Tumor BiologyPub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-SY06-02
T. Hasan
{"title":"Abstract SY06-02: Optically activated nanomedicines: Photochemical activation as a priming and imaging tool in pancreatic cancer","authors":"T. Hasan","doi":"10.1158/1538-7445.AM2021-SY06-02","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-SY06-02","url":null,"abstract":"Optical activation of materials leads to thermal, photochemical and radiative processes which can be captured for response-based therapeutic design. The ability to use light as a reagent to provide free radical and activated oxygen-mediated cytotoxicity, combined with a control of conventional drug release, allows for the fabrication of light-controllable intelligent multiagent nanoconstructs that attack multiple pathways making nanomedicines more effective against cancer. This optically activated approach allows for a mechanistically diverse and spatiotemporally controlled strategy to tumor destruction. The molecules used for light activation have, in addition to therapeutic capabilities, finite fluorescence, creating an imaging handle and providing a built-in Theranostic process. Strategies for syntheses and applications of these nanoagents in biology and medicine will be discussed. Citation Format: Tayyaba Hasan. Optically activated nanomedicines: Photochemical activation as a priming and imaging tool in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr SY06-02.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49045450","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}
Tumor BiologyPub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2681
Courtney Todorov, M. Gozo, H. Nunns, E. Parnell, J. Kuo, E. Leones, M. Nagy, Q. Au
{"title":"Abstract 2681: Co-detection of a tumor-infiltrating lymphocyte immunofluorescence (IF) panel and cytokine RNA in-situ hybridization (ISH) markers in non-small cell lung cancer (NSCLC) tumor microenvironment using combined MultiOmyx and RNAscope platforms","authors":"Courtney Todorov, M. Gozo, H. Nunns, E. Parnell, J. Kuo, E. Leones, M. Nagy, Q. Au","doi":"10.1158/1538-7445.AM2021-2681","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2681","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49193761","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}
Tumor BiologyPub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2831
Amber Gonda, Jay V. Shah, Jake N. Siebert, Nanxia Zhao, M. Kwon, P. Moghe, Nicola L Francis, V. Ganapathy
{"title":"Abstract 2831: Exosome gene signatures characterize metastatic dynamicity","authors":"Amber Gonda, Jay V. Shah, Jake N. Siebert, Nanxia Zhao, M. Kwon, P. Moghe, Nicola L Francis, V. Ganapathy","doi":"10.1158/1538-7445.AM2021-2831","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2831","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48345612","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}
Tumor BiologyPub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-LB009
G. Friedman, Oshrat Levi-Galibov, Eyal David, Chamutal Bornstein, Amir Giladi, M. Dadiani, A. Mayo, Coral Halperin, M. Pevsner-Fischer, H. Lavon, Shimrit Mayer, R. Nevo, Yan Stein, Nora Balint-Lahat, I. Barshack, H. R. Ali, C. Caldas, E. Gal-Yam, U. Alon, I. Amit, Ruth Scherz-Shouval
{"title":"Abstract LB009: Dynamic changes in the compositions of cancer associated-fibroblasts correlate with clinical outcome in breast cancer","authors":"G. Friedman, Oshrat Levi-Galibov, Eyal David, Chamutal Bornstein, Amir Giladi, M. Dadiani, A. Mayo, Coral Halperin, M. Pevsner-Fischer, H. Lavon, Shimrit Mayer, R. Nevo, Yan Stein, Nora Balint-Lahat, I. Barshack, H. R. Ali, C. Caldas, E. Gal-Yam, U. Alon, I. Amit, Ruth Scherz-Shouval","doi":"10.1158/1538-7445.AM2021-LB009","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB009","url":null,"abstract":"Cancer associated fibroblasts (CAFs) are prevalent in carcinomas. CAFs are also heterogeneous and perform various tumor-promoting tasks. Understanding whether distinct CAF-subsets exert specific functions, and how the composition of CAFs changes as tumors evolve could improve the accuracy of cancer treatment. Here, we analyzed thousands of CAFs by single-cell RNA-sequencing and index-sorting at several timepoints along breast tumor progression in mice, revealing distinct CAF-subsets. We discovered that the transcriptional programs of these subsets change over time, shifting from an immune-regulatory program at earlier timepoints to wound-healing and antigen-presenting programs at later timepoints, indicating that the composition and functions of CAFs are dynamic. We also found the two main CAF subsets in human breast tumors, wherein their ratio was associated with disease outcome. This association was particularly correlated with BRCA mutations in triple-negative breast cancer. Our findings indicate that the diverse composition of CAFs in breast cancer changes over time as tumors progress, and that these changes are linked to disease outcome. Citation Format: Gil Friedman, Oshrat Levi-Galibov, Eyal David, Chamutal Bornstein, Amir Giladi, Maya Dadiani, Avi Mayo, Coral Halperin, Meirav Pevsner-Fischer, Hagar Lavon, Shimrit Mayer, Reinat Nevo, Yaniv Stein, Nora Balint-Lahat, Iris Barshack, H. Raza Ali, Carlos Caldas, Einav Nili Gal-Yam, Uri Alon, Ido Amit, Ruth Scherz-Shouval. Dynamic changes in the compositions of cancer associated-fibroblasts correlate with clinical outcome in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB009.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45309453","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}
Tumor BiologyPub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-3096
Yan Xu, Qipeng Fan, R. Emerson
{"title":"Abstract 3096: A novel ZIP4-NOTCH3-HDAC4 axis in ovarian cancer stem cells","authors":"Yan Xu, Qipeng Fan, R. Emerson","doi":"10.1158/1538-7445.AM2021-3096","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-3096","url":null,"abstract":"High grade serous ovarian cancer (HGSOC) is one of the most deadly and heterogenic cancers. We have recently shown that ZIP4 (gene name SLC39A4), a zinc transporter, is a novel cancer stem cell (CSC) marker in HGSOC. 100-200 ZIP4+, but not ZIP4-, cells from both PE04 and PEA2 cells formed larger tumors than those from 100-200 ALDH+ cells in mice. Mechanistically, we found that ZIP4 was an upstream regulator of another CSC-marker, NOTCH3, in HGSOC cells. NOTCH3 was functionally involved in spheroid formation in vitro and tumorigenesis in vivo in HGSOC. Drug-resistance is one of the main characteristics of CSCs, While ZIP4 converts drug-resistance to cisplatin (CDDP) and doxorubicin (DOX) as we reported previously, we unexpectedly found that ZIP4 induced a sensitization of HGSOC cells to histone deacetylase inhibitors (HDACis). In particular, only those HDACis against the Class IIa HDACs showed ZIP4-dependent sensitization. ZIP4 selectively up-regulated HDAC IIa HDACs, including HDAC4 and 5, with little or no effects to HDACs in other classes. ZIP4 knockout (KO) and HDAC4 knockdown (KD) increased cell resistance to LMK-235, a selective HDAC4/5 inhibitor. LMK-235 and HDAC4 knockdown (KD) inhibited spheroid formation in vitro and tumor development in vivo. Collectively, we revealed a novel ZIP4-NOTCH3-HDAC4 axis, which is functionally involved and important in CSC-related activities in vitro and tumorigenesis in vivo, and provide an innovative targeting strategy to CSC. Citation Format: Yan Xu, Qipeng Fan, Robert Emerson. A novel ZIP4-NOTCH3-HDAC4 axis in ovarian cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3096.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45914469","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}
Tumor BiologyPub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-3176
Tzer-Min Kuo, Chin-Chan Lee, J. Lai, C. Su, M. Lai
{"title":"Abstract 3176: Inhibitory activity of Globo-H and SSEA-4 on activated T-cells","authors":"Tzer-Min Kuo, Chin-Chan Lee, J. Lai, C. Su, M. Lai","doi":"10.1158/1538-7445.AM2021-3176","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-3176","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46261848","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}
Tumor BiologyPub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-LB250
N. Banerjee, Dianne W. Moore, Abhisek Gangrade, D. Buchsbaum, L. Nabors, T. Broker, L. Chow
{"title":"Abstract LB250: Development of organoid raft cultures of cervical, breast and glioblastoma tumors as quick economical ex vivo human cancer models for pre-clinical drug evaluation","authors":"N. Banerjee, Dianne W. Moore, Abhisek Gangrade, D. Buchsbaum, L. Nabors, T. Broker, L. Chow","doi":"10.1158/1538-7445.AM2021-LB250","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-LB250","url":null,"abstract":"Background: In the past few years, 3D organoid cultures of patient-derived tumors or patient-derived xenografts have gained significant attention as faster and more economical ex vivo alternatives to animal models for the pre-clinical evaluation of therapeutics. We reported previously that raft cultures of ex vivo epithelial warts, normal human epithelia from various anatomic sites, as well as cancer cell lines (cervical and melanoma) grown at the liquid:air interface recapitulate parental tissue phenotypes. Here we describe adaptation of the above technique to develop Organoid Raft Culture (ORC) of tumors of various origin and validation as preclinical models for drug evaluation. Methods: A stromal equivalent (SE) consisting of buffered rat-tail collagen and J2 mouse fibroblasts was prepared in 24-well tissue culture plates. Freshly harvested tumors from patients or patient-derived xenografts of cervical cancers were minced to Citation Format: Nilam Sanjib Banerjee, Dianne W. Moore, Abhisek Gangrade, Donald J. Buchsbaum, Luise Burt Nabors, Thomas R. Broker, Louise T. Chow. Development of organoid raft cultures of cervical, breast and glioblastoma tumors as quick economical ex vivo human cancer models for pre-clinical drug evaluation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB250.","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46491860","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}
Tumor BiologyPub Date : 2021-07-01DOI: 10.1158/1538-7445.am2021-3173
K. Raghavan, Debora Vendramini, R. Francescone, J. Franco-Barraza, E. Cukierman
{"title":"Abstract 3173: NetrinG1's pro-tumor role on stroma-derived extracellular vesicles in pancreatic cancer","authors":"K. Raghavan, Debora Vendramini, R. Francescone, J. Franco-Barraza, E. Cukierman","doi":"10.1158/1538-7445.am2021-3173","DOIUrl":"https://doi.org/10.1158/1538-7445.am2021-3173","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42471343","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}
Tumor BiologyPub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-2753
Elizabeth A. Yu, Wei Wu, Philippe Gui, C. McCoach, C. Blakely, S. Christenson, T. Bivona
{"title":"Abstract 2753: Deciphering macrophage function in lung tumor microenvironment and disease progression","authors":"Elizabeth A. Yu, Wei Wu, Philippe Gui, C. McCoach, C. Blakely, S. Christenson, T. Bivona","doi":"10.1158/1538-7445.AM2021-2753","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-2753","url":null,"abstract":"","PeriodicalId":23364,"journal":{"name":"Tumor Biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42856942","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}