Bax、Bcl-2ASODN联合转染增强宫颈癌HeLa细胞放射敏感性的实验研究

目的:研究凋亡抑制基因bcl-2反义寡核苷酸(ASODN)和促凋亡基因bax联合转染对宫颈癌HeLa细胞凋亡的影响,进而探求其放射增敏作用。方法:用逆转录病毒颗粒感染HeLa细胞,获得HeLa-bax细胞后,将bcl-2ASODN转染HeLa及HeLa-bax细胞,36h后放射治疗,通过MTT法、细胞形态学及流式细胞仪检测细胞增殖与凋亡,半定量RT-PCR测bcl-2及bax基因的表达。结果:(1)HeLa细胞经bcl-2ASODN及bax联合转染并放疗后,光镜观察有明显凋亡趋势;(2)MTT法及流式细胞仪检测其凋亡率明显高于单基因转染+放疗组(P<0.05);(3)RT-PCR结果显示,bax基因表达显著增强,而bcl-2基因表达较各对照组明显减弱。结论:凋亡抑制基因bcl-2ASODN和促凋亡基因bax联合转染诱导HeLa细胞凋亡效果明显优于单基因转染,可有效提高HeLa细胞的放射敏感性。     

胎鼠心肌细胞凋亡调控基因bcl-2和bax的表达及意义

目的:探讨孕鼠肝内胆汁淤积症时胎鼠心肌细胞凋亡及调控基因bcl-2和bax的表达及意义.方法:应用雌孕激素建立妊娠期肝内胆汁淤积症大鼠模型,光镜观察胎鼠心脏的病理改变.采用原位末端标记法(TUNEL)和免疫组织化学方法检测妊娠第21天时胎鼠心肌细胞凋亡及调控基因bcl-2和bax的表达.结果:①肝内胆汁淤积症组(胆淤组)胎鼠心脏光镜下见心肌组织中心肌细胞空泡变性、水肿.②胆淤组胎鼠心肌细胞凋亡指数为39.79%4±2.3421%,对照组为19.29%±2.4624%,两组比较,差异有非常显著性,P＜0.01.③胆淤组胎鼠心肌细胞bcl-2基因的表达明显低于对照组,差异有非常显著性,P＜0.01;胆淤组和对照组胎鼠心肌细胞bax基因的表达比较,差异无显著性,P＞0.05.结论:孕鼠肝内胆汁淤积症时出现胎鼠心肌细胞凋亡,bcl-2基因表达下调可能参与调控胎鼠心肌细胞凋亡.     

子宫颈癌组织中水通道蛋白8和bcl-2蛋白的表达及其相关性

目的 探讨水通道蛋白(AQP)8、bcl-2蛋白在宫颈癌组织中的表达及其相关性.方法 采用免疫组化Envision二步法检测AQP8和bcl-2蛋白在74例宫颈癌(其中鳞癌46例、腺癌28例)、34例宫颈上皮内瘤变(CIN)和15例正常宫颈组织中的表达情况,并分析两者的相关性.结果 AQP8和bcl-2蛋白主要在CIN异型细胞和宫颈癌细胞的细胞质内表达,AQP8蛋白在宫颈鳞癌、腺癌、CIN和正常宫颈组织中的阳性表达率分别为98%、61%、71%和53%,鳞癌高于腺癌、CIN和正常宫颈组织,差异有统计学意义(P＜0.01);腺癌与CIN、正常宫颈组织比较,CIN与正常宫颈组织比较,差异均无统计学意义(P＞0.05).bcl-2蛋白在宫颈鳞癌、腺癌、CIN和正常宫颈组织中的阳性表达率分别为74%、71%、53%和20%,鳞癌与腺癌组织比较,差异无统计学意义(P＞0.05);鳞癌、腺癌高于CIN、正常宫颈组织,CIN也高于正常宫颈组织,差异均有统计学意义(P＜0.01).AQP8和bcl-2蛋白在宫颈癌组织中的表达呈明显正相关(rs=0.463,P=0.000).结论 AQP8和bcl-2蛋白在宫颈癌组织中的表达呈明显正相关,AQP8蛋白表达上调可能与宫颈癌的发生、发展有一定的关系.     

凋亡调节基因在Ⅲ、Ⅳ期子宫内膜异位症中的表达

目的 :检测凋亡调节基因 bcl- 2、bax和 c- myc在 、 子宫内膜异位症异位内膜中的表达 ,以探讨凋亡调节基因在子宫内膜异位症发病中的作用。方法 :2 0例子宫内膜异位症患者 ,按 r AFS分期 : 期 8例 , 期 12例。用免疫组化法检测上述患者异位内膜中 bcl- 2、bax和 c- m yc的表达。结果 :bcl- 2、bax和 c- myc主要定位于子宫内膜异位症的腺上皮中 ,其中 bcl- 2的总体阳性率为 5 5 % ,bax的阳性率为 75 % ,c- myc阳性率为 5 5 % ,且 bcl- 2的表达与 c- myc表达正相关(P<0 .0 1) ,而与 bax的表达负相关 (P<0 .0 5 ) ,相关性有统计学意义。按疾病分期比较三者的表达情况 ,bcl- 2在 期中表达高于 期者 ,差异有显著性 (P<0 .0 5 ) ;按月经周期比较三者表达情况 ,则差异无显著性 (P>0 .0 5 )。结论 :子宫内膜异位症患者异位内膜存在一定程度凋亡 , 期较 期细胞更易凋亡 ,而与月经周期无关 ,bcl- 2和 bax起主要调节作用 ,c- myc可能与 bcl- 2协同作用     

宫颈癌中细胞凋亡指数与放射治疗临床效果关系的研究

目的:研究宫颈癌中细胞凋亡指数与放射治疗（放疗）临床效果的关系。方法:对35例宫颈癌患者分别于放疗前和放疗1周后[用肿瘤剂量（DT）900-1000cGy],取标本,采用原位DNA末端终止法和免疫组化法（IHCA）分别检测细胞凋亡指数（AI）和凋亡相关基因bcl-2/bax。结果:放疗前和放疗第1周后AI分别为1.21％±0.78％、29.8％±8.4％,差异有高度显著性（P<0.01）;AI与bcl-2/bax的表达及与患者的临床疗效密切相关,RT前基础细胞凋亡指数（BAI）≥1.21％的临床疗效明显高于BAI<1.21％者（P<0.01）。结论:AI和患者的临床疗效具有相关性,检测BAI可预测患者对RT的敏感性。     

格尔德霉素对宫颈癌HeLa细胞中bcl-2表达的影响

目的:观察格尔德霉素(geldanamycin,GA)在体外对宫颈癌HeLa细胞抗凋亡基因bcl-2和mRNA转录、蛋白表达水平的影响。方法:分别给予宫颈癌HeLa细胞0,0.02,0.2,2,10μmol/L浓度GA处理24h,用annexin V方法检测细胞凋亡,半定量PCR检测bcl-2、Hsp90 mRNA转录水平,用10μmol/L的GA处理HeLa细胞3、12、24、48h后,Western blot检测bcl-2、Hsp90蛋白表达水平的变化。结果:宫颈癌HeLa细胞经不同浓度的GA作用24h,细胞凋亡指数呈剂量依赖性增加,bcl-2 mRNA表达呈剂量依赖性降低,bcl-2蛋白表达水平呈时间依赖性降低,处理组与对照组之间的差异有统计学意义;但GA对Hsp90 mRNA和蛋白表达水平无明显影响。结论:GA可抑制宫颈癌HeLa细胞抗凋亡基因bcl-2的转录和表达,促进凋亡。     

抗细胞凋零基因bcl-2和bax与卵巢上皮性肿瘤的关系

目的:研究抗凋零基因bcl-2和bax与卵巢上皮性肿瘤发生及预后的关系。方法:通过免疫组化方法,用抗bcl-2及抗bax抗体检测卵巢上皮肿瘤76份(良性27份、交界性24份、恶性25份)中bcl-2和bax的表达产物,并以正常卵巢12份做对照。结果:正常卵巢组织12份中bcl-2和bax阳性检出率为0,在良性、交界性及恶性肿瘤组织中bcl-2和bax的阳性检出率分别为7.4%(2/27)、16.7%(4/24)、36.0%(9/25),22.2%(6/27)、45.8%(11/24)、56.0%(14/25),良性与恶性肿瘤之间差异有显著性(P<0.05),而且bax的表达率比bcl-2高(P<0.05),bax在恶性肿瘤组Ⅰ级与Ⅲ级间差异有显著性(P<0.05)。结论:抗细胞凋零基因bcl-2和bax过度表达可能与卵巢上皮性肿瘤发生有关,推测bax不仅参与细胞凋零的调控,而且可能与肿瘤分化及预后有关。     

调强放射治疗在中晚期宫颈癌放疗中的临床价值

目的探讨调强放射治疗(IMRT)在无淋巴结转移中晚期宫颈癌患者放疗中的临床应用价值。方法选取2007年6月至2008年12于哈尔滨医科大学附属第三医院行放射治疗的无淋巴结转移中晚期宫颈癌患者35例,其中IMRT组15例,常规放疗(CRT)组20例,观察两组患者的近期疗效及放疗反应的发生率。结果 IMRT组与CRT组近期总有效率(完全缓解+部分缓解)分别为86.7%、75.0%,差异无统计学意义(P0.05)。IMRT组1、2年生存率分别为86.7%、60.0%,CRT组1、2年生存率分别为80.0%、50.0%,差异无统计学意义(P0.05)。近期胃肠道及泌尿系放疗反应IMRT组发生率明显低于CRT组(P0.05);骨髓抑制发生率两组差异无统计学意义(P0.05);两组均未出现严重的Ⅲ、Ⅳ级胃肠反应及泌尿系反应。远期放射性直肠炎、膀胱炎、肠梗阻、盆腔及腹壁纤维化发生率IMRT组分别为20.0%、6.7%、6.7%和6.7%,均低于CRT组(P0.05)。阴道粘连发生率两组差异无统计学意义(P0.05)。结论在无淋巴结转移中晚期宫颈癌患者放疗中,与常规放疗相比,IMRT未能改善近期生存率,但可明显降低急慢性放疗反应的发生率。     

SHP-2在宫颈病变组织中的表达及其与HPV感染的关系

目的研究SHP-2在宫颈病变组织中的表达及其与HPV感染的关系。方法选取2013年1月~12月在我院妇产科住院治疗的70例宫颈鳞癌患者(宫颈癌组)、50例宫颈上皮内肿瘤患者(CIN组)及20例宫颈正常患者(正常组),取宫颈组织,采用免疫组化染色检测宫颈组织中SHP-2的表达。结果宫颈癌组SHP-2的表达明显高于正常组,差异有统计学意义(P0.05);宫颈癌组SHP-2的表达明显高于CIN组,差异有统计学意义(P0.05);CIN组与正常组SHP-2表达水平比较,差异无统计学意义(P0.05);HPV16/18在正常组的感染率为15.0%,在CIN组的感染率为74.0%,在宫颈癌组的感染率为82.9%,差异有统计学意义(P0.05);采用Spearman相关分析,结果证实HPV感染和SHP-2在宫颈癌组织中的表达有相关性差异有统计学意义(r=0.331,P0.05)。结论 SHP-2在宫颈癌患者组织中高表达,HPV感染与宫颈癌发生有关,在宫颈癌组织中HPV感染与SHP-2的表达存在相关性。     

邻苯二甲酸二(2-乙基己)酯对原代培养的人早孕绒毛细胞滋养细胞凋亡的影响

目的 探讨邻苯二甲酸二(2-乙基己)酯(DEHP)对原代培养的人早孕绒毛细胞滋养细胞凋亡及凋亡相关基因Bcl-2和bax表达的影响.方法 用浓度为0、25、50、100 μmol/L的DEHP作用于原代培养的人早孕绒毛细胞滋养细胞24 h,逆转录(RT)PCR法检测滋养细胞凋亡相关基因Bcl-2和bax的mRNA表达水平;蛋白印迹法检测Bcl-2和bax的蛋白表达水平;原位末端脱氧核苷酸转移酶标记(TUNEL)法和双染流式细胞术检测细胞滋养细胞凋亡情况.结果 (1)Bcl-2表达水平:当DEHP浓度为0、25、50、100 μmol/L时,Bcl-2 mRNA表达水平分别为1.00±0.05、1.03±0.04、1.04±0.03、1.04±±0.04,分别比较,差异均无统计学意义(P>0.05);Bcl-2蛋白表达水平分别为0.11±0.02、0.11±0.04、0.12±0.02、0.12±0.03,分别比较,差异也无统计学意义(P>0.05).(2)bax表达水平:当DEHP浓度为50、100 μmol/L时,bax mRNA表达水平分别为0.96±0.04、1.02±0.04,与DEHP浓度为0 μmol/L时(0.81±0.05)比较,差异有统计学意义(P<0.05),bax蛋白表达水平分别为0.63±0.04、0.81±0.04,与DEHP浓度为0 μmol/L时(0.23±0.05)比较,差异也有统计学意义(P<0.05).(3)细胞凋亡率:浓度为50、100 μmol/L的DEHP作用24 h后,双染流式细胞术检测细胞滋养细胞凋亡率分别为(18.8±2.6)%和(20.3±2.0)%,与DEHP浓度为0 μmol/L时[(10.6±1.4)%]比较,差异有统计学意义(P<0.05);TUNEL法检测细胞滋养细胞凋亡率为(18.1±4.6)%和(19.5±1.2)%,与DEHP浓度为0 μmol/L时[(11.2±3.1)%]比较,差异也有统计学意义(P<0.05).结论 DEHP可通过增加细胞凋亡相关基因bax的表达,促进细胞滋养细胞凋亡,但对Bcl-2的表达无明显影响.     

Presence of Oncogenic HPV DNAs in Cervical Carcinoma Tissues and Pelvic Lymph Nodes Associating with Proliferating Cell Nuclear Antigen Expression

The presence of oncogenic HPV DNAs (HPV-16/18) in cervical carcinomas and their normal and metastatic pelvic lymph nodes and the expression patterns of proliferating cell nuclear antigen (PCNA) in cervical carcinomas were retrospectively studied to elucidate the possible roles of them in malignant transformation and progression of the disease. HPV-16/18 DNAs were detected by polymerase chain reaction using HPV E6 type-specific primers in 79 patients with cervical cancer: 31 patients who had pelvic lymph node metastasis (group I) and 48 patients without pelvic lymph node metastasis (group II) who were proven by pathologic examination of surgical specimens. HPV-16 or -18 DNAs were detectable in cervical carcinoma tissues in 60 patients from 79 cervical cancer patients (75.9%; HPV-16 was 67.1% and HPV-18 was 8.9%). HPV DNAs were amplified from metastatic pelvic lymph nodes in 13 patients of group I (42%) and from nonmetastatic lymph nodes in 7 group I patients (22.5%). Recurrence was identified in 9 group I patients (29.0%) in 3 years of follow-up. HPV DNAs were amplified from nonmetastatic lymph nodes in 11 group II patients (22.9%). Two group II patients, who had HPV-16 DNA by PCR in nonmetastatic nodes, were recurrent. PCNA was overexpressed in 66.7% of HPV-16- or -18-positive cervical cancers and 16.7% of HPV-16- or -18-negative cervical cancers. However, the expression levels of PCNA in cervical cancers were not influenced by the presence of oncogenic HPV DNA or pathologic metastasis in the pelvic lymph nodes. In conclusion, HPV DNA could be amplified from some metastatic and nonmetastatic pelvic lymph nodes and the detectability of oncogenic HPV DNA in pelvic lymph nodes may represent the poor outcome in the treatment of disease. The expression of PCNA protein which was associated with presence of oncogenic HPV DNAs in cervical cancers, suggesting activation of S phase of cell cycle, may contribute to the malignant progression by HPV-16 or -18.     

PCNA、P16蛋白在卵巢癌组织中的表达及其临床价值的探讨

目的：研究PCNA、P16蛋白在卵巢癌中的表达及临床价值。方法：应用免疫组化法检测89份卵巢癌组织PCNA、P16蛋白的表达。结果：PCNA表达在上皮性,中、低分化以及晚期卵巢癌中的表达显著高于非上皮性,高分化及早期卵巢癌（P＜0．05）,PCNA表达与残存癌灶大小、是否发生淋巴结转移无关（P＞0．05）。在晚期、残存癌灶≥2cm的卵巢癌中P16蛋白的表达明显低于早期、残存癌灶＜2cm者（P＜0．05）;P16蛋白表达与组织类型、组织分化、淋巴结有无转移无关（P＜0．05）。生存分析表明,PCNA、P16蛋白尚不能作为卵巢癌的独立预后因素。结论：肿瘤细胞的过度增殖在卵巢癌的发生、发展中起一定作用。P16蛋白表达的缺失与卵巢癌的进展有关。测定卵巢癌组织P16、PCNA的表达,对客观评价肿瘤的增殖状态,进行“个体化”治疗有指导价值。     

Neoadjuvant intraarterial infusion chemotherapy in patients with stage IB2-IIIB cervical cancer

OBJECTIVES: The purpose of this study was determine the effect of neoadjuvant intraarterial chemotherapy (NAIC) on the prognosis of patients with locally advanced cervical cancer. METHODS: From January 1992 to December 1997, 26 previously untreated patients with stage IB2-IIIB cervical cancer were enrolled in the study. NAIC was administered for more than two courses every 3 weeks using a combination of 17.5 mg/m(2) bleomycin, 7 mg/m(2) mitomycin-C, and 75 mg/m(2) cisplatin via the bilateral internal iliac artery. Pathologic findings were evaluated with histologic examinations of surgical specimens. A nonrandomized control group of 120 patients who underwent conventional treatment between 1980 and 1991 was used for comparison. RESULTS: Nineteen (73.1%) of the 26 patients responded to initial chemotherapy, permitting a radical hysterectomy with pelvic lymphadenectomy in 14 patients. The remaining 5 patients received radiotherapy. One of 7 nonresponders was able to undergo radical surgery. Pathologic complete responses were found in 4 of the 15 patients who underwent radical surgery. The incidence of lymph node metastasis, parametrial infiltration, and vascular space involvement in the 15 patients who received NAIC followed by radical surgery was significantly lower than that in the control group (13.3, 6.7, and 13.3% vs 54.2, 43.8, and 60.4%). The overall 5-year estimated survival rate was significantly higher for all 26 patients who received NAIC (80.0%) than for the control group (59.6%). In stage II and III, the 5-year survival rate for patients who received NAIC was significantly higher than that in the control group (83.3 and 77.8% vs 68.1 and 49.8%). CONCLUSIONS: These preliminary results suggest that NAIC is able to eliminate effectively the pathologic risk factors in the pelvic cavity, to improve the operability in patients with stage IIIB cervical cancer, considered inoperable, and to improve the prognosis of patients with locally advanced cervical cancer.     

大剂量米非司酮和孕激素联合应用治疗子宫内膜癌的临床研究

目的　研究大剂量米非司酮、大剂量孕激素以及二者联合应用对子宫内膜癌患者的治疗效果 ,并探讨其作用机制。方法　将 3 0例经诊刮确诊的子宫内膜癌患者随机分为 3组 ,每组 10例 ,术前用药 5d。米非司酮组术前用米非司酮 ( 10 0mg d) ,醋酸甲羟孕酮组术前用醋酸甲羟孕酮 ( 50 0mg d) ,联合组术前用米非司酮 ( 10 0mg d)、醋酸甲羟孕酮 ( 50 0mg d)。各组用药前后行自身对照 ,观察癌细胞组织形态学改变及雌激素受体 (ER)、孕激素受体 (PR)、增殖细胞核抗原 (PCNA)、凋亡相关基因 (bcl 2、bax)及CD44 v6基因表达的变化。结果　各组治疗后 ,癌细胞分化均趋向成熟 ,分泌活跃 ,可在癌组织中观察到凋亡的癌细胞 ,联合组治疗后变化最明显。醋酸甲羟孕酮组治疗前后 ,免疫组织化学 (免疫组化 )评分分别为PR( 2 9± 1 1、1 6± 0 8)、ER( 2 8± 0 9、1 4± 0 9)、PCNA( 0 84± 0 11、0 60±0 12 )、bcl 2 ( 0 2 3 6± 0 0 89、0 157± 0 981)和CD44 v6( 4 6± 1 8、2 5± 1 9) ,表达均降低 (所有P <0 0 1) ,bax( 0 2 0± 0 10、0 42± 0 0 7)表达增多 (P <0 0 1)。米非司酮组治疗前后免疫组化评分分别为PR( 3 4± 1 0、1 9± 0 8)、ER( 2 7± 0 9、1 2± 0 7)、PCNA( 0 80± 0 15、0     

Fractionated Palliative Pelvic Radiotherapy as an Effective Modality in the Management of Recurrent/Refractory Epithelial Ovarian Cancers: An Institutional Experience

Background

The advent of effective chemotherapeutic agents for ovarian carcinoma has made radical abdomino-pelvic radiation redundant. Nevertheless, palliative pelvic radiotherapy still has a role in palliating local symptoms. However, its effect on progression-free survival (PFS) may be debated.

Aims

To study the outcome of fractionated palliative pelvic radiotherapy in relapsed ovarian cancers in terms of symptom control and PFS.

Methods

Twenty-three patients of ovarian cancers, heavily pretreated with chemotherapy and with recurrent or residual pelvic masses, were planned for palliative pelvic radiotherapy to the dose of 46–50 Gy in 23–25 fractions in 4.5–5 weeks. Symptom control and outcomes have been analyzed.

Results

Post-radiotherapy, abdominal pain was controlled in 15 out of 17 patients (88.2 %), bleeding per vaginum in all 5 patients and vaginal discharge stopped in 4 out of 5 patients (80 %). On follow-up, of 23 patients, 17 (74 %) had progressive disease post-radiation, and median time to disease progression was 10 months (range 1–49). On univariate analysis, increased PFS was observed in patients who received radiation late in their course of disease, those with serous histology, and with lesser disease bulk in pelvis (≤2 cm) prior to radiation initiation.

Conclusion

Fractionated palliative pelvic radiotherapy is an efficient method for symptom palliation in relapsed ovarian cancers. Patients who are heavily pretreated with chemotherapy and have a small-volume pelvic disease may show a prolonged PFS with addition of pelvic radiotherapy. Indications of radiotherapy, however, need to be defined.

     

HIF-1α与TRAIL-DR4在宫颈癌组织中的表达及与放疗敏感性的研究

目的:研究缺氧诱导因子-1α(HIF-1α)及肿瘤坏死因子相关的凋亡诱导配体(TRAIL)受体在宫颈癌组织中的表达变化,及与放疗敏感性的关系。方法:收集2003年7月至2005年1月宫颈癌活检组织45例,用原位杂交组织化学法检测宫颈癌组织中HIF-1αmRNA及TRAIL-DR4mRNA水平。结果:(1)在45例宫颈癌组织中27例(60%) HIF-1αmRNA呈阳性表达,Ⅰ/Ⅱ期肿瘤HIF-1αmRNA的表达显著低于Ⅲ/Ⅳ期肿瘤的表达(X~2=9．07,P＜0．05),随着组织分化的降低,HIF-1αmRNA的表达增强(X~2=8．03,P＜0．05),放疗敏感患者中HIF-1αmRNA表达明显低于放疗不敏感患者(X~2=10．37,P＜0．05);(2)TRAIL-DR4mRNA阳性表达率为57．8%。Ⅰ/Ⅱ期肿瘤DR4mRNA的表达显著高于Ⅲ/Ⅳ期肿瘤的表达(X~2=9．01,P＜0．05),中高分化宫颈癌的表达明显高于低分化宫颈癌(X~2=18．18,P＜0．05),放疗敏感患者中TRAIL-DR4mRNA表达明显高于放疗不敏感患者(X~2=6．91,PP＜0．05)。结论:HIF-1αmRNA及TRAIL-DR4mRNA与宫颈癌的放疗敏感有相关性。     

同步放化疗治疗中晚期宫颈癌50例临床疗效观察

目的:探讨同步放化疗治疗中晚期宫颈癌的疗效及毒副反应。方法:选择宫颈癌患者100例,随机分为2组,单纯放疗组50例,同步放化疗组50例。两组放疗方法相同,同步放化疗组于放疗前、中及放疗结束后给予CTB(卡铂加吡柔比星加博来霉素)腹壁下动脉灌注化疗,每周期间隔28天,共化疗3周期。比较两组病例近期、远期疗效及毒副反应。结果:同步放化疗组与单纯放疗组近期有效率分别为96%、72%,(P<0.05),同步放化疗组与单纯放疗组的5年生存率分别为64%、44%,(P<0.05),同步放化疗组骨髓抑制及消化道反应发生率均高于单纯放疗组(P<0.05),及时对症治疗后,患者均可耐受治疗。结论:同步放化疗治疗中晚期宫颈癌可提高近期疗效及5年生存率。以铂类为基础的化疗疗效肯定,患者能耐受,与放疗联合应用安全、合理。     

Postoperative adjuvant concurrent chemoradiotherapy improves survival rates for high-risk, early stage cervical cancer patients

OBJECTIVE: This study was undertaken to evaluate the efficacy of postoperative concurrent chemoradiotherapy (CCRT) and to investigate the recurrence and survival rates after adjuvant CCRT in high-risk early cervical cancer (stages IA2, IB, IIA) patients who were treated by radical hysterectomy and pelvic lymphadenectomy. METHODS: From July 1994 to June 2001, we retrospectively reviewed the medical records of 151 patients who had undergone radical abdominal hysterectomy with pelvic lymphadenectomy and paraaortic lymph nodes dissection at Ajou University Hospital for early cervical cancer (stages IA2, IB, IIA). CCRT was performed in 30 patients with high-risk factors such as positive pelvic lymph nodes, parametrial involvement, or positive surgical margins. Adjuvant chemotherapy consisted of cisplatin (70 mg/m(2) on day 1) and 5-fluorouracil (5-FU; 1000 mg/m(2) on days 2-5) for four cycles every 4 weeks beginning 2-3 weeks after surgery. Pelvic radiotherapy was started concurrently at the second and third cycle of chemotherapy. We also analyzed the recurrence pattern and survival rates of 114 patients (control group) who received no adjuvant therapy after surgery. The mean follow-up period was 49 months (24-98 months). RESULTS: There were recurrences in three patients after CCRT (10%) and in five patients in the control group (4.4%). The actuarial 5-year overall survival rates for patients in CCRT and control group were 96.7% vs. 97.7%, respectively. The progression-free survival rates were 88.7% for the high-risk group and 95.4% for the non-high-risk group. CONCLUSIONS: This study confirms good local control and 5-year overall and progression-free survival rates in high-risk cervical cancer patients after CCRT, which is comparable with the results of the control group. Our results indicate that adjuvant concurrent chemoradiotherapy seems to be effective in stages IA2-IIA cervical cancer patients with high-risk factors.     

Low-risk endometrial carcinoma: assessment of a treatment policy based on tumor ploidy and identification of additional prognostic indicators.

OBJECTIVES: The aims of this study were (1) to assess a treatment policy for patients with low-risk endometrioid endometrial carcinoma where adjuvant treatment decisions have been based on ploidy status of the tumor, and (2) to screen diploid, low-risk tumors for additional features of prognostic significance. METHODS: Between 01/1992 and 08/1996, 406 patients were referred to the B.C. Cancer Agency-Vancouver Clinic with typical endometrial adenocarcinomas limited to <50% myometrial invasion and no vascular space invasion or grade 3 disease on pathology review ("low-risk stage I endometrial carcinoma"). Patients were prospectively assigned to treatment groups based on tumor ploidy. Those patients with aneuploid tumors (n = 91) were treated with adjuvant vaginal vault radiotherapy while those with diploid tumors (n = 315) were followed and treated only at relapse. The hysterectomy specimens from all 14 patients in the untreated, diploid group who relapsed, as well as 28 stage- and grade-matched diploid controls who did not fail, were analyzed by immunohistochemical staining for estrogen receptor (ER), Bcl-2, and p53 proteins. RESULTS: There were no significant differences in the stage (Ia vs Ib) and grade (G1 vs G2) distribution for the diploid and aneuploid groups. Overall median age was 64 years (range 27-90 years) and was also not significantly different for the two groups. The median follow-up for the entire cohort is 45 months (range 1-76 months). There have been 14 failures in the diploid group and 4 failures in the aneuploid group with actuarial 5-year disease-free survival rates of 95.0 and 95.2%, respectively (P = NS). Eight of the failures in the diploid group occurred at the vaginal vault and were all subsequently salvaged with radiotherapy. All but 1 of the failures in the aneuploid group were considered incurable. Of the 14 diploid tumors from patients who failed, 7 stained positively for p53, compared to 4 of 28 diploid controls (P = 0.02). No significant differences were seen in the diploid tumors that recurred, compared to controls, with respect to Bcl-2 or ER expression. CONCLUSIONS: Patients with diploid, low-risk stage I endometrial cancers have excellent prospects for relapse-free and overall survival. Patients with aneuploid tumors treated with adjuvant radiotherapy have the same risk of relapse as untreated patients with diploid tumors; however, their ultimate survival may be lower as a smaller proportion of aneuploid failures are salvageable. While p53 expression in diploid tumors is associated with increased risk of relapse, Bcl-2 and ER are not useful prognostic indicators in this setting.     

妊娠滋养细胞疾病Cyclin B1、PCNA表达的研究

目的 :检测CyclinB1和增殖细胞核抗原 (PCNA)蛋白在妊娠滋养细胞疾病(GTD)中的表达 ,探讨二者的相关性及与GTD的关系。方法 :采用免疫组化S P法检测 1 5例正常绒毛、38例葡萄胎 (HM)、42例侵蚀性葡萄胎 (IM)和 1 8例绒毛膜癌 (CC)组织中Cy clinB1和PCNA蛋白表达情况。结果 :葡萄胎、IM、CC组织中的CyclinB1和PCNA蛋白表达水平显著高于正常绒毛。术前未化疗的IM和CC组织中CyclinB1的表达水平明显高于葡萄胎。CC组织PCNA的表达水平高于葡萄胎 (P =0 .0 0 5)。葡萄胎恶变者CyclinB1和PCNA的表达显著高于未恶变者。术前未化疗的滋养细胞肿瘤患者 (包括IM和CC)Cy clinB1表达显著高于术前化疗≥3疗程者 (P =0 .0 0 2 )。WHO预后评分为高危者及中危者的CyclinB1表达显著高于低危者 (P =0 .0 0 5)。PCNA的表达与滋养细胞肿瘤是否化疗、WHO分期、WHO评分无关。PCNA与CyclinB1的表达呈正相关 (P =0 .0 0 0 )。结论 :GTD中存在CyclinB1的调节紊乱 ,CyclinB1异常表达可能与葡萄胎滋养细胞的增生、恶变及滋养细胞肿瘤的恶性生物学行为有关