bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3594: Impact of metformin on HCC prognosis
Authors: Akmal Khan , Hassabo Hesham , Botrus Gehan , Shah Neeraj , Soliman Khalid , Khalaf Rossa , Li Donghui , Kaseb Ahmed , Hassan Manal 
Published: August 2012

Abstract
Concurrent with the increase in hepatocellular carcinoma (HCC) incidence, the prevalence of metabolic syndrome has increased in the USA. Metabolic syndrome is currently considered a major health problem. Moreover, long term diabetes mellitus is an independent risk factor for HCC. We have previously shown that use of metformin among diabetics was associated with 70% risk reduction of HCC as compare to the use of other types of antidiabetic treatment. It is not known, however, if diabetic patients with HCC who used metformin had a better prognosis. Between 2001 and 2010 we interviewed 438 patients with pathologically confirmed HCC for multiple risk factors of HCC including prior history of diabetes and type of antidiabetic treatment. Survival times were calculated from the date of pathology diagnosis and were censored for patients who were alive at the last follow up. Median survival was calculated using Kaplan Meier product-limit method and survival rates were compared using the log rank test. Cox proportional hazards model (CPHM) was used to estimate the multivariate Hazard Risk Ratios (HRR) and 95% Confidence Interval (CI). Total of 130 HCC patients (29.7%) recalled prior history of diabetes with more than 1 year prior to HCC diagnosis. Most subjects were considered to have type 2 diabetes mellitus and were on an oral antidiabetic regimen. The survival duration for HCC patients with diabetes did not significantly differs from those without diabetes in men and women. However, HCC diabetic men who received metformin had a better survival outcome. The median survival was 14.9 months (95% CI, 1.3-28.9) for metformin users compared to 12.7 months (95% CI. 6.2-10.1) among HCC diabetic men who received other treatments, Log Rank p value=.04. CPHM, which included age, hepatitis C virus infection, alcohol consumption, treatment of HCC (chemotherapy and surgical treatment), history of cirrhosis, and Liver Italian Program (CLIP) staging score yielded 40% improvement of overall survival in HCC men with diabetes who received metformin as compared to other treatments. The estimated HRR (95% CI) was 0.56 (.35-.91), P =.02. These results suggest a possible beneficial role of metformin in diabetic men with HCC. Such observations need to be confirmed in other populations and with correlation with duration of metformin intake.
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 3594. doi:1538-7445.AM2012-3594
Abstract 360: Tumor specific imaging by L-5-F-18-ethoxy-Tryptophan mediated by LAT1 and IDO1
Authors: Borkowski Sandra , Siebeneicher Holger , Gekeler Volker , Brumby Thomas , Dinkelborg Ludger 
Published: August 2012

Abstract
Purpose Radiolabeled tryptophan is capable of visualizing the amino acid metabolism of tumor cells. We investigated the indirectly labeled derivative L-5-F-18-ethoxy-Trp for its potential to differentiate tumors from inflammation by Positron-Emission-Tomography (PET) and for its possible intracellular trapping after catabolism by indoleamine-2,3-dioxygenase 1 (IDO1). Methods Human NCI-H460 lung cancer and PC-3 prostate cancer cells were used for in vitro studies. Cellular influx and efflux of L-5-F-18-ethoxy-Trp at 37°C was measured by a gamma-counter and via HPLC. Blocking studies were carried out under similar conditions to examine the transporter family being relevant for Trp uptake. The effect of IDO1 was investigated after stimulation of cells with 100 IU interferon-gamma (IFN-γ). Human plasma stability of 5-F-18-ethoxy-Trp was measured by radio-HPLC. The imaging potential was examined in tumor-bearing rodents and inflammation models. NCI-460 tumors in rats and PC-3 tumors in mice were subcutaneously inoculated. A sterile inflammation was induced by Complete Freund's Adjuvant (CFA) and an infection inflammation was induced by E.coli injection into rats. PET/CT imaging after 1 hour was conducted by an Inveon microPET camera. Results High cellular uptake of L-5-F-18-ethoxy-Trp was found in NCI-H460 and PC-3 cells with 10% of the applied radioactive dose per 100,000 cells and 30% per 100,000 cells, respectively. Uptake could be blocked by an excess of L-Trp, L-Leu and bicycloheptan-carboxylic acid indicating transport by the heterodimeric amino acid transporters of the SLC7 family with predominant transport by LAT-1. Both cellular uptake and retention were increased after stimulation of IDO1 activity by IFN-γ. HPLC of the efflux supernatant showed strict IDO1 dependence of the intracellular Trp catabolism. The tracer was rather instable in human plasma in vitro and degraded already after 15 min incubation. Nevertheless, PET imaging revealed good uptake of L-5-F-18-ethoxy-Trp in NCI-H460 and PC-3 tumors in rodents with low background. No uptake was found in both inflammation models in rats. Conclusion Tryptophan derivatives are promising tracers for cancer imaging utilizing enhanced metabolism by IDO1 which has been shown to be overexpressed in tumors to suppress the immune response of their microenvironment. Differentiation between malignant lesions and inflammation seems to be possible which would give this PET tracer an advantage over the currently used FDG.
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 360. doi:1538-7445.AM2012-360
Abstract 3604: Elevated sigma-2 receptor/Pgrmc1 (progesterone receptor membrane component 1) levels as a potential cancer biomarker in tumors and plasma
Authors: Mir Shakeel UR , Jin Ling , Craven Rolf J. 
Published: August 2012

Abstract
Cancers of the lungs and head and neck are one of the leading causes of death, particularly in Kentucky, which leads the nation in multiple categories related to smoking. Thus, there is an urgent need for new biomarkers and therapeutic targets for airway cancers. The sigma-2 receptor is an intracellular receptor for numerous drugs and metabolites and was recently found to be identical to Pgrmc1 (progesterone receptor membrane component 1), a cytochrome-related protein implicated in metabolism and hormone signaling. S2RPgrmc1 is up-regulated in multiple types of cancer and is required for tumor cell proliferation and motility in vitro and tumor formation and metastasis in vivo. Furthermore, small molecule inhibitors of S2RPgrmc1 suppressed the growth of lung, breast and cervical cancer cell lines. In the present study, we have analyzed S2RPgrmc1 levels in clinical tumor samples from squamous cell lung cancers (SqCLC), lung adenocarcinomas, head and neck cancers and others. S2RPgrmc1 levels were increased in tumors throughout and correlated with survival in lung cancer (n=43, p=0.02) and with grade in head and neck cancer (higher in grade 2 versus 1, p=0.007). One of the cancer types with highest S2RPgrmc1 expression was squamous cell lung cancer (SqCLC), and treatment options for SqCLC are limited. S2RPgrmc1 was highly expressed in SqCLC cell lines, and SqCLC cell survival was inhibited by siRNA knockdown of S2RPgrmc1 or the S2RPgrmc1 inhibitor AG-205. S2RPgrmc1 is part of a family of secreted cytochromes, and we found that S2RPgrmc1 was significantly elevated in the plasma of 42 lung cancer patients compared to non-cancer patients and was significantly higher in the plasma of stage I lung cancer patients compared to stage 2-4 patients. Purified, recombinant S2RPgrmc1 increased the proliferation of NSCLC cell lines, suggesting that secreted S2RPgrmc1 may contribute to lung tumor growth. Together, the results demonstrate that S2RPgrmc1 correlates with key clinical endpoints in tumors and is a therapeutic target in some cancers with few therapeutic options, particularly squamous cell lung cancer. Furthermore, S2RPgrmc1 is a potential plasma biomarker for early stage lung 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 3604. doi:1538-7445.AM2012-3604
Abstract 3607: Differential protein expression and miR content of sorted subsets of circulating microvesicles from cancer patients and healthy controls
Authors: Smith Shannon E. , Holterman Daniel A. , Brown Kirk M. , Duncan Janet E. , Zhong Jason , Stark Adam , Millis Meredith , Tinder Teresa , Spetzler David 
Published: August 2012

Abstract
MicroRNAs (miRs) are small non-coding RNAs that are 20 to 25 nucleotides in length and regulate expression of entire families of genes. A major source of circulating miRs in cancer patients is believed to be circulating microvesicles (cMV) within biologic fluids such as blood. The transfer of these modifiers of RNA translation from diseased cells into the bloodstream can have broad impacts on disease detection, progression and/or prognosis. The goal of these studies was to determine whether there are differences in miR composition within different subpopulations of cMV based on surface protein composition. We used flow cytometry to phenotype and sort plasma-derived cMV from 20 individuals (3 breast cancer, 2 lung cancer, 6 prostate cancer, 1 bladder cancer and 6 non-cancer controls). cMV were stained for proteins associated with membranes such as tetraspanins (CD9, 63, 81) Ago2 and/or GW182 using a Beckman Coulter MoFlo XDP. For phenotypic analysis, events were gated on tetraspanin expression to distinguish cMV from nano-sized irrelevant debris, and co-expression of GW182 and Ago2 was determined. Quadrant-based sorting was performed for single- and double-positive events. miR content was determined using conventional Taqman probes with the ABI 7900 thermal cycler on extracted RNA from the sorted cMV. The results of these studies demonstrate that unfractionated cMV were not able to discriminate cancers from non-cancers using miRs-let-7a, -16, -22, -148a or -451 in this population of patients. When sorted tetraspanin+, Ago2+ and/or GW182+ populations of cMV were compared, miR expression was generally 5-fold higher in cancer patients than in healthy controls. These studies demonstrate that cMV can be consistently phenotyped, analyzed and sorted using a flow cytometer and that subpopulations of cMV contain unique miR profiles which can be useful in distinguishing cancer plasma from non-cancer plasma.
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 3607. doi:1538-7445.AM2012-3607
Abstract 3617: A novel competition-based antibody array technology as a potential platform for cancer biomarker discovery
Authors: Jiang Weidong , Chen Yunru , Wu Lisha , Zhang Ying , Jones Valerie , Huang Ruopan 
Published: August 2012

Abstract
A novel competition-based antibody array assay has been developed. This assay, which is named the EIA array, adopts the principle of competition-based enzyme immunoassay (cEIA), in which an endogenous antigen and a labeled antigen competitively bind to a capture antibody fixed on a matrix. In this EIA array platform, 11 anti-adipokine antibodies are spotted onto membranes in an array format. After blocking, the capture antibodies can interact with either the endogenous adipokines in the sample or with the biotinylated adipokines spiked into the sample. Antibody-bound biotinylated adipokines are then detected by streptavidin-horseradish peroxidase (SA-HRP), which catalyzes a color development reaction. The intensity of colorimetric signal is directly proportional to the amount of biotinylated peptide-SA-HRP complex and inversely proportional to the amount of adipokines in the standards or samples. The signal is standardized against a cocktail of unlabeled adipokine peptides, allowing the unknown concentrations to be quantified. All 11 adipokines were detected at pg/ml and ng/ml levels with a CV of less than 20%, indicating that the EIA array has high sensitivity and reproducibility. Furthermore, no cross-reactivity was found among the 11 adipokine markers, indicating high specificity. Using this novel competition-based antibody array, we screened adipokine expression profiles in cancer cell lines HepG2 and MCF-7 with and without treatment of 100µM H2O2 and 100ng/ml EGF. Among these adipokine markers, visfatin was significantly increased in culture supernatants of both cell lines after H2O2 treatment, but not increased in cell lysates. The upregulation of visfatin after H2O2 treatment was confirmed by both EIA array and Western blot. Currently, studies investigating the role of visfatin in liver carcinogenesis are underway using serum samples from clinically diagnosed pre-operative hepatocellular carcinoma patients with age and sex-matched controls. In summary, our results suggest that the novel competition-based EIA array has great potential for cancer biomarker discovery.
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 3617. doi:1538-7445.AM2012-3617
Abstract 3621: Polymorphisms in genes related to DNA repair and to apoptosis: Link with the outcome after radiochemotherapy in head and neck cancer patients
Authors: Borchiellini Delphine , Etienne-Grimaldi Marie-Christine , Thariat Juliette , Chateau Yann , Formento Jean-Louis , Formento Patricia , Llorca Laurence , Milano Gerard 
Published: August 2012

Abstract
Background For patients with locally-advanced head and neck cancer (LAHNC), treatment with irradiation (RT), associated or not with chemotherapy (CT), remains a valuable alternative to surgery and is currently being actively investigated. Identification of individual factors able to discriminate good candidates for radiochemotherapy (RCT) would allow optimal handling of RCT (doses, associated drugs). We examined whether functional single nucleotide polymorphisms (SNPs) in genes related to DNA repair and to apoptosis could be related to the outcome of patients with LAHNC treated with RCT. Methods A homogeneous group of 90 patients with LAHNC were treated by either RT (29%) or cisplatin-based RCT (71%). For all study patients, we used DNA extracted from tumor samples stored in liquid nitrogen from 1992 to 2006. The following SNPs (rs) were analysed by PCR-RFLP: ERCC2 (XPD) 751Lys≫Gln (rs13181), XRCC1 399Arg≫Gln (rs25487), TP53 72Arg≫Pro (rs1042522) and MDM2 309T&gt;G (rs2279744). The SNPs ERCC1 259Lys≫Thr (rs735482) and ERCC5 46His C&gt;T (rs1047768) were investigated by Single Base Extension. Results Univariate analyses showed no link between the studied SNPs and overall response rate evaluated at 3 months or 6 months from the end of the treatment. In contrast, there was a significant association between the polymorphism MDM2 309T&gt;G and the occurrence of cutaneous toxicity, since G/G subjects had a higher risk of severe radiation dermatitis (p=0.047). Similarly, the Gln allele of ERCC2 751Lys≫Gln was specifically related to a risk of acute radiation dermatitis following exclusive RT (p=0.009). Also, homozygous patients for XRCC1 399Arg≫Gln (Arg/Arg or Gln/Gln) had an increased risk of developing early osteoradionecrosis, particularly for patients receiving RCT (p=0.032). The occurrence of late toxicities (cervical fibrosis, p=0.011 or xerostomia, p=0.043) was associated with the genotype T/T of ERCC5 46His C&gt;T. Conclusion Individually-based decision criteria are eagerly needed in the context of concurrent chemoradiation in LAHNC, especially with the introduction of anti-EGFR targeted therapies, which increase both anti-tumor efficacy and side-effects (radiation dermatitis). We believe that analyses of gene polymorphisms such as MDM2 and ERCC2 could be of clinical value in establishing the necessary guidelines.
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 3621. doi:1538-7445.AM2012-3621
Abstract 3637: Loss of prostate derived Ets (E-twenty six) transcription factor (PDEF) predicts patients at the highest risk of metastatic prostate cancer
Authors: Haller Andrew C. , Morrison Carl , Tan Wei , Payne-Ondracek Rochelle , Underwood Willie , Poch Michael , Tian Lili , Mohler James , Li Fengzhi 
Published: August 2012

Abstract
PSA has ability to detect prostate cancer (CaP) at an early stage, but many CaP tumors are slow to progress, and many patients are overtreated for a disease that will not become life-threatening. Since there remains no reliable way to distinguish indolent from aggressive disease, doctors who advise and patients on active surveillance worry about progression to incurable disease. Therefore, new prognostic tools must be developed to identify patients with potentially metastatic, life threatening CaP. Prostate derived Ets transcription factor (PDEF) has shown to be a master negative regulator of transcriptional networks controlling migration and invasion in many cancer tissues, including CaP. Therefore we studied the expression of PDEF in radical prostatectomy specimens to determine retrospectively whether PDEF expression is predictive of clinical outcome. Patients’ tumor PDEF expression was determined by immunohistochemical staining of a 724 patient tissue microarray (TMA). CaP patients were stratified into groups based on PDEF expression (high, mid, low, null) and a Cox proportional hazards model was used to compare clinical outcomes. Univariate analysis showed that loss of PDEF expression significantly increased risk of metastatic disease (HR = 5.38, PDEF mid; to HR = 43.48, PDEF null; p=0.0059), although it did not correlate with incidence of biochemical failure detected using the American Urological Association (AUA) or National Comprehensive Cancer Network (NCCN) definitions. This result was confirmed in the Kaplan-Meier survival analysis that showed that patients whose CaP were PDEF low/null had significantly shorter metastases-free survival (p=0.0151). Multivariate analysis also demonstrated CaP with low/null PDEF expression were associated with increased risk of developing metastatic disease (HR = 6.21/10.53), although it was not statistically significant, in part due to the low incidence of patients with metastatic disease in the TMA. Therefore, we studied PDEF and vimentin (stem-like marker, repressed by PDEF) tumor expression in a cohort of patients matched for Gleason score, stage, age, and follow-up who developed metastatic disease versus those who did not. Patients that developed metastatic disease had a significantly lower PDEF (3.9 vs 1.7, p&lt;0.0001) and higher vimentin (0.43 vs. 4.1, p&lt;0.0001) expression compared to matched controls. We propose that intact PDEF expression in CaP can be used to distinguish patients who are suitable for active surveillance from those who require aggressive treatment.
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 3637. doi:1538-7445.AM2012-3637
Abstract 3645: Integrative molecular profiling in serous epithelial ovarian cancer for identification of biomarkers of chemoresistance
Authors: Koti Madhuri , Vidal Ricardo , Nuin Paulo , Haslehurst Alexandria , Weberpals Johanne , Childs Timothy , Bryson Peter , Dharsee Moyez , Evans Ken , Feilotter Harriet E. , Park Paul C. , Squire Jeremy A. 
Published: August 2012

Abstract
Ovarian cancer is the fifth leading cause of death due to gynecological cancers in women in the western world. Development of primary resistance to carboplatin and paclitaxel poses a major challenge in the management of serous epithelial ovarian cancer. To identify the molecular mechanisms underlying the development of instrinsic resistance upon exposure to standard first-line therapy for ovarian cancer, we used microarrays to profile the 1) copy number alteration and SNP, 2) mRNA, 3) miRNA and 4) methylation signatures in a cohort comprising 11 chemoresistant and 14 chemosensitive tumour samples. Copy number analysis showed significant copy number alterations in the chemoresistant group (gains on chromosomal regions, 4q, 6q, 8p, 8q, 19q, 7q and 22q; losses on 8p and 10q) compared to the sensitive group. Gene expression data analysis using R/bioconductor revealed a set of 248 discriminating genes in the two cohorts. Pathway analysis of these genes using Ingenuity Pathway Analysis revealed enrichment in genes primarily involved in epithelial to mesenchymal transition and PI3 Kinase pathway. Additionally, genes related to the pro-inflammatory cytokine pathways, as well as drug transport demonstrated significant differential expression between the two groups. Ongoing concurrent comparative analyses of miRNA profiles within this cohort have also identified several differentially expressed transcripts including mir-34b, mir-155, mir-214, mir-200c and mir-143. Some of these miRNAs have been earlier reported to be associated with tumour progression. Further integrated analysis will elucidate the synergistic roles that the genetic and epigenetic alterations in the deregulation of these and other pathways involved in primary chemoresistance. Our research findings will yield diagnostic and prognostic biomarkers that will lead to development of specific treatment regimens for the improved control of serous epithelial ovarian 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 3645. doi:1538-7445.AM2012-3645