Mechanism of drug resistance and reversal with ligustra-zine and cyclosporin A in cisplatin--inducedhuman epithelial ovarian cancer resistant cell line 3Ao/cDDP

Objective: To investigate the mechanism of resistance and reversal effect of ligustrazine and cyclosporin A in cisplatin--induced multidrug resistance ovarian cancer cell line 3Ao/cDDP. Methods: Using the corresponding dose calculated from clinical chemotherapy at 30 mg cisplatin per cycle, we established 3Ao/cDDP with 3Ao exposed at regular intervals and repeatedly to high-level concentration of cisplatin at 10 mg/ml for 24 hours each time. Expressions of LRP, MRP, P-gp, GSTp and TopoII were quantitatively detected with FCM. For drug resistance reversal, cyclosporin A and ligustrazine were administered singly or in combination at the maximal dose without cytotoxicity. Inhibition rates were determined by MTT assay. Results: 3Ao/cDDP was established after 4.5 months, with resistance factor 1.6 which was similar to clinical resistance degree. Low expression levels of MRP and P-gp were found in both 3Ao and 3Ao/cDDP (P>0.05), and LRP and GSTp expression levels in 3Ao/cDDP were significantly higher than those in 3Ao (P<0.005 and P<0.05, respectively), and TopoII in 3Ao/cDDP was significantly lower vs 3Ao (P<0.05). The inhibition rate of cDDP was 20.807±0.015%, cDDP plus ligustrazine 27.421±0.07% (P>0.05 vs cDDP), cDDP plus cyclosporin A 49.635±0.021% (P<0.01 vs cDDP), and cDDP plus ligustrazine and cyclosporin A 58.861±0.014% (P<0.01 vs cDDP). Conclusions: 3Ao/cDDP, induced by cisplatin and established by imitating the characteristics of clinical chemotherapy for epithelial ovarian cancer, was an ideal model for investigation of cisplatin resistance in vitro. Cisplatin resistance in 3Ao/cDDP could be accounted for by higher LRP, GSTp and lower TopoII expression and was not associated with MRP or P-gp. Ligustrazine had no significant reversal effect on cisplatin resistance, but cyclosporin A could reverse the resistance effectively.

SCREENING OF DRUG RESISTANCE-RELATED GENES FROM HUMAN OVARIAN CANCER CELL LINE OC3/ADR BY DD-PCR

Objective: To screen novel genes related to adriamycin (Adr) resistance from human ovarian cancer resistance cell line OC3/Adr. Methods: Multidrug resistant ovarian cancer cell line OC3/Adr was induced by intermittent treatment of the human parent cell line OC3 with high concentration Adr. The difference of gene expression was screened by using different display analysis to the acquired Adr-resistance subline OC3/Adr and its parent cell line OC3. Results: OC3/Adr cell line was obtained which was more resistance to Adr than the parent cell line OC3 with the resistance index (RI) of 15.4. The OC3/Adr cell line also showed cross-resistance to other anti-cancer drugs (VP16, CDDP,5FU). It grew slowly and exhibited changes of cell cycle. A number of differentially expressed ESTs (Expressed Sequence Tags, ESTs) were identified at mRNA level between the OC3/Adr and OC3. Four of 18 different ESTs were sequenced. The 431/432 base pair S1 was homologous to human sperm zona pellucida binding protein, while the other two ESTs, S3 and S4, were new gene segments, which were registered to GenBank with the number of AF 117656 and AF 126507 respectively. Particularly, the expression of S2 sequence increased in all the drug-resistance cell lines and S3 sequence overexpressed in human ovarian cancer tissues as compared with benign ovarian tumors. Conclusion: Drug resistance induced by Adr in ovarian cancer OC3/Adr is involved with changes of multiple gene expressions.

Surgery in platinum-resistant recurrent epithelial ovarian carcinoma

BACKGROUND Ovarian cancer is one of the three most common malignant tumors of the female reproductive tract and ranks first in terms of mortality among gynecological tumors.Epithelial ovarian carcinoma(EOC)is the most common ovarian malignancy,accounting for 90%of all primary ovarian tumors.The clinical value of cytoreductive surgery in patients with platinum-resistant recurrent EOC remains largely unclear.AIM To evaluate the feasibility of secondary cytoreductive surgery for treating platinum-resistant recurrent EOC.METHODS This was a retrospective study of the clinical data of patients with platinumresistant EOC admitted to the Cancer Hospital of the University of Chinese Academy of Sciences between September 2012 and June 2018.Patient baseline data were obtained from clinical records.Routine follow-up of disease progression was performed as follows.CA125 assessment and physical examination were performed every 3 wk during treatment,including gynecological examination.Imaging assessment was carried out every 12 wk by B-mode ultrasound,computed tomography,or magnetic resonance imaging.The primary outcome was progression-free survival(PFS).Secondary outcomes included overall survival(OS),chemotherapy-free interval(CFI),and complications.Follow-up ended on April 15,2019.RESULTS A total of 38 patients were included.R0 resection was achieved in 25(65.8%) patients and R1/2 in 13 (34.2%). Twenty-five (65.8%) patients required organ resection. Nine(23.7%) patients had operative complications, 36 (94.7%) received chemotherapy, and five (13.2%)had targeted therapy. Median PFS and OS were 10 (95%CI: 8.27-11.73) months and 28 (95%CI:12.75-43.25) months, respectively;median CFI was 9 (95%CI: 8.06-9.94) months. R0 resection andpostoperative chemotherapy significantly prolonged PFS and OS (all P < 0.05), and R0 resectionalso significantly prolonged CFI (P < 0.05). Grade ≥ 3 complications were observed, includingrectovaginal fistula (n = 1), intestinal and urinary fistulas (n = 1), and renal failure-associated death(n = 1). Except for the patient who died after surgery, all other patients with complications weresuccessfully managed. Two patients developed intestinal obstruction and showed improvementafter conservative treatment.CONCLUSIONSecondary cytoreductive surgery is feasible for treating platinum-resistant recurrent EOC. Thesefindings provide important references for the selection of clinical therapeutic regimens.

DIFFERENTIAL EXPRESSION OF ADHESION MOLECULES (CD44,CD29,ICAM-1 AND E-CADHERIN) IN OVARIAN CANCER SK-OV-3ip1 CELLS GROWN AS MONOLAYER AND MULTICELLULAR AGGREGATES

Objective: To detect mRNA levels and expression ofCD44, CD54, CD29 and E-cadherin (E-cad) and to discuss their relationship with formation and drug resistance ofovarian cancer SKOV3ip1 multicellular aggregates.Methods: Liquid overlay system was employed to obtainmulticellular aggregates. mRNA levels and expression ofCD44, CD54, CD29 and E-cad were investigated with RTPCR and flow cytometry (FCM) respectively. Results:Compared with monolayer cells, RT-PCR results showed a decrease in CD44 mRNA level by 0.626-fold and a decrease in CD29 mRNA level by 0.792-fold in multicellularaggregates. However, an increase in CD54 mRNA level by 1.815-fold and an increase in E-cadherin mRNA level by1.344-fold were found in multicellular aggregates. Theresults revealed the downregulation of CD44 and CD29 and the upregulation of CD54 and E-cad genes activity. CD44 expression in monolayer cells and multicellular aggregates were 75.995?.046 and 50.700?.351 (%) respectively andthere was a significant decrease in multicellular aggregates (P=0.001). Compared with control cells, no expression of CD54 was detected in monolayer cells (P=0.563) but markedly elevated CD54 expression was detected in multicellular aggregates (15.780?.217) (%) (P<0.01). High expression of CD29 was seen in monolayer cells and also in multicellular aggregates with positive rates of 96.290+1.201 (%) and 92.494?.055 (%). However, the expression of CD29 in multicellular aggregates was significantly reduced (P=0.014). Also no expression of E-cadherin was found in monolayer cells compared with control cells (4.490?.283) (%) (P=0.65) while significantly increased expression in aggregates cells (17.258?5.572) (%) (P=0.003) was observed. Conclusion: Significant differences in mRNA levels and expression of CD44, CD54, CD29 and E-cadherin clearly exist between monolayer cells and multicellular aggregates, which may be associated with the formation of multicellular aggregates and its drug resistance.

MULTICELLULAR-MEDIATED RESISTANCE TO CISPLATIN AND TAXOL IN HUMAN OVARIAN CANCER SK-OV-3IP1 MULTICELLULAR AGGREGATES

Objective: To investigate the chemosensitivity of ovarian cancer SK-OV-3ip1 multicellular aggregates (MCA) to cisplatin and taxol and to explore the possible mechanisms. Methods: Liquid overlay system was employed to obtain MCA. We detected the resistance using trypan blue exclusion testing, clonogenic assay, cell cycle profiles and apoptosis with flow cytometry (FCM). Results: After cisplatin exposure, MCA cells showed nearly equal cell viability with monolayer cells (P=0.05). After 40μM cisplatin exposure for 12 h, no clone (≥50 cells) was formed, but more viable cells attached to the bottom of 24-well plate in MCA group than monolayer. Furthermore, apoptosis rate and cell cycle profiles with FCM had no significant change between MCA and monolayer cells. After taxol exposure, however, trypan blue exclusion testing demonstrated higher cell viability in MCA cells (P=0.003) and higher clone formation rate in 100-cell group than monolayer cells (0.01<P<0.025). No significant difference was found in 50-cell or 200-cell group but more viable cells in MCA group were observed. Taxol exposure caused significantly decreased apoptosis rate in MCA cells than monolayer cells (P=0.012). Taxol induced significant cell arrest at G2-M phase in monolayer cells (P=0.001), but abrogation of G2-M arrest was observed in MCA cells (P=0.002). Conclusion: Compared with monolayer cells, MCA cells from the same SK-OV-3ip1 cell line appear to be more resistant to taxol but not to cisplatin. Cell cycle redistribution and multicellular-mediated inhibition of apoptosis can partially account for the resistance.

MULTICELLULAR-MEDIATED EXPRESSION OF P-GP AND MRP AND RELATIONSHIP WITH CELL CYCLE PROFILES IN HUMAN OVARIAN CANCER SK-OV-3ip1 MULTICELLULAR AGGREGATES

Objective: To investigate the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP) and the relationship with cell cycle profiles in ovarian cancer SK-OV-3ip1 multicellular aggregates. Methods: Liquid overlay system was employed to obtain multicellular aggregates. Expression of P-gp and MRP was detected with flow cytometry (FCM). Outer, intermediate and inner cells from multicellular aggregates were collected by layer-trypsinized method. Cell cycle profiles were also analyzed by FCM. Results: Compared with control cells, no expression of P-gp and MRP was detected in monolyer cells (P=0.128 and P=0.604), but expression of P-gp and MRP in aggregate cells was significantly elevated (P<0.01). P-gp expression in every layer cells was also obviously increased (P<0.01). Furthermore, P-gp expression in every layer cells was also obviously increased (P=0.071). Tendency to increased G0–G1 phase and reduced S phase cells existed from outer through intermediate to inner layers in multicellular aggregates but with no statistical difference. Cell percentages in G2-M phase also had no difference. However, compared with monolayer cells, cells in G0–G1 phase increased and cells in S and G2-M phases lowered significantly in every layer and in the whole multicellular aggregates. Expression elevation of P-gp and MRP was consistent with increased G0–G1 percentage in aggregate cells. Conclusion: Expression of P-gp and MRP increases in cells of SK-OV-3ip1 multicellular aggregates and is consistent with increased G0–G1 percentage, which implies the possible relationship between them and the possible role in multicellular-mediated drug resistance.

WHAT SHOULD BE KEPT IN MIND FOR MANAGEMENT OF THE TOXIC SIDE-EFFECTS INDUCED BY POSTOPERATIVE CHEMO-AND RADIOTHERAPY FOR OVARIAN TUMOR?

Ovarian tumor may occur in women ofany age, but mostly seen in women duringtheir child-bearing period. The disease shouldbe treated mainly by surgical operation,supplemented by radiotherapy and chemo-therapy. However, the above therapies maycause a series of toxic side-effects, such asalopecia, diarrhea, edema, anorexia, nausea,dry mouth, spontaneous perspiration, headache,

Toxicity of Paclitaxel and Cisplatin in Combination for Advanced Ovarian Cancer

Objective:To evaluate the toxicity of paclitaxel and cisplatin combination in patients with advanced ovarian cancer.Methods:A retrospective review was performed on patients with stage Ⅲ or stage Ⅳ ovarian cancer treated in QiLu hospital between October 1996 and June 1999 Results:26 patients received adjuvant paclitaxel and cisplatin chemotherapy.The significant toxicity included:anemia 7/26(27%),thrombocytopenia 10/26(38%),neutropenia 19/26(73%),nausea or vomiting 24/26(92%) and neurotoxicity 11/26(42%).No patient delayed.No patient died during treatment.Conclusion:The dosages of primary paclitaxel and cisplatin chemotherapy is reasonably well tolerated for patients with stage Ⅲ or Ⅳ ovarian cancer.

卵巢癌化疗耐药预测模型的建立及效果评价

目的探讨卵巢癌患者术后化疗发生耐药的影响因素,构建预测模型并评价模型效能。方法收集经肿瘤细胞减灭术及化疗的407例卵巢癌患者的临床资料,至随访终点根据是否复发分为复发组363例和未复发组44例,其中复发组根据化疗耐药将其分为耐药组59例和敏感组304例。使用单因素分析和Lasso回归筛选变量,建立Logistic模型,用R软件建立列线图并进行评价。结果与未复发组比较,复发组年龄偏低,低分化比例及FIGO分期Ⅲ—Ⅳ期比例较高(P<0.05)。与敏感组比较,耐药组淋巴结增大、病理类型为非浆液性、FIGO分期Ⅲ—Ⅳ期比例、肿瘤组织免疫组化重组蛋白Ki-67(Ki-67)、蛋白53(P53)、血管内皮生长因子(VEGF)及肾母细胞瘤基因1(WT-1)阳性率较高,手术前后糖类抗原125(CA125)变化率、化疗前后罗马指数(绝经前)变化率及免疫组化蛋白16(P16)阳性率较低(P<0.05)。以Lasso回归筛选出的8个自变量进行Logistic回归,结果显示:术前全腹增强CT有淋巴结增大、病理类型为非浆液性、FIGO分期Ⅲ—Ⅳ期、免疫组化WT1、VEGF阳性,P16阴性是卵巢癌患者发生化疗耐药的独立危险因素。据此建立的列线图模型受试者工作特征曲线下面积为0.837(0.783~0.880),Hosmer-Lemeshow检验结果示模型拟合优度较好,校准曲线及临床决策曲线提示模型有较高的校准度及临床使用度。结论根据临床数据成功构建了卵巢癌化疗耐药Logistic模型,据此建立的列线图预测模型可有效评估卵巢癌患者发生化疗耐药的风险。

血流向量成像技术评估卵巢癌术后化疗后左心室舒张功能

目的观察血流向量成像(VFM)技术评估卵巢癌(OC)术后化学治疗(简称化疗)后左心室舒张功能改变的价值。方法前瞻性以37例OC术后接受化疗患者为化疗组,以同期40名健康成人为对照组。对化疗组分别于化疗前、化疗3及6个周期后,对照组于入组时行常规超声心动图及VFM检查,比较化疗前组间及化疗组内不同时间点资料,分析化疗组VFM与血红蛋白及常规超声心动图结果的相关性。结果化疗组年龄、体质量、体表面积(BSA),化疗前血红蛋白水平、常规超声心动图及VFM结果与对照组差异均无统计学意义(P均>0.05)。化疗组内,随化疗周期增加,血红蛋白水平渐次降低、等容舒张期(IR)及心房收缩期(AS)左心室内压力差(IVPD)及压力差梯度(IVPG)逐渐增大(校正P均<0.05);而常规超声心动图仅化疗6个周期后左心房容积指数(LAVI)及二尖瓣舒张早期血流峰值速度/二尖瓣环舒张早期平均运动峰值速度(E/e’)较化疗前升高(校正P均<0.05)。化疗组舒张期各时相VFM结果均与血红蛋白水平呈强相关(|r|=0.718~0.836,P均<0.05),与LAVI呈弱至中度相关(|r|=0.375~0.525,P均<0.05),与E/e’呈中度相关(|r|=0.424~0.537,P均<0.05)。结论OC术后化疗早期即可出现左心室舒张功能受损。VFM可较常规超声心动图更敏感地检出左心室舒张早期功能轻微改变。

PARP抑制剂在上皮性卵巢癌中的耐药机制及解决策略

上皮性卵巢癌(epithelial ovarian cancer,EOC)的致死率在女性生殖系统恶性肿瘤中居首位。EOC的传统治疗方案是肿瘤细胞减灭术联合铂类药物为基础的化疗,但2年内仍有约70%的患者复发或耐药。多腺苷二磷酸核糖聚合酶[poly(ADP-ribose)polymerase,PARP]抑制剂通过对乳腺癌相关基因(breast cancer-related gene,BRCA)突变的肿瘤细胞发挥合成致死效应,为EOC提供了全新的治疗模式。PARP抑制剂为EOC靶向维持治疗带来重大突破,然而仍有患者在治疗中逐步耐药,主要的耐药机制包括同源重组修复途径恢复、药物靶点变化和致死性DNA损伤减少,目前的解决策略包括PARP抑制剂联合DNA损伤修复抑制剂、联合抑制同源重组修复通路的药物、联合传统抗癌方案、联合P-糖蛋白(P-glucoprotein,P-gp)抑制剂以及更换其他类型的PARP抑制剂。

乳腺癌易感基因联合癌抗原125动态监测在预测晚期上皮性卵巢癌病人铂敏感性及预后中的价值

目的评估胚系乳腺癌易感基因(BRCA)联合动态监测血清癌抗原125(CA125)在晚期上皮性卵巢癌(EOC)病人初治铂敏感性预测及判断预后中的价值。方法收集并回顾性分析2017年1月至2020年1月在蚌埠医学院第一附属医院行满意减瘤术且术后采用TC(紫杉醇+卡铂)/TP(紫杉醇+顺铂)方案静脉化疗的EOC病人151例的临床病理资料。分析胚系BRCA与EOC病人临床病理特征之间的关系;计算曲线下面积(AUC)值等评估胚系BRCA、治疗早期血清CA125水平及两者联合预测晚期EOC病人初治铂敏感性的效能;分析胚系BRCA、治疗早期血清CA125与晚期EOC病人无进展生存期(PFS)的关系;并对所有EOC病人的PFS进行多因素生存分析。结果胚系BRCA致病突变率为28.5%(43/151)。胚系BRCA与确诊年龄、治疗前血清CA125、遗传性乳腺癌和卵巢癌(HBOC)家族史等具有相关性(P<0.05);胚系BRCA、第一周期化疗后血清CA125单独预测晚期EOC病人初治铂敏感性的AUC为0.63、0.76;胚系BRCA与第一周期化疗后血清CA125串联预测晚期EOC病人初治铂敏感性的效能最高,AUC为0.79,95%CI:(0.69,0.90),灵敏度为69.7%,特异度为89.2%;在晚期EOC病人中,BRCA野生型+第一周期化疗后CA125>35 U/mL组病人的PFS生存曲线显著低于BRCA突变型+第一周期化疗后CA125≤35 U/mL组、BRCA突变型+第一周期化疗后CA125>35 U/mL组、BRCA野生型+第一周期化疗后CA125≤35 U/mL组(P=0.013、0.007、0.003)。多因素Cox回归分析显示第一周期化疗后血清CA125水平是EOC病人肿瘤无进展生存时间(PFS)的独立预后因素。结论胚系BRCA联合血清CA125动态监测对晚期EOC病人铂敏感性及预后有一定的预测价值。胚系BRCA野生型且第一周期化疗后血清CA125水平未正常提示EOC病人铂耐药及易复发的风险高。

微流控技术在卵巢癌疾病建模、药物评估、精准医疗中的应用

卵巢癌是全球第三大常见的女性生殖系统恶性肿瘤,5年生存率仅为40%,早期诊断手段的缺乏和化疗耐药是目前卵巢癌诊疗面临的巨大的挑战。微流控技术(microfluidic technology)作为一种利用微芯片调控流体流动实现的集成化分析技术,具有高敏感度、高通量和低成本等显著优势,而且,该技术能在微纳尺度下模拟肿瘤微环境,有利于研究肿瘤细胞与免疫系统的交互作用。近年来微流控技术已广泛用于医学研究、药物研发、精准医疗等生命健康领域。在卵巢癌研究方面,微流控技术可用于肿瘤建模、早期肿瘤生物标志物的检测和抗肿瘤药物的筛选等,为卵巢癌早期诊断和精准治疗提供了创新视角与未来导向。

卵巢癌铂耐药及其治疗研究进展

卵巢癌是恶性程度最高的妇科恶性肿瘤之一。以铂为基础的化疗是卵巢癌治疗的重要组成部分,因此铂耐药也是卵巢癌治疗中棘手的问题。铂耐药是一个复杂的过程,涉及多种机制。本文就卵巢癌细胞铂耐药的分子机制及治疗进展作一综述,以期为该病的临床治疗提供借鉴。

雄黄对荷人卵巢癌裸鼠移植瘤细胞凋亡的基础研究

目的:观察中药雄黄诱导卵巢癌细胞凋亡及血管生成的作用。方法:应用流式细胞术、荧光显微镜、透射电子显微镜和免疫组织化学等技术,以细胞凋亡和VEGF为主要观测指标,观察中药雄黄对荷人卵巢癌裸鼠移植瘤抗肿瘤作用。结果:雄黄可诱导荷人卵巢癌裸鼠移植瘤细胞凋亡,抑制荷瘤裸鼠肿瘤的生长,阻止血管生成抑制细胞DNA的合成,并可延长小鼠存活时间。结论:雄黄可通过诱导卵巢癌细胞凋亡,阻止血管生成,抑制细胞DNA的合成等多种途径发挥抗肿瘤作用,具有广阔的应用前景。

三氧化二砷对人卵巢癌耐药细胞株细胞增殖和转移能力的影响

背景与目的:卵巢恶性肿瘤细胞对顺铂的耐药性及早期发生转移严重影响着卵巢恶性肿瘤患者的化疗效果。本研究探讨三氧化二砷(arsenictrioxide,As2O3)对人卵巢癌耐药细胞株3AO/cDDP细胞增殖和转移能力的影响及其机制。方法:采用四甲基偶氮唑蓝(MTT)法检测不同浓度As2O3对3AO/cDDP细胞的生长抑制率;采用流式细胞技术(FCM)检测As2O3对细胞凋亡率、细胞周期以及Fas、N-myc基因和nm23H1、MTA1基因表达的影响。所有结果均与对照组比较。采用透射电镜技术观察As2O3作用后3AO/cDDP细胞的形态变化。结果:As2O3明显抑制3AO/cDDP细胞的增殖,抑制作用呈时间和剂量依赖性(P<0.05)。在一定浓度范围内,3AO/cDDP细胞凋亡率与As2O3的浓度和作用时间呈依赖关系,诱导凋亡的最适浓度是3μmol/L。低浓度As2O3作用下,3AO/cDDP细胞周期S期通过受阻,高浓度时诱导S期细胞凋亡;As2O3作用后,两种细胞株Fas和nm23H1基因的表达均上调,N-myc和MTA1基因的表达均下调,差异均有显著性(P>0.05);形态学观察可看到As2O3作用后3AO/cDDP形成典型的凋亡小体。结论:As2O3通过上调Fas、nm23H1和下调N-myc、MTA1基因的表达,有效地降低人卵巢癌耐药细胞株细胞的增殖和转移能力。

复发性卵巢癌的化放疗研究

目的：分析化疗结合放疗对复发性卵巢癌治疗的疗效。方法：30例复发性卵巢癌采用铂类或紫杉醇为主的二线化疗，并根据患者肿瘤复发部位或再次手术后腹盆腔内残留病灶选用盆腔或全腹放疗。结果：平均二线化疗7个（3—14）个疗程，20例患者二线化疗后获临床完全缓解。21例患者接受了再次肿瘤细胞减灭术，16例术后残留病灶≤1cm。二线化疗期间结合放疗，23例行盆腔放疗，平均总量42．2（30．0～45．12）Gy，7例行全腹分段超分割放疗，平均总量30．2（29．96～31．2）Gy，其中4例盆腔加量至45．1（44．98～45．12）Gy。平均随访41．0个月，中位总生存时间57．0个月，患者3年、5年总生存率分别为73．33％、46．67％。复发后中位生存时间38．9个月，复发后3年生存率达56．34％。单因素和多因素分析结果提示二线化疗疗效（HR=0．26，P〈0．01）和停铂化疗间期（HR=-0．21，P〈0．01）影响复发患者的总生存期，二线化疗也是决定患者复发后生存期的独立因素（HR=0．25，P〈0．01）。结论：二线化疗是决定复发性卵巢癌生存期的重要因素，在二线化疗的基础上配合盆腔或全腹放疗可延长患者的生存期，特别是在二线化疗达临床缓解后加用放疗可提高腹盆腔局部肿瘤控制率，延缓肿瘤的再复发。

ER和MDM2及ERK1／2信号通路与卵巢癌耐药关系的研究

目的:探讨ER、MDM2和ERK1/2信号通路在卵巢癌中的相关性及与卵巢癌耐药的关系。方法:采用免疫组织化学SP法检测40例卵巢癌标本中ER、MDM2及P-糖蛋白(P-gp)的表达水平;采用MTT比色分析法检测该40例标本对紫杉醇(PTX)、表柔比星(EADM)、顺铂(DDP)和卡铂(CBP)的药物敏感性;通过酶活性测定,检测ERK1/2酶活性。结果:PTX和EADM耐药者ERK1/2酶活性分别增高1.5倍,P值分别为0.015和0.004;ERK1/2酶活性与PTX和EADM的抑制率负相关,r分别为-0.531和-0.488,P<0.01;ER和MDM2不同表达水平间ERK1/2酶活性差异均有统计学意义,P值分别为0.001和0.034;P-gp阳性组ERK1/2酶活性是阴性组的1.4倍,P=0.022;P-gp阴性组PTX和EADM的抑制率分别是阳性组的1.5和2.0倍,P值分别为0.021和0.004;P-gp与MDM2的表达正相关,r=0.396,P<0.05;MDM2不同表达水平,PTX和EADM抑制率的差异有统计学意义,P值分别为0.024和0.039;ER与MDM2的表达正相关,r=0.671,P<0.01;DDP和CBP在本实验中差异无统计学意义。结论:ER、MDM2及ERK1/2激酶活性之间存在正相关性;ERK1/2激酶活性和MDM2的表达均与P-gp的表达正相关;卵巢癌PTX和EADM耐药的产生与ERK1/2酶活性的升高和P-gp及MDM2表达的增强有关。

新辅助化疗联合手术治疗晚期卵巢癌近期及远期疗效观察

目的探讨新辅助化疗联合手术治疗在治疗晚期卵巢癌中的作用和疗效。方法选择60例晚期卵巢癌患者作为研究对象,按照不同治疗方法分为两组,30例患者[新辅助化疗组(NACT)组]采用新辅助化疗,然后进行肿瘤减灭术;另外30例患者(对照组)首先行肿瘤减灭术,再行化疗。结果 NACT组理想肿瘤减灭率为73.3%,对照组为36.7%,两组比较差异有统计学意义(P<0.05);NACT组术中出血量及手术时间较对照组少(短),两组比较差异有统计学意义(P<0.05);合并脏器切除率分别为16.7%和20.0%,并发症发生率为13.3%和20.0%,组间比较差异无统计学意义(P>0.05);新辅助化疗组的中位生存时间(37月)较先期手术组(30月)长,1年生存率分别为90.0%和83.3%(P>0.05),3年生存率分别为50.0%和26.7%(P>0.05)。结论对晚期卵巢癌患者行新辅助化疗有助于提高患者的手术效果和近期生存率,具有较好的临床安全性。

国产紫杉醇对晚期卵巢癌患者腹腔化疗药代动力学的研究

目的：研究国产紫杉醇腹腔用药的药代动力学及其副作用。方法：对８例初治晚期卵巢上皮性癌应用国产紫杉醇１７５ｍｇ／ｍ２作腹腔化疗，３ｗ１次，观察副作用。对其中６例进行药代动力学研究，在用药前、后取腹水及血浆测定紫杉醇的药物浓度，测定药代动力学参数。结果：腹水中的药物浓度及浓度—时间曲线下面积远高于血浆中的相应情况。紫杉醇代谢模型为二室型，具有药代动力学优势。其副作用主要是骨髓抑制及腹痛，但较静脉用药的副作用小。结论：国产紫杉醇腹腔用药具有药代动力学优势，副作用小。