Visceral Metastasis

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Gina Chia-yi Chu - One of the best experts on this subject based on the ideXlab platform.

  • Abstract 177: Src family kinase Fyn promotes the neuroendocrine phenotype and Visceral Metastasis in advanced prostate cancer
    Molecular and Cellular Biology Genetics, 2016
    Co-Authors: Karen A. Cavassani, Murali Gururajan, Margarit Sievert, Peng Duan, Michael R. Freeman, Gina Chia-yi Chu, Neil A. Bhowmick, Leland W.k. Chung, Edward Posadas
    Abstract:

    FYN is a SRC family kinase (SFK) that has been shown to be up-regulated in human prostate cancer (PCa) tissues and cell lines. In this study, we observed that FYN is strongly up-regulated in human neuroendocrine PCa (NEPC) tissues and xenografts, as well as cells derived from a NEPC transgenic mouse model. In silico analysis of FYN expression in prostate cancer cell line databases revealed an association with the expression of neuroendocrine (NE) markers such as CHGA, CD44, CD56, and SYP. The loss of FYN abrogated the invasion of PC3 and ARCaPM cells in response to MET receptor ligand HGF. FYN also contributed to the metastatic potential of NEPC cells in two mouse models of Visceral Metastasis with two different cell lines (PC3 and TRAMPC2-RANKL). The activation of MET appeared to regulate neuroendocrine (NE) features as evidenced by increased expression of NE markers in PCa cells lines treated with HGF. Importantly, the overexpression of FYN protein in DU145 cells was directly correlated with the increase of CHGA. Thus, our data demonstrated that the neuroendocrine differentiation that occurs in PCa cells is, at least in part, regulated by FYN kinase. Understanding the role of FYN in the regulation of NE markers will provide further support for ongoing clinical trials of SFK and MET inhibitors in castration-resistant PCa patients. Citation Format: Karen Cavassani, Murali Gururajan, Margarit Sievert, Peng Duan, Michael Freeman, Gina Chia-Yi Chu, Neil Bhowmick, Leland Chung, Edward Posadas. Src family kinase Fyn promotes the neuroendocrine phenotype and Visceral Metastasis in advanced prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 177.

  • SRC family kinase FYN promotes the neuroendocrine phenotype and Visceral Metastasis in advanced prostate cancer
    Oncotarget, 2015
    Co-Authors: Murali Gururajan, Karen A. Cavassani, Margarit Sievert, Peng Duan, Jake Lichterman, Jen-ming Huang, Bethany Smith, Sungyong You, Srinivas Nandana, Gina Chia-yi Chu
    Abstract:

    FYN is a SRC family kinase (SFK) that has been shown to be up-regulated in human prostate cancer (PCa) tissues and cell lines. In this study, we observed that FYN is strongly up-regulated in human neuroendocrine PCa (NEPC) tissues and xenografts, as well as cells derived from a NEPC transgenic mouse model. In silico analysis of FYN expression in prostate cancer cell line databases revealed an association with the expression of neuroendocrine (NE) markers such as CHGA, CD44, CD56, and SYP. The loss of FYN abrogated the invasion of PC3 and ARCaPM cells in response to MET receptor ligand HGF. FYN also contributed to the metastatic potential of NEPC cells in two mouse models of Visceral Metastasis with two different cell lines (PC3 and TRAMPC2-RANKL). The activation of MET appeared to regulate neuroendocrine (NE) features as evidenced by increased expression of NE markers in PC3 cells with HGF. Importantly, the overexpression of FYN protein in DU145 cells was directly correlated with the increase of CHGA. Thus, our data demonstrated that the neuroendocrine differentiation that occurs in PCa cells is, at least in part, regulated by FYN kinase. Understanding the role of FYN in the regulation of NE markers will provide further support for ongoing clinical trials of SFK and MET inhibitors in castration-resistant PCa patients.

Margarit Sievert - One of the best experts on this subject based on the ideXlab platform.

  • Abstract 177: Src family kinase Fyn promotes the neuroendocrine phenotype and Visceral Metastasis in advanced prostate cancer
    Molecular and Cellular Biology Genetics, 2016
    Co-Authors: Karen A. Cavassani, Murali Gururajan, Margarit Sievert, Peng Duan, Michael R. Freeman, Gina Chia-yi Chu, Neil A. Bhowmick, Leland W.k. Chung, Edward Posadas
    Abstract:

    FYN is a SRC family kinase (SFK) that has been shown to be up-regulated in human prostate cancer (PCa) tissues and cell lines. In this study, we observed that FYN is strongly up-regulated in human neuroendocrine PCa (NEPC) tissues and xenografts, as well as cells derived from a NEPC transgenic mouse model. In silico analysis of FYN expression in prostate cancer cell line databases revealed an association with the expression of neuroendocrine (NE) markers such as CHGA, CD44, CD56, and SYP. The loss of FYN abrogated the invasion of PC3 and ARCaPM cells in response to MET receptor ligand HGF. FYN also contributed to the metastatic potential of NEPC cells in two mouse models of Visceral Metastasis with two different cell lines (PC3 and TRAMPC2-RANKL). The activation of MET appeared to regulate neuroendocrine (NE) features as evidenced by increased expression of NE markers in PCa cells lines treated with HGF. Importantly, the overexpression of FYN protein in DU145 cells was directly correlated with the increase of CHGA. Thus, our data demonstrated that the neuroendocrine differentiation that occurs in PCa cells is, at least in part, regulated by FYN kinase. Understanding the role of FYN in the regulation of NE markers will provide further support for ongoing clinical trials of SFK and MET inhibitors in castration-resistant PCa patients. Citation Format: Karen Cavassani, Murali Gururajan, Margarit Sievert, Peng Duan, Michael Freeman, Gina Chia-Yi Chu, Neil Bhowmick, Leland Chung, Edward Posadas. Src family kinase Fyn promotes the neuroendocrine phenotype and Visceral Metastasis in advanced prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 177.

  • Abstract 4962: Very-small-nuclear circulating tumor cell (vsnCTC) as a putative biomarker for Visceral Metastasis in metastatic castration-resistant prostate cancer (mCRPC)
    Clinical Research (Excluding Clinical Trials), 2016
    Co-Authors: Jie-fu Chen, Margarit Sievert, Elisabeth Hodara, Alexander Ureno, Elizabeth Kaufman, Daniel Luthringer, Jiaoti Huang, Leland W.k. Chung
    Abstract:

    Introduction and Objective: Patients with metastatic castration-resistant prostate cancer (mCRPC) who develop Visceral metastases (VM) have poorer clinical outcomes in comparison to those without VM. Currently, VM are discovered late in the clinical course of mCRPC-VM and this aggressive natural history typically culminates in organ failure. There are no existing tests that identify men at risk for VM other than radiography. Our team performed circulating tumor cell (CTC) enumeration using NanoVelcro CTC Assay on prostate cancer patients across the spectrum of metastatic states: no Metastasis, non-Visceral Metastasis, and VM. We identified an association between the presence of very-small-nuclear CTCs (vsnCTCs, DAPI+/Cytokeratin+/CD45- with nuclear size Methods: We identified mCRPC patients who had progressed through next generation hormonal maneuvers such as abiraterone, enzalutamide, or an equivalent drug. Serial blood specimens were used for vsnCTC enumeration using NanoVelcro CTC Assay as previously published. The vsnCTC counts were related to the presence and development of VM (evaluated by radiography) as well as the response to anti-cancer treatment. Results: Blood specimens were identified from 28 patients who met the eligibility criteria; 15/28 patients presented with VM and 13/28 had bone-only disease at their first CTC enumeration. Five out of 13 non-VM patients developed VM during follow-up, and vsnCTCs were detected 86-196 days prior to radiographic detection of VM (true positive); 4/13 had vsnCTCs detected but no VM was found by the time of analysis (false positive). None of the vsnCTC(-) patients developed VM. vsnCTCs were detected in 20/20 VM patients compared to 4/8 non-VM patients. Reduction of vsnCTC count occurred at initiation of anti-cancer treatment; transition from vsnCTC(-) to vsnCTC(+) was seen prior to progression under the treatment. Of the patients who have VM, 14 passed away at the time of this abstract submission including all the patients converting from non-VM to VM during the time of follow-up. Two out of 8 non-VM patients passed away including one patient who had vsnCTCs detected around 6 months prior to death. Conclusions: vsnCTCs are associated with the presence of VM. The vsnCTC is a potential biomarker for predicting the development of VM and monitoring the treatment response in mCRPC. Transition from vsnCTC(-) to vsnCTC(+) was associated with the development of VM and progression under the treatment. Citation Format: Jie-Fu Chen, Hao Ho, Elisabeth Hodara, Alexander Ureno, Ann Go, Elizabeth Kaufman, Margarit Sievert, Daniel J. Luthringer, Jiaoti Huang, Leland Chung, Zunfu Ke, Ker-Chau Li, Hsian-Rong Tseng, Edwin M. Posadas. Very-small-nuclear circulating tumor cell (vsnCTC) as a putative biomarker for Visceral Metastasis in metastatic castration-resistant prostate cancer (mCRPC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4962.

  • Very small nuclear circulating tumor cell (vsnCTC) as a putative biomarker for Visceral Metastasis in metastatic castration-resistant prostate cancer (mCRPC).
    Journal of Clinical Oncology, 2016
    Co-Authors: Jie-fu Chen, Margarit Sievert, Leland W.k. Chung, Elisabeth Hodara, Alexander Ureno, Elizabeth Kaufman, Hsian-rong Tseng
    Abstract:

    64 Background: Patients with metastatic castration-resistant prostate cancer (mCRPC) who develop Visceral Metastasis (VM) have a poorer clinical outcome in comparison to those without VM. Their clinical course is aggressive and culminates in organ failure as this process is often discovered late in the disease course. There are no existing tests that identify men at risk for VM. Our team has identified an association between the presence of very small nuclear circulating tumor cells (vsnCTCs) and VM. We hypothesized that vsnCTC that can predict the development of VM and monitor the response to anticancer treatment. Methods: In our database we identified mCRPC patients who had progressed through next generation hormonal maneuvers such as abiraterone, enzalutamide, or an equivalent drug. Serial blood specimens were used for vsnCTC enumeration using published methods. The vsnCTC counts were related to the presence and development of VM as well as the response to anticancer treatment. Results: Blood specimens...

  • SRC family kinase FYN promotes the neuroendocrine phenotype and Visceral Metastasis in advanced prostate cancer
    Oncotarget, 2015
    Co-Authors: Murali Gururajan, Karen A. Cavassani, Margarit Sievert, Peng Duan, Jake Lichterman, Jen-ming Huang, Bethany Smith, Sungyong You, Srinivas Nandana, Gina Chia-yi Chu
    Abstract:

    FYN is a SRC family kinase (SFK) that has been shown to be up-regulated in human prostate cancer (PCa) tissues and cell lines. In this study, we observed that FYN is strongly up-regulated in human neuroendocrine PCa (NEPC) tissues and xenografts, as well as cells derived from a NEPC transgenic mouse model. In silico analysis of FYN expression in prostate cancer cell line databases revealed an association with the expression of neuroendocrine (NE) markers such as CHGA, CD44, CD56, and SYP. The loss of FYN abrogated the invasion of PC3 and ARCaPM cells in response to MET receptor ligand HGF. FYN also contributed to the metastatic potential of NEPC cells in two mouse models of Visceral Metastasis with two different cell lines (PC3 and TRAMPC2-RANKL). The activation of MET appeared to regulate neuroendocrine (NE) features as evidenced by increased expression of NE markers in PC3 cells with HGF. Importantly, the overexpression of FYN protein in DU145 cells was directly correlated with the increase of CHGA. Thus, our data demonstrated that the neuroendocrine differentiation that occurs in PCa cells is, at least in part, regulated by FYN kinase. Understanding the role of FYN in the regulation of NE markers will provide further support for ongoing clinical trials of SFK and MET inhibitors in castration-resistant PCa patients.

Edward Posadas - One of the best experts on this subject based on the ideXlab platform.

  • Abstract 177: Src family kinase Fyn promotes the neuroendocrine phenotype and Visceral Metastasis in advanced prostate cancer
    Molecular and Cellular Biology Genetics, 2016
    Co-Authors: Karen A. Cavassani, Murali Gururajan, Margarit Sievert, Peng Duan, Michael R. Freeman, Gina Chia-yi Chu, Neil A. Bhowmick, Leland W.k. Chung, Edward Posadas
    Abstract:

    FYN is a SRC family kinase (SFK) that has been shown to be up-regulated in human prostate cancer (PCa) tissues and cell lines. In this study, we observed that FYN is strongly up-regulated in human neuroendocrine PCa (NEPC) tissues and xenografts, as well as cells derived from a NEPC transgenic mouse model. In silico analysis of FYN expression in prostate cancer cell line databases revealed an association with the expression of neuroendocrine (NE) markers such as CHGA, CD44, CD56, and SYP. The loss of FYN abrogated the invasion of PC3 and ARCaPM cells in response to MET receptor ligand HGF. FYN also contributed to the metastatic potential of NEPC cells in two mouse models of Visceral Metastasis with two different cell lines (PC3 and TRAMPC2-RANKL). The activation of MET appeared to regulate neuroendocrine (NE) features as evidenced by increased expression of NE markers in PCa cells lines treated with HGF. Importantly, the overexpression of FYN protein in DU145 cells was directly correlated with the increase of CHGA. Thus, our data demonstrated that the neuroendocrine differentiation that occurs in PCa cells is, at least in part, regulated by FYN kinase. Understanding the role of FYN in the regulation of NE markers will provide further support for ongoing clinical trials of SFK and MET inhibitors in castration-resistant PCa patients. Citation Format: Karen Cavassani, Murali Gururajan, Margarit Sievert, Peng Duan, Michael Freeman, Gina Chia-Yi Chu, Neil Bhowmick, Leland Chung, Edward Posadas. Src family kinase Fyn promotes the neuroendocrine phenotype and Visceral Metastasis in advanced prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 177.

  • Fyn: A Key Regulator of Metastasis in Prostate Cancer
    2013
    Co-Authors: Edward Posadas
    Abstract:

    Abstract : In this fourth and final year of DoD funding we have been finalizing a peer-reviewed manuscript entitled SRC family kinase FYN promotes the neuroendocrine phenotype and Visceral Metastasis in advanced prostate cancer. This manuscript is under review at Oncotarget. In this manuscript, we show that the loss of FYN abrogates the invasion of PC3 cells in response to the MET receptor ligand HGF. We also demonstrate that FYN contributes to the metastatic potential of NEPC cells in two mouse models of Visceral Metastasis. After the first submission of this manuscript, the reviewers expressed strong interest in our findings but they voiced a concern regarding the lack of data from a second prostate cancer cell line. During this past year, we have incorporated data from other prostate cancer lines including ARCaPm and LNCaP cells and we continue to been couraged that FYN is an attractive therapeutic and diagnostic target in PC. Also, our current data provide further support for ongoing clinical trials of FYN and MET inhibitors in castration-resistant PCa patients. As for future research directions, we have begun to explore the role of FYN in PDL1 expression in metastatic prostate cancer and the manner in which this kinase might be involved in prostate CTC activation.

Karen A. Cavassani - One of the best experts on this subject based on the ideXlab platform.

  • Abstract 177: Src family kinase Fyn promotes the neuroendocrine phenotype and Visceral Metastasis in advanced prostate cancer
    Molecular and Cellular Biology Genetics, 2016
    Co-Authors: Karen A. Cavassani, Murali Gururajan, Margarit Sievert, Peng Duan, Michael R. Freeman, Gina Chia-yi Chu, Neil A. Bhowmick, Leland W.k. Chung, Edward Posadas
    Abstract:

    FYN is a SRC family kinase (SFK) that has been shown to be up-regulated in human prostate cancer (PCa) tissues and cell lines. In this study, we observed that FYN is strongly up-regulated in human neuroendocrine PCa (NEPC) tissues and xenografts, as well as cells derived from a NEPC transgenic mouse model. In silico analysis of FYN expression in prostate cancer cell line databases revealed an association with the expression of neuroendocrine (NE) markers such as CHGA, CD44, CD56, and SYP. The loss of FYN abrogated the invasion of PC3 and ARCaPM cells in response to MET receptor ligand HGF. FYN also contributed to the metastatic potential of NEPC cells in two mouse models of Visceral Metastasis with two different cell lines (PC3 and TRAMPC2-RANKL). The activation of MET appeared to regulate neuroendocrine (NE) features as evidenced by increased expression of NE markers in PCa cells lines treated with HGF. Importantly, the overexpression of FYN protein in DU145 cells was directly correlated with the increase of CHGA. Thus, our data demonstrated that the neuroendocrine differentiation that occurs in PCa cells is, at least in part, regulated by FYN kinase. Understanding the role of FYN in the regulation of NE markers will provide further support for ongoing clinical trials of SFK and MET inhibitors in castration-resistant PCa patients. Citation Format: Karen Cavassani, Murali Gururajan, Margarit Sievert, Peng Duan, Michael Freeman, Gina Chia-Yi Chu, Neil Bhowmick, Leland Chung, Edward Posadas. Src family kinase Fyn promotes the neuroendocrine phenotype and Visceral Metastasis in advanced prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 177.

  • SRC family kinase FYN promotes the neuroendocrine phenotype and Visceral Metastasis in advanced prostate cancer
    Oncotarget, 2015
    Co-Authors: Murali Gururajan, Karen A. Cavassani, Margarit Sievert, Peng Duan, Jake Lichterman, Jen-ming Huang, Bethany Smith, Sungyong You, Srinivas Nandana, Gina Chia-yi Chu
    Abstract:

    FYN is a SRC family kinase (SFK) that has been shown to be up-regulated in human prostate cancer (PCa) tissues and cell lines. In this study, we observed that FYN is strongly up-regulated in human neuroendocrine PCa (NEPC) tissues and xenografts, as well as cells derived from a NEPC transgenic mouse model. In silico analysis of FYN expression in prostate cancer cell line databases revealed an association with the expression of neuroendocrine (NE) markers such as CHGA, CD44, CD56, and SYP. The loss of FYN abrogated the invasion of PC3 and ARCaPM cells in response to MET receptor ligand HGF. FYN also contributed to the metastatic potential of NEPC cells in two mouse models of Visceral Metastasis with two different cell lines (PC3 and TRAMPC2-RANKL). The activation of MET appeared to regulate neuroendocrine (NE) features as evidenced by increased expression of NE markers in PC3 cells with HGF. Importantly, the overexpression of FYN protein in DU145 cells was directly correlated with the increase of CHGA. Thus, our data demonstrated that the neuroendocrine differentiation that occurs in PCa cells is, at least in part, regulated by FYN kinase. Understanding the role of FYN in the regulation of NE markers will provide further support for ongoing clinical trials of SFK and MET inhibitors in castration-resistant PCa patients.

Murali Gururajan - One of the best experts on this subject based on the ideXlab platform.

  • Abstract 177: Src family kinase Fyn promotes the neuroendocrine phenotype and Visceral Metastasis in advanced prostate cancer
    Molecular and Cellular Biology Genetics, 2016
    Co-Authors: Karen A. Cavassani, Murali Gururajan, Margarit Sievert, Peng Duan, Michael R. Freeman, Gina Chia-yi Chu, Neil A. Bhowmick, Leland W.k. Chung, Edward Posadas
    Abstract:

    FYN is a SRC family kinase (SFK) that has been shown to be up-regulated in human prostate cancer (PCa) tissues and cell lines. In this study, we observed that FYN is strongly up-regulated in human neuroendocrine PCa (NEPC) tissues and xenografts, as well as cells derived from a NEPC transgenic mouse model. In silico analysis of FYN expression in prostate cancer cell line databases revealed an association with the expression of neuroendocrine (NE) markers such as CHGA, CD44, CD56, and SYP. The loss of FYN abrogated the invasion of PC3 and ARCaPM cells in response to MET receptor ligand HGF. FYN also contributed to the metastatic potential of NEPC cells in two mouse models of Visceral Metastasis with two different cell lines (PC3 and TRAMPC2-RANKL). The activation of MET appeared to regulate neuroendocrine (NE) features as evidenced by increased expression of NE markers in PCa cells lines treated with HGF. Importantly, the overexpression of FYN protein in DU145 cells was directly correlated with the increase of CHGA. Thus, our data demonstrated that the neuroendocrine differentiation that occurs in PCa cells is, at least in part, regulated by FYN kinase. Understanding the role of FYN in the regulation of NE markers will provide further support for ongoing clinical trials of SFK and MET inhibitors in castration-resistant PCa patients. Citation Format: Karen Cavassani, Murali Gururajan, Margarit Sievert, Peng Duan, Michael Freeman, Gina Chia-Yi Chu, Neil Bhowmick, Leland Chung, Edward Posadas. Src family kinase Fyn promotes the neuroendocrine phenotype and Visceral Metastasis in advanced prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 177.

  • SRC family kinase FYN promotes the neuroendocrine phenotype and Visceral Metastasis in advanced prostate cancer
    Oncotarget, 2015
    Co-Authors: Murali Gururajan, Karen A. Cavassani, Margarit Sievert, Peng Duan, Jake Lichterman, Jen-ming Huang, Bethany Smith, Sungyong You, Srinivas Nandana, Gina Chia-yi Chu
    Abstract:

    FYN is a SRC family kinase (SFK) that has been shown to be up-regulated in human prostate cancer (PCa) tissues and cell lines. In this study, we observed that FYN is strongly up-regulated in human neuroendocrine PCa (NEPC) tissues and xenografts, as well as cells derived from a NEPC transgenic mouse model. In silico analysis of FYN expression in prostate cancer cell line databases revealed an association with the expression of neuroendocrine (NE) markers such as CHGA, CD44, CD56, and SYP. The loss of FYN abrogated the invasion of PC3 and ARCaPM cells in response to MET receptor ligand HGF. FYN also contributed to the metastatic potential of NEPC cells in two mouse models of Visceral Metastasis with two different cell lines (PC3 and TRAMPC2-RANKL). The activation of MET appeared to regulate neuroendocrine (NE) features as evidenced by increased expression of NE markers in PC3 cells with HGF. Importantly, the overexpression of FYN protein in DU145 cells was directly correlated with the increase of CHGA. Thus, our data demonstrated that the neuroendocrine differentiation that occurs in PCa cells is, at least in part, regulated by FYN kinase. Understanding the role of FYN in the regulation of NE markers will provide further support for ongoing clinical trials of SFK and MET inhibitors in castration-resistant PCa patients.