Inhibition of LDHA suppresses tumor progression in prostate cancer.

A key hallmark of cancer cells is their altered metabolism, known as Warburg effect. Lactate dehydrogenase A (LDHA) executes the final step of aerobic glycolysis and has been reported to be involved in the tumor progression. However, the function of LDHA in prostate cancer has not been studied. In current study, we observed overexpression of LDHA in the clinical prostate cancer samples compared with benign prostate hyperplasia tissues as demonstrated by immunohistochemistry and real-time qPCR. Attenuated expression of LDHA by siRNA or inhibition of LDHA activities by FX11 inhibited cell proliferation, migration, invasion, and promoted cell apoptosis of PC-3 and DU145 cells. Mechanistically, decreased Warburg effect as demonstrated by reduced glucose consumption and lactate secretion and reduced expression of MMP-9, PLAU, and cathepsin B were found after LDHA knockdown or FX11 treatment in PC-3 and DU145 cells. Taken together, our study revealed the oncogenic role of LDHA in prostate cancer and suggested that LDHA might be a potential therapeutic target.

[Influences of three surgical approaches to urethral stricture on the erectile function of the patients].

OBJECTIVE: To evaluate the impacts of three different surgical approaches to urethral stricture on the erectile function of the patients. METHODS: This study included 126 male patients with urethral stricture, 35 treated by substitution urethroplasty (group A), 52 by anastomotic urethroplasty (group B), and 39 by internal urethroplasty (group C). We evaluated the pre- and postoperative erectile function of the patients using IIEF-5 scores by telephone calls and interviews. We also monitored their nocturnal penile tumescence (NPT). RESULTS: The IIEF-5 scores in groups A, B and C were 13.5 +/- 4.5, 11.1 +/- 4.8 and 14.5 +/- 4.41 respectively after surgery, all significantly decreased as compared with 17.1 +/- 2.6, 17.1 +/- 3.0 and 17.6 +/- 2.2 preoperatively (P < 0.05). CONCLUSION: All the three surgical approaches can reduce IIEF-5 scores in patients with urethral stricture, but anastomotic urethroplasty may induce a higher incidence of erectile dysfunction than the other two approaches.

Exosomal PGAM1 promotes prostate cancer angiogenesis and metastasis by interacting with ACTG1.

Tumor-derived exosomes and their contents promote cancer metastasis. Phosphoglycerate mutase 1 (PGAM1) is involved in various cancer-related processes. Nevertheless, the underlying mechanism of exosomal PGAM1 in prostate cancer (PCa) metastasis remains unclear. In this study, we performed in vitro and in vivo to determine the functions of exosomal PGAM1 in the angiogenesis of patients with metastatic PCa. We performed Glutathione-S-transferase pulldown, co-immunoprecipitation, western blotting and gelatin degradation assays to determine the pathway mediating the effect of exosomal PGAM1 in PCa. Our results revealed a significant increase in exosomal PGAM1 levels in the plasma of patients with metastatic PCa compared to patients with non-metastatic PCa. Furthermore, PGAM1 was a key factor initiating PCa cell metastasis by promoting invadopodia formation and could be conveyed by exosomes from PCa cells to human umbilical vein endothelial cells (HUVECs). In addition, exosomal PGAM1 could bind to γ-actin (ACTG1), which promotes podosome formation and neovascular sprouting in HUVECs. In vivo results revealed exosomal PGAM1 enhanced lung metastasis in nude mice injected with PCa cells via the tail vein. In summary, exosomal PGAM1 promotes angiogenesis and could be used as a liquid biopsy marker for PCa metastasis.

Over-expression of extracellular matrix metalloproteinase inducer in prostate cancer is associated with high risk of prostate-specific antigen relapse after radical prostatectomy.

PURPOSE: The prognostic efficiency of clinical grading and staging in patients with confined or moderately differentiated prostate cancer (PCa) has been markedly improved, which underscores the importance of new prognostic markers. Extracellular matrix metalloproteinase inducer (EMMPRIN) has been demonstrated to be involved in cancerangiogenesis, metastasis and invasion. EMMPRIN expression was evaluated by measuring mRNA and protein levels in a large cohort of patients with PCa following prostatectomy and the findings were compared with clinico-pathological parameters, including prostate-specific antigen (PSA) relapse time. METHODS: EMMPRIN mRNA levels in 20 pairs of normal and cancerous prostate tissues were determined by quantitative real-time PCR. Protein expression in paraffin-embedded specimens of prostates gathered from 300 patients with PCa was detected by immunohistochemistry using a monoclonal antibody against EMMPRIN. The associations of EMMPRIN protein expression with the clinico-pathological parameters and PSA relapse-free time after radical prostatectomy were subsequently assessed. RESULTS: Both EMMPRIN mRNA and protein levels were higher in PCa tissue, compared with adjacent normal tissue. In addition, the positive expression rates of EMMPRIN in PCa tissues were significantly associated with preoperative PSA levels (p=0.008), AJCC stage (p=0.006) and Gleason Score (p < 0.001), Risk classification (p < 0.001), lymph node status post-surgery (p < 0.001) and surgical margin status (p < 0.001) were also determined. Multivariate analysis, using the Cox proportional hazards model, revealed that positive EMMPRIN expression was an independent prognostic factor for an increased risk of PSA relapse. CONCLUSION: Over-expression of EMMPRIN correlated with the aggressiveness of PCa, and the PSA relapse-free time, and may be a novel and useful biomarker for follow-up and treatment decisions for PCa.

Surgical treatment of patients with intermediate-terminal pancreatic cancer.

AIM: To investigate the surgical treatment of patients with intermediate-terminal pancreatic cancer. METHODS: A retrospective analysis was made of the clinical data of 163 patients with intermediate-terminal pancreatic cancer who were surgically treated between August 1994 and August 2003. RESULTS: A total of 149 patients underwent palliative surgery. The mortality rate of those who underwent cholecystojejunostomy alone was 14.2%, the icterus or cholangitis recurrence rate was 61.9% with an average survival period of 7.1 mo. The mortality rate for those who received hepatic duct-jejunostomy (HDJS) was 5.7%, the icterus or cholangitis recurrence rate was 6.8% with an average survival period of 7.1 mo. But 31.8% of the patients developed duodenum obstruction within 6 mo after the surgery, six of seven patients with severe pain were given peri-abdominal aorta injection with absolute alcohol and their pain was alleviated. The other patients underwent percutaneous transhepatic cholangial drainage (PTCD) and their icterus index returned to normal level within 40 d with an average survival period of 7.5 mo. CONCLUSION: Roux-en-Y HDJS combined with prophylactic gastrojejunostomy is recommended for patients with intermediate-terminal pancreatic cancer, and biliary prosthesis can partly relieve biliary obstruction in a short term.

[Common failure reasons and improvement ways in treatment of gallstones by choledochoscope in operation].

OBJECTIVE: To analyze common problems, failing causes and improvement ways for curing gallstones by choledochoscope in operation. METHOD: To analyze a case group of 762 individual patients who had undergone choledochoscope operations in the period of Jan, 1995 approximately Sep, 2005. RESULTS: 136 cases are found with residual stones in the bile duct after the operations. Residual stone rate amounts to 17.8%. 55 patients are known that bile duct stones could not be remove completely during operations. 81 patients are proved that stones still remain in their bile ducts by T-tube cholangiography and choledochoscope after operations. Among them, 29 patients complicate with narrow in intrahepatic bile ducts and debouch of bile ducts, 39 patients complicate with stones of intrahepatic bile and variation of bile duct, 13 patients complicate with stones and narrow at the inferior segment of choledochus. CONCLUSIONS: It is important to pay attention for bile duct variation and debouch of affection bile duct or inferior segment of choledochus stenosis. B-ultrasound is useful to reduce residual stones in operations. The surgeon should check different lengths of the duct methodically, and use the endoscope to explore the bile duct in order not to omit any stones.

[Causes of failure in choledochoscopic diagnosis and removal of gallstone].

OBJECTIVE: To discuss the causes for failure in diagnosis and removal of gallstone using choledochoscope. METHOD: A retrospective analysis was conducted in 714 cases of gallstone treated with choledochoscopic operations. RESULTS: Residual stones in the bile duct were found in 132 (18.5%) cases after the operation. In 54 cases the bile duct stones failed to be completely removed even before the closure. By T-tube cholangiography and choledochoscopy after the operation, 78 cases were found to have residual bile duct stones, among them 29 were complicated with intrahepatic bile duct and bile duct opening stenosis, 37 with intrahepatic bile stone and bile duct variation, and 12 with choledochus inferior segment stenosis and stone formation. CONCLUSION: Due attention should be paid during the choledochoscopic operation to bile duct variation, bile duct opening stenosis or choledochus inferior segment stenosis, which should be carefully inspected by segments in succession to minimize the possibility of residual stones.