bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 538: ROS differentially regulates prostate cancer cell survival
Authors: Chetram Mahandranauth A. , Bethea Danaya A. , Stowers Taylor J. , Hinton Cimona V. 
Published: August 2012

Abstract
In vitro and in vivo studies have shown that ROS accumulation correlates with increasing aggressiveness of prostate cancer cells, and increased expression of oncogenic molecules, such as CXCR4. CXCR4 is a G-Protein Coupled Receptor that is heavily implicated in the metastatic dissemination of prostate tumor cells to bone marrow. In cancer and other cell models, CXCR4 expression and activity increases in response to hypoxic environments and/or oxidative stress. Cells react by inducing expression of a HIF1α transcription factor, which enhances expression of targeted genes involved in adjusting to oxidative stress and cell survival. HIF1α has been shown to directly induce the expression of CXCR4 in prostate cancer cells. Therefore, generation of ROS in tumor tissues may critically influence CXCR4-mediated expression and functions, ultimately encouraging cancer progression. In this study, we elucidate a mechanism by which ROS induces CXCR4 expression and function in prostate cancer cells. We initially investigated the role of ROS on the phosphorylation of AKT (p-AKT) and ERK1/2 (p-ERK1/2) in DU145 and 22Rv1 prostate cancer cell lines. Using H2O2 as our model of ROS, we found that H2O2 induced a gradual expression of p-AKT and p-ERK1/2 by western blot analysis, which was abrogated by the ROS scavenger N-acetyl cysteine (NAC). It has been shown that PTEN is a negative regulator of AKT and ERK1/2 signaling, and that ROS accumulation inactivates PTEN phosphatase function; hence, we determined whether the increase in p-AKT and p-ERK1/2 expression was due to loss of PTEN function. By performing a phosphatase assay, we found that H2O2 inhibited PTEN catalytic activity compared to untreated cells, while NAC abrogated these effects in both cell lines. The increase in ROS and loss of PTEN has been shown to correlate with CXCR4-mediated function; therefore, we determined the role of H2O2 on CXCR4 expression. We found that H2O2 induced CXCR4 expression in DU145 cells, but not in 22Rv1 cells. Furthermore, we investigated whether ROS-mediated induction of CXCR4 was HIF1α dependent. Interestingly, H2O2 induced expression of HIF1α in DU145 cells, which was abrogated by siRNA for HIF1α. HIF1α expression decreased in 22Rv1 cells, which correlated with apoptosis, as confirmed by Annexin-V analysis. Finally, we observed that the H2O2-mediated increase in CXCR4 enhanced transendothelial invasion and migration in DU145 cells in a CXCR4 dependent manner. Our study suggests that ROS differentially regulates CXCR4 expression and function in prostate cancer cells, suggesting that ROS plays a differential role on heterogeneous tumor mass.
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 538. doi:1538-7445.AM2012-538
Abstract 5397: The SOCS-1 derived peptides inhibit tumor development
Authors: Scutti Jorge Augusto Borin , Matsuo Alisson , Massaoka Mariana , Figueiredo Carlos , Girola Natália , Valença Felipe , Melo Filipe Menegatti de , Travassos Luiz 
Published: August 2012

Abstract
Introduction: Melanoma is the most aggressive form of skin cancer and its incidence has increased dramatically over the years. The murine B16F10 melanoma in syngeneic C57Bl/6 mice has been used as a highly aggressive model to investigate tumor development. In our previous work, we demonstrate in the B16F10-Nex2 subclone that silencing of SOCS-1, a negative regulator of Jak/Stat pathway, leads to reversal of the tumorigenic phenotype and inhibition of melanoma cell metastasis. SOCS-1 silencing with shRNA affected tumor growth, cell cycle regulation with arrest at the S phase with large-sized nuclei, reduced cell motility and decreased melanoma cell invasion through Matrigel. In vivo, silencing of SOCS- 1 inhibited subcutaneous tumor growth and metastatic development in the lungs. Objectives: Since SOCS-1 is expressed in most melanoma cell lines and bears a relation with tumor invasion, thickness and stage of disease, we synthetized five SOCS-1 peptides based hydrophilic regions suggest regulating protein can be a target of cancer therapy. Suppressor of cytokine signalling 1 (SOCS 1) proteins are negative feedback regulators of several pathways involved in immune response, particularly the JAK/STAT (Janus kinase/Signal Transducer and Activator of Transcription. Results: No effect was found directly on B16F10 Nex 2 in vitro. In this work we hypothesized that SOCS-1 mimetic peptides should act on immune cells. Murine splenocytes from challenged animals and peptide treated was stimulated whole B16F10 Nex 2 lysate and supernatant was measure for ELISA to IFN-gama, IL-6, TNF-alfa and IL-10.The peptides increased the production of IFN-gama, IL-6, TNF-alfa and reduced IL-10 cytokine levels. Moreover, macrophages was stimulated and activation assay was performed. In vivo, the peptides are able to reduced significantly melanoma gorwth in metastatic and subcutaneous model.Additionally, mice knockout IFN-γ and CD1d revealed a inhibition of melanoma cell growth and metastasis. In the present study SOCS-1 derived peptides can be a target of cancer 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 5397. doi:1538-7445.AM2012-5397
Abstract 5469: Detection of deoxyguanosine adducts in the oral tissues of mice treated with the environmental carcinogen dibenzo[a, l]pyrene by LC-MS/MS
Authors: Zhang Shang-Min , Chen Kun-Ming , Aliaga Cesar , Gowdahalli Krishnegowda , Amin Shantu , El-Bayoumy Karam 
Published: August 2012

Abstract
Oral cancer is the major form of head and neck squamous cell carcinoma, which is the fifth most common cancer worldwide. Tobacco smoking is one of the leading causes of oral cancer. Dibenzo[a, l]pyrene (DB[a, l]P) is the most potent carcinogenic polycyclic aromatic hydrocarbon found in tobacco smoke. Our laboratory had developed a mouse model of oral cancer induced by DB[a, l]P. Our working hypothesis is that the stereochemical course of DB[a, l]P metabolism, the conformations of the DNA adducts formed and their removal by mammalian DNA repair enzymes, and their mutagenic properties if not removed in an error-free manner, all play critical roles during the induction of oral carcinogenesis. As an initial study to test our hypothesis, we have previously developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to detect and quantify DB[a, l]PDE-N6-dA adducts in oral tissues of mice treated with DB[a, l]P. We have shown that (-)-anti-cis- and (-)-anti-trans-DB[a, l]PDE-N6-dA adducts were detected from oral tissues of mice treated with DB[a, l]P. In the present study, to further test our hypothesis, we report on the development of a LC-MS/MS method to detect DB[a, l]PDE-N2-dG adducts in vivo. (±)-anti-[15N5]-DB[a, l]PDE-N2-dG adducts were synthesized as internal standards. The stereochemistry of adducts were characterized. Following the addition of internal standards, DNA isolated from oral tissues of mice treated with DB[a, l]P or DB[a, l]PDE was enzymatically hydrolyzed to 2′-deoxyribonucleosides and partially purified by solid-phase extraction. The LC-MS/MS analysis was carried out by monitoring transitions m/z 620 [M+H]+→ m/z 504 [(M+H)+−2′-deoxyribose] for DB[a, l]PDE-N2-dG adducts and m/z 625α m/z 509 for the internal standards. We have detected two N2-dG adducts from oral tissues of mice treated with DB[a, l]P, and four N2-dG adducts from oral tissues of mice treated with (±)-anti-DB[a, l]PDE. Collectively, the in vivo detection of dA and dG adducts indicated that DB[a, l]P is predominantly metabolized to (-)-anti-DB[a, l]PDE in oral tissues of mice. This sensitive LC-MS/MS method, is capable of simultaneously detecting both dA and dG adducts derived from anti-DB[a, l]PDE. Our results indicated that levels of dA adducts are significantly higher than dG adducts in vivo, which are consistent with those reported in literature in organs other than oral tissues, demonstrating that fjord region diol epoxide of DB[a, l]P predominantly form dA adducts than dG adducts.
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 5469. doi:1538-7445.AM2012-5469
Abstract 547: Mapping of estrogen receptor-dependent and independent signaling pathways for xeno- and phytoestrogens
Authors: Katchy Anne C. , Pinto Caroline , Bondesson Maria , Williams Cecilia 
Published: August 2012

Abstract
Xenoestrogens (e.g. bisphenol A) and phytoestrogens (isoflavones) are endocrine disrupting chemicals (EDC) that are capable of disrupting hormonal signaling in mammary and reproductive systems. These compounds are similar in structure to estrogen and bind to the estrogen receptors (ER). Estrogen receptors are involved in the regulation of cell cycle, proliferation, and apoptosis. It is likely that these compounds could affect the same biological processes or have their own subsets of target pathways. Here, we extensively identify target genes and signaling pathways for selected xeno- and phytoestrogens. Dose response curves for these compounds were measured using real-time PCR (RT-PCR) and transactivation assays of known estrogen target genes. Gene expression profilings for each EDC were performed on MCF-7 breast cancer cell lines using dual-color comparative array. Validations of array results were carried out using RT-PCR. Gene ontology and gene network mapping studies were done to identify the mechanism of action of these compounds. Non-ER mediated targets and the kinetics of each EDC were investigated in detail. Results show that many target genes regulated by bisphenol A and Genistein were involved in biological processes including cell cycle and proliferation, similar to that of estrogen. This contributes to an increased understanding of the mechanisms of EDC action, which may be implicated in development of diseases such as breast cancer and reproductive disorders, and would contribute to a more reliable risk assessment of different EDC compounds.
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 547. doi:1538-7445.AM2012-547
Abstract 5473: Integrative approach towards the functionality of CIAO1 gene
Authors: Lin Mau-Ting , Albertson Donna G. 
Published: August 2012

Abstract
Previous genome-wide analysis of copy number aberrations in oral squamous cell carcinoma (SCC) and oral epithelial dysplasia, a pre-malignant lesion, by array CGH has revealed that the genomes of these cancers and pre-cancers frequently harbor narrow (∼3Mb) regions of amplification on chromosome 2q11 region. Overexpression of CIAO1, a putative cytosolic iron-sulfur protein within this region, has been observed in patients’ cancerous samples and oral SCC lines. Knockdown of CIAO1 protein by RNAi results in growth retardation in oral SCC lines. Therefore, three HaCaT cell clones with an inducible Tet-on CIAO1 gene have been established to unravel the nature of the CIAO1 signaling network. Through the triangulation of protein-protein interactions, quantitative PCR array and transcription factor reporter array, we have investigated the early effects of CIAO1 overexpression in immortalized HaCaT cells, which may add to the understanding of oral cancer tumorigenesis.
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 5473. doi:1538-7445.AM2012-5473
Abstract 5509: Liver cancer risk prediction model from a large prospective cohort in Taiwan
Authors: Wen Chi-Pang , Lin Jie , Yang Yi-Chen , Tsao Chwen-Keng , Etzel Carol , Huang Maosheng , Tsai Min-Kuang , Ye Yuanqing , Lopa Mishra , Hawk Ernest , Wu Xifeng 
Published: August 2012

Abstract
Models predicting liver cancer are only available for the high risk population with hepatitis carriers but not for the general population. we developed risk prediction models for liver cancer using data collected from a large health screening program in Taiwan with long term follow up. The cohort included 444,023 subjects at baseline. During a median follow up time of 7.4 years, 1,668 subjects developed liver cancer. Epidemiologic data, medical history and routine blood panel including serum transaminases data were collected with optional additional testing for HBV or HCV status. Liver cancer cases were ascertained by computerized record linkage with both the National Cancer Registry and the National Death Certification profiles in Taiwan. Stepwise Cox regression analysis was performed to identify significant predictors in the multivariate models. Individualized risk of developing liver cancer in 10 years was calculated from baseline probability and relative risk profile estimated from the Cox regression model. Models were developed separately to provide risk prediction for subjects who chose to have HCV tested (130,533 subjects at baseline and 416 liver cancer cases) and who chose otherwise (313,490 subjects and 1,252 liver cancer cases). Since the results for both sub-cohorts are comparable and we only reported results for the sub-cohort with HCV tested. In the sub-cohort with HCV tested, the model with only questionnaire data identified significant main effects for male gender, older age, prior history of diabetes, pack year of smoking, alcohol use, and physical inactivity. This epidemiologic model had an AUC of 0.798 (95% CI=0.772-0.815) for 10-year risk prediction. With only data from measures of Transaminases, the model achieved an AUC of 0.927 (95% CI=0.911-0.938), a significant increase as compared to the model with only epidemiologic variables. The addition of HBV improved the AUC to 0.936 (95% CI=0.913-0.958). Similar results were obtained for sub-cohort without HCV testing. The addition of HCV status in combination with HBV status, the AUC improve to 0.941 (95% CI=0.918-0.967). Among models using key history and blood panels, the use of serum Transaminases only, available in routine health check-ups, was able to provide most information needed in predicting liver cancer in the general public. Additional testing of HBV and /or HCV further increased the prediction power. This simple transaminase-based model for the general public can be valuable in clinical practice for identifying high risk individuals.
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 5509. doi:1538-7445.AM2012-5509
Abstract 5510: Assessing the level of breast cancer awareness among recently diagnosed patients in Ain Shams University Hospital
Authors: El-Shinawi Mohamed , Youssef AlMoataz , Aly Mohamed K. , Mostafa Mohamed , Alsara Mohamed , Yehia Ahmed , Hurlbert Marc , Mohamed Mona M. , El-Tawab Reda Abd 
Published: August 2012

Abstract
Introduction: 97% of Egyptian breast cancer patients are diagnosed at advanced stage, 70.6% possess positive lymph node metastasis on diagnosis while only 29.4% are free of metastasis reflecting late presentation of Egyptian patients. PURPOSE: Assess the level of knowledge about breast cancer among recently diagnosed breast cancer patients at Ain Shams University Hospitals. METHODS: In a cross-sectional, analytical observational study, we randomly enrolled 289 breast cancer patients with 45 of them who were recently diagnosed at Ain Shams University Hospitals meeting our inclusion criteria.Recurring patients or those unaware of diagnosis were excluded. Patients were interviewed using a specially designed questionnaire -of 75 questions over 60 minutes. Questionnaire gathered socio-demographic information, maternity history and tested knowledge of risk factors, signs and symptoms, screening options, management and prognosis of breast cancer was tested. Data was correlated to TNM staging. RESULTS: Patients’ age ranged between 30-72 years (mean 48±10.19). 40% were illiterate and only 15.6% finished higher education with 6-month average delay in seeking medical attention. Among the 45, TNM staging was assessed in 19 patients. Although 93% knew painless mass was symptom of breast cancer, 69% presented with painless mass and 47% knew someone with breast cancer prior to diagnosis, yet 24% thought they might have breast cancer. Regarding regular clinical breast exam 58% agreed to have it but 60% didn't know what was mammography, 56% didn't hear about breast self-exam and only 22% knew breast cancer had risk factors. Moreover, 58% thought treatment caused patients to be very ill, 29% thought breast cancer had good survival, yet 75% thought breast cancer is curable. Total breast cancer knowledge scores were low, with a median of 13 (out of 35) and mean of 12.64 ±5.12. CONCLUSIONS: Patients had acceptable awareness about breast cancer symptoms yet displayed gross ignorance about risk factors and poor awareness about screening, management and prognosis, correlating with their advanced TNM score. Therefore, raising breast cancer awareness and promoting education and early detection among our community is important.
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 5510. doi:1538-7445.AM2012-5510
Abstract 5527: Overexpression of protein phosphatase 4 is associated with poor prognosis in patients with pancreatic ductal adenocarcinoma
Authors: Weng Shaofan , Chen Weihong , Stanley Hamilton R. , Chatterjee Deyali , Katz Matthew H. , Lee Jeffrey E. , Pisters Peter W. , Gomez Henry F. , Abbruzzese James L. , Fleming Jason B. , Wang Huamin , Wang Hua 
Published: August 2012

Abstract
Background: PP4 has been reported to be overexpressed in breast and lung cancers. While previous studies have identified the role of PP4 in activating NFκB and JNK signaling pathway, the expression and functions of PP4 in pancreatic cancer has not been studied in detail. Methods: We examined the expression of PP4 protein in 133 patient samples of stage II pancreatic ductal adenocarcinoma (PDA) samples by immunohistochemistry (IHC). To confirm our IHC results, we measured the expression levels of PP4 mRNA in 15 PDA samples and 15 benign pancreatic tissue sample by real time RT-PCR. We also measured PP4 protein levels in in 9 fresh frozen PDA samples and their paired benign pancreatic tissues by Western blot. Using univariate and multivariate analysis, we correlated PP4 expression with survival and other clinicopathologic features. Results: PP4 was overexpressed in 75 of 133 (56%) stage II PDA samples by immunohistochemistry. Compared to benign pancreatic tissue, PP4 protein levels were higher in 9 of 9 PDA samples by Western blot analysis. PP4 mRNA expression levels in PDA samples were significantly higher than benign pancreatic tissue, suggesting that overexpression of PP4 in PDA is due to increase mRNA expression. PP4 overexpression was associated with higher frequencies of distant metastasis (p=0.02) and poor overall and recurrence-free survivals (p = 0.002 and 0.005) independent of tumor size, margin status, and lymph node status (stage) in patients with stage II PDAs. Conclusions: Our study shows that PP4 is frequently overexpressed in PDA samples and is associated with poor prognosis in patients with stage II PDA. Therefore, targeting PP4 signaling pathway may represent a new approach for the treatment of PDA.
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 5527. doi:1538-7445.AM2012-5527
Abstract 5530: Fluorescence laparoscopy improves metastatic detection in both early and advanced colon cancer
Authors: Menen Rhiana , Kaushal Sharmeela , Snyder Cynthia , Hoffman Robert M. , Bouvet Michael 
Published: August 2012

Abstract
The aim of the present study was to improve detection and treatment of colon cancer with the use of fluorescence laparoscopy in an orthotopic mouse model of human colon cancer. The orthotopic model was established by intra-cecal injection of GFP-expressing HCT-116 human colon cancer cells into 12 six-week-old female athymic mice. Two models were then established: one of early disease and the second of widely metastatic disease. Two weeks after implantation, 6 mice underwent diagnostic laparoscopy. Laparoscopy was performed first under standard brightfield lighting, followed by fluorescent lighting. The number of metastatic foci identified within each of the four quadrants of the peritoneal cavity was recorded in three mice in each light mode. This process was repeated in the second group 4 weeks after implantation. Following laparoscopy, all animals were sacrificed. Fluorescence imaging was used as a positive control to identify metastasis at necropsy. Tumors and metastases were collected and processed for histologic review. Fluorescence laparoscopy enabled visualization of colon cancer metastatic foci which could not be visualized with standard brightfield laparoscopy in both the early (p= 0.028) and late (p= 0.001) models of colon cancer. When compared to the positive control of open fluorescence imaging, standard brightfield laparoscopy was significantly inferior in both the early (p= 0.03) and late (p= 0.0005) groups. Conversely, fluorescence laparoscopy was not significantly different from open fluorescence imaging in either the early (p= 0.94) or late (p= 0.56) groups. Fluorescence laparoscopy thus allowed identification and localization of sub-millimeter micrometastases that could not be distinguished from surrounding tissue under brightfield laparoscopy. Metastatic lesions were histologically confirmed. This report illustrates the important clinical potential of fluorescence laparoscopy in the surgical treatment of cancer.
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 5530. doi:1538-7445.AM2012-5530