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Re: Marked Protection against Acute Renal and Hepatic Injury after Nitrited Myoglobin + Tin Protoporphyrin Administration
Urological Survey Uro-Science Re: Infiltrating Neutrophils Promote Renal Cell Carcinoma (RCC) Proliferation via Modulating Androgen Receptor (AR) / c-Myc Signals W. Song, L. Li, D. He, H. Xie, J. Chen, C. R. Yeh, L. S. Chang, S. Yeh and C. Chang Sex Hormone Research Center, Department of Urology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China, Sex Hormone Research Center, China Medical University and Hospital, Taichung, Taiwan, and George Whipple Lab for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, Rochester, New York Cancer Lett 2015; 368: 71e78. doi: 10.1016/j.canlet.2015.07.027
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26231735 Editorial Comment: Neutrophils are among the key tumor infiltrating myeloid cells in the tumor environment. Similar to the myeloid macrophages, neutrophils have a tumor associated subpopulation, and the relationship between tumor associated neutrophil infiltration and prognosis in human cancers has been systematically discussed. Epidemiological evidence had suggested that neutrophil infiltration within human cancers was associated with a poor clinical outcome in the clear cell carcinomas and hepatocellular carcinoma. Early studies suggested that most diseases with gender differences might link to their differential expression of sex hormone receptors. Recent results show that androgen receptor could promote renal cell carcinoma metastasis via modulating HIF2a-VEGF signaling,1 which also partly explains why renal cell carcinoma has a gender difference in tumor incidence (male-tofemale ratio of 1.6:1) and may link androgen receptor signaling to renal cell carcinoma progression. In this study the authors further evaluated the role of androgen receptor on infiltrating neutrophil mediated renal cell carcinoma progression and found that infiltrated neutrophils may function through modulating the androgen receptor to c-Myc signals to promote renal cell carcinoma cell proliferation. This newly identified signal pathway may provide us with a new potential therapeutic approach to better battle renal cell carcinoma progression via targeting these newly identified signals. Anthony Atala, MD 1. Mancuso A and Sternberg CN: New treatments for metastatic kidney cancer. Can J Urol, suppl., 2005; 12: 66.
Suggested Reading Langner C, Ratschek M, Rehak P et al: Steroid hormone receptor expression in renal cell carcinoma: an immunohistochemical analysis of 182 tumors. J Urol 2004; 171: 611.
Re: Marked Protection against Acute Renal and Hepatic Injury after Nitrited Myoglobin + Tin Protoporphyrin Administration R. A. Zager Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington, Seattle, Washington Transl Res 2015; 166: 485e501. doi: 10.1016/j.trsl.2015.06.004
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26117289
0022-5347/16/1956-1947/0 THE JOURNAL OF UROLOGY® Ó 2016 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2016.03.016 Vol. 195, 1947-1950, June 2016 Printed in U.S.A.
www.jurology.com
j
1947
1948
URO-SCIENCE
Editorial Comment: Administration of nitrited myoglobin along with, an inhibitor of its degradation (SnPP) leads to dramatic increases in a number of cytoprotective proteins in the kidney. Within 18 hours of its administration nitrited myoglobin plus SnPP evoked dramatic protection against 3 diverse models of acute kidney injury, namely glycerol induced rhabdomyolysis, maleate induced proximal tubule ATP depletion and postischemic acute kidney injury progression to chronic kidney disease. Surprisingly nitrited myoglobin plus SnPP administration also induced synergistic increases in cytoprotective proteins in the liver, leading to dramatic protection against hepatic ischemic reperfusion injury and hepatotoxicity. Finally, nitrited myoglobin plus SnPP can up-regulate cytoprotective proteins in the heart, suggesting the potential for cardiac protection and thus broad ranging cytoprotective effects. Each of these responses was induced in the absence of discernable renal, hepatic or cardiac toxicity. These data suggest that administration of nitrited myoglobin plus SnPP could potentially develop into a clinical prophylactic strategy for protecting against renal and extrarenal injuries, such as those resulting during cardiopulmonary bypass, aortic aneurysm repair and other complex, high risk surgeries. This strategy could potentially meet a number of significant unmet clinical needs. Anthony Atala, MD
Suggested Reading Sprenkle PC, Wren J, Maschino AC et al: Urine neutrophil gelatinase-associated lipocalin as a marker of acute kidney injury after kidney surgery. J Urol 2013; 190: 159.
Re: Autophagy Defects Suggested by Low Levels of Autophagy Activator MAP1S and High Levels of Autophagy Inhibitor LRPPRC Predict Poor Prognosis of Prostate Cancer Patients X. Jiang, W. Zhong, H. Huang, H. He, F. Jiang, Y. Chen, F. Yue, J. Zou, X. Li, Y. He, P. You, W. Yang, Y. Lai, F. Wang and L. Liu Department of Urology, Fifth Affiliated Hospital, Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, Guangzhou Medical University and Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China, and Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas Mol Carcinog 2015; 54: 1194e1204. doi: 10.1002/mc.22193
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25043940 Editorial Comment: The authors detected that levels of MAP1S, LRPPRC, P62 and g-H2AX labeled DNA double strand breaks and genome instability were increased from prostatic intraepithelial neoplasia to prostate adenocarcinomas developed in PTEN deficient mice, and that they were similarly increased from benign prostatic hyperplasia to prostate adenocarcinomas in humans. Therefore, a similar mechanism of tumor suppression through MAP1S mediated autophagy may occur in PTEN deficiency induced prostate adenocarcinomas in mice and naturally grown prostate adenocarcinomas in humans. However, MAP1S mediated autophagy activity was complicated. Similar to MAP1S deficiency in mouse hepatocellular carcinomas, MAP1S levels in patients with prostate adenocarcinoma were significantly correlated to overall survival. Patients with increased levels of MAP1S survived for a longer period, while those with decreased levels of MAP1S exhibited a poor prognosis. Higher levels of oxidative stress and genome instability enhanced the expression of MAP1S and activated autophagy to suppress oxidative stress and genome instability. Because of such a feedback regulatory loop, P62 and g-H2AX lost their values as prognostic markers. The MAP1S levels were negatively correlated to LRPPRC levels, while high levels of LRPPRC predicted poor prognosis and short survival. MAP1S levels and LRPPRC levels served as good markers for the prognosis of patients with prostate cancer. Further decrease of MAP1S levels in patients with high LRPPRC levels led to shorter survival. Anthony Atala, MD
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26231735 Editorial Comment: Neutrophils are among the key tumor infiltrating myeloid cells in the tumor environment. Similar to the myeloid macrophages, neutrophils have a tumor associated subpopulation, and the relationship between tumor associated neutrophil infiltration and prognosis in human cancers has been systematically discussed. Epidemiological evidence had suggested that neutrophil infiltration within human cancers was associated with a poor clinical outcome in the clear cell carcinomas and hepatocellular carcinoma. Early studies suggested that most diseases with gender differences might link to their differential expression of sex hormone receptors. Recent results show that androgen receptor could promote renal cell carcinoma metastasis via modulating HIF2a-VEGF signaling,1 which also partly explains why renal cell carcinoma has a gender difference in tumor incidence (male-tofemale ratio of 1.6:1) and may link androgen receptor signaling to renal cell carcinoma progression. In this study the authors further evaluated the role of androgen receptor on infiltrating neutrophil mediated renal cell carcinoma progression and found that infiltrated neutrophils may function through modulating the androgen receptor to c-Myc signals to promote renal cell carcinoma cell proliferation. This newly identified signal pathway may provide us with a new potential therapeutic approach to better battle renal cell carcinoma progression via targeting these newly identified signals. Anthony Atala, MD 1. Mancuso A and Sternberg CN: New treatments for metastatic kidney cancer. Can J Urol, suppl., 2005; 12: 66.
Suggested Reading Langner C, Ratschek M, Rehak P et al: Steroid hormone receptor expression in renal cell carcinoma: an immunohistochemical analysis of 182 tumors. J Urol 2004; 171: 611.
Re: Marked Protection against Acute Renal and Hepatic Injury after Nitrited Myoglobin + Tin Protoporphyrin Administration R. A. Zager Fred Hutchinson Cancer Research Center and Department of Medicine, University of Washington, Seattle, Washington Transl Res 2015; 166: 485e501. doi: 10.1016/j.trsl.2015.06.004
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26117289
0022-5347/16/1956-1947/0 THE JOURNAL OF UROLOGY® Ó 2016 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
http://dx.doi.org/10.1016/j.juro.2016.03.016 Vol. 195, 1947-1950, June 2016 Printed in U.S.A.
www.jurology.com
j
1947
1948
URO-SCIENCE
Editorial Comment: Administration of nitrited myoglobin along with, an inhibitor of its degradation (SnPP) leads to dramatic increases in a number of cytoprotective proteins in the kidney. Within 18 hours of its administration nitrited myoglobin plus SnPP evoked dramatic protection against 3 diverse models of acute kidney injury, namely glycerol induced rhabdomyolysis, maleate induced proximal tubule ATP depletion and postischemic acute kidney injury progression to chronic kidney disease. Surprisingly nitrited myoglobin plus SnPP administration also induced synergistic increases in cytoprotective proteins in the liver, leading to dramatic protection against hepatic ischemic reperfusion injury and hepatotoxicity. Finally, nitrited myoglobin plus SnPP can up-regulate cytoprotective proteins in the heart, suggesting the potential for cardiac protection and thus broad ranging cytoprotective effects. Each of these responses was induced in the absence of discernable renal, hepatic or cardiac toxicity. These data suggest that administration of nitrited myoglobin plus SnPP could potentially develop into a clinical prophylactic strategy for protecting against renal and extrarenal injuries, such as those resulting during cardiopulmonary bypass, aortic aneurysm repair and other complex, high risk surgeries. This strategy could potentially meet a number of significant unmet clinical needs. Anthony Atala, MD
Suggested Reading Sprenkle PC, Wren J, Maschino AC et al: Urine neutrophil gelatinase-associated lipocalin as a marker of acute kidney injury after kidney surgery. J Urol 2013; 190: 159.
Re: Autophagy Defects Suggested by Low Levels of Autophagy Activator MAP1S and High Levels of Autophagy Inhibitor LRPPRC Predict Poor Prognosis of Prostate Cancer Patients X. Jiang, W. Zhong, H. Huang, H. He, F. Jiang, Y. Chen, F. Yue, J. Zou, X. Li, Y. He, P. You, W. Yang, Y. Lai, F. Wang and L. Liu Department of Urology, Fifth Affiliated Hospital, Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, Guangzhou Medical University and Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China, and Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas Mol Carcinog 2015; 54: 1194e1204. doi: 10.1002/mc.22193
Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25043940 Editorial Comment: The authors detected that levels of MAP1S, LRPPRC, P62 and g-H2AX labeled DNA double strand breaks and genome instability were increased from prostatic intraepithelial neoplasia to prostate adenocarcinomas developed in PTEN deficient mice, and that they were similarly increased from benign prostatic hyperplasia to prostate adenocarcinomas in humans. Therefore, a similar mechanism of tumor suppression through MAP1S mediated autophagy may occur in PTEN deficiency induced prostate adenocarcinomas in mice and naturally grown prostate adenocarcinomas in humans. However, MAP1S mediated autophagy activity was complicated. Similar to MAP1S deficiency in mouse hepatocellular carcinomas, MAP1S levels in patients with prostate adenocarcinoma were significantly correlated to overall survival. Patients with increased levels of MAP1S survived for a longer period, while those with decreased levels of MAP1S exhibited a poor prognosis. Higher levels of oxidative stress and genome instability enhanced the expression of MAP1S and activated autophagy to suppress oxidative stress and genome instability. Because of such a feedback regulatory loop, P62 and g-H2AX lost their values as prognostic markers. The MAP1S levels were negatively correlated to LRPPRC levels, while high levels of LRPPRC predicted poor prognosis and short survival. MAP1S levels and LRPPRC levels served as good markers for the prognosis of patients with prostate cancer. Further decrease of MAP1S levels in patients with high LRPPRC levels led to shorter survival. Anthony Atala, MD