非肌层浸润性膀胱癌膀胱灌注治疗策略

经尿道膀胱肿瘤电切术（TURBT）后行膀胱灌注已经成为目前公认的预防和治疗非肌层浸润性膀胱肿瘤（NMIBC）最重要、最有效的手段。现阶段TURBT术后灌注治疗主要选择化疗药物和卡介苗（BCG ）。 对于所有非肌层浸润型的患者,术后及早期都应给予膀胱灌注治疗;对于G1-2Ta期患者使用术后单次的化学药物灌注治疗即可;对于中危患者,推荐使用单次药物灌注+诱导灌注或持续灌注的治疗模式,但灌注药物使用的具体方案应根据患者具体情况制定相应的治疗计划;对于高危患者,术后应首选BCG 的灌注治疗;化疗药物和BCG 联合的序灌疗法对于治疗膀胱肿瘤有无优势,其疗效还需进一步验证。虽然膀胱药物灌注治疗的研究已经有很长的历史,但在药物的使用方面,如药物的选择,使用时间,及剂量方面仍没有统一的观点。本文对非肌层浸润型膀胱肿瘤TURBT术后膀胱灌注治疗的策略进行综述。     

Radiotherapy Management of Muscle Invasive Bladder Cancer: Evaluation of a National Cohort

AimsWith the failure to improve outcomes of patients with bladder cancer over the last 30 years, this study was developed to benchmark contemporary UK radiotherapy practice for the management of muscle invasive bladder cancer (MIBC) against published national guidance.Materials and methodsAll UK radiotherapy centres were invited to complete a questionnaire for each patient with MIBC starting bladder radiotherapy over a 16-week period from December 2016.ResultsSixty-nine per cent (41/59) of UK radiotherapy centres completed a detailed questionnaire for 508 patients. The median age was 78 years and 64% (n = 323 patients) had stage II or III disease. Treatment intent was radical in 54% (n = 275). From transurethral resection of the bladder tumour, patients waited 57 days before starting neoadjuvant chemotherapy (NAC) (interquartile range 46–72 days). Patients who had radical radiotherapy as their first definitive treatment waited a median of 82 days (interquartile range 62–105 days). NAC was considered in 66% (n = 182) of all radical cases and given in 43% (n = 119). Concurrent radiosensitisation (CRT) was considered for 53% (n = 146) and delivered in 40% (n = 109) of patients. The most common fractionation was 55 Gy/20 fractions/4 weeks in 49% (n = 134) for radical patients and 36 Gy/6 fractions/6 weeks in 25% (n = 57) for palliative patients.ConclusionThis is the largest multicentre prospective study to define contemporary management of MIBC in patients receiving radiotherapy within the UK. The population studied is the oldest described to date. Timelines to starting definitive treatment confirm an urgent need to streamline the pathway. An increasing use of NAC is described, although the penetrance of CRT is disappointingly low. Areas for improvement with regards to the delivery and quality of radiotherapy have been identified. The detail within this study can be used to inform practice and future trial design, ultimately with the aim of improving outcomes for patients with MIBC.     

Efficacy of Postoperative Bladder Irrigation with Water for Injection in Reducing Recurrence Rates of Non Muscle Invasive Bladder Cancer

The aim of the study was to investigate the results of bladder irrigation with Water for Injection (WFI)after transurethral resection of bladder tumours for comparison with those for adjuvant use of BCG. A total of239 patients (158 with single tumours, group A, and 81 with multiple tumours, group B) received continuousintravesical postoperative irrigation with WFI. Some 128 patients received intravesical irrigation with WFI,followed by weekly instillations of BCG (group C). Recurrence-free rate (RFR) and recurrence-free intervals(RFI) were recorded. RFR for those patients who received only intravesical irrigation with WFI (groups A andB) was 75.8%, 66.2% and 63.2% at the 1st, 2nd and 3rd year of follow up, respectively. Corresponding ratesfor group C were 61.7%, 55.4% and 49%. Median RFI in group B were 18, 11, 15, 15 and 12 months for Ta, T1,grade 1, grade 2 and grade 3 tumours, respectively. In group C corresponding intervals were 20, 33, 8, 20 and 42months. BCG improved RFR only in T1 (p=0.014) and grade 3 tumours (p=0.007). In conclusion, postoperativebladder irrigation with WFI could increase RFR during the first and second year of follow up.     

Background Variables for the Patients with Invasive Bladder Cancer Suitable for Bladder-preserving Therapy

OBJECTIVE: The present study was undertaken to identify the patients suitable for bladder preservation by analysis of our data. METHODS: The subjects of this study were all 72 patients with T2-3N0M0 bladder cancer who underwent bladder-preserving therapy in our institute. The therapy involved intra-arterial chemotherapy with MTX and CDDP and concomitant radiotherapy. RESULTS: Of the evaluable 70 cases, complete response (CR) was confirmed in 57 cases (81.4%). Among 56 bladder preserved cases, 47 (83.9%) preserved their functioning bladder, and 9 underwent salvage radical cystectomy at the following period. The median follow-up was 45.3 months. The 5-year cause-specific survival rate was 81% and the 5-year overall survival rate was 66%. On the basis of the results of univariate analysis, variables contributing to CR were selected. In T2, tumor size of 3 cm was scored 1, whereas single tumor was scored 0 and multiple were scored 1. In T3, tumor size of 3 cm was scored 1, whereas G2 was scored 0 and G3 scored 1. The CR rates were 93.8, 92.6, and 62.9% for total scores of 0, 1, and 2, respectively (P = 0.003; score 0 or 1 versus 2). The overall survival rate was significantly higher in the former group (P = 0.003). CONCLUSION: Bladder-preserving therapy can be acceptable for cases of single T2N0M0 tumor with a size of 相似文献   

非肌层浸润性膀胱癌患者经尿道膀胱肿瘤电切术后复发的影响因素

目的 分析非肌层浸润性膀胱癌(NMIBC)患者经尿道膀胱肿瘤电切术(TURBT)后复发的影响因素.方法 回顾性分析168例NMIBC患者临床资料,患者均进行TURBT治疗.术后随访2年,统计患者复发情况,根据结果分为复发组与未复发组,分析NMIBC患者术后复发的影响因素.结果 随访2年,168例NMIBC患者有34例出...     

吉西他滨联合羟喜树碱术后膀胱灌注防治初发非肌层浸润性膀胱癌术后复发的效果观察

目的 探讨吉西他滨联合羟喜树碱术后膀胱灌注防治初发非肌层浸润性膀胱癌术后复发的效果.方法将80例初发非肌层浸润性膀胱癌患者分为试验组(40例)和对照组(40例).2组患者均行经尿道膀胱肿瘤切除手术(TURBT).对照组于术后行羟喜树碱膀胱灌注,试验组采用吉西他滨联合羟喜树碱膀胱灌注.定期对患者进行随访,时间为5年,观察对比2组患者术后6个月、术后1年、术后2年、术后3年和术后5年的复发率和进展率,以及不良反应发生情况.结果治疗后,试验组和对照组在术后6个月、术后1年和术后2年的复发率方面不具有统计学差异(P均>0.05),但是在术后3年和术后5年的复发率方面差异具有统计学意义(P<0.05);术后5年2组的进展率具有统计学意义(P<0.05).试验组不良反应发生率与对照组相比,差异具有统计学意义(P<0.05).结论采用吉西他滨联合羟喜树碱术后膀胱灌注防治初发非肌层浸润性膀胱癌术后复发和单纯采用羟喜树碱防治的近期效果相近,但是远期效果显著,值得推广.     

非肌层浸润性膀胱癌行二次电切术的临床疗效分析

目的：观察二次电切治疗非肌层浸润性膀胱癌的疗效,并进一步探讨二次电切的意义及指征。方法28例初次电切诊断为非肌层浸润性膀胱癌（Ta、T1）患者于4~6周后行二次电切,进一步明确肿瘤的临床分期。结果二次电切中发现3例（10.7％）存在肿瘤残留情况。9例初次电切分期为Ta 的肿瘤中,二次电切后2例（22.2％）的病理结果为T1期,1例（3.6％）病理为T2期;而19例初次电切分期为T1的肿瘤中,二次电切结果有5例（26.3％）的病理为T2期。根据二次电切结果及镜检情况,4例行膀胱部分切除,2例行全膀胱切除＋回肠代膀胱术,均得到治愈。结论二次电切可进一步明确非肌层浸润性膀胱癌的临床分期,并指导进一步治疗。     

Integrative Multi-Omics Analysis for the Determination of Non-Muscle Invasive vs. Muscle Invasive Bladder Cancer: A Pilot Study

Objectives: The molecular landscape of non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) bladder cancer based on molecular characteristics is essential but poorly understood. In this pilot study we aimed to identify a multi-omics signature that can distinguish MIBC from NMIBC. Such a signature can assist in finding potential mechanistic biomarkers and druggable targets. Methods: Patients diagnosed with NMIBC (n = 15) and MIBC (n = 11) were recruited at a tertiary-care hospital in Nanjing from 1 April 2021, and 31 July 2021. Blood, urine and stool samples per participant were collected, in which the serum metabolome, urine metabolome, gut microbiome, and serum extracellular vesicles (EV) proteome were quantified. The differences of the global profiles and individual omics measure between NMIBC vs. MIBC were assessed by permutational multivariate analysis and the Mann–Whitney test, respectively. Logistic regression analysis was used to assess the association of each identified analyte with NMIBC vs. MIBC, and the Spearman correlation was used to investigate the correlations between identified analytes, where both were adjusted for age, sex and smoking status. Results: Among 3168 multi-omics measures that passed the quality control, 159 were identified to be differentiated in NMIBC vs. MIBC. Of these, 46 analytes were associated with bladder cancer progression. In addition, the global profiles showed significantly different urine metabolome (p = 0.029), gut microbiome (p = 0.036), and serum EV (extracellular vesicles) proteome (p = 0.039) but not serum metabolome (p = 0.059). We also observed 17 (35%) analytes that had been developed as drug targets. Multiple interactions were obtained between the identified analytes, whereas for the majority (61%), the number of interactions was at 11–20. Moreover, unconjugated bilirubin (p = 0.009) and white blood cell count (p = 0.006) were also shown to be different in NMIBC and MIBC, and associated with 11 identified omics analytes. Conclusions: The pilot study has shown promising to monitor the progression of bladder cancer by integrating multi-omics data and deserves further investigations.     

Optimisation of Radiation Therapy in Bladder Preservation Therapy for Patients With Clinical Stage T2N0M0 Bladder Cancer

AimsA novel bladder preservation therapy, the OMC (Osaka Medical College) regimen, which combines radiation therapy with balloon-occluded arterial infusion of anticancer agents, is a treatment option for patients with muscle-invasive bladder cancer (MIBC). We retrospectively analysed the effects of changes in radiation dose and irradiation field on treatment efficacy and adverse events.The purpose of this study is to use the results of this study to help determine a course of radiation therapy for bladder preservation therapy of cT2N0M0 MIBC.Materials and methodsWe examined 352 patients with clinical stage T2N0M0 (cT2N0M0) MIBC classified into the following groups based on the irradiation method: group A, the whole pelvis (50 Gy/25 fractions) + local bladder (10 Gy/5 fractions); group B, the small pelvis (50 Gy/25 fractions) + local bladder (10 Gy/5 fractions); group C, the whole pelvis (40 Gy/20 fractions) + local bladder (10 Gy/5 fractions).ResultsThe complete response rate, 3-year overall survival and progression-free survival rates in group A were 92.9%, 94.9% and 82.1%, respectively; in group B were 87.2%, 86.7% and 76.7%, respectively; and in group C were 95.2%, 92.6% and 71.1%, respectively. No significant differences between the groups were noted. The incidence of ≥grade 3 urinary tract and gastrointestinal toxicities were not significantly different among the groups (group A: 7.8%, 1.7%; B, 11.1%, 0%; C, 7.1%, 1.8%, respectively). The 3-year progression-free rates of the common iliac lymph node (CILN) region in patients who received whole-pelvis and small-pelvis irradiation were 99.0 and 89.0% (P < 0.01), respectively, with the latter group having significantly high lymph node recurrence in the CILN region.ConclusionsOur findings showed that the optimal radiation therapy for patients with cT2N0M0 MIBC undergoing the OMC regimen is whole-pelvis irradiation including the CILN region, with a total dose of 50 Gy/25 fractions.     

Pyk2蛋白在非肌层浸润性膀胱癌中的表达及与该肿瘤预后的相关性

目的探讨富含脯氨酸的蛋白酪氨酸激酶2(Pyk2)蛋白在非肌层浸润性膀胱癌中的表达及与该肿瘤预后的相关性。方法选取62例非肌层浸润性膀胱癌患者为研究对象,患者经手术切除后取膀胱癌病灶标本为观察组,另取相应患者的癌旁正常黏膜组织标本为对照组。采用免疫组化法对观察组、对照组Pyk2蛋白的阳性表达率、表达水平进行统计对比。分析Pyk2蛋白与非肌层浸润性膀胱癌临床病理特征的关系,并对Pyk2蛋白的表达情况与非肌层浸润性膀胱癌预后效果间的相关性进行探讨。结果观察组Pyk2蛋白阳性表达率、表达水平均高于对照组,组间对比差异有统计学意义(P<0.05)。Pyk2蛋白表达与非肌层浸润性膀胱癌患者年龄、性别、病灶大小、病灶数等因素无关,而与患者的肿瘤分期、分化程度有关。Pyk2蛋白阳性表达组患者的复发率高于阴性表达组,无进展生存期(PFS)、总生存期(OS)水平均低于Pyk2蛋白阴性表达患者。结论Pyk2蛋白在非肌层浸润性膀胱癌患者病灶组织中呈现高表达,其表达情况与非肌层浸润性膀胱癌病灶的浸润、转移、分期有密切关系,并与患者的肿瘤预后效果显著相关。Pyk2蛋白的检测对于非肌层浸润性膀胱癌病情评估、预后效果判断有指导意义。     

经尿道钬激光切除术与等离子电切术治疗非肌层浸润性膀胱肿瘤的疗效及安全性对比

目的 探讨经尿道钬激光切除术与等离子电切术治疗非肌层浸润性膀胱肿瘤的疗效及安全性.方法 选择60例非肌层浸润性膀胱癌患者,根据入院时间先后,分为TURBT组(31例)及钬激光切除组(29例).观察2组的手术时间、术后膀胱冲洗时间、术中闭孔神经反射发生率、术中穿孔率、住院时间、住院费用、留置尿管时间及术后1年复发率.结果 TURBT的手术时间、术后膀胱冲洗时间均明显长于钬激光切除组,而其术中闭孔神经反射发生率及术中膀胱穿孔发生率也高于钬激光切除组,P均＜0.05.钬激光切除组的住院时间、平均住院花费、平均留置导管时间及术后1年复发率均明显低于TURBT组,P均＜0.05.结论 相较于等离子电切术,钬激光切除术治疗非肌层浸润性膀胱肿瘤,术中术后情况均更好.     

根治性放疗与根治性手术治疗肌层浸润性膀胱癌的Meta分析

[目的]系统评价根治性放疗与根治性手术治疗膀胱癌临床效果.[方法]应用END-NOTE软件全面检索Pubmed(1973～2013年)数据库,对符合纳入标准的临床对照试验,采用RevMan 4.3软件进行Meta分析.对于无对照临床研究资料,采用同质合并分析.[结果]共纳入6个临床对照试验,共1 264例患者,Meta分析结果显示,根治性放疗与根治性手术切除治疗膀胱癌患者的5年生存率无统计学差异(P=0.36),合并比值比(OR)为1.10 (95％CI:0.86～1.40).18篇无对照临床研究共纳入根治性放疗治疗膀胱癌患者1 749例,多数文献采用全膀胱放疗40～60Gy,联合以顺铂为基础的化疗方案,完全反应率达到65％以上,平均5年总生存率在50％以上,最低为37％,最高可达82％.[结论]根治性放疗不会降低膀胱癌患者生存率,且能维持正常膀胱功能,提高了患者生存质量.     

膀胱癌中雄激素受体与Pax2的表达研究

[目的]探讨雄激素受体（AR）和Pax2在膀胱癌中的表达及与膀胱癌的侵袭、转移及预后的关系。[方法]用免疫组织化学SP法检测103例膀胱癌组织中AR和Pax2的表达。[结果]AR在103例膀胱癌肿瘤组织中有48例表达,阳性率为46.6%。AR的表达在膀胱癌不同的病理分级、T分期、远处转移及复发情况时差异有统计学意义（P〈0.05）。Pax2在103例肿瘤组织中有49例阳性表达,阳性率为47.6%。Pax2在不同T分期、有无远处转移时差异有统计学意义（P〈0.05）。Spearman等级相关分析表明Pax2和AR表达明显相关。[结论]AR及Pax2可能参与了膀胱癌的侵袭与转移,可作为预后判断因子,结合病理分级和T分期分析能提高对膀胱癌患者预后判断的准确性。     

Distribution and Role of N-acetyltransferase 2 Genetic Polymorphisms in Bladder Cancer Risk in a Lebanese Population

Background: In Lebanon, bladder cancer (BC) has an unusually high prevalence. Individuals who are exposed to aromatic amines from smoking or certain occupations and carrying the slow N-acetyl transferase 2 (NAT2) acetylator’ phenotype may be at a higher risk. Methods: Data and DNA from 115 Lebanese BC cases and 306 controls were examined. Ten NAT2 single nucleotide polymorphisms were genotyped, seven of which were then included in haplotype and phenotype analysis. Results: BC patients were more likely to be males (87.8% vs. 54.9%) and current smokers (60.9% vs. 26.5%) when compared to controls. In both groups, most participants had the slow NAT2 acetylator phenotype (66.1% of BC cases vs 62.7% of controls; P=0.302) with the NAT2*5B and *6A haplotypes being the most common. The odds ratio (95%CI) of having BC among slow NAT2 acetylators was 1.157 (0.738-1.815) and remained non-significant after adjustment [1.097 (0.666-1.806)]. Sensitivity analysis with a subgroup of 113 cases and 84 controls for which occupational history was available revealed a statistically significant association between slow NAT2 acetylators and BC in females only. The sample size was however very small and the CI quite wide. Conclusions: This is the first study to evaluate the distribution of NAT2 haplotypes and their potential role in BC in a Lebanese population. The absence of any significant association may be due to the relatively small sample size, the unavailability of matching by gender, and the lack of evaluation of genetic interactions with extent of active and passive smoking, exposure to environmental pollutants, diet, and other genes. The potential association limited to females needs further evaluation.     

浸润性膀胱癌不同治疗方案预后的Meta分析

目的探讨保留膀胱手术后灌注化疗与膀胱全切术对浸润性膀胱癌预后的效果差异性。方法利用Medline、中国生物医学文献数据库、中国期刊全文数据库、中文科技期刊数据库等,检索国内外已发表的相关文献并进行评估,提取资料后对行保留膀胱手术后灌注化疗或膀胱全切术的浸润性膀胱癌患者5年生存率进行Meta分析。结果计算两种治疗方案检验统计量Z=1.22,P=0.22,差异无统计学意义,总体相对危险度的95％可信区间为(0.94~1.29)。结论对于浸润性膀胱癌患者,局部切除加灌注化疗5年生存率与全切组无差别,可以谨慎地接受保留膀胱策略,提高患者生存质量。     

Accuracy of Preoperative Urinary Symptoms,Urinalysis, Computed Tomography and Cystoscopic Findings for the Diagnosis of Urinary Bladder Invasion in Patients with Colorectal Cancer

Background: To determine the accuracy of preoperative urinary symptoms, urinalysis, computed tomography (CT) and cystoscopic findings for the diagnosis of urinary bladder invasion in patients with colorectal cancer. Materials and Methods: Records of patients with colorectal cancer and a suspicion of bladder invasion, who underwent tumor resection with partial or total cystectomy between 2002 and 2013 at the Faculty of Medicine Siriraj Hospital, were reviewed. Correlations between preoperative urinary symptoms, urinalysis, cystoscopicfinding, CT imaging and final pathological reports were analyzed. Results: This study included 90 eligible cases (71% male). The most common site of primary colorectal cancer was the sigmoid colon (44%), followed by the rectum (33%). Final pathological reports showed definite bladder invasion in 53 cases (59%). Significant features for predicting definite tumor invasion were gross hematuria (OR 13.6, sensitivity 39%, specificity 73%), and visible tumor during cystoscopy (OR 5.33, sensitivity 50%, specificity 84%). Predictive signs in CT imagingwere gross tumor invasion (OR 7.07, sensitivity 89%, specificity 46%), abnormal enhancing mass at bladder wall (OR 4.09, sensitivity 68%, specificity 66%), irregular bladder mucosa (OR 3.53, sensitivity 70%, specificity 60% ), and loss of perivesical fat plane (OR 3.17, sensitivity 81%, specificity 43%). However, urinary analysis and other urinary tract symptoms were poor predictors of bladder involvement. Conclusions: The present study demonstrated that the most relevant preoperative predictors of definite bladder invasion in patients with colorectal cancer are gross hematuria, a visible tumor during cystoscopy, and abnormal CT findings.     

肌层浸润性膀胱尿路上皮癌MDM2扩增与PD-1/PD-L1抑制剂耐药机制TCGA数据库资料分析

目的免疫检测点抑制剂能延长晚期膀胱尿路上皮癌患者的生存,但仍面临耐药问题,其机制是目前的研究热点。本研究通过分析癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中肌层浸润性膀胱尿路上皮癌的鼠双微基因2(murine double minute 2,MDM2)扩增情况及相关基因表达,寻找免疫检查点抑制剂耐药的潜在机制。方法于2019-04-01从TCGA数据库下载自建库至2014-11-15肌层浸润性膀胱尿路上皮癌数据包"bladder cancer(TCGA,cell2017)",含临床信息、基因拷贝数变异与核糖核酸测序数据,共412例患者,其中408例患者有基因拷贝数信息。对比MDM2扩增(36例)和未扩增(372例)的2组患者间临床特征和预后差异;利用cBioportal和DAVID6.8在线分析mRNA表达与MDM2扩增相关基因,并进行功能富集分析;进一步采用cBioportal和GeneSpringGX软件筛选出MDM2扩增和未扩增组间表达有差异的基因。结果肌层浸润性膀胱尿路上皮癌中MDM2扩增发生率为8.8%(36/408)。MDM2基因扩增组和未扩增组,总人群的中位生存期为33.1和35.0个月(χ^2=0.759,P=0.384),根治术后患者的中位无疾病生存期为18.0和35.7个月(χ^2=2.921,P=0.087),差异均无统计学意义。对mRNA水平与MDM2扩增相关的357个基因进行KEGG功能富集分析显示,36个基因富集于代谢通路(校正P=0.090),14个基因富集于内吞作用通路(校正P=0.280),但差异无统计学意义。MDM2扩增时自身mRNA水平增高,并与FRS2、RAB3IP、YEATS4、RAP1B和CPSF6mRNA水平中度正相关;其中FRS2、RAB3IP、RAP1B、CPSF6与MDM2常同时扩增。MDM2扩增与常见免疫抑制因子PD-1(PDCD1)、PD-L1(PDCD1LG2)、CTLA4、LAG3和IDO1的mRNA水平低度负相关。结论MDM2扩增与非扩增肌层浸润性膀胱尿路上皮癌患者的多个基因mRNA表达水平存在差异,可能为研究免疫检测点抑制剂耐药机制提供线索。     

Bcl-2 Overexpression Inhibits Generation of IntracellularReactive Oxygen Species and Blocks Adriamycin-inducedApoptosis in Bladder Cancer Cells

Resistance to induction of apoptosis is a major obstacle for bladder cancer treatment. Bcl-2 is thought to beinvolved in anti-apoptotic signaling. In this study, we investigated the effect of Bcl-2 overexpression on apoptoticresistance and intracellular reactive oxygen species (ROS) generation in bladder cancer cells. A stable Bcl-2overexpression cell line, BIU87-Bcl-2, was constructed from human bladder cancer cell line BIU87 by transfectingrecombinant Bcl-2 [pcDNA3.1(+)-Bcl-2]. The sensitivity of transfected cells to adriamycin (ADR) was assessed byMTT assay. Apoptosis was examined by flow cytometry and acridine orange fluorescence staining. IntracellularROS was determined using flow cytometry, and the activities of superoxide dismutase (SOD) and catalase (CAT)were also investigated by the xanthinoxidase and visible radiation methods using SOD and CAT detection kits.The susceptibility of BIU87-Bcl-2 cells to ADR treatment was significantly decreased as compared with controlBIU87 cells. Enhanced expression of Bcl-2 inhibited intracellular ROS generation following ADR treatment.Moreover, the suppression of SOD and CAT activity induced by ADR treatment was blocked in the BIU87-Bcl-2case but not in their parental cells. The overexpression of Bcl-2 renders human bladder cancer cells resistant toADR-induced apoptosis and ROS might act as an important secondary messenger in this process.     

T-786C,G894T,and Intron 4 VNTR (4a/b) Polymorphisms of the Endothelial Nitric Oxide Synthase Gene in Bladder Cancer Cases

The aim of the present study was to determine whether endothelial nitric oxide synthase (eNOS) genepolymorphisms play a role in development of bladder cancer in the Turkish population. The study was performedon 75 patients (64 men, 11 women) with bladder cancer and 143 healthy individuals (107 men, 36 women) withany kind of cancer history. Three eNOS gene polymorphisms (T-786C promoter region, G894T and intron 4VNTR 4a/b) were determined with polymerase chain reaction and restriction fragment lenght polymorphismmethods. In our study, GT and TT genotypes for eNOS G894T polymorphism were found to significantly varyamong patients with bladder cancer and control group (OR: 0.185, CI: 0.078-0.439, p=0.0001 and OR: 0.324,CI: 0.106-0.990, p=0.026). Also, the frequency of the 894T allele was significantly higher in patients with bladdercancer (51%). No association was identified for eNOS T-786C and intron 4 VNTR 4a/b polymorphisms betweenpatients with bladder cancer and control groups in our Turkish population.     

A Comprehensive Model for Predicting Recurrence and Survival in Cases of Chinese Postoperative Invasive Breast Cancer

We investigated relationships between clinical pathologic data, molecular biomarkers and prognosis of invasive breast cancer based on a Chinese population. Immunohistochemistry (IHC) was used to assess the status of ER, PR, HER-2 and Ki-67, with fluorescence in situ hybridization (FISH) performed to further confirm HER-2 positivity with an equivocal result (IHC 2+). Subsequently, Kaplan-Meier univariate and multivariate COX regression analyses of ER, PR, HER-2, Ki-67, clinical features, therapeutic status and follow-up data were performed according to the establishment principle of the Nottingham prognostic index (NPI). From this study, age, tumor size, lymph node status, ER, HER-2, Ki-67 status were found to be associated with prognosis. Eventually, a prognostic model of (PI= (1.5×age) - size + (0.1×lymph node status) - (0.5×ER) + (2×HER-2) - (0.2×Ki-67)) was established with 288 randomly selected patients and verified with another 100 cases with invasive breast cancer. Pearson correlation analysis demonstrated a significant positive correlation index of 0.376 (P=0.012<0.05) between the prognostic index (PI) and actual prognosis. Remarkably, the consistency with the model predicted recurrence was 93% in the validation set. Therefore, it appears feasible to predict the prognosis of individuals with invasive breast cancer and to determine optimal therapeutic strategy with this model.