Prostate cancer is one of the most common tumors in Western countries, but its incidence in China is rising annually. Up to now, there is no effective therapy for those late stage, recurrent or hormone resistant patients. Gene therapy is the focus of study of prostate cancer in recent years both domestically and abroad. As a brand new therapeutic method,the pre clinical experimental researches have shown an encouraging future. This article reviews the major strategies and research progress in the field of gene therapy of prostate cancer.

Objective To study the inhibitory effect of CD/5 FC system on the prostate cancer cell DU145,RM 1 in vitro. Methods In vitro prostate cancer cells DU145 and RM 1 were infected by recombinant adenoviral vector and then the inhibitory effect and the bystander effect of CD/5 FC system were observed. Results CD/5 FC system had a remarkable inhibitory effect on prostate cancer cell DU145 and RM 1 in vitro, the inhibition rates being higher than 97% when infected by AdCMVCD after 4 days added with 15.5mmol/L 5 FC. A strong bystander effect could also be observed, more than 75% tumor cells being killed when only 10% were infected. Conclusions CD/5 FC system may serve as an effective gene therapeutic method.The existence of bystander effect makes itself available in the use of tumor treatment in vivo.

ObjectiveTo investigate the clinical efficacy and safety of solifenacin for female overactive bladder (OAB) who failed in toherodine treatment. MethodsFrom Jan 2010 to Oct 2010,48 cases of female OAB were treated with 5 mg/d solifenacin for 4 weeks after the failure of tolterodine treatment.The improvement of the perception of bladder condition as well as the mean numbers of day-time micturition,urgency episodes,urge incontinence episode per day,nocturia and pads usage were used as objective indexes for the evaluation of therapeutic effect. ResultsAfter 4-week solifenacin treatment,the mean numbers of day-time micturition,urgency episodes,urge incontinence episode per day,nocturia and pads usage were respectively decreased from the baselines ( 8.7 ± 1.5),(3.4 ± 2.1 ),( 2.4 ± 1.8 ),(2.1 ± 1.8 ) and (2.2 ±1.6) to be (7.2 ±2.5),(2.0 ±1.8),(1.5 ±1.2),(1.2 ±0.8) and (1.4 ±0.8).The perception of bladder condition was improved in 42 cases.The withdrawal from the treatment was seen in 3 cases due to headache and dry mouth.No severe adverse event was found in the rest 45 patients. Conclusion Solifenacin might be an effective and safe alternative agent in the treatment of female OAB who failed in tolterodine treatment.

Objective To evaluate the complications and long-term efficacy of inside-out transobturator transvaginal tape ( TVT-O) for the treatment of stress urinary incontinence ( SUI) .Methods From January 2008 to December 2013,236 consecutive female patients (mean age 56 ±9 years,range 44-88 years)with the symptom of incontinence when abdominal pressure increasing (such as walking), underwent TVT-O operation.All these patients needed pads and were diagnosed with SUI by cough test and Marshall -bonny test before surgery , with the mean international consultation committee on incontinence questionnaire short form ( ICI-Q-SF) score of 15.6 ±3.9.Two grouping methods were used:the mid-term group including patients whose follow-up time was between 6 months and 3 years, the long-term group including patients whose follow-up time >3 years,the group of patients who underwent TVT-O only and the group of patients who underwent TVT-O plus pelvic floor repair at the same time . Their clinical and follow-up data , intraoperative and postoperative complications , subjective and objective effects were recorded and analyzed.Results Of these 236 patients,there were 1 case of bladder perforation (0.4%) and 1 case of intraoperative sling exposure to vagina ( 0.4%) .Postoperative complications included 36 ( 19.1%) groin/puncture point pain ,18 (9.5%) de novo frequency of micturition ,8 (4.2%) urinary retention /difficulty of urination.All the complications were relieved after symptomatic treatment or surgery except 2 cases of urinary retention/difficulty of urination.Their symptom kept existing after urethral dilatation and sling dissection and long-term intermittent self-catheterization was needed .One hundred and eighty-nine patients completed more than six months of follow-up, with mean follow-up time of ( 35.0 ±12.5 ) months.One hundred and sixteen (61.4%) cases was arranged to mid-term group and 73(38.6%) was arranged to long-term group.88.9%patients ( 168/189 ) were cured objectively and 9.5% patients ( 18/189 ) improved. There was also a significant subjective improvement ( ICI-Q-SF scores:15.6 ±3.9 preoperative versus 6.7 ± 2.3 postoperative,P<0.01).There was no significant difference of both objective and subjective efficacy between mid-term group and long-term group ( cured +improved rate 97.4% versus 95.9%;ICI-Q-SF scores 14.3 ±2.8 versus 16.7 ±3.4 preoperative ,5.8 ±1.2 versus 7.9 ±2.0 postoperative , P>0.05 ) . Patients who underwent TVT-O and those who underwent TVT-O +pelvic floor repair had no significant difference in efficacy (cured +improved rate 97.8%versus 100.0%,P>0.05).Conclusion TVT-O is a safe,effective and durable treatment for SUI , whether or not with concomitant procedure of pelvic floor repairment.

OBJECTIVETo investigate the antitumor and anti-metastatic effect of in situ transduction of adenovirus encoding cytosine deaminase (AdCD) followed by the systemic use of 5-fluorocytosine (5-FC) in the orthotopic (o.t.) prostate cancer mouse model.

METHODSThe o.t. prostate cancer model of C57BL/6 mouse was developed by o.t. inoculation of RM-1 cells to the subcapsular area of the prostate gland. In situ transduction of the CD gene, followed by systemic use of 5-FC at a daily dosage of 300 mg/kg for 14 days, was performed two days later.

RESULTSCompared with mice treated with Adbeta-gal/5-FC, 5-FC and PBS, mice of the o.t. model receiving in situ treatment of AdCD/5-FC had significant prolongation of survival and suppression of local tumor growth. More importantly, pathological observations showed that metastatic activity occurred in all mice of the PBS, 5-FC and Adbeta-gal groups including metastasis to the iliac lymph node (10/10, 10/10, 10/10) and the lung (8/10, 7/10, 7/10). However, only two out of ten had iliac lymphatic metastasis in the AdCD/5-FC group with no systemic or preaotic lymphatic metastasis, suggesting a strong metastatic inhibitory effect.

CONCLUSIONSIn situ transduction of AdCD followed by systemic use of 5-FC leads to the inhibitory effect on tumor growth and metastatic activity in the o.t. mouse model of prostate cancer. Clinically, it may be possible to treat metastatic or recurrent prostate cancer with a novel gene therapy using in situ injection techniques in future.

Adenoviridae ; genetics ; Animals ; Cell Division ; drug effects ; genetics ; Cytosine Deaminase ; Disease Models, Animal ; Flucytosine ; pharmacology ; Lymphatic Metastasis ; genetics ; pathology ; prevention & control ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Nucleoside Deaminases ; genetics ; Prostatic Neoplasms ; genetics ; mortality ; prevention & control ; Survival Rate ; Transfection ; Tumor Cells, Cultured

ObjectiveTo investigate the expression and activity of histone deacetylase (HDAC) in prostate cancer.Methodshe pathological samples of 37 cases of PCa were collected. The mean age of the patients was 73 (53 - 88 ) years, the preoperative t-PSA was 81.69 ( 3.13 - 2000 ) ng/ml, Gleason score: 13 cases were ≤7, 24 cases were ＞7. Twenty-seven cases of BPH were set as controls. The mean age of the BPH patients was 69 (52 - 84) years, the preoperative t-PSA was 10.93 ( 1.11 - 55.07 ) ng/ml.Western blotting and colorimetric Assay kits were used to determine the HDAC expression and activity. The difference of HDAC activity in benign prostatic hyperplasia and prostate cancer was statistically analyzed.The correlation of the HDAC expression level and values of PSA and Gleason score was also assessed.ResultsHDACs were over-expressed in most cases of prostate cancer, the expression rates were HDAC1 :57％, HDAC2: 68％, HDAC3: 84％ and HDAC4: 73％, respectively. The HDAC activity (P ＜0.05)was significantly different between the prostate cancer and benign prostatic hyperplasia groups. The expression level of HDAC did not correlate with the values of PSA and Gleason score.ConclusionsHDAC was highly expressed and strongly active in prostate cancer. The results suggest that HDAC might be a potential target for the management of prostate cancer patients.

Objective: To explore the effects of fosinopril on oxidative stress and vascular function in experimental rats with spontaneous hypertension. Methods: The rats were divided into 3 groups: Control group, with normal healthy rats (n=15), Spontaneous hypertension (SH) group (n=15), SH rats received intragastric administration of normal saline and Treatment group (n=15), SH rats received intragastric administration of fosinopril 10mg/(kg?d). All animals were treated for 7 weeks. Caudal artery systolic blood pressure (SBP) was measured at each week. blood levels of superoxide dismutase (SOD), reactive oxygen species (ROS), malonaldehyde (MDA) and NO2-/NO3- were determined in different groups respectively after 7 weeks. Moreover, thoracic aorta was taken to examine its diastolic reactive rate by acetylcholine (Ach)/sodium nitroprusside (SNP) induction. Results: From the 1st week until the end of experiment, compared with SH group, Treatment group had decreased SBP,P<0.05. With 7 weeks treatment, compared with Control group, SH group had decreased SOD activity, while increased protein levels of MDA and ROS, allP<0.05; compared with SH group, Treatment group showed elevated SOD activity (P=0.010), while reduced protein levels of MDA (P=0.021) and ROS (P=0.009). Compared with Control group, SH group had the lower content of NO2-/NO3-(P<0.001); both SH group and Treatment group had decreased diastolic rates by Ach/SNP induction,P<0.05. Compared with SH group, Treatment group presented the higher content of NO2-/NO3- and higher diastolic rate by Ach induction, allP<0.001. Conclusion: Fosinopril could improve vascular diastolic function via anti-oxidative stress in experimental SH rats, which might be one of its anti-hypertensive mechanisms.

Objective To establish rat models of polycystic ovary syndrome(PCOS) induced by different methods,to assess the serum levels of several related hormones,to examine the morphological changes in the ovaries,and to discuss their significance.Methods Letrozol,sodium prasterone sulfate,or sodium prasterone sulfate combined with human chorionic gonadotropin were used to establish rat models of PCOS.Radioimmunoassay was used to measure the serum levels of hteinizing hormone(LH),follicle-stimulating hormone(FSH),estrogen(E_2),progesterone(P),testosterone(T),prolactin(PRL),and insulin(INS).HE staining was used to examine the morphological changes of the ovaries.Results Comparing with the normal group A,the serum FSH was increased and the serum progesterone was reduced in the group B,with a statistically significant difference(P<0.05).The serum testosterone was significantly higher in the group B than in the group A(P<0.01).The levels of serum sex hormones and insulin were not significantly different in the group D and C(P>0.05).In comparison with the group C,the levels of serum testosterone and LH/FSH ratio was significantly increased in the group E.(P<0.05).Comparing with the group D,the serum levels of progesterone and testosterone were significantly increased in the group E(P<0.05).The ovaries in the rats of groups A and C showed almost a normal histyology,with mature follicles and dominant follicles.Polycystic changes were observed only in the ovaries of groups B,D and E.Conclusion At the aspect of affecting the level of sex hormones in serum and changing the ovarian morphology.adopting letrozol tablets or sodium prasterone sulfate combined with HCG to induce rat PCO model is more close to clinic manifestations and meets the criteria of PCO animals.In the rat PCOS models induced with letrozol or with sodium prasterone sulfate combined with HCG,either the serum levels of sex hormones and ovarian histology are quite similar to those of human clinical appearance,and may well meet the modeling requirements for future experimental studies of polycystic ovary syndrome.

OBJECTIVE:To observe the clinical efficacy and safety of Buzhong yiqi wuling decoction combined with western medicine in the treatment of chronic congestive heart failure(CHF). METHODS:120 CHF patients were divided into observation group and control group by random number table method,with 60 cases in each group. Control group received conventional western medicine treatment as rest,low salt diet and diuretics. Observation group was additionally given Buzhong yiqi wuling decoction,one dose a day,at twice,on the basis of control group. Treatment course of 2 groups lasted for 2 weeks. Average TCM symptom score, level of plasma NT-proBNP,6 min walk test(6MWT)distance before and after treatment,clinical efficacy and the occurrence of ADR were compared between 2 groups. RESULTS:Before treatment,there was no statistical significance in average TCM symptom score,level of plasma NT-proBNP and 6MWT distance between 2 groups(P>0.05). After treatment,average TCM symptom score and level of plasma NT-proBNP of 2 groups were decreased significantly,and the observation group was more significant than the control group,with statistical significance(P<0.05);6MWT distance of 2 groups were improved significantly compared to before treatment,and the observation group was significantly longer than the control group,with statistical significance(P<0.05). After treatment,total effective rate of observation group(93.33%)was significantly higher than that of control group(83.33%),with sta-tistical significance(P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:Buzhong yiqi wuling decoction is an ef-fective prescription to treat CHF,and can relieve clinical symptoms,improve the cardiac function,decrease NT-proBNP level and en-hance the patient exercise tolerance with good safety.

Objective To explore the clinical significance of B7 family homology factor-3 (B7-H3),an expression membrane type of myeloid-derived suppressor cell (MDSC),in patients with acute pancreatitis (AP).Methods A total of 63 patients with AP initially treated in the Emergency Department at the First Affiliated Hospital of Soochow University from January,2014 to December,2015 were selected.Of them,25 suffered from mild AP (MAP),20 had moderate AP (MSAP) and 18 had severe AP (SAP).Another 20 healthy subjects with matching age and gender served as the control group.All patients with AP conformed to the diagnostic criteria of Guidelines or Diagnosis and Treatment of Acute Pancreatitis set in 2013 in China.Patients with other underlying diseases that might influence the clinical outcomes were excluded,including those with tumors,autoimmune diseases,viral infections,trauma and other disorders.A flowcytometer was used to detect the expression rate of MDSC in peripheral venous blood and the expression of B7-H3 on MDSC membrane.The continuous monitoring was carried out for 24 h,48 h and 72 h in patients with AP.Results Compared with healthy subjects,the MDSC cells in patient groups 24 hours after AP onset increased notably (P ＜0.01) especially the highest increase in the SAP group,followed by the MSAP group and the lowest in the MAP group.There were significant differences in pairwise comparisons (P ＜ 0.05).From successive observation of each group,there was no significant difference in MDSC between the MAP group and the MSAP group 24 hours,48 hours and 72 hours after AP onset.However,MDSC reached its peak 48 hours after AP onset,but it declined 72 hours after AP onset in the SAP group (P ＜ 0.05).B7-H3 expressed significantly 24 hours after AP onset,but there was no expression of B7-H3 in the healthy group.Meanwhile,B7-H3 was expressed most highly in the SAP group,followed by the MSAP group and lowest in the MAP group.There were significant differences in expression of B7-H3 found in pairwise comparisons (P ＜ 0.05).The successive observation showed that there was no significant difference in B7-H3 expression between the MAP group and the MSAP group 24 hours,48 hours and 72 hours after AP onset.However,there was a trend of increase in B7-H3 expression as time prolonged found among 24 hours,48 hours and 72 hours after AP onset in the SAP group (P ＜ 0.05).Conclusions The expressions of MDSC and B7-H3 were high in AP,and there were significant differences in both expressions among MAP,MSAP and SAP groups.These phenomena offer clues in further understanding about the immunological disorders during AP giving better guidelines for clinical practice.