bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4483: Early life exposures and promoter methylation in breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study
Authors: Tao Menghua , Marian Catalin , Shields Peter , Postischman Nancy , Nie Jing , Ambrosone Christine , Edge Stephen , Krishnan Shiva , Vito Dominica , Trevisan Maurizio , Freudenheim Jo 
Published: August 2012

Abstract
Abstract Background: Exposures in the peri- and post-natal period (in utero, infancy, childhood, and adolescence) are associated with breast cancer risk, particularly premenopausal breast cancer. Epigenetic alterations in response to these exposures may play a critical role in early life, and then influence breast cancer risk in adult life. Using archived tumor blocks from incident breast cancer cases in a population-based the Western New York Exposures and Breast Cancer Study (WEB Study), we examined the association between early life exposures and promoter methylation of three tumor suppressor genes (p16, E-cadherin, and RARα2). Method: DNA samples isolated from 803 paraffin embedded tumor tissue were analyzed for hypermethylation status using real time methylation-specific polymerase chain reaction (MSP). Unconditional logistic regression was used for case-case comparisons of those with and without promoter methylation to estimate odds ratios (ORs) and 95% confidence intervals (95% CI) for associations of early life exposure with the likelihood of promoter methylation. Results: Among premenopausal breast tumors, compared to those with normal birth weight (2.6-3.9 kg), there was increased likelihood of E - cadherin gene hypermethylation in tumors from lower birth weight (≥ 2.5 kg) (OR = 2.79, 95% CI, 1.15-6.82). Height was positively associated with the likelihood of hypermethylation of RAR-α2 gene in premenopausal tumors (OR =3.34, 95% CI, 1.19-9.39). For p16, there was significant differences in the likelihood of promoter methylation of p16 in relation to not having been breast fed in premenopausal tumors (OR = 2.75, 95% CI, 1.14-6.62). Among postmenopausal breast cancers, birth order was associated with increased likelihood of p16 promoter methylation. The likelihood of promoter methylation of the individual genes did not differ by maternal age at delivery, maternal height, age at menarche, age of first live birth, and weight at age 20 in either strata of menopause Conclusion: We found lower birth weight, not having been breast fed, and higher height were associated with promoter methylation of E - cadherin, p16 and RAR-α2 premenopausal breast tumors, respectively, suggesting that early life exposures may affect breast carcinogenesis among younger women through aberrant DNA methylation. Further studies of more genes and larger sample size may provide additional insight.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4483. doi:1538-7445.AM2012-4483
Abstract 4573: Enriched driver genes based on histology and smoking status in Asian patients with non-small cell lung cancer
Authors: An She-Juan , Chen Zhi-Hong , Su Jian , Zhang Xu-Chao , Zhong Wen-Zhao , Yang Jin-Ji , Zhou Qing , Yang Xue-Ning , Huang Ling , Guan Ji-Lin , Nie Qiang , Yan Hong-Hong , Mok Tony S , Wu Yi-Long 
Published: August 2012

Abstract
Purpose Patient selection is needed as target therapy had efficacy only to the subsets of patients with specific genetic alterations. We aimed to clarify the subgroups for enriching the patients with candidate driver genes. Patients and Methods The patients who performed clinical genetic tests at Guangdong General Hospital with primary lung cancer were enrolled. Driver genes were detected by sequencing, high-resolution melting analysis, qPCR, or multiple PCR and RACE methods. Results 524 patients were enrolled in this study and the differences of driver genes among subgroups on histology and smoking status were analyzed. In adenocarcinoma with non-smoker subgroup, EGFR mutation was the most frequently altered gene with 49·8%, followed by EML4-ALK (9·3%), PTEN (9·1%), PIK3CA (5·2%), c-Met (4·8%), KRAS (4·5%), and BRAF (1·9%). The three most frequently altered genes in adenocarcinoma with smoker subgroup were EGFR (22·0%), KRAS (12·0), and EML4-ALK (4·5%). We only found EGFR (8·0 %), c-Met (2·8%), and PIK3CA (2·6%) alterations in squamous cell carcinoma (SCC) with non-smoker subgroup. PTEN (16·1%), PIK3CA (7·2%), and EML4-ALK (6·5%) were the three most frequently enriched genes in SCC with smoker subgroup. DDR2 and FGFR2 only presented in SCC with smoker subgroup (4·4% and 2·2%, respectively). Among these four subgroups, the differences of EGFR, KRAS, and PTEN mutations were statistically significant. Conclusion The distinct features of driver genes in different subgroups based on histology and smoking status were very helpful to enrich the patients for guiding the future clinical trials target these genes. The study also suggested that we can consider the patients with infrequently alteration rates of driver genes as an orphan disease and should provide special management model with special molecular targeted therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4573. doi:1538-7445.AM2012-4573
Abstract 4588: Frequency and clinical characteristics of c-MET mutation in malignant melanoma
Authors: Kim Sharon , Gonzalez Nydia , Luthra Raja , Aldape Kenneth , Zuo Zhuang , Liu Ping , Barron David , Kim Kevin B. 
Published: August 2012

Abstract
Purpose: C-MET is over-expressed in metastatic melanoma and have copy number gains at chromosome 7 in late stages of melanoma progression. However, the presence of C-MET mutation is not well known in melanoma. We analyzed tumor samples of patients with malignant melanoma to identify the frequency and the clinicopathology of C-MET mutations. Methods: We identified 103 patients with metastatic mutation who underwent testing for c-MET mutation and reviewed the clinical data of these patients. The sequencing analyses were performed by Sequenom Assay, and the mutations were confirmed with Sanger Sequencing analysis. Clinical characteristics were correlated with C-MET mutation status, and a survival analysis was performed to identify significant associations. Results Among the 103 patients, eleven (11%) patients had melanoma harboring a C-MET mutation. Five (4.5%) patients had N375S mutation; two (1.8%) patients had R988C mutation; two (1.8%) had T1010I; one (1%) patient had H1112R and another patient had N375/T1010 mutation. A median age at diagnosis, sex, race and the status of ulceration at the primary site and the stages at diagnosis were similar between patients with a C-MET mutation and those with wild type. There were no significant differences in the overall survival from the time of stage IV diagnosis between the two groups, but there was a trend of a shorter median duration from the time of the initial diagnosis to distant metastases among patients with a C-MET mutation. (23.6 months vs. 15.9 months, p=0.09). Conclusions We found C-MET mutations in 11% of patients with malignant melanoma. There was a tendency to have distant metastasis at an earlier time in patients with a C-MET mutation. This is the first report describing the frequency and clinical characteristics of C-MET mutations in patients with malignant melanoma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4588. doi:1538-7445.AM2012-4588
Abstract 4590: Genome-wide identification of possible methylation markers chemosensitive to targeted regimens in colorectal cancers
Authors: Kim Jin Cheon , Lee Han Cheol , Cho Dong Hyung , Choi Eung Young , Cho Yoon Kyung , Ha Ye Jin , Roh Seon Ae , Kim Seon Young , Kim Yong Sung 
Published: August 2012

Abstract
Purpose Few efficient methylation markers of chemosensitivity have been discovered. The genome-wide analysis of methylation markers is needed to identify chemosensitive candidates to targeted therapy. Methods This study describes a two-step process to select chemosensitive candidates of methylation genes. A genome-wide screening of methylation genes was performed using a beadarray and an in vitro chemosensitivity assay of 119 colorectal cancers (CRCs). Results Ten candidate genes identified during the initial screening were verified by biological utility assessment using cell viability assays of transfected CRC cells. Five methylation genes related to sensitivity to bevacizumab regimens (RASSF1, MMP25, KCNQ1, ESR1, and GALR2) or cetuximab regimens (SCL18A2, GPX7, NID2, IGFBP3, and ALX4) were chosen during the first step. A viability assay revealed that GALR2-overexpressing HCT116 cells were significantly more chemosensitive to bevacizumab regimens than control cells (P = 0.022 and 0.019 for bevacizumab with FOLFIRI and FOLFOX, respectively), concurrently verified on a caspase-3 activity assay. GPX7- or ALX4-overexpressed RKO cells were significantly less viable to cetuximab regimens compared to control cells (GPX7: P = 0.027 each for cetuximab with FOLFIRI and FOLFOX; ALX4: P = 0.049 and 0.003 for cetuximab with FOLFIRI and FOLFOX, respectively), but caspase-3 activity was not prominent in GPX7-overexpressed RKO cells. Conclusions Two novel genes, GALR2 and ALX4, have been identified as chemosensitive methylation candidates to bevacizumab and cetuximab regimens, respectively. As our study did not include a clinical association study, the two candidates should be validated in large clinical cohorts, hopefully predicting responsive patients to targeted regimens.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4590. doi:1538-7445.AM2012-4590
Abstract 4592: Sox8 as a molecular marker of oligodendroglial tumors
Authors: Iuchi Toshihiko , Yokoi Sana , Ohira Miki , Kageyama Hajime , Itami Makiko , Hasegawa Yuzo , Kawasaki Koichiro , Sakaida Tsukasa , Nakagawara Akira 
Published: August 2012

Abstract
Backgournd: The precise diagnosis of oligodendroglial tumors from astrocytic tumors is required because the sensitivity to treatments and outcome of patients are different between these two types of gliomas. However, morphological diagnosis of these tumors is not always easy and sometimes different among pathologists. The aim of this study is to clarify the clinical significance of Sox8 as a molecular marker of oligodendroglial tumors. Materials and Methods: The expression level of Sox8 was evaluated by real-time PCR in 74 gliomas (OII: 7, OIII: 15, AIII: 5, GBM: 47), and was compared with morphological diagnosis and other molecular markers as follows: 1p/19q co-deletion evaluated by array CGH, methylation of MGMT gene promoter by methylation-specific PCR, and IDH-1 mutation by immunohistochemistry. For the evaluation of diagnostic value of Sox8-expression, tumors were divided into two groups owing to the expression level of Sox8 (threshold: 2000), and the clinical outcome of patients were compared between these two groups. Furthermore, these diagnostic significances of Sox8 were compared with those of Olig-1 and Olig-2. Results: The expression level of Sox8 was significantly higher in oligodendroglial tumors (p&lt;0.0001), 1p/19q co-deleted tumors (p&lt;0.0001) and tumors with mutant IDH-1 protein (p&lt;0.0001). The frequency of MGMT methylation was higher in tumors with high Sox8-expression, although statistical significance was not proven. In oligodendroglial tumors, the survival of patients with tumors exhibiting high Sox8-expression was significantly better than those with low SOX8-expression (hazard ratio: 6.2, p=0.031). High-expression of Olig-2 (hazard ratio: 4.5, p=0.026) and 1p/19q co-deletion (hazard ratio: 5.1, p=0.020) were also correlated with favorable outcome of patients, but no significant correlation between the expression of Olig-1 and patients’ outcome was observed. Conclusions: Sox8 was highly expressed in 1p/19q co-deleted oligodendroglial tumors. In oligodendroglial tumors, the expression of Sox8 was the significant prognostic factor of patients’ survival.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4592. doi:1538-7445.AM2012-4592
Abstract 4599: Comprehensive molecular oncogenomic profiling & miRNA analysis of prostate cancer
Authors: Sethi Seema , Kong Dejuan , Sakr Wael , Land Susan , Dyson Greg , Sarkar Fazlul 
Published: August 2012

Abstract
Background: Comprehensive molecular oncogenomic and microRNA (miRNA) profiling of tumors can provide tumor specific oncogenomic and miRNA signatures which can be useful to improve diagnostic accuracy, refine prognostic and predictive capabilities, and may serve as therapeutic targets. In prostate cancer (PCa) such a comprehensive analysis has not been reported. Design: DNA and RNA obtained from scant amounts of fresh frozen PCa tumor tissue samples (n=36) were profiled by (1) Mutation analysis: Sequenom Massarray & OncoCarta VI panel that profiles 238 common cancer mutations in 19 oncogenes (known predictors of response or resistance to targeted therapies);(2) Whole-genome gene expression Microarrays: Illumina Chip;(3) Single Nucleotide Polymorphisms (SNP) with genome-wide coverage:Illumina Omni microarrays. (4)miRNA analysis was done on RNA from FFPE PCa tumor tissues (n=126) using RT-PCR. Data was statistically analyzed & correlated with clinical & pathologic variables. Results: Massarray analysis identified a MET oncogene mutation, variant T992I, in a 49 year old patient with Gleason score 7 (4+3) tumor. Of the 47,224 genes analyzed by gene expression microarrays, 74 genes were significant predictors of high tumor grade by ordinal regression analysis (p&lt;0.0001). TGIF1 was the most significant gene. Of the 731,442 SNP's analyzed, 638 significantly predicted high tumor grade by logistic regression analysis (p&lt;0.0001). There was significant interaction between gene and SNPs in 531 SNP/gene pairs (p&lt;0.05). Ingenuity Pathway analysis revealed the significant predictor genes (p&lt;0.05) were involved in biological pathways for Gene Expression, Cell Cycle, Cancer,” “Inflammatory Response, Cell Death, Infection Mechanism & Cellular Assembly, Organization, Gene Expression, Cancer. P53 gene was found to be at the center hub of significant predicting pathways. Loss of miR-34a expression was found in PCa tissues consistent with the central role of p53. Conclusions: Using high throughput genomic profiling & miRNA analysis of small amounts of fresh-frozen and FFPE PCa tumor samples, we identified clinically relevant hot spot mutation in MET oncogene and several significant genes & SNPs to predict tumor grade. P53 gene is at the center hub of all significant pathways. Loss of miR-34a was consistent with p53 function in PCa. MET oncogene mutation is a novel finding, not previously reported in PCa against which small molecule inhibitors are under development. These molecular signatures may have a significant clinical impact on improving diagnostic and predictive capabilities & in designing targeted therapies to achieve the goal of personalized medicine.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4599. doi:1538-7445.AM2012-4599
Abstract 4601: The role of nicotine-induced oxidative stress in oral cancer cells
Authors: Tang Xiaofei , Zhang Yanhua , Zhang Min 
Published: August 2012

Abstract
Objective To investigate the role of nicotine-induced oxidative stress in SCC15 oral cancer cells. Methods The growth, apoptosis, ROS level, Prx1 expression and NF-αb DNA binding activity were detected in SCC15 oral cancer cell using MTT assay, RT-PCR, Western blotting, flow cytometry, ELISA. Results The ROS level was elevated in SCC15 cells treated with nicotine for 24h at different concentrations (0.1μM, 1μM, 10μM). Cell growth was induced by nicotine for 24h, 48h at different concentrations. Few SCC15 cells were induced apoptotic cell death treated with nicotine for 24h, there was no obvious changes in cell apoptosis for 48h, 72h, compared with control. Prx1 mRNA and protein expression were up-regulation treated with nicotine. NF-αb DNA binding activity was increased treated with nicotine for 24h, 48h, 72h. Conclusion Nicotine induced oxidative stress and cell proliferation, which maybe regulated by Prx1/NF-αb axis in oral cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4601. doi:1538-7445.AM2012-4601
Abstract 4605: Neurotrophin system expression in human lung cancer stem cells
Authors: Mancini Rita 
Published: August 2012

Abstract
The availability of in vitro and in vivo systems which reproduce the natural heterogeneity of spontaneous human cancers is of critical importance to assess the potential of new combination treatments and to establish better correlations between molecular signatures and response to therapy. We have focused our attention on the subset of non small cell lung cancers (NSCLC) classified as Lung Adenocarcinomas (AdenoCa) which account for approximately 40% of lung cancer cases and have recently reported that Malignant Pleural Effusions (MPEs) represent an excellent source to culture a wide variety of Lung AdenoCa cells from different donors (Mancini et al, PlosOne, 2011). Reproducible protocols for rapid cancer cell isolation from MPEs and growth in adherent and spheroid conditions have been established in our lab. In order to avoid long periods of adaptations in cell culture that may lead to the selection of subpopulation of cells with particular growth advantages all samples are banked at early passages, on average one month following MPE collection. Furthermore we have observed that these cells can achieve efficient tumor engraftment in recipient NOD/SCID mice, also upon inoculation of small number of cells, thus suggesting indirectly the presence of tumor initiating cells. We believe to have a set up solid system for the study of AdenoCa biology. Recently, we have started to study the expression of neurotrophins (NTs) in cultured lung adenocarcinoma cells from malignant pleural effusion. Using enzyme-linked immunosorbent assays in cancer stem cells and adherent cells from the same patients we have detected nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3), and their levels are higher as compared with adhesion and spheroid cells. We have documented, using molecular biology and immunocytochemistry, a different expression of the NTs and their cognate receptors, in lung cancer stem cells in comparison with differentiated cancer cells. Furthermore, the expression on these peptides resembles the previously documented pattern demonstrated in human embryonic stem cells. These data further support the possible role of NTs in cancer cell behavior.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4605. doi:1538-7445.AM2012-4605
Abstract 4608: RRBP1 overexpression is frequently found In lung cancer patients and alleviates intracellular stress induced apoptosis through positive regulation of GRP78 in lung cancer
Authors: Tsai Hong-Yuan , Hsiao Michael 
Published: August 2012

Abstract
How tumors evade apoptotic signals and survive during cancer progression has not yet been resolved. To unravel the molecular mechanisms involved in lung carcinogenesis will greatly improve therapy. Endoplasmic reticulum is a cellular organelle in which secretory and proteins are synthesized and modified. These processes are always enhanced in cancer cells. Ribosome binding protein1(RRBP1) was originally reported as a ribosome-binding protein on the rough endoplasmic reticulum. In this report, we showed that RRBP1 was highly expressed in the early stage of lung cancer compared to their adjunct normal tissue samples by utilizing lung cancer tissue array(n=87). Depletion of RRBP1 by short-hairpin RNAs significantly reduced cell growth and induced apoptosis in A549 and CL1-5 cells, but not in normal lung cells(BEAS2B). Furthermore, RRBP1-depleted NSCLC cells could activate CD95/caspase signaling pathways. Treatment with caspase8 inhibitor (ZVAD-FMK) or with shRNA against caspase8 was sufficient to suppress apoptosis in RRBP1-depleted cells. This effect is associated with significantly reduction in the expression of GRP78. GRP78, an antiapoptotic protein widely upregulated in cancer, plays a critical role in chemotherapy resistance in some cancers. According to our data, ectopic expression of RRBP1 alleviated tunicamycin induced apoptosis by upregulation GRP78 protein level in lung cancer cells. A strong correlation was observed between the expression of RRBP1 and GRP78 in tumor biopsies from NSCLC patients, supporting the concept that GRP78 expression levels are controlled by RRBP1. Taken together, this study not only showed that GRP78 is regulated by RRBP1 but also report that RRBP1 and GRP78 expression is involved in NSCLC growth and progression. suggest that RRBP1 is required for lung cancer growth and development, which may be a useful target in lung cancer treatment and expected to provide the basis for a rational approach for the development of new molecular targeted therapies
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4608. doi:1538-7445.AM2012-4608