bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5340: MicroRNA-720 promotes cell proliferation and invasion in prostate cancer cells.
Authors: Yamamura Soichiro , Chiyomaru Takeshi , Fukuhara Shinichiro , Saini Sharanjot , Majid Shahana , Deng Guoren , Shahryary Vary , Arora Sumit , Chang Inik , Tanaka Yuichiro , Carroll Peter , Dahiya Rajvir 
Published: August 2014

Abstract
MicroRNAs (miRNAs) are highly conserved, single stranded, non-coding RNAs of approximately 21 - 24 nucleotides that regulate gene expression by posttranscriptional silencing of specific target RNAs, by repressing translation or cleaving RNA transcripts by binding to the 3’ untranslated region (3’UTR) of the target messenger RNAs. miRNAs regulate diverse cellular processes such as cell-cycle progression, proliferation, apoptosis and development. miRNAs also have been shown to function as oncogenes or tumor suppressor genes.
MicroRNA profiling has shown that miR-720 was up-regulated in cancer tissues, however the function of miR-720 in cancer has not been studied. Here we studied the functional effects of miR-720 on prostate cancer cells. We found that miR-720 was up-regulated in human prostate cancer tissues compared to adjacent normal tissues. We also found that miR-720 was up-regulated in prostate PC-3 cancer cell line compared with normal prostate cell line, RWPE1 cells. Transfection of miR-720 into prostate cancer cells, PC-3 and DU145 cells, decreased apoptosis, promoted cell proliferation and cell invasion. Transfection of anti-miR-720 into PC-3 cells increased apoptosis, inhibited cell proliferation and cell invasion. These results indicated that miR-720 has oncogenic functions in prostate cancer cells. In-silico analysis suggests that miR-720 targets genes of DR1, a down-regulator of global transdcription, and SWI5, a component of a complex required for double-strand break repair, which have tumor suppressive functions. Luciferase assays indicated that miR-720 binds to the 3’ UTR of these genes in prostate cancer cells, suggesting that these genes are targets of miR-720. Our results suggest that miR-720 promotes malignancy by targeting DR1 and SWI5 in prostate cancer cells.
Funding: National Institutes of Health through Grant Number RO1CA138642, RO1CA130860 and RO1CA160079 and VA Merit Review and VA Program Project.
Citation Format: Soichiro Yamamura, Takeshi Chiyomaru, Shinichiro Fukuhara, Sharanjot Saini, Shahana Majid, Guoren Deng, Vary Shahryary, Sumit Arora, Inik Chang, Yuichiro Tanaka, Peter Carroll, Rajvir Dahiya. MicroRNA-720 promotes cell proliferation and invasion in prostate cancer cells. [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 5340. doi:10.1158/1538-7445.AM2013-5340
Abstract 5378: Inhibition of 15-hydroxyprostaglandin dehydrogenase by Helicobacter pylori in human gastric carcinogenesis.
Authors: Ryu Yeon Mi , Myung Seung-Jae , Park3 Young Soo , Song Ho June , Yang Dong-Hoon , Jeong Jin-Yong , Lee Sun Mi , Song Miyeoun , Kim Do Hoon , Lee Hyo-Jeong , Fink Stephen P. , Markowitz Sandy D. , Jung Kee Wook , Kim Kyung-Jo , Ye Byong Duk , Byeon Jung-Sik , Jung Hwoon-Yong , Yang Suk-Kyun , Kim Jin-Ho 
Published: August 2014

Abstract
Helicobacter pylori (H pylori) infection induces a chronic inflammatory response, which promotes gastric carcinogenesis. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) plays a key role as a tumor suppressor in gastrointestinal cancers. The aim of this study was to elucidate the role of 15-PGDH in gastric carcinogenesis associated with H pylori. 15-PGDH expression in gastric biopsies from H pylori-infected (n=25) and non-infected (n=15) subjects was analyzed by quantitative real-time PCR, western blot analysis, and immunohistochemisty. 15-PGDH DNA methylation was evaluated by methylation specific PCR and pyrosequencing. The expression of 15-PGDH, Snail, ERK1/2, TLR4 and MyD88 in response to H pylori infection was assessed by immunoblot analysis. Compared to negative specimens, H pylori positive specimens had 2-fold lower 15-PGDH mRNA levels and significantly less 15-PGDH protein. In four H pylori infected subjects with longitudinal follow-up, the suppression of 15-PGDH expression was reversed by H pylori eradication therapy. In parallel with suppressing 15-PGDH expression, H pylori infection activated expression of TLR4 and MyD88 expression, increased levels of phospho-ERK1/2, and increased expression of Snail. Inhibition of MyD88 reversed suppression of 15-PGDH expression and reduced phosphorylated ERK1/2. Similarly, treatment with an ERK1/2 inhibitor also restored 15-PGDH expression. Heliocobacter pylori appeared to promote gastric carcinogenesis by suppressing15-PGDH. This process is mediated by the TLR4/MyD88 pathway via ERK1/2 and Snail transcriptional regulation. 15-PGDH may be a useful marker and a potential therapeutic target in H pylori-induced gastric carcinogenesis.
Citation Format: Yeon Mi Ryu, Seung-Jae Myung, Young Soo Park3, Ho June Song, Dong-Hoon Yang, Jin-Yong Jeong, Sun Mi Lee, Miyeoun Song, Do Hoon Kim, Hyo-Jeong Lee, Stephen P. Fink, Sandy D. Markowitz, Kee Wook Jung, Kyung-Jo Kim, Byong Duk Ye, Jung-Sik Byeon, Hwoon-Yong Jung, Suk-Kyun Yang, Jin-Ho Kim. Inhibition of 15-hydroxyprostaglandin dehydrogenase by Helicobacter pylori in human gastric carcinogenesis. [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 5378. doi:10.1158/1538-7445.AM2013-5378
Abstract 5381: p62/IMP2 promotes hepatocellular carcinoma (HCC) progression.
Authors: Lei Ningjing , Peng Bo , Li Yang , Chai Yurong , Zhang Jianying 
Published: August 2014

Abstract
Autoantibodies to autologous cellular antigens in cancer patients have been considered as reporters identifying antigenic changes in cellular factors involved in the transformation process. We have made use of such autoantibodies from hepatocellular carcinoma patients to immunoscreen a cDNA expression library and have identified a cytoplasmic RNA-binding protein p62. Autoantibodies to p62 have been detected in up to 21% of a cohort of hepatocellular carcinoma (HCC) patients. Further study has demonstrated that p62 is a member of insulin-like growth factor 2 mRNA binding protein family (IMPs), which is an isoform of IMP2. The three members of the IMP family (IMP1, 2 and 3) have been found to regulate translation of insulin-like growth factor 2 (IGF2) mRNA in a post-transcriptional manner. Since several studies have suggested that IMP1 and IMP3 play important roles in cancer progression, whether p62/IMP2 can also play a role in cancer formation remains to be investigated. In this study, we intend to interrogate the role of p62/IMP2 in HCC formation. We found that the expression of p62/IMP2 (57.5%) is significantly higher in HCC specimen than that in normal liver tissue (15.4%) by immunohistochemistry study. Furthermore, p62/IMP2 is detected to be overexpressed in several liver cancer cell lines. Depletion of p62/IMP2 via lentivirus-mediated knockdown in SNU449 liver cancer cell line decreased the cell proliferation. On the contrary, the ectopic overexpression of p62/IMP2 increased cell proliferation. Our data suggested that p62/IMP2 is overexpressed in liver cancer and is functionally correlated with cancer cell growth.
Citation Format: Ningjing Lei, Bo Peng, Yang Li, Yurong Chai, Jianying Zhang. p62/IMP2 promotes hepatocellular carcinoma (HCC) progression. [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 5381. doi:10.1158/1538-7445.AM2013-5381
Abstract 5397: MYC-driven glutamine metabolism promotes antiestrogen resistance in breast cancer.
Authors: Shajahan Ayesha N. , Cook Katherine L. , Schwartz-Roberts Jessica L. , Eltayeb Ahreej E. , Demas Diane M. , Warri Anni , Hilakivi-Clarke Leena , Metallo Steven , Clarke Robert 
Published: August 2014

Abstract
About 70% of newly diagnosed cases of invasive breast cancer in the U.S. will be estrogen receptor alpha positive (ER+). Endocrine therapy is the least toxic and most effective means to manage the hormone-dependent breast cancer, administered as an antiestrogen, e.g., Tamoxifen (TAM) or Faslodex (FAS; Fulvestrant; ICI 182,780) or an aromatase inhibitor (AI), e.g., Letrozole (LET). However, advanced ER+ breast cancer that has become resistant to endocrine therapy remains a significant clinical problem. Here we show that in breast cancer cells and rat tumors with acquired antiestrogen resistance, MYC, a oncogenic transcription factor, is overexpressed. Inhibition of MYC with small molecule inhibitor or siRNA resensitizes resistant cells to antiestorgens by inducing apoptosis. MYC inhibition in resistant cells also inhibited glutamine uptake and decreased levels of ASCT2/SLC1A5, a glutamine transporter. Resistant cells showed significant increase in cell proliferation in response to glutamine than sensitive cells. Moreover, resistant cells showed increased sensitivity to an inhibitor of glutaminase, GLS, an enzyme that hydrolysis of glutamine to glutamate. Thus, MYC promotes increased dependence on glutamine in antiestrogen resistant cells, and targeting glutamine metabolism could help circumvent antiestrogen resistance. Overreaching goal of this study is to and to identify effective therapies to treat endocrine resistant breast cancer.
Citation Format: Ayesha N. Shajahan, Katherine L. Cook, Jessica L. Schwartz-Roberts, Ahreej E. Eltayeb, Diane M. Demas, Anni Warri, Leena Hilakivi-Clarke, Steven Metallo, Robert Clarke. MYC-driven glutamine metabolism promotes antiestrogen resistance 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 5397. doi:10.1158/1538-7445.AM2013-5397
Abstract 5398: TARDBP regulates glycolysis in hepatocellular carcinoma by regulating PFKP through miR-520.
Authors: Park Yun-Yong , Kim Sang Bae , Han Hee Dong , Sohn Bo-Hwa , Liang Jiyong , Lu Yiling , Mills Gordon , Sood Anil , Lee Ju-Seog 
Published: August 2014

Abstract
Metabolic changes are common features of many cancer cells and are frequently associated with the clinical outcome of patients with various cancers including hepatocellular carcinoma (HCC). Thus, aberrant metabolic pathways in cancer cells are attractive targets for cancer therapy. However, our understanding of cancer-specific regulatory mechanisms of cell metabolism is still very limited. We found that Tat activating regulatory DNA-binding protein (TARDBP) is a novel regulator of glycolysis in HCC cells. TARDBP regulates expression of the platelet isoform of phosphofructokinase (PFKP), the rate-limiting enzyme of glycolysis that catalyzes the irreversible conversion of fructose-6-phosphate to fructose-1,6-bisphosphate. Silencing of TARDBP expression in multiple HCC cell lines leads to impaired glucose metabolism and inhibition of in vitro and in vivo growth of HCC cells. Notably, the miR-520 family is an intermediate regulator of TARDBP-mediated regulation of glycolysis. Mechanistically, TARDBP suppressed expression of the miR-520 family, which in turn inhibited expression of PFKP. We further showed that expression of PFKP is significantly associated with the overall survival of patients with HCC. Our study provides new mechanistic insights into the regulation of glycolysis in HCC cells and reveals TARDBP as a potential therapeutic target for HCC.
Citation Format: Yun-Yong Park, Sang Bae Kim, Hee Dong Han, Bo-Hwa Sohn, Jiyong Liang, Yiling Lu, Gordon Mills, Anil Sood, Ju-Seog Lee. TARDBP regulates glycolysis in hepatocellular carcinoma by regulating PFKP through miR-520. [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 5398. doi:10.1158/1538-7445.AM2013-5398
Abstract 5404: Metabolic stress played a role in dasatinib-induced EGFR degradation and apoptosis in head and neck cancer.
Authors: Lin Yu-Chin , Wu Meng-Hsuan , Wei Tzu-Tang , Chen Kuen-Feng , Cheng Ann-Lii , Chen Ching-Chow 
Published: August 2014

Abstract
Head and neck squamous cell carcinoma (HNSCC) is a worldwide disease with aggressive course and dismal outcome. Dasatinib, a Bcr-abl and Src in hibitor, has been approved clinically for CML and shown activities against solid tumors in vitro. In our recent work, degradation of epidermal growth factor receptor (EGFR) plays a role in dasatinib-induced apoptosis in HNSCC cells. We further revealed the role of metabolic stress in dasatinib-induced EGFR degradation and apoptosis. Dasatinib decreased cellular ATP, and activated AMPK activation and induced endoplasmic reticulum stress (ER stress) as well. Inhibition or knockdown of AMPK reversed dasatinib-induced EGFR degradation, and pharmacological activation of AMPK led to ER stress and EGFR degradation. Addition of ER stress inhibitor to dasatinib reversed EGFR degradation and apoptosis, and pharmacologic activation of ER stress resulted in EGFR degradation. In conclusion, metabolic stress may play a role in dasatinib-induced EGFR degradation and apoptosis in HNSCC cells.
Citation Format: Yu-Chin Lin, Meng-Hsuan Wu, Tzu-Tang Wei, Kuen-Feng Chen, Ann-Lii Cheng, Ching-Chow Chen. Metabolic stress played a role in dasatinib-induced EGFR degradation and apoptosis in 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 5404. doi:10.1158/1538-7445.AM2013-5404
Abstract 5408: Enhancement of the anti-tumor activity of afatinib by inhibition of glycolysis in non-small cell lung cancer harboring the EGFR T790M mutation .
Authors: Cho Byoung Chul , Kim Hyun-Jung , Lim Sun Min 
Published: August 2014

Abstract
The secondary epidermal growth factor receptor (EGFR) T790M is the most common mechanism of resistance to reversible EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC) patients with activating EGFR mutations. Although afatinib (BIBW2992), a second-generation irreversible EGFR TKI, was expected to overcome the acquired resistance, it showed limited efficacy in a recent phase III clinical study. In this study, we found that the inhibition of glycolysis using 2-deoxy-D-glucose (2DG) improves the efficacy of afatinib in H1975 and PC9-GR, which are NSCLC cells with EGFR T790M. Treatment with a combination of 2DG and afatinib induced intracellular ATP depletion in both H1975 and PC9-GR cells, resulting in activation of AMP-activated protein kinase (AMPK). AMPK activation played a central role in the cytotoxicity of the combined treatment with 2DG and afatinib through inhibition of mammalian target of rapamycin (mTOR). The alteration of the AMPK/mTOR signaling pathway by inhibition of glucose metabolism induced specific downregulation of Mcl-1, a member of anti-apoptotic Bcl-2 family, through translational control. The enhancement of afatinib sensitivity by treatment of 2DG was confirmed in in vivo PC9-GR xenograft model. In conclusion, this study examined whether inhibition of glucose metabolism using 2DG enhances the sensitivity to afatinib in NSCLC cells with EGFR T790M through regulation of AMPK/mTOR/Mcl-1 signaling pathway. These data suggest that the combined use of an inhibitor of glucose metabolism and afatinib is a potential therapeutic strategy for treatment of patients with acquired resistance to reversible EGFR TKIs due to secondary EGFR T790M.
Citation Format: Byoung Chul Cho, Hyun-Jung Kim, Sun Min Lim. Enhancement of the anti-tumor activity of afatinib by inhibition of glycolysis in non-small cell lung cancer harboring the EGFR T790M mutation . [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 5408. doi:10.1158/1538-7445.AM2013-5408
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 5410: Modulating metabolic homeostasis as a therapeutic tool for leukemia.
Authors: Attia Ramy R. , Min Jaeki , Guy Rodney K. 
Published: August 2014

Abstract
Genetic studies in humans and rodents support the notion that alterations in metabolic homeostasis can directly contribute to carcinogenesis and metabolic processes may be targets for therapy. The nuclear hormone receptors (NR) control a wide variety of metabolic processes by regulating the expression of genes encoding key enzymes, transporters, and other mediators. Therefore we explored potential links between cellular metabolic control by NRs and viability of cancer cells. In this study we tested the effect of 127 NR modulators, targeting receptors known to be important in regulating metabolism or known to be viable cancer targets on the growth of different leukemic cells lines. Of the compounds tested 8, mainly targeting ER and RAR, induced significant apoptosis in these leukemias. The effects of the 8 active compounds on mitochondrial metabolism were tested in Jurkat cells and 5 compounds significantly reduced lactate levels. However, only the synthetic retinoid (CD437) significantly affected pyruvate dehydrogenase complex activity. CD437 also effected the expression of genes involved in leukemia development and therapeutic responses with the PKC pathway being the primary target. CD437 induced PKC Kinase activity and activated its downstream signals AKT and JNK. CD437 downregulated CPT-1a,and decreased the overall O2 consumption rate. Additional CD437 induced genes included those involved in the mitochondrial respiratory complex I and III and increased the production of ROS. Our results indicate that the apoptotic effect of CD437 can be linked to its regulation of mitochondrial oxidative metabolism.
Citation Format: Ramy R. Attia, Jaeki Min, Rodney K. Guy. Modulating metabolic homeostasis as a therapeutic tool for leukemia. [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 5410. doi:10.1158/1538-7445.AM2013-5410
Abstract 5415: Targeting lipogenic signaling to repress cancer cell growth.
Authors: Wang Chenguang , Li Weihua , Zhou Jie , Tai Yanhong , Gu Weiting , Das Bhaskar C. , Ji Junyuan 
Published: August 2014

Abstract
The significantly enhanced lipogenesis is a metabolic hallmark of rapidly proliferating tumor cells. Although most normal cells acquire the bulk of their fatty acids from circulation, tumor cells synthesize more than 90% of required lipids de novo. The sterol regulatory element-binding protein 1 (SREBP1), encoded by SREBF1 gene, is a master regulator of lipogenic gene expression. Although it is known that SREBP1 and its target genes are overexpressed in a variety of cancers, the role of SREBP1 in endometrial cancer is largely unknown. Herein, we screened a panel of endometrial cancer specimen for their lipogenic gene expression by quantitative PCR and showed a significant increase in mRNA abundance of SREBF1, SREBF2, and FASN genes in cancer compared to normal endometrium. Immunohistochemical staining confirmed SREBP1 protein overexpression and further demonstrated increased nuclear distribution of SREBP1 in EC. SREBP1 promotes cellular proliferation in cell culture and enhances tumor growth in a xenograft model. Knockdown of endogenous SREPF1 gene impaired the viability of cells cultured in medium supplemented with lipid-depleted serum. BF175, a small molecule inhibitor designed to target SREBP1, repressed SREBP1-dependent gene expression and cell growth and induced EC cell death. We extended our observation to over 100 cancer cell lines from 12 different cancer types and showed promising results of BF175 in repressing tumor growth and inducing cell death. Together, this study established a role of SREBP1 in tumor growth and validated BF175 for its therapeutic effectiveness in targeting SREBP1 and lipogenesis to block cancer cell growth.
Citation Format: Chenguang Wang, Weihua Li, Jie Zhou, Yanhong Tai, Weiting Gu, Bhaskar C. Das, Junyuan Ji. Targeting lipogenic signaling to repress cancer cell growth. [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 5415. doi:10.1158/1538-7445.AM2013-5415
Abstract 5425: Epidermal respiratory uncoupling blocks skin carcinogenesis by inhibiting Akt.
Authors: Nowinski Sara M. , Rundhaug Joyce E. , Rho Okkyung , Lago Cory U. , Fischer Susan M. , DiGiovanni John , Mills Edward M. 
Published: August 2014

Abstract
Metabolic reprogramming, characterized by increased glycolysis and decreased oxygen consumption, is now considered a hallmark of malignancy. Mitochondrial uncoupling proteins oppose this phenotype by driving futile mitochondrial respiration that is uncoupled from ATP synthesis, and mice expressing a keratin 5 - uncoupling protein 3 (K5-UCP3) transgene in the epidermis are completely protected from the formation of chemically induced skin carcinomas. We crossed these mice with Tg.AC mice that express a cutaneous oncogenic v-Ha-Ras transgene, bypassing tumor initiation. Bi-transgenic Tg.AC/K5-UCP3 mice were still remarkably resistant to 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumorigenesis, indicating that UCP3 likely inhibits tumor promotion. Accordingly, K5-UCP3 mice exhibited striking resistance to epidermal proliferation induced by TPA as measured using a bromodeoxyuridine (BrdU) based labeling assay. In agreement with these data, K5-UCP3 epidermis failed to show activation of Akt (Ser473 & Thr308 phosphorylation) and phosphorylation of downstream signaling molecules in response to TPA treatment. This effect corresponded to decreased expression of cyclins D1 and A, and increased expression of the cell cycle inhibitory proteins p21 and p27. Decreased Akt activation was also observed in vitro in response to epidermal growth factor (EGF) treatment of serum starved, isolated K5-UCP3 primary keratinocytes. To test the notion that the lack of Akt signaling was responsible for the lack of TPA induced proliferation and tumorigenesis, we bred bi-transgenic K5-UCP3/K5-Akt mice, and found that over-expression of wild type Akt recovered proliferation following TPA treatment. Future experiments will elucidate the mechanism underlying UCP3-induced inhibition of Akt activation and signaling.
Citation Format: Sara M. Nowinski, Joyce E. Rundhaug, Okkyung Rho, Cory U. Lago, Susan M. Fischer, John DiGiovanni, Edward M. Mills. Epidermal respiratory uncoupling blocks skin carcinogenesis by inhibiting Akt. [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 5425. doi:10.1158/1538-7445.AM2013-5425