Application of fluorescence in situ hybridization in the detection of bladder transitional-cell carcinoma: A multi-center clinical study based on Chinese population.

OBJECTIVE: To evaluate the diagnostic value of fluorescence in situ hybridization (FISH) in bladder cancer. METHODS: We enrolled healthy volunteers and patients who were clinically suspected to have bladder cancer and conducted FISH tests and cytology examinations from August 2007 to December 2008. Receiver operating characteristic (ROC) curve analysis was performed and the area under curve (AUC) values were calculated for both the FISH and urine cytology tests. RESULTS: A cohort of 988 healthy volunteers was enrolled to establish a reference range for the normal population. A total of 4807 patients with hematuria were prospectively, randomly enrolled for the simultaneous analysis of urine cytology, FISH testing, and a final diagnosis as determined by the pathologic findings of a biopsy or a surgically-excised specimen. Overall, the sensitivity of FISH in detecting transitional-cell carcinoma was 82.7%, while that of cytology was 33.4% (p < 0.001). The sensitivity values of FISH for non-muscle invasive and muscle invasive bladder transitional-cell carcinoma were 81.7% and 89.6%, respectively (p = 0.004). The sensitivity values of FISH for low and high grade bladder cancer were 82.6% and 90.1%, respectively (p = 0.002). CONCLUSION: FISH is significantly more sensitive than voided urine cytology for detecting bladder cancer in patients evaluated for gross hematuria at all cancer grades and stages. Higher sensitivity using FISH was obtained in high grade and muscle invasive tumors.

IL­23 concentration­dependently regulates T24 cell proliferation, migration and invasion and is associated with prognosis in patients with bladder cancer.

Interleukin­23 (IL­23, also known as IL23A), is an important proinflammatory cytokine whose role in the development and progression of tumors remains controversial. The present study on IL­23 focused on its impact on the tumor microenvironment. Existing studies on its direct role on tumor cells are limited. Previously, we reported that the expression level of IL­23 in human bladder urothelial carcinoma was significantly higher than that in adjacent tissues as determined by immunohistochemistry. In this study, we further validated the results of immunohistochemistry using the Oncomine database and we found that IL23A expression in non­muscle invasive bladder urothelial carcinoma (NMIBC) was significantly higher than that in muscle invasive bladder urothelial carcinoma (MIBC). Expression of IL23A was negatively correlated with the clinical stage of bladder urothelial carcinoma and had a positive correlation with prognosis. In vitro experiments revealed that different concentrations of IL­23 had different effects on T24 cells. A low concentration of 20 ng/ml IL­23 promoted T24 cell proliferation, migration, invasion and EMT transformation, while a high concentration of 40 ng/ml IL­23 inhibited these functions. These results indicated that IL­23 plays a dual role in the progression of bladder cancer. Low concentrations of IL­23 promote bladder tumor progression, while high concentrations of IL­23 have the opposite effect.

Triptorelin relieves lower urinary tract symptoms in Chinese advanced prostate cancer patients: a multicenter, non-interventional, prospective study.

BACKGROUND: Although triptorelin is increasingly used in China for biochemical castration, its effects on primary prostate cancer symptoms remain unclear. This study aimed to assess the prevalence of lower urinary tract symptoms (LUTS) in Chinese prostate cancer patients and the effectiveness of triptorelin on LUTS. METHODS: In this 48-week multicenter, non-interventional, prospective study, we enrolled patients with locally advanced or metastatic prostate cancer. Patients received triptorelin (15 mg) intramuscularly at baseline and at weeks 12, 24, and 36 with symptom assessment using the International Prostate Symptoms Score (IPSS). The primary endpoints were the prevalence of LUTS at baseline per IPSS categories and the percentage of patients with moderate to severe LUTS (IPSS > 7) at baseline, having at least a 3-point reduction of IPSS score at week 48. RESULTS: A total of 398 patients were included; 211 (53.0%) and 160 (40.2%) among them had severe and moderate LUTS, respectively. Of the patients with IPSS scores available at baseline and at week 48 (n = 213), 81.2% achieved a reduction in IPSS of at least 3 points. Of the patients with moderate to severe LUTS at baseline and IPSS scores available at baseline and at week 48 (n = 194), 86.6% achieved a total IPSS reduction of at least 3 points. CONCLUSIONS: The vast majority of Chinese patients with locally advanced or metastatic prostate cancer scheduled to receive triptorelin as part of their standard treatment have severe or moderate LUTS. Triptorelin therapy resulted in sustained improvement of LUTS in these patients.

Enhanced recovery after surgery for radical cystectomy with ileal urinary diversion: a multi-institutional, randomized, controlled trial from the Chinese bladder cancer consortium.

PURPOSE: Enhanced recovery after surgery (ERAS) has played an important role in recovery management for radical cystectomy with ileal urinary diversion (RC-IUD). This study is to evaluate ERAS compared with the conventional recovery after surgery (CRAS) for RC-IUD. METHODS: From October 2014 and July 2016, bladder cancer patients scheduled for curative treatment from 25 centers of Chinese Bladder Cancer Consortium were randomly assigned to either ERAS or CRAS group. Primary endpoint was the 30-day complication rate. Secondary endpoints included recovery of fluid and regular diet, flatus, bowel movement, ambulation, and length of stay (LOS) postoperatively. Follow-up period was 30-day postoperatively. RESULTS: There were 144 ERAS and 145 CRAS patients. Postoperative complications occurred in 25.7 and 30.3% of the ERAS and CRAS patients with 55 complications in each group, respectively (p = 0.40). There was no significant difference between groups in major complications (p = 0.82), or type of complications (p = 0.99). The ERAS group had faster recovery of bowel movements (median 88 versus 100 h, p = 0.01), fluid diet tolerance (68 versus 96 h, p < 0.001), regular diet tolerance (125 versus 168 h, p = 0.004), and ambulation (64 versus 72 h, p = 0.047) than the CRAS group, but similar time to flatus and LOS. CONCLUSIONS: ERAS did not increase 30-day complications compared with CRAS after RC. ERAS may be better than CRAS in terms of bowel movement, tolerance of fluid and regular diet, and ambulation.

Transurethral endoscopic treatment of seminal vesicle cysts (report of seven cases).

OBJECTIVE: Seminal vesicle cysts are a rare disorder of the male reproductive system. The goal of this report was to summarize the radiological manifestations and transurethral endoscopic treatment of large seminal vesicle cysts. MATERIALS AND METHODS: The clinical data of seven cases of giant seminal vesicle cysts, including their symptoms, radiological images, transurethral endoscopic treatment, and postoperative follow-up, were retrospectively reviewed. RESULTS: Computerized tomography and magnetic resonance imaging (MRI) demonstrated the cysts behind the bladder, above the prostate, and away from the midline. The lesions ranged in size from 8.26 cm × 7.98 cm × 4.85 cm to 9.27 cm × 8.95 cm × 8.15 cm. Two cases were associated with ipsilateral renal and ureteral agenesis and were classified as congenital malformations. The other five cases were simple seminal vesicle cysts thought to be secondary to acquired ejaculatory duct obstruction. All seven cases were successfully treated using transurethral endoscopic unroofing with cautery of the mucosa. All the seminal vesicle cysts were confirmed by pathologic examination. No malignant disease was found. All preoperative symptoms resolved after surgery. No complications were observed. No patient developed abnormalities of erection, ejaculation, or orgasm. No bladder or rectal injuries were noted. The seminal vesicle cysts were significantly decreased in size or absent 3-6 months after treatment. CONCLUSION: MRI best characterized seminal vesical cysts and their cause. Transurethral unroofing with cautery of the mucosa is an extension of well-accepted cystoscopic techniques. It is safe, easy to perform, and effective. It is the preferred method for the treatment of large seminal vesicle cysts.

Current status of diagnosis and treatment of bladder cancer in China - Analyses of Chinese Bladder Cancer Consortium database.

OBJECTIVE: To investigate current status of diagnosis and treatment of bladder cancer in China. METHODS: A database was generated by Chinese Bladder Cancer Consortium (CBCC). From January 2007 to December 2012, 14,260 cases from 44 CBCC centers were included. Data of diagnosis, treatment and pathology were collected. RESULTS: The average age was 63.5 year-old and most patients were male (84.3%). The most common histologic types were urothelial carcinoma (91.4%), adenocarcinoma (1.8%), and squamous carcinoma (1.9%). According to 1973 and 2004 WHO grading system, 42.0%, 41.0%, and 17.0% of patients were grade 1, 2, and 3, and 16.0%, 48.7%, and 35.3% of patients were papillary urothelial neoplasms of low malignant potential, low, and high grade, respectively. Non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) were 25.2% and 74.1%, respectively (0.8% not clear). Carcinoma in situ was only 2.4%. Most patients were diagnosed by white-light cystoscopy with biopsy (74.3%). Fluorescence and narrow band imaging cystoscopy had additional detection rate of 1.0% and 4.0%, respectively. Diagnostic transurethral resection (TUR) provided detection rate of 16.9%. Most NMIBCs were treated with TUR (89.2%). After initial TUR, 2.6% accepted second TUR, and 45.7%, 69.9%, and 58.7% accepted immediate, induced, and maintenance chemotherapy instillation, respectively. Most MIBCs were treated with radical cystectomy (RC, 59.7%). Laparoscopic RCs were 35.1%, while open RC 63.4%. Extended and standard pelvic lymph node dissection were 7% and 66%, respectively. Three most common urinary diversions were orthotopic neobladder (44%), ileal conduit (31%), and ureterocutaneostomy (23%). Only 2.3% of patients accepted neo-adjuvant chemotherapy and only 18% of T3 and T4 patients accepted adjuvant chemotherapy. CONCLUSION: Disease characteristics are similar to international reports, while differences of diagnosis and treatment exist. This study can provide evidences for revisions of the guideline on bladder cancer in China.

A novel experimental hypoxia chamber for cell culture.

Tissue hypoxia is a common pathophysiological process. Since 1990s, numerous studies have focused on investigating cellular adaptation to experimental hypoxia. A modular incubator chamber made of solid materials has frequently been used in the experiments that require hypoxic conditions. Here, we introduce a novel and inflatable chamber for hypoxia experiments. In experiments detecting hypoxia-induced accumulation of hypoxia-inducible factor 1α (HIF-1α) and hypoxia-induced expression of HIF-1-regulated genes, the new chamber yielded reproducible and comparable results as the modular incubator chamber did. The new chamber did not create inner chamber pressure during its use. Other properties of the new chamber were low-cost, easy to use, and leakage-free. Moreover, the size of the new chamber was adjustable, and the smaller one could be placed onto an inverted microscope for real-time studies. The successful examples of real-time studies included the real-time recording of GFP-HIF-1α fusion nuclear translocation and endothelial cell tubular formation.

Prostate cancer in Asia: A collaborative report.

The incidence of prostate cancer (PCa) within Asian population used to be much lower than in the Western population; however, in recent years the incidence and mortality rate of PCa in some Asian countries have grown rapidly. This collaborative report summarized the latest epidemiology information, risk factors, and racial differences in PCa diagnosis, current status and new trends in surgery management and novel agents for castration-resistant prostate cancer. We believe such information would be helpful in clinical decision making for urologists and oncologists, health-care ministries and medical researchers.

Surgical management of intractable chyluria: a comparison of retroperitoneoscopy with open surgery.

BACKGROUND: Retroperitoneoscopic renal pedicle lymphatic disconnection has been described in the management of intractable chyluria. METHODS: We retrospectively reviewed the clinical outcomes of 76 patients with intractable chyluria undergoing renal pedicle lymphatic disconnection via a retroperitoneoscopic (n = 59) or conventional open approach (n = 17). Operative time, intraoperative blood loss, volume of postoperative drainage, postoperative draining time, postoperative intestinal recovery, intraoperative and postoperative complications, and postoperative hospital stay were evaluated. RESULTS: Compared with open surgery, retroperitoneoscopy was superior in terms of operative time, intraoperative blood loss, postoperative drainage, postoperative draining time, postoperative intestinal recovery time, and postoperative hospital stay. Recurrence developed in 2 patients due to the contralateral chylous efflux confirmed by cystoscopy during the period of 9-85 months of follow-up. CONCLUSIONS: With minimal invasion, sparing operative time, less blood loss, and rapid recovery, retroperitoneoscopic renal pedicle lymphatic disconnection can achieve at least the same clinical efficacy as open surgery.

Detection on dynamic changes of endothelial cell specific molecule-1 in acute rejection after renal transplantation.

OBJECTIVE: To investigate the value of dynamic monitoring of endothelial cell specific molecule-1 (ESM-1) in diagnosing acute rejection after renal transplantation. METHODS: ESM-1 expression was observed in peripheral blood circulating endothelial cells and renal allografts after renal transplantation, and was compared to the flow cytometry (FCM) results of urine HLA-DR(+) lymphocytes. RESULTS: In patients with acute rejection, ESM-1 mRNA and protein expression increased significantly (P < .01). Real-time polymerase chain reaction detection of ESM-1 mRNA in peripheral blood cells was more sensitive and specific than FCM detection of urine HLA-DR(+) lymphocytes. Moreover, real-time PCR detection is characterized by convenient sampling and good reproducibility. CONCLUSION: ESM-1 is a new marker for endothelial cell activation. However, its significance during acute rejection in renal transplantation is still unclear. Our study demonstrates that ESM-1 may reflect the degree of endothelial cell injury in renal allografts, and that it may serve as a highly sensitive and specific marker for acute rejection after renal transplantation.

Resveratrol induces apoptosis associated with mitochondrial dysfunction in bladder carcinoma cells.

OBJECTIVE: Resveratrol shows chemopreventive activity in a variety of human cancers by targeting mitochondria and triggering apoptosis. The purpose of this study was to investigate the antitumor action of resveratrol in bladder cancer and its underlying mechanism. METHODS: Using two different bladder cell lines, BTT739 and T24, the cytotoxicity of resveratrol were determined by MTT assay. The apoptosis induced by resveratrol was assayed by transferase dUTP nick end labeling staining. To show whether the mitochondrial dysfunction involved in the effects of resveratrol, mitochondrial function was detected by mitochondrial membrane potential, reactive oxygen species production and adenosine 5'-triphosphate content. In addition, the markers of apoptosis in the intrinsic mitochondrial-dependent pathway were analyzed by the release of cytochrome c and the activities of caspase-9 and caspase-3. RESULTS: Resveratrol effectively decreased cell viability and induced apoptosis in a concentration- and time-dependent manner. In addition, resveratrol significantly disrupted the mitochondrial membrane potential in both intact cells and isolated mitochondria. Resveratrol also increased reactive oxygen species production and reduced adenosine 5'-triphosphate concentrations. Western blot analysis showed that resveratrol provoked the release of cytochrome c from mitochondria to the cytosol. Furthermore, resveratrol significantly promoted the activation of caspase-9 and caspase-3. CONCLUSIONS: These findings suggest that resveratrol efficiently triggers apoptosis in bladder cancer cells through the intrinsic mitochondrial-dependent pathway, which is associated with mitochondrial dysfunction. Resveratrol might have great pharmacological promise in the treatment of bladder cancer.

A novel DNA/peptide combined vaccine induces PSCA-specific cytotoxic T-lymphocyte responses and suppresses tumor growth in experimental prostate cancer.

OBJECTIVE: To develop a completely novel DNA peptide-combined vaccine and determine whether it can efficiently improve tumor-specific cytotoxic T lymphocyte (CTL) responses and inhibit tumor progression in experimental prostate cancer models. METHODS: The DNA/peptide combined vaccine was prepared by the self-assembly of a cationic peptide ([K]18P9) containing 18 lysines and a CTL epitope peptide, prostate stem cell antigen (PSCA (14-22)) (HLA-A2 restricted) with a recombinant plasmid encoding human full-length PSCA gene (pcDNA3.1(+)-PSCA) through electrostatic interactions. The formation of a DNA/peptide complex was examined by DNA retardation assay, DNase I protection assay, and transmission electron microscopy. The efficacy of vaccination using this complex was demonstrated in terms of the PSCA-specific CTL activity and antitumor immunity to PSCA(+) tumors in a murine model. RESULTS: This form of DNA/peptide complex could efficiently transfer the plasmid encoding full-length PSCA gene into mammalian cells and induced potent CTLs cytotoxicity against a human prostate carcinoma cell line established from the left supraclavicular lymph node metastasis from a 50-year-old man with prostate carcinoma in 1977. Expressing PSCA compared with pcDNA3.1(+)-PSCA, [K]18P9 peptide, or pcDNA3.1(+). Moreover, the vaccination of mice with this complex induced a potent antitumor immunity to prostate carcinomas in a xenograft tumor model in nude mice. CONCLUSION: This study suggests that a specific antitumor immune response can be induced by this DNA/peptide combined vaccine, which represents a new strategy for use in the immunotherapy of prostate cancer.

Imaging diagnosis, transurethral endoscopic observation, and management of 43 cases of persistent and refractory hematospermia.

The goal of this study was to explore minimally invasive transurethral imaging and surgery for the treatment of severe, persistent hematospermia in cases that were refractory to conservative treatments. The study included 43 patients (aged 22-77 years; average, 44.6 years) with long-lasting, severe hematospermia, accompanied by discomfort or pain in the lumbosacral or perineal region, dysuria, frequent micturition, decreased semen volume, and/or azoospermia. Patient symptoms had persisted for 1 to 10 years (average, 5.3 years). Computed tomography or magnetic resonance imaging of each patient was evaluated, and transurethral surgery was performed. The causes of hematospermia were identified in all 43 patients, and their ejaculatory duct obstruction or seminal vesiculitis was successfully treated. No serious intraoperative or postoperative complications occurred. Pathologic analyses revealed that all of the resected or biopsied seminal vesicle tissues had chronic nonspecific inflammation in the seminal vesicle wall, and no tumors were identified. Preoperative symptomology of hematospermia disappeared in all patients followed up for 2 to 30 months (average, 16 months). A single patient experienced recurrence at 11 months and had a second minimally invasive surgery that was curative. A total of 95.3% (41 of 43) of the patients experienced normal orgasmic intensity after surgery. Magnetic resonance imaging is a valuable and accurate diagnostic method for the identification of causative factors underlying hematospermia. Transurethral dilation of ejaculatory ducts, incision of the verumontanum or the distal end of the ejaculatory ducts, and incision or resection of the relevant cysts represent simple, safe, and reliable approaches for the management of refractory cases of hematospermia that do not respond to conservative treatments.

Pedicled greater omentum graft: a new technique to repair recurrent urinary fistulae after kidney transplantation.

Urinary fistula is the most frequent urologic complication within the first month after kidney transplantation, which often leads to graft loss and mortality. Open surgery is the most popular approach for the treatment of these fistulae; however, it is associated with high failure rates. Here, we present a new technique of pedicled greater omentum graft to repair recurrent urinary fistulae after kidney transplantation. We used this technique in the repair of recurrent urinary fistulae in 13 post-kidney transplant patients. All operations were successful at the first attempt, and there was no fistula recurrence. Further, no complications associated with the technique have been observed during the follow-up (1-7 years). In conclusion, the use of pedicled greater omentum graft for the repair of recurrent urinary fistulae after kidney transplantation is both effective and safe.

Transumbilical laparoendoscopic single-site renal pedicle lymphatic disconnection for refractory chyluria.

PURPOSE: To report our preliminary techniques and experience with transumbilical laparoendoscopic single-site renal pedicle lymphatic disconnection (LESS-RPLD) in seven patients with refractory chyluria. PATIENTS AND METHODS: Between June 2009 and September 2010, seven patients with refractory chyluria underwent LESS-RPLD. In the patients, a 2- to 3-cm single inverted U-shaped supraumbilical incision was made, and a homemade single multichannel port using a surgical glove and three conventional trocars was placed into the abdominal cavity. Flexible electric coagulation hook and pliers were used for renal pedicle dissection. A straight ultrasound knife was used for lymphatic disconnection. RESULTS: All the operations were successfully completed without conversion to open surgery, although an additional 3-mm trocar was used to push the liver in one patient. The mean operative time was 125 (96-165) minutes. The mean blood loss was estimated to be 112 (50-250) mL. Chyluria disappeared in all patients after surgery and did not recur during the follow-up period (3-15, mean 8.3 mos). CONCLUSION: LESS-RPLD is safe and feasible, with favorable short-term outcomes and aesthetic effect.

FSCB phosphorylation in mouse spermatozoa capacitation.

It is generally accepted that spermatozoa capacitation is associated with protein kinase A-mediated tyrosine phosphorylation. In our previous study, we identified the fibrous sheath CABYR binding protein (FSCB), which was phosphorylated by PKA. However, the phosphorylation status of FSCB protein during spermatozoa capacitation should be further investigated. To this aim, in this study, we found that phosphorylation of this 270-kDa protein occurred as early as 1 min after mouse spermatozoa capacitation, which increased over time and remained stable after 60 min. Immunoprecipitation assays demonstrated that the tyrosine and Ser/Thr phosphorylation of FSCB occurred during spermatozoa capacitation. The extent of phosphorylation and was closely associated with the PKA activity and spermatozoa motility characteristics. FSCB phosphorylation could be induced by PKA agonist DB-cAMP, but was blocked by PKA antagonist H-89.Therefore, FSCB contributes to spermatozoa capacitation in a tyrosine-phosphorylated format, which may help in further elucidating the molecular mechanism of spermatozoa capacitation.

[One-hole high ligation of internal spermatic vein by embryonic natural orifice transumbilical laparoscopy: a recommendable treatment of varicocele].

OBJECTIVE: To evaluate the one-hole method for high ligation of the internal spermatic vein by embryonic natural orifice transumbilical laparoscopy. METHODS: We used the one-hole method for high ligation of the internal spermatic vein by embryonic natural orifice transumbilical laparoscopy in the treatment of 15 cases of varicocele, 13 in the left and 2 in the right side, and appraised the treatment results by follow-up 1 month after the surgery. RESULTS: All the operations succeeded and no complications developed. The average operation time was 28 minutes and the mean hospital stay was 4 days. Symptoms were significantly relieved in all the patients and the scars were inconspicuous at follow-up. CONCLUSION: The one-hole method is a novel option for high ligation of the internal spermatic vein by embryonic natural orifice transumbilical laparoscopy in the treatment of varicocele. It is recommendable for its advantages of simple procedure, less pain, few complications, quick recovery, mini-invasiveness and cosmetic acceptability.

Comparison of urological complications with primary ureteroureterostomy versus conventional ureteroneocystostomy.

Urological complications after kidney transplantation may be serious and carry a high risk of graft loss. The purpose of this study was to compare urological complications with primary ureteroureterostomy versus conventional ureteroneocystostomy retrospectively. Between December 1993 and April 2008, 1287 kidney transplants were performed at our institution. Urological complications such as urine leakage, ureteral obstruction and vesicoureteral reflux (VUR) were summarized according to the different ways of urinary tract reconstruction, ureteroureterostomy (U-U) and ureteroneocystostomy (U-C). Overall, urological complications were encountered in 94 (7.3%) cases, including urine leakage (n = 44, 3.4%), ureteral obstruction (n = 36, 2.8%), VUR (n = 14, 1.1%). Seventy-six cases (7.8%) were in the U-C group and 18 cases (5.8%) were in the U-U group. Ninety-three recipients were successfully treated, and one lost the graft because of pelvis and ureteral necrosis. There was no recipient loss secondary to these complications. In conclusion, U-U does not change the overall incidence of urological complications comparing to U-C, but it can decrease the incidence of urine leakage. It is a good first option with a greater possibility of resolving a ureteral stenosis with endourology and no risk of reflux.

Construction of a DNA vaccine encoding Flk-1 extracellular domain and C3d fusion gene and investigation of its suppressing effect on tumor growth.

Although the critical role of complement component C3d as a molecular adjuvant in preventing virus infection is well established, its role in cancer prophylaxis and treatment is unclear. In this study, we constructed a recombinant plasmid encoding Flk-1 and C3d3 fusion proteins and investigated its transient expression in vitro in transfected eukaryotic cells and its antibody response in immunized mice. Subsequently, we investigated the vaccine's ability to elicit an immune response leading to suppression of angiogenesis and tumor growth in mice bearing bladder transitional cell carcinoma. Using Western blotting, immunocytochemistry, and flow cytometry, we detected the expression of Flk-1 and C3d3 fusion proteins in COS-7 cells transfected with these recombinant plasmids. Further binding experiment using CR2 (C3d receptor) positive Raji cells that were incubated with transfected COS-7 supernatant indicated that C3d was successfully fused to Flk-1. Although both vaccines elicited peak antibody levels at 5 weeks, Flk-1-specific antibody titer in pSG.SS.Flk-1(ECD).C3d3.YL-immunized mice was significantly higher when compared to pSG.SS.Flk-1(ECD).YL-immunized mice. The results of experiments with bladder tumor-bearing mice showed that the vaccine inhibited tumor growth significantly. These results suggest that C3d plays a critical role in tumor immunotherapy by promoting antibody response in Flk-1-based DNA vaccines. This approach may provide a new strategy for the rational design of anti-angiogenic therapies for the treatment of solid tumors and provide a basis for the further exploitation and application of the anti-angiogenesis DNA vaccines.

Relationship between glucocorticoid receptor signal pathway and androgen-independent prostate cancer.

OBJECTIVE: To study the role of the glucocorticoid receptor (GR) signal pathway and downstream cytokine interleukin-6 (IL-6) in androgen-independent growth of prostate cancer (PC). METHODS: The human androgen-dependent PC (ADPC) cell line LNCaP and androgen-independent PC (AIPC) cell line DU145 were cultured in vitro. Immunocytochemistry was used to examine the expression of the androgen receptor (AR), GR, HSP90 and IL-6. The GR antagonist RU486 was used to treat cultured cells, and the effects of RU486 on the proliferation of both cell lines were analyzed by MTT assay. Expression of HSP90 and IL-6 mRNA and protein was assessed by RT-PCR and Western blots, respectively. RESULTS: LNCaP cells were AR-positive and GR-negative, whereas DU145 cells were GR-positive and AR-negative. The expression of HSP90 and IL-6 in DU145 cells were significantly stronger than that in LNCaP cells (p < 0.01). RU486 had no obvious effects on the growth of LNCaP cells, but exerted a significant time- and dose-dependent growth inhibition on DU145 cells at doses as low as 0.1 micromol/l. RU486 treatment of DU145 cells also resulted in a dose-dependent decrease in the expression of HSP90 and IL-6 mRNA and protein. CONCLUSIONS: The GR signal pathway may be the main survival pathway for DU145 cells. Abnormal hyperactivation of the GR signal pathway and its promoting the expression of HSP90 and IL-6 contribute to the progression of ADPC to AIPC after androgen ablation.