OBJECTIVETo detect serum levels of MMP-9 and VEGF in patients with bladder cancer.

METHODSSerum levels of MMP-9 and VEGF in 58 patients with bladder cancer and 45 healthy controls were measured by sandwich-ELISA.

RESULTSSerum levels of MMP-9 and VEGF (737.12 micro g/L and 1148.88 ng/L) were significantly higher in the cancer patients than those of controls (423.51 micro g/L and 846.96 ng/L, P < 0.01). The serum levels were associated with tumor stage and grade. In patients with invasive cancer, the levels were significantly higher than those of superficial cancer (P < 0.01). Patients with distant metastasis had significantly higher levels of MMP-9 and VEGF than those with localized invasion (P < 0.01). But there was no significant difference between patients with superficial cancer and controls. Patients with G(3) tumors had significantly higher levels of MMP-9 and VEGF than those of patients with G(1) and G(2) tumors (P < 0.01).

CONCLUSIONSElevated MMP-9 and VEGF levels are associated with a high stage and grade of bladder cancer and they may serve as markers of tumor progression in the future.

Aged ; Humans ; Matrix Metalloproteinase 9 ; blood ; Middle Aged ; Neoplasm Staging ; Urinary Bladder Neoplasms ; blood ; pathology ; Vascular Endothelial Growth Factor A ; blood

OBJECTIVETo investigate the effect of phosphodiesterase type 5 (PDE5) small interfering RNA (siRNA) on the cGMP in the smooth muscle cells of human corpus cavernosum, and to provide an experimental groundwork for the gene therapy of erectile dysfunction (ED).

METHODSSmall interfering RNAs targeting PDE5 gene were synthesized by using web design software provided by Ambion, three siRNAs and a control siRNA were synthesized by Ambion. siRNAs were transfected into the smooth muscle cells of human corpus cavernosum by using siPORT Lipid reagent. cGMP was detected by ELISA at different times (24, 48, 72 and 96 h) after transfection.

RESULTSThe cGMP levels of the siRNA1, siRNA2 and siRNA3 groups were significantly higher than those of the siRNA control and blank control groups (P < 0.05), and so was it in the siRNA1 group than the siRNA2 and siRNA3 groups (P < 0.05), with significant difference between the siRNA control and the blank control group (P > 0.05).

CONCLUSIONThe synthesized siRNAs in vitro are capable of increasing the level of cGMP in the smooth muscle cells of human corpus cavernosum, different siRNAs with different capabilities. The siRNA technique could provide not only an extremely powerful tool for the functional analysis of genome but also a new approach to ED gene therapy.

3',5'-Cyclic-GMP Phosphodiesterases ; genetics ; Cells, Cultured ; Cyclic GMP ; metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Gene Silencing ; Humans ; Male ; Myocytes, Smooth Muscle ; drug effects ; metabolism ; Penis ; metabolism ; RNA, Small Interfering ; pharmacology ; Transfection

OBJECTIVEThe aim of the present study is to compare the effects of two alpha1-adrenoceptor antagonist terazosin and alfuzosin together with one alpha-adrenoceptor antagonist phenoxybenzamine on androgen-independent prostate cancer cell lines PC-3 and DU145.

METHODSTwo androgen- independent cell lines, PC-3 and DU145, were used to determine the cell viability, colony-forming ability as well as cell cycle characteristics after exposure to these three drugs.

RESULTSThis study showed that terazosin inhibited not only prostate cancer cell growth but also colony-forming ability, which is the main target of clinical treatment. On the other hand, alfuzosin and phenoxybenzamine have no effect on cell viability and colony forming ability of PC-3 and DU145. In addition, the terazosin inhibits cell growth through G(1) phase cell cycle arrest.

CONCLUSIONThis study provided the evidence that alpha1-adrenoceptor antagonist terazosin may have a therapeutic potential in the treatment of advanced androgen-independent prostate cancer.

Adrenergic alpha-Antagonists ; pharmacology ; Antineoplastic Agents ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Dose-Response Relationship, Drug ; Humans ; Male ; Phenoxybenzamine ; pharmacology ; Prazosin ; administration & dosage ; analogs & derivatives ; pharmacology ; Prostatic Neoplasms ; pathology ; Quinazolines ; pharmacology

OBJECTIVETo investigate whether the heat shock protein (HSP) 70 antisense oligomers can enhance the sensitivity of bladder cancer cell EJ to mitomycin C.

METHODSThe HSP70 mRNA of EJ cells was blocked by the 10 micromol/L HSP70 antisense oligomers, while its effect on cell growth was evaluated by methyl thiazolyl tetrazolium (MTT) and colony forming ability test.

RESULTSThe HSP70 expressions in HSP70 antisense treated group were lower than the corresponding sense and nonsense treated groups (P < 0.01). While, the increased sensitivity of EJ to mitomycin C was found in antisense treated group, compared with the corresponding sense and nonsense treated groups (P < 0.01).

CONCLUSIONThe sensitivity of bladder cancer cell EJ to mitomycin C was enhanced by the blockage of the HSP70 expression.

Cell Division ; drug effects ; Cell Line, Tumor ; HSP70 Heat-Shock Proteins ; antagonists & inhibitors ; biosynthesis ; genetics ; Humans ; Mitomycin ; pharmacology ; Oligonucleotides, Antisense ; pharmacology ; RNA, Messenger ; biosynthesis ; genetics ; Urinary Bladder Neoplasms ; genetics ; metabolism ; pathology

OBJECTIVETo investigate the expression of cyclooxygenase-2 (COX-2) in bladder transitional cell carcinoma tissues, and understand its clinical significance.

METHODSReversal transcription polymerase chain reaction (RT-PCR) was used to assess the expression of COX-2 mRNA in 52 cases of bladder transitional cell carcinoma tissues and 17 cases of normal bladder tissues far from neoplasm; Western blot was used to assess the expression of COX-2 protein in 49 cases of bladder cancerous tissues and 17 cases of normal tissues.

RESULTSPositive expression of COX-2 mRNA was detected in 83% (43/52) of bladder cancer tissues and in 29% (5/17) of normal tissues by RT-PCR and there was significant difference in expression of COX-2 mRNA between cancer tissues and normal tissues. Western blot analysis showed that expression of COX-2 protein was correlation with the stage and grade of cancer.

CONCLUSIONCOX-2 is overexpressed in bladder transitional cell carcinoma. COX-2 maybe play a certain role in carcinogenesis and progression of bladder cancer and turn into a useful target of chemoprevention of bladder cancer.

Adult ; Aged ; Aged, 80 and over ; Blotting, Western ; Carcinoma, Transitional Cell ; enzymology ; pathology ; Cyclooxygenase 2 ; biosynthesis ; genetics ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; RNA, Messenger ; biosynthesis ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Urinary Bladder ; enzymology ; Urinary Bladder Neoplasms ; enzymology ; pathology

OBJECTIVETo analyse retrospectively the diagnosis and treatment of severe pneumonia in kidney transplantation recipients.

METHODSBetween January 1999 and December 2003, 172 adult patients underwent kidney transplantation at our department. In all severe pneumonia cases, empirical therapy was initiated with aztreonam, erythromycin and ganciclovir. And the therapy was switched to proper antibiotics according to the results of sensitivity testing. Responsible pathogen was detected by study of BAL (bronco-alveolar-lavage), sputum and blood specimen. Analyses included cell differential count, cytopathologic examination and cultures for bacteria, fungi and viruses. The immunosuppressive therapy was drastically reduced. Hypoxia was relieved by BiPAP (Bi-level Positive Airway Pressure) or mechanical ventilation if necessary.

RESULTSSeventeen cases (9.9%) of pneumonia were observed in the 172 recipients, only 11 (65%) patients experienced severe pneumonia, 1 (9%) of them died. Fever was the most common symptom on presentation (82%). On presentation 46% of the patients presented with classical clinical syndrome of fever accompanied by cough and dyspnea. Positive rate of BAL and blood culture were 100% and 46% respectively. BiPAP and mechanical ventilation were required in 6 and 2 cases respectively.

CONCLUSIONBAL is preferred for early detection of responsible pathogen. A combination of drastic reduction of the immunosuppressive regimen, implementation of appropriate empirical antibiotics, proper BiPAP or mechanical ventilation are important.

Adult ; Combined Modality Therapy ; Female ; Humans ; Kidney Transplantation ; adverse effects ; Male ; Middle Aged ; Pneumonia ; diagnosis ; etiology ; therapy ; Respiration, Artificial ; Retrospective Studies ; Transplantation, Homologous ; adverse effects

OBJECTIVESTo investigate the effects of antisense oligodeoxynucleotide(ASON) on the cyclic nucleotide monophosphates (cNMP) in smooth muscle cells of human corpus cavernosum, and provide experimental groundwork for the gene therapy of erectile dysfunction.

METHODSPDE5 gene ASON(containing exon 1) was transfected into the corpus cavernosum smooth muscle cells with the presence of liposome DOTAP. Another sense oligodeoxynucleotide(SON) and 1% of bovine serum were also transducted into the cells as controls. Two of cNMP, cAMP and cGMP, were probed and measured by ELISA at 1, 2, 4, 6, 10, 24 and 48 h after transfection.

RESULTSAfter transfection, the level of cGMP(1-6 h) in human corpus cavernosum smooth muscle cells was significantly higher than that in controls(P < 0.01).

CONCLUSIONSThe PDE5 gene ASON had been showed to manifest stimulative effect on the cGMP in smooth muscle cells of human corpus cavernosum in vitro, and it provides experimental groundwork for the gene therapy of erectile dysfunction.

3',5'-Cyclic-GMP Phosphodiesterases ; antagonists & inhibitors ; genetics ; Cyclic AMP ; metabolism ; Cyclic GMP ; metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Humans ; Male ; Muscle, Smooth ; drug effects ; metabolism ; Oligodeoxyribonucleotides, Antisense ; pharmacology ; Penis ; cytology

BACKGROUNDBladder cancer is a relatively common tumor in the urinary system, in which mitomycin C (MMC)-based chemotherapy or combination chemotherapy has been mainly used to treat patients with advanced bladder cancer. The prognosis of patients with advanced bladder cancer is still extremely poor in spite of recent therapeutic advances. To improve the prognosis, the sensitivity of tumor cells to mitomycin C by the induction of apoptosis with the abating heat shock protein 70 (HSP70) expression in human bladder cancer cell lines of BIU-87 was investigated.

METHODSHSP70 expression was abated in BIU-87 cells by HSP mRNA antisense oligomers. MTT assay and the clone-forming test were used for evaluating the sensitivity of cells to MMC. Apoptosis was assessed using both fluorescent microscopy after staining the cells with Hoechst 33258 and DNA fragment ladder agarose electrophoresis. Thirty-two male six-week-old BALB/c nude mice, at the beginning of the experiment, were used to evaluate the effect of antisense oligomers (ASO) on the tumor formation in vivo.

RESULTSHSP70 expression in BIU-87 was effectively abated by HSP70 mRNA antisense oligomers. The percentage of apoptotic cells in ASO group was greater than in sense oligomers (SO) [P < 0.05, (18.31 +/- 2.89)% vs (1.89 +/- 0.74)%], nonsense oligomers (NO) [P < 0.05, (18.31 +/- 2.89)% vs (1.78 +/- 0.92)%] and blank groups [P < 0.05, (18.31 +/- 2.89)% vs (1.87 +/- 0.84)%], while the sensitivity of tumor cells to mitomycin C was enhanced. The in vivo tumor inhibition rate of ASO plus MMC (> 50%) was more than that of ASO or MMC group alone (all P < 0.05).

CONCLUSIONSThe abating level of HSP70 expression can strengthen the sensitivity of BIU-87 to MMC. One of this effect might be related to the induction of apoptosis by abating HSP70 expression.

Apoptosis ; drug effects ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; drug effects ; HSP70 Heat-Shock Proteins ; antagonists & inhibitors ; genetics ; physiology ; Humans ; Mitomycin ; pharmacology ; Oligodeoxyribonucleotides, Antisense ; pharmacology ; RNA, Messenger ; analysis ; Urinary Bladder Neoplasms ; drug therapy ; metabolism ; pathology

OBJECTIVETo evaluate the efficacy and safety of neoadjuvant chemotherapy in patients with locally advanced gastric cancer, and to analyze the relevant factors of recurrent death of gastric cancer after adjuvant chemotherapy.

METHODSClinical data of 49 patients who underwent neoadjuvant chemotherapy for locally advanced gastric cancer between July 2007 and June 2011 were reviewed. Preoperative staging was determined by endoscopic ultrasonography and abdominal computer tomography (CT) or magnetic resonance imaging (MRI). Chemotherapy was administered for regimen of two or three drugs. Prognostic factors were analyzed by univariate and multivariate analysis with Cox proportional hazard model.

RESULTSThe response rate was 33.3% (16/48) and disease control rate was 93.8% (45/48). Forty-four (89.8%, 44/49) patients received curative resection after neoadjuvant chemotherapy, among whom 90.9% (40/44) underwent D2 lymphadenctomy. Thirty-two cases had pathological response and 2 patients had pathological complete response. The average hospital stay was 11.6 days and 2 patients had longer hospitalization because of postoperative pancreatic complications. The toxicities were most in grade 1-2. All the patients were followed up postoperatively and the median follow-up was 21.6 months. Median progression-free survival was 29.6 (95%CI:24.0-35.2) months and median overall survival was 34.6 months (95%CI:29.8-39.4). Imaging response (P=0.038, RR=0.168, 95%CI:0.031-0.904) and pathological response (P=0.007, RR=0.203, 95%CI:0.064-0.642) were identified as independent prognostic factors with COX multivariate analysis.

CONCLUSIONSNeoadjuvant chemotherapy has quite high disease control rate and R0 resecting rate for patients with locally advanced gastric cancer. Imaging response and pathological response are most important prognostic factors in those patients.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Chemotherapy, Adjuvant ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; methods ; Preoperative Care ; Proportional Hazards Models ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; surgery ; Treatment Outcome

OBJECTIVETo study the effect of vitamin B on treatment of hyperhomocysteinemia and endothelial dysfunction in renal-transplant recipients.

METHODSThirty-six stable hyperhomocysteinemic renal-transplant recipients were randomly assigned to vitamin treatment (group A, n = 18, folic acid 5 mg/d, vitamin B(6) 50 mg/d, B(12) 1000 microg/d) or controlled group (group B, n = 18) for 6 months. All subjects underwent assessment of levels for creatinine, creatinine clearance, average pressure, total cholesterol, triglyceride and fasting homocysteine. Endothelial function was evaluated using high-resolution vascular ultrasound.

RESULTSThe levels of homocysteine markedly decreased in group A [(13 +/- 4) micromol/L vs (20 +/- 5) micromol/L, t = 5.3, P < 0.01] after treatment, whereas no significant changes were observed in group B. In group A, endothelium dependent [(12 +/- 5)% vs (9 +/- 5)%, t = 2.9, P < 0.01] and independent [(18 +/- 4)% vs (12 +/- 5)%, t = 3.4, P < 0.01] vasodilatation responses significantly increased after treatment, no significant changes were observed in group B. Endothelium dependent [(9 +/- 6)%, t = 2.8, P < 0.01] and independent [(12 +/- 5)%, t = 3.5, P < 0.01] vasodilatation responses of group A were significantly lower than that of group B after treatment.

CONCLUSIONSVitamin B supplementation can reduce the levels of homocysteine and improve the endothelial function in hyperhomocysteinemic renal-transplant recipients.

Adult ; Drug Therapy, Combination ; Endothelium, Vascular ; drug effects ; physiopathology ; Female ; Folic Acid ; administration & dosage ; Humans ; Hyperhomocysteinemia ; drug therapy ; physiopathology ; Kidney Transplantation ; Male ; Middle Aged ; Treatment Outcome ; Vitamin B 12 ; administration & dosage ; Vitamin B 6 ; administration & dosage