人类表皮生长因子受体-2和拓扑异构酶Ⅱ在卵巢上皮癌中的表达及其临床意义

目的 探讨原癌基因人类表皮生长因子受体-2(HER-2)和拓扑异构酶Ⅱ(TOPO-Ⅱα)在卵巢上皮癌组织中的表达及其相关性.方法 采用免疫组化SP方法检测经病理确诊的58例卵巢上皮癌、20例卵巢良性上皮肿瘤及10例正常卵巢组织标本中HER-2及TOPO-Ⅱα的表达情况,并结合临床病理特征进行分析.结果 HER-2在卵巢正常组织、卵巢良性上皮性肿瘤组织中的阳性表达率分别为10.0%(1/10)、15.0%(3/20),显著低于卵巢上皮癌组织[46.6%(27/58),x2值分别为4.705、6.225,P均＜0.05];卵巢上皮癌组织中TOPO-Ⅱα的阳性表达率显著高于卵巢正常组织和卵巢良性上皮性肿瘤组织[53.4%(31/58)、10.0%(1/10)、15.0%(3/20),x2值分别为6.463、8.941,P均＜0.05];而良性肿瘤组织和正常组织间比较差异均无统计学意义(P均＞0.05).HER-2和TOPO-Ⅱα的表达与卵巢上皮癌临床分期(x2值分别为5.295、6.665)、细胞组织学分化(x2值分别为5.376、8.981)有显著相关性(P均＜0.05),而与年龄、组织学类型无相关性(P均＞0.05);卵巢上皮癌中HER-2和TOPO-Ⅱα蛋白的表达呈正相关(rs=0.324,P＜0.05).结论 HER-2在卵巢上皮癌的发生发展中起重要作用,对临床诊断及预后评估具有一定的指导意义.

Abstract：

Objective To observe the expression of HER-2 and TOPO-Ⅱα in ovarian epithelial cancer,analyze the correlation between their expression and provide theoretical basis for clinical diagnosis,prognosis and treatment. Methods Expression levels of HER-2 and TOPO- Ⅱα in 10 normal ovarian tissues,20 benign tumors and 58 cases of ovarian epithelial cancers were detected by immunohistochemical method, and their correlations with pathological features were analyzed. Results The positive expression rate of HER-2 in normal ovarian and benign tumor tissues were significantly lower than ovarian epithelial cancers respectively ( 10. 0% , 15.0% VS 46. 6% ;P ＜ 0. 05 ). The positive expression rate of TOPO- Ⅱα in ovarian epithelial cancers was significantly higher than normal and benign epithelial ovarian tumor tissue (53.4% vs 10. 0%, and 15.0%,Ps ＜ 0. 05 ), but we did not find significant difference in the comparison between normal and benign epithelial ovarian tumor tissue ( Ps ＞ 0. 05 ). The expression of HER-2 and TOPO- Ⅱα were significantly correlated with clinical stages, histological differentiation of tumor cells (Ps ＜ 0. 05 ) ,but there were no correlations between the age or histological type. In ovarian cancer tissues, a positive correlation between the expression of HER-2 and TOPO- Ⅱα was observed ( r = 0. 324, P ＜ 0. 05 ) . Conclusion The overexpression of HER-2 and TOPO- Ⅱαplay an important role in ovarian carcinogenesis and development. The expression of HER-2 is positively correlated with TOPO- Ⅱα in ovarian epithelial cancers. Coexpression of the two moleculars may be involved in the development and progression of ovarian epithelial cancer, which should be further studied.     

Biodistribution and bioimaging studies of hybrid paclitaxel nanocrystals: Lessons learned of the EPR effect and image-guided drug delivery

Paclitaxel (PTX) nanocrystals (200 nm) were produced by crystallization from a solution. Antitumor efficacy and toxicity were examined through a survival study in a human HT-29 colon cancer xenograft murine model. The antitumor activity of the nanocrystal treatments was comparable with that by the conventional solubilization formulation (Taxol®), but yielded less toxicity as indicated by the result of a survival study. Tritium-labeled PTX nanocrystals were further produced with a near infrared (NIR) fluorescent dye physically integrated in the crystal lattice. Biodistribution and tumor accumulation of the tritium-labeled PTX nanocrystals were determined immediately after intravenous administration and up to 48 h by scintillation counting. Whole-body optical imaging of animals was concurrently carried out; fluorescent intensities were also measured from excised tumors and major organs of euthanized animals. It was found that drug accumulation in the tumor was less than 1% of 20 mg/kg intravenous dose. Qualitatively correlation was identified between the biodistribution determined by using tritium-labeled particles and that using optical imaging, but quantitative divergence existed. The divergent results suggest possible ways to improve the design of hybrid nanocrystals for cancer therapy and diagnosis. The study also raises questions of the general role of the enhanced permeability and retention (EPR) effect in tumor targeting and the effectiveness of bioimaging, specifically for theranostics, in tracking drug distribution and pharmacokinetics.     

Farletuzumab in epithelial ovarian carcinoma

Importance of the field: Ovarian cancer is the leading cause of death from a gynecologic malignancy. Recurrence is both common and lethal, necessitating the development of novel targeted therapies. Farletuzumab (MORAb-003) is a humanized mAb with high affinity for folate receptor α (FRα), a 38 kDa GPI-anchored protein that is overexpressed in 90% of epithelial ovarian cancers.

Areas covered in this review: Preclinical and clinical trials, published or presented at national meetings from 2006 to the present, are presented in this review.

What the reader will gain: Preclinical studies have demonstrated robust antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity in vitro, inhibition of tumor growth in ovarian tumor xenografts and a safe toxicology profile in non-human primates. Phase I and II studies have demonstrated single agent and combination therapy efficacy with minimal drug-specific toxicity. The Phase III development plan in ovarian cancer patients includes combination chemotherapy studies in both platinum-sensitive (recently launched) and platinum-resistant (planned) recurrent disease.

Take home message: FRα is overexpressed in ovarian cancers but largely absent from normal tissue, making it an attractive therapeutic target. Farletuzumab is a novel inhibitor of FRα and has shown clinical efficacy in early phase trials.     

卵巢癌组织NFkB家族蛋白的表达和临床意义

目的　研究卵巢癌组织NFkB家族蛋白的表达及其临床意义。方法　采用免疫组化方法检测卵巢良性上皮性肿瘤、卵巢交界性上皮性肿瘤和卵巢癌中NFkB蛋白的表达。结果　在卵巢良性上皮性肿瘤、卵巢交界性上皮性肿瘤和卵巢癌中NFkB的阳性表达率分别为 3 3 3 %、3 7 5 %和 65 % ;在卵巢癌组织 ,p65核染色阳性与分化程度、淋巴结转移、临床分期及肿瘤大小明显相关 (P <0 0 5 )。结论　NFkB与卵巢癌的发生、发展有关 ;NFkB可望成为判断卵巢癌预后新的标志物。     

真核细胞起始因子3和人附睾蛋白4在卵巢癌组织中的表达及临床意义

目的探讨真核细胞起始因子3(el F3a)和人附睾蛋白4(HE4)在卵巢癌组织中的表达及其与卵巢癌发生发展的关系。方法采用免疫组织化学染色法检测79例卵巢癌术后组织表标本、40例卵巢良性肿瘤组织标本、40例正常卵巢组织标本中的el F3a、HE4蛋白表达水平,分析el F3a、HE4蛋白表达与卵巢癌患者的临床病理学关系。结果卵巢癌中el F3a、HE4蛋白阳性表达率64.56%、39.25%,卵巢良性肿瘤中el F3a、HE4蛋白阳性表达率22.50%、7.50%,正常卵巢组织中el F3a、HE4蛋白阳性表达率0%、0%。3种组织el F3a、HE4蛋白阳性表达率有显著差异(P0.05)。卵巢癌中el F3a、HE4蛋白阳性表达呈显著的正相关性(P0.001);卵巢癌中el F3a蛋白阳性表达与患者的发生淋巴结转移、组织分化程度有关(P0.05);卵巢癌中HE4蛋白阳性表达与患者的发生淋巴结转移有关(P0.05)。结论卵巢癌组织中el F3a、HE4蛋白阳性表达显著升高,二者呈正相关关系。     

Tumor-penetrating microparticles for intraperitoneal therapy of ovarian cancer

Intraperitoneal chemotherapy prolongs survival of ovarian cancer patients, but its utility is limited by treatment-related complications and inadequate drug penetration in larger tumors. Previous intraperitoneal therapy used the paclitaxel/Cremophor EL (polyethoxylated castor oil) formulation designed for intravenous use. The present report describes the development of paclitaxel-loaded microparticles designed for intraperitoneal treatment (referred to as tumor-penetrating microparticles or TPM). Evaluation of TPM was performed using intraperitoneal metastatic, human ovarian SKOV3 xenograft tumor models in mice. TPM were retained in the peritoneal cavity and adhered to tumor surface. TPM consisted of two biocompatible and biodegradable polymeric components with different drug release rates; one component released the drug load rapidly to induce tumor priming, whereas the second component provided sustained drug release. Tumor priming, by expanding interstitial space, promoted transport and penetration of particulates in tumors. These combined features resulted in the following advantages over paclitaxel/Cremophor EL: greater tumor targeting (16-times higher and more sustained concentration in omental tumors), lower toxicity to intestinal crypts and less body weight loss, greater therapeutic efficacy (longer survival and higher cure rate), and greater convenience (less frequent dosing). TPM may overcome the toxicities and compliance-related problems that have limited the utility of intraperitoneal therapy.     

Ki-67在卵巢癌中的表达及其临床意义

目的研究Ki-67在卵巢癌中的表达及其临床意义。方法应用免疫组织化学法（SP方法）,检测15例正常卵巢组织,15例卵巢良性肿瘤组织及60例卵巢癌组织中Ki-67的表达情况。结果Ki-67在正常卵巢组织中为阴性表达;Ki-67在良性卵巢肿瘤组织中的阳性表达率为33.3%,在卵巢癌组织中的阳性表达率为75.0%;卵巢癌临床分期越晚、组织学分化越差,Ki-67阳性表达率越高,阳性表达率与临床分期及组织学分级有关,与病理类型无关。结论Ki-67在卵巢癌的发生、发展过程中起着重要的作用。     

Targeted radiotherapy with tumor vascular homing trimeric GEBP11 peptide evaluated by multimodality imaging for gastric cancer

Targeted radiopharmaceutical is an effective treatment for solid tumors. By labeling with radionuclides, targeting peptide could achieve both noninvasive diagnosis and targeted radionuclide therapy. In order to evaluate the potential applicability of GEBP11 peptides in diagnosis and radiotherapy of gastric cancer, in this study, iodine 131 labeled GEBP11 peptides, including a novel bifid PEGlylated GEBP11 trimer and its corresponding monomer, were developed. The clinical potential of GEBP11 peptides, such as tumor binding affinity and antitumor efficacy was demonstrated and assessed with multimodality imaging methods. Cerenkov and SPECT imaging showed higher tumor uptake for ¹³¹I-2PEG-(GEBP11)₃ (P < 0.05, day 1; P < 0.01, day 2; vs. monomer). Biodistribution studies indicated higher tumor accumulation and better T/NT of ¹³¹I-2PEG-(GEBP11)₃. Bioluminescence imaging exhibited a significant tumor growth suppression in ¹³¹I-2PEG-(GEBP11)₃ treated group (P < 0.001 vs. control; P < 0.01 vs. monomer). After treatment with ¹³¹I-2PEG-(GEBP11)₃, the tumor volume and vasculature decreased significantly, and the survival time was prolonged to 75.5 days. Meanwhile, no significant hepatic or renal toxicity was observed with ¹³¹I-2PEG-(GEBP11)₃ administered. In conclusion, ¹³¹I-2PEG-(GEBP11)₃ could be a promising candidate for peptide-based targeting therapy of gastric cancer. 2PEG-(GEBP11)₃ might be a potential drug delivery vehicle for the antiangiogenic therapy of gastric cancer.     

卵巢癌患者组织中miR-135b的表达及临床意义

目的 探讨miR-135b在卵巢癌组织中的表达及意义。方法 选取2015年1月～2017年12月在解放军第一七四医院和南方医科大学深圳医院接受手术的卵巢病变患者的卵巢组织,包括28例卵巢癌组织和10例卵巢良性肿瘤组织,所有的组织均经过病理确认。运用荧光定量PCR(RT-PCR)的方法检测28例卵巢癌及10例卵巢良性肿瘤组织中miR-135b的表达水平,并分析其与卵巢癌患者年龄、组织学类型、分化程度、临床分期及淋巴结转移的关系。结果 ①28例卵巢癌组织中miR-135b 的表达量(1.90± 0.53)与10例卵巢良性肿瘤组织中miR-135b表达量(1.45±0.45)比较,差异有统计学意义(t=2.03,P<0.05); ②19例≥50岁卵巢癌患者组织中miR-135b的表达量(1.97±0.51)和20例浆液性囊腺癌组织中miR-135b的表达量(1.96±0.50)分别与9例<50岁卵巢癌患者组织中miR-135b的表达量(1.77±0.57)和8例黏液性腺癌组织中miR-135b的表达量(1.77±0.61)比较,差异均无统计学意义(t=0.743～0.846,均P<0.05)。20例中低分化组织中miR-135b的表达量(2.05±0.54),17例临床分期Ⅲ～Ⅳ期组织中miR-135b的表达量(2.10±0.46)和15例有淋巴结转移的组织中miR-135b的表达量(2.10±0.53)均分别高于8例高分化组织中miR-135b的表达量(1.55±0.25),11例临床分期I～II组织中miR-135b的表达量(1.60±0.49)和13例无淋巴结转移的组织中miR-135b的表达量(1.68±0.44)比较,差异均有统计学意义(t=5.036～7.517,均P<0.05)。结论 miR-135b在卵巢癌组织中高表达,miR-135b 的表达水平与卵巢癌的分化程度、临床分期和淋巴结转移有关。     

缺氧诱导因子-1α和血管内皮生长因子在卵巢癌中的表达及相关性

目的：探讨卵巢癌组织中缺氧诱导因子-1α和血管内皮生长因子的表达及相关性。方法：采用免疫组织化学S—P方法检测145例不同卵巢组织中HIF—1α和VEGF的表达情况。结果：交界性卵巢肿瘤和卵巢癌组织中HIF-1α的表达高于正常卵巢和良性卵巢肿瘤，差异有显著性（P〈0．05）；卵巢癌组织中HIF—1α表达与病理分级呈正相关，有统计学差异（P〈0．01）。VEGF表达在正常卵巢和良性卵巢肿瘤组织中均明显低于交界性卵巢肿瘤和卵巢癌（P〈0．01）。卵巢癌组织中HIF—1α表达与VEGF表达之间呈明显正相关（rs=0．439，P=0．000）。结论：在缺氧状态下，卵巢癌组织中HIF-1α基因被激活，过渡表达HIF-1α蛋白，并通过VEGF的上调而刺激肿瘤新生血管的生成，促进卵巢癌的转移。     

Sodium iodide symporter-mediated radioiodide imaging and therapy of ovarian tumor xenografts in mice

Ovarian cancer represents the fifth leading cause of cancer death among women in the United States, with >16 000 deaths expected this year. This study was carried out to investigate the potential of sodium iodide symporter (NIS)-mediated radioiodide therapy as a novel approach for ovarian cancer treatment. Radioiodide is routinely and effectively used for the treatment of benign and malignant thyroid disease as a result of native thyroidal expression of NIS, which mediates iodide uptake. In vitro gene transfer studies in ovarian cancer cells revealed a 12- and five-fold increase in iodide uptake when transduced with Ad/CMV/NIS or Ad/MUC1/NIS, respectively. Western blot/immunohistochemistry confirmed NIS protein expression. In vivo ovarian tumor xenografts were infected with the adenoviral constructs. (123)I imaging revealed a clear image of the CMV/NIS-transduced tumor, with a less intense image apparent following infection with MUC1/NIS. Therapeutic doses of (131)I following CMV/NIS infection caused a mean 53% reduction in tumor volume (P<0.0001). MUC1/NIS-transduced tumors did not regress, although at 8 weeks following therapy, tumor volume was significantly less that of control animals (166 versus 332%, respectively, P<0.05). This study represents a promising first step investigating the potential for NIS-mediated radioiodide imaging and therapy of ovarian tumors.     

血清人附睾蛋白4对妇女盆腔疾病的诊断价值

目的探讨血清人附睾蛋白4(HE4)对妇女盆腔疾病诊断的临床价值。方法分别采用酶联免疫吸附试验(ELISA)、免疫化学发光法测定43名健康妇女(正常对照组)和133例妇女盆腔疾病(包括卵巢癌7例、子宫恶性肿瘤40例、卵巢良性病变34例、子宫良性病变52例)患者血清HE4和糖类抗原125(CA125)水平。患者根据术后包块切片病理报告分组。以正常对照组x珋±2s作为正常参考范围,计算血清HE4和CA125水平对妇女盆腔恶性疾病的灵敏度和特异性等诊断性能。结果 HE4的正常参考范围上限为55.86 pmoL/L、CA125为35 kU/L。卵巢良性病变组、子宫良性病变组及正常对照组血清HE4及CA125水平差异无统计学意义(P>0.05);卵巢癌组患者HE4及CA125水平明显高于正常参考范围上限,且高于子宫恶性肿瘤、卵巢良性病变、子宫良性病变及正常对照组(P<0.01);子宫恶性肿瘤组血清HE4水平也高于正常参考范围上限,亦高于卵巢良性病变、子宫良性病变及正常对照组(P<0.05);但血清CA125水平4组间差异无统计学意义(P>0.05)。卵巢癌组和子宫恶性肿瘤组HE4与CA125呈正相关[相关系数(r)分别为0.467、0.380,P<0.05],其他3组之间无明显相关性。HE4和CA125在卵巢癌、子宫恶性肿瘤、卵巢良性性病变、子宫良性病变及正常对照组中的阳性率分别为100.00%、71.43%,37.50%、30.00%,14.70%、11.76%,19.23%、32.69%,2.32%、2.32%;HE4及CA125对卵巢癌的灵敏度分别为100.00%、71.43%,特异性为82.35%、85.29%,阳性预测值53.85%、50.00%,阴性预测值为100.00%9、3.50%;卵巢癌组HE4的受试者工作特征(ROC)曲线下面积(AUC)明显大于CA125(P<0.01)。将卵巢癌组和子宫恶性肿瘤组合并为盆腔恶性肿瘤组,血清HE4、CA125、HE4+CA125对其诊断的灵敏度分别为46.80%、36.17%、54.41%,特异性为82.60%、75.58%、47.22%,阳性预测值为59.50%、44.74%4、9.33%,阴性预测值为74.00%、68.42%、52.31%。结论血清HE4水平除了可以作为卵巢癌与部份子宫恶性肿瘤的辅助诊断标志物外,还应注意部份妇女盆腔良性疾病患者血清HE4水平也可增高。     

神经轴突导向分子Sema3A在卵巢癌中的表达及其临床意义

目的:检测卵巢上皮细胞肿瘤中Sema3A的表达情况,并探讨其与临床病理间的关系,分析Sema3A检测在上皮性卵巢癌诊断中的作用。方法:收集80例卵巢肿瘤石蜡标本,采用免疫组织化学法对不同病理分级的卵巢上皮性肿瘤进行Sema3A检测,并用蛋白印迹法检测Sema3A在另8对新鲜良、恶性卵巢肿瘤组织中的表达变化。结果:免疫组织化学检测结果示,在上皮性卵巢癌(卵巢癌)、上皮性交界性肿瘤(交界性肿瘤)及上皮性良性肿瘤(良性肿瘤)中,Sema3A表达存在差异。卵巢癌中Sema3A的表达与其病理分级(r=-0.624;P<0.001);而不同组织学分类的卵巢癌(浆液性乳头状腺癌、子宫内膜样腺癌、透明细胞癌、黏液样腺癌)间Sema3A的表达亦有显著差异(P<0.05)。8对卵巢上皮性良、恶性肿瘤组织的蛋白印迹检测结果与免疫组织化学检测结果完全相符,卵巢良、恶性肿瘤中的Sema3A表达有显著差异(P<0.001)。结论:Sema3A在卵巢癌、卵巢交界性肿瘤及卵巢良性肿瘤中的表达呈明显递降趋势。卵巢癌中Sema3A的表达水平随肿瘤恶性程度增高而增高,表明Sema3A阳性表达在卵巢癌诊断中有一定价值,并可提示肿瘤的恶性程度。     

血清学CA724、CA125检测联合ROMA值在卵巢癌诊断中的价值

目的探讨血清糖类抗原(CA)724、CA125检测联合ROMA值在卵巢癌诊断中的应用价值。方法采用回顾性分析,选取赣南医学院第一附属医院2017年10月至2018年7月,经术后病理确诊为卵巢恶性肿瘤的63例患者作为卵巢癌组,同期72例卵巢良性肿瘤患者作为卵巢良性肿瘤组,71例与卵巢无关其他原因入院患者为对照组。采用罗氏试剂化学发光免疫分析法测定患者血清CA724、人附睾蛋白4(HE4)及CA125水平,并计算ROMA值。结果卵巢癌组中血清CA724、CA125表达及ROMA值高于卵巢良性肿瘤组和对照组,差异有统计学意义(P<0.05);卵巢良性肿瘤组中血清CA125水平高于对照组,差异有统计学意义(P<0.001);血清CA724水平、ROMA值在卵巢良性肿瘤组与对照组比较,差异无统计学意义(P>0.05)。CA724、CA125检测联合ROMA值在卵巢癌组、卵巢良性肿瘤组及对照组比较,差异有统计学意义(P<0.001),灵敏度、特异度、准确度、假阴性率和假阳性率分别为89.06%、50.34%、71.5%、10.09%和49.65%。受试者工作特征曲线分析表明,以卵巢良性肿瘤组及对照组为参照,卵巢癌组CA125+CA724+ROMA值、CA125单独检测、CA724单独检测和ROMA值单独的曲线下面积分别为0.893、0.630、0.801、0.735。结论血清CA724、CA125水平及ROMA值的表达均与卵巢癌有密切关系,3项指标联合应用于卵巢癌的灵敏度高于各单项指标的使用,在卵巢癌检测中具有很高的临床价值,可以在早期更加准确地预测卵巢恶性肿瘤的风险。     

EGFR在卵巢癌中的表达及其临床意义

目的研究表皮生长因子受体在卵巢癌中的表达及其临床意义。方法应用免疫组织化学法（印方法），检测15例正常卵巢组织，15例卵巢良性肿瘤组织及60例卵巢癌组织中EGFR的表达情况。结果EGFR在正常卵巢组织中为阴性表达；EGFR在良性卵巢肿瘤组织中的阳性表达率分别为40．0％，在卵巢癌组织中的阳性表达率为80.0％；卵巢癌临床分期越晚、组织学分化越差，EGFR阳性表达率越高，阳性表达率与临床分期及组织学分级有关，与病理类型无关。结论EGFR在卵巢癌的发生、发展过程中起着重要的作用。     

p27蛋白在卵巢肿瘤中的表达及临床意义

目的探讨p27蛋白在卵巢肿瘤中的表达及临床意义。方法采用SP免疫组化的方法对15例良性卵巢肿瘤,45例上皮性卵巢癌对照进行检测,阳性程度用半定量法评价。结果在45例卵巢癌中p27表达阳性反应(57·8%),其中强阳性6例(13·3%),在15例良性卵巢肿瘤中11例呈阳性反应(73·3%),强阳性7例(46·7%),p27表达在良性卵巢肿瘤及恶性卵巢癌对照组比较,两者差异显著(P<0·05)。结论p27与卵巢癌发生、分化程度及淋巴结转移有关,其对临床综合治疗有意义。     

PIK3CA mutations in patients with advanced cancers treated with PI3K/AKT/mTOR axis inhibitors

Preclinical data suggest that PIK3CA mutations predict response to PI3K/AKT/mTOR inhibitors. Concomitant KRAS or BRAF mutations may mediate resistance. Therefore, tumors from patients referred to the phase I program for targeted therapy starting in October 2008 were analyzed for PIK3CA mutations using PCR-based DNA sequencing of exons 9 and 20. Consecutive patients with diverse tumor types and PIK3CA mutation were treated whenever possible with agents targeting the PI3K/AKT/mTOR pathway. Overall, PIK3CA mutations were detected in 25 of 217 patients (11.5%; exon 9, n = 11; exon 20, n = 14). In tumor types with more than 10 patients tested, PIK3CA mutations were most frequent in endometrial (3 of 14, 21%), ovarian (5 of 30, 17%), colorectal (9 of 54, 17%), breast (2 of 14, 14%), cervical (2 of 15, 13%), and squamous cell cancer of the head and neck (1 of 11, 9%). Of the 25 patients with PIK3CA mutations, 17 (68%) were treated on a protocol that included a PI3K/AKT/mTOR pathway inhibitor, and 6 (35%) achieved a partial response. In contrast, only 15 of 241 patients (6%) without documented PIK3CA mutations treated on the same protocols responded (P = 0.001). Of the 17 patients with PIK3CA mutations, 6 (35%) had simultaneous KRAS or BRAF mutations (colorectal, n = 4; ovarian, n = 2). Colorectal cancer patients with PIK3CA and KRAS mutations did not respond to therapy, whereas both ovarian cancer patients with PIK3CA and KRAS or BRAF mutations did. In conclusion, PIK3CA mutations were detected in 11.5% of patients with diverse solid tumors. The response rate was significantly higher for patients with PIK3CA mutations treated with PI3K/AKT/mTOR pathway inhibitors than for those without documented mutations.     

CDFI血流分级联合收缩期与舒张末期流速比值鉴别卵巢良恶性肿瘤的临床价值

目的探讨CDFI血流分级和收缩期与舒张末期流速比值(S/D)在鉴别卵巢良恶性肿瘤中的临床价值。方法选取我院确诊的卵巢癌患者96例(病例组)和同期卵巢良性病变患者96例(对照组),均行CDFI检查卵巢并测定血流分级、S/D值。以病理学检查为标准,绘制受试者工作特征(ROC)曲线评估血流分级、S/D值及二者联合应用时鉴别卵巢良恶性肿瘤的效能。结果病例组血流分级、S/D值均明显高于对照组,差异均有统计学意义(均P<0.05)。以血流分级Ⅱ级为截断值,其鉴别卵巢良恶性肿瘤的敏感性、特异性、准确率分别为81.25%、83.33%、82.29%;以S/D值2.20为截断值,其鉴别卵巢良恶性肿瘤的敏感性、特异性、准确率分别为87.50%、81.25%、84.38%;两者联合应用时诊断敏感性、特异性、准确率分别为95.83%、93.75%、94.79%,明显高于单独应用,差异均有统计学意义(均P<0.05)。结论CDFI血流分级及ROC曲线评价S/D值对鉴别卵巢良恶性肿瘤的效能良好,二者联合应用可提高诊断准确率。