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Multidrug resistance is a major cause of clinical failure of tumor chemotherapy, study on the mechanisms of tumor multidrug resistance has been becoming a fascinating area in the field of tumor chemotherapy. The tumor multidrug resistance is generally considered to be due to the gene mutation, amplification or epigenetic changes that affect the uptake , metabolism or excretion of tumor drugs . P-glycoprotein is a transmembrane glycoprotein encoded by multidrug resistance gene MDR1, which leads to the principal contributor to tumor multidrug resistance. Research suggests that P-glycoprotein can metastasize through the tumor cells, thereby affecting tumor resistance. This article reviews the role of intercellular transfer of P-glycoprotein in tumor drug resistance.
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BACKGROUND:At present, there are few reports about the non-human primate models of type 2 diabetes mel itus in domestic and abroad, so it lacks of standardized production methods and evaluation criteria. OBJECTIVE:To establish a safe and effective type 2 diabetes mel itus model of rhesus monkey and evaluation method. METHODS:Twelve rhesus monkeys were randomly assigned to experimental group (n=9) and control group (n=3). Rhesus monkeys in the experimental group were fed with high-glucose and high-fat diet for 4 weeks, and intraperitoneal y injected with 30 mg/kg streptozotocin to establish models of type 2 diabetes mel itus. Rhesus monkeys in the control group were fed with an equal volume of physiological saline. At 12 weeks after injection, peripheral blood serum was col ected to measure fasting blood glucose, lipids, insulin, and C-peptide levels. Intravenous glucose tolerance test and C-peptide release test were used to detect pancreatic gland and pancreatic islet function. Histopathological examination was performed in pancreas, kidney and liver. RESULTS AND CONCLUSION:(1) 12 weeks after injection, fasting blood glucose, triglycerides, and total cholesterol levels were significantly higher in the experimental group than in the control group (P<0.05). Insulin and C-peptide levels were significantly lower in the experimental group than in the control group (P<0.05). (2) The area under the curve for intravenous glucose tolerance test was increased in the experimental group than in the control group (P<0.05). The area under the curve for C-peptide response test was significantly reduced in the experimental group than in the control group (P<0.05). (3) The pathological sections of pancreas, kidney and liver showed typical pathological changes of diabetes in the experimental group. (4) It is confirmed that we got high achievement about rhesus monkey models of type 2 diabetes mel itus made by high-glucose and high-fat diet combined with low-dose streptozotocin. It is a feasible, safe and effective method.
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BACKGROUND:Traditional cel transplantation tracer methods require histological analysis and identification in vitro, which limits the clinical application of stem cel transplantation. So it is urgent to establish an in vivo noninvasive and repeatable tracer method. OBJECTIVE:To observe the effect of SPIO and DAPI double labeling on survival and proliferation of bone marrow mesenchymal stem cel s from macaques. METHODS:Bone marrow mesenchymal stem cel s were derived from bone marrow aspirates of healthy macaques using whole bone marrow adherence method. Then, the cel s were identified using flow cytometry detection. Bone marrow mesenchymal stem cel s were labeled using SPIO and DAPI. Fluorescent microscope was used to detect DAPI positive rate, and Prussian blue staining and transmission electron microscope were employed to measure SPIO positive rate. MTT assay was used to detect cel viability and proliferation. RESULTS AND CONCLUSION:Bone marrow mesenchymal stem cel s were successful y isolated from healthy macaques using the whole bone marrow adherence method, and the cel purity was up to 95.1%. SPIO and DAPI were both successful to label the bone marrow mesenchymal stem cel s with a positive rate of 95%-98%, but had no influence on cel viability and proliferation.
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BACKGROUND: It is easy and feasible to treat anterior urethral stricture using internal urethrotomy, however, its drawback is high recurrence in the long-term follow-up. OBJECTIVE: To evaluate the effect of submucosal injected verapamil on prevention of anterior urethral stricture recurrence after internal urethrotomy. METHODS: Totally 60 consecutive males with anterior urethral stricture underwent internal urethrotomy with or without urethral submucosal injection of verapamil, in the Department of Urology, First Affiliated Hospital of Fujian Medical University, from December 2006 to April 2008, were selected. All cases were followed up at least 24 months.RESULTS AND CONCLUSION: All cases were followed up for 24-39 months, with an average of 28.5 months. Urethral stricture recurred in two cases in the verapamil-treated group but 8 cases in the untreated group. This difference in stricture recurrence between the two groups was statistically significant (P < 0.05). The results demonstrated that submucosal injection of verapamil at the stricture site significantly reduces the stricture recurrence rate after internal urethrotomy. Further studies involving larger number of cases and longer follow-up are warranted to confirm the efficacy and safety of this therapy.
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Objective Detrusor overactivity (DO) is one known cause of overactive bladder (OAB) symptoms in benign prostatic hyperplasia (BPH).In this study,OAB symptoms suggestive of DO in BPH were treated with α1-blocker monotherapy or α1-blocker and antimuscarinics add-on therapy,and the efficacy and safety were assessed.Methods BPH patients who suffered from OAB symptoms for at least 3 month were enrolled in a prospective self-control study from August 2010 to April 2012.The inclusion criteria are total international prostate symptom score (IPSS) ≥8,OAB Symptom Score (OABSS) ≥3,OABSS urgency score ≥2,Postvoid residual volume (PVR) ＜ 100 ml,and maximum urinary flow rate (Qmax) ≥ 5 ml/s.All the patients who met the inclusion criteria were treated with α1-blocker ( tamsulosin 0.2 mg/day or doxazosin 4 mg/day) for 2 weeks.After 2 weeks,patients with no symptomatic improvement ( OABSS≥3) underwent pressure-flow test,and those whose Pdet≥ 40 cm H2O and DO presented more than one time were added antimuscarinics (solifenacin 5 mg/day or tolterodine 4 mg/day) for an additional 2 weeks.OABSS,IPSS,QOL,Qmax and PVR were re-evaluated every 2 weeks.Results Ninety-four cases of BPH/OAB patients met the inclusion criteria and completed 4 weeks treatment.The baseline of total OABSS was 7.0 ± 1.3,IPSS was 17.0 ± 1.7,QOL was 5.0 ±0.7,Qmax was (8.8 ±2.5) ml/s and PVR was (86.0 ± 16.5) ml.After 2 weeks treatment with α1-blocker alone,OABSS was 5.2 ± 0.8,IPSS was 14.2 ± 1.9,QOLwas4.O±0.8,Qmaxwas (11.4±2.4) ml/s and PVR was (67.9±12.9) ml.After another2 weeks treatment with α1-blocker plus antimuscarinics,OABSS was 3.1 ± 0.8,IPSS was 11.1 ± 1.9,QOL was 3.1 ± 0.7,Qmax was ( 10.8 ± 2.4) ml/s and PVR was (71.8 ± 11.9 ) ml.Compared with baseline values,OABSS,IPSS,QOL,Qmax and PVR significantly improved (P ＜ 0.01 ) in α1-blocker monotherapy group and α1-blocker plus antimuscarinic group.The improvement of OABSS,IPSS,QOL scores of α1-blocker plus antimuscarinic group were greater than α1-blocker monotherapy group (p ＜ 0.05 ),while Qmax and PVR showed no differences between the two groups.No acute urinary retention (AUR) was deteted.Conclusion Both of α1-blocker monotherapy and α1-blocker with antimuscarinics add-on therapy can improve OAB symptoms.
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Objective To analyse the operation technique and therapeutic effect of "inserting" uretero-intestinal anastomosis in orthotopic bladder substitution.Methods Thirty-eight patients undergoing orthotopic bladder substitution operations were followed up,and the way of uretero-intestinal anastomosis in all Datients was the "inserting"uretero-intestinal anastomosis.The therapeutic effect was observed by radiation,cystoscopy,pathologic biopsy and blood test.Results The average follow-up time was(3 1.65±14.14)montll8.and the stricture rate was 4%(3/75),but no vesicoureteric reflux was found.The rate of leakage was 0.Nipples were formed at the site of anastomosis under the view of cystoscope,and among the 7 patients whose nipples were taken to be examined by histology,2 cases were intestinal epithelium which were taken at the base of nipple8.while the others were transitional epithelium which were taken at the top of nipples.The renal function of all patients was normal (Cr 54-135 μmol/L,BUN 3.2-9.4 mmol/L).Conclusion "Inserting"uretem-intestinal anastomosis is an ideal antireflux uretero-intestinal anastomosis method.
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Objective To study the application of pediculated skin flaps in the treatment of com-plicated long urethratresia. Methods From March 1999 to May 2006, a total of 18 male patients with complicated long urethratresia were treated by using the pediculated skin flaps. The causes of urethratresia were 7 cases of postoperative pelvic fractures with posterior urethral stricture, 4 cases of transurethral intravesical chemotherapy, 3 cases of postoperative bulbar urethral stricture, 2 cases of gonorrhea, and 2 cases of long-time urethral catheter placement. Four cases were urethratresia nf cor-pus penis, 7 cases were anterior urethral obliteration, 7 cases were posterior urethral and anterior ure-thral obliteration. Urethro-perineal fistulas were found in 8 cases, posterior urethrorectal fistulas in 7 cases, false passage formations in 8 cases. The average length of urethratresia was 15.1 cm (range 8. 7 to 23. 0 cm). The urethral scar was rasected, the posterior urethrorectal fistula was repaired, and different kinds of pediculated skin flaps depending on the length of urethratreaia was used. Results All the patients were followed up for 12 to 18 months (mean 14 months). Fifteen patients voided well 3 months postoperatively, none of the urography showed stricture. The mean peak urinary flow rate was 16. 9 ml/s (range from 16. 5 to 21.7 ml/s). Of the other 3 cases, 1 case experienced difficult voi-ding due to the long and circuitous tabularized skin flap but recovered after proper shortening;1 case had restenosis for the infection of anastomosis but voided well after excision and reanastomnsis;1 casehad a urinary fistula resulting from hematoma and infection, but was successfully treated by the neo-plasty of the urinary fistula. The mean peak urinary flow rate was 17.0 ml/s (range 15.0 to 22.0 ml/s) for 17 patients 6 months postoperatively, except for one who experienced genuine urinary incon-tinence. At 9-18 months after operations, the mean peak urinary flow rate was 17.5 ml/s (range 15.8 to 22.5 ml/s) for 17 patients. Conclusion The single-stage urethroplasty based on pediculated skin flaps is a reliable and durable method for complicated long urethratresia.
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Objective To evaluate the efficacy of mitomycin (MMC) intravesical chemotherapy for superficial bladder carcinoma by in vitro chemosensitivity using histoculture drug response assay (HDRA).Methods Forty-one cases of superficial bladder transitional cell carcinoma(TCC) were obtained,including 30 males and 11 females with mean age of 55 years.Of them,10 cases were Ta and 31 were T1 according to TNM stage system (UICC 2002) while 9 cases were G1,22 were G2 and 10 were G3 (WHO1973).All cases had no chemotherapy history before operation and were operated to retain bladder.Tumor specimens were cultured by three-dimensional histoculture.HDRA with im-proved MTT assay was utilized for chemosenstivity test of MMC with 1 g/L concentration and 2 hours exposure.Growth inhibition rate (GI) exceeding 70% was defined as high-sensitive while less than 50% GI was defined as insensitive,others were moderate-sensitive.All cases were performed standard intravesical chemotherapy with MMC 40 mg plus 40 mt saline.Every case was followed up every 3 months.The patients were followed up for 5 years or untill recurrence.Results The MMC chem-osensitivity was different among 41 patients.Thirteen cases were insensitive including 1 of Ta,12 of T1 (P=0.009) and 1 of G1,7 of G2,5 of G3(P=0.101).Total recurrence rate was 39%(16/41) af-ter 3 to 5 years follow-up.There were 1 of Ta,15 of T1 (P=0.059) and 10 of G2 6 of G3 (P=0.016).Insensitive group recurrence rate was 77% (10/13) while sensitive group was 21% (6/28,P= 0.004).Patients in sensitive group showed a longer median time(49.2 months) than patients in insen-sitive group (16.5 months,P<0.001) according to Kaplan-Meier analysis with Log-rank test.The MMC chemosensitivity was independent prognostic factor examed by Cox regression analysis (P= 0.008).There was a 78% correlation rate of chemosensitivity by HDRA to clinical effect of MMC in-travesical chemotherapy.Conclusion HDRA could evaluate MMC intravesical chemotherapy for su-perficial bladder TCC,improve therapeutic effect and lower tumor recurrence rate.