymorphisms for association with lung cancer risk
Authors: Buch Shama C. , Nukui Tomoko , Weissfeld Joel , Romkes Marjorie 
Published: February 2011

Abstract
There is increasing evidence that decreased nucleotide excision repair (NER) capacity may be associated with increased risk of cancer, including non-small cell lung cancer (NSCLC). We have studied the relationship of the NER pathway gene single nucleotide polymorphisms and haplotypes with NSCLC risk. Using a custom-designed Illumina GoldenGate assay 384 single nucleotide polymorphism (SNP) panel, we have screened for polymorphisms in nucleotide excision repair genes, cell cycle control genes, GSTP1 and ABCB1 and a set of ancestry informative markers in 797 Caucasian incident cases and 992 controls frequency matched for age (range 50-79) and gender. All subjects were ever smokers with a minimum 10 packyear smoking history. Our SNP selection strategy incorporates six SNP classes, i.e. haplotype tagSNPs defined by predicted LD scores; functional SNPs characterized by amino acid substitutions, SNPs that alter protein stability; evolutionary conservation across species; entromics and published epidemiological data. For the estimation of individual SNP and haplotype-specific associations with risk, unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals in a dominant model adjusting for age, gender and packyear. A total of 26 unique SNPs in 14 genes were significantly associated with lung cancer risk. Haplotypes were reconstructed for each gene using HPlus and associations with risk were evaluated using the Cox proportional hazards model. The most frequent haplotype was used as the referent group for the estimation of hazard ratios (HR). Hazard ratios were calculated for common haplotypes i.e. those that were present at a frequency greater than 2% and were adjusted for age, gender and packyears. Among these 14 genes, 7 haplotypes were significant. These data suggest that NER pathway genotypes may serve to define an elevated risk subgroup. Supported in part by NIH 5P50 CA090440.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1868.
Abstract 1870: Genotype polymorphisms of DNA repair genes interact with estrogen exposure to breast cancer susceptibility
Authors: Cheng Chun-Wen , Yu Jyh-Cherng , Wang Hsiao-Wei , Hsiung Chia-Ni , Ding Shian-ling , Wu Pei-Ei , Wu Cheng-Wen , Shen Chen-Yang 
Published: February 2011

Abstract
Endogenous estrogen is suggested to initiate cell proliferation and cause oxidative DNA damage during breast tumorigenesis. Cells eliminate DNA damages by repair enzymes. Genotypic variants of DNA damage repair genes, participating base excision repair (BER) and nucleotide excision repair (NER) pathways, may act as modifiers that affect the association between estrogen exposure and breast cancer. In a hospital-based case-control study of female breast cancer, DNA samples from 401 cases and 533 healthy controls were enrolled among Chinese women in Taiwan. Genotyping polymorphisms of XRCC1 (Arg194Trp and Arg399Gln), OGG1 (Ser326Cys and Arg229Gln), ERCC2 Lys751Gln, ERCC4 Pro662Ser, and ERCC5 His1104Asp were determined and used to evaluate breast cancer susceptibility. Of these non-synonymous polymorphisms, ERCC5 1104Asp variant was significantly associated with breast cancer (OR=1.42; 95%CI=1.08-1.97), and this was more pronounced in women with prolonged estrogen exposure. A trend toward an increased risk of developing breast cancer was observed in women who carried greater numbers of combined high-risk genotypes of BER and NER genes (Ptrend = 0.038). The synergistic effect of multiple genes on risk elevation was significant in women having a longer period of estrogen exposure (&gt;26 years), a longer menarche-to-FFTP interval (&gt;11 years), greater age at the first full-term pregnancy (&gt;26 years), and higher body mass index (&gt;22) (all P&lt;0.05). In conclusion, this study demonstrates that genotype polymorphisms for the DNA damage repair confer higher risk in individual susceptibility to endogenous estrogen on female breast cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1870.
Abstract 1871: Honokiol, a natural plant product, inhibits ultraviolet radiation-induced skin tumorigenesis in mice through inhibition of inflammation and inflammatory mediators
Authors: Sharma Som D. , Vaid Mudit , Katiyar Santosh K. 
Published: February 2011

Abstract
Chronic exposure of solar ultraviolet (UV) radiation is the major etiologic agent for over one million new cases of non-melanoma skin cancers in the US each year. These cutaneous malignancies thus have a tremendous impact on public health and healthcare expenditures. The use of natural plant products has received considerable interest to protect skin from adverse biological effects of UV radiation since the protective clothing and use of sunscreens are not adequate for skin photoprotection. The photoprotective effect of honokiol, a plant product from Magnolia species, therefore assessed using SKH-1 hairless mouse model. To determine the skin cancer chemopreventive effect and associated mechanism of honokiol, a hydrophilic cream based topical formulation was developed. Different groups of mice (n=20) treated with or without honokiol were subjected to photocarcinogenesis protocol. Mice were irradiated to UVB (180 mJ/cm2) three times a week. At the termination of the experiment at 24th week, we found that topical application of honokiol (1mg & 3mg/mouse) inhibited UVB-induced skin tumor development in terms of tumor incidence (10-20%), tumor multiplicity (40-60%) and tumor size (50-75%). Since UV-induced inflammation plays a crucial role in the development of skin tumors, we examined the effect of honokiol on UVB-induced biomarkers of inflammation, such as the expression levels of cyclooxygenase-2 (COX-2), prostaglandins (PG), proliferating cell nuclear antigen (PCNA), infiltration of inflammatory leukocytes, development of edema and epidermal hyperplastic response using immunostaining, western blotting and RT-PCR. Our data revealed that topical application of honokiol before each exposure of UVB radiation resulted in a dose-dependent inhibition of UVB-induced expression of COX-2, PGE2, developments of edema and infiltration of leukocytes at the UVB-irradiated skin sites. Honokiol also inhibited the levels of PCNA (hyperplastic potential) in epidermal keratinocytes of UVB-exposed skin. The inhibitory effects of honokiol on inflammatory mediators were also found in skin tumor samples. The results of this study suggest that honokiol has the ability to inhibit UVB radiation-induced skin tumor development in mice and it is associated with the inhibition of UVB-induced inflammation and inflammatory mediators in mouse skin and skin tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1871.
Abstract 1872: Treatment of colon cancer with black raspberries reduces DNA Methyltransferase 1-associated gene methylation
Authors: Seguin Claire M. , Huang Yi-Wen , Huang Tim , Yang Guang-Yu , Arnold Mark , Martin Edward , Sardo Christine , Stoner Gary D. , Wang Li-Shu 
Published: February 2011

Abstract
Black raspberries (BRB) confer anti-cancer effects in gastrointestinal organs via a number of mechanisms. Recently, we have shown that BRB are capable of reversing aberrant promoter-region methylation and silencing of tumor suppressor genes in colorectal cancers in two separate clinical trials. Familial adenomatous polyposis (FAP) is characterized by inherited mutation of the APC gene resulting in uncontrolled growth of pre-cancerous polyps and 100% risk of colon cancer by age 40. In a 9-month clinical trial, a total of fourteen FAP patients were treated with two 700 mg BRB suppositories intra-rectally once a day. Seven of the 14 patients consumed a slurry containing 20g freeze-dried BRB powder three times a day while the other seven received a placebo slurry. In the second study, twenty-five colorectal cancer patients consumed a slurry containing 20g of BRB powder three times a day for a short period (2-4 weeks) before surgery. DNA from both studies was extracted from paraffin-embedded biopsies of normal and tumor tissue before and after treatment. Methylation status of the promoter regions of tumor suppressor genes were studied using MassARRAY/EpiTyper which quantifies the percent methylation of C-G units (each containing 1-3 CpGs) in target gene promoter regions The five genes studied, including p16, a cell cycle regulator, PAX6a, a development regulator, and three Wnt pathway inhibitors, SFRP2, SFRP5 and WIF1, were all positively regulated by BRB in colon tumors, however, only p16, SFRP2 and WIF1 were demethylated in rectal polyps from FAP patients. In both studies, 75% of both normal and tumor tissues showed decreased methylation of at least one tumor suppressor gene. Multiple-gene demethylation was different in the two studies. More than one gene was found to be reduced in methylation in a greater percentage of colon tumors (55%) than in normal tissues (26%) from colon cancer patients. In contrast, in the FAP study, more than one gene was demethylated in a greater percentage of normal tissue (23%) than in polyps (7%). However, the effect of BRB on the expression of DNA Methyltransferase 1 (DNMT1), a maintenance methylation enzyme, was similar in both colon cancers and polyps from FAP patients. In both FAP and colon cancers, demethylation of at least one gene coincided with DNMT1 decrease in a greater percentage of tumor tissues (63%, 79%) than in normal tissues (20%, 50%), respectively. This correlation suggests that in both polyps from FAP patients and in colon cancers, BRB action on methylation acts through DNMT1 reduction to a greater extent in tumor tissue than in normal tissue.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1872.
Abstract 1877: Involvement of mitochondrial respiratory complexes in capsaicin mediated ROS generation and apoptosis in pancreatic cancer cells
Authors: Pramanik Kartick C. , Boreddy Srinivas Reddy , Kandala Prabodh K. , Srivastava Sanjay K. 
Published: February 2011

Abstract
Capsaicin (N-vanillyl-8-methyl-nonenamide) is a homovanillic acid derivative and the spicy component of chili pepper. In our previous study, we have shown that capsaicin induced apoptosis in pancreatic cancer cells was associated with the generation of ROS and persistent disruption of mitochondrial membrane potential. However, the exact mechanism by which capsaicin causes ROS generation and cell death was not fully clear. We now evaluated the effect of capsaicin on mitochondrial respiratory complexes and ROS generation. The generation of ROS was about 3 fold and as early as 2h after capsaicin treatment in BxPC-3 cells and inhibited by rotenone and antimycin-A but not by 4-nitropropionic acid or sodium azide. Rotenone, 4-nitropropionic acid, antimycin A and sodium azide are the inhibitors of NADH-ubiquinone oxidoreductase (Complex I), succinate ubiquinone oxidoreductase (Complex II), ubiquinol cytochrome c reductase (Complex III) and cytochrome c oxidase (Complex IV) respectively. To further delineate the mechanism of ROS generation, effect of capsaicin was evaluated on the enzymatic activities of above-mentioned mitochondrial complexes in BxPC-3 cells. Our results show that capsaicin treatment significantly reduced complex I and complex III enzymatic activities suggesting the involvement of mitochondrial complex I and III in capsaicin mediated ROS generation. Capsaicin however did not affected complex II or complex IV activities. Our results further revealed that about 3 fold apoptosis induced by capsaicin in BxPC-3 cells was inhibited by rotenone and antimycin-A. Moreover, capsaicin mediated release of cytochrome c and AIF and cleavage of caspase-9 and caspase-3 were significantly inhibited by rotenone and antimycin-A. On the other hand, catalase or EUK (a mimetic of catalase) pretreatment block capsaicin-mediated ROS generation and apoptosis. Taken together, our results suggest the involvement of mitochondrial complex I and III in capsaicin mediated ROS generation and apoptosis. [Supported in part by RO1 grants CA 106953 and CA129038 (to SKS) awarded by National Cancer Institute].
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1877.
Abstract 1878: Dietary intake of pterostilbene, a constituent of blueberries, inhibits the β-catenin/p65 downstream signaling pathway and colon carcinogenesis in rats
Authors: Paul Shiby , DeCastro Andrew , Lee Hong Jin , Smolarek Amanda K. , So Jae Young , Simi Barbara , Wang Chung Xiou , Zhou Renping , Rimando Agnes M. , Suh Nanjoo 
Published: February 2011

Abstract
Stilbenes are phytochemicals present in grapes, berries, peanuts and red wine. A widely studied stilbene, resveratrol (trans-3,5,4’-trihydroxystilbene), has been shown to exert anti-oxidant, anti-inflammatory, chemopreventive, and anti-aging effects in a number of biological systems. Recently, pterostilbene (trans-3,5-dimethoxy-4’-hydroxystilbene), a structurally related stilbene found in blueberries, has been shown to exhibit significant effects against cell proliferation, inflammation, invasion and metastasis in various models. We reported earlier that pterostilbene was effective in reducing the incidence and multiplicity of aberrant crypt foci (ACF) formation in the colon of rats injected with the carcinogen, azoxymethane (AOM). Our present study was to identify the chemopreventive potential of pterostilbene with colonic tumor formation as an end point, and further to evaluate the mechanistic action of pterostilbene during colon carcinogenesis. F344 rats were given two AOM injections subcutaneously when they were 7 and 8 weeks old, and continuously fed the control or 40 ppm pterostilbene diet for 45 weeks. Overall analyses indicated that pterostilbene reduced colon tumor multiplicity of non-invasive adenocarcinomas, lowered a cell proliferation marker, proliferating cell nuclear antigen (PCNA), and down-regulated the expression of β-catenin and cyclin D1. Pterostilbene decreased mucosal levels of the pro-inflammatory cytokines TNF-α, IL-1β and IL-4. Colon tumors from pterostilbene fed animals showed reduced expression of the inflammatory enzymes iNOS and COX-2, as well as nuclear staining for phospho-p65, a key molecule in the NF-κB pathway. In cell culture studies using HT-29 cells, pterostilbene reduced the protein levels of β-catenin, cyclin D1 and c-MYC, altered the cellular localization of β-catenin, and inhibited the phosphorylation of p65. Our data with pterostilbene in suppressing colon tumorigenesis, cell proliferation as well as key inflammatory markers in vivo and in vitro suggest the potential use of pterostilbene for colon cancer prevention.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1878.