BCG与IL-2联合膀胱灌注预防膀胱癌术后复发的效果

丝裂霉素(ＭＭＣ)被认为是有效的预防膀胱癌复发的膀胱内灌注药物。但由于药物用量大,长时间治疗费用昂贵,使部分患者不能坚持治疗。近年来ＢＣＧ已被公认为预防膀胱癌手术复发的有效手段之一,但仍有30%病例对ＢＣＧ无反应,且多数有ＢＣＧ膀胱炎或其他全身反应。为此,近年来开始探索ＢＣＧ与其他免疫制剂,如干扰素、ＩＬ2等联合用药,以便减少ＢＣＧ并发症,提高预防效果。作者选膀胱癌术后患者65例,术后病理检查均为膀胱移行上皮细胞癌。随机分为两组,对照组33例,用丝裂霉素(ＭＭＣ)20ｍｇ加生理盐水60ｍｌ,每周灌注1次,共8次,以后每2周1次,4…     

透明质酸钠膀胱灌注治疗间质性膀胱炎的研究

目的探讨问质性膀胱炎(Interstitial cystitis,IC)新的治疗方法。方法29例IC患者随机分为A、B两组,A组(治疗组)15例,B组(对照组)14例。A组2％利多卡因20ml膀胱灌注10min后,0.2％透明质酸钠100 ml+地塞米松10 mg膀胱灌注,每周1次,共6周。B组用1:5000呋喃西林溶液替代0.2％透明质酸钠溶液,方法类同A组,观察两组用药后临床症状评分及治疗前后尿动力学指标。结果两组用药后临床症状评分比较差异具有显著性意义(P<0.01)。A组治疗前后尿动力学指标比较差异有显著意义(P<0.01),13例患者临床症状消失,10例患者膀胱容量明显增加。B组用药前后尿动力学指标比较差异无显著意义(P>0.05),4例患者临床症状消失,膀胱容量无明显改善。结论透明质酸钠膀胱灌注治疗间质性膀胱炎是一种有效、简便、易行的新治疗途径。     

卡介苗加α-干扰素膀胱灌注预防膀胱癌术后复发的疗效

目的　探讨卡介苗 (BCG)加α 干扰素 (α IFN)膀胱灌注预防膀胱癌术后复发的疗效。方法　对 66例经病理证实为膀胱癌的患者分为BCG组与BCG加α IFN组 ,分别进行疗效对比观察。结果　BCG组复发率为2 6.7% ,BCG加α IFN组复发率为 8.3 % ,两组比较差异有显著性意义 ,(χ2 =3 .96,P <0 .0 5 )。结论　BCG加α IFN联合用药能明显降低膀胱癌的复发率     

奥美拉唑对反流性食管炎的疗效观察

目的探讨奥美拉唑对治疗反流性食管炎的疗效分析及观察。方法将我院收治120例经胃镜证实RE患者随机分为2组,治疗组与对照组各60例。治疗组用奥美拉唑20mg,每天1次,口服;对照组用雷尼替丁150mg,每晚睡前1次口服。2个月后观察烧心、反酸、胸骨后疼痛等症状改善情况。结果治疗组明显优于对照组差异有显著性(P<0.01)。结论奥美拉唑是治疗反流性食管炎的理想药物用药简单方便。     

地卡因雾化吸入改善全麻术后咽喉部不良反应的疗效观察

目的观察地卡因雾化吸入改善气管插管全麻术后咽喉部不良反应的疗效。方法将120例气管插管全麻术后有咽喉部疼痛不适,上呼吸道分泌增多的患者随机分为2组:一组为观察组,一组为对照组,每组各60例。对照组用常规雾化吸入,观察组用地卡因雾化吸入,观察2组患者气管插管全麻术后咽喉部不良反应的改善情况。结果观察组的疼痛不适,上呼吸道分泌物增多的症状改善情况远远优于对照组,对统计学有意义(P<0.05)。结论地卡因雾化吸入能明显提高改善气管插管全麻术后引起的咽喉部不良反应的疗效,值得在临床推广应用。     

氟比洛芬酯超前镇痛对胃癌术后镇痛的疗效观察

目的观察氟比洛芬酯超前镇痛对胃癌术后镇痛的临床效果。方法选择56例行胃癌手术的患者,随机分为对照组和观察组。对照组术后泵内应用芬太尼1mg+生理盐水共100mL;观察组术前15min、关腹时分别静注氟比洛芬酯50mg,术后泵内应用芬太尼0.5mg+生理盐水共100mL;观察术后24h内(2、4、8、24h)的镇痛评分(VAS),PCA使用次数、不良反应及芬太尼的用量。结果术后2、4、8h观察组的VAS评分明显低于对照组组,差异有统计学意义(P<0.05)。术后24h内PCA按压次数2组相比,差异无统计学意义(P>0.05)。观察组的芬太尼用量明显少于对照组,差异有统计学意义(P<0.05)。2组不良反应发生率差异无统计学意义。结论氟比洛芬酯复合芬太尼对胃癌术后静脉镇痛效果良好,且有一定超前镇痛作用。可明显减少PCIA期间芬太尼的用量,不增加不良反应的发生率。     

依匹斯汀联合复方甘草酸苷治疗慢性荨麻疹疗效观察

目的探讨依匹斯汀联合复方甘草酸苷治疗慢性荨麻疹的疗效。方法72例慢性尊麻疹患者随机分为两组,试验组口服依匹斯汀10mg,复方甘草酸苷2片;对照组单用依匹斯汀10mg。两组用药4周,于治疗结束及治疗后4周观察疗效。结果治疗前两组的症状总积分比较,差异无统计学意义(t=0.19,P>0.05)。治疗4周时实验组有效率为90%,对照组为56.25%.两组有效率比较差异有统计学意义(x~2=10.80,P<0.01)。两组分别各有3例出现不适,停药后不良反应消失。结论依匹斯汀联合复方甘草酸苷治疗慢性荨麻疹可以提高慢性荨麻疹的治愈率,亦可提高其远期疗效,值得临床推广应用。     

手术联合米非司酮对子宫内膜异位症的疗效观察

目的探讨手术联合米非司酮对子宫内膜异位症的临床效果及安全性。方法将我院120例行保守性手术病理诊断为子宫内膜异位症患者,随机分为治疗组及对照组,对照组术后未继续药物巩固治疗,治疗组使用米非司酮,3个月后比较两组患者的卵泡刺激素(FSH)、黄体生成素(LH)、血清雌二醇(E2)水平改善和症状缓解情况。结果所有患者术前术后诊断相符合,术后症状均有不同程度的缓解,治疗组缓解率显著高于对照组,复发率显著低于对照组,治疗组用药前后除E2明显减少外,其余性激素水平无显著变化,对照组的血清性激素水平均低于治疗前,以上差异有统计学意义(P<0.05)。结论手术后应用米非司酮治疗内膜异位症是有效的,可缓解症状、免除多次开腹之苦,而且它没有其他治疗药物大多伴有的类绝经期症状、男性化表现、肝功能损     

碳酸利多卡因复合丁丙诺啡用于断指再植臂丛神经阻滞的临床观察

目的观察丁丙诺啡对碳酸利多卡因臂丛神经阻滞的断指再植患者麻醉效果的影响。方法利用便携式超声定位仪,进行臂丛神经阻滞麻醉的96例断指再植患者,随机分为观察组和对照组(n=58),观察组为碳酸利多卡因(6mg·kg-1)加丁丙诺啡0.15mg;对照组为碳酸利多卡因(6mg·kg-1)加同体积生理盐水。观察记录两组患者围术期生命体征变化和围术期各时间点的疼痛评分、麻醉起效和痛觉消失时间、维持时间,评价麻醉效果及并发症发生情况。结果两组患者的麻醉起效和痛觉消失时间无显著性差异(P>0.05);观察组的麻醉维持时间、麻醉效果和术后镇痛评分明显优于对照组(P<0.05);两组患者的生命体征变化和并发症相比,差异无统计学意义(P>0.05)。结论丁丙诺啡能够增强碳酸利多卡因臂丛神经阻滞效果,延长术后镇痛时间,不良反应发生率低,值得临床采用。     

曲美他嗪治疗慢性心力衰竭疗效观察

目的探讨曲美他嗪(万爽力)治疗心力衰竭(CHF)的疗效。方法CHF患者共125例,随机分为2组:曲美他嗪治疗组、常规治疗组,用药期间监测肝、肾功能及电解质等,观察左室射血分数(LVEF)、左室收缩末容积指数(LVESVI)和左室舒张末容积指数(LVEDVI)6min步行距离,临床症状及体征改变,对比改善情况。结果1年中再住院率,常规治疗组32.2%,曲美他嗪治疗组13.6%,两组差异有显著性(P<0.05);1年中死亡率,常规治疗组24.2%,曲美他嗪治疗组5.08%,两组差异有显著性(P<0.05);1年中治疗总有效率,常规组65.6%,曲美他嗪治疗组85.2%,两组有显著性差异(P<0.05)。结论曲美他嗪治疗慢性心力衰竭疗效显著,无明显不良反应。     

Establishment of Three-Dimensional Bioprinted Bladder Cancer-on-a-Chip with a Microfluidic System Using Bacillus Calmette–Guérin

Immunotherapy of bladder cancer is known to have favorable effects, although it is difficult to determine which patients will show a good response because of the different tumor microenvironments (TME). Here, we developed a bladder cancer-on-a-chip (BCOC) to mimic the TME using three-dimensional (3D) bioprinting and microfluidic technology. We fabricated a T24 and a 5637-cell line-based BCOC that also incorporated MRC-5, HUVEC, and THP-1 cells. We evaluated the effects of TME and assessed the immunologic reactions in response to different concentrations of Bacillus Calmette–Guérin (BCG) via live/dead assay and THP-1 monocytic migration, and concentrations of growth factors and cytokines. The results show that cell viability was maintained at 15% filling density in circle-shaped cell constructs at 20 μL/min microfluidic flow rate. A 3D co-culture increased the proliferation of BCOCs. We found that the appropriate time to evaluate the viability of BCOC, concentration of cytokines, and migration of monocytes was 6 h, 24 h, and three days after BGC treatment. Lastly, the immunotherapeutic effects of BCOC increased according to BCG dosage. To predict effects of immunotherapeutic agent in bladder cancer, we constructed a 3D bioprinted BCOC model. The BCOC was validated with BCG, which has been proven to be effective in the immunotherapy of bladder cancer.     

Artesunate Induces Apoptosis of Bladder Cancer Cells by miR-16 Regulation of COX-2 Expression

Bladder cancer is the most common malignant tumor of the urinary tract and remains one of the major causes of cancer death worldwide. In this study, we investigated the effect and mechanism of Artesunate (ART), a traditional Chinese medicine, on inducing apoptosis of human bladder cancer cells. In vivo antitumor activity was investigated in bladder cancer in rat by subcutaneous injection of different concentration of ART. The effect of ART on growth inhibition and apoptosis of bladder cancer cells was evaluated using dimethylthiazoly-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis, respectively. Cyclooxygenase-2 (COX-2) and miR-16 expression levels were determined with real-time PCR. The concentrations of prostaglandin E2 (PGE2) in the supernatants of bladder cancer cells were measured with an ELISA kit. The miR-16 inhibitor or mimic were transfected into cells to up- or down-regulate miR-16 expression. ART efficiently inhibited orthotopic tumor growth in the bladder cancer rat, which is accompanied with an increase of miR-16 expression and a decrease of COX-2 expression. In vitro, ART could induce cytotoxicity and apoptosis in bladder cancer cells, but presented a much lighter toxicity effect against normal human urothelial cells. ART significantly increased miR-16 expression and decreased the expression of COX-2 and the production of PGE2. More importantly, down-regulation of miR-16 expression could reverse the effect of ART on apoptosis and COX-2 expression in bladder cells. Moreover, exogenous PGE2 could inhibit apoptosis of bladder cancer cells treated with ART. In conclusion, ART can elicit an anti-tumor effect against bladder cancer by up-regulation of miR-16 expression, which resulted in the decrease of COX-2 expression and PGE2 production. Hence, ART might be an effective drug for the treatment of bladder cancer.     

Improving Anti-PD-1/PD-L1 Therapy for Localized Bladder Cancer

In high-risk non-muscle invasive bladder cancer (HR-NMIBC), patient outcome is negatively affected by lack of response to Bacillus-Calmette Guérin (BCG) treatment. Lack of response to cisplatin-based neoadjuvant chemotherapy and cisplatin ineligibility reduces successful treatment outcomes in muscle-invasive bladder cancer (MIBC) patients. The effectiveness of PD-1/PD-L1 immune checkpoint inhibitors (ICI) in metastatic disease has stimulated its evaluation as a treatment option in HR-NMIBC and MIBC patients. However, the observed responses, immune-related adverse events and high costs associated with ICI have provided impetus for the development of methods to improve patient stratification, enhance anti-tumorigenic effects and reduce toxicity. Here, we review the challenges and opportunities offered by PD-1/PD-L1 inhibition in HR-NMIBC and MIBC. We highlight the gaps in the field that need to be addressed to improve patient outcome including biomarkers for response stratification and potentially synergistic combination therapy regimens with PD-1/PD-L1 blockade.     

双歧杆菌介导HSV-tk/GCV系统治疗大鼠膀胱癌的疗效

目的观察双歧杆菌介导的单纯疱疹病毒胸苷激酶(Herpes simplex virus thymidine kinase,HSV-tk)/丙氧鸟苷(Gancyclovir,GCV)系统治疗大鼠膀胱癌的疗效,并初步探讨其可能的作用机制。方法采用N-甲基亚硝基脲(N-methyl-nitrosourea,MNU)膀胱灌注法建立大鼠膀胱癌模型,将模型大鼠随机分为3组,分别经尾静脉注射生理盐水、携带空载体pGEX-5X-1的双歧杆菌和携带重组质粒pGEX-tk的双歧杆菌(含婴儿双歧杆菌4.4×109个/ml),再联合腹腔灌注GCV(50 mg/kg)治疗,治疗结束后称量各组大鼠膀胱重量;TUNEL染色法检测各组大鼠膀胱组织细胞凋亡情况,RT-PCR和Western blot法检测各组大鼠膀胱肿瘤组织细胞色素C(Cyt-C)和半胱氨酸天冬氨酸蛋白酶-9(caspase-9)基因mRNA的转录水平和蛋白的表达水平。结果治疗后,双歧杆菌重组质粒组大鼠膀胱重量明显低于生理盐水对照组和双歧杆菌空载体组(P<0.001),膀胱组织细胞凋亡指数明显高于生理盐水对照组和双歧杆菌空载体组(P<0.001),膀胱肿瘤组织Cyt-C和caspase-9基因mRNA的转录水平和蛋白的表达水平均明显高于生理盐水对照组和双歧杆菌空载体组(P<0.001)。结论双歧杆菌介导的HSV-tk/GCV治疗系统治疗大鼠膀胱癌疗效显著;该治疗系统可能通过以Cyt-C为中心的内源性凋亡途径导致膀胱癌细胞凋亡。     

Biomarker-Oriented Therapy in Bladder and Renal Cancer

Treatment of patients with urothelial carcinoma (UC) of the bladder or renal cancer has changed significantly during recent years and efforts towards biomarker-directed therapy are being investigated. Immune checkpoint inhibition (ICI) or fibroblast growth factor receptor (FGFR) directed therapy are being evaluated for non-muscle invasive bladder cancer (NMIBC) patients, as well as muscle-invasive bladder cancer (MIBC) patients. Meanwhile, efforts to predict tumor response to neoadjuvant chemotherapy (NAC) are still ongoing, and genomic biomarkers are being evaluated in prospective clinical trials. Currently, patients with metastatic UC (mUC) are usually treated with second-line ICI, while cisplatin-ineligible patients with programmed death-ligand 1 (PD-L1) positive tumors can benefit from first-line ICI. Platinum-relapsed UC patients harboring FGFR2/3 mutations can be treated with erdafitinib, while enfortumab vedotin has emerged as a novel third-line treatment option for mUC. In metastatic (clear cell) renal cell carcinoma (RCC), ICI was first introduced as second-line treatment after vascular endothelial growth factor receptor—tyrosine kinase inhibition (VEGFR-TKI). Currently, ICIs have also been introduced as first-line treatment in metastatic RCC. Although there is no evidence up to now for beneficial adjuvant treatment after surgery with VEGFR-TKIs in high-risk non-metastatic RCC, several trials are underway investigating the potential beneficial effect of ICIs in this setting.     

Androgen Receptor Signaling Induces Cisplatin Resistance via Down-Regulating GULP1 Expression in Bladder Cancer

The underlying molecular mechanisms of resistance to cisplatin-based systemic chemotherapy in bladder cancer patients remain to be elucidated, while the link between androgen receptor (AR) activity and chemosensitivity in urothelial cancer has been implicated. Our DNA microarray analysis in control vs. AR knockdown bladder cancer lines identified GULP1 as a potential target of AR signaling. We herein determined the relationship between AR activity and GULP1 expression in bladder cancer cells and then assessed the functional role of GULP1 in cisplatin sensitivity. Androgen treatment in AR-positive cells or AR overexpression in AR-negative cells considerably reduced the levels of GULP1 expression. Chromatin immunoprecipitation further showed direct interaction of AR with the promoter region of GULP1. Meanwhile, GULP1 knockdown sublines were significantly more resistant to cisplatin treatment compared with respective controls. GULP1 knockdown also resulted in a significant decrease in apoptosis, as well as a significant increase in G2/M phases, when treated with cisplatin. In addition, GULP1 was immunoreactive in 74% of muscle-invasive bladder cancers from patients who had subsequently undergone neoadjuvant chemotherapy, including 53% of responders showing moderate (2+)/strong (3+) expression vs. 23% of non-responders showing 2+/3+ expression (P = 0.044). These findings indicate that GULP1 represents a key downstream effector of AR signaling in enhancing sensitivity to cisplatin treatment.     

治疗用卡介苗抗肿瘤动物实验方法的建立

目的 建立治疗用卡介苗在小鼠体内抗肿瘤的药效学实验方法。方法 观察治疗用卡介苗(BCG)对小鼠实体瘤S180和腹水瘤(EC)的抑瘤作用。结果BCG可明显减轻S180荷瘤鼠的瘤重,其瘤重抑制率>30％;可明显延长EC腹水瘤小鼠的生存时间,其生命延长率>75％。其中以12.5％和6.25mg/kg两剂量组的效果较佳。结论 该方法可用于卡介苗抗肿瘤动物药学实验。     

Using Copy Number Alterations to Identify New Therapeutic Targets for Bladder Carcinoma

Bladder cancer represents the ninth most widespread malignancy throughout the world. It is characterized by the presence of two different clinical and prognostic subtypes: non-muscle-invasive bladder cancers (NMIBCs) and muscle-invasive bladder cancers (MIBCs). MIBCs have a poor outcome with a common progression to metastasis. Despite improvements in knowledge, treatment has not advanced significantly in recent years, with the absence of new therapeutic targets. Because of the limitations of current therapeutic options, the greater challenge will be to identify biomarkers for clinical application. For this reason, we compared our array comparative genomic hybridization (array-CGH) results with those reported in literature for invasive bladder tumors and, in particular, we focused on the evaluation of copy number alterations (CNAs) present in biopsies and retained in the corresponding cancer stem cell (CSC) subpopulations that should be the main target of therapy. According to our data, CCNE1, MYC, MDM2 and PPARG genes could be interesting therapeutic targets for bladder CSC subpopulations. Surprisingly, HER2 copy number gains are not retained in bladder CSCs, making the gene-targeted therapy less interesting than the others. These results provide precious advice for further study on bladder therapy; however, the clinical importance of these results should be explored.