bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2979: Wolf-Hirschhorn syndrome candidate 1 plays an important role in the pathogenesis of head and neck cancer.
Authors: Saloura Vassiliki , Cho Hyun-Soo , Lingen Mark , Li Terri , Gong Can , Tanguy Seiwert , Cohen Ezra , Hamamoto Ryuji , Nakamura Yusuke 
Published: August 2014

Abstract
Wolf-Hirschhorn syndrome candidate 1 (WHSC1) is a histone lysine methyltransferase (HMT) which was initially found to be deregulated in a subset of multiple myeloma cells with the t(4;14) (p16;q32) translocation and poor prognosis. Recently, our group as well as others found that WHSC1 was overexpressed in a variety of tumors, including lung and esophageal squamous cell carcinomas, with low or no expression in normal tissues except the testis. Long-term survival of patients with squamous cell carcinoma of the head and neck (SCCHN) remains poor and thus new therapeutic strategies are urgently needed. Epigenetic alterations have mainly been studied as a potential mechanism of progression from dysplasia to squamous cell carcinoma. Given the promising potential of HMTs as novel drug targets and the aforementioned interesting expression patterns, we further investigated the role of WHSC1 in carcinogenesis through immunohistochemical analysis (IHC) using tissue microarrays of 123 locoregionally advanced SCCHN patients, and 6 samples of fibroepithelial hyperplasia lesions obtained from oral biopsies. We classified its expression levels with a scoring scale of 0 (no expression), +1 (mild), +2 (moderate) or +3 (strong). WHSC1 expression in the nucleus and cytoplasm was moderate (score +2, 37%) or strong (score +3, 38%) in 75% of SCCHN samples, while 25% showed mild (score +1, 24%) or no (score 0, 1%) expression. WHSC1 staining of normal epithelial regions revealed an exclusively nuclear expression pattern in the basal and parabasal layers. This is consistent with reports suggesting a physiologic role of the Wnt-pathway, which was recently found to be induced by WHSC1, in the differentiation process of the squamous epithelium. We also performed Western blot analysis of WHSC1 in 8 SCCHN cells lines, 3 control fibroblast cell lines and 1 keratinocyte cell line. We observed moderate to strong overexpression of WHSC1 in 4 of 8 SCCHN cell lines, while no expression was detected in the normal keratinocytes or the fibroblast cell lines. These findings support a potential role of the WHSC1 pathway in the pathogenesis of SCCHN and provides a new therapeutic avenue for drug discovery in this fatal disease.
Citation Format: Vassiliki Saloura, Hyun-Soo Cho, Mark Lingen, Terri Li, Can Gong, Seiwert Tanguy, Ezra Cohen, Ryuji Hamamoto, Yusuke Nakamura. Wolf-Hirschhorn syndrome candidate 1 plays an important role in the pathogenesis of head and neck cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2979. doi:10.1158/1538-7445.AM2013-2979
Abstract 2983: Gene resilencing following decitabine therapy is initiated by nucleosome reoccupancy and is related to CpG island shore methylation.
Authors: Patil Vibha , Sloane Mathew A. , Wong Jason Wh , Liu Jia , Ward Robyn L. , Hesson Luke B. 
Published: August 2014

Abstract
Decitabine is a front line therapy for myelogenous leukaemias and is in clinical trials for various solid tumour types. This DNA demethylating agent reactivates genes silenced by promoter hypermethylation in cancer. However upon drug withdrawal reexpressed genes undergo remethylation (resilencing) which may underlie drug resistance and presents a barrier to effective therapy. We aimed to define the ordered sequence of epigenetic events associated with resilencing. Using biallelically methylated MLH1 as a model gene, we profiled epigenetic changes at the MLH1 promoter associated with reexpression and resilencing in a colorectal cancer cell line before, during and after Decitabine treatment. In contrast to the closed chromatin structure observed before treatment, Decitabine induced increased MLH1 expression and 54% decreased promoter methylation. We show that gene resilencing, which occurs 6-8 days following removal of therapy, is not due to promoter remethylation but is initiated by reoccupancy of nucleosomes to demethylated promoter alleles. Furthermore, long-term monitoring of cells following treatment showed MLH1 expression never reverts to pretreatment levels with low-level expression and demethylated promoter alleles persisting up to 118 days after withdrawal of Decitabine. Genome-wide methylation profiling was used to categorise promoter CpG Islands (CGI) based on their degree of demethylation after treatment. This revealed that CGIs with persistence of demethylated promoter alleles after long-term recovery (n=108) showed significantly lower levels of CGI shore methylation (p=0.0231). Our findings suggest a role for shore methylation in susceptibility to CGI remethylation and that therapeutic targeting of nucleosome assembly may provide a novel strategy to prevent gene resilencing.
Citation Format: Vibha Patil, Mathew A. Sloane, Jason Wh Wong, Jia Liu, Robyn L. Ward, Luke B. Hesson. Gene resilencing following decitabine therapy is initiated by nucleosome reoccupancy and is related to CpG island shore methylation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2983. doi:10.1158/1538-7445.AM2013-2983
Abstract 2997: SOX2 contributes towards invasive phenotype of serous ovarian cancer by up-regulating MMP2.
Authors: Mohapatra Gayatry , Kikuchi Junko , Birrer Michael J. 
Published: August 2014

Abstract
SOX2 encodes a member of the SRY-related HMG-box (SOX) family of transcription factors involved in the regulation of embryonic development and in the determination of cell fate. SOX2 maps to 3q26.33, a region frequently amplified in HGSOvCa as reported in the TCGA and other large array-based CGH studies. However, the role of SOX2 in HGSOvCa oncogenesis and progression has not been studied yet. Given the importance of SOX2 in maintenance of stem cell phenotype and its overexpression in solid tumors, we sought to define the role of SOX2 in HGSOvCa.
In order to establish a direct role for SOX2 in vivo, we conducted DNA copy number analysis and qRT-PCR analysis in two independent panels of primary HGSOvCa and 25 serous OVCA lines. We overexpressed SOX2 in T29, OVCA433, A2780, SKOV3 and OVCAR5 cells and/or knockdown SOX2 in UCI101 and OV90 cells. Ectopic expression of SOX2 resulted in decreased cell proliferation, soft agar colony formation, in vivo tumorigenicity but higher degree of invasion relative to cells with empty vectors. SOX2 overexpression increased MMP2 activity as determined by gelatin zymography. We also performed mRNA profiling to identify SOX2 target genes. SOX2 knockdown cells decreased migration,andinvasion but increased tumorigenicity. Differentially expressed genes in cells overexpressing SOX2 will be presented. Increased SOX2 expression in HGSOvCa appears to produce a more invasive yet quiestant cell. Overexpression of SOX2 may induce a stem-like transcriptional program in HGSOvCa. Thus, identifying SOX2 target genes may offer new insight into the understanding of ovarian cancer biology.
Citation Format: Gayatry Mohapatra, Junko Kikuchi, Michael J. Birrer. SOX2 contributes towards invasive phenotype of serous ovarian cancer by up-regulating MMP2. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2997. doi:10.1158/1538-7445.AM2013-2997
Abstract 3000: New epigenetic biomarker for colorectal cancer.
Authors: Takane Kiyoko , Midorikawa Yutaka , Yagi Koichi , Sakai Ayako , Aburatani Hiroyuki , Takayama Tadatoshi , Kaneda Atsuhi 
Published: August 2014

Abstract
DNA is released and circulate in the blood of cancer patients. Epigenetic changes in the levels of circulating DNA has been associated with tumor burden and malignant progression. Public physical examination recommends occult fecal blood test for colorectal cancer (CRC) screening but its false positive rate is too high. As for serum marker for CRC including CEA and CA19-9, their sensitivity are nor satisfactory especially in early stage CRC patients and therefore, the potential use of circulating DNA for CRC screening has emerged. The aim of this study is the clinical utility of cell-free DNA as blood biomarkers. Based on our previous report about the new methylation markers for CRC on a genome-wide scale, we selected 4 methylation markers positive for CRC and established CRC screening panel. First, we collected plasma DNA from blood samples of 100 CRC patients preoperatively and 50 age-matched healthy volunteers. Then, we performed pyrosequence about plasma DNA after bisulfite treatment. Using this cancer screening panel, 82 CRC patients were positive for at least 1 marker. On the other hand, no control samples were positive for any markers and therefore, sensitivity and specificity using this cancer screening panel for CRC were 82.0% and 100%, respectively. According to TNM classification, positive rate for earlier stage including 1 and 2 patients were lower than advanced CRC patients. Similarly, the patients with abnormal serum CEA level harbored higher positive rate for the cancer panel, but serum CA19-9 level which is another CRC marker was not associated with positive rate. Two markers of the panel were relatively high in old age although they were negative for control samples. Considering that no hypermethylation was detected in control samples, this cancer panel is superior to preexisting blood tumor markers for CRC and available for cancer screening.
Citation Format: Kiyoko Takane, Yutaka Midorikawa, Koichi Yagi, Ayako Sakai, Hiroyuki Aburatani, Tadatoshi Takayama, Atsuhi Kaneda. New epigenetic biomarker for colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3000. doi:10.1158/1538-7445.AM2013-3000
Abstract 3013: Elucidating the functional role of microfibril-associated glycoprotein-2 (MAGP-2) in human ovarian cancer.
Authors: Na Young-Jeong , Vathipadiekal Vinod , Wei Wei , Kwok Tim , Birrer Michael 
Published: August 2014

Abstract
Epithelial ovarian cancer, is the most fatal gynecologic cancer, resulting in approximately 15,000 deaths annually in the US. Our understanding of molecular events relating to the patient survival and overall prognosis is not clear. Using transcriptional profiling technology combined with Cox regression analysis in microdissected serous ovarian cancers, we have identified microfibril-associated glycoprotein 2 (MAGP-2) as a strong prognostic factor toward poor patient outcome. Ectopic overexpression of MAGP-2 was employed to evaluate its functional role in ovarian cancer. MAGP-2 overexpression increased cell migration and resistance to cisplatin in vitro. Moreover, the conditioned medium from MAGP-2 overexpression cells promoted endothelial cell motility. In an orthotopic model using luciferase labeled ovarian cancer cells, MAGP-2 overexpression increased the intraperitoneal tumor growth. In addition, the tumor with high MAGP-2 expression showed increased microvessel density. Our results suggest MAGP2 positively modulates the ovarian cancer tumorigenecity and angiogenesis, which may subsequently lead to poor patient survival.
Citation Format: Young-Jeong Na, Vinod Vathipadiekal, Wei Wei, Tim Kwok, Michael Birrer. Elucidating the functional role of microfibril-associated glycoprotein-2 (MAGP-2) in human ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3013. doi:10.1158/1538-7445.AM2013-3013
Abstract 3025: Receptor tyrosine kinase ErbB2/HER2 translocates into mitochondria and regulates cellular metabolism.
Authors: Ding Yan , Liu Zixing , Desai Shruti , Pannell Lewis , Yi Hong , Wright Elizabath , Owen Laurie , Dean-Colomb Windy , Fodstad Oystein , Lu Jianrong , Tan Ming 
Published: August 2014

Abstract
It is well accepted that ErbB2, an important oncoprotein, localizes on the plasma membrane as a receptor tyrosine kinase. This study describes a novel observation that ErbB2 localizes in mitochondria of multiple cancer cell lines and patient samples.
We identified an endogenous mitochondrial targeting sequence in ErbB2 and found that ErbB2 translocates into mitochondria through the association with mtHSP70, a key player in the canonical mitochondrial protein importation pathway. Additionally, we observed that mitochondrial ErbB2 (mtErbB2) negatively regulates mitochondrial respiratory functions. Oxygen consumption and activities of complex I, II and IV of the mitochondrial electron transport chain were decreased in mtErbB2-overexpressing cells. Mitochondrial membrane potential and the cellular ATP level also were decreased by mtErbB2. In contrast, mtErbB2 enhanced cellular glycolysis. The translocation of ErbB2 and its impact on mitochondrial function are kinase dependent. Mitochondrial ErbB2 regulates the phosphorylation and activity of COX II and consequently the cytochrome c release and apoptosis. Additional studies showed that cancer cells with higher levels of mtErbB2 were more resistant to Trastuzumab and deletion of the mitochondrial targeting sequence of ErbB2 sensitized the cells to Trastuzumab.
Our study provides a novel perspective on the metabolic regulatory functions of ErbB2 and reveals that mtErbB2 plays an important role in the regulation of cellular metabolism and cancer cell resistance to therapeutics. Since ErbB2 plays important roles in multiple organs and multiple types of cancers, the study may have broad impact on the fields of cancer biology.
The work was supported by The Vincent F. Kilborn Jr. Cancer Research Foundation and National Institutes of Health Grant RO1CA149646.
Citation Format: Yan Ding, Zixing Liu, Shruti Desai, Lewis Pannell, Hong Yi, Elizabath Wright, Laurie Owen, Windy Dean-Colomb, Oystein Fodstad, Jianrong Lu, Ming Tan. Receptor tyrosine kinase ErbB2/HER2 translocates into mitochondria and regulates cellular metabolism. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3025. doi:10.1158/1538-7445.AM2013-3025
Abstract 3027: A novel function of EGFR in epigenetic modulation via hMOF in breast cancer .
Authors: Lim Seung-Oe , Li Chia-Wei , Chang Shih-Shin , Shen Jia , Hung Mien-Chie 
Published: August 2014

Abstract
The epidermal growth factor receptor (EGFR) is aberrantly active in breast cancer, initiates and drives tumorigenic pathways, and has been implicated in multiple tumorigenic processes including hyperplasia, chemo-resistance and metastasis. Histone lysine modifications directly influence activation and repression of transcription. MYST family acetyltransferase, human males absent on the first (hMOF), plays an important role in transcription activity through histone H4K16 acetylation. Loss of hMOF and subsequently the absence of H4K16 acetylation have been shown to be a common feature in human cancer including breast cancer. However, the regulation of hMOF remains largely unknown. Recently, we have discovered the acetylation of EGFR in human breast cancer cells. Thus, we screened a set of EGFR-interacting acetyltransferases using co-immunoprecipitation analysis and ingenuity pathway analysis (IPA). Here, we found that EGFR directly interacts with and phosphorylates hMOF. EGFR-induced phosphorylation hMOF was significantly reduced in the hMOF YF mutant. Indeed, hMOF YF mutant showed a higher histone acetyltransferase (HAT) activity compare to wild type hMOF. In addition, tyrosine kinase inhibitor (TKI) also enhanced the HAT activity of wild type hMOF. Furthermore, we found that EGFR modulates acetylation status of histone H4K16 via phosphorylating hMOF. We anticipate our study of EGFR and hMOF to be of therapeutic relevance, possibly leading to novel discovery in drug development targeting the receptor tyrosine kinase and the acetylation process.
Citation Format: Seung-Oe Lim, Chia-Wei Li, Shih-Shin Chang, Jia Shen, Mien-Chie Hung. A novel function of EGFR in epigenetic modulation via hMOF in breast cancer . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3027. doi:10.1158/1538-7445.AM2013-3027
Abstract 303: A tissue microarray-based study of the basal cell in canine prostatic hyperplastic, pre-neoplastic and neoplastic lesions.
Authors: Amorim Renée Laufer , Fonseca-Alves Carlos Eduardo , Rodrigues Marcela M p , Rogatto Silvia Regina 
Published: August 2014

Abstract
It has been stated that dog is the best natural model to study carcinogenesis in comparison with men. In addition, the loss of the basal cell layer integrity is one of the main characteristics in human pre-neoplastic and neoplastic prostatic lesions. In human normal prostate, the basal cells selectively express p63 in their nuclei, demonstrating basal cell layer integrity. However, in both primary and metastatic prostate carcinomas, has been described absence of p63 immunoexpression. This study aimed to evaluate the involvement of basal cells (p63 and 34βE12) and proliferative index (ki-67) in prostatic pre-neoplastic and neoplastic lesions from dogs. A tissue microarray (TMA) was constructed using 66 canine prostatic paraffin-embedded lesions, selecting appropriate and representative areas of normal tissue (n=7), benign prostatic hyperplasia (BPH, n= 18), prostatic inflammatory atrophy (PIA, n=22) and prostatic carcinoma (PCa, n=19). Immunohistochemistry was performed using peroxidase method and DAB. The immunohistochemical staining was assessed by scores according the distribution of positive cells for p63 and 34βE12 (score 1: &lt;25% cells positive, 2: 26% to 50%, 3: being 51% and 75% and 4:&gt; 75%) and for Ki67, positive nuclei were counted in each lesion. Chi-square or Fisher exact test was used to determine the association between the categorical variables and student t test to compare proliferative index among lesions. Concerning the p63 protein, we found higher number of cases with more than 75% of positive basal cells in CaP (p=0.002) and PIA (p= 0.0042) when compared to normal tissue and BPH. CaP and PIA showed 34βE12 protein expression when compared to normal prostatic tissue and BPH (p= 0.032, p=0.0064). There was no statistically significant difference in the comparison between PIA and BPH. Ki67 showed higher proliferative index in PCa (p= 0.0028) and PIA (p= 0.01) compared to normal tissue and BPH. Higher p63 and 34βE12 immunohistochemical staining as well as higher proliferative index in these cells were observed in canine pre-neoplastic lesion (PIA) and prostate carcinoma indicate the involvement of basal cells in these lesions in dogs, different from humans. These results do not support the dog as the best natural model to the study of all types of prostatic carcinomas in men.
Financial support: Fapesp
Citation Format: Renée Laufer Amorim, Carlos Eduardo Fonseca-Alves, Marcela M p Rodrigues, Silvia Regina Rogatto. A tissue microarray-based study of the basal cell in canine prostatic hyperplastic, pre-neoplastic and neoplastic lesions. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 303. doi:10.1158/1538-7445.AM2013-303
Abstract 3038: Epithelial Membrane Protein-2 (EMP2) promotes glioblastoma growth via upregulating invasion and angiogenesis.
Authors: Qin Yu 
Published: August 2014

Abstract
Recent data suggests that EMP2 is a novel oncogene in a number of tumors including breast, ovarian, endometrial and primary central nervous system malignancies. Its expression correlates with poor survival and can serve as a prognostic indicator in many tumors. Glioblastoma multiforme (GBM) is an aggressive brain tumor with a medium survival of 18 months, and we have found that EMP2 is expressed in the majority of GBM tumors but not in healthy brains. In order to therapeutically exploit the expression of EMP2 on these tumors, we have developed recombinant antibodies to this oncogene. In experimental models, use of the anti-EMP2 antibodies showed profound efficacy in reducing GBM tumor load. We further dissected the underlying molecular mechanisms and found that EMP2 accelerated GBM tumor growth through increasing αvβ3 integrin surface expression in GBM cells, activating downstream FAK and Src kinases and promoting cell migration and invasion. Furthermore, EMP2 upregulated vascular endothelial growth factor (VEGF) in several GBM cell lines. This increase appeared to be functionally relevant as conditioned medium from GBM cells with forced overexpression of EMP2 increased human umbilical vein endothelial cell (HUVEC) migration and capillary tube formation, suggesting a role for EMP2 in the regulation of tumor angiogenesis. Our results suggest the importance of this oncogene in the control of the tumor microenvironment and that targeting EMP2 expression may be a novel therapy for GBM.
Citation Format: Yu Qin. Epithelial Membrane Protein-2 (EMP2) promotes glioblastoma growth via upregulating invasion and angiogenesis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3038. doi:10.1158/1538-7445.AM2013-3038