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Wang XH, Fu YL, Xu YN, Zhang PC, Zheng TX, Ling CQ, Feng YL. Ginsenoside Rh1 regulates the immune microenvironment of hepatocellular carcinoma via the glucocorticoid receptor. JOURNAL OF INTEGRATIVE MEDICINE 2024; 22:709-718. [PMID: 39455405 DOI: 10.1016/j.joim.2024.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 09/05/2024] [Indexed: 10/28/2024]
Abstract
OBJECTIVE Ginsenoside Rh1 (G-Rh1) has been confirmed to inhibit the growth of breast cancer and colon cancer, but its therapeutic effect on hepatocellular carcinoma (HCC) is unclear. This study investigates the therapeutic effect of G-Rh1 on HCC as well as the underlying mechanism. METHODS Bioinformatics methods were used to analyze glucocorticoid receptor (GR) expression and the tumor microenvironment in HCC tissues from HCC patients. The effect of G-Rh1 on HCC cells was investigated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The therapeutic effect of G-Rh1 was investigated in vivo using subcutaneous transplantation models in C57BL/6J and nude mice. Additionally, the proportion of infiltrating immune cells in tumors was analyzed using flow cytometry, the GR and major histocompatibility complex class-I (MHC-I) expression of HCC cells after G-Rh1 treatment was analyzed using Western blotting, and G-Rh1-treated Hepa1-6 cells were cocultured with bone marrow-derived dendritic cells and B3Z T cells to further analyze the ability of G-Rh1 to induce dendritic cell (DC) maturation and CD8+ T cell activation. RESULTS GR expression was upregulated in HCC tissues, and high GR expression was associated with a worsened immune microenvironment. In vitro studies showed that G-Rh1 had no significant effect on the proliferation of HCC cells, while in vivo studies showed that G-Rh1 exerted antitumor effects in C57BL/6J mice but not in nude mice. Further research revealed that G-Rh1 ameliorated the immunosuppressive tumor microenvironment, thereby enhancing the antitumor effects of lenvatinib by increasing the infiltration of CD8+ T cells, mature DCs, and MHC-I-positive cells. MHC-I was upregulated by G-Rh1 via GR suppression. Moreover, overexpression of GR abolished the G-Rh1-mediated promotion of MHC-I expression in Huh7 cells, as well as the maturation of DCs and the activation of CD8+ T cells. CONCLUSION G-Rh1 can regulate the immune microenvironment of HCC by targeting GR, thus increasing the antitumor effect of lenvatinib. Please cite this article as: Wang XH, Fu YL, Xu YN, Zhang PC, Zheng TX, Ling CQ, Feng YL. Ginsenoside Rh1 regulates the immune microenvironment of hepatocellular carcinoma via the glucocorticoid receptor. J Integr Med. 2024; 22(6): 710-720.
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Affiliation(s)
- Xiong-Hui Wang
- Department of Traditional Chinese Medicine, First Affiliated Hospital of Naval Medical University, Shanghai 200433, China; PLA Joint Logistics Support Force No. 967 Hospital, Dalian 116021, Liaoning Province, China
| | - Ya-Lan Fu
- Department of Integrated Traditional Chinese and Western Medicine, Medical College of Qingdao University, Qingdao 266071, Shandong Province, China
| | - Yan-Nan Xu
- Department of Traditional Chinese Medicine, First Affiliated Hospital of Naval Medical University, Shanghai 200433, China; PLA Joint Logistics Support Force No. 920 Hospital, Kunming 650100, Yunnan Province, China
| | - Peng-Cheng Zhang
- First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
| | - Tian-Xiao Zheng
- Department of Traditional Chinese Medicine, First Affiliated Hospital of Naval Medical University, Shanghai 200433, China
| | - Chang-Quan Ling
- Department of Traditional Chinese Medicine, First Affiliated Hospital of Naval Medical University, Shanghai 200433, China.
| | - Ying-Lu Feng
- Department of Traditional Chinese Medicine, PLA Navy No. 971 Hospital, Qingdao 266071, Shandong Province, China.
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Wu CC, Liu CH, Hung CC, Liao GS, Chang CH. Experts' opinions progress and trends in the surgical management of breast cancer in Taiwan. JOURNAL OF CANCER RESEARCH AND PRACTICE 2022. [DOI: 10.4103/jcrp.jcrp_36_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Prognostic Significance of Glucocorticoid Receptor Expression in Cancer: A Systematic Review and Meta-Analysis. Cancers (Basel) 2021; 13:cancers13071649. [PMID: 33916028 PMCID: PMC8037088 DOI: 10.3390/cancers13071649] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 03/17/2021] [Accepted: 03/24/2021] [Indexed: 01/30/2023] Open
Abstract
Simple Summary In solid tumours, emerging evidence indicates that signalling through the glucocorticoid receptor (GR) can encourage the growth and spread of tumours and so drugs targeting this receptor are in development for use in cancer treatment. For these reasons, GR may be useful in anticipating a patient’s outcome upon their cancer diagnosis or to predict their tumours response to drugs targeting this receptor. In this review we aim to ascertain whether GR expression in tumours affects cancer patient survival. Overall, GR expression did not affect patient survival when assessing all cancer types. However, we found that in certain cancer subtypes such as gynaecological cancers (endometrial and ovarian) and early stage, untreated triple negative breast cancers, high GR expression is linked with cancer progression and therefore a poorer patient prognosis. Further studies are needed to uncover the exact role of GR in specific tumour (sub)types in order to provide the correct patients with GR targeting therapies. Abstract In solid malignancies, the glucocorticoid receptor (GR) signalling axis is associated with tumour progression and GR antagonists are in clinical development. Therefore, GR expression may be a useful potential prognostic or predictive biomarker for GR antagonist therapy in cancer. The aim of this review is to investigate if GR expression in tumours is predictive of overall survival or progression free survival. Twenty-five studies were identified through systematic searches of three databases and a meta-analysis conducted using a random effects model, quantifying statistical heterogeneity. Subgroup analysis was conducted for cancer types and publication bias was assessed via funnel plots. There was high heterogeneity in meta-analysis of the studies in all cancer types, which found no association between high GR expression with overall survival (pooled unadjusted HR 1.16, 95% CI (0.89–1.50), n = 2814; pooled adjusted HR 1.02, 95% CI (0.77–1.37), n = 2355) or progression-free survival (pooled unadjusted HR 1.12, 95% CI (0.88–1.42), n = 3365; pooled adjusted HR 1.04, 95% CI (0.6–1.81), n = 582) across all cancer types. However, subgroup meta-analyses showed that high GR expression in gynaecological cancers (endometrial and ovarian) (unadjusted HR 1.83, 95% CI (1.31–2.56), n = 664) and early stage, untreated triple negative breast cancers (TNBCs) (unadjusted HR 1.73, 95% CI (1.35–2.23), n = 687) is associated with disease progression. GR expression in late stage, chemotherapy treated TNBC was not prognostic (unadjusted HR 0.76, 95% CI (0.44, 1.32), n = 287). In conclusion, high GR expression is associated with an increased risk of disease progression in gynaecological and early stage, untreated TNBC. Additional studies are required to elucidate the tumour specific function of the GR receptor in order to ensure GR antagonists target the correct patient groups.
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Lai Q, Iesari S, Finkenstedt A, Hoppe-Lotichius M, Foguenne M, Lehner K, Otto G, Lerut J. Hepatocellular carcinoma recurrence after acute liver allograft rejection treatment: A multicenter European experience. Hepatobiliary Pancreat Dis Int 2019; 18:517-524. [PMID: 31151807 DOI: 10.1016/j.hbpd.2019.05.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Accepted: 05/10/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND During the last decades, several risk factors for the recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) have been investigated. However, the impact of two important drivers of oncogenesis, namely the immunosuppression and the treatment of acute cellular rejection (ACR) have been marginally addressed. This study aimed at investigating the impact of ACR treatment on the incidence of tumor recurrence in a large European HCC-LT population. METHODS Seven hundred and eighty-one adult patients transplanted between February 1, 1985 and June 30, 2016 were retrospectively analyzed. After propensity score match, 116 patients treated for ACR using steroid boluses were compared with 115 patients who did not present any ACR or a histologic but clinical irrelevant ACR. RESULTS Steroid boluses treated patients had a 18-fold higher overall incidence of HCC recurrence than those non-treated patients (16.4% vs. 0.9%; P<0.0001). At multivariate Cox regression analysis, steroid boluses used to treat ACR were an independent risk factor for HCC recurrence (HR=14.2; 95% CI: 1.8-110.4; P = 0.010). CONCLUSIONS The decision to treat ACR as well as to reinforce immunosuppression load should be cautiously taken in view of the presented results. Prospective studies are needed to further elucidate the clinical impact of immunosuppression on HCC recurrence after transplantation.
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Affiliation(s)
- Quirino Lai
- Starzl Unit of Abdominal Transplantation, University Hospitals Saint Luc, Université catholique Louvain, Brussels, Belgium; Hepato-biliary Surgery and Liver Transplantation Unit, Sapienza University of Rome, Umberto I Hospital, Rome, Italy.
| | - Samuele Iesari
- Starzl Unit of Abdominal Transplantation, University Hospitals Saint Luc, Université catholique Louvain, Brussels, Belgium; Department of Bio-technological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy
| | - Armin Finkenstedt
- Department of Internal Medicine I, Innsbruck Medical University, Innsbruck, Austria
| | - Maria Hoppe-Lotichius
- Department of Transplantation and Hepatobiliary Surgery, University of Mainz, Mainz, Germany
| | - Maxime Foguenne
- Starzl Unit of Abdominal Transplantation, University Hospitals Saint Luc, Université catholique Louvain, Brussels, Belgium
| | - Konrad Lehner
- Department of Internal Medicine I, Innsbruck Medical University, Innsbruck, Austria
| | - Gerd Otto
- Department of Transplantation and Hepatobiliary Surgery, University of Mainz, Mainz, Germany
| | - Jan Lerut
- Starzl Unit of Abdominal Transplantation, University Hospitals Saint Luc, Université catholique Louvain, Brussels, Belgium
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Wei Q, Gao F, Zhuang R, Ling Q, Ke Q, Wu J, Shen T, Zhang M, Zhang M, Xu X, Zheng S. A national report from China Liver Transplant Registry: steroid avoidance after liver transplantation for hepatocellular carcinoma. Chin J Cancer Res 2017; 29:426-437. [PMID: 29142462 DOI: 10.21147/j.issn.1000-9604.2017.05.07] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Objective We aimed to evaluate the efficacy and safety of steroid-free immunosuppression after liver transplantation (LT) for hepatocellular carcinoma (HCC). Methods We retrospectively analyzed HCC recipients without steroids after LT (SF group, n=368) based on the China Liver Transplant Registry (CLTR) database. These recipients were matched 1:2 with patients using steroids (S group, n=736) for the same period after LT for HCC, according to propensity scores. Results Multivariate analysis indicates that recipients with younger age [odds ratio (OR), 1.053; P=0.011], preoperative hepatitis B virus (HBV) DNA ≥1,000 copies/mL (OR, 2.597; P=0.004) and beyond Milan criteria (OR, 4.255; P<0.001) were identified as the risk factors associated with tumor recurrence in steroid avoidance recipients after LT. The patients fulfilling the Milan criteria in the SF group presented higher overall and tumor-free survival rates than those in the S group (P<0.05). Multivariate analysis revealed that recipient beyond Milan criteria was an independent prognostic factor for overall survival (OR, 1.690; P<0.001) and tumor-free survival (OR, 2.066; P<0.001). The incidences of new-onset diabetes mellitus (21.20%vs. 33.29%, P<0.001), new-onset hypertension (10.05%vs. 18.61%, P<0.001) and hyperlipidemia (4.08%vs. 7.20%, P=0.042) were significantly lower in the SF group. Conclusions Steroid-free immunosuppression could be safe and feasible for HBV-related HCC patients in LT. Age, HBV DNA level and Milan criteria maybe risk factors associated with tumor recurrence in steroid avoidance recipients. Recipient beyond Milan criteria was an independent prognostic factor and recipient fulfilling Milan criteria can benefit the most from steroid-free immunosuppression.
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Affiliation(s)
- Qiang Wei
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Feng Gao
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Runzhou Zhuang
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Qi Ling
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Qinghong Ke
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Jian Wu
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Tian Shen
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Mangli Zhang
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Min Zhang
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Xiao Xu
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China
| | - Shusen Zheng
- Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.,Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, China
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Vacca M, Degirolamo C, Massafra V, Polimeno L, Mariani-Costantini R, Palasciano G, Moschetta A. Nuclear receptors in regenerating liver and hepatocellular carcinoma. Mol Cell Endocrinol 2013; 368:108-19. [PMID: 22789748 DOI: 10.1016/j.mce.2012.06.025] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2012] [Revised: 06/28/2012] [Accepted: 06/29/2012] [Indexed: 12/22/2022]
Abstract
A comprehensive understanding of the pathways underlying hepatocyte turnover and liver regeneration is essential for the development of innovative and effective therapies in the management of chronic liver disease, and the prevention of hepatocellular carcinoma (HCC) in cirrhosis. Nuclear receptors (NRs) are master transcriptional regulators of liver development, differentiation and function. NRs have been implicated in the modulation of hepatocyte priming and proliferation in regenerating liver, chronic hepatitis and HCC development. In this review, we focus on NRs and their pathways regulating hepatocyte proliferation and liver regeneration, with a perspective view on NRs as candidate biomarkers and novel pharmacological targets in the management of liver disease and HCC.
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Affiliation(s)
- Michele Vacca
- Laboratory of Lipid Metabolism and Cancer, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy
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Chen ZS, He F, Zeng FJ, Jiang JP, Du DF, Liu B. Early steroid withdrawal after liver transplantation for hepatocellular carcinoma. World J Gastroenterol 2007; 13:5273-6. [PMID: 17876900 PMCID: PMC4171311 DOI: 10.3748/wjg.v13.i39.5273] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the impact of early steroid withdrawal on the incidence of rejection, tumor recurrence and complications after liver transplantation for advanced-stage hepatocellular carcinoma.
METHODS: Fifty-four patients underwent liver transplantation for advanced-stage hepatocellular carcinoma from April 2003 to June 2005. These cases were divided into a steroid-withdrawal group (group A, n = 28) and a steroid-maintenance group (group B, n = 26). In group A, steroid was withdrawn 3 mo after transplantation. In group B, steroid was continuously used postoperatively. The incidence of rejection, 6-mo and 1-year recurrence rate of carcinoma, 1-year survival rate, mean serum tacrolimus trough level, and liver and kidney function were compared between the two groups.
RESULTS: In the two groups, no statistical difference was observed in the incidence of rejection (14.3 vs 11.5%, P > 0.05), mean serum tacrolimus trough levels (6.9 ± 1.4 vs 7.1 ± 1.1 μg/L, P > 0.05), liver and kidney function after 6 mo [alanine aminotransferase (ALT): 533 ± 183 vs 617 ± 217 nka/L, P > 0.05; creatinine: 66 ± 18 vs 71 ± 19 μmol/L, P > 0.05], 6-mo recurrence rate of carcinoma (25.0 vs 42.3%, P > 0.05), and 1-year survival rate (64.2 vs 46.1%, P > 0.05). The 1-year tumor recurrence rate (39.2 vs 69.2%, P < 0.05), serum cholesterol level (3.9 ± 1.8 vs 5.9 ± 2.6 mmol/L, P < 0.01) and fasting blood sugar (5.1 ± 2.1 vs 8.9 ± 3.6 mmol/L, P < 0.01) were significantly different. These were lower in the steroid-withdrawal group than in the steroid-maintenance group.
CONCLUSION: Early steroid withdrawal was safe after liver transplantation in patients with advanced-stage hepatocellular carcinoma. When steroids were withdrawn 3 mo post-operation, the incidence of rejection did not increase, and there was no demand to maintain tacrolimus at a high level. In contrast, the tumor recurrence rate and the potential of adverse effects decreased significantly. This may have led to an increase in long-term survival rate.
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Affiliation(s)
- Zhi-Shui Chen
- Institution of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China.
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Voutsas IF, Gritzapis AD, Alexis MN, Katsanou ES, Perez S, Baxevanis CN, Papamichail M. A novel quantitative flow cytometric method for measuring glucocorticoid receptor (GR) in cell lines: correlation with the biochemical determination of GR. J Immunol Methods 2007; 324:110-9. [PMID: 17582432 DOI: 10.1016/j.jim.2007.05.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2006] [Revised: 04/11/2007] [Accepted: 05/11/2007] [Indexed: 01/01/2023]
Abstract
Currently, a time consuming biochemical method is used for GR quantification. Here we compare the biochemical approach with a newly developed flow cytometric method of measuring GR in cell lines, which is less time consuming and does not requires the use of radioactive materials. The biochemical assay is easy to apply but the cells need to be grown in media free of endogenous glucocorticoids, in order to prevent them from interfering with radiolabelled hormone binding to the receptor. The presence of endogenous GR ligands is known to reduce receptor levels and to often produce false negative results. The immunofluorescent method is free of such limitations, as it depends entirely on detecting the receptor using a highly specific monoclonal antibody. Additionally, the biochemical assay cannot measure heterogeneity in individual cells, in contrast the flow cytometric one enables the enumeration of the receptor on a per cell basis, allowing exact description of differences in receptor levels amongst intact cells. Our results demonstrate that the flow cytometric method is of similar accuracy but of higher precision compared to the biochemical one. Also, the data we obtained using the immunofluorescent method correlated well with the biochemical one (R(2)=0.9712). In conclusion, flow cytometric method requires small cell numbers, is more accurate and lesser time consuming than the biochemical one. Thus, it could be useful for the quantification of GR in lymphocyte subpopulations, in lymphoproliferative disorders and in tumor cells from cancer patients, in order to design more efficient clinical treatment protocols.
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Affiliation(s)
- Ioannis F Voutsas
- Cancer Immunology and Immunotherapy Center, Saint Savvas Cancer Hospital, 171 Alexandras Ave., 11522 Athens, Greece.
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Lin MC, Wu CC, Cheng SB, Liu TJ, P'eng FK. The Influence of High Serum Testosterone Levels on the Long-term Prognosis in Male Patients Undergoing Hepatectomy for Early Stage Hepatocellular Carcinoma without Vascular Invasion. World J Surg 2007; 31:1469-73. [PMID: 17534543 DOI: 10.1007/s00268-007-9094-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND The influence of high serum testosterone levels on the long-term prognosis in male patients undergoing hepatectomy for hepatocellular carcinoma (HCC) remains to be fully elucidated. The aim of the present study was to conduct a retrospective investigation of the impact of high serum testosterone levels on the risk of tumor recurrence and long-term prognosis in male patients undergoing hepatectomy for early stage HCC without vascular invasion. METHODS Between August 1995 and March 1999, 42 male patients undergoing curative hepatectomy for HCC of tumor-node-metastasis (TNM) stages I and II without vascular invasion were enrolled in the study. Preoperative serum testosterone concentration was measured. The clinicopathological features, tumor recurrence rates, and 5-year disease-free and actuarial survival after hepatectomy were compared between the patients with serum testosterone levels in the upper half (group I, n = 21) and the patients in the lower half (group II, n = 21). RESULTS The background and clinicopathological features did not differ significantly between groups I and group II. All survivors were followed up for more than 5 years. Until March 2005, patients in group I, with serum testosterone levels in the upper half, had a significantly higher percentage of 5-year tumor recurrence than group II, with lower testosterone levels (76.2% versus 28.6%; p < 0.005). The patients in group I also had a significantly inferior 5-year disease-free (p < 0.01) and actuarial (p < 0.05) survival rates than patients in group II. CONCLUSIONS Male patients with high serum testosterone levels undergoing hepatectomy for early stage HCC without vascular invasion have significantly higher 5-year tumor recurrence rates and an inferior long-term prognosis than patients with low testosterone levels. These findings signal a strategy of adjuvant anti-androgen treatment selectively targeted for the male patients with high serum testosterone levels after hepatectomy for early stage HCC without vascular invasion to achieve better long-term outcome.
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Affiliation(s)
- Min-Che Lin
- Department of Surgery, Taichung Veterans General Hospital, No.160, Sec 3, Chung-Kang Road, Taichung, Taiwan.
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Yeh DC, Cheng SB, Yu CC, Ho WL, Wu CC, Liu TJ, P'eng FK. Role of glucocorticoid receptor in serosa-involved gastric carcinoma after gastrectomy. J Gastrointest Surg 2006; 10:706-11. [PMID: 16713543 DOI: 10.1016/j.gassur.2005.10.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2005] [Accepted: 10/03/2005] [Indexed: 01/31/2023]
Abstract
Glucocorticoid receptor (GR) was first found in the cytosol of gastric cancer tissue more than 15 years ago. At present, most gastric cancers are diagnosed at the advanced stage. To elucidate the role of GR in gastric cancer, the GR levels of the cancer tissue of 75 consecutive patients with grossly serosa-involved gastric carcinoma were determined by the dextran-coated charcoal method. The clinicopathologic characteristics and long-term survival duration were compared in patients with GR-positive and GR-negative cancer cells. We found that GR could be detected in the cytosol of cancer cells in 31 (41.3%) of the gastric cancer patients with a median concentration of 18.5 (range, 1.03-73.9) fmol/mg protein. No significant differences could be found in any clinicopathologic characteristic between the patients with GR-positive and GR-negative cancers. After multivariate analysis, gross Borrmann's type, metastatic lymph node number, and GR positivity were the independent prognostic factors after gastrectomy for serosa-involved gastric carcinoma. GR-positive gastric cancer had a worse survival rate than GR-negative gastric cancer. Multimodality adjuvant therapies should be considered in patients with GR-positive serosa-involved gastric carcinoma.
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Affiliation(s)
- Dah-Cherng Yeh
- Department of Surgery, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan
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