bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1431: Gene expression analysis of argininosuccinate synthetase loss and the effects of pegylated arginine deiminase in malignant pleural mesothelioma
Authors: Cutts Rosalind , Jithesh Puthen V. , Delage Barbara , Luong Phuong , Thomas Gareth , Chelala Claude , Szlosarek Peter W. 
Published: May 2015

Abstract
Malignant pleural mesothelioma (MPM) is a devastating asbestos-related malignancy that is increasing in many countries worldwide with few systemic treatment options beyond platinum and antifolate chemotherapy. Deficiency of the arginine biosynthetic enzyme argininosuccinate synthetase (ASS1) occurs in up to 50% of MPM cell lines and primary tumors and is being validated as a biomarker in patients treated with the arginine-depleting agent, pegylated arginine deiminase (ADI-PEG20). To understand the role of ASS1 loss and the effect of the ADI-PEG20 in MPM we used pathway analysis tools on microarray gene expression data from a representative panel of MPM cell lines. First, we identified that ASS1 loss was linked to several protumorigenic functions including increased cell invasiveness and migration, which were confirmed subsequently using invasion assays and organotypic modelling, respectively. We also detected a large number of enriched pathways connected to the immune response including communication between innate and adaptive immune cells and interferon signalling. Furthermore, ASS1 deficiency was linked to worse outcome with a median survival of 6 months in ASS1 low expressors compared to 12 months for ASS1 high expressors using a retrospective dataset (n=41; p=0.003). Second, ADI-PEG20 treatment modulated numerous pathways in ASS1-deficient cells including suppression of mTOR and folate metabolism, while promoting stress, oxidant and amino acid signalling. Third, bioinformatics analyses of drug interactions using Connectivity map revealed that arginine deprivation using ADI-PEG20 may potentiate several chemotherapeutic and targeted agents in the clinic. Taken together, our bioinformatics approach links loss of ASS1 in MPM cells to a more aggressive phenotype and identifies several potential combination strategies with ADI-PEG20 for further clinical investigation.
Citation Format: Rosalind Cutts, Puthen V. Jithesh, Barbara Delage, Phuong Luong, Gareth Thomas, Claude Chelala, Peter W. Szlosarek. Gene expression analysis of argininosuccinate synthetase loss and the effects of pegylated arginine deiminase in malignant pleural mesothelioma. [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 1431. doi:10.1158/1538-7445.AM2014-1431
Abstract 1445: Thyroid hormone receptor represses microRNA-130b to enhance cell metastasis
Authors: Lin Yang Hsiang , Wu Meng-Han , Yeh Yung-Hsin , Chao Angel , Lin Kwang-Huei 
Published: May 2015

Abstract
Thyroid hormone (T3) and its receptor (TR) are involved in cell growth and cancer progression. Although deregulation of miRNA expression has been detected in many tumor types, the mechanisms underlying functional impairment and specific involvement of miRNA in tumor metastasis remain unclear. We proposed that deregulation of specific miRNAs and target gene expressions mediated by T3/TR constitute critical steps of cancer progression. In the current study, we demonstrated that T3/TR negatively regulates microRNA-130b (miR-130b) expression, both in vitro and in vivo. Overexpression of miR-130b markedly inhibited cell migration and invasion in vitro and in vivo, which was mediated via suppression of interferon regulatory factor 1 (IRF1). Cell migration ability was promoted by T3, but partially suppressed upon miR-130b overexpression. Furthermore, miR-130b suppressed the expression of epithelial-mesenchymal transition (EMT)-related genes, matrix metalloproteinase (MMP)-9, p-AKT and p-signal transducer and activator of transcription (STAT)-3. Notably, miR-130b was downregulated in hepatoma samples and inversely correlated with TR and IRF1. Our data collectively highlight a novel pathway interlinking T3/TR, miR-130b, EMT-related genes, MMP9, p-AKT and p-STAT3 cascade that regulates the motility and invasion of hepatoma cells. Thus, miR-130b activation may be a useful strategy for cancer treatment in metastatic HCC.
Citation Format: Yang Hsiang Lin, Meng-Han Wu, Yung-Hsin Yeh, Angel Chao, Kwang-Huei Lin. Thyroid hormone receptor represses microRNA-130b to enhance cell metastasis. [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 1445. doi:10.1158/1538-7445.AM2014-1445
Abstract 1452: MicroRNA-375 impairs head and neck squamous cell carcinoma invasion by suppressing invadopodia activity
Authors: Jimenez Lizandra , Sharma Ved P. , Lim Jihyeon , Angeletti Ruth , Condeelis John , Harris Thomas , Prystowsky Michael B. , Childs Geoffrey , Segall Jeffrey E. 
Published: May 2015

Abstract
Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer, with a five-year survival rate of around 50%. Our goal is to improve patient outcome through understanding the mechanisms determining HNSCC invasiveness. Our research group previously reported that miR-375 expression levels correlate with patient survival, recurrence and distant metastasis. We have previously observed diminished HNSCC invasion in vitro correlates with increased miR-375 expression. To assess whether the miR-375 over-expressing transductant lines have reduced matrix degradation properties, a fluorescent matrix degradation assay was used. We have observed that miR-375 over-expression in HNSCC cells suppresses extracellular matrix degradation. We further determined whether miR-375 over-expressing cells show reduced invadopodium formation and maturation. We observed miR-375 expression in HNSCC cell lines reduces the number of mature invadopodia, but does not affect levels of invadopodium precursors. We examined the phosphorylation and total levels of key invadopodia components (Tks5 and cortactin) to determine whether changes in regulation or expression of these components may lead impaired matrix degradation properties. We determined that miR-375 expression in HNSCC cell lines does not reduce cellular levels of cortactin and Tks5, nor is tyrosine phosphorylation of cortactin altered. To identify candidate proteins regulated by miR-375, we are utilizing stable isotope labeling of cells in cell culture (SILAC). Candidate target proteins are being validated as targets of miR-375 and tested for involvement in the diminished invasive properties of HNSCC as a result of miR-375 expression. In conclusion, increased miR-375 expression may suppress the invasive properties of HNSCC through diminished invadopodia activity.
Citation Format: Lizandra Jimenez, Ved P. Sharma, Jihyeon Lim, Ruth Angeletti, John Condeelis, Thomas Harris, Michael B. Prystowsky, Geoffrey Childs, Jeffrey E. Segall. MicroRNA-375 impairs head and neck squamous cell carcinoma invasion by suppressing invadopodia activity. [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 1452. doi:10.1158/1538-7445.AM2014-1452
Abstract 1454: MiR-517a mediates cisplatin sensitivity in bladder cell carcinoma
Authors: Ibrahim Ahmed , Chakravarti Arnab , Lautenschlaeger Tim 
Published: May 2015

Abstract
Cisplatin-containing neoadjuvant chemotherapy is the standard of care treatment for patients with muscle-invasive bladder cancer. We sought out to assess if miR-517a modulates sensitivity to cisplatin in bladder cancer cell lines. We used four transitional cell carcinoma cell lines T24, J82, UM-UC3 and TCCSUP. Cells were transfected with miR-517a mimic or inhibitor using lipofectaime according to manufacturer's instruction. Mtt assay was performed to assess viability after 96 hrs and clonogenic survival assays were performed to assess colony forming ability of cell lines.
We found that miR-517a reduced proliferation and increased cisplatin sensitivity. Overexpression of miR-517a resulted in reduction of proliferation by 53%, 45%, 62% and 67% respectively (t-test p&lt;0.05 for comparison with respective control cell lines). Transfection with miR-517a followed by cisplatin treatment resulted in a dramatic reduction in viability and colony forming ability of cells compared to cisplatin treatment alone. This reduction in viability was not observed after transfection with the miR-517a inhibitor. To our knowledge, this is the first report indicating that miR-517a functions as a sensitizer to cisplatin therapy in bladder cancer. Bioinformatics and microRNA target prediction databases identified several candidate genes.
Note: This abstract was not presented at the meeting.
Citation Format: Ahmed Ibrahim, Arnab Chakravarti, Tim Lautenschlaeger. MiR-517a mediates cisplatin sensitivity in bladder 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 1454. doi:10.1158/1538-7445.AM2014-1454
Abstract 1469: Functional roles of SCAL1 expression in lung cancer and progression
Authors: Statt Sarah , Thai Philip , Chen Ching-Hsien , Cheng Ya-Wen , Belinsky Steven , Wu Reen 
Published: May 2015

Abstract
Our group has identified a novel long non-coding RNA (lncRNA), SCAL1 (smoke and cancer-associated lncRNA 1), whose expression is associated with smoking and related to cancer malignancy (Thai et al., 2013, AJRCMB). Currently, we have found that SCAL1 expression is necessary in lung epithelial cells during injury in order to initiate repair after exposure to smoke. In lung cancer cells, SCAL1 expression is needed for cancer cells to combat DNA double stranded breaks associated with chemotherapy treatment, especially cisplatin, doxyrubcin, and possibly other DNA damaging reagents. Most interestingly, the induction of SCAL1 expression is regulated by NRF-2. While NRF2 may protect normal cells from injury, it becomes persistently activated in some cancers and may enhance their malignant characteristics. Therefore, SCAL1 expression is an early marker for lung cellular injury and may be involved in lung cancer progression. We believe that smoke-induced SCAL1 expression leads to epithelial repair and enhances cancer cell resistance to chemotherapy. Our hypothesis is that SCAL1 expression in lung cancer is associated with increased malignant potential and is a poor prognostic marker.
Citation Format: Sarah Statt, Philip Thai, Ching-Hsien Chen, Ya-Wen Cheng, Steven Belinsky, Reen Wu. Functional roles of SCAL1 expression in lung cancer and progression. [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 1469. doi:10.1158/1538-7445.AM2014-1469
Abstract 1497: A novel long non-coding RNA associated with poor prognosis in epithelial ovarian cancer
Authors: Lawrenson Kate , Spindler Tassja , Gayther Simon A. 
Published: May 2015

Abstract
Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy in the Western world. In the US, there are ∼22,000 new diagnoses and ∼15,500 deaths from the disease each year. Identifying novel biomarkers associated with disease outcome, which may represent novel therapeutic targets, is critical to improve survival rates and reduce mortality from the disease. Research in this area has traditionally focused on protein-coding genes, and while this has yielded many insights into tumor biology, prognoses for women diagnosed with EOC have improved very little over the last four decades. However, protein-coding genes make up only ∼2% of the human genome. Recent studies show that the 98% non-coding ‘dark matter’ of the genome contains a myriad of RNA transcripts that are never translated, including long non-coding RNAs (lncRNAs).
The existence and potential functional significance of lncRNAs is a relatively recent discovery, and the lncRNA transcriptome remains poorly characterized for most human diseases. In this study, we used RNA sequencing to profile lncRNAs in ovarian cancer and normal ovarian epithelial cells. We identified 294 significantly lncRNAs that were differentially expressed between the two cell types, the majority of which were novel antisense or intergenic RNAs. One of the most highly overexpressed lncRNAs in EOC was UCA1, which was expressed in cell lines representing the major subtypes of EOC (n=39) but not in normal ovarian or fallopian tube epithelial cells (n=10). We validated UCA1 overexpression in primary EOCs using data from 489 ovarian cancers analyzed by The Cancer Genome Atlas (TCGA) compared to expression in 8 normal fallopian tube tissue specimens (P=4.66x10-8). Overexpression or amplification of UCA1 was associated with a significantly worse prognosis, both overall survival (P=5.60x10-4) and disease-free survival (P=4.79x10-4). Using TCGA data, we also found that UCA1 amplification/overexpression occurred exclusively in patients without either germline or somatic BRCA1 mutations (P=6x10-4), suggesting functional redundancy between UCA1 and a failure in homologous recombination (HR) and defective double-stranded DNA break repair. This was supported by in silico analyses of HR and EOC associated susceptibility genes and the finding that, in contrast to UCA1, EOC patients with mutations in BRCA1 and BRCA2 have improved survival. Finally, functional knockdown of UCA1 in EOC cell lines caused a significant reduction in proliferation and migration in vitro, further suggesting that UCA1 plays and important role in EOC development.
Citation Format: Kate Lawrenson, Tassja Spindler, Simon A. Gayther. A novel long non-coding RNA associated with poor prognosis in epithelial ovarian cancer. [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 1497. doi:10.1158/1538-7445.AM2014-1497
Abstract 152: Galectin-7 increases the invasive behavior of ovarian cancer cells and promotes tumor escape
Authors: Labrie Marilyne , Vladoiu Maria Claudia , Grosset Andrée-Anne , Gaboury Louis , St-Pierre Yves 
Published: May 2015

Abstract
Ovarian cancer is the fifth leading cause of cancer-related deaths in the Western world, the second most common gynecological cancer and the leading cause of death from gynecological malignancies. Epithelial ovarian cancer (EOC) accounts for the majority of ovarian cancers. Here, we have investigated the role of galectin-7 in EOC. Galectin-7 is an epithelial cell marker which has been shown to play an important role in the progression of many types of cancer, including breast cancer and colon cancer. Galectins play an important role in several physiological processes, including cell migration, programmed cell death and regulation of the immune response. They are also involved in a number of pathological conditions, including cancer. In fact, galectins have been shown to create an immunosuppressive tumor microenvironment by killing helper and effector T cells. They can also bind to the surface of tumor cells to form cell surface lattice that stabilizes the expression of key growth factor receptors, thereby increasing cell growth, motility, and production of matrix metalloproteinases. Using tissue microarrays, we found that gal-7 expression increases in malignant tumors compared to normal tissues and benign tumors. Detection of galectin-7 was also more frequent in tissue samples with metastasis as compared to non-metastatic primary tumor samples. Western blot analysis showed that OVCAR-3 EOC cells secrete gal-7, while no expression was detected in COV-434, A2780 and SK-OV-3 cell lines. Treatment of EOC cells with recombinant gal-7 increased their invasive behavior through matrigel and their ability to express MMP-9, an extracellular protease which confers an invasive phenotype to cancer cells. Treatment of freshly isolated human PBMCs with gal-7 also showed gal-7 increased apoptosis of monocytes, T CD4+ and T CD8+ cells. Overall, these data provide impetus for further studies to determine the potential of gal-7 as a therapeutic target for the treatment of EOC.
Citation Format: Marilyne Labrie, Maria Claudia Vladoiu, Andrée-Anne Grosset, Louis Gaboury, Yves St-Pierre. Galectin-7 increases the invasive behavior of ovarian cancer cells and promotes tumor escape. [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 152. doi:10.1158/1538-7445.AM2014-152
Abstract 1571: The tumor suppressor Liver Kinase B1 inhibits triple-negative breast cancer cell metastasis via regulation of AP-1 signaling
Authors: Rhodes Lyndsay V. , Tate Chandra R. , Burks Hope E. , Hoang Van T. , Gilliam Diari , Martin Elizabeth C. , Elliott Steven , Miller David F. , Buechlein Aaron , Rusch Douglas , Tang Haixu , Nephew Kenneth P. , Burow Matthew E. , Collins-Burow Bridgette M. 
Published: May 2015

Abstract
The basal sub-type, which shares features with triple-negative breast cancer (TNBC), is among the most lethal breast cancer subtype, characterized by a highly aggressive and metastatic phenotype. Although pathways that may represent targets for novel therapeutic intervention for basal like breast cancer (BLBC) have begun to be elucidated, the ability to define and selectively target the invasive and metastatic phenotype of basal-type/TNBC remains a major challenge facing the breast cancer field.
Liver kinase B1 (LKB1), also known as serine/threonine kinase 11 (STK11), is a known tumor suppressor in many cancers including breast. Low LKB1expression has been observed in breast cancer patients and we report a significant association between loss of LKB1 expression and poor prognosis specifically in the basal sub-type of breast cancer. Induction of LKB1 expression in BLBC cell lines inhibited invasiveness in vitro as well as lung and brain metastatic burden in an orthotopic xenograft tumor model. Further analysis of BLBC cell lines overexpressing LKB1 by next generation sequencing (RNA-seq) revealed striking regulation of metastasis-associated pathways, including cell adhesion, extra cellular matrix remodeling, and epithelial-to-mesenchymal transition (EMT). We further demonstrated marked inhibition of matrix metalloproteinase 1 (MMP-1) expression and activity via regulation AP-1 family member cJun. Additionally, LKB1 overexpression inhibited EMT-associated genes (CDH2, Vimentin, Twist) and induced the epithelial cell marker CDH1, indicating a reversal of the EMT phenotype in a triple-negative breast cancer cell line MDA-MB-231. We have demonstrated a role for LKB1 expression in the regulation of cell invasion and metastasis in addition to tumorigenesis. Taken together these data support future development of therapeutic agents to induce the LKB1 signaling pathway in BLCB/triple-negative breast cancer.
Citation Format: Lyndsay V. Rhodes, Chandra R. Tate, Hope E. Burks, Van T. Hoang, Diari Gilliam, Elizabeth C. Martin, Steven Elliott, David FB Miller, Aaron Buechlein, Douglas Rusch, Haixu Tang, Kenneth P. Nephew, Matthew E. Burow, Bridgette M. Collins-Burow. The tumor suppressor Liver Kinase B1 inhibits triple-negative breast cancer cell metastasis via regulation of AP-1 signaling. [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 1571. doi:10.1158/1538-7445.AM2014-1571
Abstract 1949: P38MAPK plays a tumor suppressive role through differentiation of ALDHhigh/CD44high tumor iniating cells in primary human lung adenocarcinoma
Authors: Liu Jing , Leung Lai-han , Xiao Zhi-jie , Tin Vicky P. , Wong Maria Pik 
Published: May 2015

Abstract
The p38 MAPK cascade regulates body responses to a wide range of stress stimuli in a context-dependent and tissue-specific manner. The isoform p38alpha (p38) mediates both tumor suppressive and tumor-supportive functions in different cancer models. However, its role in lung cancer is not clear. Since EGFR is frequently mutated in lung adenocarcinomas in non-smoking women and p38 is a downstream target of EGFR signaling, it is possible that p38 plays a tumor-supportive role. Using immunohistochemistry to analyze nuclear activated p38 expression in 90 lung adenocarcinomas, we observed p38 expression was significantly associated with well differentiated compared to poorly-differentiated carcinomas (p&lt;0.001) and better patient outcome (p=0.019, disease-free survival; p=0.03, overall survival). In vitro p38 suppression in lung cancer cell lines did not lead to enhanced cell death. On the other hand, p38 suppression alone or in combination with EGFR inhibition led to increased CD44high/ALDHhigh lung tumor initiating cells (TIC); isolated lung TIC also showed higher p38 expression. Together, the data implicate p38 plays a tumor suppressive role in lung cancer by driving tumor cell differentiation. Disrupting pathways that inhibit p38 expression or enhancement of p38 expression might be useful for lung cancer treatment.
Citation Format: Jing Liu, Lai-han Leung, Zhi-jie Xiao, Vicky PC Tin, Maria Pik Wong. P38MAPK plays a tumor suppressive role through differentiation of ALDHhigh/CD44high tumor iniating cells in primary human lung 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 1949. doi:10.1158/1538-7445.AM2014-1949