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1.
Emeline Colomba Patricia Pautier Fanny Pommeret Alexandra Leary 《Expert review of anticancer therapy》2019,19(6):437-446
Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings.
Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research.
Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited. 相似文献
2.
Elisa Malacarne Marta Devesa Francisca Martinez Ignacio Rodriguez Buenaventura Coroleu 《Journal of assisted reproduction and genetics》2020,37(12):3069
PurposeBreast cancer is the most common cancer diagnosed during childbearing age, and fertility preservation is becoming increasingly more essential. However, recent studies indicate a possible poorer response to controlled ovarian hyperstimulation (COH) in cancer patients than in non-cancer controls and a negative impact of BRCA mutations on female fertility. This study aims to evaluate ovarian response and the number of mature oocytes (MII) vitrified in women with breast cancer, with or without BRCA mutation, comparing them to the expected response according to an age-related nomogram.MethodsThis is a retrospective observational study involving sixty-one breast cancer patients who underwent COH for oocyte cryopreservation. The age-specific nomogram was built using 3871 patients who underwent COH due to oocyte donation, fertility preservation for non-medical reasons, or FIVET for male factor exclusively.ResultsThe mean number of oocytes retrieved was 13.03, whereas the mean number of MII oocytes was 10.00. After the application of the z-score, no statistically significant differences were found compared with the expected response in the general population, neither by dividing patients according to the presence or absence of BRCA mutation nor according to the phase in which they initiated stimulation.ConclusionThe results obtained do not support the notion of a negative impact of the BRCA mutation on the ovarian response of women with breast cancer. Women with breast cancer undergoing COH for fertility preservation can expect the ovarian response predicted for their age. 相似文献
3.
目的:探讨彩色多普勒超声诊断卵巢肿瘤蒂扭转的临床意义。方法方便选取2012―2015年该院收治的58例疑似卵巢肿瘤蒂扭转患者作为观察目标,入选病例均应用彩色多普勒超声进行检查,并将检查结果同术后病理检查结果进行比较。结果58例患者中,术后病理证实卵巢肿瘤蒂扭转者51例,彩色多普勒超声共确诊49例,检查准确率为96.1%;囊壁增厚、腹腔或盆腔积液、可见混合型团块是卵巢肿瘤蒂扭转的主要彩超表现。结论卵巢肿瘤蒂扭转应用彩色多普勒超声诊断,可显著提高诊断准确率,具有积极的临床使用和推广价值。 相似文献
4.
Dominique Trudel Luminita-Mihaela Avarvarei Michèle Orain Stéphane Turcotte Marie Plante Jean Grégoire Reinhild Kappelhoff David P. Labbé Dimcho Bachvarov Bernard Têtu Christopher M. Overall Isabelle Bairati 《Pathology, research and practice》2019,215(6):152369
Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance. 相似文献
5.
6.
M. Iachina P.M. Ljungdalh R.G. Sørensen L. Kaerlev J. Blaakær O. Trosko N. Qvist B.M. Nørgård 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(2):115-123
Aims
To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer.Materials and methods
The analyses were based on all patients who underwent surgical treatment for endometrial, ovarian or cervical cancer who were registered in the Danish Gynecological Cancer Database in the years 2007–2014 (3059 patients with ovarian cancer, 5100 patients with endometrial cancer and 1150 with cervical cancer). Logistic regression model and Cox regression model, adjusted for relevant confounders, were used to estimate the effect of pre-existing psychiatric disorder on the course of cancer treatment. Our outcomes were (i) presurgical oncological treatment, (ii) macroradical surgery for patients with ovarian cancer, (iii) radiation/chemotherapy within 30 days and 100 days after surgery and (iv) time from surgery to first oncological treatment.Results
In the group of patients with ovarian cancer, more patients with a psychiatric disorder received macroradical surgery versus patients without a psychiatric disorder, corresponding to an adjusted odds ratio of 1.24 (95% confidence interval 0.62–2.41) and the chance for having oncological treatment within 100 days was odds ratio = 1.26 (95% confidence interval 0.77–2.10). As for patients with endometrial cancer, all outcome estimates were close to unity. The adjusted odds ratio for oncological treatment within 30 days after surgery in patients with cervical cancer with a history of psychiatric disorder was 0.20 (95% confidence interval 0.03–1.54).Conclusions
We did not find any significant differences in the treatment of ovarian and endometrial cancer in patients with pre-existing psychiatric diagnoses. When it comes to oncological treatment, we suggest that increased attention should be paid to patients with cervical cancer having a pre-existing psychiatric diagnosis. 相似文献7.
Tianjiao Lyu Yahui Jiang Nan Jia Xiaoxia Che Qin Li Yinhua Yu Keqin Hua Robert C. Bast Jr Weiwei Feng 《International journal of cancer. Journal international du cancer》2020,146(6):1553-1567
Detachment of cancer cells from the primary tumor and formation of spheroids in ascites is required for implantation metastasis in epithelial ovarian cancer (EOC), but the underlying mechanism of this process has not been thoroughly elucidated. To mimic this process, ovarian cancer cells were grown in 3D and 2D culture. Hey and OVCA433 spheroids exhibited decreased cell proliferation and enhanced adhesion and invasion. SMYD3 expression was elevated in ovarian carcinoma spheroids in association with increased H3K4 methylation. Depletion of SMYD3 by transient siRNA, stable shRNA knockdown and the SMYD3 inhibitor BCI-121 all decreased spheroid invasion and adhesion. Gene expression arrays revealed downregulation of integrin family members. Inhibition assays confirmed that invasion and adhesion of spheroids are mediated by ITGB6 and ITGAM. SMYD3-deficient cells regained the ability to invade and adhere after forced overexpression of SMYD3, ITGB6 and ITGAM. However, this biological ability was not restored by forced overexpression of SMYD3 in ITGB6- and/or ITGAM-deficient cancer cells. SMYD3 and H3K4me3 binding at the ITGB6 and ITGAM promoters was increased in spheroids compared to that in monolayer cells, and the binding was decreased when SMYD3 expression was inhibited, consistent with the expression changes in integrins. SMYD3 expression and integrin-mediated adhesion were also activated in an intraperitoneal xenograft model and in EOC patient spheroids. In vivo, SMYD3 knockdown inhibited tumor metastasis and reduced ascites volume in both the intraperitoneal xenograft model and a PDX model. Overall, our results suggest that the SMYD3-H3K4me3-integrin pathway plays a crucial role in ovarian cancer metastasis to the peritoneal surface. 相似文献
8.
Nicola Flaum Emma J. Crosbie Richard J. Edmondson Miriam J. Smith Dafydd G. Evans 《Clinical genetics》2020,97(1):54-63
Ovarian cancer is the fourth most common cause of cancer-related death in women in the developed world, and one of the most heritable cancers. One of the most significant risk factors for epithelial ovarian cancer (EOC) is a family history of breast and/or ovarian cancer. Combined risk factors can be used in models to stratify risk of EOC, and aid in decisions regarding risk-reduction strategies. Germline pathogenic variants in EOC susceptibility genes including those involved in homologous recombination and mismatch repair pathways are present in approximately 22% to 25% of EOC. These genes are associated with an estimated lifetime risk of EOC of 13% to 60% for BRCA1 variants and 10% to 25% for BRCA2 variants, with lower risks associated with remaining genes. Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) thought to explain an additional 6.4% of the familial risk of ovarian cancer, with 34 susceptibility loci identified to date. However, an unknown proportion of the genetic component of EOC risk remains unexplained. This review comprises an overview of individual genes and SNPs suspected to contribute to risk of EOC, and discusses use of a polygenic risk score to predict individual cancer risk more accurately. 相似文献
9.
目的:研究D-二聚体(D-dimer,D-D)和中性粒细胞/淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)与卵巢癌临床病理特征及预后的关系。方法:回顾性分析2012年1月至2015年12月于我院妇科行手术治疗的卵巢恶性肿瘤患者387例和卵巢良性肿瘤患者250例临床资料。比较血清D-D和外周血NLR在卵巢良、恶性肿瘤中的表达水平;确定D-D和NLR临界值,D-D+NLR=0(D-D≤0.555 mg/L和NLR≤2.792),D-D+NLR=1(D-D>0.555 mg/L或NLR>2.792),D-D+NLR=2(D-D>0.555 mg/L和NLR>2.792),分析两者联合的评分系统与卵巢癌临床病理特征和预后的关系。结果:血清D-D和外周血NLR在卵巢良、恶性肿瘤患者中的表达水平有统计学差异(P<0.001)。D-D高水平组与低水平组相比,患者的分期、分级、淋巴结转移、腹水、CA125水平、残余瘤大小有统计学差异(P<0.05)。NLR高水平组与低水平组相比,患者的年龄、分期、淋巴结转移、腹水、CA125水平、残余瘤大小有统计学差异(P<0.05)。D-D+NLR为0、1、2分的平均总生存期(OS)分别为70个月、58个月、40个月。D-D+NLR评分是影响OS的独立预后因素。结论:术前血清D-D和外周血NLR与卵巢癌临床病理特征和OS相关,D-D+NLR评分可以作为评估卵巢癌预后的指标。 相似文献
10.
Effects of Paclitaxel and Carboplatin Combination on Mechanical Myocardial and Microvascular Functions: A Transthoracic Doppler Echocardiography and Two‐Dimensional Strain Imaging Study 下载免费PDF全文