bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5085: Radiosensitization of castration-resistant prostate cancer via modulating autophagic cell death
Authors: Qu Yang , Lian Jiqin , Wu Xiaoqing , Tang Wenhua , He Fengtian , Ji Min , Xu Liang 
Published: June 2012

Abstract
Radioresistance markedly impair the efficacy of cancer therapy. Anti-apoptotic Bcl-2 family proteins such as Bcl-xL, Bcl-2 and Mcl-1 are overexpressed in castration-resistant prostate cancer (CRPC) and contribute to prostate tumor initiation, progression and resistance to radiotherapy. A natural BH3-mimetic, small molecule inhibitor of Bcl-2, (−)-gossypol, shows promise in ongoing Phase II clinical trials for human prostate cancer. We have recently shown that (−)-gossypol preferentially induces autophagy in CRPC cells that have high levels of Bcl-2 and are resistant to apoptosis, both in vitro and in vivo, but not in androgen-dependent cells with low Bcl-2 and sensitive to apoptosis. Our results demonstrate for the first time that (−)-gossypol can interrupt the interaction between Beclin1 and Bcl-2/Bcl-xL at the endoplasmic reticulum, thus releasing the BH3-only pro-autophagic protein Beclin1, which in turn triggers the autophagic cascade. (−)-Gossypol-induced autophagy is Beclin1- and Atg5-dependent, together with Bcl-2 downregulation and Beclin1 upregulation. (−)-Gossypol increased autophagic cell death induced by X-ray radiation in the CRPC cells. Orally administered (−)-gossypol achieved a much greater efficacy with long-term tumor regression when used in combination with ionizing radiation. We have also explored a series of gossypol derivatives and identified two novel BH3-mimetic lead compounds that are more potent than the parental compound in inducing autophagic cell death in CRPC. Taken together, (−)-gossypol significantly enhances the anti-tumor activity of radiotherapy in vitro and in vivo, and represents a promising new regime for treatment of castration-resistant human prostate cancer with overexpression of Bcl-2. Our data provide new insights into the mode of cell death induced by Bcl-2 inhibitors, which would facilitate the rational design of clinical trials by selecting patients who are most likely to benefit from the Bcl-2-targeted molecular therapy.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5085. doi:10.1158/1538-7445.AM2011-5085
Abstract 5092: Variants at 6q21 implicate PRDM1 in the etiology of therapy-induced second malignancies after Hodgkin's lymphoma
Authors: Onel Kenan , Best Timothy , Skol Andrew D. , Li Dalin , Kirchhoff Tomas , Yasui Yutaka , Bhatia Smita , Strong Louise C. , Domchek Susan M. , Nathanson Katherine L. , Olopade Olufunmilayo , Mack Thomas M. , Conti David V. , Offit Kenneth , Cozen Wendy , Robison Leslie L. 
Published: June 2012

Abstract
Survivors of Hodgkin's lymphoma (HL) are at increased risk for second malignant neoplasms (SMNs) induced by exposure to radiation therapy (RT). Although SMNs are a leading cause of death in survivors of HL, it is not possible to identify those patients at greatest risk. We performed a genome-wide association study (GWAS) of 99 HL survivors who developed SMNs and 86 who did not, all of whom were treated for HL with RT. We then tested three SNPs in a replication set of 120 RT-treated HL patients with SMNs and 112 without SMNs. The functional effects of risk-associated variants on gene expression were assessed in lymphoblastoid cell lines before and after exposure to radiation. Two variants at 6q21 between PRDM1 and ATG5 were associated with SMNs in younger but not older HL patients treated with RT [rs4946728: P = 1.26×10-9, and rs1040411: P = 4.68×10-8]; individuals homozygous for the rs4946728 risk allele comprise 50% of the general population and were found to be at an eleven-fold increased risk for SMNs as compared to those homozygous for the protective allele. The risk variants comprise a haplotype that was associated with decreased PRDM1 expression (p=0.03) and protein levels. Furthermore, the risk variants were associated with a marked attenuation in the induction of PRDM1 following radiation exposure (p=0.002). Thus, we identified a new risk locus for SMNs following radiation treatment for HL at 6q21. This locus is associated with both basal and radiation-induced expression of PRDM1. These findings demonstrate a novel gene-exposure interaction associated with radiation-induced carcinogenesis and suggest that patients homozygous for the risk variants may benefit from early cancer screening.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5092. doi:10.1158/1538-7445.AM2011-5092
Abstract 5096: Identification of biomarkers and therapeutic targets in oral squamous cell carcinomas through comparative proteomic analyses
Authors: Tan Kee-Koon , Tsay Yeou-Guang , Lo Jeng-Fan 
Published: June 2012

Abstract
Background: Oral squamous carcinoma cell (OSCC) is the sixth most common worldwide cancer and responsible for about 640,000 new cases each year worldwide. Recently, a small subpopulation of oral cancer tumor cells with self-renewal capacity, or oral cancer-tumor initiating cells (OC-TICs), have been characterized in our lab. Accumulating evidence suggests that these OC-TICs contribute to tumor initiation, maintenance and metastasis while they are resistant to radiotherapy and chemotherapy. Thus, identification of the biomarkers and therapeutic targets for these cells should help the development of new diagnostics and therapeutics for oral cancers.
Methods: Sphere formation assay was used to enrich the OC-TIC population, whose proteins were resolved in a SDS polyacrylamide gel along with those from parental cells. The proteins within the gels were subjected to tryptic digestion and subsequent 18O peptide labeling. Liquid chromatography-mass spectrometry was programed to collect the tandem mass spectra (MS/MS) of peptides from proteins with &gt;2-fold increase in OC-TICs. These MS/MS were matched against the NCBI protein database with TurboSequest search engine and the results were interpreted by bioinformatics tools.
Results: With such a new platform, we found that 61 proteins were up-regulated in OC-TICs proteomes. In order to define collective functional roles of the identified proteins, these proteins were categorized based on the information in Gene Ontology database. Molecular function analyses showed that, besides binding, catalytic activity and transporter activity, a majority of proteins appear to participate in protein metabolism and modification, protein/vesicle trafficking and carbohydrate metabolism. Meanwhile, cellular compartment studies revealed that most proteins appear to be from plasma membrane and mitochondria.
Conclusion: Our results indicate that OC-TICs behave differently in protein metabolism/trafficking and carbohydrate metabolism. This data set will be used to identify novel biomarkers or therapeutic targets for oral cancer-tumor initiating cells (OC-TICs).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5096. doi:10.1158/1538-7445.AM2011-5096
Abstract 5099: Identification of lung cancer biomarkers using lung cancer in female never smokers
Authors: Park Yun Gyu 
Published: June 2012

Abstract
On a worldwide level, lung cancer in never smokers (LCINS) occupies 25% of total lung cancer incidence and this disease shows the 7th leading cause of cancer death. It is known that LCINS occurs frequently in asian women. It has been reported that 75% of female lung cancer occurred in never smokers in Republic of Korea. The clinico-pathological and molecular differences as well as geographic and gender variations between lung cancers in never smokers and smokers, indicate that two types of lung cancers should be regarded as a different disease entity. However, data for molecular understanding of LCINS are limited. We designed this study to identify the protein differentially expressed in lung cancer in female never smokers through proteomic analysis including 2-DE and MALDI-TOF-MS. To increase the probability of finding LCINS-associated proteins, the clinical specimens including sera and cancer tissues were classified as the following: normal female smokers, normal female never-smokers, lung cancer in female smokers, and lung cancer in female never smokers. Out of the proteins differentially expressed in LCINS tissues, levels of 10 proteins were increased and those of 8 proteins were decreased. Levels of 6 proteins were increased and those of 5 proteins were decreased in serum of patients with LCINS. The identified proteins were verified by performing Western blot analysis not only in the same sample used in proteomic analysis but also in samples obtained from lung cancer in female smokers. The serum protein, which was difficult to be identified in Western blotting, was verified by ELISA. Seven proteins identified in tissues and serum of patients with LCINS were verified by Western blot analysis and ELISA. These identified proteins might be applicable to biomarker development for diagnosis of LCINS and provide a more comprehensive understanding of tumor maintenance or progression.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5099. doi:10.1158/1538-7445.AM2011-5099
Abstract 5104: Serum metabolomic profiles acquired by gas chromatography-mass spectrometry (GC-MS) distinguish patients with pancreatic adenocarcinoma from those with benign pancreatic disease
Authors: McConnell Yarrow J. , Weljie Aalim M. , Kopciuk Karen A. , Dixon Elijah , Sutherland Francis , Dunse Nicole , Bathe Oliver F. 
Published: June 2012

Abstract
Introduction: Pancreatic adenocarcinoma is often difficult to accurately distinguish from benign pancreatic lesions such as pancreatitis. Accurate preoperative identification of patients with benign disease may reduce the number of highly invasive and costly pancreatic resections conducted in this group. This study aims to identify differences in the metabolomic profile of serum between patients with pancreatic adenocarcinoma versus benign pancreatic disease.
Methods: Fasting serum samples were collected, as part of an institutional biorepository program (IRB#E20846), from patients with pancreatic adenocarcinoma or benign pancreatic disease. Accompanying clinical data were collected prospectively. Gas chromatography-mass spectrometry (GC-MS) spectra were acquired for aqueous metabolites and analyzed using multivariate methods (orthogonal partial least squares-discriminant analysis, OPLS-DA) using SIMCA-P+ (V12.0.1) software. Metabolite identification was conducted using the TargetSearch approach.
Results: Of the 136 included patients, 101 had pancreatic adenocarcinoma and 35 had benign pancreatic disease (26 pancreatitis/pseudocyst, 7 serous cystic neoplasm, 2 other). Median patient age was 66 years, 51.4% were male, 22.8% were jaundiced, and 79.4% presented with a common bile duct stricture or pancreatic mass. The metabolomic profile of serum from patients with pancreatic adenocarcinoma was significantly different from that of patients with benign pancreatic disease based on OPLS-DA modelling (p=0.0004). Overall, the profile contained 168 targeted metabolites, of which 14 were significantly different between malignant and benign pancreatic disease on multivariate modeling.
Conclusion: The serum metabolomic profiles of pancreatic adenocarcinoma and benign pancreatic disease differ significantly. Further analysis of these differences may yield a novel serum test to distinguish these lesions in clinical practice.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5104. doi:10.1158/1538-7445.AM2011-5104
Abstract 5109: Proteomics of murine BRCA1 deficient breast tumors identifies DNA repair proteins with prognostic value in human breast cancer
Authors: Warmoes Marc O. , Jaspers Janneke , Massink Maarten P.G. , Pham Thang , Piersma Sander R. , Rottenberg Sven , Boven Epie , Meijers-Heijboer Hanne , Waisfisz Quinten , Jonkers Jos , Jimenez Connie R. 
Published: June 2012

Abstract
Background: Breast cancer is the most common malignancy in women in the western world. The outcome of breast cancer would be strongly improved if patients could be diagnosed and treated early. This especially holds for patients with hereditary breast cancer.
Aim: Our aim is to identify proteins that are associated with BRCA1 deficient hereditary breast cancer. These proteins could have potential use as screening, prognostic or predictive biomarkers.
Approach: In-depth proteome profiling of tumor tissues of mouse breast cancer models was employed to identify BRCA1-associated proteins. To this end, tumor tissue lysates of five BRCA1 deficient and five proficient mouse models (Liu et al., 2007) were fractionated using SDS-PAGE followed by tryptic in-gel digestion, nanoLC-MS/MS and database searching. Normalized spectral counting was used for protein quantification and beta binomial statistics to discover significantly regulated proteins. Ingenuity Pathway Analysis and COFECO protein complex analysis was used to support data interpretation. The prognostic power was assessed by the use of publicly available gene expression human breast cancer data sets.
Results: We identified a total of 3614 proteins, of which 804 were differential between the genomic instable BRCA1-deficient and the genomic stable BRCA1-proficient breast tumors. Pathway analysis and protein complex identified DNA-repair and associated function like chromatin modeling and RNA processing as the major functions associated with the upregulated proteins of the BRCA1 deficient tumors. We created a core DNA-repair protein signature using pathway and protein Complex analysis. When the signature proteins were mapped to human breast cancer gene-expression data sets, they were shown to have prognostic power.
Conclusion: Proteomics of genetic mouse models for familial breast cancer is a powerful strategy to discover novel candidate BRCA1 deficiency proteins with human relevance. The major upregulation of DNA-repair complexes may indicate a compensatory mechanism for loss of BRCA1 DNA-repair. Further validation studies are required to investigate prognostic candidates in tissue microarrays. Integration with data on tumor and cancer cell-secreted proteins will pinpoint which of the BRCA1 deficiency associated proteins may have potential for screening of BRCA1 tumors and whether they have predictive value for sensitivity to PARP1 inhibition and Cisplatin treatment in BRCA1 as well as non-BRCA1-deficient tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5109. doi:10.1158/1538-7445.AM2011-5109
Abstract 511: Adipocyte-derived fibroblasts contribute to the desmoplastic reaction in breast cancer: A new link between breast cancer and obesity
Authors: Bochet Ludivine , Dauvillier Stéphanie , Dirat Béatrice , Dabek Marta , Gonidec Sophie Le , Mari Pierre-Olivier , Escourrou Ghislaine , Valet Philippe , Muller Catherine 
Published: June 2012

Abstract
Now, it is widely established that malignant tumors, not merely grow into a preexisting interstitial tissue, but they actively form a new stroma and modify their composition. Accordingly, one of the features of many carcinomas, particularly breast, is the presence of a dense collagenous stroma, the so-called desmoplastic response, comprising fibroblast-like cells which play a crucial role in tumor progression. Peritumoral fibroblasts are composed of several subpopulations that are morphologically undistinguishable and their origins remain debated. Our results suggest that a part of this fibroblast could arise from the “reorientation” of mature adipocytes, highly represented in breast tumour microenvironment. Using an original 2D coculture system, we show that mature adipocytes cocultivated with breast tumour cells for 3 to 8 days lose their lipid content as well as their adipocyte differentiation markers (HSL, Adipsin, Adiponectin, C/EBPα, PPARγ, Resistin). This process is associated with intense morphological and functional changes leading to an activated fibroblast phenotype (exhibition of actin stress fibers, increase of focal adhesion sites). In this way, we have identified for the first time a new fibroblastic population called Adipocyte Derived Fibroblast (ADF). Interestingly, the reorientation occur in vivo since the injection of far red fluorescent tumour cells into a mice fatpad containing GFP-expressing adipocytes induce the apparition of GFP-fibroblast-like cells that interdigitate with tumour cells. Moreover, our results show that the ADF phenotype depends on the reactivation of the Wnt/β-catenin pathway. Finally, ADFs exhibit an increase of migratory and invasive abilities, with enhanced profibrotic secretions (fibronectin and collagen 1) suggesting that these cells could be key players in desmoplastic reaction. Ongoing experiments are performed to assess the presence of ADFs in breast human tumors. Our results might provide an explanation for the poor prognosis observed in localized breast cancer in obese women, since the nature of the desmoplastic reaction and the secretion pattern of ADF might be profoundly altered in this physiopathogical condition.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 511. doi:10.1158/1538-7445.AM2011-511
Abstract 5118: Comparative study on feature selection methods in ovarian cancer diagnosis using chemometrics tools
Authors: Yoon Seongkyu , Lee Hae Woo , Liu Jay , Na Young Jung 
Published: June 2012

Abstract
Ovarian cancer has the poorest prognosis of the gynecological cancers. 75% of the patients are diagnosed with stage III-IV on their diagnosis. The 5 year survival rate of ovarian cancer patients whose disease was diagnosed at stage III or IV is less than 20%, but that of the patients diagnosed with stage I is higher than 90%. The early detection and diagnosis of cancer is one of the major application areas in omics technology and has received tremendous attention in last few years.
The main focus of this study is aimed at the investigation of robust formulations for the feature selection algorithms which are utilized during the statistical analysis of omics profiles in diagnosing ovarian cancer. The common difficulty in the feature selection for cancer-specific biomarker discovery is the inconsistency of the feature sets selected among different samples or by different selection methods. This issue is particularly crucial in biological applications where subsequent biomedical analysis of selected features requires relatively considerable time and costs. In this study, we analyzed the reproducibility of different feature selection algorithms usually employed in chemometrics and investigated their stability to provide valuable insight for designing proper feature selection algorithms in the domain of cancer-specific biomarker discovery. Two data sets of MALDI-TOF-MS (proteomics) and LC/TOF-MS (metabolomics) spectra measured from serum samples to diagnose ovarian cancer were analyzed. To evaluate the feature selection methods in terms of their consistency, we systematically quantified a measure of similarity (similarity≤1) for the outcome of each method by running each selection procedures repetitively.
The results show that, in general, the multivariate feature selection methods outperformed the univariate methods, in that they selected more consistent features regardless of training set perturbations. The results clearly show that some feature selection methods can suffer severely from the irreproducibility issue and this might deflate the potential benefits of omics technology for cancer diagnosis. A possible remedy might be multi-objective formulation of the feature selection problem by simultaneously optimizing stability and accuracy of classification models, and this will be investigated further in future research.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5118. doi:10.1158/1538-7445.AM2011-5118
Abstract 5130: Neuropilin-1 expression in breast, colorectal and lung cancer
Authors: Jubb Adrian M. , Strickland Laura A. , Chen Daniel S. , Schmidt Maike , Koeppen Hartmut 
Published: June 2012

Abstract
Neuropilin-1 is a coreceptor for vascular endothelial growth factor, which is expressed by endothelial cells and tumor cells. Preclinical data suggest that targeting neuropilin-1 would directly inhibit tumor cell growth and invasion, in addition to suppressing angiogenesis with indirect suppression of tumor growth. A humanized monoclonal antibody to neuropilin-1 is currently being evaluated in a phase one clinical trial of patients with solid malignancies. The aim of this study was to characterize the in situ expression of neuropilin-1 in normal and neoplastic human tissues.
A monoclonal antibody to human neuropilin-1 was generated and validated for immunohistochemistry by comparison with isotopic in situ hybridization data, use of formalin-fixed human embryonic kidney (HEK)-293 cell pellets transfected with neuropilin-1, western blotting and quantitative reverse transcriptase (RT)-PCR on microdissected pure cell populations. Neuropilin-1 expression was assessed in whole sections of 65 primary breast carcinomas, 95 primary colorectal adenocarcinomas and 80 primary non-small cell lung carcinomas. An additional 50 breast, colorectal and lung metastases were also evaluated.
The neuropilin-1 monoclonal antibody showed appropriate reactivity by western blotting and in formalin-fixed cell pellet controls, with co-localization of protein (immunohistochemistry) and mRNA (in situ hybridization and laser-capture microdissection followed by quantitative RT-PCR). Immunoreactivity for neuropilin-1 was seen in endothelium from normal tissues adjacent cancer and 98 to 100% of primary and secondary carcinomas. Tumor cell expression of neuropilin-1 was also observed in 34% of primary non-small cell lung carcinomas and 6% of primary breast carcinomas, but no colorectal adenocarcinomas.
This is the first comprehensive analysis of neuropilin-1 protein expression in neoplastic human tissue with validated reagents. The assay will inform the likely activity and toxicity of agents that target neuropilin-1 and warrants evaluation as a biomarker of anti-neuropilin-1 activity.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5130. doi:10.1158/1538-7445.AM2011-5130