bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2533: Sox2 promotes cell proliferation of esophageal squamous cell carcinoma through the miR-17-92 cluster ,PTEN,AKT,mTORC1 pathway
Authors: Terasaki Kei 
Published: July 2017

Abstract
SOX2, a member of the SOX family of transcription factors, play an important role of differentiation and morphogenesis of the esophagus. We previously revealed that SOX2 is the target of gene amplification at 3q26 in esophageal squamous cell carcinoma (ESCC) (Cancer Genet Cytogenet. 2010), and that SOX2 promotes ESCC cell proliferation in vitro and in vivo through the activation of the AKT/mTORC1 signaling pathway (Cancer Sci. 2013). However, the mechanisms by which SOX2 promotes AKT/mTORC1 signaling remain unknown. It is known that PTEN is a negative regulator of AKT and the PTEN gene is a target of the miR-17-92 cluster. In the present study, we showed that SOX2 up-regulated the expression of miR-17-92 cluster and repressed PTEN expression using RNA interference (RNAi)-mediated knockdown of SOX2 and enforced expression of SOX2. In summary, SOX2 promotes cell proliferation of ESCC through the miR-17-92 cluster /PTEN/AKT/mTORC1 pathway.
Citation Format: Kei Terasaki. Sox2 promotes cell proliferation of esophageal squamous cell carcinoma through the miR-17-92 cluster ,PTEN,AKT,mTORC1 pathway [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2533. doi:10.1158/1538-7445.AM2017-2533
Abstract 2534: miRNA expression as potential biomarker for synovial sarcoma
Authors: Pazzaglia Laura , Pollino Serena , Vitale Mattia , Conti Amalia , Picci Piero , Benassi Maria Serena 
Published: July 2017

Abstract
Synovial sarcoma (SS) is a rare tumor, with dismal survival when metastatic. SS contains a characteristic translocation (X;18)(p11;q11), representing the fusion of SYT on chromosome 18 with either SSX1, SSX2, or rarely SSX4 on chromosome X The resulting fusion genes appear to be mutually exclusive and concordant in primary and metastatic tumours. New prognostic and predictive factors are needed. Chemokine receptor 4 (CXCR4) is a seven-transmembrane G protein-coupled chemokine receptor and it is the chemokine receptor most commonly expressed in tumour cells, involved in cell migration and invasion, as well as angiogenesis. microRNAs (miRNAs) are involved in post-transcriptional gene expression regulation and control important physiological processes like development, cell differentiation and cell signaling. Altered expression of miRNAs is strongly correlated with the malignant phenotype and there is data reporting a strong association between microRNA expression, patient age and STS prognosis. By three different databases (miRBase, TargetScan , miRanda) and by literature data we identified two miRNA regulators of CXCR4, miR-133b and miR-494. The expression of these miRNAs was evaluated by RT-PCR in 42 SS primary samples stored at Rizzoli biobank. 20 tissues from non oncologic patients were used as control. Our results showed a significant lower expression of miR-133b and miR-494 (respectively p=0.0005 and p=0.001) when compared to non tumor tissue. In vitro study on SW982 cell line with miR-133b precursor show a CXCR4 downregulation and a decrease of cell proliferation. Our preliminary data confirmed a miR-133b and miR-494 downregulation in SS. Correlation with clinical data, with CXCR4 expression and in vitro studies also with miR-494 in several SS cell lines are on-going to better investigate their role as potential prognostic and therapeutic markers.
Citation Format: Laura Pazzaglia, Serena Pollino, Mattia Vitale, Amalia Conti, Piero Picci, Maria Serena Benassi. miRNA expression as potential biomarker for synovial sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2534. doi:10.1158/1538-7445.AM2017-2534
Abstract 2536: miR-187-5p and miR-219a-1-3p: potential biomarkers associated with chemotherapeutic response and prognosis in ovarian cancer
Authors: Huang Chia-Yen , Huang Hsien-Da 
Published: July 2017

Abstract
Background: Epithelial ovarian cancer (EOC) is the fifth-most common cause of female cancer death and is associated with high recurrence and mortality despite recent advancements in therapeutic strategies. Chemoresistance remains the main cause of treatment failure in EOC patients. The aim of this study is to identify specific miRNA markers closely associated with the chemoresponse in EOC patients.
Methods: We analyzed 374 serous ovarian cancer patients who receiving combination chemotherapy from The Cancer Genome Atlas (TCGA) and identified the most significantly altered miRNAs between different groups patients of chemotherapy response. We then used Kaplan-Meier and log-rank methods to analyze the relationship between these miRNAs and progression-free and overall survival in TCGA (n = 460) and Bagnoli (n = 130) datasets. In vitro study for response to chemotherapy agents were performed in human ovarian cancer cell lines and their transfectants. The biological relevance of putative miRNA targets was also analyzed using bioinformatics.
Results: MiR-187-5p and miR-219a-1-3p were associated with better response to chemotherapy and longer progression-free and overall survival in two independent epithelial ovarian cancer patient cohorts (all p &lt;0.05). These two miRNAs also sensitized ovarian cancer cells to chemotherapy, thus recapitulating the clinical observation.
Conclusions: This study showed that miR-187-5p and miR-219a-1-3p could be useful biomarker for prediction of chemotherapy response and survival in serous ovarian cancers. MiR-187-5p and miR-219a-1-3p may be potential molecules in the treatment of EOC for sensitizing cancer cells to chemotherapy.
Citation Format: Chia-Yen Huang, Hsien-Da Huang. miR-187-5p and miR-219a-1-3p: potential biomarkers associated with chemotherapeutic response and prognosis in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2536. doi:10.1158/1538-7445.AM2017-2536
Abstract 2537: MicroRNA targeting anti-apoptotic and G2/M pathways as therapeutic targets for castration resistant prostate cancer
Authors: Tarapore Pheruza , To Sarah , Ouyang Bin , Leung Yuet-Kin , Cheong Ana , Ho Shuk-mei 
Published: July 2017

Abstract
Prostate cancer (PC) is one of the most common cancers in men. Unfortunately, limited treatment options currently exist for those who have developed advanced castration-resistant PC (CRPC). G-1 is a GPER1/GPR30 agonist, and a promising candidate for CRPC therapy. G-1 is effective in halting the growth of CR tumors but not those grown in intact hosts. These findings suggest GPER1 is a therapeutic target for CRPC. We found that G-1, through activation of GPER1, inhibited growth of CRPC cells via cell-cycle arrest at the G2-M phase, probably leading to mitotic catastrophy. However, the exact mode of action of G-1 was not known. To better understand the pathways involved in G-1 action, we conducted a genome-wide mRNA-seq and miRNA-seq study on G-1 treated xenografts. We identified a panel of novel G-1-associated tumor suppressive miRNAs and genes. Moreover, Ingenuity Pathway Analysis revealed that the G-1 differentially regulated genes are involved in “Cellular Growth and Proliferation”, “endocrine function” and “Cancer” pathways. We validated the expression of the key miRNA (miR-34c, miR-10b, miR-138 and miR218) and genes in G-1 treated castration resistant xenografts and cell lines (C4-2 and 22Rv1). Furthermore, we have shown the tumor suppressor function of these miRNA in cell survival, migration, and invasion. The predicted target genes were next examined for decreased expression by qRT-PCR. We confirmed decreased expression of some of the downstream targets, which consist of genes involved in cell cycle regulation (CCNA and CCND, CDK1, CDK4, PLK1), cell survival (Bcl2, Survivin), cell migration/F-actin formation (LASP, PCDH7, ITGA9, ROBO1, SLIT1) and G2/M checkpoint (CDK1, PLK1, BCL-2 Survivin). Thus these miRNAs - miR-34c, miR-10b, miR-138 and miR218 - are ideal candidates for therapy of CRPC.
Citation Format: Pheruza Tarapore, Sarah To, Bin Ouyang, Yuet-Kin Leung, Ana Cheong, Shuk-mei Ho. MicroRNA targeting anti-apoptotic and G2/M pathways as therapeutic targets for castration resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2537. doi:10.1158/1538-7445.AM2017-2537
Abstract 254: The potential of Lactobacillus probiotic treatments in colorectal cancer (CRC)
Authors: Kahouli Imen , Malhotra Meenakshi , Westfall Susan , Alaoui-Jamali Moulay , Prakash Satya 
Published: July 2017

Abstract
Colorectal cancer (CRC) is the third leading cause of death worldwide. It is known to be a type of cancer that is preventable by changes in diet and lifestyle. Mounting evidence are supporting the role of gut microbiome in the etiology of CRC and emphasize on the potential of probiotics as biotherapeutics in the prevention and management of CRC. Lactobacillus probiotic bacteria were suggested to balance pathogenic and oncogenic microbial community in the colon and produce anti-tumorigenic and anti-inflammatory effects in healthy individuals at risk and CRC patients. There is a need, however, for studies that focus on identifying potent probiotic strains with activity against CRC and inhibit cancer growth. This report discusses and present findings about the formulation of novel probiotic Lactobacillus biotherapeutic for CRC based on anti-CRC proliferative effect, immune modulation and metabolic activity, in vitro and in vivo, using a genetically-induced animal CRC model. Results and metabolomic analysis demonstrated the potential acrion of probiotic treatment to change host and gut microbiome co-metabolic profiles, produce local and systemic anti-inflammatory effects, inhibit cancer-causing events, and improve overall gut health.
Note: This abstract was not presented at the meeting.
Citation Format: Imen Kahouli, Meenakshi Malhotra, Susan Westfall, Moulay Alaoui-Jamali, Satya Prakash. The potential of Lactobacillus probiotic treatments in colorectal cancer (CRC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 254. doi:10.1158/1538-7445.AM2017-254
Abstract 2558: MYC-dependent transformation model of triple-negative breast cancer in vivo
Authors: Lourenco Corey , Kalkat Manpreet , Dingar Dharmesh , Melo Jason De , Yu Rosemary , Penn Linda 
Published: July 2017

Abstract
Recent comprehensive breast cancer studies examining mutations and genomic alterations have determined that deregulation of MYC and the PI3K pathway occur frequently during breast cancer progression and may be useful targets for therapy. As a result, there have been large efforts to develop PI3K, AKT and mTOR inhibitors (PAM inhibitors) for clinical use, however clinical trial data demonstrates that many patients treated with PAM inhibitors develop resistant disease. An alternative strategy would be to target Myc, though a lack of effective and specific inhibitors makes this difficult. To identify the core vulnerabilities in these cancers we developed an in vivo xenograft model of triple-negative breast cancer driven by deregulated PI3K signaling and MYC. We hypothesize that determining how these pathways co-operate to transform normal human breast cells into breast carcinomas will reveal a tumor progression signature and highlight new therapeutic opportunities. We developed our model using the spontaneously immortalized, basal, triple-negative MCF10A cell line. By expressing the hotspot PIK3caH1047R protein alone in MCF10A cells (MCF10.H) in addition to MYC (MCF10.HM), we can model normal/early breast cancer and invasive ductal carcinoma respectively. This is the first in vivo human model of breast cancer dependent on MYC for transformation. When injected into female NOD-SCID mice, MCF10A.H cells form organized acinar ducts embedded in extracellular matrix. MCF10A.H ducts form with hollow lumen and a single layer of myoepithelial cells, recapitulating normal human breast histology. Alternatively, MCF10A.HM cells grow as high-grade carcinomas indicative of invasive disease. MCF10A.H benign growths and MCF10A.HM tumors remain basal-like and triple-negative by immunohistochemistry. Importantly, MCF10A.HM tumors are sensitive to MYC repression and therefore may be a suitable model to evaluate direct and indirect anti-MYC therapies. Having relevant human xenograft samples representing both normal and IDC tissue, we performed RNA-seq to identify a MYC-signature driving breast cancer transformation. Our current work will involve targeting the resulting MYC-driven pathways identified by RNA-seq to therapeutically target MYC in breast cancer.
Citation Format: Corey Lourenco, Manpreet Kalkat, Dharmesh Dingar, Jason De Melo, Rosemary Yu, Linda Penn. MYC-dependent transformation model of triple-negative breast cancer in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2558. doi:10.1158/1538-7445.AM2017-2558
Abstract 2565: VCP/p97 segregase-mediated regulation of chromatin-bound PTEN stability
Authors: He Jinshan , Wani Gulzar , Zhu Qianzheng , Wani Altaf A 
Published: July 2017

Abstract
Phosphatase and Tensin homolog (PTEN) tumor suppressor protein is associated with many human cancers. PTEN has been shown to accumulate in the nucleus and control DNA repair in response to genotoxic stress. PTEN down-regulation impairs the capacity of global genomic nucleotide excision repair by suppressing the early DNA damage sensor, Xeroderma pigmentosum C (XPC), protein. Our recent work has demonstrated that the Valosin-containing protein (VCP)/p97 segregase participates in proteolytic processing of XPC and Cockayne syndrome B (CSB) proteins. Here, we show that (i) VCP/p97 segregase, in conjunction with its adaptor proteins, specifically extracts PTEN from damaged chromatin for targeted proteasomal degradation, (ii) inhibition of VCP/p97 activity induces the accumulation of PTEN on chromatin, and (iii) VCP/p97 physically interacts with PTEN. Depletion of VCP/p97, in p97-knockout cells or siRNA-mediated ablation in normal cells, affects the stability of PTEN in response to cellular UV irradiation. Results show that compromising the proteasome and VCP/p97 functions causes the accumulation of PTEN accompanied by an increase of UBXD7, proteasomal RPN2 and Sug1 within the chromatin compartment. To our knowledge, this is the first report to reveal that VCP/p97 segregase extracts tumor suppressor PTEN from damaged chromatin. (This work was supported by NIH grants ES002388 and ES012991 to AAW).
Citation Format: Jinshan He, Gulzar Wani, Qianzheng Zhu, Altaf A Wani. VCP/p97 segregase-mediated regulation of chromatin-bound PTEN stability [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2565. doi:10.1158/1538-7445.AM2017-2565
Abstract 2568: Mutant p53 regulates HSP70 expression and nuclear localization
Authors: Polireddy Kishore , Singh Kanchan , Pruski Melissa , Dar Wasim , Bynon John S. , Bailey Jennifer M. 
Published: July 2017

Abstract
Pancreatic cancer is the 3rd leading cause of cancer related deaths in the US with a median survival of less than one year. No effective therapies or early detection tests are available for these patients. Scientists have been studying cellular origins of pancreatic cancer to aid in the development of novel treatments and biomarkers. Several studies have demonstrated that acinar cells have a high propensity to undergo acinar to ductal metaplasia and form precursor lesions of pancreatic ductal adenocarcinoma. We have recently shown that simultaneous expression of Kras and mutant TP53 can generate invasive ductal adenocarcinoma from ductal cells. We hypothesized specific mutations in TP53 have different mechanisms of transforming ductal cells. In order to understand the role of mutant TP53 in transforming pancreatic ductal cells into invasive ductal adenocarcinoma, we used a lentiviral system to express mutant TP53R175H and TP53R273H, two of the most frequently mutated TP53 alleles in pancreatic cancer patients, in immortalized pancreatic ductal epithelial cells carrying a Kras mutation (HPNE-KrasG12D). Trypan blue dye exclusion assay and Spheroid formation assays were used to study cellular proliferation and cancer stem cell (CSC) populations. Mutant TP53 over expression enhanced CSC populations without altering cellular proliferation in HPNE-KrasG12D cells. Reverse phase protein array (RPPA) was carried out to detect gene expression changes in HPNE-KrasG12D cells upon mutant TP53 over expression. RPPA assay results suggested that TP53R175H uniquely induced HSP70 expression in HPNE-KrasG12D cells, as cells expressing either vector control or TP53R273H failed to do so. HSP70 expression was further validated by transiently overexpressing TP53R175H and TP53R273H. Surprisingly, TP53R175H specifically promoted nuclear localization of HSP70 without altering the expression of a recently identified HSP70 nuclear transporter, Hikeshi. Future studies will determine 1) whether HSP70 is required for p53-mediated stemness in HPNE-KrasG12D cells and 2) the function of nuclear HSP70. In summary, over expression of mutant p53 enhanced cancer stem cell properties of HPNE-KrasG12D cells, through upregulation HSP70. The exact mechanism behind HSP70 nuclear localization and increased cancer stem cell properties is being more rigorously explored.
Citation Format: Kishore Polireddy, Kanchan Singh, Melissa Pruski, Wasim Dar, John S. Bynon, Jennifer M. Bailey. Mutant p53 regulates HSP70 expression and nuclear localization [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2568. doi:10.1158/1538-7445.AM2017-2568
Abstract 2571: DBC1, a novel CBP-interacting protein, promotes p53 stability by regulating CBP-dependent p53 polyubiquitination
Authors: Akande Oluwatoyin E. , Damle Priyadarshan K. , Sherman Nicholas E. , Grossman Steven R. 
Published: July 2017

Abstract
The acetyltransferase CBP, in conjunction with the E3 ubiquitin ligase enzyme, Mdm2, maintains physiologic levels of the tumor suppressor protein p53 in the absence of cellular stress, via a cytoplasmic, but not nuclear, p53-directed E4 polyubiquitin activity. CBP also possesses cytoplasmic, but not nuclear, E3 ubiquitin ligase, autoubiquitination activity. To understand the mechanism by which the ubiquitin ligase activities of CBP are compartmentalized in the cell, we have employed Multidimensional Protein Identification Technology (MudPIT) to identify cytoplasmic and nuclear CBP interacting proteins. MudPIT analysis revealed that Cell Cycle and Apoptosis Regulator protein (CCAR2), also known as Deleted in Breast Cancer 1 protein (DBC1), is a novel CBP- interacting protein in both the nucleus and cytoplasm. The N-terminus of DBC1 bound to multiple CBP domains, including the putative E3/E4 domain of CBP located at the N-terminus. Interaction between DBC1 and CBP suppressed the in vitro E3 autoubiquitination activity of CBP. Functional studies demonstrated that DBC1 directly regulates the cellular compartmentalization of CBP E3 and p53-directed E4 ubiquitin ligase activities. Knockdown of DBC1 in U2OS cells stimulated normally absent nuclear p53 polyubiquitination, and also caused a decrease in p53-dependent and p53-independent apoptosis, rescued by CBP/DBC1 double knockdown. Further, over-expression of DBC1 rescued the increase in nuclear p53 polyubiquitination and decrease in p53 half-life observed in DBC1 depleted cells. Together, these results identify DBC1 as a novel binding partner of CBP and a critical regulator of CBP ubiquitin ligase activities. Based on our data that DBC1 loss inactivates p53 function through destabilization, we queried the TCGA database for co-occurrence of DBC1 loss with maintenance of wild-type p53 status which showed that 33% of breast, 40% of lung, and 96% of prostate cancer cases with DBC1 alterations maintained wild-type p53 status. Therefore, by restoring DBC1 function, this work could lead to reactivation of p53 tumor suppressor activity in tumors with DBC1 alterations maintaining wild-type p53 status.
Citation Format: Oluwatoyin E. Akande, Priyadarshan K. Damle, Nicholas E. Sherman, Steven R. Grossman. DBC1, a novel CBP-interacting protein, promotes p53 stability by regulating CBP-dependent p53 polyubiquitination [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2571. doi:10.1158/1538-7445.AM2017-2571
Abstract 2573: TP73's regulation and expression in human cancer cell lines
Authors: Yao Zhixing , Yao David R. , Yu William , Brim Hassan , Ashktorab Hassan , Sherif Zaki A. 
Published: July 2017

Abstract
TP73 is the homologue of the master tumor suppressor TP53. It is involved in cellular responses to stress and development. The TP73 gene encodes two different proteins, TAp73 and ΔNp73 and maps to a region on chromosome 1p36 that is frequently deleted in neuroblastoma and other tumors, and thought to contain multiple tumor suppressor genes. However, the analysis of p73-knockout mice yielded conflicting results with respect to tumor suppression. World-wide efforts in sequencing the TP73 gene in patient tumor samples have not provided evidence for genetic alterations as a common cause of p73 inactivation in human cancer. The role of TP73 in tumorigenesis has remained elusive to date. In this study, we isolated two stem cell lines from normal young and old human liver tissues and determined TP73 expression in human breast cancer cell lines (MCF7 & MDA321), human hepatocellular carcinoma (HCC) cell lines (HepG2, SNU398, SNU449 & SNU475), neuroblastoma cell lines (IMR32 & SK-N-SH), normal liver stem cell, non-cancerous Li-Fraumeni Syndrome (LFS) skin fibroblasts cells and normal skin fibroblasts. Results show that TAp73 only expresses in cancer cell lines. Moreover, when HepG2 and MDA231 were treated with paclitaxel, a cytoskeletal drug that targets tubulin, TAp73 expression was drastically down-regulated in HepG2 cells and abrogated in MDA231 cells at 1 to 5 µmol/L concentrations. Furthermore, ChIP assay results demonstrated that TP53 and CTCF (a chromosomal networking protein CCCTC binding factor) bind to TP73 promoter and regulate TP73 expression. Our observation may prove significant for the development of future therapeutic and diagnostic applications.
*These authors contributed equally to this work.
Citation Format: Zhixing Yao, David R. Yao, William Yu, Hassan Brim, Hassan Ashktorab, Zaki A. Sherif. TP73's regulation and expression in human cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2573. doi:10.1158/1538-7445.AM2017-2573