The critical role played by stroma-epithelium crosstalk in carcinogenesis and progression of prostate cancer has been increasingly recognized. These interactions are mediated by a variety of paracrine factors secreted by cancer cells and/or stromal cells. In human prostate cancer, reactive stroma is characterized by an increase in myofibroblasts and a corresponding amplification of extracellular matrix production and angiogenesis. Permanent genetic mutations have been reported in stromal cells as well as in tumour cells. Transforming growth factor-beta, vascular endothelial growth factor, platelet-derived growth factor and fibroblast growth factor signalling pathways are involved in the process of angiogenesis, whereas hepatocyte growth factor, insulin-like growth factor-1, epidermal growth factor, CXC12 and Interleukin-6 play active roles in the progression, androgen-independent conversion and distal metastasis of prostate cancer. Some soluble factors have reciprocal interactions with androgens and the androgen receptor (AR), and can even activate AR in the absence of the androgen ligand. In this article, we review the complex interactions between cancer cells and the surrounding microenvironment, and discuss the potential therapeutic targets in the stromal compartment of prostate cancer.
Cell Communication ; physiology ; Disease Progression ; Epithelial Cells ; pathology ; physiology ; Humans ; Male ; Neovascularization, Pathologic ; physiopathology ; Prostatic Neoplasms ; pathology ; physiopathology ; Receptor Cross-Talk ; physiology ; Stromal Cells ; pathology ; physiology

In a large clinical trial, finasteride reduced the rate of low-grade prostate cancer (PCa) while increasing the incidence of high-grade cancer. Whether finasteride promotes the development of high-grade tumors remains controversial. We demonstrated the role of fibroblasts and c-Jun in chemopreventive and therapeutic effect of finasteride on xenograft models of PCa. LNCaP (PC3) cells or recombinants of cancer cells and fibroblasts were implanted in male athymic nude mice treated with finasteride. Tumor growth, cell proliferation, apoptosis, p-Akt, and p-ERK1/2 were evaluated. In LNCaP (PC3) mono-grafted models, finasteride did not change the tumor growth. In recombinant-grafted models, fibroblasts and c-Jun promoted tumor growth; finasteride induced proliferation of LNCaP cells and repressed PC3 cell apoptosis. When c-Jun was knocked out, fibroblasts and/or finasteride did not promote the tumor growth. Finasteride inhibited p-Akt and p-ERK1/2 in mono-culture cancer cells while stimulating the same signaling molecules in the presence of fibroblasts. Reduced p-Akt and p-ERK1/2 were noted in the presence of c-Jun-/- fibroblasts. Fibroblasts and c-Jun promote PCa growth; finasteride further stimulates tumor growth with promoted proliferation, repressed apoptosis, and up-regulated pro-proliferative molecular pathway in the presence of fibroblasts and c-Jun. Stromal-epithelial interactions play critical roles in finasteride′s therapeutic effects on PCa. Our findings have preliminary implications in using finasteride as a chemopreventive or therapeutic agent for PCa patients.

OBJECTIVE: To compare the outcomes of endoscopic combined ultrasound-guided access (EUGA) with the conventional ultrasound-guided access (UGA) to achieve percutaneous renal access in endoscopic combined intrarenal surgery (ECIRS). METHODS: A retrospective review of 53 patients undergoing ECIRS to treat upper urinary tract calculi between January 2017 and October 2019 was con-ducted. All of the cases were of complex upper urinary tract stones larger than 2 cm in diameter. The com-plex stone situations, such as multiple renal calyces calculi or staghorn calculi necessitated ECIRS. Under general anesthesia, the patients were placed in the galdakao-modified supine valdivia (GMSV) position, thus allowing both antegrade and retrograde accesss. The patients were divided to UGA and EUGA groups according to the protocol of achieving percutaneous renal access. In 28 cases, endoscopic combined ultrasound-guided accesss were obtained. Puncture and dilation were performed under direct flexible ureteroscopic visualization, while percutaneous renal access of 25 cases were performed with the conventional technique employing ultrasound guidance. Demographic and perioperative information, such as stone burden, presence of hydronephrosis and number of calyces involved was compared. Primary outcomes included total operative time, renal access time, repeat puncture, hemoglobin level, perioperative complications, and stone-free rate. RESULTS: No major intra-operative complication was recorded in all the 53 ECRIS. No significant difference was observed between the groups in age and gender. There was no significant difference in body mass index[BMI (29.21±3.14) kg/m² vs.(28.53±2.56) kg/m²], stone burden (37.68±6.89) mm vs. (35.53±6.52) mm, number of calyces involved 2.72±0.68 vs. 2.86±0.71, presence of hydronephrosis (56.0% vs. 46.4%), total operative time (93.0±12.2) min vs. (96.8±14.2) min, hemoglobin level reduction (6.56±2.16) g/L vs. 97.54±2.64) g/L, stone-free rate (92.0% vs. 92.8%), hospital stay (5.52±0.59) d vs. (5.64±0.62) d, perioperative complication rate (8.0% vs. 7.2%). Two patients in EUGA group experienced perioperative complications (one urinary tract infection and one hematuria) while two patients in UGA group experienced perioperative urinary tract infection. None in both groups received blood transfusion. The patients undergoing EUGA had shorter renal access time [(4.0±0.7) min vs. (6.8±2.6) min, P < 0.01] and less repeat puncture (0 vs. 4 cases, P < 0.05). CONCLUSION EUGA is an optimal technique to establish percutaneous renal access in ECIRS, which minimizes access time and repeated procedures.
Humans ; Kidney Calculi ; Nephrostomy, Percutaneous ; Retrospective Studies ; Treatment Outcome ; Ultrasonography, Interventional ; Ureteroscopy

Objective To investigate the anti-apoptotic function of clusterin in LNCaP cell line and the role of clusterin antisense oligodcoxynucleotide(AS-ODN)in TNF-?-induced death of LNCaP cell. Methods The wild type LNCaP(group L),LNCaP transfected with the control vector(group M),LNCaP transfected with full-length clusterin expression vector(group A,ie,study group)were cultured.For the de- tection of cytotoxic effect of TNF-?,MTT and ELISA methods were used to determine the cell proliferation and apoptosis of the 3 clones,and the changes of proliferation and apoptosis in A cell after transfection of clusterin AS-ODN were also assessed.Results MTT method showed that the cell proliferation activity(A value)of groups L,M,and A were 0.84?0.03,0.85?0.04,0.95?0.03,respectively;the difference be- tween groups L and M was not significant(P＞0.05);but compared with group A the cell proliferation activ- ity was significantly lower in groups L and M(P＜0.01 for both).ELISA resuhs showed that the A values of groups L,M,and A were 0.59?0.04,0.62?0.03,0.33?0.04,respectively;the difference between groups L and M was not significant(P＞0.05);but compared with group A,the apoptosis rates were significantly higher in groups L and M(P＜0.01 for both).In group A,A values of cell proliferation activity in subgroups control,AS-ODN,TNF-?,TNF-?+AS-ODN were 1.30?0.03,1.25?0.03,0.99?0.03,0.80?0.03, respectively;the differences between each group were significant(P＜0.05 for all).And the A values of cell apoptosis in the above 4 groups were 0.02?0.00,0.21?0.02,0.63?0.07,1.16?0.04,respectively,the differences between each group were significant(P＜0.01 for all).Conclusions Stable transfection and subsequent expression of clusterin result in resistance to the cytotoxic effect of TNF-?.Transfection with clus- terin AS-ODN enhances cytotoxic effect of TNF-?in A cells.These results suggest that clusterin plays an im- portant role in anti-apoptotic function in LNCaP cell line.

BACKGROUNDVascular control and tissue dissection are crucial steps in successful laparoscopic surgery. Recently, a new commercially available vessel sealing technology, the LigaSure vessel sealing system (Valleylab, Boulder, USA), has been introduced. The aim of the present study was to evaluate the benefits of the LigaSure in laparoscopic nephrectomy.

METHODSFrom January 2005 to March 2010, 170 laparoscopic nephrectomies were performed with the LigaSure vessel sealing system, including simple and radical nephrectomy and nephroureterectomy. In a retrospective study, the laparoscopic operating time, estimated intraoperative blood loss, duration of postoperative drainage, total amount of postoperative drainage, as well as postoperative hospital stay, were recorded and studied.

RESULTSAll 170 laparoscopic nephrectomies using LigaSure were accomplished successfully without conversion to open surgery. There was no severe vascular complication or other serious complications. The mean laparoscopic operating time was 124.2 minutes (range, 14 - 230 minutes); mean blood loss was 148.6 ml (range, 20 - 540 ml); mean time for postoperative drainage was 3.1 days (range, 1 - 7 days); mean amount of postoperative drainage was 206.5 ml (range, 27 - 435 ml) and mean postoperative hospital stay was 6.9 days (range, 3 - 18 days).

CONCLUSIONSLaparoscopic nephrectomy using LigaSure appears technically feasible and easy, and produces satisfactory results. The LigaSure provides a safe and fast way to seal vessels and tissue bundles during nephrectomy.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Laparoscopy ; methods ; Male ; Middle Aged ; Nephrectomy ; methods ; Retrospective Studies ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of management of renal stone in non-dilated collecting system by percutaneous nephrolithotripsy (PCNL) under ultrasound guidance.

METHODFrom September 2003 to April 2005, 132 cases of renal stone in non-dilated collecting system were performed by percutaneous nephrolithotripsy. A stent was first inserted into the pelvis through cystoscope, and saline was instilled to dilate collecting system. Antegrade percutaneous access was obtained by B-type ultrasound guidance. A combination pneumatic and ultrasonic lithotrite were used to disintegrate and remove stone under direct vision. Clinical data including operation time, complications and stone free rate were analyzed retrospectively.

RESULTSThe percutaneous renal access was successfully established under B-type ultrasound guidance in all patients, immediate phase I lithotripsy was performed in 129 cases and delayed phase II lithotripsy in 3 cases. Operation time ranged from 70 to 130 minutes, average time was (89 +/- 11) minutes, 3 cases were supported by blood transfusion, severe complications did not occur during nephrolithotripsy. Stones were cleared in 114 out of 132 cases (86.4%) during immediate phase I lithotripsy, residual stone fragment was found in 18 cases who received second PCNL or adjuvant extracorporeal shock wave lithotripsy.

CONCLUSIONThe management of renal stone in non-dilated collecting system using PCNL appears to be efficacious and safe under B-type ultrasound guidance.

Adult ; Aged ; Female ; Humans ; Kidney Calculi ; therapy ; Kidney Calices ; diagnostic imaging ; Lithotripsy ; methods ; Male ; Middle Aged ; Nephrostomy, Percutaneous ; methods ; Punctures ; methods ; Retrospective Studies ; Treatment Outcome ; Ultrasonography

OBJECTIVETo define changes in clusterin expression following short-term neoadjuvant hormone therapy (NHT) and its biological significance in prostate cancer tissues.

METHODSTwenty-six archival radical prostatectomy (RP) specimens without receiving NHT, 19 needle biopsies and corresponding 19 RP specimens following 3-month NHT, were subjected to immunohistochemical clusterin staining.

RESULTSStaining for clusterin was mainly found in cytoplasm and part of extracellular matrix. Clusterin expression was significantly greater in RP specimens with preoperative NHT (t = 2.91, P < 0.01); Needle biopsies obtained before NHT consistently demonstrated lower staining intensity (1.42 +/- 0.51) than corresponding RP specimens (2.16 +/- 0.60) following 3-month NHT (t = 7.10, P < 0.01).

CONCLUSIONSUpregulation of clusterin in part accounts for malignant progression of prostate cancer through its anti-apoptotic action following androgen withdrawal. These findings support that adjuvant therapy targeting clusterin may enhance androgen ablation therapy in advanced prostate cancer.

Aged ; Clusterin ; genetics ; metabolism ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Neoadjuvant Therapy ; methods ; Oligonucleotides, Antisense ; therapeutic use ; Prostatic Neoplasms ; metabolism ; pathology ; therapy

The inhibition of 5-α reductase type 2 (SRD5A2) by finasteride is commonly used for the management of urinary obstruction resulting from benign prostatic enlargement (BPE). Certain BPE patients showing no SRD5A2 protein expression are resistant to finasteride therapy. Our previous work showed that methylated cytosine-phosphate-guanine (CpG) islands in the SRD5A2 gene might account for the absence or reduction of SRD5A2 protein expression. Here, we found that the expression of the SRD5A2 protein was variable and that weak expression of the SRD5A2 protein (scored 0-100) occurred in 10.0% (4/40) of benign adult prostates. We showed that the expression of SRD5A2 was negatively correlated with DNA methyltransferase 1 (DNMT1) expression. In vitro SRD5A2-negative BPH-1 cells were resistant to finasteride treatment, and SRD5A2 was re-expressed in BPH-1 cells when SRD5A2 was demethylated by 5-Aza-2'-deoxycytidine (5-Aza-CdR) or N-phthalyl-L-tryptophan (RG108). Furthermore, we determined the exact methylation ratios of CpG dinucleotides in a CpG island of SRD5A2 through MassArray quantitative methylation analysis. Ten methylated CpG dinucleotides, including four CpG dinucleotides in the promoter and six CpG dinucleotides in the first exon, were found in a CpG island located from -400 bp to +600 bp in SRD5A2, which might lead to the silencing of SRD5A2 and the absence or reduction of SRD5A2 protein expression. Finasteride cannot exert a therapeutic effect on patients lacking SRD5A2, which may partially account for the resistance to finasteride observed in certain BPE patients.