The Experts below are selected from a list of 68469 Experts worldwide ranked by ideXlab platform
Elaine A. Ostrander - One of the best experts on this subject based on the ideXlab platform.
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Spontaneous Tumor Regression in Tasmanian Devils Associated with RASL11A Activation.
Genetics, 2020Co-Authors: Mark J. Margres, Manuel Ruiz-aravena, Rodrigo Hamede, Kusum Chawla, Austin H. Patton, Matthew F. Lawrance, Alexandra K. Fraik, Amanda R. Stahlke, Brian W. Davis, Elaine A. OstranderAbstract:Spontaneous Tumor Regression has been documented in a small proportion of human cancer patients, but the specific mechanisms underlying Tumor Regression without treatment are not well understood. Tasmanian devils are threatened with extinction from a transmissible cancer due to universal susceptibility and a near 100% case fatality rate. In over 10,000 cases,
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The genomic basis of Tumor Regression in Tasmanian devils (Sarcophilus harrisii)
Genome biology and evolution, 2018Co-Authors: Mark J. Margres, Manuel Ruiz-aravena, Rodrigo Hamede, Austin H. Patton, Matthew F. Lawrance, Brian W. Davis, Elaine A. Ostrander, Menna E. Jones, Sarah A. Hendricks, Hamish MccallumAbstract:Understanding the genetic basis of disease-related phenotypes, such as cancer susceptibility, is crucial for the advancement of personalized medicine. Although most cancers are somatic in origin, a small number of transmissible cancers have been documented. Two such cancers have emerged in the Tasmanian devil (Sarcophilus harrisii) and now threaten the species with extinction. Recently, cases of natural Tumor Regression in Tasmanian devils infected with the clonally contagious cancer have been detected. We used whole-genome sequencing and FST-based approaches to identify the genetic basis of Tumor Regression by comparing the genomes of seven individuals that underwent Tumor Regression with those of three infected individuals that did not. We found three highly differentiated candidate genomic regions containing several genes related to immune response and/or cancer risk, indicating that the genomic basis of Tumor Regression was polygenic. Within these genomic regions, we identified putative regulatory variation in candidate genes but no nonsynonymous variation, suggesting that natural Tumor Regression may be driven, at least in part, by differential host expression of key loci. Comparative oncology can provide insight into the genetic basis of cancer risk, Tumor development, and the pathogenicity of cancer, particularly due to our limited ability to monitor natural, untreated Tumor progression in human patients. Our results support the hypothesis that host immune response is necessary for triggering Tumor Regression, providing candidate genes that may translate to novel treatments in human and nonhuman cancers.
Dean W. Felsher - One of the best experts on this subject based on the ideXlab platform.
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Abstract B02: The role of the immune system in sustained Tumor Regression following oncogene inactivation
Modeling Myc in Mouse, 2015Co-Authors: Stephanie C. Casey, Rachel K., Dean W. FelsherAbstract:The MYC oncogene has been implicated in the pathogenesis of many types of human cancer. The Felsher laboratory uses a conditional Tet-off MYC mouse model to study the formation of Tumors in multiple tissue types, such as lymphoma, and has demonstrated that MYC-induced Tumorigenesis is reversible. We have found that many cancers are “oncogene addicted” to MYC. Our laboratory has shown that an adaptive T cell-mediated immune response is essential for sustained Tumor Regression upon MYC inactivation (Rakhra et al, Cancer Cell, 2010). Now, we have found evidence suggesting that upon MYC inactivation in Tumors, B cells are activated and are critical to Tumor Regression. MYC inactivation in a Tumor was associated with the induction of an antibody-mediated response against Tumor cells. This humoral response could mediate the killing of Tumor cells in an Antibody-Dependent Cellular Cytotoxicity (ADCC) assay. Our work suggests that MYC inactivation results in a B cell-mediated immune response and that ADCC may contribute to Tumor Regression. Citation Format: Stephanie C. Casey, Rachel K. Do, Dean W. Felsher. The role of the immune system in sustained Tumor Regression following oncogene inactivation. [abstract]. In: Proceedings of the AACR Special Conference on Myc: From Biology to Therapy; Jan 7-10, 2015; La Jolla, CA. Philadelphia (PA): AACR; Mol Cancer Res 2015;13(10 Suppl):Abstract nr B02.
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cellular senescence is an important mechanism of Tumor Regression upon c myc inactivation
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Chi Hwa Wu, Pavan Bachireddy, Alper Yetil, Jan Van Riggelen, Alice C Fan, Dean W. FelsherAbstract:Oncogene-induced senescence is an important mechanism by which normal cells are restrained from malignant transformation. Here we report that the suppression of the c-Myc (MYC) oncogene induces cellular senescence in diverse Tumor types including lymphoma, osteosarcoma, and hepatocellular carcinoma. MYC inactivation was associated with prototypical markers of senescence, including acidic β-gal staining, induction of p16INK4a, and p15INK4b expression. Moreover, MYC inactivation induced global changes in chromatin structure associated with the marked reduction of histone H4 acetylation and increased histone H3 K9 methylation. Osteosarcomas engineered to be deficient in p16INK4a or Rb exhibited impaired senescence and failed to exhibit sustained Tumor Regression upon MYC inactivation. Similarly, only after lymphomas were repaired for p53 expression did MYC inactivation induce robust senescence and sustained Tumor Regression. The pharmacologic inhibition of signaling pathways implicated in oncogene-induced senescence including ATM/ATR and MAPK did not prevent senescence associated with MYC inactivation. Our results suggest that cellular senescence programs remain latently functional, even in established Tumors, and can become reactivated, serving as a critical mechanism of oncogene addiction associated with MYC inactivation.
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Cellular senescence programs are an important mechanism of Tumor Regression upon MYC inactivation
Cancer Research, 2007Co-Authors: Jan Van Riggenlen, Alper Yetil, Dean W. FelsherAbstract:4505 The targeted inactivation of oncogenes may be an effective therapy for the treatment of cancer. Previously, we have found that there are circumstances when even brief inactivation of the MYC oncogene can result in sustained Tumor Regression. Here we show that upon MYC inactivation both lymphomas and sarcomas undergo cellular senescence. MYC inactivation induced global epigenetic changes resulting in heterochromatin formation. In particular, we observed a global reduction of Histone H4 acetylation, and an increase of Histone H3 K9 methylation, which was previously implicated in cellular senescence. MYC inactivation was associated with an increase in markers of senescence including β-galactosidase staining and induction of p16INK4a expression. Tumors defective in p53 or p16INK4a, exhibited impaired senescence and no longer exhibited complete Tumor Regression upon MYC inactivation. Similarly, the restoration of p53 protein expression in Tumor cells now permitted them to undergo senescence and Tumor Regression. Thus, cellular senescence may be a critical mechanism by which oncogene inactivation induces Tumor Regression.
Mark J. Margres - One of the best experts on this subject based on the ideXlab platform.
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Spontaneous Tumor Regression in Tasmanian Devils Associated with RASL11A Activation.
Genetics, 2020Co-Authors: Mark J. Margres, Manuel Ruiz-aravena, Rodrigo Hamede, Kusum Chawla, Austin H. Patton, Matthew F. Lawrance, Alexandra K. Fraik, Amanda R. Stahlke, Brian W. Davis, Elaine A. OstranderAbstract:Spontaneous Tumor Regression has been documented in a small proportion of human cancer patients, but the specific mechanisms underlying Tumor Regression without treatment are not well understood. Tasmanian devils are threatened with extinction from a transmissible cancer due to universal susceptibility and a near 100% case fatality rate. In over 10,000 cases,
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The genomic basis of Tumor Regression in Tasmanian devils (Sarcophilus harrisii)
Genome biology and evolution, 2018Co-Authors: Mark J. Margres, Manuel Ruiz-aravena, Rodrigo Hamede, Austin H. Patton, Matthew F. Lawrance, Brian W. Davis, Elaine A. Ostrander, Menna E. Jones, Sarah A. Hendricks, Hamish MccallumAbstract:Understanding the genetic basis of disease-related phenotypes, such as cancer susceptibility, is crucial for the advancement of personalized medicine. Although most cancers are somatic in origin, a small number of transmissible cancers have been documented. Two such cancers have emerged in the Tasmanian devil (Sarcophilus harrisii) and now threaten the species with extinction. Recently, cases of natural Tumor Regression in Tasmanian devils infected with the clonally contagious cancer have been detected. We used whole-genome sequencing and FST-based approaches to identify the genetic basis of Tumor Regression by comparing the genomes of seven individuals that underwent Tumor Regression with those of three infected individuals that did not. We found three highly differentiated candidate genomic regions containing several genes related to immune response and/or cancer risk, indicating that the genomic basis of Tumor Regression was polygenic. Within these genomic regions, we identified putative regulatory variation in candidate genes but no nonsynonymous variation, suggesting that natural Tumor Regression may be driven, at least in part, by differential host expression of key loci. Comparative oncology can provide insight into the genetic basis of cancer risk, Tumor development, and the pathogenicity of cancer, particularly due to our limited ability to monitor natural, untreated Tumor progression in human patients. Our results support the hypothesis that host immune response is necessary for triggering Tumor Regression, providing candidate genes that may translate to novel treatments in human and nonhuman cancers.
Erika J Crosby - One of the best experts on this subject based on the ideXlab platform.
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CD4+ T Cells Contribute to the Remodeling of the Microenvironment Required for Sustained Tumor Regression upon Oncogene Inactivation
Cancer Cell, 2010Co-Authors: Kavya Rakhra, Pavan Bachireddy, Tahera Zabuawala, Andrew M. Kopelman, Robert Zeiser, Lior Z Braunstein, Liwen Xu, Qiwei Yang, Erika J CrosbyAbstract:Summary Oncogene addiction is thought to occur cell autonomously. Immune effectors are implicated in the initiation and restraint of Tumorigenesis, but their role in oncogene inactivation-mediated Tumor Regression is unclear. Here, we show that an intact immune system, specifically CD4 + T cells, is required for the induction of cellular senescence, shutdown of angiogenesis, and chemokine expression resulting in sustained Tumor Regression upon inactivation of the MYC or BCR-ABL oncogenes in mouse models of T cell acute lymphoblastic lymphoma and pro-B cell leukemia, respectively. Moreover, immune effectors knocked out for thrombospondins failed to induce sustained Tumor Regression. Hence, CD4 + T cells are required for the remodeling of the Tumor microenvironment through the expression of chemokines, such as thrombospondins, in order to elicit oncogene addiction.
Pavan Bachireddy - One of the best experts on this subject based on the ideXlab platform.
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CD4+ T Cells Contribute to the Remodeling of the Microenvironment Required for Sustained Tumor Regression upon Oncogene Inactivation
Cancer Cell, 2010Co-Authors: Kavya Rakhra, Pavan Bachireddy, Tahera Zabuawala, Andrew M. Kopelman, Robert Zeiser, Lior Z Braunstein, Liwen Xu, Qiwei Yang, Erika J CrosbyAbstract:Summary Oncogene addiction is thought to occur cell autonomously. Immune effectors are implicated in the initiation and restraint of Tumorigenesis, but their role in oncogene inactivation-mediated Tumor Regression is unclear. Here, we show that an intact immune system, specifically CD4 + T cells, is required for the induction of cellular senescence, shutdown of angiogenesis, and chemokine expression resulting in sustained Tumor Regression upon inactivation of the MYC or BCR-ABL oncogenes in mouse models of T cell acute lymphoblastic lymphoma and pro-B cell leukemia, respectively. Moreover, immune effectors knocked out for thrombospondins failed to induce sustained Tumor Regression. Hence, CD4 + T cells are required for the remodeling of the Tumor microenvironment through the expression of chemokines, such as thrombospondins, in order to elicit oncogene addiction.
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cellular senescence is an important mechanism of Tumor Regression upon c myc inactivation
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Chi Hwa Wu, Pavan Bachireddy, Alper Yetil, Jan Van Riggelen, Alice C Fan, Dean W. FelsherAbstract:Oncogene-induced senescence is an important mechanism by which normal cells are restrained from malignant transformation. Here we report that the suppression of the c-Myc (MYC) oncogene induces cellular senescence in diverse Tumor types including lymphoma, osteosarcoma, and hepatocellular carcinoma. MYC inactivation was associated with prototypical markers of senescence, including acidic β-gal staining, induction of p16INK4a, and p15INK4b expression. Moreover, MYC inactivation induced global changes in chromatin structure associated with the marked reduction of histone H4 acetylation and increased histone H3 K9 methylation. Osteosarcomas engineered to be deficient in p16INK4a or Rb exhibited impaired senescence and failed to exhibit sustained Tumor Regression upon MYC inactivation. Similarly, only after lymphomas were repaired for p53 expression did MYC inactivation induce robust senescence and sustained Tumor Regression. The pharmacologic inhibition of signaling pathways implicated in oncogene-induced senescence including ATM/ATR and MAPK did not prevent senescence associated with MYC inactivation. Our results suggest that cellular senescence programs remain latently functional, even in established Tumors, and can become reactivated, serving as a critical mechanism of oncogene addiction associated with MYC inactivation.
