bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2497: Differential requirement of amino acids on cell survival of ovarian cancer cells
Authors: Furusawa Akiko , Inoue Jun , Tsuda Hitoshi , Miyasaka Naoyuki , Inazawa Johji 
Published: July 2017

Abstract
Amino acids (AAs) are traditionally classified into nutritionally essential AAs (EAAs) or nonessential AAs (NEAAs) for animals and humans. Recent studies have demonstrated that not only EAAs but also NEAAs play important roles on energy metabolisms in cancer cells. However, which AAs are indispensable for human cancer cell survival has not been fully elucidated. The purposes of this study were 1) to determine the indispensable AAs for ovarian cancer (OVC) cells and 2) to investigate the relationship between the AAs synthetase and cancer cell survival.
Firstly, OVC cell lines were cultured with different medium in which each AA was depleted and cancer cell survival was examined. Among 17 OVC cell lines, EAAs were required in 12 cell lines, whereas others did not require EAAs for cell survival. Interestingly, cancer cell lines which required EAA also required at least one NEAAs, including arginine, cystine, glutamine, serine and tyrosine. Although extracellular glutamine has been known to be a critical factor for cancer cell survival and growth, 3 OVC cell lines did not require extracellular glutamine. Hence, we next examined glutamine synthetase (GS) gene, which is a critical enzyme for production of endogenous glutamine from glutamate. In OVC cell lines which did not require extracellular glutamine, GS expression level was positively correlated with cell survival rate under glutamine-depleted condition. Furthermore, we found that the expression of GS protein was negative in 38 of 645 primary OV tumors (5.9 %). Taken together, these results suggest that GS-down-regulated OVC cells require extracellular glutamine for their survival. Therefore, uptake inhibition of extracellular glutamine or reduction of extracellular glutamine level may be a novel therapeutic strategy for patients with ovarian cancer with “GS down-regulation”, as well as development of an AA-based precision medicine of OVC.
Citation Format: Akiko Furusawa, Jun Inoue, Hitoshi Tsuda, Naoyuki Miyasaka, Johji Inazawa. Differential requirement of amino acids on cell survival of ovarian cancer cells [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 2497. doi:10.1158/1538-7445.AM2017-2497
Abstract 252: Resveratrol and pterostibene selectively chemosensitize Burkitt’s lymphoma cells to 5-Fluorouracil
Authors: Peck Connor J. , Townsend Michelle H. , O'Neill Kim L. 
Published: July 2017

Abstract
In the current study, we assess the chemosensitization activity of the naturally occurring polyphenols resveratrol (RES) and pterostilbene (PTER) to 5-Fluorouracil (5-FU) in Burkitt’s B-cell lymphoma. RES is a stilbenoid compound found in a variety of fruits, plants, and nuts. In addition to antioxidant and anti-aging properties, RES has been shown to exhibit significant anti-tumor activity against a variety of malignancies. Since the compound is typically protective of normal cells, its anti-cancer activity makes it a promising candidate as both a chemopreventative nutritional supplement and a chemotherapeutic agent. PTER, an analog of RES, has likewise shown anti-cancer activity. Its therapeutic potential, however, is much less understood. Recent studies have investigated the use of these and other natural compounds in adjuvant chemotherapy strategies, many of which continue to produce underwhelming rates of response. Here, we investigate the chemosensitization capacity of both RES and PTER to 5-FU, a commonly used drug in chemotherapy, in healthy lymphocytes and in Burkitt’s B-cell lymphoma (Raji) cells. MTS assays are used to measure the viability of malignant and normal lymphocytes after 5-FU treatment with or without co-incubation of RES, PTER, or RES/PTER combinations. We find that Raji co-incubation with physiologically relevant concentrations (&lt;10uM) of either RES or PTER significantly increases 5-FU toxicity in Raji cells, with data suggesting PTER to be slightly more effective than RES. Interestingly, RES/PTER combinatorial treatments further increase chemosensitization, an important finding considering the typically low bioavailability of each individual compound in vivo. Together, these data support the potential use of RES as a chemosensitizing adjuvant and provide new evidence that its analog, PTER, also possesses significant chemosensitization capacity. Furthermore, our studies suggest that low physiological concentrations of PTER and RES may be still be sufficient to induce significant anti-cancer effects.
Citation Format: Connor J. Peck, Michelle H. Townsend, Kim L. O'Neill. Resveratrol and pterostibene selectively chemosensitize Burkitt’s lymphoma cells to 5-Fluorouracil [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 252. doi:10.1158/1538-7445.AM2017-252
Abstract 2521: Inhibition of metabolic reprogramming by zerumbone alters the tumorigenic potential of hepatocellular cancer
Authors: Wani Nissar A. , Zhang Bo , Teng Kun-yu , Barajas Juan , Ghoshal Kalpana , Brüschweiler Rafael , Jacob Samson T. 
Published: July 2017

Abstract
Incidence of hepatocellular carcinoma (HCC) that represents ~90% of all cases of primary liver cancer is on the rise worldwide. Sorafenib, the only approved targeted therapy, prolongs median survival only by ∼3 months. Thus, new therapeutic strategies are urgently needed. In this study, we investigated therapeutic potential of zerumbone, a sesquiterpene from an edible ginger, against HCC. Zerumbone inhibited proliferation and clonogenic survival of HCC cells by blocking glycolysis and pentose phosphate pathway, arresting cells at G2/M phase of cell cycle and inducing apoptosis. To uncover the underlying molecular mechanisms of its action on HCC cells, we employed several unbiased approaches. First, phosphokinase array showed significant inhibition PI3K/AKT/mTOR and STAT3 signaling in zerumbone-treated HCC cells. Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) of the microarray data revealed that zerumbone-deregulated genes showed positive correlation with PI3/AKT/mTOR and STAT3 pathways and those involved in metabolism, apoptosis and cell cycle. Notably, the alteration in expression of genes regulated by PI3/AKT/mTOR or STAT3 pathways and downregulated by zerumbone in HCCs is associated with poor patient survival. These results implicate that treatment with this dietary sesquiterpene might lead to a better outcome in HCC patients. Indeed, zerumbone treatment significantly inhibited growth and lung metastasis of orthotopic HCC xenografts in NSG mice. These findings reveal novel therapeutic strategies targeting cancer metabolism. Collectively, these observations underscore the therapeutic potential of zerumbone in HCC.
Citation Format: Nissar A. Wani, Bo Zhang, Kun-yu Teng, Juan Barajas, Kalpana Ghoshal, Rafael Brüschweiler, Samson T. Jacob. Inhibition of metabolic reprogramming by zerumbone alters the tumorigenic potential of hepatocellular 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 2521. doi:10.1158/1538-7445.AM2017-2521
Abstract 2532: High expression of MiR-432-3p is associated with the chemoresistance by NRF2 stabilization via directly targeting KEAP1
Authors: Akdemir Burak , Inoue Jun , Kawano Tatsuyuki , Inazawa Johji 
Published: July 2017

Abstract
NF-E2-related factor 2 (NRF2) is a master transcriptional regulator that integrates cellular stress responses and is negatively regulated by Kelch-like ECH-associated protein 1 (KEAP1) at the post-translational level. In human cancers, aberrantly stabilized NRF2, either by mutation of NRF2 or KEAP1, plays a vital role in chemoresistance through the activation of target genes, suggesting that targeted inhibition of NRF2 is a potential therapy for NRF2-stabilized tumors. MicroRNAs (miRNA) are endogenous small noncoding RNAs that can negatively regulate gene expression by interfering with the translation or stability of target transcripts. Previously, we identified miRNAs negatively regulating NRF2 pathway via directly targeting NRF2 itself by a reporter-coupled miRNA library screening and demonstrated the potential of miRNA-based therapy against NRF2-stabilized tumors in esophageal squamous cell carcinoma (ESCC) (Mol. Cancer Res 2014, Cancer Res 2015).
In the present study, we further identified miR-432-3p as a miRNA positively regulating NRF2 pathway. MiR-432-3p could directly targeted KEAP1 via binding to its seed sequence within the cording region. Overexpression of miR-432-3p resulted in enhanced resistance to cisplatin via activation of NRF2 in ESCC cell lines. Furthermore, miR-432-3p was overexpressed in 55 of 84 primary ESCC tumors, compared with that of corresponding non-cancerous esophageal mucosa (65.5%). Importantly, we showed the negative correlation between the expression level of KEAP1 and miR-432-3p in primary ESCC tumors. Taken together, these findings suggest that the high expression of miR-432-3p may contribute to the chemoresistance by NRF2 stabilization via down-regulation of KEAP1 expression in ESCC.
Citation Format: Burak Akdemir, Jun Inoue, Tatsuyuki Kawano, Johji Inazawa. High expression of MiR-432-3p is associated with the chemoresistance by NRF2 stabilization via directly targeting KEAP1 [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 2532. doi:10.1158/1538-7445.AM2017-2532
Abstract 2538: MiR-638 promotes autophagy and malignant phenotypes of cancer cells via directly suppressing DACT3
Authors: Yang Ming 
Published: July 2017

Abstract
Dyregulation of autophagy is implicated in human cancers and the mechanism details remains largely unclear. Herein we report the regulatory role of miR-638 in autophagy of esophageal squamous cell carcinoma (ESCC) and breast cancer cells. We found that miR-638 overexpression promotes starvation- and rapamycin-induced autophagy. In ESCC and breast cancer cells, miR-638 acts as an oncogene and promote cell proliferation, migration, as well as invasion in vitro and in vivo. In accordance with this, we observed significantly higher miR-638 expression in ESCC and breast cancer tissues compared to normal tissues. To further elucidate regulatory mechanisms of miR-638 in autophagy, we performed a computational nomination of its target genes through intersecting the results of multiple prediction algorithms. DACT3, a key regulator of Wnt/β-catenin signaling, was predicted to be regulated by miR-638 by all programs and confirmed by experimental results. Depletion of DACT3 phenocopied effects of miR-638 overexpression, demonstrating its importance in autophagy. These results elucidate that the miR-638-DACT3 axis might be an important molecular pathway in controlling and autophagy and tumorigenesis. Our data in clinical tissue samples highlight miR-638 and DACT3 with histological marker for cancer detection and potentially therapeutic implications.
Citation Format: Ming Yang. MiR-638 promotes autophagy and malignant phenotypes of cancer cells via directly suppressing DACT3 [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 2538. doi:10.1158/1538-7445.AM2017-2538
Abstract 2539: MiR-96-5p functions as an oncogenic miRNA by inhibiting apoptosis in hepatocellular carcinoma
Authors: Iwai Naoto , Yasui Kohichiroh , Tomie Akira , Teasaki Kei , Kitaichi Tomoko , Dohi Osamu , Gen Yasuyuki , Ito Yoshito 
Published: July 2017

Abstract
Hepatocellular carcinoma (HCC) is one of the most aggressive cancers with high mortality worldwide. MicroRNAs (miRNAs) are small non-coding RNAs that have been used as cancer-related biomarkers and expected to be therapeutic agents. We performed genome-wide miRNA expression profiling of paired HCC tumors and non-tumorous liver tissues from patients with primary HCCs using the miRNA microarray (Agilent). We found that miR-96-5p was most significantly up-regulated in HCC tumors compared to non-tumor tissues. Although miR-96-5p is suggested to be an oncogenic miRNA, the function of miR-96-5p remains largely unknown. We identified the caspase-9 gene (CASP9) as a novel target of miR-96-5p, in addition to the forkhead box O1 gene (FOXO1) which is the known target of it. Caspase-9 protein is thought to play a central role in apoptosis and to be a tumor suppressor. Overexpression of miR-96-5p decreased caspase-9 protein expression and resulted in resistance to apoptosis induced by doxorubicin and UV in HCC cells. Our results suggested that miR-96-5p functions as an oncogenic miRNA by inhibiting apoptosis through decreasing caspase-9 expression in HCC.
Citation Format: Naoto Iwai, Kohichiroh Yasui, Akira Tomie, Kei Teasaki, Tomoko Kitaichi, Osamu Dohi, Yasuyuki Gen, Yoshito Ito. MiR-96-5p functions as an oncogenic miRNA by inhibiting apoptosis in hepatocellular carcinoma [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 2539. doi:10.1158/1538-7445.AM2017-2539
Abstract 2540: miR-196b as a potential biomarker for human esophageal cancer
Authors: Tan Xiaohui , Chen Tao , Siegel Robert , Fu Sidney 
Published: July 2017

Abstract
Esophageal cancer is the sixth most common cause of cancer related death. Although multiple genetic and epigenetic alterations have been detected in esophageal cancer, molecular markers for early diagnosis and prediction of prognosis or treatment responses are quite limited. microRNA (miRNA) is a class of small-regulatory non-coding RNA, acting as either a tumor suppressor or oncogene by regulating gene expression through pairing with complementary seed of the targeted messenger RNAs (mRNA). A number of miRNA expression profiling studies have been conducted in esophageal. In our current study, we analyzed the most recent studies on miRNAs expression profiles in esophageal cancer. Consistently dysregulated miRNAs have been identified in esophageal cancer, including upregulation of miR-196b, miR-135a, and downregulation of miR-141, miR-200a-5p, miR-200b-3p, miR-27b, miR-210. We first assessed expression of miRNAs in esophageal cancer cell lines and primary esophageal cancer tissues by real-time reverse transcriptase-polymerase chain reaction (qRT-PCR). Significantly overexpressed miR-196b was observed in human esophageal squamous cell carcinoma KYSE-70 and KYSE-180 compared with normal esophageal squamous cell line, HET-1A. Furthermore, overexpression of miR-196b was detected in 12 out of 14 (86%) cancer tissues compared to the matched normal tissues. Forced expression of miR-196b promotes the proliferation and invasion in esophageal cancer cell lines. TargetScanS and miRanda were used to identify the target genes of miR-196b. A list of targets genes were predicted, including GATA6, ARHGAP28, EPS15 and EPHA7. Forced expression of miR-196b resulted in significant downregulated EPS15 and EPHA7 expression in esophageal cancer cell lines. Our present work suggested that miR-196b acts as an oncomiR by regulating EPS15 and EPHA7. Therefore, miR-196b could be used as a biomarker for esophageal cancer.
Citation Format: Xiaohui Tan, Tao Chen, Robert Siegel, Sidney Fu. miR-196b as a potential biomarker for human esophageal 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 2540. doi:10.1158/1538-7445.AM2017-2540
Abstract 2541: Two miR-34 loci, miR-34a and miR-34b/c, have differential anticancer effects in lung adenocarcinomas
Authors: Kim Jeong Seon , Ahn Young-Ho 
Published: July 2017

Abstract
Three miR-34 family members (miR-34a, miR-34b, and miR-34c) are clustered on two different chromosomal loci, miR-34a and miR-34b/c, and have identical seed-sequences predicted to target the same set of genes; however, miR-34a and miR-34c have different sets of negatively correlated genes in TCGA data of human lung adenocarcinomas. Therefore, we hypothesized that miR-34 family members, which are tumor suppressive miRNAs, might have differential effects on lung tumorigenesis. To prove this, we overexpressed each miR-34 cluster, miR-34a and miR-34b/c, in murine lung cancer cells. miR-34b/c enhanced cancer cell attachment and suppressed cell growth and invasion compared with miR-34a. In a syngeneic mouse model, both miR-34a and miR-34b/c blocked lung metastasis; whereas, miR-34b/c suppressed tumor growth more than miR-34a. miR-34b/c also decreased mesenchymal markers (Cdh2 and Fn1), and increased epithelial markers (Inadl, Crb3, Ocln, and Dsp) and miR-200 family members better than miR-34a, implying that miR-34b and miR-34c partially inhibit EMT. Furthermore, miR-34b and miR-34c are better prognostic markers than miR-34a in human lung adenocarcinoma patients. Collectively, we suggest that miR-34b and miR-34c are more effective tumor suppressors than miR-34a.
Citation Format: Jeong Seon Kim, Young-Ho Ahn. Two miR-34 loci, miR-34a and miR-34b/c, have differential anticancer effects in lung adenocarcinomas [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 2541. doi:10.1158/1538-7445.AM2017-2541
Abstract 2542: MSI2 binds LncRNAs and promotes self-renewal and oncogenesis through MYC expression
Authors: Siddique Hifzur , Narayan Padmani , Punj Vasu , Feldman Douglas E. , Machida Keigo 
Published: July 2017

Abstract
Backgrounds and Aims: RNA-binding protein MSI2 is elevated in several cancers and is linked to poor prognosis. Here, we sought to elucidate the role of MSI2 in regulating the expression of proto-oncogenes or tumor suppressor genes in hepatocellular carcinoma (HCC).
Methods: We performed RIP-seq using anti-MSI2 antibody in tumor-initiating stem-like cells (TICs) and subsequent validation by qPCR analysis.
Results: Among the MSI2-bound RNAs, MYC mRNA and long noncoding RNA (LncRNA) miR22 host gene (MIR22HG) and MARAT1 were identified by RIP-qPCR analysis. MSI2-MARAT1 binding dereppresses polycomb reppressor to recruit E2F1 in MYC promoter regions. It is known that the 5’-untranslated region of MYC contains an internal ribosome entry sequence (IRES) which allows IRES-dependent translation initiation along with canonical cap-dependent mechanisms. Our data show that MSI2 acts as an IRES trans-acting factors for MYC mRNA translation. MSI2 does not have any effect on the steady state level of MYC mRNA but significantly increases MYC protein levels, indicating that MSI2 regulates MYC at the post-transcriptional level. Further, we observed that MSI2 reduced the level of mature miR22 derived from MIR22HG processing. We showed that miR22 suppresses the expression of MYC thorough a 3’-UTR dependent process. Overexpression of MSI2 promotes TIC self-renewal and tumor initiation property in xenograft tumor mouse models, whereas silencing MSI2 reduces this occurrence.
Conclusion: we demonstrate that MSI2 promotes liver tumorigenesis by maintenance of MYC expression through dereppression of polycomb repressor and an IRES-dependent translation mechanism and possibly by inhibition of miR22 processing. Thus, MSI2 may be a useful prognostic factor for HCC and MSI2 targeted therapy and thus may be beneficial in the treatment of HCC patients.
Citation Format: Hifzur Siddique, Padmani Narayan, Vasu Punj, Douglas E. Feldman, Keigo Machida. MSI2 binds LncRNAs and promotes self-renewal and oncogenesis through MYC expression [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 2542. doi:10.1158/1538-7445.AM2017-2542
Abstract 2547: Discovery and characterization of late-stage breast cancer estrogen receptor alpha 1 bound long non-coding RNAs
Authors: Silva-Fisher Jessica Monique , Eteleeb Abdallah M. , Nielsen Torsten , Perou Charles M. , Reis-Filho Jorge S. , Ellis Mathew J. , Mardis Elaine R. , Maher Christopher A. 
Published: July 2017

Abstract
Breast cancer (BC) is the second most common newly diagnosed cancer and the second leading cause of cancer death among women in the United States. Despite the proven benefits of adjuvant endocrine therapy in women with hormone receptor positive BC, relapses still occur even after initial treatment with endocrine therapy for 5 years, referred to as late-stage relapse. Long non-coding RNAs (lncRNAs) have been shown to be dysregulated in breast cancer. Recent studies have also shown lncRNAs to function by interfacing with corresponding RNA binding proteins to play critical regulatory roles of diverse cellular processes. Therefore, we hypothesize that lncRNAs may interact with ER to regulate genes promoting late-stage relapse. To address this, we aimed to identify lncRNAs bound to the estrogen receptor alpha 1 protein (ESR1) that promote late-stage relapse breast cancer. We first used transcriptome sequencing to identify altered expression levels of lncRNAs between 72 primary tumors and 24 late-stage relapse breast cancer patients. We detected 1192 altered lncRNAs when comparing the metastatic to the primary samples (FDR &lt;0.05). Next, to identify ESR1 bound lncRNAs associated with late-stage BC, we conducted RNA Immunoprecipitation Sequencing of all transcripts bound to ESR1 as compared to an IgG control in the ER+ T47D cell line. We identified 217 lncRNAs bound to ESR1 of which 50 were up-regulated in late-stage BC, termed Late-Stage Relapse BC ESR1-bound lncRNAs (LASERs). Next, we focused on characterizing the most up-regulated differentially expressed lncRNA, LASER1. We found that LASER1 has increased expression in ER+ breast cancer cell lines. Further, elevated expression of LASER1 was also detected in MCF7 long-term estrogen deprived cells lines that have amplified ER+, suggesting an ER dependent mechanism. Preliminary functional studies indicate LASER1 to promote proliferation and invasion in BC cell lines. Ongoing studies will decipher how LASERs interact with ESR1 to promote late-stage relapse. Overall, this is the first study to discover ESR1 bound lncRNAs that may be contributing to late-stage relapse in BC patients.
Citation Format: Jessica Monique Silva-Fisher, Abdallah M. Eteleeb, Torsten Nielsen, Charles M. Perou, Jorge S. Reis-Filho, Mathew J. Ellis, Elaine R. Mardis, Christopher A. Maher. Discovery and characterization of late-stage breast cancer estrogen receptor alpha 1 bound long non-coding RNAs [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 2547. doi:10.1158/1538-7445.AM2017-2547