Metabolic Changes in Ovarian Cancer最新文献

{"title":"Abstract A28: Beta-escin inhibits ovarian cancer metastasis by targeting the tumor microenvironment","authors":"H. Kenny, Madhu Lal, M. Shen, Betul Kara, Chun-Yi Chiang, K. Watters, Peter C. Hart, M. Ferrer, E. Lengyel","doi":"10.1158/1557-3265.OVCA17-A28","DOIUrl":"https://doi.org/10.1158/1557-3265.OVCA17-A28","url":null,"abstract":"","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74116975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract A57: Drug sensitivity and resistance testing (DSRT) of clinically important compounds on primary ovarian cancer cell lines","authors":"P. Roering, Piia Mikkonen, S. Potdar, K. Wennerberg, J. Hynninen, S. Grénman, A. Auranen, O. Carpén, Katja Kaipio","doi":"10.1158/1557-3265.OVCA17-A57","DOIUrl":"https://doi.org/10.1158/1557-3265.OVCA17-A57","url":null,"abstract":"","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81625273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract A51: FOXM1 inhibition by thiostrepton synergizes with olaparib by attenuating adaptive response in ovarian cancer cells","authors":"Pingping Fang, Jill A. Madden, Lisa Neums, J. Chien","doi":"10.1158/1557-3265.OVCA17-A51","DOIUrl":"https://doi.org/10.1158/1557-3265.OVCA17-A51","url":null,"abstract":"","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84384924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract IA08: Kinase-mediated modulation of paclitaxel sensitivity in ovarian cancer","authors":"Zhen-Fu Lu","doi":"10.1158/1557-3265.ovca17-ia08","DOIUrl":"https://doi.org/10.1158/1557-3265.ovca17-ia08","url":null,"abstract":"","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"87 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81110028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract A30: Autotaxin-induced miRNA exportation and associated mechanisms contributing to tumorigenesis and immune modulation","authors":"Sudeepti S. Kuppa, Balázs Rada, Mandi M. Murph","doi":"10.1158/1557-3265.ovca17-a30","DOIUrl":"https://doi.org/10.1158/1557-3265.ovca17-a30","url":null,"abstract":"","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87103928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract PR06: ARIEL3: A phase 3, randomized, double-blind study of rucaparib vs placebo following response to platinum-based chemotherapy for recurrent ovarian cancer (OC)","authors":"R. Coleman, A. Oza, D. Lorusso, C. Aghajanian, A. Oaknin, A. Dean, N. Colombo, J. Weberpals, A. Clamp, G. Scambia, A. Leary, R. Holloway, D. O’Malley, T. Cameron, L. Maloney, S. Goble, K. Lin, James X. Sun, H. Giordano, J. Ledermann","doi":"10.1158/1557-3265.OVCA17-PR06","DOIUrl":"https://doi.org/10.1158/1557-3265.OVCA17-PR06","url":null,"abstract":"Background: Rucaparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, is approved in the United States for treatment of women with deleterious BRCA mutation (germline and/or somatic) associated advanced OC who have been treated with two or more chemotherapies. Rucaparib has also demonstrated antitumor activity in the treatment setting in patients (pts) with BRCA wild-type associated recurrent OC whose tumor has high genomic loss of heterozygosity (LOH). ARIEL3 evaluated rucaparib vs placebo as maintenance treatment in pts with recurrent platinum-sensitive OC. Methods: Eligible pts received ≥2 prior platinum-based therapies, had platinum-sensitive OC (disease progression ≥6 mo after penultimate platinum), and achieved a complete response (RECIST v1.1) or partial response (RECIST v1.1 or Gynecologic Cancer InterGroup CA-125 criteria) to their most recent platinum. All pts were required to have CA-125 less than the upper limit of normal. Pts were randomized 2:1 to receive oral rucaparib 600 mg BID or placebo. Investigator-assessed progression-free survival (PFS) (primary endpoint) was assessed in a step-down procedure for 3 nested cohorts: (1) BRCA mutant (deleterious germline or somatic BRCA mutation); (2) homologous recombination deficient (HRD) (BRCA mutant or BRCA wild type/LOH high); and (3) intent-to-treat (ITT) population. PFS was also assessed by blinded independent central review (BICR) (secondary endpoint) and LOH status in pts with BRCA wild type OC (exploratory endpoint). Adverse events (AEs) were summarized descriptively. Results: ARIEL3 enrolled 564 pts (375, rucaparib; 189, placebo). Nearly 200 pts (n=196) had BRCA mutation-associated OC. Of these pts, 130 had a germline BRCA mutation (82 [21.9%], rucaparib; 48 [25.4%], placebo), 56 had a somatic BRCA mutation (40 [10.7%], rucaparib; 16 [8.5%], placebo), and 10 pts had tumors with germline and/or somatic BRCA status unknown (8 [2.1%], rucaparib; 2 [1.1%], placebo). Median investigator-assessed PFS in the BRCA-mutant cohort (130, rucaparib; 66 placebo) was 16.6 mo vs 5.4 mo (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.16-0.34; P Conclusion: Rucaparib significantly improved PFS vs placebo in pts with platinum-sensitive, recurrent OC in all primary analysis groups of pts with platinum-sensitive, recurrent OC. Additionally, rucaparib significantly improved PFS vs placebo in pts with BRCA wild-type OC (LOH high and LOH low). Clinical trial identification: NCT01968213. This abstract is also being presented as Poster A47. Citation Format: Robert L. Coleman, Amit M. Oza, Domenica Lorusso, Carol Aghajanian, Ana Oaknin, Andrew Dean, Nicoletta Colombo, Johanne I. Weberpals, Andrew Clamp, Giovanni Scambia, Alexandra Leary, Robert W. Holloway, David M. O’Malley, Terri Cameron, Lara Maloney, Sandra Goble, Kevin Lin, James Sun, Heidi Giordano, Jonathan A. Ledermann. ARIEL3: A phase 3, randomized, double-blind study of rucaparib vs placebo following response to platinum-based chemothera","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88878627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract A38: Modeling ascites-induced changes in peritoneal mechanobiology and ovarian cancer metastatic success","authors":"Y. Klymenko, R. B. Wates, Yueying Liu, R. Lombard, Holly E. Weiss-Bilka, L. Campbell, D. Wagner, M. Ravosa, M. Stack","doi":"10.1158/1557-3265.OVCA17-A38","DOIUrl":"https://doi.org/10.1158/1557-3265.OVCA17-A38","url":null,"abstract":"","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79280395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract A50: EP4 receptor antagonism in paclitaxel-resistant ovarian clear cell carcinomas","authors":"Conghong Fan, J. Reader, Gautam G. Rao, Paul N. Staats, M. Ching, A. Fulton, D. Roque","doi":"10.1158/1557-3265.OVCA17-A50","DOIUrl":"https://doi.org/10.1158/1557-3265.OVCA17-A50","url":null,"abstract":"","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72735246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract A15: Fatty acid binding protein 4 is indispensable for ovarian cancer metastasis","authors":"A. Mukherjee, F. Coscia, J. Fahrmann, Chun-Yi Chiang, Justin Smith, K. Nieman, A. Ladányi, Iris L. Romero, O. Fiehn, M. Mann, E. Lengyel","doi":"10.1158/1557-3265.OVCA17-A15","DOIUrl":"https://doi.org/10.1158/1557-3265.OVCA17-A15","url":null,"abstract":"Introduction: Omental metastasis is a defining feature of ovarian cancer and other cancers with peritoneal spread. We and others have previously shown that ovarian cancer (OvCa) cells readily home to the omentum in an adipokine-dependent manner and take up lipids from omental adipocytes to fuel metastasis. The complex interactions between omental adipocytes and OvCa cells, and the mechanisms by which OvCa cells adapt to this unique lipid-rich microenvironment, are still unclear and warrant further study. Here we used multiple omics platforms to study adipocyte-induced alterations in OvCa cells. Methods: We cocultured human primary adipocytes (HPA) with OvCa cell lines and then used mass spectrometry-based proteomic and global untargeted metabolomic analysis to study the altered cellular physiology of cancer cells upon encountering omental adipocytes. Stable cell lines were generated using lentivirus-mediated gene silencing and, subsequently, functional characterization was carried out using microarray and cell-based metabolic analysis. Since fatty acid binding protein 4 (FABP4) was identified in this analysis, we used a small-molecule inhibitor against FABP4 in an orthotopic xenograft mouse model to determine its role in promoting metastatic tumor burden. Results: Proteomic analysis revealed that HPA increases the expression of several proteins, especially those involved in lipid metabolism, such as cluster of differentiation 36 (CD36), FABP4, and alcohol dehydrogenase 1 (ADH1) in OvCa cancer cells. While we found that CD36 was essential for lipid uptake by the cancer cells, we determined that FABP4 was indispensable for their retention of intracellular lipid accumulation. Corollary metabolomic analysis showed that FABP4 knockdown dramatically reduced intracellular triacylglycerol levels induced by adipocyte coculture. We also found that FABP4 was responsible for the increased rate of β-oxidation observed in adipocyte cocultured cancer cells. Moreover, cancer cells exhibited increased oxidative stress when cultured with adipocytes or adipocyte conditioned media as evidenced by flow-cytometry analysis of reactive oxygen species. These observations were corroborated by detection of elevated oxidative stress markers such as oxidized lipids (15-HETE, 9-HODE, and 2-hydroxypalmitate), oxidized cholesterol (7-beta-hydroxy cholesterol), and oxidized glutathione. This increase in reactive oxygen species was found to be dependent on the levels of adipocyte-induced FABP4, suggesting that FABP4 plays a critical role in the alteration of cancer cells in contact with adipocytes. To determine the functional consequence of FABP4 inhibition in cancer cells, we carried out microarray and ingenuity pathway analysis (IPA) analysis after FABP4 knockdown, which revealed that FABP4 makes a significant contribution to proliferative and metastatic signatures in cancer cells. Knockdown of FABP4 also reduced colony-forming capacity in clonogenic assays and targeting FABP4 ","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80790883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abstract IA07: Targeting micrometastasis for the treatment of ovarian cancer","authors":"A. Ahmed","doi":"10.1158/1557-3265.OVCA17-IA07","DOIUrl":"https://doi.org/10.1158/1557-3265.OVCA17-IA07","url":null,"abstract":"","PeriodicalId":18646,"journal":{"name":"Metabolic Changes in Ovarian Cancer","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85785312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}