This study was designed to investigate the association between immune inflammation and androgen receptor （AR） expression in benign prostatic hyperplasia （BPH）. We retrospectively analyzed 105 prostatectomy specime...This study was designed to investigate the association between immune inflammation and androgen receptor （AR） expression in benign prostatic hyperplasia （BPH）. We retrospectively analyzed 105 prostatectomy specimens. An immune inflammation score for each specimen was defined by combining three immunohistochemical markers （CD4, CD8 and CD20）. The immunohistochemical markers were CD4 and CD8 for T lymphocytes, CD20 for B lymphocytes and AR antibody for the AR in BPH samples. Rates of CD4, CD8, CD20 and AR expression in BPH were 20 （19.0%）, 21 （20.0%）, 101 （96.2%） and 48 （45.7%）, respectively. Total prostate volume （TPV） was higher in the immune inflammation group than in the non-immune inflammation group （62.7 ml vs. 49.2 ml, t=-2.482, P〈0.05）. Patients in the immune inflammation group had a higher serum prostate-specific antigen （PSA） than those in the non-inflammation group （7.5 ng m1-1 vs. 5.4 ng m1-1, t=-2.771, P〈0.05）. Specifically, the immune inflammation group showed a higher rate of AR expression than the non-inflammation group （56.1% vs. 28.2%, χ2=7.665, P〈0.05）. Our study revealed a strong association between immune inflammation and TPV, serum PSA and AR expression in BPH tissue. Prostate hyperplasia caused by an immune inflammatory process may contribute to BPH progression over time. Therefore, the inflammatory response involved in BPH may be a prime therapeutic target.展开更多
Benign prostatic hyperplasia(BPH)is a benign enlargement of the prostate in which incidence increases linearly with age,beginning at about 50 years old.BPH is a significant source of morbidity in aging men by causing ...Benign prostatic hyperplasia(BPH)is a benign enlargement of the prostate in which incidence increases linearly with age,beginning at about 50 years old.BPH is a significant source of morbidity in aging men by causing lower urinary tract symptoms and acute urinary retention.Unfortunately,the etiology of BPH incidence and progression is not clear.This review highlights the role of the androgen receptor(AR)in prostate development and the evidence for its involvement in BPH.The AR is essential for normal prostate development,and individuals with defective AR signaling,such as after castration,do not experience prostate enlargement with age.Furthermore,decreasing dihydrotestosterone availability through therapeutic targeting with 5a-reductase inhibitors diminishes AR activity and results in reduced prostate size and symptoms in some BPH patients.While there is some evidence that AR expression is elevated in certain cellular compartments,how exactly AR is involved in BPH progression has yet to be elucidated.It is possible that AR signaling within stromal cells alters intercellular signaling and a“reawakening”of the embryonic mesenchyme,loss of epithelial AR leads to changes in paracrine signaling interactions,and/or chronic inflammation aids in stromal or epithelial proliferation evident in BPH.Unfortunately,a subset of patients fails to respond to current medical approaches,forcing surgical treatment even though age or associated co-morbidities make surgery less attractive.Fundamentally,new therapeutic approaches to treat BPH are not currently forthcoming,so a more complete molecular understanding of BPH etiology is necessary to identify new treatment options.展开更多
The growth of prostate cancer is sensitive to androgen, and hormonal therapy has been used for treatment of ad-vanced cancer. About 80% of prostate cancers initially respond to hormonal therapy, howerver, more than ha...The growth of prostate cancer is sensitive to androgen, and hormonal therapy has been used for treatment of ad-vanced cancer. About 80% of prostate cancers initially respond to hormonal therapy, howerver, more than half of the re-sponders gradually become resistant to this therapy. Changes in tumors from an androgen-responsive to an androgen-unre-sponsive state have been widely discussed. Since androgen action is mediated by androgen receptor (AR), abnormalitiesof AR is believed to play an important role of the loss of androgen responsiveness in prostate cancer. This article focusedon the role of AR in the progression of prostate cancer. (Asian J Androl 1999 Sep; 1: 81-85)展开更多
Objective:Herbal medicine is an important therapeutic option for benign prostatic hyperplasia(BPH),a common disease in older men that can seriously affect their quality of life.Currently,it is crucial to develop agent...Objective:Herbal medicine is an important therapeutic option for benign prostatic hyperplasia(BPH),a common disease in older men that can seriously affect their quality of life.Currently,it is crucial to develop agents with strong efficacy and few side effects.Herein we investigated the effects of the extract of Rauwolfia vomitoria,a shrub grown in West Africa,on BPH.Methods:Rats with testosterone-induced BPH were treated with R.vomitoria.Prostates were histologically analyzed by Hematoxylin and eosin staining.Proliferation index and the expression levels of androgen receptor and its associated proteins were quantified through immunohistochemistry and immunoblotting.Androgen receptor target genes were examined by quantitative real-time polymerase chain reaction.The sperm count and body weight of rats were also measured.Results:The oral administration of R.vomitoria extract significantly reduced the prostate weight and prostate weight index in BPH rats,supported by the decreased thickness of the prostate epithelial layer and increased lumen size.Similar effects were observed in the BPH rats treated with the reference drug,finasteride.R.vomitoria extract significantly reduced the testosterone-induced proliferation markers,including proliferating cell nuclear antigen and cyclin D1,in the prostate glands of BPH rats;it also reduced levels of androgen receptor,its associated protein steroid 5 a-reductase 1 and its downstream target genes(FK506-binding protein 5 and matrix metalloproteinase 2).Notably,compared with the finasteride group,R.vomitoria extract did not significantly reduce sperm count.Conclusion:R.vomitoria suppresses testosterone-induced BPH development.Due to its milder side effects,R.vomitoria could be a promising therapeutic agent for BPH.展开更多
We evaluated the effect of isoquercetin(quercetin-O-3-glucoside-quercetin,IQ)as a functional component of Abeliophyllum disistichum Nakai ethanol extract(ADLE)on prostate cell proliferation and apoptosis and its effec...We evaluated the effect of isoquercetin(quercetin-O-3-glucoside-quercetin,IQ)as a functional component of Abeliophyllum disistichum Nakai ethanol extract(ADLE)on prostate cell proliferation and apoptosis and its effects on the IGF-1/PI3K/Akt/mTOR pathway in benign prostatic hyperplasia(BPH).Metabolites in ADLE were analyzed using UHPLC-qTOF-MS and HPLC.IQ was orally administered(1 or 10 mg/kg)to a testosterone propionate-induced BPH rat model,and its effects on the prostate weight were evaluated.The effect of IQ on androgen receptor(AR)signaling was analyzed in LNCaP cells.Whether IGF-1 and IQ affect the IGF-1/PI3K/Akt/mTOR pathway in BPH-1 cells was also examined.The metabolites in ADLE were identified and quantified,which confirmed that ADLE contained abundant IQ(20.88 mg/g).IQ significantly reduced the prostate size in a concentration-dependent manner in a BPH rat model,and significantly decreased the expression of AR signaling factors in the rat prostate tissue and LNCaP cells in a concentration-dependent manner.IQ also inhibited the PI3K/AKT/mTOR pathway activated by IGF-1 treatment in BPH-1 cells.In BPH-1 cells,IQ led to G0/G1 arrest and suppressed the expression of proliferation factors while inducing apoptosis.Thus,IQ shows potential for use as a pharmaceutical and nutraceutical for BPH.展开更多
Background The failure of endocrine treatment for advanced prostate cancer might be related to aberrant activation of androgen receptor (AR) Prostate cancer cell line LNCaP contains AR that can be activated by andr...Background The failure of endocrine treatment for advanced prostate cancer might be related to aberrant activation of androgen receptor (AR) Prostate cancer cell line LNCaP contains AR that can be activated by androgen, estrogen and progesterone This study was set to investigate the effects of antisense AR RNA on growth of LNCaP cultured in medium containing varied concentrations of R1881, 17β-estradiol, and progesterone, respectively Methods LNCaP cells transfected with antisense AR RNA retroviral vector pL-AR-SN were designated as LNCaP as-AR . LNCaP cells containing empty vector pLXSN served as LNCaP Neo . LNCaP and LNCaP Neo were taken as controls In vitro cell growth assay, proliferative cells of LNCaP and tranfected LNCaPs were counted by typan staining when they cultured with synthetic androgen R1881, 17β-estradiol, and progesterone, respectively Results Growth of LNCaP as-AR was inhibited significantly ( P <0 05) compared with that of LNCaP and LNCaP Neo at 1 nmol/L R1881, 10 nmol/L 17β-estradiol, and 1 nmol/L progesterone, respectively No difference was seen between LNCaP and LNCaP Neo ( P >0 05) Microscopic observation showed that LNCaP and LNCaP Neo cells grew well, but only few LNCaP as-AR cells were alive Conclusions Our observations indicate that antisense AR RNA retroviral vector pL-AR-SN could change androgen-independent characteristics of LNCaP cells, which might shed some novel insights into the treatment of androgen-independent prostate cancer展开更多
Benign prostatic hyperplasia(BPH)is a chronic male disease characterized by the enlarged prostate.Celtis choseniana Nakai(C.choseniana)is medicinally used to alleviate pain,gastric disease,and lung abscess.In this stu...Benign prostatic hyperplasia(BPH)is a chronic male disease characterized by the enlarged prostate.Celtis choseniana Nakai(C.choseniana)is medicinally used to alleviate pain,gastric disease,and lung abscess.In this study,the effect of C.choseniana extract on BPH was investigated using testosterone-induced rats.Sprague Dawley rats were divided into five groups:control,BPH(testosterone 5 mg·kg^(−1)),Fina(finasteride 2 mg·kg^(−1)),and C.choseniana(50 and 100 mg·kg^(−1)).After four weeks of TP treatment with finasteride or C.choseniana,prostate weights and DHT levels were measured.In addition,the prostates were histopathologically examined and measured for protein kinase B(Akt)/nuclear factor-κB(NF-κB)/AR signaling,proliferation,apoptosis,and autophagy.Pro-state weight and epithelial thickness were reduced in the C.choseniana groups compared with that in the BPH group.The extract of C.choseniana acted as a 5αreductase inhibitor,reducing DHT levels in the prostate.Furthermore,the extract of C.choseniana blocked the activation of p-Akt,nuclear NF-κB activation and reduced the expression of AR and PSA compared with BPH.Moreover,the ex-pression of Bax,PARP-1,and p53 increased,while the expression of bcl-2 decreased.The present study demonstrated that C.choseni-ana extract alleviated testosterone-induced BPH by suppressing 5αreductase and Akt/NF-κB activation,reducing AR signaling and in-ducing apoptosis and autophagy in the prostate.These results suggested that C.choseniana probably contain potential herbal agents to alleviate BPH.展开更多
文摘This study was designed to investigate the association between immune inflammation and androgen receptor （AR） expression in benign prostatic hyperplasia （BPH）. We retrospectively analyzed 105 prostatectomy specimens. An immune inflammation score for each specimen was defined by combining three immunohistochemical markers （CD4, CD8 and CD20）. The immunohistochemical markers were CD4 and CD8 for T lymphocytes, CD20 for B lymphocytes and AR antibody for the AR in BPH samples. Rates of CD4, CD8, CD20 and AR expression in BPH were 20 （19.0%）, 21 （20.0%）, 101 （96.2%） and 48 （45.7%）, respectively. Total prostate volume （TPV） was higher in the immune inflammation group than in the non-immune inflammation group （62.7 ml vs. 49.2 ml, t=-2.482, P〈0.05）. Patients in the immune inflammation group had a higher serum prostate-specific antigen （PSA） than those in the non-inflammation group （7.5 ng m1-1 vs. 5.4 ng m1-1, t=-2.771, P〈0.05）. Specifically, the immune inflammation group showed a higher rate of AR expression than the non-inflammation group （56.1% vs. 28.2%, χ2=7.665, P〈0.05）. Our study revealed a strong association between immune inflammation and TPV, serum PSA and AR expression in BPH tissue. Prostate hyperplasia caused by an immune inflammatory process may contribute to BPH progression over time. Therefore, the inflammatory response involved in BPH may be a prime therapeutic target.
基金supported by grants 1R01DK117906 and 1P20DK116185 from National Institute of Diabetes and Digestive and Kidney Diseases(NIDDK)by the North-Shore Foundation.
文摘Benign prostatic hyperplasia(BPH)is a benign enlargement of the prostate in which incidence increases linearly with age,beginning at about 50 years old.BPH is a significant source of morbidity in aging men by causing lower urinary tract symptoms and acute urinary retention.Unfortunately,the etiology of BPH incidence and progression is not clear.This review highlights the role of the androgen receptor(AR)in prostate development and the evidence for its involvement in BPH.The AR is essential for normal prostate development,and individuals with defective AR signaling,such as after castration,do not experience prostate enlargement with age.Furthermore,decreasing dihydrotestosterone availability through therapeutic targeting with 5a-reductase inhibitors diminishes AR activity and results in reduced prostate size and symptoms in some BPH patients.While there is some evidence that AR expression is elevated in certain cellular compartments,how exactly AR is involved in BPH progression has yet to be elucidated.It is possible that AR signaling within stromal cells alters intercellular signaling and a“reawakening”of the embryonic mesenchyme,loss of epithelial AR leads to changes in paracrine signaling interactions,and/or chronic inflammation aids in stromal or epithelial proliferation evident in BPH.Unfortunately,a subset of patients fails to respond to current medical approaches,forcing surgical treatment even though age or associated co-morbidities make surgery less attractive.Fundamentally,new therapeutic approaches to treat BPH are not currently forthcoming,so a more complete molecular understanding of BPH etiology is necessary to identify new treatment options.
文摘The growth of prostate cancer is sensitive to androgen, and hormonal therapy has been used for treatment of ad-vanced cancer. About 80% of prostate cancers initially respond to hormonal therapy, howerver, more than half of the re-sponders gradually become resistant to this therapy. Changes in tumors from an androgen-responsive to an androgen-unre-sponsive state have been widely discussed. Since androgen action is mediated by androgen receptor (AR), abnormalitiesof AR is believed to play an important role of the loss of androgen responsiveness in prostate cancer. This article focusedon the role of AR in the progression of prostate cancer. (Asian J Androl 1999 Sep; 1: 81-85)
基金supported by The Beljanski Foundation(to JY)and Military Laboratory Animal Fund(Grant No.SYDW[2017]15to TF)。
文摘Objective:Herbal medicine is an important therapeutic option for benign prostatic hyperplasia(BPH),a common disease in older men that can seriously affect their quality of life.Currently,it is crucial to develop agents with strong efficacy and few side effects.Herein we investigated the effects of the extract of Rauwolfia vomitoria,a shrub grown in West Africa,on BPH.Methods:Rats with testosterone-induced BPH were treated with R.vomitoria.Prostates were histologically analyzed by Hematoxylin and eosin staining.Proliferation index and the expression levels of androgen receptor and its associated proteins were quantified through immunohistochemistry and immunoblotting.Androgen receptor target genes were examined by quantitative real-time polymerase chain reaction.The sperm count and body weight of rats were also measured.Results:The oral administration of R.vomitoria extract significantly reduced the prostate weight and prostate weight index in BPH rats,supported by the decreased thickness of the prostate epithelial layer and increased lumen size.Similar effects were observed in the BPH rats treated with the reference drug,finasteride.R.vomitoria extract significantly reduced the testosterone-induced proliferation markers,including proliferating cell nuclear antigen and cyclin D1,in the prostate glands of BPH rats;it also reduced levels of androgen receptor,its associated protein steroid 5 a-reductase 1 and its downstream target genes(FK506-binding protein 5 and matrix metalloproteinase 2).Notably,compared with the finasteride group,R.vomitoria extract did not significantly reduce sperm count.Conclusion:R.vomitoria suppresses testosterone-induced BPH development.Due to its milder side effects,R.vomitoria could be a promising therapeutic agent for BPH.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF)funded by the Ministry of Education,Science and Technology (NRF2020R1A2C1014798 to E-K Kim)。
文摘We evaluated the effect of isoquercetin(quercetin-O-3-glucoside-quercetin,IQ)as a functional component of Abeliophyllum disistichum Nakai ethanol extract(ADLE)on prostate cell proliferation and apoptosis and its effects on the IGF-1/PI3K/Akt/mTOR pathway in benign prostatic hyperplasia(BPH).Metabolites in ADLE were analyzed using UHPLC-qTOF-MS and HPLC.IQ was orally administered(1 or 10 mg/kg)to a testosterone propionate-induced BPH rat model,and its effects on the prostate weight were evaluated.The effect of IQ on androgen receptor(AR)signaling was analyzed in LNCaP cells.Whether IGF-1 and IQ affect the IGF-1/PI3K/Akt/mTOR pathway in BPH-1 cells was also examined.The metabolites in ADLE were identified and quantified,which confirmed that ADLE contained abundant IQ(20.88 mg/g).IQ significantly reduced the prostate size in a concentration-dependent manner in a BPH rat model,and significantly decreased the expression of AR signaling factors in the rat prostate tissue and LNCaP cells in a concentration-dependent manner.IQ also inhibited the PI3K/AKT/mTOR pathway activated by IGF-1 treatment in BPH-1 cells.In BPH-1 cells,IQ led to G0/G1 arrest and suppressed the expression of proliferation factors while inducing apoptosis.Thus,IQ shows potential for use as a pharmaceutical and nutraceutical for BPH.
基金ThisworkwassupportedbyagrantfromtheNationalNaturalScienceFoundationofChina (No 3 9770 740 )
文摘Background The failure of endocrine treatment for advanced prostate cancer might be related to aberrant activation of androgen receptor (AR) Prostate cancer cell line LNCaP contains AR that can be activated by androgen, estrogen and progesterone This study was set to investigate the effects of antisense AR RNA on growth of LNCaP cultured in medium containing varied concentrations of R1881, 17β-estradiol, and progesterone, respectively Methods LNCaP cells transfected with antisense AR RNA retroviral vector pL-AR-SN were designated as LNCaP as-AR . LNCaP cells containing empty vector pLXSN served as LNCaP Neo . LNCaP and LNCaP Neo were taken as controls In vitro cell growth assay, proliferative cells of LNCaP and tranfected LNCaPs were counted by typan staining when they cultured with synthetic androgen R1881, 17β-estradiol, and progesterone, respectively Results Growth of LNCaP as-AR was inhibited significantly ( P <0 05) compared with that of LNCaP and LNCaP Neo at 1 nmol/L R1881, 10 nmol/L 17β-estradiol, and 1 nmol/L progesterone, respectively No difference was seen between LNCaP and LNCaP Neo ( P >0 05) Microscopic observation showed that LNCaP and LNCaP Neo cells grew well, but only few LNCaP as-AR cells were alive Conclusions Our observations indicate that antisense AR RNA retroviral vector pL-AR-SN could change androgen-independent characteristics of LNCaP cells, which might shed some novel insights into the treatment of androgen-independent prostate cancer
文摘Benign prostatic hyperplasia(BPH)is a chronic male disease characterized by the enlarged prostate.Celtis choseniana Nakai(C.choseniana)is medicinally used to alleviate pain,gastric disease,and lung abscess.In this study,the effect of C.choseniana extract on BPH was investigated using testosterone-induced rats.Sprague Dawley rats were divided into five groups:control,BPH(testosterone 5 mg·kg^(−1)),Fina(finasteride 2 mg·kg^(−1)),and C.choseniana(50 and 100 mg·kg^(−1)).After four weeks of TP treatment with finasteride or C.choseniana,prostate weights and DHT levels were measured.In addition,the prostates were histopathologically examined and measured for protein kinase B(Akt)/nuclear factor-κB(NF-κB)/AR signaling,proliferation,apoptosis,and autophagy.Pro-state weight and epithelial thickness were reduced in the C.choseniana groups compared with that in the BPH group.The extract of C.choseniana acted as a 5αreductase inhibitor,reducing DHT levels in the prostate.Furthermore,the extract of C.choseniana blocked the activation of p-Akt,nuclear NF-κB activation and reduced the expression of AR and PSA compared with BPH.Moreover,the ex-pression of Bax,PARP-1,and p53 increased,while the expression of bcl-2 decreased.The present study demonstrated that C.choseni-ana extract alleviated testosterone-induced BPH by suppressing 5αreductase and Akt/NF-κB activation,reducing AR signaling and in-ducing apoptosis and autophagy in the prostate.These results suggested that C.choseniana probably contain potential herbal agents to alleviate BPH.
