1.Salmonella-mediated blood‒brain barrier penetration, tumor homing and tumor microenvironment regulation for enhanced chemo/bacterial glioma therapy.
Ze MI ; Qing YAO ; Yan QI ; Jinhai ZHENG ; Jiahao LIU ; Zhenguo LIU ; Hongpei TAN ; Xiaoqian MA ; Wenhu ZHOU ; Pengfei RONG
Acta Pharmaceutica Sinica B 2023;13(2):819-833
Chemotherapy is an important adjuvant treatment of glioma, while the efficacy is far from satisfactory, due not only to the biological barriers of blood‒brain barrier (BBB) and blood‒tumor barrier (BTB) but also to the intrinsic resistance of glioma cells via multiple survival mechanisms such as up-regulation of P-glycoprotein (P-gp). To address these limitations, we report a bacteria-based drug delivery strategy for BBB/BTB transportation, glioma targeting, and chemo-sensitization. Bacteria selectively colonized into hypoxic tumor region and modulated tumor microenvironment, including macrophages repolarization and neutrophils infiltration. Specifically, tumor migration of neutrophils was employed as hitchhiking delivery of doxorubicin (DOX)-loaded bacterial outer membrane vesicles (OMVs/DOX). By virtue of the surface pathogen-associated molecular patterns derived from native bacteria, OMVs/DOX could be selectively recognized by neutrophils, thus facilitating glioma targeted delivery of drug with significantly enhanced tumor accumulation by 18-fold as compared to the classical passive targeting effect. Moreover, the P-gp expression on tumor cells was silenced by bacteria type III secretion effector to sensitize the efficacy of DOX, resulting in complete tumor eradication with 100% survival of all treated mice. In addition, the colonized bacteria were finally cleared by anti-bacterial activity of DOX to minimize the potential infection risk, and cardiotoxicity of DOX was also avoided, achieving excellent compatibility. This work provides an efficient trans-BBB/BTB drug delivery strategy via cell hitchhiking for enhanced glioma therapy.
2.Correlation of metallothionein-2A, E-cadherin and cyclin E with biochemical recurrence in prostate cancer
Wei CHENG ; Ding MA ; Bin YANG ; Jiwen SHANG ; Zhenguo MI ; Yangang ZHANG
Cancer Research and Clinic 2019;31(6):395-400
Objective To investigate the expressions of metallothionein-2A (MT-2A), E-cadherin, interleukin-6 (IL-6), cyclin E, proliferating cell nuclear antigen (PCNA) and bcl-2 in prostate cancer tissues and their correlation with biochemical recurrence of prostate cancer. Methods Tissue specimens from 128 cases of prostate cancer who underwent radical prostatectomy in Shanxi Dayi Hospital from October 2012 to October 2017 were processed and transferred into tissue microarrays, the clinicopathological parameters of patients were also recorded. The expression levels of MT-2A, E-cadherin, IL-6, cyclin E, PCNA and bcl-2 were detected by immunohistochemical avidin-biotin complex (ABC) staining. The correlation between different molecular markers and biochemical recurrence of prostate cancer was analyzed. Results The biochemical recurrence rate of 128 patients with prostate cancer was 30.5% (39/128). The biochemical recurrence rates of low-risk, intermediate-risk and high-risk prostate cancer patients were 14.8%(8/54), 38.7%(24/62) and 58.3% (7/12), respectively. The risk classification and pathological T stage of patients with prostate cancer were associated with the expressions of MT-2A, cyclin E, IL-6 and E-cadherin (all P< 0.05). Multivariate Cox risk model showed that the high risk classification (HR= 1.81, 95%CI 1.56-2.19, P=0.042), MT-2A positive expression (HR= 2.01, 95%CI 1.08-3.15, P= 0.005), cyclin E positive expression (HR= 1.79, 95%CI 1.08-2.21, P= 0.042) and E-cadherin negative expression (HR= 1.92, 95% CI 1.22-2.45, P= 0.020) were the independent risk factors for biochemical recurrence of prostate cancer. Conclusion The expression of MT-2A, cyclin E and E-cadherin may serve as independent predictors for biochemical recurrence of prostate cancer.
3.Efficacy of transurethral en bloc resection of bladder tumor with 2 micrometer laser in the treatment of the high-risk elderly patients with bladder cancer under local anesthesia
Bin YANG ; Yangang ZHANG ; Jingyu WANG ; Wenjin ZHANG ; Zhenguo MI ; Wei CHENG
Chinese Journal of Postgraduates of Medicine 2018;41(2):116-120
Objective To evaluated the clinical efficacy of transurethral en bloc resection of bladder tumor with 2 μm laser in the high-risk elderly patients with bladder cancer under local anesthesia. Methods All of 64 high-risk elderly patients having underwent surgical treatment from April 2015 to October 2016 were divided into 2 groups,2 μm laser group(30 patients)and transurethral resection of bladder tumor(TURBT)group(34 group)according to surgical methods.The area and degree of pain was observed and recorded using visual analogue scales(VAS)during the 2 μm laser operation. The operation time,bladder irrigation time,catheter indwelling time,hospital stay,complications and 1-year cumulative recurrence rate were compared between 2 groups. Results The ASA grade in 2 μm laser group was higher than that in TURBT group and there was significant difference(P<0.05).During the 2 μm laser operation,the urethra pain was 53.33%(16/30),bladder pain was 20.00%(6/30), both urethra and bladder pain was 26.67%(8/30).The VAS scores were(2.50 ± 1.38)points,all the patients tolerated the pain in the 2 μm laser group.There was no significant difference in operation time between 2 groups(P>0.05).The bladder irrigation time,catheter indwelling time and hospital stay were shorter in 2 μm laser group than those in TURBT group:(40.00 ± 19.06)h vs.(56.47 ± 14.55)h,(4.33 ± 1.40)d vs. (5.65 ± 0.93) d,(4.13 ± 1.51) d vs. (6.24 ± 0.75) d,P<0.05 or<0.01. The overall incidence of complications was lower in 2 μm laser group than that in TURBT group:13.33%(4/30) vs. 64.71% (22/34),χ2=8.719,P=0.003.Compared with that of pre-treatment,the quality of life was higher after treatment in two groups,but there were no significant differences between the two groups.There were no significant differences in 1-year cumulative recurrence rate between the two groups after treatment (χ2= 0.496,P = 0.481). Conclusions Transurethral 2 μm laser treatment in bladder cancer under urethral surface anesthesia is safe and reliable for the high-risk elderly patients and complications are fewer than TURBT.The recent curative effect is satisfied.
4.Clinical study of intravesical instillation with Sufuning lotion for prevention of postoperative recurrence of bladder cancer
Xuebing HAN ; Jianwu LIU ; Xihua YANG ; Dongzi PANG ; Zhibin LI ; Bin WANG ; Jiwen SONG ; Huiqing CHEN ; Liansheng REN ; Zhenguo MI
Cancer Research and Clinic 2018;30(2):116-119
Objective To investigate the efficacy and safety of intravesical instillation with Sufuning (SFN) lotion for prevention of postoperative recurrence of bladder cancer. Methods A total of 240 bladder cancer patients who were diagnosed as bladder cancer and accepted trans-urethral resection of bladder tumor from January 2010 to June 2016 in Shanxi Provincial Cancer Hospital were randomly divided into the experimental group (120 cases) and the control group (120 cases) according to the envelope method. The patients in the experimental group were treated with SFN lotion for immediate intravesical instillation(250 mg for once), and the patients in the control group were treated with pirarubicin (THP) for immediate intravesical instillation (30 mg for once). The patients of two groups were treated with intravesical chemotherapy once a week for 8 times, and the chemotherapy was performed once a month for 1 year. The recurrence rate, progression-free survival (PFS) rate, overall survival (OS) rate and recent side effects were compared between the two groups. Results The patients were followed up for 6 to 60 months. The median follow-up time was 36.5 months.In the experimental group,6 patients were lost and 8 patients were lost in the control group.The experimental group, the total recurrence rate was 26.3 % (30/114). The control group, the overall recurrence rate was 25.0 % (28/112) (χ2= 0.142, P = 0.781). Five years of PFS rate in the experimental group and the control group was 73.7 % (84/114) and 75.0 % (84/112) respectively, and there was no significant difference between the two groups (χ2= 2.011, P= 0.615). Five years of OS rate in the experimental group and the control group was 95.6 % and 92.9 % respectively, and there was no significant difference between the two groups (χ 2= 1.611, P= 0.425). The major side effects included chemical cystitis and hematuria. The incidence of chemical cystitis and hematuria in the experimental group was significantly lower than that in the control group(χ2=5.991,P=0.018;χ2=4.925,P=0.036).There was a statistically significant difference of the hematological side effects (blood routine changes) between the two groups (χ 2= 4.891, P= 0.032). Conclusion It is safe and effective for intravesical instillation of SFN lotion to prevent the recurrence of bladder cancer.
5.Efficacy of Emergency Endoscopic Hemostasis Combined with Somatostatin in Treatment of Upper Gastrointestinal Hemorrhage
Zhenguo WU ; Lei DONG ; Yongyong CHEN ; Youjun ZHANG ; Mi HUANG ; Gaodong ZHOU
Progress in Modern Biomedicine 2017;17(22):4289-4291,4238
Objective:To discuss the efficacy of emergency endoscopic hemostasis combined with somatostatin in treatment of upper gastrointestinal hemorrhage.Methods:100 patients with upper gastrointestinal hemorrhage were selected and divided into two groups randomly.The control group (48 cases) was given conventional hemostatic measures.The observation group (52 cases) was given emergency endoscopic hemostasis combined with somatostatin.The efficacy of emergency endoscopic hemostasis combined with somatostatin in treatment of upper gastrointestinal hemorrhage was evaluated by efficacy,the curative success rate and the improvement situation of clinical symptoms.Results:The effective rate was 88.5 % in the observation group,and the effective rate was 70.8 % in the control group,and the effective rate of observation group was higher than that of the control group (P<0.05).The success rate for different lesion size was higher in the observation group compared with control group (P<0.05).According to the success rate,with the increased size of lesion,the hemostasis rate was decreased.The hospitalization,negative fecal occult and haematemesis disappeared time of observation group was shorter than that of the control group (P<0.05).The postoperative bleeding rate of observation group was lower than that of the control group (P<0.05).Conclusions:The emergency endoscopic hemostasis combined with somatostatin has a good therapeutic effect on upper gastrointestinal hemorrhage.It can improve the clinical symptoms and shorten the hospitalization time,but its effect is limited on large lesion of upper gastrointestinal hemorrhage.
6.The efficacy of 125I radioactive particle implantation combined with surgery plus chemotherapy in the treatment of locally advanced upper tract urothelial carcinoma
Xuebing HAN ; Jianwu LIU ; Dongzi PANG ; Zhibin LI ; Bin WANG ; Jiwen SONG ; Huiqing CHEN ; Zhenguo MI
Chinese Journal of Urology 2017;38(12):905-909
Objective To investigate the efficacy of 125I radioactive particle implantation combined with surgery and chemotherapy in the treatment of locally advanced urinary tract urothelial carcinoma (UTUC).Methods The clinical data of 128 patients of locally advanced (T3,T4) UTUC treated with surgery with radioactive particle implantation plus postoperative GC chemotherapy (experimental group) and surgery plus postoperative GC chemotherapy (control group) were retrospectively analyzed.All the patients underwent complete resection of the tumor.The postoperative pathology was urinary tract epithelium cancer.In the experimental group,there were 45 (69.2%) males and 20 (30.8%) females,with median age 56.5 years.There were 39 (60.0%) patients diagnosed with renal pelvic cancer,including 13 (33.3 %) patients with local lymph node metastasis;26 patients (40.0%) with ureteral cancer,11 patients (42.3%) with local lymph node metastasis.In the control group,there were 46 males (73.0%) and 17 females (27.0%),with median age 57.1 years.There were 40 (63.5%) patients with renal pelvic cancer,including 12 (30%) cases of local lymph node metastasis;23 patients with ureteral carcinoma (36.5%),including 10 patients (43.4%) with local lymph node metastasis.There was no significant difference in basehne data between the two groups (P > 0.05).The recurrence and distant metastasis,recurrence-free survival,distant disease free survival(DDFS),disease-specific survival(DSS),overall survival (OS) and comphcations of two groups were compared.Results The follow-up time was 50.5 months (ranged 5 to 62 months).In experimental group,there were 2 cases,5 cases,11 cases,16 cases and 21 cases occurred recurrence and distant metastasis in 6 months,1 year,2 years,3 years and 5 years respectively,and the 5-year cumulative recurrence and distant rate was 32.3% (21/65).In control group,there were 3 cases,5 cases,17 cases,21 cases and 32 cases,occurred recurrence and distant metastasis in 6 months,1 year,2year,3 year,5 year respectively,and the 5-year cumulative recurrence and distant rate was 50.8%(32/63).There was significant difference between the two groups (P =0.034).In the experimental group and the control group,the 5-year non-metastatic survival rates were 61.5% (40/65)and 41.3% (26/63),respectively.There was significant difference in 5-year non-metastatic survival rate between the two groups (P =0.033).The 5-year DSS rates were 69.2% (45/65) and 50.8% (32/63),respectively.The 5-year DSS rate of the two groups was significantly different (P =0.033).The 5-year OS rates were 53.8% (35/65) and 36.5% (23/63) respectively.There was significant difference in the 5-year OS rate between the two groups (P =0.049).Condusions Compared with surgery and chemotherapy,the use of 125I radioactive particle implantation combined with surgery and chemotherapy in the treatment of locally advanced stage (T3-T4) UTUC could achieve the total survival benefit,and less adverse reactions.
7.Preoperative and postoperative intravesical instillation versus alone postoperative intravesical instillation of pirarubicin for the prevention of postoperative recurrence of non-muscle invasive bladder cancer: a prospective randomized controlled trial
Bin WANG ; Jiwen SONG ; Huiqing CHEN ; Jianwu LIU ; Zhenguo MI
Cancer Research and Clinic 2017;29(3):155-159
Objective To evaluate the efficacy of preoperative and postoperative intravesical instillation of pirarubicin for the prevention of postoperative recurrence of non-muscle invasive bladder cancer (NMIBC). Methods From September 2012 to March 2014, 120 patients who were diagnosed as NMIBC and accepted trans-urethral resection of bladder tumor (TUR-Bt) were collected and randomly divided into two groups, including treatment group (60 cases) and control group (60 cases). 30 minutes before the operation, instillation of pirarubicin (40 mg) was performed in the treatment group, then pirarubicin perfusion was given within 24 h after operation, once a week for 8 weeks, and once a month for 10 months after operation. In control group, instillation of pirarubicin (40 mg) was given within 24 h after operation, and other treatments were the same as the treatment group. The differences of lesion detection probability, the 2-year recurrent rate and the adverse reaction rate were compared between the two groups. Results The lesion detection rates were 42.70 % (38/89) and 1.85 % (2/108) in the treatment group and control group, respectively (χ2=50.303, P<0.05). 119 patients were follow-up for 24 months. The 2-year recurrence rates were 8.47%(5/59), 21.67% (13/60) in treatment group and control group respectively (χ2= 4.033, P< 0.05). The adverse reactions mainly included hematuria (3 cases in treatment group, 3 cases in control group), urinary tract irritation (3 cases in treatment group, 2 cases in control group) and urethral stricture (1 case in treatment group, 1 case in control group). The difference of the adverse reaction incidence between the two groups was not significant statistically [11.86 % (7/59) vs. 10.00 (6/60), χ 2 = 0.106, P > 0.05]. Conclusions The preoperational intravesical instillation of pirarubicin can fix and diagnose malignant lesions in the bladder without adverse reactions, which will improve the rate of tumor resection and prevent postoperative recurrence of tumors.
8.Clinical effects of Compound Biejia Ruangan Tablet combined with entecavir in patients with chronic hepatitis B with hepatic fibrosis
Zhenguo WU ; Gaodong ZHOU ; Yongyong CHEN ; Mi HUANG ; Youjun ZHANG
Drug Evaluation Research 2017;40(3):351-355
Objective To investigate the clinical effects of Compound Biejia Ruangan Tablet (CBRT) combined with entecavir in patients with chronic hepatitis B with hepatic fibrosis.Methods Totally 92 cases of patients with hepatic fibrosis of chronic hepatitis B in Ankang people's hospital from January 2013 to May 2016 were divided into observation group (n =45) and control group (n =47),patients in observation group were treated with CBRT combined with entecavir,and patients in the control group were treated with entecavir.Treatment was for 48 weeks.The liver function,liver fibrosis,serum inflammatory factors,and adverse reactions were compared between two groups.Results After treatment,the ALT,AST,TBIL,and ALB/GLB levels of two group were significantly lower than those before treatment (P < 0.05),but there was no significant difference between two groups after treatment.After treatment,the PCⅢ,IV-C,HA,LN,IL-6,IL-4,IL-10,and TNF-α levels of two group were significantly lower than those before treatment (P < 0.05),and the PCⅢ,IV-C,HA,LN,IL-6,IL-4,IL-10,and TNF-α levels of observation group were significantly lower than those of control group (P < 0.05);there was no statistically significant difference in the incidence of adverse reactions between two groups (P < 0.05).Conclusion CBRT combined with entecavir is safe and effective to treat liver fibrosis of chronic hepatitis b,and it could significantly improve liver function,improve the degree of liver fibrosis,and reduce the level of serum inflammatory factors.
9.Efficacy observation of 125I radioactive seed implantation for the local advanced urinary tract epithelial carcinoma without total surgical resection
Zhibin LI ; Huiqing CHEN ; Jiwen SONG ; Jianwu LIU ; Zhenguo MI
Cancer Research and Clinic 2016;28(3):187-191
Objective To evaluate the efficacy and feasibility of 125I radioactive seed interstitial implantation for the local advanced urinary tract epithelial carcinoma without total resection.Methods The clinical data of 21 patients with local advanced urothelial carcinoma without completely surgical resection who were treated by 125I radioactive particles implantation were retrospectively analyzed.The patients were divided into two groups and received preoperative plan.In group A, 14 patients received implants during operations, including 7 bladder transitional cell carcinoma patients who underwent a transurethral resection surgery or partial bladder resection and another 7 ureteral carcinoma cases who underwent semi urine road resection.After these operations, all of patients had tumor residues.After furthest resection of the tumor, the 125I seeds were implanted at the residual suspicious tumors and their surroundings.In group B, 7 patients were implanted under the guidance of color ultrasound or CT.According to the evaluation criteria of solid tumor in 2009, the tumor remission rate, survival rate, distribution and the mobile information of the particles were observed.Results The operations were successfully completed in all of 21 patients, and serious complications did not appear during the operation.Particle distribution and lesions were basic coincidence.A total of 2 particles displaced, but every patient had no adverse reactions.There were 2 patients with local fever after operation within 4 months, while the rest of patients had no adverse reactions.After median follow-up for 36 months (3-75 months) , the 1-year survival rate was 100.0 % (21/21), the 2-year survival rate was 90.5 % (19/21), and the 3-year survival rate was 61.9 % (13/21).The tumor remission rate of group A was 85.7 % (12/14) after 6-9 months, and was 42.9 % (6/14) after 12 months.The bladder was preserved in 7 cases with bladder tumors with the 2-year survival rate of 100.0 % (7/7) and the 5-year survival rate of 71.4 % (5/7).The tumor remission rate of group B after 6-9 months was 71.4 % (5/7), and was 42.9 % (3/7) after 12 months.Conclusion 125I seed implantation is a good choice for locally advanced urothelial carcinoma with high local tumor control rate, which is expected to be applied in the individual treatment of advanced urothelial cancer.
10.Application of barbed absorbable suture line in retroperitoneoscopic partial nephrectomy
Bin WANG ; Jiwen SONG ; Huiqing CHEN ; Jianwu LIU ; Zhenguo MI
Cancer Research and Clinic 2016;28(9):616-619
Objective To investigate the safety and feasibility of barbed absorbable suture line in retroperitoneoscopic partial nephrectomy. Methods 45 patients who were suitable for retroperitoneoscopic partial nephrectomy from February 2013 to February 2014 were collected and randomly divided into V-Loc group and the control group. 23 cases of V-Loc barbed absorbable suture line were chosen by suture kidney in V-Loc group.There were 22 cases of coated vicryl plus antibacterial suture and Hem-o-lok clip in the control group. The differences of operative time, blood loss, warm ischemia time, suture time, hospital stay and suture material costs were compared respectively between the two groups. Results All 45 cases of retroperitoneoscopic partial nephrectomy were successfully performed, without conversion to open surgery and important intraoperative complications. Postoperative pathology report showed that there were 37 cases with renal clear cell carcinoma, 3 cases with papillary renal cell carcinoma, 2 cases with chromophobe renal cell carcinoma with negative surgical margin, 3 cases with renal angiomyolipomas. In the V-Loc group and the control group, the average operative time were (90.8±9.6) and (96.9±9.1) min (P>0.05), the mean blood loss were (80.4±24.2) and (99.5±24.8) ml (P>0.05), the mean warm ischemia time were (21.5±3.4) and (25.3±1.9) min (P<0.05), suture time were (10.8±1.7) and (16.8±3.1) min (P<0.05), respectively, postoperative hospital stay were (5.7±1.7) and (7.1±1.9) d (P>0.05), the average cost of renal parenchymal suture material were (1 215.5±101.4) and (2 073.5±301.8) yuan (P<0.05). The warm ischemia time,suture time and suture material costs in the V-Loc group were significantly lower than those in the control group (all P<0.05). Conclusion The application of barbed absorbable suture line in retroperitoneoscopic partial nephrectomy can shorten warm ischemia time and suture time, and save hospitalization costs, with favorable safety and feasibility.

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