BRCA基因在上皮性卵巢癌中的研究进展

卵巢癌(ovarian carcinoma,OC)是女性患病率和致死率相对较高的肿瘤,其中上皮性卵巢癌(epithelial ovarian cancer,EOC)诊断率明显高于其他类型的OC。EOC的产生与乳腺癌易感基因(breastcancer susceptibility gene,BRCA)有明显的关联性。BRCA基因是一种恶性肿瘤易感基因,可以调整DNA损伤修补,保持细胞生长和细胞凋亡,保持细胞基因遗传稳定性。BRCA基因突变会明显增加患EOC风险,与此同时,BRCA基因影响着EOC的临床诊治、病理和愈后等。具备BRCA基因突变的EOC(BMOC)对铂类DNA损伤剂以及聚腺苷二磷酸核糖聚合酶抑制剂(PARPi)治疗更加敏感。临床上以BRCA基因为主对卵巢癌患者进行多基因检验,可以为卵巢癌的发病机制、风险评价、治疗和愈后提供临床基础。融合最新研究成果,文中就BRCA基因的基本情况以及BRCA基因与上皮性卵巢癌具体关联性作一具体综述。     

超声引导下穿刺活检在卵巢癌诊断中的应用价值

目的探讨超声引导下穿刺活检在卵巢癌诊断中的应用价值。方法对69例常规影像学检查发现附件区包块、怀疑卵巢癌的患者进行超声引导下穿刺活检,并对其临床资料进行回顾性分析。穿刺后有29例患者进行手术治疗,将穿刺病理结果与手术病理结果相比较。结果 69例穿刺患者中,62例诊断为卵巢癌(原发卵巢癌46例、继发卵巢癌12例),3例为良性病变,4例未获得病理结果。其中29例患者进行手术,穿刺病理结果与手术病理结果符合率89.7%。1例患者出现穿刺部位短时间明显疼痛,余患者无明显不良反应。结论超声引导下穿刺活检方法简单、安全、准确,在严格掌握适应证的情况下,可用于卵巢癌的诊断及鉴别诊断。     

卵巢癌患者与健康者的C型行为特征问卷调查

探讨卵巢癌发病与行为特征的关系,寻求进行干预的可能性。对68例经临床、影像学、病理学确诊的卵巢癌患者(卵巢癌组)进行了C型行为特征问卷测评,其结果与68例健康人(对照组)比较。卵巢癌患者中的焦虑、抑郁、愤怒、愤怒向内、愤怒向外、社会支持评分明显高于对照组。提示卵巢癌患者个体行为特征与发病有密切联系。     

复发卵巢癌再次细胞减灭术的价值

原发性卵巢癌标准治疗方案是初次肿瘤细胞减灭术和以顺铂为基础的联合化疗。理想的初次肿瘤细胞减灭术能暂时阻断肿瘤的自然进程并提高对一线化疗的敏感性,从而提高5年生存率。但晚期卵巢癌(Ⅲ～Ⅳ期)患者,经过首次系统治疗,临床症状消失,且体格、血清学和影像学检查全部阴性者,复发率仍>80%[1]。卵巢癌的复发是当今治疗的难点之一,再次手术对复发卵巢癌是否有积极的治疗价值尚有不同的观点。本文将综述复发卵巢癌的临床特点,复发卵巢癌手术的理论基础和手术范围,以及手术的临床价值及对预后的影响。1复发卵巢癌的部位及特点卵巢癌患者在接…     

卵巢癌患者与健康者的C型行为特征问卷调查

探讨卵巢癌发病与行为特征的关系，寻求进行干预的可能性。对68例经临床、影像学、病理学确诊的卵巢癌患者(卵巢癌组)进行了C型行为特征问卷测评，其结果与68例健康人(对照组)比较。卵巢癌患者中的焦虑、抑郁、愤怒、愤怒向内、愤怒向外、社会支持评分明显高于对照组。提示卵巢癌患者个体行为特征与发病有密切联系。     

18F-FDG PET/CT在卵巢癌转移和复发中的诊断价值

卵巢癌是妇科死亡率最高的恶性肿瘤之一,5年生存率仅为25%～30%.其主要原因除了早期诊断困难外,还有治疗后易复发,早期不易探及复发和转移灶.常规影像学检查,包括超声、CT等对早期复发和转移缺乏敏感性.PET/CT可从肿瘤细胞代谢旺盛的角度早期发现病变,并与CT融合准确定位,能够提高卵巢癌转移和复发的早期检出率,并指导进一步的临床治疗[1].本文对21例卵巢癌患者的18F-脱氧葡萄糖(FDG)PET/CT及常规影像学检查结果进行总结分析,现报道如下.     

卵巢癌的误诊与循证策略分析

卵巢癌是女性常见的恶性肿瘤之一,占女性恶性肿瘤的21%～51%。它是临床上最棘手的肿瘤之一,特别是卵巢正常大小的卵巢癌,早期无症状,常规的影像学检查很难发现。约2/3的卵巢上皮性癌患者在确诊时已属晚期,错过了治疗的最好时机,预后很差。由于卵巢癌误诊率较高,死亡率为妇科恶性肿瘤之首。     

卵巢癌诊断的研究进展

卵巢癌是常见的妇科恶性肿瘤之一。卵巢癌的发病率位于宫颈癌和子宫内膜癌之后,而死亡率一直居于女性生殖器恶性肿瘤的首位。由于80％的卵巢癌患者在确诊时已属晚期,晚期卵巢癌5年生存率不到30％,而早期卵巢癌的5年生存率可达90％,表明卵巢癌的生存率随着分期不同而明显不同。卵巢癌发病隐匿,临床症状、体征不典型且缺乏有效的早期诊断方法,目前,卵巢癌的诊断包括症状学、查体、肿瘤标记物、影像学、蛋白质组学等方法。     

卵巢癌病人生活质量调查与分析

目的 了解卵巢癌患者的生活质量,分析其影响因素,为提高卵巢癌患者的生活质量提供依据。方法 采用生活质量核心问卷对2002年l～12月在我院住院的卵巢癌患者115名进行生活质量的问卷调查。结果 治疗卵巢癌的不同阶段、不同因素在治疗的不同时期、恶心呕吐、疼痛、疲乏等症状、不同学历等对卵巢癌患者生活质量都有所影响。结论 护理人员应根据病人的实际情况针对性地进行健康教育及心理干预,以改善病人的生活质量。     

超声引导穿刺瘤内化疗治疗晚期卵巢癌临床研究

由于卵巢癌起病隐匿,出现临床症状就诊的患者中多有转移,或为晚期,临床治疗效果较差,5年存活率为25％-30％^[1]。为提高对晚期卵巢癌患者的治疗疗效,我院近年来采用超声引导穿刺瘤内化疗术对30例晚期卵巢癌患者进行治疗,结果报道如下。     

Deep exploration of PARP inhibitors in breast cancer: monotherapy and combination therapy

ObjectiveNearly 5% of patients with breast cancer carry germline BRCA mutations, which are more common in triple-negative breast cancer (TNBC). Previous clinical trials demonstrated the therapeutic efficacy of poly (ADP-ribose) polymerase inhibitors (PARPis) against BRCA-mutated metastatic breast cancer. The current study conducted a systemic review and meta-analysis of the clinical efficiency and safety of PARPis, either alone or combined with chemotherapy, in patients with TNBC.MethodsWe searched PubMed, EMBASE, and ClinicalTrials.gov to identify randomized controlled trials comparing PARPi therapy with chemotherapy, and comparisons of chemotherapy plus PARPis with chemotherapy alone were included. The study endpoints included the clinical response, progression-free survival, and adverse event rates.ResultsPARPi therapy was revealed to improve progression-free survival in patients with advanced breast cancer, either alone or in combination with chemotherapy. Subgroup analysis illustrated that patients with mutant BRCA1 and mutant BRCA2 and those who had not been treated with platinum-based agents could specifically benefit from PARPis.ConclusionPARPi monotherapy can significantly improve clinical outcomes in patients with advanced breast cancer, especially those with TNBC, those who had not previously received platinum therapy, and those with mutant BRCA1/2. PARPis combined with chemotherapy represent new treatment options for patients with advanced cancer.     

Eliminating hypoxic tumor cells improves response to PARP inhibitors in homologous recombination–deficient cancer models

Hypoxia, a hallmark feature of the tumor microenvironment, causes resistance to conventional chemotherapy, but was recently reported to synergize with poly(ADP-ribose) polymerase inhibitors (PARPis) in homologous recombination–proficient (HR-proficient) cells through suppression of HR. While this synergistic killing occurs under severe hypoxia (<0.5% oxygen), our study shows that moderate hypoxia (2% oxygen) instead promotes PARPi resistance in both HR-proficient and -deficient cancer cells. Mechanistically, we identify reduced ROS-induced DNA damage as the cause for the observed resistance. To determine the contribution of hypoxia to PARPi resistance in tumors, we used the hypoxic cytotoxin tirapazamine to selectively kill hypoxic tumor cells. We found that the selective elimination of hypoxic tumor cells led to a substantial antitumor response when used with PARPi compared with that in tumors treated with PARPi alone, without enhancing normal tissue toxicity. Since human breast cancers with BRAC1/2 mutations have an increased hypoxia signature and hypoxia reduces the efficacy of PARPi, then eliminating hypoxic tumor cells should enhance the efficacy of PARPi therapy.     

Enhancement of Synthetic Lethality via Combinations of ABT-888, a PARP Inhibitor, and Carboplatin In Vitro and In Vivo Using BRCA1 and BRCA2 Isogenic Models

Individuals with an inherited BRCA1 or BRCA2 mutation have an elevated risk of developing breast cancer. The resulting tumors typically lack homologous recombination repair as do a subset of sporadic tumors with acquired BRCA deficiency. Clinical responses to monotherapy with platinum drugs or poly PARP inhibitors (PARPi) have been shown for BRCA-associated cancers. However, there are limited data on combination therapy with PARPi and platinum drugs, the mechanism of action of this combination, and the role of BRCA1 or BRCA2 in chemosensitivity. We compared the efficacy of ABT-888 (a PARPi) with that of cisplatin or carboplatin (platinum drugs) alone or in combinations by examining the survival of treated Brca-proficient and -deficient mouse embryonic stem cells. In addition, drug-induced growth inhibition of a BRCA1 and a BRCA2 null cell line were compared with their isogenic BRCA-complemented lines. Although each monotherapy killed or inhibited proliferation of Brca/BRCA-deficient cells, an enhanced effect was observed after treatment with ABT-888 in combination with carboplatin. Moreover, the ABT-888/carboplatin combination delayed tumor growth in Brca2 xenografts. The drugs caused DNA damage and apoptosis. Along with greater PARP activity in Brca/BRCA-deficient cells, these effects correlated with increased chemosensitivity. Our data suggest that ABT-888 and carboplatin combination treatment will be more successful than monotherapy in addressing many BRCA-associated cancers. A randomized phase II trial has recently been initiated to test this hypothesis to assist in the discovery of more effective therapies for patients with BRCA. Mol Cancer Ther; 11(9); 1948-58. ?2012 AACR.     

卵巢癌早期诊断及治疗分析

目的探讨卵巢癌的早期诊断和治疗方法。方法回顾性分析68例早期卵巢癌患者的临床资料。结果所有患者都顺利通过手术或内科治疗过程后,出院后经随访,5年生存率达76.5%。结论卵巢癌的早期诊断对卵巢癌的预后影响很大,其主要的治疗手段是手术和化疗。     

人附睾蛋白4在上皮性卵巢癌中的应用价值

近年来卵巢恶性肿瘤的发病率逐年升高并趋于年轻化。上皮性卵巢癌因早期常无明显症状,亦无有效监测手段,故多于晚期发现,预后较差。即使通过规范的手术及化疗,晚期上皮性卵巢癌的5年生存率为20%~30%,而早期上皮性卵巢癌(I~II期)患者5年生存率可达90%。上皮性卵巢癌患者的生存率与其分期及治疗效果相关。临床上一直在探索一种有效的监测手段,以期早期诊断并准确评估晚期上皮性卵巢癌的治疗效果,从而提高患者的生存率。人附睾蛋白4(human epididymis protein 4,HE4)作为近年来新发现的肿瘤标志物,在正常组织中呈限制性表达,在良性肿瘤组织中表达水平较低,在上皮性卵巢癌组织及血清中呈高水平表达。多项研究表明,HE4在早期上皮性卵巢癌的诊断、卵巢癌治疗效果及预后中有一定的应用价值。     

Recurrent epithelial ovarian cancer and hormone therapy

The role of hormone therapy in the treatment of ovarian cancer is not clear. Data on the efficacy and safety of antiestrogens and aromatase inhibitors in recurrent ovarian cancer have been accumulated through phase Ⅱ clinical studies. Most of these studies were conducted in platinum-resistant recurrent ovarian cancer, and although complete response rates were not high, reported adverse events were low. If administered to patients who are positive for estrogen receptors, hormone therapy may become a viable option for the treatment of recurrent ovarian cancer.     

白蛋白结合型紫杉醇联合卡铂治疗复发性卵巢癌的效果及患者总生存期影响因素分析

目的 分析白蛋白结合型紫杉醇(ab-P)联合卡铂治疗复发性卵巢癌的效果及患者总生存期(OS)的影响因素.方法 纳入2016年1月至2018年12月富平县医院收治的70例复发性卵巢癌患者为研究对象,根据治疗方法的不同将其分为常规组和ab-P组,各35例.常规组采用溶剂型紫杉醇联合卡铂进行治疗,ab-P组采用ab-P联合卡...     

降期转化联合手术治疗卵巢癌肝转移1例并文献复习

目的探讨降期转化联合手术治疗方案对卵巢癌肝转移患者的有效性和可行性。方法回顾1例67岁卵巢癌肝转移患者的诊疗经过,患者2018年12月就诊于广州中医药大学第一附属医院妇科中心,经妇科、肝胆外科、肿瘤科等多学科联合会诊拟定具体治疗方案。结果经"新辅助化疗-原始肿瘤减灭术-辅助化疗-靶向药物-肝转移灶切除术"一系列治疗后患者实现无瘤生存。结论降期转化联合手术治疗卵巢癌肝转移可取得较为满意的疗效。     

D-二聚体在未治卵巢癌患者深静脉血栓发生诊断中的价值

目的探讨血清D-二聚体检测在未接受临床治疗的卵巢癌患者中诊断深静脉血栓发生的价值。方法选取2017年6月至2019年3月在新疆医科大学第一附属医院经手术或病理诊断的卵巢癌患者110例,于临床干预治疗前完善卵巢肿瘤标志物糖类抗原125(CA125)和人附睾蛋白4(HE4)检测,血浆D-二聚体(DD)检测,以及妇科B超、双下肢血管B超、肺部血管造影(CTA)检查。分析卵巢癌患者中深静脉血栓的发生情况,比较CA125、HE4和DD水平在卵巢癌不同分期中的差异,以及CA125、HE4、DD在卵巢癌患者深静脉血栓发生诊断中的价值。结果 15.5%的卵巢癌患者在临床干预治疗前发生了深静脉血栓,其中94.2%的深静脉血栓患者为晚期卵巢癌,88.2%的深静脉血栓患者无明显临床症状。在未治卵巢癌患者中,形成深静脉血栓与未形成深静脉血栓组间比较,血浆DD水平差异有统计学意义(P<0.001);血清CA125及HE4水平差异无统计学意义(P>0.05)。血浆DD水平诊断卵巢癌深静脉血栓形成的灵敏度为70.6%,特异度为89.2%,阳性预测值54.5%,阴性预测值94.3%,截断值为1 894.0ng/mL。结论未治卵巢癌患者无症状性深静脉血栓发生的概率较高;血浆DD水平对未治卵巢癌深静脉血栓发生有诊断价值;选择合适的血浆DD诊断截断值,可有效协助临床诊断未治卵巢癌深静脉血栓的发生。     

CA125监测进展期卵巢癌疗效和复发的意义

目的　评估CA12 5监测进展期卵巢癌疗效及复发的应用价值。方法　采用ES3 0 0全自动酶免疫分析系统检测 5 4例Ⅲ、Ⅳ期原发卵巢癌患者、42例综合治疗后随访卵巢癌患者、2 4例治疗后复发或远处转移患者、15例卵巢良性肿瘤和65例健康女性血清CA12 5水平。结果　 ( 1) 5 4例进展期原发卵巢癌患者血清CA12 5水平显著高于正常人和卵巢良性肿瘤患者。以 3 5U/ml为限定值 ,卵巢上皮癌 10 0 %阳性 ,非上皮癌中 2例内胚窦瘤为阴性 ,其余均阳性。良性肿瘤 13 .3 %假阳性。Ⅲ、Ⅳ期间无显著差异。 ( 2 )原发卵巢癌患者经综合治疗后 ,CA12 5明显下降 ,病情转归与CA12 5下降的幅度相关 ,但与治疗前水平无关。 ( 3 ) 42例随访未出现复发者 ,10 2次检测CA12 5平均值为 2 7.85± 12 .66U /ml ,连续 2次CA12 5升高者 2例 ,治疗后复发或远处转移者 2 4例 ,CA12 5平均值为 3 3 9.5 5± 2 46.6U/ml,其中 95 .8% ( 2 3 /2 4)高于限定值。CA12 5判断复发的准确率为 95 .4% ( 63 /66)。结论　CA12 5的连续监测可作为进展期卵巢癌疗效评价、复发转移及预后的一个有用指标。