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Zigang Dong - One of the best experts on this subject based on the ideXlab platform.
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abstract 2469 rcc2 promotes esophageal Cancer Growth by regulating activity and expression of the sox2 transcription factor
Cancer Research, 2020Co-Authors: Ali Calderonaparicio, Hiroyuki Yamamoto, Humberto De Vitto, Tianshun Zhang, Qiushi Wang, Ann M Bode, Zigang DongAbstract:RCC2 is a protein located in the centrosome, which ensures that cell division proceeds properly. Previous reports show that RCC2 is overexpressed in some Cancers and could play a key role in tumor development, but the mechanisms concerning how this occurs are not understood. Further, no evidence exists regarding its role in esophageal Cancer. We studied the relevance of RCC2 in esophageal Cancer Growth and the mechanisms explaining how this process occurs. RCC2 was highly expressed in mouse and human tissues as well as esophageal Cancer cell lines, and this overexpression was associated with tumorigenicity. RCC2 promoted cell proliferation, anchorage-independent Growth, and migration. These oncogenic effects were accompanied by overexpression of Sox2, an important transcription factor promoting esophageal Cancer. RCC2 upregulated and stabilized Sox2 expression by inhibiting proteasome degradation. Likewise, RCC2 increased the transcriptional activity and promoter binding of Sox2. In vivo studies indicated that RCC2 and Sox2 were overexpressed in esophageal tumors compared to normal controls, and this upregulation occurs in the basal cell layer for both proteins. In conditional knockout mice, RCC2 deletion decreased the tumor nodule formation and progression in the esophagus compared with “wild type” mice. PCNA expression, a cell proliferation marker, was also downregulated in RCC2 knockout mice. Overall, our data show for the first time that RCC2 is an important protein for the stabilization and transcriptional activation of Sox2 and further promotion of malignancy in Cancer. Citation Format: Ali J. Calderon-Aparicio, Hiroyuki Yamamoto, Humberto de vitto, Tianshun Zhang, Qiushi Wang, Ann M. Bode, Zigang Dong. RCC2 promotes esophageal Cancer Growth by regulating activity and expression of the Sox2 transcription factor [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2469.
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rcc2 promotes esophageal Cancer Growth by regulating activity and expression of the sox2 transcription factor
Molecular Cancer Research, 2020Co-Authors: Ali Calderonaparicio, Hiroyuki Yamamoto, Humberto De Vitto, Tianshun Zhang, Qiushi Wang, Ann M Bode, Zigang DongAbstract:Regulator of chromosome condensation 2 (RCC2) is a protein located in the centrosome, which ensures that cell division proceeds properly. Previous reports show that RCC2 is overexpressed in some Cancers and could play a key role in tumor development, but the mechanisms concerning how this occurs are not understood. Furthermore, no evidence exists regarding its role in esophageal Cancer. We studied the relevance of RCC2 in esophageal Cancer Growth and its regulation on Sox2, an important transcription factor promoting esophageal Cancer. RCC2 was overexpressed in esophageal tumors compared with normal tissue, and this overexpression was associated with tumorigenicity by increasing cell proliferation, anchorage-independent Growth, and migration. These oncogenic effects were accompanied by overexpression of Sox2. RCC2 upregulated and stabilized Sox2 expression and its target genes by inhibiting ubiquitination-mediated proteasome degradation. Likewise, RCC2 increased the transcriptional activity and promoter binding of Sox2. In vivo studies indicated that RCC2 and Sox2 were overexpressed in esophageal tumors compared with normal tissue, and this upregulation occurs in the esophageal basal cell layer for both proteins. In conditional knockout mice, RCC2 deletion decreased the tumor nodule formation and progression in the esophagus compared with wild-type mice. Proliferating cell nuclear antigen expression, a cell proliferation marker, was also downregulated in RCC2 knockout mice. Overall, our data show for the first time that RCC2 is an important protein for the stabilization and transcriptional activation of Sox2 and further promotion of malignancy in esophageal Cancer. IMPLICATIONS: This study shows that RCC2 controls Sox2 expression and transcriptional activity to mediate esophageal Cancer formation.
Adnan R. Munkarah - One of the best experts on this subject based on the ideXlab platform.
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metformin prevents aggressive ovarian Cancer Growth driven by high energy diet similarity with calorie restriction
Oncotarget, 2015Co-Authors: Z Alwahab, Ismail Mert, Calvin Tebbe, Jasdeep Chhina, Miriana Hijaz, Rouba Alifehmi, Shailendra Giri, Robert T. Morris, Adnan R. MunkarahAbstract:Caloric restriction (CR) was recently demonstrated by us to restrict ovarian Cancer Growth in vivo. CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian Cancer Growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian Cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking water. Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of Growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice. Metformin resulted in activation of AMPK and SIRT1 and inhibition of pAkt and pmTOR, similar to CR. Thus metformin can closely mimic CR's tumor suppressing effects by inducing similar metabolic changes, providing further evidence of its potential not only as a therapeutic drug but also as a preventive agent.
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metformin prevents aggressive ovarian Cancer Growth driven by high energy diet similarity with calorie restriction
Oncotarget, 2015Co-Authors: Z Alwahab, Ismail Mert, Calvin Tebbe, Jasdeep Chhina, Miriana Hijaz, Rouba Alifehmi, Shailendra Giri, Robert T. Morris, Adnan R. Munkarah, Ramandeep RattanAbstract:// Zaid Al-Wahab 1 , Ismail Mert 1, 2 , Calvin Tebbe 2 , Jasdeep Chhina 2 , Miriana Hijaz 2 , Robert T. Morris 1 , Rouba Ali-Fehmi 3 , Shailendra Giri 4, 5 , Adnan R. Munkarah 2, 5 , Ramandeep Rattan 2, 5 1 Wayne State University, Detroit, MI, USA 2 Division of Gynecologic Oncology, Department of Women’s Health, Henry Ford Hospital, Detroit, MI, USA 3 Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA 4 Department of Neurology, Henry Ford Hospital, Detroit, MI, USA 5 Josephine Cancer Institute, Henry Ford Hospital, Detroit, MI, USA Correspondence to: Ramandeep Rattan, e-mail: Rrattan1@hfhs.org Keywords: ovarian Cancer, metformin, calorie restriction, AMPK, mTOR Received: February 05, 2015 Accepted: February 23, 2015 Published: March 26, 2015 ABSTRACT Caloric restriction (CR) was recently demonstrated by us to restrict ovarian Cancer Growth in vivo . CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian Cancer Growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian Cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking water. Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of Growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice. Metformin resulted in activation of AMPK and SIRT1 and inhibition of pAkt and pmTOR, similar to CR. Thus metformin can closely mimic CR’s tumor suppressing effects by inducing similar metabolic changes, providing further evidence of its potential not only as a therapeutic drug but also as a preventive agent.
Ismail Mert - One of the best experts on this subject based on the ideXlab platform.
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metformin prevents aggressive ovarian Cancer Growth driven by high energy diet similarity with calorie restriction
Oncotarget, 2015Co-Authors: Z Alwahab, Ismail Mert, Calvin Tebbe, Jasdeep Chhina, Miriana Hijaz, Rouba Alifehmi, Shailendra Giri, Robert T. Morris, Adnan R. MunkarahAbstract:Caloric restriction (CR) was recently demonstrated by us to restrict ovarian Cancer Growth in vivo. CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian Cancer Growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian Cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking water. Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of Growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice. Metformin resulted in activation of AMPK and SIRT1 and inhibition of pAkt and pmTOR, similar to CR. Thus metformin can closely mimic CR's tumor suppressing effects by inducing similar metabolic changes, providing further evidence of its potential not only as a therapeutic drug but also as a preventive agent.
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metformin prevents aggressive ovarian Cancer Growth driven by high energy diet similarity with calorie restriction
Oncotarget, 2015Co-Authors: Z Alwahab, Ismail Mert, Calvin Tebbe, Jasdeep Chhina, Miriana Hijaz, Rouba Alifehmi, Shailendra Giri, Robert T. Morris, Adnan R. Munkarah, Ramandeep RattanAbstract:// Zaid Al-Wahab 1 , Ismail Mert 1, 2 , Calvin Tebbe 2 , Jasdeep Chhina 2 , Miriana Hijaz 2 , Robert T. Morris 1 , Rouba Ali-Fehmi 3 , Shailendra Giri 4, 5 , Adnan R. Munkarah 2, 5 , Ramandeep Rattan 2, 5 1 Wayne State University, Detroit, MI, USA 2 Division of Gynecologic Oncology, Department of Women’s Health, Henry Ford Hospital, Detroit, MI, USA 3 Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA 4 Department of Neurology, Henry Ford Hospital, Detroit, MI, USA 5 Josephine Cancer Institute, Henry Ford Hospital, Detroit, MI, USA Correspondence to: Ramandeep Rattan, e-mail: Rrattan1@hfhs.org Keywords: ovarian Cancer, metformin, calorie restriction, AMPK, mTOR Received: February 05, 2015 Accepted: February 23, 2015 Published: March 26, 2015 ABSTRACT Caloric restriction (CR) was recently demonstrated by us to restrict ovarian Cancer Growth in vivo . CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian Cancer Growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian Cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking water. Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of Growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice. Metformin resulted in activation of AMPK and SIRT1 and inhibition of pAkt and pmTOR, similar to CR. Thus metformin can closely mimic CR’s tumor suppressing effects by inducing similar metabolic changes, providing further evidence of its potential not only as a therapeutic drug but also as a preventive agent.
Z Alwahab - One of the best experts on this subject based on the ideXlab platform.
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metformin prevents aggressive ovarian Cancer Growth driven by high energy diet similarity with calorie restriction
Oncotarget, 2015Co-Authors: Z Alwahab, Ismail Mert, Calvin Tebbe, Jasdeep Chhina, Miriana Hijaz, Rouba Alifehmi, Shailendra Giri, Robert T. Morris, Adnan R. MunkarahAbstract:Caloric restriction (CR) was recently demonstrated by us to restrict ovarian Cancer Growth in vivo. CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian Cancer Growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian Cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking water. Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of Growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice. Metformin resulted in activation of AMPK and SIRT1 and inhibition of pAkt and pmTOR, similar to CR. Thus metformin can closely mimic CR's tumor suppressing effects by inducing similar metabolic changes, providing further evidence of its potential not only as a therapeutic drug but also as a preventive agent.
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metformin prevents aggressive ovarian Cancer Growth driven by high energy diet similarity with calorie restriction
Oncotarget, 2015Co-Authors: Z Alwahab, Ismail Mert, Calvin Tebbe, Jasdeep Chhina, Miriana Hijaz, Rouba Alifehmi, Shailendra Giri, Robert T. Morris, Adnan R. Munkarah, Ramandeep RattanAbstract:// Zaid Al-Wahab 1 , Ismail Mert 1, 2 , Calvin Tebbe 2 , Jasdeep Chhina 2 , Miriana Hijaz 2 , Robert T. Morris 1 , Rouba Ali-Fehmi 3 , Shailendra Giri 4, 5 , Adnan R. Munkarah 2, 5 , Ramandeep Rattan 2, 5 1 Wayne State University, Detroit, MI, USA 2 Division of Gynecologic Oncology, Department of Women’s Health, Henry Ford Hospital, Detroit, MI, USA 3 Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA 4 Department of Neurology, Henry Ford Hospital, Detroit, MI, USA 5 Josephine Cancer Institute, Henry Ford Hospital, Detroit, MI, USA Correspondence to: Ramandeep Rattan, e-mail: Rrattan1@hfhs.org Keywords: ovarian Cancer, metformin, calorie restriction, AMPK, mTOR Received: February 05, 2015 Accepted: February 23, 2015 Published: March 26, 2015 ABSTRACT Caloric restriction (CR) was recently demonstrated by us to restrict ovarian Cancer Growth in vivo . CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian Cancer Growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian Cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking water. Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of Growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice. Metformin resulted in activation of AMPK and SIRT1 and inhibition of pAkt and pmTOR, similar to CR. Thus metformin can closely mimic CR’s tumor suppressing effects by inducing similar metabolic changes, providing further evidence of its potential not only as a therapeutic drug but also as a preventive agent.
Gordana Radosavljevic - One of the best experts on this subject based on the ideXlab platform.
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the organic ester o o diethyl s s ethylenediamine n n di 2 3 cyclohexyl propanoate dihydrochloride attenuates murine breast Cancer Growth and metastasis
Oncotarget, 2018Co-Authors: Milena Jurisevic, Aleksandar Arsenijevic, Jelena Pantic, Nevena Gajovic, Jelena Milovanovic, Marija Milovanovic, Jelena Poljarevic, Tibor J Sabo, Danilo Vojvodic, Gordana RadosavljevicAbstract:// Milena Jurisevic 1, 2 , Aleksandar Arsenijevic 1 , Jelena Pantic 1 , Nevena Gajovic 1 , Jelena Milovanovic 1, 3 , Marija Milovanovic 1 , Jelena Poljarevic 4 , Tibor Sabo 4 , Danilo Vojvodic 5 , Gordana D. Radosavljevic 1 and Nebojsa Arsenijevic 1 1 Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia 2 Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia 3 Department of Histology and Embryology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia 4 Faculty of Chemistry, University of Belgrade, Belgrade, Serbia 5 Institute of Medical Research, Faculty of Medicine, Military Medical Academy, Belgrade, Serbia Correspondence to: Gordana D. Radosavljevic, email: perun.gr@gmail.com Milena Jurisevic, email: milena.jurisevic13@gmail.com Keywords: O,O’ -diethyl-( S,S )-ethylenediamine- N,N’ -di-2-(3-cyclohexyl)propanoate dihydrochloride; breast Cancer Growth; metastasis; apoptosis; proliferation Received: December 30, 2017 Accepted: May 24, 2018 Published: June 15, 2018 ABSTRACT Pharmacological treatment of Cancer is mostly limited by drug-toxicity and resistance. It has been noticed that new organic ester ligand, O,O’- diethyl-( S,S )-ethylenediamine- N,N’ -di-2-(3-cyclohexyl)propanoate dihydrochloride (named DE-EDCP) showed effective cytotoxic capacities against several human and mouse Cancer cell lines. However, its effects on tumor Growth and metastasis are unexplored. The aim of present study was to examine the ability of DE-EDCP to inhibit 4T1 murine breast Cancer Growth and progression and to explore possible molecular mechanisms. DE-EDCP exhibited significant tumoricidal activity on human and murine breast Cancer cell lines. Further, marked reduction of murine breast Cancer Growth and progression by DE-EDCP was shown. DE-EDCP exhibits fewer side-effects compared to cisplatin as a conventional chemotherapeutic. Results obtained from in vivo and in vitro experiments indicate that DE-EDCP induces apoptosis and inhibits proliferation of 4T1 cells. DE-EDCP increases percentage of 4T1 cells in late apoptosis, expression of pro-apoptotic Bax and caspase-3, while decreases expression of anti-apoptotic Bcl-2. DE-EDCP treatment increased the percentage of TUNEL-positive nuclei and reduced Ki-67 expression in breast Cancer tissue. DE-EDCP decreased expression of cyclin D3 and Ki-67, increased expression of cyclin-dependent kinase inhibitors p16, p21 and p27 and arrested 4T1 cells in G0/G1 cell cycle phase. Expression of STAT3 and downstream regulated molecules, NANOG and SOX2, was reduced in 4T1 cells after DE-EDCP treatment. In conclusion, DE-EDCP impairs breast Cancer Growth and progression by triggering Cancer cell death and inhibition of Cancer cell proliferation. DE-EDCP might be of interest in the development of the new antiCancer agent.
