放射线联合p53基因及内皮抑素治疗小鼠前列腺癌皮下移植瘤

Objective To test the hypothesis that p53 gene therapy combined with endostatin can enhance tumor response to radiation therapy of RM-1 mouse xenograft prostate cancer and to investigate its mechanism. Methods A mouse prostate cancer model was established. Then mice with xenograft tumor were randomly divided into group A (control), B (radiation), C (radiation and rAdp53), D (radiation and rh-endostatin) and E (radiation and rAdp53 and rh-endostatin). On day 1, rAdp53 was injected intra-tumorously with 1 × 1010 vp per animal to group C and E. From day 1 to 14, rh-endostatin was given 15 mg/kg intraperitoneally daily to group D and E. On day 4 single fraction of 15 Gy was given to tumors in groups B, C, D and E. Normal saline was injected intra-tumorously or intraperitoneaUy accordingly as control. No treatment was done to group A. Tumor volume was measured daily. Samples were collected on Days 5, 10 and 15. Ki67, CD31, p53 and VEGF were detected by means of immunohistochemistry. Results (1) Radiation alone, radiation combined with intra-tumorous injection of Adp53 and/or intraperitoneal injection of rh-endostatin resulted in tumor growth arrest of RM-1 cells in vivo (P = 0.000). Radiation combined with both rAdp53 and rh-endostatin was the most effective treatment (P < 0.05). (2) All the four treatment groups had a decreased expression of mutant type P53 (P = 0.000). The expression of Ki67 in groups B and C were equal (P 0.05) and increasing (P = 0.000), respectively. Group D had a up-down-up curve (P < 0.05), but group E had a up-down one. On day 5 the expresion of VEGF in group E was the lowest (P < 0.05). An increased expression of MVD compared with the control was shown, and MVD in groups C, D and E were always higher than that in the control (P < 0.05). Conclusions The limitation of radiotherapy could be overcome by combination with beth p53 gene therapy and endostatin on the growth of mouse prostate cancer cell. Radiation, rAdp53 and endostatin have their own role but they can be interacted with each other.     

放射线联合p53基因及内皮抑素治疗小鼠前列腺癌皮下移植瘤

Objective To test the hypothesis that p53 gene therapy combined with endostatin can enhance tumor response to radiation therapy of RM-1 mouse xenograft prostate cancer and to investigate its mechanism. Methods A mouse prostate cancer model was established. Then mice with xenograft tumor were randomly divided into group A (control), B (radiation), C (radiation and rAdp53), D (radiation and rh-endostatin) and E (radiation and rAdp53 and rh-endostatin). On day 1, rAdp53 was injected intra-tumorously with 1 × 1010 vp per animal to group C and E. From day 1 to 14, rh-endostatin was given 15 mg/kg intraperitoneally daily to group D and E. On day 4 single fraction of 15 Gy was given to tumors in groups B, C, D and E. Normal saline was injected intra-tumorously or intraperitoneaUy accordingly as control. No treatment was done to group A. Tumor volume was measured daily. Samples were collected on Days 5, 10 and 15. Ki67, CD31, p53 and VEGF were detected by means of immunohistochemistry. Results (1) Radiation alone, radiation combined with intra-tumorous injection of Adp53 and/or intraperitoneal injection of rh-endostatin resulted in tumor growth arrest of RM-1 cells in vivo (P = 0.000). Radiation combined with both rAdp53 and rh-endostatin was the most effective treatment (P < 0.05). (2) All the four treatment groups had a decreased expression of mutant type P53 (P = 0.000). The expression of Ki67 in groups B and C were equal (P 0.05) and increasing (P = 0.000), respectively. Group D had a up-down-up curve (P < 0.05), but group E had a up-down one. On day 5 the expresion of VEGF in group E was the lowest (P < 0.05). An increased expression of MVD compared with the control was shown, and MVD in groups C, D and E were always higher than that in the control (P < 0.05). Conclusions The limitation of radiotherapy could be overcome by combination with beth p53 gene therapy and endostatin on the growth of mouse prostate cancer cell. Radiation, rAdp53 and endostatin have their own role but they can be interacted with each other.     

14例恶性潜能未定的前列腺间质肿瘤病例分析

目的: 探讨恶性潜能未定的前列腺间质肿瘤(stromal tumor of uncertain malignant potential,STUMP)的临床及影像学表现、病理特点、治疗及预后情况。方法: 回顾性分析2008年10月至2020年4月北京大学第一医院泌尿外科诊治的14例STUMP患者的临床资料,年龄27~78岁(平均54岁), 病程1~180个月(平均46个月)。以排尿困难、尿路刺激症状为主要表现,直肠指诊可提示前列腺肿物,血清前列腺特异性抗原(prostate specific antigen, PSA)正常或轻度升高,经直肠超声及磁共振提示前列腺肿瘤或前列腺增生结节。结果: 3例仅行前列腺穿刺活检术,2例仅行经尿道前列腺切除术,9例经病理明确诊断后行根治性前列腺切除术或经尿道前列腺切除术。镜下观察前列腺间质细胞过度增生,呈梭形细胞,细胞异型性不明显,核分裂像少见。免疫组织化学检查,PSA均为阴性,波形蛋白均为阳性,CD34及孕激素受体多呈阳性,Ki67阳性指数为1%~20%(平均6%)。病理诊断为恶性潜能未定的前列腺间质肿瘤。随访时间10~96个月(平均65个月), 失访2例,死亡1例,9例术后未见复发,2例因局部复发而多次行经尿道前列腺切除术。结论: STUMP的影像学表现具有特征性,可通过前列腺穿刺活检获得病理学诊断;早期发现确诊,结合临床制定手术为主的综合治疗方案,有助于改善患者预后。     

经阴道超声对女性尿道憩室的诊断价值

目的探讨经阴道超声检查女性尿道憩室的声像图表现及诊断价值。方法回顾性分析40例女性尿道憩室患者临床及超声资料,总结其声像图特点。结果 40例经阴道超声诊断为尿道憩室。其中38例为单发憩室,2例多发憩室。均位于尿道中段,背侧为主。环形11个,马鞍形25个,类圆形7个。复杂性憩室37个,单纯性憩室6个。憩室最大径0.9~6.2 cm(中位3.0 cm),其中复杂性憩室最大径1.5~6.2 cm(中位3.0 cm),单纯性憩室最大径0.9~2.2 cm(中位1.5 cm)。壁厚0.2~0.5 cm(中位0.3 cm)。32个憩室呈无回声,11个憩室为片絮状弱回声。34个憩室内多发分隔,9个憩室内无分隔。26个憩室内点片状强回声结石,17个无强回声。43个憩室内均未见实性肿瘤。29个憩室开口位置与术中所见相符,14个憩室开口与术中所见不相符或未得到手术证实。28个憩室壁或分隔可见少量低速高阻动脉血流信号。结论女性尿道憩室的声像图具有特征性,有助于术前诊断及鉴别诊断。     

射频消融治疗肾肿瘤

近十年来，越来越多的资料表明保留肾单位的手术已经成为肾肿瘤的新治疗标准，对于选择性病例可以获得非常好的治疗效果^[1]。保留肾单位的手术包括开放或者腹腔镜肾部分切除术以及各种组织消融治疗，如射频消融（radiofrequency ablation，RFA）、冷冻、高能聚焦超声以及微波热疗等。其中RFA因其可以在局麻下经皮穿刺进行操作，     

原发性附睾肿瘤——附42例报告

目的探讨原发性附睾肿瘤的临床特点、病理类型及临床诊治方法。方法回顾性总结42例接受手术治疗的原发性附睾肿瘤患者临床资料。42例附睾肿瘤中良性肿瘤37例（88．1％），其中附睾腺瘤样瘤21例，平滑肌瘤9例，纤维假瘤2例，其余5例分别为乳头状囊腺瘤、血管平滑肌脂肪瘤、纤维瘤、纤维脂肪瘤和硬化性m管瘤。恶性肿瘤5例（11．9％），为附睾腺癌2例，非霍奇金淋巴瘤、横纹肌肉瘤和平滑肌瘤肉瘤变各1例。良性肿瘤作单纯肿瘤或患侧附睾切除，恶性肿瘤（除平滑肌瘤肉瘤变患者外）行根治眭附睾睾丸切除术，术后辅助放和／或化疗。结果良性肿瘤27例获随访，预后良好，术后无复发。恶性肿瘤5例均获随访，预后差，2例腺癌患者均于术后12个月死亡，横纹肌肉瘤患者术后20个月时广泛转移，非霍奇金淋巴瘤患者和平滑肌瘤肉瘤变患者健在。结论附睾肿瘤大部分为良性，手术切除效果好。恶性肿瘤少见，但预后较差，综合治疗可能会提高疗效。     

经腹腔与腹膜后腹腔镜肾癌根治术疗效比较

目的比较经腹腔与经腹膜后入路腹腔镜肾癌根治术的临床效果。方法分析2010年4月至2012年2月间在北京大学第一医院接受腹腔镜肾癌根治术的141例患者资料,其中经腹腔入路组61例、经腹膜后腔入路组80例,比较两种手术入路患者在手术时间、出血量、术后住院日等方面的差异。结果所有141例手术均在腹腔镜下完成。对于经腹腔入路组和经腹膜后腔组,平均手术时间分别为192.1及147.2min（P=0.000）;平均术后住院日分别为5.8d及7.2d（P=0.000）;平均肿瘤长径分别为5.6cm及4.3cm（P=0.001）。在术中出血量、并发症及输血情况等方面无显著性差异。结论经腹腹腔镜和经后腹膜腹腔镜肾癌根治术围手术期均有良好效果,经腹腔入路适合治疗体积较大的肿瘤,术后恢复快,而经腹膜后腔入路具有手术时间短的优势。     

ELL慢病毒表达载体的构建及其感染前列腺癌PC3细胞的研究

目的构建ELL基因的慢病毒表达质粒,探讨其感染人前列腺癌PC3细胞的可行性。方法将含有全长ELL的质粒和慢病毒表达载体经双酶切后连接,构建成重组慢病毒载体质粒pCDH1-MCS1-EF1-copGFP-ELL。对慢病毒载体质粒进行双酶切和测序鉴定后,制备包装病毒并转染人前列腺癌细胞系PC3。结果慢病毒载体质粒pCDH1-MCS1-EF1-copGFP-ELL的酶切和测序结果与预计的序列一致。慢病毒感染人前列腺癌PC3细胞后能稳定高表达ELL。结论成功构建了ELL的慢病毒表达载体,ELL可被成功转染入人前列腺癌细胞。     

3～4期慢性肾脏病对肾癌术后患者的预后影响分析

目的:分析患有3～4期慢性肾脏病(CKD)的肾癌患者术后的预后状况及其影响因素。方法:回顾性分析2002年1月～2010年12月病理证实的1 353例肾癌患者的临床资料,根据患者术前肾小球滤过率(eGFR)水平,将eGFR≥60ml·min~(-1)·(1.73m~2)~(-1)(1～2期CKD)的1 182例患者设为对照组,将15ml·min~(-1)·(1.73m~2)~(-1)≤eGFR60ml·min~(-1)·(1.73m~2)~(-1)(3～4期CKD)的171例患者设为试验组,比较两组患者临床资料和预后情况。结果:试验组患者中位年龄55(25～84)岁,对照组中位年龄55(24～87)岁。男性患者试验组110例(64.3%),对照组837例(70.8%)。两组BMI、高血压病、糖尿病比较差异无统计学意义(P0.05)。试验组eGFR显著低于对照组[(50.77±8.49)ml·min~(-1)·(1.73m~2)~(-1) vs.(92.00±34.65)ml·min~(-1)·(1.73m~2)~(-1),P0.01]。试验组行肾根治性切除术患者明显多于对照组(85.4%vs.76.1%,P0.01)。试验组和对照组5年肿瘤特异性生存率(CSS)分别为91.2%和89.1%(P=0.171),5年总体生存率(OS)分别为89.3%和87.4%,两组比较差异无统计学意义(P0.05)。多因素分析中,eGFR60ml·min~(-1)·(1.73m~2)~(-1)均不是影响CSS或OS的独立危险因素。结论:本研究单因素及多因素分析显示术前存在3～4期CKD并不影响肾癌患者的预后。     

舒尼替尼治疗转移性肾癌的疗效和安全性分析:单中心37例总结

目的 评价舒尼替尼治疗转移性肾细胞癌的疗效和安全性.方法 2008年6月至2010年4月37例转移性肾细胞癌患者接受舒尼替尼治疗.其中男28例,女9例.年龄17～74岁,中位年龄52岁.行根治性肾切除手术33例,肾穿刺活检3例,腋窝转移淋巴结穿刺活检1例.vonHippel-Lindau综合征患者2例.肾透明细胞癌36例,其中伴颗粒细胞成分1例、伴肉瘤样分化4例,肾乳头状细胞癌1例.一线治疗30例,细胞因子或索拉非尼治疗进展后二线治疗7例.其中34例采用4/2方案,即口服舒尼替尼50.0 mg/d 4周,停用2周,6周为1个周期;3例予口服37.5 mg/d持续治疗,直至疾病进展或者出现不可耐受的不良反应.结果 中位随访时间12个月(8个周期).34例患者治疗2周期以上,可进行疗效评估.根据RECIST标准评价最佳疗效,部分缓解9例(26.5%),疾病稳定24例(70.6%),疾病进展1例(2.9%).客观反应率26.5%,疾病控制率97.1%.1年生存率95.8%(23/24),1年无进展生存率62.5%(15/24).主要不良反应包括血小板减少30例(81.1%)、甲状腺功能异常18/22例(81.8%)、手足反应27例(73.0%),白细胞减少23例(62.2%)、高血压18例(48.6%)等.大多数不良反应为1～2级,3级以上不良反应包括血小板降低8例(21.6%)、甲状腺功能异常4/22例(18.2%)、手足反应4例(10.8%)、血磷降低4例(10.8%)和腹泻2例(5.4%)等.10例(27.0%)在治疗过程中减量或停药,1例因严重乏力不能耐受终止治疗.通过对症支持,减量或停药,不良反应可控制并耐受.结论 舒尼替尼一线及二线治疗晚期转移性肾细胞癌可取得较高的疾病控制率,不良反应发生率多数轻而易耐受,严重不良反应较少且可控.

Abstract：

Objective To evaluate the efficacy and safety of sunitinib in the treatment of metastatic renal cell carcinoma (RCC). Methods A total of 37 patients with metastatic RCC were treated with between June 2008 and April 2010, including 28 males and 9 females. The median age was 52 (17-74) years. All patients received a pathologic diagnosis of RCC, which consisted of 1 papillary cell carcinoma and 36 clear cell carcinomas, 4 of which accompanied with partial sarcoma differentiation. Thirty cases were treated with first line therapy and 7 cases showed progression on first-line cytokine or sorafinib therapy. Sunitinib monotherapy was administered in repeated 6-week cycles of daily oral therapy for 4 weeks, followed by 2 weeks off in 34 patients, while another 3 patients received 37. 5 mg Qd continuously until disease progression or unacceptable toxicities occurred. Overall response rate and safety were evaluated. Results The median follow up was 12 months (8 cycles),range 1.5-19. 5 months (1-13 cycles). 26.5% (9/34) patients achieved partial responses, 70.6%(24/34) patients demonstrated stable disease over≥3 months and 1 (2. 9%) patient developed progressive disease. The objective response rate was 26.5%, and the disease control rate was 97. 1%.The 12 months' overall survival rate was 95.8% (23/24), and 12 months' progression-free survival rate was 62.5 % (15/24). The most common treatment-related adverse events were thrombocytopenia (30 cases, 81.1%), thyroid dysfunction (18/22, 81.8%) ,hand-foot syndrome (27 cases, 73.0%),neutropenia (23 cases, 62.2%) and hypertension (18 cases, 48.6%). The major grade 3 adverse events included thrombocytopenia (8 cases, 21.6%), hand-foot syndrome (4 cases, 10.8%) and diarrhea (2 cases, 5. 4%). Most adverse events were ameliorated by treatment interruption. Ten (27.0%) patients had dose decrement or drug discontinuation and 1 patient quit the treatment for intolerable fatigue. Conclusion The efficacy and manageable adverse event profile of sunitinib as a single agent in first- or second-line therapy for patients with metastatic RCC.