{"title":"Abstract 2442: Chondroitin sulfatases and transcription factors Gli, Tcf/Lef, and c-Myc in prostate stem cells","authors":"J. Tobacman, S. Bhattacharyya, L. Feferman","doi":"10.1158/1538-7445.AM2021-2442","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2442","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84185770","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}
M. Rada, Migmar Tsamchoe, A. Kapelanski-Lamoureux, Jesse D. Bloom, S. Petrillo, Sébastien Tabariès, Diane H. Kim, Peter Younan, A. Gregorieff, P. Siegel, A. Lazaris, P. Metrakos
{"title":"Abstract 1927: Cancer cells induce apoptosis in hepatocytes as one of the mechanisms to displace hepatocytes in vessel co-opted colorectal cancer liver metastases","authors":"M. Rada, Migmar Tsamchoe, A. Kapelanski-Lamoureux, Jesse D. Bloom, S. Petrillo, Sébastien Tabariès, Diane H. Kim, Peter Younan, A. Gregorieff, P. Siegel, A. Lazaris, P. Metrakos","doi":"10.1158/1538-7445.AM2021-1927","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-1927","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77802153","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}
I. Datta, Tathianne Malta, Thaís S. Sabedot, Ruicong She, A. Iavarone, H. Noushmehr, L. Poisson
{"title":"Abstract 2085: The evolutionary trajectory of epigenomics in adult glioma","authors":"I. Datta, Tathianne Malta, Thaís S. Sabedot, Ruicong She, A. Iavarone, H. Noushmehr, L. Poisson","doi":"10.1158/1538-7445.AM2021-2085","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2085","url":null,"abstract":"Background: Glioma is the most common malignant tumor of the central nervous system, often behaving very aggressively. Recently, The Cancer Genome Atlas (TCGA) and others have shown that epigenomic alterations in primary glioma tumors have prognostic and predictive roles, but there is a gap in knowledge of the molecular alterations after glioma treatment. In order to fill this gap, the Glioma Longitudinal AnalySiS (GLASS) Consortium, a multi-national collaboration from 13 institutions, is investigating genome-wide molecular data from primary and recurrent matched pairs. The current data freeze has DNA methylation data for 266 primary-recurrent pairs fromIllumina 450K and EPIC array platforms. Methods: We hypothesize that there will be evidence of aggressivity in the DNA methylation profiles of recurrent tumors relative to their matched primary, and we explored this through tumor subtyping, patterns of differentially methylated CpGs (DMPs), and epigenomic aging. Results: The subtype classification in the primary tumors was as follows for IDH wildtype tumors - 43.8%Classical, 47.3% Mesenchymal, 8.7% PA-like, none LGm6-GBM and for IDH mutant tumors 19.1% Codel, 79.4% G-CIMP-high, 1.3% G-CIMP-low. We observed that among IDH wildtype tumors 29.8% changed subtype, 47.1% of which shifted to the more aggressive Mesenchymal-like subtype. In IDH mutant tumors, 26.0% changed at recurrence, of which 57.9% shifted to the aggressive G-CIMP-low subtype. Patterns of DMPs in IDH mutant-code tumors (15 pairs) showed a loss of methylation upon recurrence, with 651 DMPs identified (paired Wilcoxon test, FDR l 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2085.","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"172 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78016003","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}
Debattama R. Sen, Sarah A. Weiss, Brian C. Miller, K. Yates, M. LaFleur, A. Sharpe, W. Haining
{"title":"Abstract NG04: Disrupting enhancers within the core epigenetic program of exhaustion improves CD8+ T cell responses and enhances tumor control","authors":"Debattama R. Sen, Sarah A. Weiss, Brian C. Miller, K. Yates, M. LaFleur, A. Sharpe, W. Haining","doi":"10.1158/1538-7445.am2021-ng04","DOIUrl":"https://doi.org/10.1158/1538-7445.am2021-ng04","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72830521","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}
I. Mittra, H. Singhavi, Aishwarya Pilankar, V. Gorantla, Sophiya Siddiqui, N. Khare, Vishal Jadhav, Kavita Pal, P. Chaturvedi
{"title":"Abstract 2514: Cell-free chromatin particles released into the microenvironment from dying tumor cells activate cancer hallmarks in surviving cells: a study in advanced squamous cell carcinoma of oral cavity with therapeutic implications","authors":"I. Mittra, H. Singhavi, Aishwarya Pilankar, V. Gorantla, Sophiya Siddiqui, N. Khare, Vishal Jadhav, Kavita Pal, P. Chaturvedi","doi":"10.1158/1538-7445.AM2021-2514","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2514","url":null,"abstract":"Background: We have reported that combination of the nutraceuticals Resveratrol (R) and Copper(Cu) results in generation of free radicals which can degrade cell-free chromatin (cfCh) particles and have potential therapeutic effects (Mittra et al., Ann. Oncol. 2017 & Mittra et al., PLos One 2020). We have also reported that cfCh particles that are released from dying tumor cells can integrate into genomes of healthy bystander cells to activate two critical hallmarks of cancer namely, genome instability and inflammation, which could lead to their oncogenic transformation (Mittra et al., Cell Death Discovery 2017). Here we show that cfCh particles released into tumor microenvironment (TME) from dying tumor cells of advanced squamous carcinoma of oral cavity activate all ten hallmarks of cancer defined by Hanahan and Weinberg, and that oral administration of R-Cu for two weeks prevents this potentially life-threatening manifestation. Patients and Methods: The study was approved by Institutional Ethics Committee, and a written consent was obtained from participants. In this exploratory study, R-Cu was administered in four escalating doses orally for two weeks, to 25 patients divided into 5 groups with 5 patients each, as follows: 1) Control: R 0, Cu 0; 2) Level I: R 5.6 mg, Cu 560 ng; 3) Level II: R 50 mg, Cu 5µg; 4) Level III: R 500 mg, Cu 50 µg; 5) Level IV: R 500 mg, Cu 5mg. A punch biopsy was obtained on the day 0 and day 14 post R-Cu treatment. FFPE histological sections were examined by 1) Fluorescence immuno-staining (FI) using anti-DNA and anti-histone H4 antibodies and confocal microscopy to detect presence of cfCh in TME; 2) Immuno-fluorescence (IF) analysis of intracellular antioxidant enzymes; and 3) IF analysis of 10 hallmarks of cancer represented by 23 biomarkers. Results: 1) FI and Confocal microscopy detected extensive presence of dually fluorescently labelled cfCh particles in TME, which were dramatically reduced following R-Cu treatment. 2) IF analysis detected significantly elevated levels of three intra-cellular anti-oxidant enzymes in post R-Cu samples, suggesting that cells had mounted a defense mechanism to counteract free radicals that had entered into them. No difference between day 0 and day 14 samples was seen in the untreated control group. 3) IF analysis of 23 cancer hallmark biomarkers showed significant down-regulation in the post R-Cu samples, which were most marked in dose levels I and II. No difference between day 0 and day 14 samples was seen in the control group. Conclusion: We show in a human tumor model that cfCh particles released into TME from dying tumor cells activate cancer hallmarks in surviving cells, and that the cfCh inactivating agent R-Cu can significantly down-regulate cancer hallmark levels suggesting its therapeutic potential. Citation Format: Indraneel Mittra, Hitesh Singhavi, Aishwarya Pilankar, Venkat Raghuram Gorantla, Sophiya Siddiqui, Naveen Kumar Khare, Vishalkumar Jadhav, Kavita Pal, Pankaj ","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79916424","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}
Shannalee R. Martinez, Adrián Pérez Aybar, C. D. Osterman
{"title":"Abstract 2460: Oncogenic regulation of lipogenesis in docetaxel resistant prostate cancer cells","authors":"Shannalee R. Martinez, Adrián Pérez Aybar, C. D. Osterman","doi":"10.1158/1538-7445.AM2021-2460","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2460","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76939946","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}
Y. Inoue, N. Kakiuchi, Kenichi Yoshida, Y. Nanya, Y. Shiozawa, Y. Takeuchi, Y. Fujii, Y. Shiraishi, K. Chiba, T. Yoshizato, S. Nagayama, Y. Sakai, S. Ogawa
{"title":"Abstract 2276: Genetic classification of colorectal cancer","authors":"Y. Inoue, N. Kakiuchi, Kenichi Yoshida, Y. Nanya, Y. Shiozawa, Y. Takeuchi, Y. Fujii, Y. Shiraishi, K. Chiba, T. Yoshizato, S. Nagayama, Y. Sakai, S. Ogawa","doi":"10.1158/1538-7445.AM2021-2276","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2276","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82170779","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}
M. Oshi, L. Le, Y. Tokumaru, Li Yan, R. Matsuyama, I. Endo, K. Takabe
{"title":"Abstract 1966: Cell proliferation-related pathway scores (G2M Checkpoint, E2F Targets, MYC Targets V1 and V2, Mitotic Spindle, p53 pathway) as predictive and prognostic biomarkers in pancreatic cancer","authors":"M. Oshi, L. Le, Y. Tokumaru, Li Yan, R. Matsuyama, I. Endo, K. Takabe","doi":"10.1158/1538-7445.AM2021-1966","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-1966","url":null,"abstract":"","PeriodicalId":18754,"journal":{"name":"Molecular and Cellular Biology / Genetics","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81295091","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}