bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1867: DNA repair gene polymorphisms and tobacco smoking and the risk of colorectal adenoma
Authors: Gao Ying , Hayes Richard , Huang Wen-Yi , Caporaso Neil , Burdett Laurie , Yeager Meredith , Chanock Stephen , Berndt Sonja 
Published: February 2011

Abstract
Genetic variants of DNA repair genes may contribute to their altered capacity to repair endogenous and exogenous DNA damage. Although rare mutations in mismatch repair genes are known to lead to hereditary non-polyposis colorectal cancer, to date studies investigating common single nucleotide polymorphisms (SNPs) in DNA repair genes and colorectal cancer or adenoma risk have only examined a small number of variants in a limited number of genes. We conducted a comprehensive analysis of DNA repair gene polymorphisms and colorectal adenoma risk using a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Effect modification by smoking, which is a known risk factor for adenoma, was also explored. A total of 1,338 advanced, left-sided colorectal adenoma cases and 1,503 frequency-matched controls without evidence of a left-sided polyp on sigmoidoscopy were included in the current study. Using DNA extracted from blood specimens, 3,401 tag SNPs in 153 DNA repair genes were genotyped. Logistic regression was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for the associations between genetic variants and adenoma risk assuming a log-additive model for the genotype. Among Caucasians, 30 SNPs were associated with adenoma risk at p&lt;0.01. The most significant finding was for a non-synonymous SNP in EXO1 (rs9350), which was predicted to be deleterious using the SIFT and PolyPhen databases. The C allele at EXO1 rs9350 was associated with a 1.30-fold increased risk (95% CI=1.11-1.51, P=0.001). The association appeared to be limited to smokers (OR=1.54, 95% CI=1.26-1.89) with the strongest risk for current smokers (OR=2.15, 95% CI=1.27-3.65), and an intermediate risk for former smokers (OR=1.45, 95% CI=1.14-1.82), compared to never smokers (OR=0.98, 95% CI=0.76-1.25) that exhibited no increased risk (Pinteraction=0.002). Among the top findings, a SNP (rs17503908) in ATM with an overall OR of 0.75 (95% CI=0.63-0.91) was also modified by smoking (Pinteraction=0.006); the T allele at ATM rs17503908 was protective among never smokers (OR=0.55, 95% CI=0.40-0.76) but not among smokers (OR=0.89, 95% CI=0.70-1.13). The study suggests that polymorphisms in EXO1 and ATM may be associated with risk of advanced colorectal adenoma with the effects modified by tobacco smoking status. Our findings warrant extended investigations of these associations for colorectal cancer risk.
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 1867.
Abstract 1869: Genetic variants of DNA repair genes and lung cancer among nonsmokers: A pooled analysis in the International Lung Cancer Consortium
Authors: Lee Yuan-Chin Amy , Hung Rayjean , Boffetta Paolo , Brennan Paul , Christiani David , Kiyohara Chikako , Lan Qing , Seow Adeline , Paolo Vineis , Zhang Zuo-Feng 
Published: February 2011

Abstract
Background
Lung cancer among nonsmokers has been considered as a different disease from that among smokers. Involuntary smoking has been suggested to be a risk factor for lung cancer among nonsmokers with a modest effect. Few studies have examined the role of single nucleotide polymorphisms (SNPs) of the DNA repair genes and their potential interactions with involuntary smoking on the development of lung cancer among nonsmokers.
Methods
We evaluated the associations between SNPs of the DNA repair genes and lung cancer based on a pooled data of the International Lung Cancer Consortium. The individual-level epidemiological data and genotyping data on eight SNPs from six participating studies were pooled, including 845 nonsmoker cases and 4,262 nonsmoker controls. Logistic regression models with adjustment by age, sex, ethnicity, study, and ever involuntary smoking status were used to obtain odds ratios (OR) and 95% confidence intervals (CI).
Results
Among nonsmokers, the associations with the polymorphisms in OGG1 S326C and XPD D312N were observed among those with involuntary smoking (for OGG1 S326C: OR=1.61, 95% CI 1.18-2.20 for CG, OR=1.74, 0.99-3.06 for GG, compared to CC; for XPD D312N: OR=1.06, 0.76-1.47 for AG, OR=1.60, 1.06-2.42 for AA, compared to GG), but not for those without involuntary smoking (for OGG1 S326C: OR=0.78, 0.39-1.54 for CG, OR=0.88, 0.25-3.06 for GG, compared to CC; for XPD D312N: OR=1.13, 0.57-2.21 for AG, OR=0.81, 0.27-2.43 for AA, compared to GG). The association with XRCC3 T241M variant was detected for adenocarcinoma and non-small cell lung cancer among those without exposure to involuntary smoking (adenocarcinoma: OR=3.52, 1.21-10.20 for AA, OR=0.94, 0.38-2.38 for GA, compared to GG; and non-small cell lung cancer: OR=2.75, 1.05-7.21 for AA, OR=1.10, 0.51-2.38 for GA, compared to GG, respectively). Due to limited power, no apparent interaction between DNA repair SNPs and involuntary smoking was detected.
Conclusion
This is the first large-scale collaborative study on the relationship between DNA repair genetic variants and lung cancer among nonsmokers, accounting for involuntary smoking. Our results show that SNPs of the DNA repair genes may play an important role for lung cancer among nonsmokers, and the associations may vary by involuntary smoking status and histological subtype.
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 1869.
Abstract 187: Epigenetic memory during breast cancer progression is sustained by Smad signaling pathway
Authors: Thiagalingam Sam , Lambert Arthur W. , Ozturk Sait , Abdolmaleky Hamid M. , Papageorgis Panagiotis 
Published: February 2011

Abstract
The molecular basis for the “epigenetic memory” that ensures maintenance of unique patterns of regulatory DNA methylation of selected genes responsible for cancer progression has remained elusive. Using a breast cancer progression model system, we found that hyperactive TGFβ-TGFβR-Smad2 signaling axis is involved in the maintenance of DNA hypermethylation mediated silencing of critical target genes to facilitate breast cancer progression. Disruption of TGFβ signaling caused a corresponding decrease in DNMT1 binding activity accompanied with increased expression of the target genes and acquisition of tumorigenic properties. These observations are consistent with passive demethylation of the newly synthesized DNA due to absence of sustained TGFβ-Smad signaling downstream events. In summary, we provide conclusive evidence that the reversal of the DNA hypermethylation status of gene promoters occurs as a result of TGFβ/Smad signaling pathway perturbation. By extension, we predict that inhibition of TGFβ-TGFβR-Smad2 signaling axis is an effective therapeutic strategy for 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 187.
Abstract 1873: Delayed progression to hormone-independent prostate cancer through modulation of mTOR by omega-3 fatty acids
Authors: Apte Shruti , Friedrichs William , Hursting Stephen , Cavazos David , Nogueira Leticia , Perkins Susan , deGraffenried Linda A. 
Published: February 2011

Abstract
Prostate cancer is the second leading cause of cancer related deaths in men. The primary obstacle in effective treatment of prostate cancer is the progression of the disease from a hormone-dependent to a hormone-independent state. Previous studies indicate that activation of the mammalian Target of Rapamycin (mTOR) signaling pathway may be involved in progression of prostate cancer. Several studies have demonstrated a significant role for mTOR in promoting androgen independence. Recent data indicate that the combination of androgen deprivation with mTOR inhibition provides an additive anti-tumor effect in vivo. mTOR is directly involved in regulating cell survival, growth, proliferation, and differentiation. Many dietary and lifestyle interventions that reduce cancer risk and progression mediate their effects through regulation of mTOR signaling. Epidemiological studies indicate an inverse relation between dietary intake of omega-3 fatty acids and prostate cancer risk. Omega-3 fatty acids have been shown to inhibit prostate cell growth both in vitro and in vivo. Preliminary data from our laboratory demonstrated that treatment of LNCaP prostate cancer cells with omega-3 fatty acids, specifically docosahexaonoic acid (DHA), delayed development of androgen independence in vitro. This delay correlated with a decrease in protein expression of downstream targets of mTOR regulation, including phosphorylated S6, Bcl-2, and cyclin D. We hypothesize that omega-3 fatty acids may prevent prostate cancer progression to a hormone independent phenotype in part through modulation of mTOR. To test this hypothesis, we transiently transfected LNCaP cells to express a constitutively active mTOR. Our results showed that expression of the constitutively active mTOR correlated with a reduction in response to hormone deprivation, resembling that observed in our previously generated hormone refractory LNCaP cell line. When exposed to hormone-ablation conditions, the proliferation rates observed compared to the that of the vector-only control cells were 64% higher in the constitutively active mTOR cells, and 55% higher in the hormone-refractory cell. Ongoing studies are using a stable transfectant of constitutively active mTOR to determine if modulation of mTOR signaling is one mechanism by which the omega-3 fatty acids delay the progression to hormone-independence. These studies suggest that inhibition of mTOR is critical for cellular response to hormone ablation, and that mTOR may be a viable target for delaying progression to a hormone refractory 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 1873.
Abstract 1874: Impact of vitamin D and calcium on PGE2 metabolism in colorectal cancer
Authors: Nittke Thomas , Horváth Henrik C. , Bises Giovanna , Thalhammer Theresia , Kállay Enikoe 
Published: February 2011

Abstract
Aberrant expression of cyclooxygenase 2 (COX2), the enzyme responsible for synthesizing prostaglandin E2 (PGE2), is one of the early events in colorectal cancer (CRC) development. Repression of COX2 results in the inhibition of prostaglandin synthesis which can delay colon tumorigenesis. It has been shown previously that in cancer cells 1α,25-dihydroxyvitamin D3 (1,25D3) downregulates the expression of COX2 and increasing that of the PGE2 catabolizing enzyme 15-prostaglandin-dehydrogenase (15-PGDH). Due to the differentiation-promoting, pro-apoptotic and anti-proliferative effects calcium and 1,25D3 have become factors of great interest for the chemoprevention of CRC.
In order to study the effect of calcium on the PGE2 pathway, we treated the colon cancer cell line Caco-2 with low calcium (0.025 mM) for 48 hours. This led to an increase in COX2 expression while decreasing that of 15-PGDH. Similar effect was seen in vivo: in mice low calcium (0.04%) diet elevated COX2 expression in the colon when compared with the control diet (0.5%). Interestingly, expression of the vitamin D catabolizing enzyme, CYP24A1 was also augmented, in parallel with an increase of crypt cell proliferation. However, expression of the 1,25D3 synthesizing CYP27B1 was not affected. These results suggested that low dietary calcium might reduce 1,25D3 levels in the colon, thereby lowering the impact of 1,25D3 on the COX2-PGE2 pathway. To investigate whether this expression profile is prevalent also in the human colon, we screened over 200 tissue specimens from CRC patients by QRT-PCR. In colon tumors, the mRNA ratio of 15-PGDH and COX2 was significantly downregulated (p&lt;0.0001). This unbalance implicates an elevated PGE2 production. In these tumor samples the CYP24A1/CYP27B1 mRNA ratio was also significantly increased (p&lt;0.05) as compared with the adjacent mucosa. Additionally, CYP24A1 staining confirmed elevated levels of the enzyme in adenocarcinomas.
Thus, in these colorectal tumors local 1,25D3 levels were most probably insufficient to inhibit PGE2 accumulation due to high CYP24A1 expression. Low dietary calcium is a promoter of CYP24A1 expression. Our data represent one of the possible molecular mechanisms for the synergistic action of calcium and vitamin D levels in CRC chemoprevention.
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 1874.
Abstract 1875: Dietary grape seed proanthocyanidins induce rapid repair of DNA damage via nucleotide excision repair genes in preventing UV-induced immunosuppression
Authors: Katiyar Santosh K. , van Steeg Harry , Sharma Som D. 
Published: February 2011

Abstract
Ultraviolet (UV) radiation-induced immunosuppression has been implicated in the development of skin cancers, including melanoma and non-melanoma. UV-induced DNA damage, predominantly the formation of cyclobutane pyrimidine dimers (CPDs), has been recognized as an important molecular trigger for the initiation of UVB-induced immunosuppression and skin carcinogenesis. We have shown earlier that administration of dietary grape (Vitis vinifera) seed proanthocyanidins (GSPs) supplemented with AIN76A control diet inhibit photocarcinogenesis in mice; however, the molecular mechanism of chemopreventive effects of GSPs are not clearly understood. To investigate the possible mechanism of action of GSPs we used genetically modified human cells and animal model. We observed that administration of dietary GSPs (0.2 and 0.5%, w/w) with supplementation of AIN76A control diet inhibited (52-65%, P&lt;0.001) UV-induced suppression of contact hypersensitivity response to a contact sensitizer, 2,4-dinitrofluorobenzene, in a contact hypersensitivity mouse (C3H/HeN) model. Dietary GSPs repaired UV-induced DNA damage (CPD-positive cells) faster in the skin of mice as demonstrated by reduced number of CPD-positive cells (59%, p&lt;0.001), and reduced the migration of CPD-positive cells from the skin to draining lymph nodes compared to non-GSPs-fed control mice, which was associated with the elevated levels of nucleotide excision repair (NER) genes. GSPs did not prevent UV-induced immunosuppression in NER-deficient mice but significantly prevented in NER-proficient mice (p&lt;0.001) concomitantly repaired UV-induced DNA damage in NER-proficient mice (p&lt;0.01) but did not repair in NER-deficient mice as indicated by immunohistochemical analysis of CPD-positive cells. Further, southwestern dot-blot analysis revealed that GSPs repaired UV-induced CPDs in xeroderma pigmentosum complementation group A (XPA)-proficient cells obtained from healthy person but did not repair in XPA-deficient cells obtained from the patients suffering from xeroderma pigmentosum disease, indicating that NER mechanism is involved in DNA repair. Together, these data identify a novel mechanism by which dietary GSPs prevent UV-induced immunosuppression which is mediated through rapid repair of damaged DNA, and that these effects lead to the prevention of UV radiation-induced skin tumors in mice.
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 1875.
Abstract 1885: Dietary stearate reduces abdominal fat, serum leptin and glucose and increases MCP-1
Authors: Shen Ming-Che T. , Evans Lynda M. , Toline Eric C. , Desmond Renee A. , Gene Siegal P. , Hardy Robert W. 
Published: February 2011

Abstract
Stearate is a dietary, long-chain saturated fatty acid (C18:0) that has been shown to decrease breast cancer cell proliferation, migration, and invasion in vitro and reduce tumor growth and metastasis in vivo. Obesity, or excess adipose tissue, is a risk factor for breast cancer. Our overall hypothesis is that dietary stearate inhibits breast cancer by decreasing body fat. Our goal was to determine whether there was an association between dietary stearate and adipose tissue. Four groups of 10 athymic nude mice each were each fed one of four different diets for 18 weeks (6% corn oil - low fat diet, 17% stearate diet, 17% corn oil diet, or 17% safflower oil diet). Body composition was assessed by nuclear magnetic resonance (NMR) and dual energy X-ray absorptionmetry (DXA). Serum concentrations of glucose, insulin, leptin, adiponectin, interleukin-6, and monocyte chemoattractant protein-1 (MCP-1) were also determined. In a repeated measures model assessing the relationship between groups, for fat and lean mass over time the following differences were found: the stearate group had significantly reduced body fat compared to the low fat and the corn oil groups (p&lt;0.001); mice on the high fat diets (stearate, corn oil, and safflower oil) had a significantly increased lean body mass compared to the low fat group (p=0.009, 0.012, and 0.022 respectively). Postmortem measurement revealed no significant changes in organ weight (brain, heart/lungs, liver, and kidney) among the four diet groups. However dietary stearate had less abdominal fat than the other diets although only the low fat - stearate difference was significant (low fat-stearate *p= 0.0043. corn oil-stearate p= 0.0565, and safflower-stearate p= 0.0636). Serum glucose and leptin concentrations were significantly reduced in the stearate diet mice (glucose, p&lt;0.039, stearate vs all other diets, leptin, p&lt;0.015, stearate vs low fat and corn oil diets). Serum MCP-1 was increased in stearate diet mice compared to either the low fat or safflower oil mice (p&lt;0.019). Significant differences were not observed with the other analytes. Studies have suggested that glucose and leptin have cancer promoting effects, while MCP-1 may promote or inhibit breast cancer. Overall these data support our hypothesis that dietary stearate decreases body fat and that this decrease in body fat may be related to stearate inhibition of 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 1885.
Abstract 189: 5-azacytidine radiosensitizes androgen-independent prostate cancer cells by impairing DNA double-strand break repair
Authors: Weterings Eric , Dino Pamela M. , Feng Yi , Sharma Sunil , Pizzorno Giuseppe 
Published: February 2011

Abstract
5-azacytidine is a cytidine analogue with cytotoxic and cytostatic activity, currently utilized for the treatment of myelodysplastic syndromes. The cytostatic activities of low-dose 5-azacytidine are attributed to its incorporation into the DNA and RNA of mammalian cells, which influences epigenetic regulation, cell cycle progression, and protein expression. We observed that treatment with 5-azacytidine significantly radio-sensitizes androgen-independent prostate cancer cells, synergistically enhancing the overall efficiency of radiation treatment both in vivo and in vitro. Furthermore, we found that exposure of androgen-independent prostate cancer cells to 5-azacytidine impairs or delays the repair of radiation induced DNA double-strand breaks through the non-homologous end-joining pathway. This observation explains the radio-sensitizing potential of 5-azacytidine and constitutes the first conclusive evidence for a DNA repair defect introduced by this compound. In addition, we found that this DNA repair defect was not introduced by the 2’-deoxy derivative of 5-azacytidine. From this finding we infer that the inhibitory effects of 5-azacytidine on DNA repair are primarily mediated by its incorporation into the RNA. We suggest that a combined treatment with 5-azacytidine and ionizing radiation would be a good candidate for clinical trials, not necessarily limited to prostate cancers.
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 189.
Abstract 1895: Phytochemicals inhibit proliferation and promote death through NADPH oxidase and G6PD
Authors: Edderkaoui Mouad , Hui Hongxiang , Li Gang , Xu Jun , Lee Wai-Nang , Go Vay Liang W. , Pandol Stephen J. 
Published: February 2011

Abstract
Background & Aims: Pancreatic cancer is a very aggressive disease that is resistant to therapy. Evidence from population studies indicates a protective effect of fruits and vegetables in the diet on cancer including pancreatic cancer. In vitro and in vivo studies, including our own, suggest that several phytochemicals, such as ellagic acid and lycopene may be involved in this beneficial effect. In this study we investigated the effect of these phytochemicals, alone and in combination, on apoptosis and proliferation of pancreatic cancer cells in vitro, and we analyzed their mechanism of action. Methods: We measured the effect of ellagic acid and lycopene on DNA fragmentation using Cell Death Detection ELISA and on proliferation using 3H-thymidine incorporation into DNA in pancreatic cancer cell line MIA PaCa-2. Molecular signaling mechanisms were evaluated with Western. NF-kB activity was measured using electromobility shift assay. Metabolic phenotype of the cells was analyzed using mass spectrometry and the glucose molecule labeled with stable isotope D-glucose (1,2-13C2). Results: Both lycopene and ellagic acid at doses from 0.1 to 30 μM induced increases in DNA fragmentation and inhibited proliferation in pancreatic cancer cells. Combinations of ellagic acid with lycopene at low doses (1 µM) induced a synergistic effect on DNA fragmentation and proliferation. Ellagic acid induced apoptosis by decreasing NF-kB activity in pancreatic cancer cells. Lycopene decreased NADPH oxidase activity. Combined compounds had a synergistic effect on the inhibition of glucose-6-phosphate dehydrogenase (G6PD) activity as measured by mass spectrometry leading to a synergistic inhibition of DNA synthesis. Conclusions: Combination of ellagic acid and lycopene induced a synergistic effect on apoptosis and proliferation in pancreatic cancer cells. The synergistic effect is due to different mechanisms of action of these phytochemicals leading to the inhibition of G6PD activity, a key step in DNA synthesis. Our study suggests a potentially beneficial role for combinations of ellagic acid and lycopene in prevention and treatment strategies of pancreatic 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 1895.