EZH2基因在膀胱移行细胞癌细胞株和癌组织标本中的表达及意义

目的 探讨EZH2基因在膀胱癌发生及进展中的作用. 方法 应用RT-PCR、蛋白质印迹及免疫细胞化学方法,以前列腺癌细胞株PC-3M作为阳性对照,检测EZH2基因在人膀胱移行细胞癌细胞株T24、EJ、MGH-U1、BIU-87中的表达;采用RT-PCR方法检测45例膀胱移行细胞癌和12例正常膀胱黏膜组织中EZH2基因表达情况.45例膀胱移行细胞癌中表浅性癌(Tis、Ta、T1)31例(68.9%),浸润性癌(T2～T4)14例(31.1%);病理分级G1 13例(28.9%),G2 21例(46.7%),G3 11例(24.4%). 结果 4种膀胱癌细胞株中均有EZH2基因表达.EZH2基因在膀胱移行细胞癌组织中的表达率(82.2%)明显高于正常膀胱黏膜(8.3%,P<0.05),在表浅性膀胱癌中的表达率为74.2%,浸润性膀胱癌中为100.0%,差异无统计学意义(P>0.05).EZH2基因在G1,G2和G3级肿瘤中的表达率分别为61.5%,85.7%和100.0%.随细胞分级程度升高.EZH2表达率有增加趋势,但差异无统计学意义(P>0.05). 结论 EZH2基因可能在膀胱癌的发生及进展中起重要作用,可能成为膀胱癌一个潜在的基因治疗靶点.     

Combined intravesical chemotherapy with mitomycin C and local bladder microwave-induced hyperthermia as a preoperative therapy for superficial bladder tumors. A preliminary clinical study.

Twelve patients suffering from superficial transitional cell carcinoma of the bladder underwent treatment combining simultaneous mitomycin C topical instillation and local endocavitary hyperthermia as a preoperative adjunct to transurethral resection in a preliminary clinical study. A specifically designed system to deliver and monitor local bladder hyperthermia was used. The feasibility, the subjective tolerance and the side effects of the combined treatment were the main target of our investigation. Endoscopic and histologic features, assessed before, during and after this combined approach, showed selective damage to neoplastic areas with minimal changes in the normal urothelium. Local intravesical concurrent chemotherapy and hyperthermia administration is found to be a safe and well-tolerated approach for superficial bladder tumor treatment. The preliminary results encourage further studies to define the limits and prospects of this regimen, in both superficial bladder tumor ablation and prophylaxis of recurrences.     

Retrospective study of efficacy of intravesical BCG alone in treatment of superficial bladder cancer

This is a review of 100 patients at our institution who were treated for superficial bladder cancer. In those patients with carcinoma in situ of the bladder who were treated with conventional therapy (resection and/or fulguration) and intravesical bacillus Calmette-Guerin (BCG) without intradermal BCG, and those patients who were treated with conventional therapy alone, we found a response rate of 60 per cent versus 40 per cent at the end of three months. In comparing those patients with superficial papillary cancer, we found a response of 39 per cent after conventional therapy and 63 per cent after conventional therapy and intravesical BCG. This suggests that intravesical BCG without intradermal BCG can be an important adjunct to the conventional therapy of bladder tumors.     

A low dose bacillus Calmette-Guerin regimen in superficial bladder cancer therapy: is it effective?

Bacillus Calmette-Guerin (BCG) intravesical therapy represents a major advance in the treatment of superficial transitional cell carcinoma of the bladder. To date, however, the optimal treatment schedule must be defined and the toxicity related to the treatment is significant. The preliminary results of a randomized ongoing study performed to evaluate the effectiveness and relative toxicity of a low dose (75 mg.) BCG regimen in the treatment of superficial bladder cancer therapy are reported. A total of 126 patients (70 for prophylaxis of recurrent stages Ta and T1 papillary tumors and 56 for treatment of carcinoma in situ or with microinfiltration of the subepithelial connective tissue) underwent a 6-week course of 75 mg. BCG (Pasteur vaccine). An additional course was given in patients who failed to respond to the induction course. Maintenance therapy was administered in complete responders monthly for 1 year and then quarterly for 1 year. The prophylaxis group (transurethral resection plus BCG) was randomized versus transurethral resection alone (63 patients, control group). A complete response in the prophylaxis, control and therapy groups was observed in 74, 17 and 57% of the patients, respectively, while 4, 17 and 12.5%, respectively, experienced tumor progression. The additional course of therapy increased the response rate. On the contrary, previous unsuccessful intravesical chemotherapy did not affect the response rate. In regard to toxicity, irritative disturbances (27%) and fever (17%) appeared to be significantly decreased compared with the rates reported in the literature. No major complications were experienced. In conclusion, a low dose (75 mg.) Pasteur strain BCG regimen was effective as prophylaxis against recurrent superficial papillary tumors and as treatment of carcinoma in situ or with microinfiltration of the subepithelial connective tissue. Toxicity related to the treatment appeared to be low.     

表阿霉素黏膜下浸润注射加单次灌注预防浅表性膀胱癌术后复发的研究

目的　探讨表阿霉素膀胱黏膜下浸润注射和术后立即单次膀胱灌注预防浅表性膀胱癌术后复发的临床效果。　方法　浅表性膀胱癌 36例 ,Ta10例 ,T12 6例 ;G111例 ,G2 2 0例 ,G3 5例 ,均行膀胱部分切除。术中采用 1mg/ml浓度的表阿霉素多中心膀胱黏膜下浸润注射 ,总量 30mg。手术结束时立即单次膀胱灌注表阿霉素 12 0mg。 36例患者术后随访 1～ 4年 ,平均 2 .8年。　结果　 36例患者术后 1、2、3年无瘤生存率分别为 10 0 .0 %、91.7%、88.9% ,总复发率 11.1% ( 4 / 36 )。手术前后肝肾功能及心电图无显著性变化。术后早期并发症主要为血尿和膀胱刺激症状 ,膀胱局部毒性反应发生率为 2 7.8% ( 10 / 36 ) ,全身性毒性反应发生率 8.3% ( 3/ 36 )。　结论　术中多中心表阿霉素膀胱黏膜下浸润注射结合单次膀胱灌注预防浅表性膀胱癌术后复发效果良好 ,操作简便 ,费用低 ,毒副作用小     

Chemoimmune prophylaxis of superficial bladder tumors: Results after treatment of 130 patients in 4 years

Since January 1978 we performed chemoimmune prophylaxis in 130 patients with superficial transitional cell carcinoma of the bladder. After complete tumor resection and exclusion of an urinary tract infection as well as an impaired global immune competence treatment consisted of one intravenous application of 700 mg Cyclophosphamide (CTX)/m2 followed by 6 intravesical instillations of 120 mg BCG/50 ml saline together with BCG skin scarifications. In a total of 12.3% of the treated patients tumor recurrences were observed until the 18th month. These results compared favourably with the high recurrence rate in a group of 80 patients without CTX/BCG prophylaxis. In 48 patients with a history of recurrent tumors statistically significant treatment effects were noted after CTX/BCG (p less than 0.01) using the Wilcoxontest. In 10% of the cases, inflammatory tumor-like lesions developed. Side effects of the treatment were generally well tolerable. From the presented data it is concluded that chemoimmune prophylaxis effectively prevents recurrences in superficial bladder cancer.     

Comparison of different schedules of cytostatic intravesical instillations in patients with superficial bladder carcinoma: final evaluation of a prospective multicenter study with 419 patients

In a prospective multicenter study we compared the value of various protocols of mitomycin C and doxorubicin instillation for the prevention of recurrent tumors in patients whose superficial bladder tumors (stages TA and T1) had been removed by transurethral resection. The 3-year and short-term instillation protocols were compared to each other and to a combination of 2 protocols. Evaluation after a mean followup of 28 months confirmed the value of cytostatic bladder instillation in preventing recurrence and progression of tumor in patients with superficial bladder carcinoma. There was no significant difference between the results of long-term and short-term prophylaxis; their combination achieved the best results. Doxorubicin and mitomycin yielded similar results; mitomycin was better tolerated.     

The recurrence of urothelial carcinoma in situ at the fossa navicularis of the urethra and the glans penis arising eight years after transurethral resection of a bladder tumor to treat superficial bladder cancer

A 63-year-old man underwent transurethral resection of a bladder tumor to treat superficial bladder cancer in 1995. Histological examination showed urothelial carcinoma, G2>G3 with carcinoma in situ (CIS) at the bladder neck. He underwent postoperative intravesical bacillus Calmette-Guerin (BCG) therapy. In June, 2003, he complained of rubor of his external urethral meatus and visited our clinic. Biopsies at the external urethral meatus and the fossa navicularis of the urethra showed CIS. Radiological examinations, cystourethroscopy and multiple biopsies from other sites of urothelium, including bladder and urethral mucosa, did not reveal any other malignancies. Thereafter, partial penectomy and bilateral inguinal lymphadenectomy were performed. Histological examinations showed CIS at the urethral mucosa of the fossa navicularis and the skin of the glans penis. Postoperative urine cytologies were negative.     

Intravesical BCG therapy in the management of multiple superficial bladder carcinoma. Comparison between Glaxo and Pasteur strains

Intravesical Bacillus Calmette-Guérin (BCG) therapy in the treatment and prophylaxis of superficial bladder cancer has shown encouraging results in North America but disappointing results have been reported in Great Britain. This was attributed to differences in quality between BCG (Glaxo strain) used in Great Britain and BCG (Pasteur and Tice strains) used in North America. Twenty-one patients with multiple superficial recurrent transitional cell carcinoma of the bladder were entered into a pilot study comparing the efficacy of BCG Glaxo (Evans Medical Ltd, Dunstable, UK) and Pasteur (L'Institut Pasteur, France) strains. Comparable and encouraging results were demonstrated, indicating that this mode of therapy is effective.     

Monoclonal antibody 486 P 3/12: a valuable bladder carcinoma marker for immunocytology

Monoclonal antibodies directed against tumor-associated antigens of bladder carcinoma were used to identify tumor cells in bladder washout specimens of 40 patients with bladder carcinoma (group 1), 41 with no bladder disease or with urinary tract infections (group 2), 41 who received long-term mitomycin C instillation therapy after excision of the tumors (group 3) and 39 who received no prophylaxis after excision of the tumors (group 4). In all groups the same bladder washout specimen was used for standard urinary cytological and immunocytological tests. True positive results were obtained in 90 per cent of the patients in group 1 according to our immunocytological criteria and in 43 per cent according to standard cytology studies. No urine specimens in group 2 (controls) were immunocytologically positive, while 16 of 41 in group 3 and 17 of 39 in group 4 were positive immunocytologically but only 4 and 5, respectively, were positive according to standard cytology studies. Further followup of these patients will show whether cells positive for monoclonal antibody 486 P 3/12 will permit early detection of recurrent bladder cancer and whether one can identify patients who require prophylaxis after removal of the superficial bladder tumors.     

Cytostatic intravesical instillation in patients with superficial bladder carcinoma for the prevention of recurrent tumors

The value of various protocols of mitomycin C and adriamycin instillation for the prevention of recurrent tumors in patients whose superficial bladder tumors (TA, T1) had been removed by transurethral resection was compared in a prospective multicenter study. Three-year and short-term instillation protocols were compared with each other and with the combination of the two. Evaluation after a mean follow-up of 20 months confirmed our previous conclusion of the great value of cytostatic bladder instillation to prevent recurrent tumors and tumor progression in patients with superficial bladder carcinoma. There is no significant difference between long-term and short-term prophylaxis, but combination has achieved the best results. Similar results were obtained with adriamycin and mitomycin but adriamycin was less well tolerated.     

浅表性膀胱癌保留膀胱术后预后影响因素分析

目的 探讨浅表性膀胱肿瘤术后预后的各种影响因素.方法 回顾性分析186例浅表性膀胱肿瘤患者保留膀胱手术治疗的资料,研究肿瘤临床病理特征及治疗措施对手术预后的影响.结果本组病例中,复发65例,初诊时为多发、大于3 cm、病理为G2级以上的高危肿瘤复发率分别要高于单发、小于3 cm、病理为C1级的中低危肿瘤;对于保留膀胱的...     

Reduced bladder capacity in patients receiving intravesical chemoprophylaxis with mitomycin C

After complete resection of superficial bladder carcinoma (Tis-2, G1-3), 75 patients were treated prophylactically with either 20 or 30 mg mitomycin C. Six patients developed a substantial reduction in bladder capacity (less than 200 ml). In 2 patients radical cystectomy of an otherwise tumour-free fibrotic bladder was necessary. The results of long-term treatment (2 years) suggest that reduced bladder capacity correlates with the cumulative dosage of mitomycin C.     

BCG vaccine therapy for treatment of superficial bladder cancer

A total of 42 patients were involved in the study of the effectiveness of BCG vaccine on superficial bladder tumours. The new Bulgarian vaccine CALGEVAX was administered intravesically in consecutive instillations once weekly and then once monthly for a period of 11 months. For intradermal application the F-70 subcellular preparation was used. On the grounds of their initial experience in the treatment of superficial bladder tumours with unspecific immunotherapy the authors would like to express their confidence in the effectiveness of the intravesical application of BCG vaccine.     

Carcinomatous meningitis from urothelial carcinoma of bladder and ureter: case report

Carcinomatous meningitis from urothelial carcinoma of the bladder and ureter is rare. A 77-year-old man with invasive bladder cancer and right ureter cancer had been treated with 3 courses M-VAC (methotrexate, vinblastine, epirubicin, cisplatin) chemotherapy. After chemotherapy we performed radical cystectomy and right nephroureterectomy (ileal-neobladder) (TCC, G3, pT3, N0, M0). Sixteen months after operation, patient complained of anorexia, muscular weakness, stiff neck. CT of chest and abdomen, and bone scintigraphy showed no metastasis. Brain CT and MRI showed hydrocephalus but no evidence of parenchymal metastasis. Because we suspected carcinomatous meningitis, we performed lumbar puncture. Cerebrospinal fluid cytology revealed class V (urothelial carcinoma). Patient died 6 days after diagnosis of carcinomatous meningitis.     

浅表性和浸润性膀胱移行细胞癌上皮钙黏素基因启动子C/A单核苷酸多态性的比较

目的 比较浅表性和浸润性膀胱移行细胞癌上皮钙黏素基因启动子近侧-160位点C/A单核苷酸多态性.方法 浅表性和浸润性膀胱移行细胞癌各33例17例.从血液中提取人基因组DNA,PCR扩增包含E-cad基因启动子近侧序列-160位点的DNA片段,长约190 bp.分别用限制性内切酶HphⅠ和AflⅢ将PCR产物消化过夜,行4%琼脂糖凝胶电泳,根据酶切产物的电泳结果判断基因型.结果 浅表膀胱移行细胞癌的CC、CA、AA基因型分别有9、14和10例;浸润膀胱移行细胞癌的CC、CA、AA基因型分别有2、3和12例.浸润性膀胱移行细胞癌A等位基因频率0.79(27/7)高于浅表性膀胱移行细胞癌0.52(34/32),差异有统计学意义(P＜0.05).结论 E-cad基因启动子近侧序列-160位点A等位基因与膀胱移行细胞癌的侵袭能力密切相关.     

Immunohistochemical markers defined by monoclonal antibodies and response to bacillus Calmette-Guérin endovesical immunotherapy for superficial bladder tumors.

As bacillus Calmette-Guérin (BCG) immunotherapy is highly effective for most but not all superficial bladder tumors, there is a need to define predictors of response to this mode of treatment. We have investigated a panel of markers defined by monoclonal antibodies, directed against tumor-associated transitional cell carcinoma antigen (G4 and E7), epidermal growth factor receptor, cytokeratin (CK) 18 and blood group antigens A, B and H, using an indirect immunoperoxidase staining on paraffin sections. Twenty superficial bladder tumors (T1) treated with intravesical BCG therapy (10 responders and 10 nonresponders) were tested with this panel. Among the responders, expression of CK18 antigen was positive in 7 and negative in 3, whereas in the nonresponder group it was positive in 2 and negative in 8. The difference was statistically significant (p less than 0.05). Loss of expression of CK18 antigenicity was associated with recurrence or progression of superficial bladder tumors following BCG therapy, indicating that changes in CK patterns should be investigated as potential predictive markers for response to BCG.     

Treatment of carcinoma in situ of the urethra with intraurethral instillations of bacillus Calmette-Guérin. Case report and review of literature.

We present the case of a 60-year-old man with carcinoma in situ of the urethra after previous successful radiotherapy of an invasive bladder tumor. Intraurethral instillations with bacillus Calmette-Guérin were given. In spite of initial success, recurrences developed after two courses of 12 intraurethral instillations, and radical surgery was performed. The use of bacillus Calmette-Guérin is reviewed with regard to the locations of superficial transitional cell carcinoma outside the bladder cavity.     

Diagnosis of vasospasm: comparison between arteriography and transcranial Doppler. A series of 112 comparative tests]

56 consecutive patients with ruptured aneurysm (An) were studied. The An localisation were: anterior communicating artery (ACoA) 26 cases, internal carotid artery (I.C.A.) 13 cases, Middle cerebral artery (M.C.A.) 11 cases, Pericallosal artery (P.C.A.) 4 cases, anterior cerebral artery (A.C.A.) 2 cases. Nimodipine infusion was started as soon as the diagnostic was established. Transcranial Doppler (T.C.D.) and angiography (A degrees) were performed at the arrival and 10 to 12 days after surgery. Surgery was performed in the 72 first hours after S.A.H. in 79% of the cases. 112 comparisons A degrees-T.C.D. were available. An A degrees vasospasm (V.S.) was assessed if the reduction of calibre was 25% or more, on T.C.D. V.S. was assessed if mean cerebral flow (M.C.F.) was equal to or more than 130 cm/sec. There were 15 cases of A degrees V.S. in 14 patients: 2 cases before surgery, 1 case before and after surgery in the same patient and 11 cases after surgery. D.T.C. exhibited 11 cases of V.S. at the level of M.C.A.; there were 11 true positive, 0 false positive, 97 true negative and 4 false negative. The diagnosis of V.S. was always correct with T.C.D. when A degrees V.S. was present at the level of M.C.A., it was not made when A degrees V.S. was restricted to the initial part of A.C.A. (A1) uni or bilaterally: 3/6 cases of ACoA. An rupture or to I.C.A.: 1/4 case of I.C.A. An. rupture.(ABSTRACT TRUNCATED AT 250 WORDS)