bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1702: A novel diagnostic approach using genome-wide single nucleotide polymorphism arrays for ovarian metastases in endometrial cancers
Authors: Ikeda Yuji , Oda Katsutoshi , Nakagawa Shunsuke , Hosokawa Satsuki Murayama , Shoji Keiko , Yamamoto Shogo , Ishikawa Shumpei , Uehara Yuriko , Koso Takahiro , Miyasaka Aki , Kashiyama Tomoko , Takazawa Yutaka , Maeda Daichi , Wada Osamu Hiraike , Kawana Kei , Fukayama Masashi , Aburatani Hiroyuki , Yano Tetsu , Kozuma Shiro , Taketani Yuji 
Published: August 2012

Abstract
[Introduction] Synchronous cancers involving ovaries as well as uterine corpus are well-known events in gynecologic malignancies. These tumors may be independently derived, non-metastatic tumors (Dual Primary tumors; DP) or a tumor from one organ with metastasis to the other (Single Primary tumor with Metastasis; SPM). In the majority of these synchronous endometrial and ovarian cancers, both tumors are histologically endometrioid adenocarcinomas, which may cause a diagnostic difficulty to distinguish DP and SPM. By genome-wide genotyping, single nucleotide polymorphism (SNP) arrays, we can obtain chromosomal copy number alterations (CNA) throughout the genome in a single assay. We hypothesized that the copy number profiles by SNP arrays might be highly informative for genetic diagnosis in the synchronous endometrioid adenocarcinomas. [Material and Methods] We genetically diagnosed ten tumors from five patients with synchronous endometrial and ovarian carcinomas, using 250K SNP typing arrays and mutational analysis of PIK3CA, PTEN, K-Ras and CTNNB1 (beta-catenin). We evaluated whether conventional pathological diagnosis is compatible with the genetic diagnosis. [Results] Three of the five patients show identical copy number alterations (CNA), including type, loci and degree of each alteration, between the endometrial and the ovarian carcinomas. The other two show CNA only in either endometrial or ovarian carcinoma. All the five tumors possess one or more genetic mutations in the genes examined. One patient showed mutations both in PIK3CA and PTEN at discordant sites between endometrial and ovarian carcinomas, whereas the other four showed concordant mutations. Together, four of the five were genetically diagnosed as SPM and the remaining one was as DP. The pathological diagnosis was not in agreement with the molecular diagnosis in four of the five cases. [Conclusion] Our data suggest that most of the copy number alterations might occur before metastases and that genome-wide genotyping may represent a useful approach to distinguish between SPM and DP in synchronous endometrial and ovarian carcinomas. As chromosomal instability is commonly observed in various types of tumors, SNP array genotyping might be applicable to synchronous tumors in other organs.
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 1702. doi:1538-7445.AM2012-1702
Abstract 1709: The effect of a XIAP inhibitor, embelin, on apoptosis of thyroid cancer cell lines
Authors: Han Ji Min , Kim Won Bae , Yim Ji Hye , Kim Won Gu , Kim Tae Young , Choi Hyun-Jeung , Kim Eui Young , Shong Young Kee 
Published: August 2012

Abstract
X-linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitor of apoptosis (IAP) protein family that selectively blocks caspases-3, -7, -9 and inhibits cell death. Embelin, a XIAP inhibitor, is known to exhibit anti-inflammatory and apoptotic activities. Recent reports suggest that embelin interferes the signal transducer and activator of transcription 3 (STAT3) pathway and nuclear factor-kB (NF-kB) signal pathway. In this study, we investigated the anti-cancer efficacy of embelin by measuring its effects on apoptosis of thyroid cancer cell lines. We also explored the mechanism underlying these effects. We found that embelin induced the apoptosis of human thyroid cancer cell lines, such as FTC-133, CAL-62, KTC-1, and 8505C. The effect was stronger in BRAF V600E-mutant thyroid cancer cell lines (KTC-1 and 8505C) than wild-type cell lines (FTC-133 and CAL-62). The effect of embelin on cell apoptosis was associated with increased phosphorylation of p38. SB203580 inhibited the embelin mediated induction of cleaved caspase-3 activity in V600E mutant thyroid cancer cell lines. Interestingly, embelin induced apoptosis in BRAF wild type cancer cell lines, even after treatment of SB203580. These results indicated that another signaling pathway, not a p38 pathway, might be existed for embelin induced apoptosis in BRAF wild type thyroid cancer cell. In conclusion, embelin-induced XIAP suppression resulted in an increase of apoptosis via phosphorylation of p38 in BRAF V600E-mutant thyroid cancer cell lines. Regulation of XIAP activity may be potentially useful as a treatment of thyroid cancer, especially in BRAF V600E-mutant thyroid 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 1709. doi:1538-7445.AM2012-1709
Abstract 171: EGCG enhances the therapeutic potential of gemcitabine and CP690550 (Tasocitinib) by inhibiting STAT3 signaling pathway in human pancreatic cancer cells
Authors: Tang Su-Ni , Fu Junsheng , Shankar Sharmila , Srivastava Rakesh K. 
Published: August 2012

Abstract
Signal Transducer and Activator of Transcription 3 (STAT3) is an oncogene, which promotes cell survival, proliferation, motility and progression in cancer cells. Targeting STAT3 signaling may lead to the development of novel therapeutic approaches for human cancers. Here, we examined the effects of epigallocathechin gallate (EGCG) on STAT3 signaling in pancreatic cancer cells, and assessed the therapeutic potential of EGCG with gemcitabine or JAK3 inhibitor CP690550 (Tasocitinib) for the treatment and/or prevention of pancreatic cancer. Cell viability and apoptosis were measured by XTT assay and TUNEL staining, respectively. Gene and protein expressions were measured by qRT-PCR and Western blot analysis, respectively. The results revealed that EGCG inhibited the expression of phospho and total JAK3 and STAT3, STAT3 transcription and activation, and the expression of STAT3-regulated genes, resulting in the inhibition of cell motility, migration and invasion, and the induction of caspase-3 and PARP cleavage. The inhibition of STAT3 enhanced the inhibitory effects of EGCG on cell motility and viability. Additionally, gemcitabine and CP690550 alone inhibited STAT3 target genes and synergized with EGCG to inhibit cell viability and induce apoptosis in pancreatic cancer cells. Overall, these results suggest that EGCG suppresses the growth, invasion and migration of pancreatic cancer cells, and induces apoptosis by interfering with the STAT3 signaling pathway. Moreover, it can be combined with other chemotherapeutic agents like gemcitabine and CP690550 for the treatment and/or prevention of pancreatic 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 171. doi:1538-7445.AM2012-171
Abstract 1716: FGFR1 gene amplification predicts the antitumor response of FGFR inhibitor LY2874455 in human lung cancer cells
Authors: Bi Chen , Zhao Genshi , Baker Jessica A. , Starling James J. , Wu Wenjuan 
Published: August 2012

Abstract
Lung cancer is the leading cause of cancer-related death for both men and women in the world. FGFR receptor tyrosine kinase signaling pathway has been implicated in tumor cell growth, survival, angiogenesis, and metastasis. Activation of the FGFR pathway via FGFR over-expression, and chromosomal amplification and translocation as well as genetic mutation contributes to the tumor progression and the resistance to anti-EGFR and -VEGF treatment in lung cancer. Targeting FGFR pathway is therefore an attractive therapeutic strategy for lung cancer. We have discovered and developed a novel, ATP competitive and orally active small molecule inhibitor of FGFR, LY2874455, currently in clinic development. LY2874455 is a potent inhibitor against four FGFRs, and demonstrates a broad-spectrum of anti-tumor activity in a number of tumor xenograft models. In the current study, we evaluated the anti-tumor activity of LY2874455 in lung tumor cells with or without FGFR1 gene amplification. FGFR1 is known to be amplified in human lung cancer cells NCI-H1581, NCI-H520 and DMS-114, but not in NCI-H460, A549 and NCI-H1299. The mRNA expression levels of FGFR1 are shown to be higher in the FGFR1 amplified cells than those in the FGFR1 non-amplified cells. Consistent with this, the FGFR1 amplified cells exhibited the much more robust b-FGF-induced phosphorylation of FRS2 and ERK, which are also more sensitive to the inhibition by LY2874455 than that in the FGFR1 non-amplified cells. Furthermore, the FGFR1 amplified cells exhibit the better responses to the growth inhibition and apoptosis induction by LY2874455 than those in the FGFR1 non-amplified cells. Therefore, these findings suggest that FGFR1 plays an important role in lung cancer cell growth and survival, and that LY2874455 may provide a promising treatment option for some lung cancer patients whose tumor harbors FGFR1 gene amplification. The in vivo anti-tumor response of LY2874455 is being further investigated in the tumor xenograft models derived from these FGFR1 amplified or non-amplified human lung 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 1716. doi:1538-7445.AM2012-1716
Abstract 172: Utility of retinoid treatment in the reversion of the malignant phenotype of mammary tumors with alterations in the expression of protein kinase C (PKC) isoforms
Authors: Bessone Maria I. Diaz , Berardi Damian E. , Ciriglaino Stefano , Campodonico Paola B. , de Kier Joffe Elisa Bal , Todaro Laura B. , Urtreger Alejandro J. 
Published: August 2012

Abstract
Some of the most promising signaling pathways for breast cancer treatment include the PKC family, involved in proliferation and apoptosis, and the retinoid system mainly involved in differentiation. In this work we have developed a murine model of mammary adenocarcinoma-derived cells (LM3) that overexpress α or ≤ PKC isoforms in order to analyze whether elevated levels of these kinases alter cell sensitivity to retinoid treatment (ATRA). LM3 cells are poorly responsive to ATRA. The overexpression of PKCα induced alterations in LM3 in vitro behavior that could be associated with tumor progression. In this sense, PKCα increased proliferation and motility (wound coverage: 69.3±8.3% vs 41.2±5.1% in control cells p&lt;0.05) of the transfected LM3 cells. Interestingly, at the same time PKCα sensitized LM3 cells to ATRA treatment as evidenced by a significant reduction in both parameters. Upon othotopic inoculation into syngeneic mice LM3-PKCα cells formed tumors with higher growth rate and metastatic potential than LM3-vector cells. In vivo treatment with an ATRA pellet reduced both the local tumor growth and the number of spontaneous lung metastases (Md [Range]: 9 [0-27] vs 55 [20-75] for LM3-PKCα treated or not respectively p&lt;0.05). On the contrary PKC ≤ overexpression did not affect LM3 cells behavior either in vitro or in vivo. LM3 cells response to ATRA was not modulated by PKC∈ either. However, through a RARE-luciferase gene reporter assay, we could determine that the overexpression of PKC∈ increased the activity of the retinoic acid receptors. Our results show that PKCα overexpression induced a more aggressive phenotype but also conferred ATRA sensitivity to mammary tumor cells. On the other side high PKC∈ levels increased the activity of retinoid receptors but did not modulate biological cell responses to retinoids. We believe that the use of retinoids may be beneficial in patients with aggressive breast tumors associated with high PKCα expression levels.
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 172. doi:1538-7445.AM2012-172
Abstract 1722: Prognostic markers in early stage non small-cell lung cancer (NSCLC)
Authors: Romkes Marjorie , Nukui Tomoko , Buch Shama , Pancoska Petr , Herazo-Maya Jose , Kaminski Naftali , Dacic Sanja , Weissfeld Joel L. , Bigbee William L. , Shapiro Steven D. , Siegfried Jill M. 
Published: August 2012

Abstract
Conventional clinical and pathologic risk factors in stage I non small-cell lung cancer (NSCLC) provide limited prognostic information. Novel prognostic biomarkers are needed to identify patients with highest recurrence risk who will receive the greatest absolute risk reduction from adjuvant chemotherapy/radiation. Transcriptome, epigenome, and global genetic variation analyses of resected NSCLC frozen tumor samples (n=81; 29 stage 1A/52 stage 1B) were performed in order to develop an integrated prognostic signature. Only tumors that were resected within 3 months of the first biopsy-proven diagnosis were used to reduce lead time bias in timing of removal of the primary tumor. Here, the association of gene expression with disease free survival (DSF) is described. Whole genome expression data were quantile-normalized using the Illumina GenomeStudio 2011.1 software. Log-transformed data were then processed in Biometric Research Branch (BRB)-Array Tools. Prognostic models were developed with the top ranking genes using the supervised principal component survival algorithm (PCA). Risk group membership was then assigned based on this multivariate model using leave-one-out cross validation and class prediction modeling. Both models adjusted for age, gender and tumor histology. For stage 1A cases, a 113 gene signature selected by fitting a Cox proportional hazard model (Cox) was able to discriminate between poor and good DFS (α=0.001). Upon further analysis using a class prediction algorithm support vector machine (SVM), we identified an 18 gene classifier that predicted outcome SN=0.952, SP=0.571). A 10-fold cross validation ROC curve reported a value of 0.748. For stage 1B cases, the Cox model identified 141 genes (α=0.01), but the SVM prediction algorithm showed reduced SN/SP (0.75/0.25) for a 12 gene classifier, indicative of possible increased heterogeneity among the 1B cases. Nine genes overlapped between the PCA and class prediction model gene signatures. These nine are members of common lung tumorigenesis pathways, i.e. G-protein signaling regulation (KRAS/BRAF/RASSFI); tyrosine protein kinase signaling (EGFR/ERBB2); nucleotide excision repair (ERRC5 and ERCC6) and genes implicated in cell differentiation regulated by miR200B (HGD) or miR338 (TXNRD1), miRNAs independently found to be associated with prognosis in our cohort. These initial results demonstrate that a gene expression profile can distinguish stage I NCSLC tumors and predict prognoses, but require further validation. Supported in part by NIH 5P50 CA090440, P30CA047904, UPMC Institutional Funds.
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 1722. doi:1538-7445.AM2012-1722
Abstract 1724: A gene expression profile test to resolve squamous cell carcinomas of head & neck from squamous cell carcinomas of the lung
Authors: Lal Anita , Panos Rebecca , Marjanovic Mira , Walker Michael , Fuentes Eloisa , Henner W. David , Buturovic Ljubomir , Halks-Miller Meredith 
Published: August 2012

Abstract
The differential diagnosis between squamous cell carcinomas of the head & neck and squamous cell carcinomas of the lung is often unresolved because the histologic appearance of these two tumor types is quite similar. We have developed and validated a gene expression profile test (Pathwork Tissue of Origin Head & Neck Test) that distinguishes head & neck squamous and lung squamous cancers in formalin-fixed, paraffin-embedded (FFPE) specimens using a 2160-gene classification model. The test was validated in a blinded study using a pre-specified algorithm and microarray data files for 76 metastatic, poorly differentiated or undifferentiated FFPE tumor specimens that had either a known head & neck squamous or lung squamous diagnosis. The study met the primary Bayesian statistical endpoint for acceptance. Measures of test performance include overall agreement with the known diagnosis of 82.9% (95% CI, 72.5% to 90.6%), an area under the ROC curve (AUC) of 0.91 and a diagnostics odds ratio (DOR) of 23.6. Head & neck squamous cancers (N=38) gave an agreement with the known diagnosis of 81.6% and lung squamous cancers (N=38) gave an agreement of 84.2%. Reproducibility in test results between three laboratories had a concordance of 91.7%. The Tissue of Origin Head & Neck Test can aid in resolving the important differential diagnostic question for head & neck and squamous cell carcinoma of the lung.
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 1724. doi:1538-7445.AM2012-1724
Abstract 1725: Molecular determinants of Sorafenib sensitivity in renal and non small cell lung - Patient derived tumors engrafted in nude mice
Authors: Vincent Vuaroqueaux , Foucault Frederic , Krumbach Rebekka , Schüler Julia , Amalou Zakia , Metz Thomas , Fiebig Heinz-Herbert 
Published: August 2012

Abstract
Introduction: Sorafenib (Nexavar(®)) is a potent multikinase inhibitor suppressing angiogenesis and promoting cell autophagy. Sorafenib has been shown to be active in a broad range of cancers models and is approved in the clinic for treatment of renal cell carcinoma and hepatocellular carcinoma. Sorafenib was shown to inhibit non small cell lung cancers (NSCLC), however a recent phase III study failed to demonstrate efficacy when given together with carboplatin and paclitaxel. Therefore, the identification of molecular determinants of Sorafenib sensitivity is of particular importance for better selecting NSCLC patients for treatment with this therapy. In the present study we used a large collection of NSCLC and renal cancer patient derived tumor models xenografted in nude mice (PDX) to compare Sorafenib anti-tumor activity in both cancer types and to identify molecular determinants of tumor sensitivity. Material and Methods: Sorafenib was tested in vivo in a panel of 33 different PDX including 8 renal and 25 NSCLC. The drug was given orally at 200 mg/kg/day for 12 days and tumor sensitivity was evaluated by tumor volume inhibition of the test group relative to the vehicle control group (T/C in %). Molecular characterization was done using targeted mutation analysis by Sequenom MassARRAY Oncocarta 3.0, Affymetrix SNP V6.0 array for gene copy number variation and HGU133 plus 2 arrays for transcriptome analysis. Results: The mean % T/C values were 42% in renal and 38% in NSCL PDX. Using a T/C value of 30% as cut-off for sensitivity, tumor response to Sorafenib were observed in 5/8 renal (62%) and in 8/25(32%) NSCL PDX. In NSCLC the response to Sorafenib was 2/5 (40%) in epidermoid, 2/7 (28%) in large cell and 3/13 (23%) in adeno subtypes. The transcriptome analysis revealed differentially expressed transcripts between tumors responding to Sorafenib and those being resistant (student t-test adjusted p&lt;0.05). Gene ontology and pathway analyzes will be presented. In addition, for some of these transcripts, differential expression was associated with gene copy number variations in PDX. None of the specific gene mutations detected by Oncocarta panel. 3 were associated with Sorafenib sensitivity. Conclusion: Sorafenib is a potent tumor inhibitor not only in renal but also in the different NSCL cancer model subtypes. Molecular analysis evidenced differentially expressed transcripts but no gene mutation associated with response to treatment. The relevance of these markers for predicting Sorafenib sensitivity should be confirmed in an independent data set.
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 1725. doi:1538-7445.AM2012-1725
Abstract 1732: DNA methylation profiling defines clinically relevant biological subsets of non-small cell lung cancer
Authors: Walter Kim , Holcomb Thomas , Januario Tom , Du Pan , Hampton Garret M. , Amler Lukas C. , Yauch Robert L. , Bourgon Richard , Shames David S. 
Published: August 2012

Abstract
Purpose: Non-small cell lung cancers (NSCLC) comprise multiple distinct biological groups with different prognoses. For example, patients with epithelial-like (EL) tumors have a better prognosis and exhibit greater sensitivity to inhibitors of the epidermal growth factor receptor (EGFR) pathway than patients with mesenchymal-like (ML) tumors. Here we test the hypothesis that EL NSCLCs can be distinguished from ML NSCLCs on the basis of global DNA methylation patterns. Experimental Design: To determine whether phenotypic subsets of NSCLC can be defined based on their DNA methylation patterns, we combined microfluidics-based gene expression analysis and genome-wide methylation profiling. We derived robust classifiers for both gene expression and methylation in cell lines and tested these classifiers in surgically resected NSCLC tumors. We validate our approach using quantitative RT-PCR and methylation specific PCR in formalin-fixed biopsies from NSCLC patients who went on to fail front-line chemotherapy. Results: We show that patterns of methylation divide NSCLCs into EL and ML subsets as defined by gene expression and that these signatures are similarly correlated in NSCLC cell lines and tumors. We show that DNA methylation differences predict EL or ML phenotypes NSCLC cell lines, surgically resected tumors, and formalin-fixed biopsies from NSCLC patients who went on to fail front-line chemotherapy. Conclusions: Our data demonstrate that patterns of DNA methylation can divide non-small lung cancers into two phenotypically distinct subtypes of tumors and provide proof of principle that differences in DNA methylation can be used as a platform for predictive biomarker discovery and development.
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 1732. doi:1538-7445.AM2012-1732