bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1532: Exome and transcriptome profiling of lung adenocarcinoma in female never-smokers
Authors: Lee Sanghyuk , Kim Pora , Jun Yukyung , Park Charny , Kim Suyeon , Lee Hee-Young , Keum Juhee , Jung Yeonhwa , Jung Yeonjoo , Seo Chaehwa , Rho Kyoohyoung , Lee Jong-Eun , Kim Wankyu , Kim Jaesang , Kim Jhingook 
Published: May 2015

Abstract
Background: Lung cancer is the leading cause of cancer-related mortality in the world. TCGA projects for lung adenocarcinoma and squamous cell carcinoma are the largest datasets publicly available so far. They include diverse subtypes and population groups and thus small population groups such as female never-smokers in Asian are under-represented. Female never-smokers are an important population cohort where mutations due to genetic factors are enriched rather than environmental factors such as smoking. We applied the high throughput deep sequencing strategy to catalog somatic mutations and to profile gene expression levels for Korean patients.
Results: Deep sequencing data of exome and transcriptome were generated for tumor and matched normal tissues from 100 non-small-cell lung cancer (NSCLC) patients in female never-smokers. The mutational catalogue includes numerous somatic mutations, indels, and gene-fusion events. Comparison with TCGA lung cancer data shows that our patients harbor much less and homogeneous somatic mutations as expected. Mutational frequency and driver gene analyses identified many novel candidates of causal genetic variations. For example, our mutation spectrum reveals 5 key modules of enriched somatic mutations such as EGFR, p53, Wnt signaling pathways, ECM organization, and cell cycle checkpoints. Furthermore, network analysis of integrating mutation and expression data illustrates the detailed mechanism of dysregulation in tumorigenesis of lung adenocarcinoma.
Conclusion: Our study elucidates clinically important mutations and regulatory elements in NSCLC. It is expected that our dataset would serve as an important resource for lung cancer research especially in Asian populations.
Citation Format: Sanghyuk Lee, Pora Kim, Yukyung Jun, Charny Park, Suyeon Kim, Hee-Young Lee, Juhee Keum, Yeonhwa Jung, Yeonjoo Jung, Chaehwa Seo, Kyoohyoung Rho, Jong-Eun Lee, Wankyu Kim, Jaesang Kim, Jhingook Kim. Exome and transcriptome profiling of lung adenocarcinoma in female never-smokers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1532. doi:10.1158/1538-7445.AM2014-1532
Abstract 1543: Systematic functional assessment of driver mutations for individual ovarian cancers
Authors: Mori Seiichi , Yokomizo Takako , Fujiwara Takeshi , Goto Osamu , Iwase Haruko , Kato Kazuyoshi , Kawaguchi Tokuichi , Noda Tetsuo 
Published: May 2015

Abstract
Although epithelial ovarian cancer is an intractable cancer and the overall five-year survival rate is approximately 40 to 50%, clinically effective molecular-targeted therapeutics to treat ovarian cancer has not been available thus far. Recent progress of massively parallel sequencing technologies has been enabling us to identify substantial number of genomic aberrations including somatic mutations, indels and translocations in variable cancer types exemplified by epithelial ovarian cancer and non-small cell lung cancer. However, it is still very difficult to identify a ‘driver’ gene, which is functionally relevant for cancer growth, from hundreds of mutations that are usually found from a single cancer sample of an individual patient. An in vitro cultured cell line, which is originated from a clinical sample, can be utilized to assess functions of the genes that are identified to have somatic aberrations in the paired clinical tumor. We have been establishing multiple ovarian cancer cell lines derived from clinical samples and analyzing pairs of the cell lines and clinical samples with exon-capture sequencing. The genes, which are somatically mutated and shared in a pair of cell line and clinical sample, are targeted with RNA interference in the cell line, and subsequently the effect on cell proliferation and survival is examined. As such, a driver mutation for an individual cancer can be identified by a set of experimental perturbations. Identified driver mutations would be then validated with publicly available databases and with clinical archive samples. As a proof-of-principle, somatic mutations of PIK3CA and KRAS were detected as drivers to promote cell proliferation of a carcinosarcoma. We believe this approach can increase an opportunity to identify molecular targets in ovarian cancer therapeutics.
Citation Format: Seiichi Mori, Takako Yokomizo, Takeshi Fujiwara, Osamu Goto, Haruko Iwase, Kazuyoshi Kato, Tokuichi Kawaguchi, Tetsuo Noda. Systematic functional assessment of driver mutations for individual ovarian cancers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1543. doi:10.1158/1538-7445.AM2014-1543
Abstract 1546: The research of the mechanism of lung cancer carcinogenesis and the target gene of microRNA-20a in lung cancer small cells
Authors: Xiaogang Tan , Mu Hu , Xiuyi Zhi , Shimeng Jin 
Published: May 2015

Abstract
Purpose: Recent studies have suggested that microRNA biomarkers could be useful for stratifying lung cancer subtypes, but microRNA signatures varied between different populations. Small cell lung cancer (SCLC) is the lowest differentiation degree and the highest malignant subtype of lung cancer that urgently needs biomarkers to aid patient management. Here, we undertook the first comprehensive investigation on microRNA in Chinese SCLC patients of limited stage.
Experimental Design: MicroRNA expression was measured in cancerous and noncancerous tissue pairs strictly collected from Chinese SCLC patients of limited stage, who had not been treated with chemotherapy or radiotherapy prior to surgery. The molecular targets of proposed microRNA were further examined.
Results: We identified that high expression of hsa-miR-20a was associated with poor survival in these 20 SCLC patients by Kaplan-Meier analysis (P=0.03), This association was independently validated in a separate cohort of 38 SCLC patients in Kaplan-Meier analysis(P=0.046). We then determined that the tumor suppressor PTEN is a target of hsa-miR-20a. Expression of hsa-miR-20a in a human lung cancer cell line repressed PTEN activity.
Conclusions: Our results identified a new prognostic biomarker of SCLC, hsa-miR-20a.
Note: This abstract was not presented at the meeting.
Citation Format: Tan Xiaogang, Hu Mu, Zhi Xiuyi, Jin Shimeng. The research of the mechanism of lung cancer carcinogenesis and the target gene of microRNA-20a in lung cancer small cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1546. doi:10.1158/1538-7445.AM2014-1546
Abstract 1548: Genomic and molecular profiling of NSCLC formalin-fixed paraffin-embedded tumors
Authors: Gaffney Dana S. , Bell Katherine , Martinez Gabriela , Rajpurohit Yashoda , Karkera Jayaprakash , Moy Christopher , Platero Suso 
Published: May 2015

Abstract
Non-Small Cell Lung Cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85% of all lung cancers worldwide. Standard therapy options include surgical resection followed by radiation and/or chemotherapy. More recently, analysis of the genomic profile of NSCLC has led to the development of molecularly targeted treatment strategies designed to enhance survival of select subsets of patients containing pre-determined genetic alterations, including gene mutations and aberrant gene expression profiles. In this study, we have developed a TaqMan-based approach to evaluate the genomic profile of 339 NSCLC FFPE tumors, consisting of 152 adenocarcinoma and 187 squamous cell carcinoma (SCC), stages I-IV. Using a custom qRT-PCR somatic mutation array, we have identified the frequencies of key mutations prevalent in NSCLC- associated genes, including EGFR: 5% SCC , 29% adenocarcinoma, cMET: 6% SCC, 4% adenocarcinoma, and KRAS: 3% SCC, 19% adenocarcinoma. Overall, these frequencies are concordant with previous reports. Additionally, we have evaluated the gene expression and IHC profiles of NSCLC-driver signaling pathways including EGFR, cMET and HGF. Various levels of expression for EGFR, cMET and HGF were observed across all samples, with a significant association detected between the presence of EGFR mutation and high EGFR expression in adenocarcinoma (p value = 0.0046). Overall, our findings represent a comprehensive catalog of common genetic aberrations with concurrent gene and protein expression profiles in NSCLC. Furthermore, this data provides insight into correlations observed across these molecular characteristics contributing to NSCLC tumor development. These insights can provide guidance for patient stratification and novel therapeutic strategies for select targeted therapies in NSCLC.
Citation Format: Dana S. Gaffney, Katherine Bell, Gabriela Martinez, Yashoda Rajpurohit, Jayaprakash Karkera, Christopher Moy, Suso Platero. Genomic and molecular profiling of NSCLC formalin-fixed paraffin-embedded tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1548. doi:10.1158/1538-7445.AM2014-1548
Abstract 155: Expressions of autophagy-related proteins positively correlate with infiltration of immune cells and disease progression in oral squamous cell carcinoma
Authors: Sakakura Koichi , Takahashi Hideyuki , Kaira Kyoichi , Toyoda Minoru , Oyama Tetsunari , Chikamatsu Kazuaki 
Published: May 2015

Abstract
Introduction: Autophagy is an endogenous process that degrades bulk proteins and organelles to maintain energy homeostasis under cellular stress and nutrient starvation. It has been still unclear whether autophagy promotes or suppresses tumor progression in various cancer patients. To date, several studies have shown that autophagy-related molecules such as LC3 and Beclin-1 play important roles in tumor progression; however, few studies regarding immunological significance of these autophagy components in tumor microenvironment exist. The objective of this study is to clarify association between the expression of autophagy-related proteins and immune infiltrates by immunohistochemistry (IHC).
Patients and methods: Expression of two representative autophagy-associated molecules, LC3 and Beclin-1, and CD1a (dendritic cell), CD3 (T cell) and CD56 (NK cell) cells were examined by IHC in 74 patients with oral squamous cell carcinoma (OSCC). HLA class I heavy chain, HLA class II, Ki-67 and p53 were also stained and assessed. Two regions, central site and peripheral site in tumor tissues were evaluated, separately. Moreover, the association with various clinicopathological parameters including progression free and overall survival was evaluated.
Results: LC3 and Beclin-1 were accumulated in both 27 of 74 cases (36.5%) OCCC examined. LC3 expression in peripheral margin was significantly associated with increasing dendritic cell (DC) and T cell infiltration. Interestingly, peripheral Beclin-1 expression showed statistically significant relation to increasing HLA class II expression on tumor cells. On the other hand, LC3 and Beclin-1 significantly correlates with several unfavorable clinicopathological parameters including short overall survival. In addition, LC3 and Beclin-1 expression in OSCC significantly related to lymphatic invasion by tumor cells.
Conclusion: Significant association between LC3 and DC/T cell infiltration suggests that autophagy is likely to actively participate in immunological phenomena within tumor microenvironment. Furthermore, peripheral Beclin-1 may contribute to antigen presentation by tumor cells, while these two autophagy components also relates to unfavorable prognosis. Taken together, autophagy seems to promote immunogenicity of cancer cells, whereas it facilitates tumor progression.
Citation Format: Koichi Sakakura, Hideyuki Takahashi, Kyoichi Kaira, Minoru Toyoda, Tetsunari Oyama, Kazuaki Chikamatsu. Expressions of autophagy-related proteins positively correlate with infiltration of immune cells and disease progression in oral squamous cell carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 155. doi:10.1158/1538-7445.AM2014-155
Abstract 1552: CCN5/wisp-2 induced growth arrest of aggressive triple negative breast cancer cells is promoted through accumulation and trafficking of p27kip1
Authors: Haque Inamul , Banerjee Snigdha , De Archana , Maity Gargi , Sarkar Sandipto , McGragor Douglas , Banerjee Sushanta K. 
Published: May 2015

Abstract
CCN5, a matricellular protein, represents promising treatment target in triple negative breast cancer (TNBC) as treatment or induced activation of CCN5 in TNBC cells promotes cell growth arrest at G0/G1 phase, reduces cell proliferation and delays tumor growth in xenograft model. Our studies found that p27Kip1 tumor suppressor protein is upregulated and relocalized to the nucleus from cytoplasm by CCN5 in these cells and that these two events (i.e., upregulation and relocalization) of p27Kip1 is required for CCN5-induced growth inhibition of TNBC cells. In the absence of CCN5, p27Kip1 remains mostly in the cytoplasm, a state of aggressive nature of cancer cells. Mechanistically, CCN5 inhibits Skp2 expression, which seems to stabilize p27Kip1 protein in these cells. On the other hand, CCN5 also recruits FOXO3a to mediate transcriptional regulation of p27Kip1. The recruitment of FOXO3a is achieved by the induction of its expression and activity through shifting from cytoplasm to the nucleus. Our data indicate that CCN5 blocks PI3K/AKT signaling to dephosphorylate at S318, S253 and Thr32 in FOXO3a for nuclear relocalization and activation of FOXO3a. Inhibition of α6β1 diminishes CCN5 action on p27Kip1 in TNBC cells. Collectively, CCN5 may have therapeutic potential for TNBC.
Citation Format: Inamul Haque, Snigdha Banerjee, Archana De, Gargi Maity, Sandipto Sarkar, Douglas McGragor, Sushanta K. Banerjee. CCN5/wisp-2 induced growth arrest of aggressive triple negative breast cancer cells is promoted through accumulation and trafficking of p27kip1 . [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1552. doi:10.1158/1538-7445.AM2014-1552
Abstract 1553: Rho guanine nucleotide exchange factor (ARHGEF) 10 is a putative tumor suppressor in pancreatic ductal adenocarcinoma
Authors: Joseph Joella , Radulovich Nikolina , Tsao Ming-Sound 
Published: May 2015

Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) accounts for over 90% of pancreatic malignancies, and is the fourth leading cause of cancer related deaths. Disease prognosis is quite poor, with less than 20% of patients eligible for curative surgical resection at time of diagnosis and overall survival rates of 2%. PDAC arises from the malignant transformation of ductal epithelial cells through progressive accumulation of loss of function mutations and deletions of tumor suppressor genes. Chromosome 8p has been shown to be a recurrent site of deletions in PDAC. Among the deleted genes is the Rho guanine nucleotide exchange factor 10 (ARHGEF10), a regulator of Rho signaling that is involved in mitotic spindle formation. Here, we evaluate ARHGEF10 for its potential role as a tumor suppressor in PDAC.
Methods: ARHGEF10 expression was assessed in 19 PDAC cell lines and in 53 patient tumor xenograft samples at both mRNA and protein levels. Publically available datasets were also used to determine correlation between ARHGEF10 mRNA expression and DNA copy number. After identifying PDAC cell lines with low ARHGEF10 expression, ARGHEF10 was stably overexpressed in these cell lines by lentiviral transduction. The effects of ARHGEF10 expression were then evaluated by in vivo tumorigenicity in immunodeficient mice, and by in vitro cell proliferation and cell motility wound healing assays.
Results: ARHGEF10 showed reduced expression in up to 70% of cell lines and patient tumor xenografts. Reduced ARHGEF10 expression correlated significantly with loss of copy number in PDAC cell lines. Stable overexpression of ARHGEF10 in PDAC cell lines significantly reduced tumor growth in immunodeficient mice. In addition, ARHGEF10 expression resulted in decreased cell motility in wound healing assays, but had minimal effect on cell proliferation. Experiments for in vitro assessment of invasion and changes in Rho activity are ongoing, and will be presented
Conclusions: This study suggests that ARHGEF10 may function as a tumor suppressor gene in PDAC.
Citation Format: Joella Joseph, Nikolina Radulovich, Ming-Sound Tsao. Rho guanine nucleotide exchange factor (ARHGEF) 10 is a putative tumor suppressor in pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1553. doi:10.1158/1538-7445.AM2014-1553
Abstract 1556: Regulation of cellular apoptosis via a novel protein-protein interaction of tumor suppressor p53 with the xenobiotic pregnane X receptor (PXR) in colon cancer cells
Authors: Robbins Delira F. , Wu Jing , Chen Taosheng 
Published: May 2015

Abstract
The cellular response to DNA damage comprises of DNA repair, cell-cycle checkpoint control and DNA damage-induced apoptosis to promote genomic integrity and suppress tumorigenesis. However, cancer cells can modulate the DNA damage response by suppressing DNA repair, altering cell cycle checkpoint control and ultimately downregulating tumor suppressors that contribute to apoptosis promoting genomic instability and avoidance of apoptosis.
Although PXR is well established as a xenobiotic nuclear receptor that plays a central role in xenobiotic metabolism and disposition, emerging evidence suggest PXR as a regulator of apoptosis, promoting a malignant phenotype, both in vitro and in vivo. The tumor suppressor p53 can be activated in the presence of DNA damage and can induce cell cycle arrest to allow for DNA repair, or ultimately apoptosis suppressing tumor formation. We hypothesized that the novel protein-protein interaction between PXR and p53 contributes to the oncogenic functions of PXR enhancing colon carcinogenesis. Using immunoprecipitation, we found that PXR forms a protein-protein interaction with p53, resulting in reduced p53 activation and expression of downstream pro-apoptotic genes. In addition, utilizing the soft agar assay, we found that PXR overexpression leads to increased malignant transformation in colon cancer cells. Our findings show for the first time that PXR can physically bind to p53, resulting in downregulation of p53 activity and increased malignant transformation in colon cancer cells. Thus, these results provide insight into the biological significance of novel protein-protein interactions with PXR and how the PXR-p53 protein-protein interaction influences p53-mediated mechanism of tumor suppression.
Citation Format: Delira F. Robbins, Jing Wu, Taosheng Chen. Regulation of cellular apoptosis via a novel protein-protein interaction of tumor suppressor p53 with the xenobiotic pregnane X receptor (PXR) in colon cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1556. doi:10.1158/1538-7445.AM2014-1556
Abstract 1568: Cellular mechanisms of tumor regression following Myc inhibition
Authors: Lu Dan , Burkhart Deborah L. , Griffin Julian L. , Littlewood Trevor D. , Evan Gerard I. 
Published: May 2015

Abstract
Myc is a pleiotropic transcription factor associated with various aspects of cell growth. Tumor cells often have deregulated Myc expression, which consequently promotes uncontrolled proliferation. Recent work in our lab using a mouse model of lung cancer has demonstrated that expression of a dominant negative form of Myc causes tumor regression whilst having mild and reversible effects on normal proliferating tissues. However the cellular mechanism of how Myc inhibition leads to tumor regression is not known. Here we show that Myc inhibition causes metabolic changes in tumor cells associated with a reduced proliferative/biosynthetic state. Furthermore, we demonstrate that Myc inhibition leads to p21 expression independently of p53 and may account for tumor cell cycle arrest.
Citation Format: Dan Lu, Deborah L. Burkhart, Julian L. Griffin, Trevor D. Littlewood, Gerard I. Evan. Cellular mechanisms of tumor regression following Myc inhibition. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1568. doi:10.1158/1538-7445.AM2014-1568
Abstract 1569: The nuclear export signal (NES) within CALM is necessary for CALM-AF10-induced leukemia
Authors: Suzuki Mai , Yamagata Kazutsune , Aikawa Yukiko , Watanabe Toshio , Kitabayashi Issay 
Published: May 2015

Abstract
The CALM-AF10 fusion gene, which results from a t(10;11) translocation, is found in a variety of hematopoietic malignancies. Certain HOXA cluster genes and MEIS1 genes are upregulated in patients and mouse models that express CALM-AF10. Wild-type CALM primarily localizes in a diffuse pattern within the cytoplasm, whereas AF10 localizes in the nucleus; however, it is not clear where CALM-AF10 acts to induce leukemia. To investigate the influence of localization on leukemogenesis involving CALM-AF10, we determined the nuclear export signal (NES) within CALM that is necessary and sufficient for cytoplasmic localization of CALM-AF10. Mutations in the NES eliminated the capacity of CALM-AF10 to immortalize murine bone-marrow cells in vitro and to promote development of acute myeloid leukemia in mouse models. Furthermore, a fusion of AF10 with the minimal NES could immortalize bone-marrow cells and induce leukemia in mice. These results suggest that during leukemogenesis, CALM-AF10 plays its critical roles in the cytoplasm.
Citation Format: Mai Suzuki, Kazutsune Yamagata, Yukiko Aikawa, Toshio Watanabe, Issay Kitabayashi. The nuclear export signal (NES) within CALM is necessary for CALM-AF10-induced leukemia. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1569. doi:10.1158/1538-7445.AM2014-1569