bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 184: miR-379/411 cluster regulates IL-18 and contributes to drug resistance in malignant pleural mesothelioma
Authors: Miyanaga Akihiko , Seike Masahiro , Yamamoto Kazuo , Takeuchi Susumu , Noro Rintaro , Minegishi Yuji , Kubota Kaoru , Gemma Akihiko 
Published: August 2015

Abstract
Malignant pleural mesothelioma (MPM) is a rapidly fatal malignancy that is increasing in incidence in Japan. In this study, we performed gene and microRNA (miRNA) expres¬sion profiling to identify novel therapeutic targets in MPM cells. Based on relative sensitivities to pemetrexed (PEM) and the histone deacetylase (HDAC) inhibitor, vorinostat (SAHA), 211H cells were determined to be the only sensitive MPM cell line out of the 6 tested. On the same series of cell lines, we performed whole genome transcriptomic profiling via DNA microarrays and pathway analysis of the derived data. Of particular note, IL-18 gene expression levels were signifi¬cantly higher in the cell lines that were either drug resistant or displayed intermediate sensitivity, compared to the sensitive 211H cell line. Pathway analysis revealed IL-18 as an impor¬tant gene associated with drug sensitivity of MPM cells. A relationship between IL-18 overexpression and drug resistance was also observed following targeted assessment of 10 cyto¬kine genes using quantitative RT-PCR. miRNA expression profiles were evaluated in the MPM cell line panel in order to discern the mechanism of IL-18 induction in the drug-resistant lines. We found that miR-379 and miR-411 belonged to the same cluster of miRNAs located on chromosome 14q32 that commonly target the IL-18 gene. Luciferase reporter assays revealed that miR-379 and miR-411 directly target the IL-18 gene. Introduction of miR-379 plus miR-411, as well as IL-18 silencing, significantly suppressed the invasive capacity of MESO1 cells in vitro. Furthermore, the use of either PEM or SAHA together with miR-379 plus miR-411 mimics mediated increased sensitivity to these drugs in MESO1 cells. These results suggest that the miR-379/411 cluster may provide new therapeutic opportunities for advanced MPM patients, depending on the nature of IL-18 gene expression.
Citation Format: Akihiko Miyanaga, Masahiro Seike, Kazuo Yamamoto, Susumu Takeuchi, Rintaro Noro, Yuji Minegishi, Kaoru Kubota, Akihiko Gemma. miR-379/411 cluster regulates IL-18 and contributes to drug resistance in malignant pleural mesothelioma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 184. doi:10.1158/1538-7445.AM2015-184
Abstract 1843: Novel actions of next-generation taxanes benefit advanced stages of prostate cancer
Authors: de Leeuw Renee , Berman-Booty Lisa , Schiewer Matthew , Ciment Stephen , Den Robert , Dicker Adam , Kelly William , Trabulsi Edouard , Lallas Costas , Gomella Leonard , Knudsen Karen 
Published: August 2015

Abstract
Purpose: To improve the outcomes of patients with castrate resistant prostate cancer (CRPC), there is an urgent need for more effective therapies and approaches that individual specific treatments for patients with CRPC. The current studies compared the novel taxane, cabazitaxel with the previous generation docetaxel, and aimed to determine which tumors are most likely to respond.
Experimental design: Cabazitaxel (CBTX) and docetaxel (DCTX) were compared via in vitro modeling to determine molecular mechanism, biochemical and cell biological impact, and cell proliferation, which was further assessed ex vivo in human tumor explants. Isogenic pairs of RB knockdown and control cells were interrogated in vitro, and in xenograft tumors for cabazitaxel response.
Results: The data herein show that i. CBTX exerts stronger cytostatic and cytotoxic response compared to DCTX, especially in CRPC; ii. CBTX induces aberrant mitosis, leading to pyknotic and multinucleated cells; iii. taxanes do not act through the androgen receptor (AR); iv. Gene expression profiling reveals distinct molecular actions for CBTX v. tumors that have progressed to castration resistance via loss of RB show enhanced sensitivity to CBTX.
Conclusions: CBTX not only induces improved cytostatic and cytotoxic effects, but also impacts distinct molecular pathways, compared to DCTX, which could underlie its efficacy after DCTX treatment has failed in CRPC patients. Finally, RB is identified as the first potential biomarker that could define the therapeutic response to taxanes in metastatic CRPC. This would suggest that loss of RB function induces sensitization taxanes, which could benefit up to 50% of CRPC cases.
Citation Format: Renee de Leeuw, Lisa Berman-Booty, Matthew Schiewer, Stephen Ciment, Robert Den, Adam Dicker, William Kelly, Edouard Trabulsi, Costas Lallas, Leonard Gomella, Karen Knudsen. Novel actions of next-generation taxanes benefit advanced stages of prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1843. doi:10.1158/1538-7445.AM2015-1843
Abstract 1844: Genome wide analysis of AR-cell cycle interplay reveals novel functions in cancer
Authors: McNair Christopher , Goodwin Jonathan , Augello Michael , Urbanucci Alfonso , Schiewer Matthew , Comstock Clay , Ertel Adam , Wang Liguo , Wang Qianben , Mills Ian , Li Wei , Carroll Jason , Knudsen Karen 
Published: August 2015

Abstract
The androgen receptor (AR) plays a vital role in prostate cancer (PCa) due in part to its ability to interact with cell cycle components in order to drive cell cycle transition. Numerous points of cross-talk have been identified, wherein specific components of the cell cycle machinery “feed back” to modulate AR function, and these interactions are thought to be altered in human malignancies. Despite these observations, the majority of genome wide analyses for AR have been performed in cells that have exited cell cycle (G0). Here, the cell cycle dependent AR transcriptome and cistrome was identified, revealing new and unexpected functions for AR in cycling tumor cells. In studies to be discussed, cells were arrested in 5 distinct phases of the cell cycle, stimulated with androgen, and AR activity assessed through gene expression and ChIP-Seq analyses. In AR binding analyses, significant overlap was seen with previously identified sites, but were accompanied by novel binding events that could be segregated into those that are specific to cycling cells and occur in all phases (“cell cycle common”) or show cell cycle stage specific binding (“phase exclusive”). Over 50% of the cell cycle common sites, and up to 95% of the phases exclusive sites were novel AR occupied sites. Additionally, using a “guilty by association” approach to determine potentially AR regulated genes from this novel cistromic data, it was determined that close to 50% of cell cycle common, and 70% of phase exclusive binding uncover novel candidates for AR regulation. Cistrome data was therefore overlaid with microarray data, to prioritize discovery of meaningful, cell cycle specific AR binding events. Analyses to be discussed reveal striking new insight into disease relevant AR function. In sum, these data rigorously demonstrate that AR acts in a cell cycle dependent manner, and that these functions of AR have a major impact on tumor cell phenotypes.
Citation Format: Christopher McNair, Jonathan Goodwin, Michael Augello, Alfonso Urbanucci, Matthew Schiewer, Clay Comstock, Adam Ertel, Liguo Wang, Qianben Wang, Ian Mills, Wei Li, Jason Carroll, Karen Knudsen. Genome wide analysis of AR-cell cycle interplay reveals novel functions in cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1844. doi:10.1158/1538-7445.AM2015-1844
Abstract 1846: Catalytic topoisomerase II inhibitors suppress the androgen receptor signaling and prostate cancer progression
Authors: Li Haolong , Xie Ning , Gleave Martin , Dong Xuesen 
Published: August 2015

Abstract
Background: Although the new generation of anti-androgens (e.g. MDV) improves survival of metastatic prostate cancer patients, tumors eventually recur indicating that additional therapeutic means is required to fully block the functions of the androgen receptor (AR). Since DNA topoisomerase II (Topo II) was demonstrated to be essential for AR to initiate gene transcription, this study tested whether catalytic inhibitors of Topo II can suppress the AR signaling and block prostate tumor growth.
Methods and Results: Androgen-dependent and MDV-resistant prostate cancer cells were treated with increasing doses of catalytic Topo II inhibitors, ICRF187 and ICRF193. Luciferase reporter assays showed that both inhibitors suppressed the transcriptional activities of wild-type AR, mutant AR (F876L and W741C), and AR-V7 splice variant. ICRF187 and ICRF193 decreased AR recruitment to its target promoters and reduced AR nuclear localization. Both ICRF187 and ICRF193 inhibited androgen-dependent and MDV-resistant cancer cell proliferation and delayed cell cycling at the G2/M stages. In castration-resistant LNCaP tumors, ICRF187 inhibited tumor growth, PSA secretion and expressions of several other AR regulated genes. These repressive effects became stronger when tumors were co-treated with MDV. Additionally, ICRF187 effectively inhibited tumor growth of MDV-resistant MR49F as well as castration-resistant 22RV1 xenografts.
Conclusions: Catalytic Topo II inhibitors can block the AR signaling and inhibit tumor growth of castration-resistant xenografts, suggesting their potential applications in treating castration-resistant cancers in patients.
Citation Format: Haolong Li, Ning Xie, Martin Gleave, Xuesen Dong. Catalytic topoisomerase II inhibitors suppress the androgen receptor signaling and prostate cancer progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1846. doi:10.1158/1538-7445.AM2015-1846
Abstract 1875: Development of a dietary inflammation score and its association with incident, sporadic colorectal adenoma
Authors: Holmes Ashley C. , Bostick Roberd M. 
Published: August 2015

Abstract
It is now well established that inflammation is linked to colorectal carcinogenesis and other chronic diseases. The ability to characterize specific dietary and lifestyle components as having pro- or anti-inflammatory effects is a promising area of cancer prevention. We developed a “dietary inflammation score” based on associations of independent dietary components with plasma C-reactive protein (CRP) in the combined Markers of Adenomatous Polyps (MAPs) case-control studies, and investigated the association of the score with incident, sporadic colorectal adenoma in the same population. First, we excluded individuals who regularly took non-steroidal anti-inflammatory drugs (NSAIDs) and multivitamins, and among those remaining (n = 369) calculated the multivariable-adjusted associations of the individual dietary components with CRP, used the strengths of associations as weights, and summed the weighted dietary components to create an overall summary dietary inflammation score. Food components were included in the score based on biological plausibility and previous literature, and included four categories of meat, nuts, pepper, coffee, tea, high- and low-fat dairy products, refined and whole grains, and twelve botanical categories. The crude odds ratio (OR) for the association of the highest dietary score tertile with log-transformed CRP was 1.92 (95% confidence interval [CI]: 1.13, 3.27); after adjusting for age, sex, total energy intake, and lifestyle inflammation score category, the OR was 1.89 (95% CI: 1.06, 3.36). The association tended to be stronger among older individuals, males, and adenoma cases. The overall score was more strongly associated with CRP than was any individual dietary component. Next, to assess the association of the dietary inflammation score with adenomas, we used the entire MAPs population (n = 188 cases and 325 controls)– including the regular NSAID and multivitamin users. The crude OR for the association of the highest dietary score tertile with incident adenoma was 1.30 (95% CI: 0.84, 2.02), an association that tended to be stronger among men and those who regularly took aspirin or other NSAIDs. Multivariable adjustment did not appreciably change these estimates. The results from this pilot study suggest that diet may contribute to systemic levels of inflammation, and support further investigation of a dietary inflammation score with colorectal neoplasms and other chronic diseases in larger studies.
Citation Format: Ashley C. Holmes, Roberd M. Bostick. Development of a dietary inflammation score and its association with incident, sporadic colorectal adenoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1875. doi:10.1158/1538-7445.AM2015-1875
Abstract 1879: Prospective study of marine ω-3 polyunsaturated fatty acids and risk of colorectal cancer according to microsatellite instability
Authors: Song Mingyang , Nishihara Reiko , Wu Kana , Qian Zhi Rong , Kim Sun A. , Sukawa Yasutaka , Mima Kosuke , Inamura Kentaro , Masuda Atsuhiro , Yang Juhong , Fuchs Charles S. , Giovannucci Edward L. , Ogino Shuji , Chan Andrew T. 
Published: August 2015

Abstract
Background: Chronic inflammation is involved in the development of colorectal cancer (CRC) and microsatellite instability (MSI), a distinct phenotype of CRC. Experimental evidence indicates an anti-inflammatory and antineoplastic effect of marine ω-3 polyunsaturated fatty acids (PUFAs). However, epidemiologic data remain inconclusive.
Methods: We investigated whether the association between marine ω-3 PUFAs and CRC varies by MSI-defined subtypes of tumors in the Nurses’ Health Study and Health Professionals Follow-up Study. We collected updated data on marine ω-3 PUFA intake and documented 1,125 CRC cases during 24-26 years of follow-up. We determined the MSI status of tumors using 10 microsatellite markers, and classified cases into MSI-high tumors in which ≥30% of the microsatellite markers demonstrated instability, and microsatellite stable (MSS) tumors in which &lt;30% of the markers demonstrated instability. Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of microsatellite stable (MSS) tumors and MSI-high tumors in relation to marine ω-3 PUFA intake.
Results: There was no statistically significant association between marine ω-3 PUFA intake and overall incidence of CRC. However, a statistically significant difference was detected by MSI status (Pheterogeneity = 0.02): high marine ω-3 PUFA intake was associated with a lower risk of MSI-high tumors (comparing ≥0.30g/d to &lt;0.10g/d: multivariable HR = 0.54, 95% CI = 0.35 to 0.83, P for linearity = 0.03) but not MSS tumors (HR = 0.97, 95% CI = 0.78 to 1.20, P for linearity = 0.28). This differential association appeared to be independent of CpG island methylator phenotype and BRAF mutation status.
Conclusions: High marine ω-3 PUFA intake is associated with lower risk of MSI-high CRC but not MSS tumors, suggesting a potential role of ω-3 PUFAs in protection against CRC through DNA mismatch repair. Further research is needed to confirm our findings and elucidate potential underlying mechanisms.
Citation Format: Mingyang Song, Reiko Nishihara, Kana Wu, Zhi Rong Qian, Sun A. Kim, Yasutaka Sukawa, Kosuke Mima, Kentaro Inamura, Atsuhiro Masuda, Juhong Yang, Charles S. Fuchs, Edward L. Giovannucci, Shuji Ogino, Andrew T. Chan. Prospective study of marine ω-3 polyunsaturated fatty acids and risk of colorectal cancer according to microsatellite instability. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1879. doi:10.1158/1538-7445.AM2015-1879
Abstract 1894: Transcriptomic profile analysis of PANC-1 cells in response to metformin and aspirin
Authors: Yue Wen , Wang Tao , Yang Chung S. , Xu Qing , DiPaola Robert S. , Tan Xiang-Lin 
Published: August 2015

Abstract
The commonly used drugs, metformin and aspirin have been studied extensively as cancer preventative and therapeutic agents. However, the underlying molecular mechanisms for the inhibitory effects of pancreatic cancer development remain largely unknown. To gain further insight into their biological function in pancreatic cancer, we conducted a transcriptomic analysis using RNA sequencing to assess the differential gene expression induced by metformin (5 mM) and aspirin (2 mM), alone or in combination, after treatment of PANC-1 cells for 48 hours. Compared to untreated control, metformin alone up-regulated 109 genes, and down-regulated 78 genes, aspirin alone down-regulated 43 genes only, while the combination of metformin and aspirin up-regulated 499 genes, and down-regulated 702 genes (fold-change &gt; 2, P &lt; 10−5). Of the top 25 genes (fold-change &gt; 10, P &lt; 10−10) regulated by the combination of metformin and aspirin, NGFR, NPTX1, and UNC5B were up-regulated more than 10-fold, while PCDH18, CCL2, RASL11A, FAM111B, BMP5, SKIDA1, and CDH18 were down-regulated more than 15-fold. The ingenuity pathway analysis (IPA) was applied to explore the top signaling pathways regulated by metformin and aspirin. The top canonical pathways, “cholesterol biosynthesis”, “cell cycle: G1/S checkpoint regulation”, and “axonal guidance signaling” were the most statistical significant pathways that were modulated by the combination of metformin and aspirin. It is worth noting that the axon guidance signaling and the cholesterol biosynthesis pathways have recently been reported to play an important role in the development of pancreatic cancer. Further studies are warranted to explore the effects of metformin and aspirin on these two pathways. Although results are preliminary and need further functional validation, these data provide, for the first time, a transcriptional profile of pancreatic cancer cells in response to metformin and aspirin.
Citation Format: Wen Yue, Tao Wang, Chung S. Yang, Qing Xu, Robert S. DiPaola, Xiang-Lin Tan. Transcriptomic profile analysis of PANC-1 cells in response to metformin and aspirin. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1894. doi:10.1158/1538-7445.AM2015-1894
Abstract 1897: Metformin as a chemoprevention agent for lung squamous cancer
Authors: Asiedu Michael K. , Barron Matthew R. , Aubry Marie Christine , Wigle Dennis 
Published: August 2015

Abstract
Background: Squamous cell carcinoma is a common type of lung cancer and accounts for about 25-30% of all non-small cell lung cancers. Metformin is a drug commonly prescribed as first-line treatment for type-2 diabetes, with some evidence showing that the drug can also act directly on cancer cells. One of the mechanisms of action is through activation of the AMP-activated protein kinase (AMPK) which is involved in control of energy homeostasis in cells. The goal of this study was to determine metformin response in different cell lines and different cellular contexts, and to use that information to work towards the generation of a metformin “sensitivity index” that could be used guide individualized chemoprevention.
Methods: We performed cell survival analysis on squamous cell carcinoma lines, skin fibroblast lines and differentiated IPS cell lines to identify differences in metformin response both for different cell lines and for cells in different cell context. Microarray profiling was used to determine differentially expressed genes that are regulated by metformin treatment in order to generate signatures of metformin response.
Results:
Cell survival analysis showed that different cell lines respond differently to metformin, and cells of identical genotypes in a variety of differentiated states or cellular contexts also show differential response to metformin. Gene expression profiling of metformin treated cells identified differentially expressed genes that may mediate metformin response.
Conclusion: Differences in response to metformin treatment across a variety of cell lines and cellular contexts suggest heterogeneity that may be patient-specific. Using genes that are differentially expressed following metformin treatment, we identified a 55-gene set that can be used as a metformin “sensitivity index” to stratify patients into metformin responders and non-responders and guide individualized chemoprevention.
Citation Format: Michael K. Asiedu, Matthew R. Barron, Marie Christine Aubry, Dennis Wigle. Metformin as a chemoprevention agent for lung squamous cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1897. doi:10.1158/1538-7445.AM2015-1897