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991.
2020年初美国临床肿瘤学会(American Society of Clinical Oncology,ASCO)首次在Journal of Clinical Oncology发布了《卵巢上皮性癌胚系和体细胞肿瘤检测指南》[1]。该指南以2007—2019年间发表的6篇Meta分析、11篇随机对照试验、2篇观察性研究的相关文献为主要参考依据,为卵巢上皮性癌肿瘤基因突变检测相关临床应用和实施提供了指导和建议。该指南的框架架构由背景、方法、结果、推荐、医患沟通、健康差异、成本影响等十几个板块组成,主要阐述了3个主要问题:应在哪些个体中进行胚系和体细胞突变肿瘤风险评估、咨询和基因检测,哪些胚系基因突变已经被证明对卵巢癌临床治疗有指导价值,以及最合适的卵巢癌基因突变检测时机。本文对该指南进行剖析和解读,以期为卵巢癌基因检测的临床应用提供相关依据和指导,为卵巢癌的规范诊治提供借鉴,也为国内同道制定相关指南提供参考。
浏览更多请关注本刊微信公众号及当期杂志。 相似文献
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Elisabeth DeMarco Nina Xu Herwig Baier Estuardo Robles 《The Journal of comparative neurology》2020,528(7):1173-1188
The larval zebrafish optic tectum has emerged as a prominent model for understanding how neural circuits control visually guided behaviors. Further advances in this area will require tools to monitor and manipulate tectal neurons with cell type specificity. Here, we characterize the morphology and neurotransmitter phenotype of tectal neurons labeled by an id2b:gal4 transgene. Whole-brain imaging of stable transgenic id2b:gal4 larvae revealed labeling in a subset of neurons in optic tectum, cerebellum, and hindbrain. Genetic mosaic labeling of single neurons within the id2b:gal4 expression pattern enabled us to characterize three tectal neuron types with distinct morphologies and connectivities. The first is a neuron type previously identified in the optic tectum of other teleost fish: the tectal pyramidal neuron (PyrN). PyrNs are local interneurons that form two stratified dendritic arbors and one stratified axonal arbor in the tectal neuropil. The second tectal neuron type labeled by the id2b:gal4 transgene is a projection neuron that forms a stratified dendritic arbor in the tectal neuropil and an axon that exits tectum to form a topographic projection to torus longitudinalis (TL). A third neuron type labeled is a projection neuron with a nonstratified dendritic arbor and a descending axonal projection to tegmentum. These findings establish the id2b:gal4 transgenic as a useful tool for future studies aimed at elucidating the functional role of tectum, TL, and tegmentum in visually guided behaviors. 相似文献
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Sedigheh Farahani Leila Solgi Sahar Bayat Atieh Abedin Do Shohreh ZareKarizi Behnam Safarpour Lima Reza Mirfakhraie 《CNS Neuroscience & Therapeutics》2020,26(12):1315
AimsRAR‐related orphan receptor (RORA) involves in regulation of several biological processes including inflammation and circadian rhythm that probably are involved in migraine pathophysiology. In the current study, the association between RORA rs11639084 and rs4774388 variants and susceptibility to migraine were investigated in a sample of Iranian migraine patients for the first time.MethodsIn a case‐control study including 400 participants, 200 migraineurs and 200 healthy controls, genotyping of RORA rs4774388 and rs11639084 polymorphisms was performed using tetra‐primer amplification refractory mutation system–polymerase chain reaction (TP‐ARMS‐PCR).ResultsThe distribution of rs4774388 C/T and T/T genotypes differed significantly between the studied groups. Moreover, an association was observed between rs4774388 and migraine under the recessive mode of inheritance (P = 0.002; OR = 1.89.; CI = 1.25‐2.87). The distribution of rs11639084 alleles and genotypes was not significantly different between migraineurs and healthy controls.ConclusionCurrent results suggest RORA, as a molecular link, may explain inflammation and circadian rhythm dysfunction in migraine. Further studies in different ethnicities are required to confirm the function of RORA in migraine development. 相似文献
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Jie Qian Wei Nie Jun Lu Lele Zhang Yanwei Zhang Bo Zhang Shuyuan Wang Minjuan Hu Jianlin Xu Yuqing Lou Yu Dong Yanjie Niu Bo Yan Runbo Zhong Wei Zhang Tianqing Chu Hua Zhong Baohui Han 《International journal of cancer. Journal international du cancer》2020,146(11):3124-3133
This study aimed to compare the differences in characteristics and prognoses between Asian and white patients receiving immunotherapy for nonsmall cell lung cancer (NSCLC). We studied 390 patients who received atezolizumab as part of the POPLAR or OAK trial, and analyzed the differences in baseline characteristics, outcomes and genetic mutations in blood samples between Asian and white patients. Overall survival (OS) was longer in Asian compared to white patients (median OS: 18.7 vs. 11.1 months; p = 0.005). Race was identified as an independent prognostic factor for OS (Asian vs. white: hazard ratio 0.647, 95% confidence interval 0.447–0.936, p = 0.021), together with performance status, histology, baseline sum of the longest tumor diameters (BLSLD) and number of metastatic sites. The two groups also differed in terms of characteristics including smoking history, BLSLD, epidermal growth factor receptor (EGFR) mutation frequency, programmed death-ligand 1 expression and blood-based tumor-mutation burden. Blood mutations of STK11, EGFR, KEAP1, POLE, GRM3, ATM and STAG2 were associated with treatment response, and TP53, KEAP1, APC, RB1, CREBBP, EPHA5 and STAG2 mutations were associated with OS. The blood-based mutation profiles differentiated between Asian and white patients, especially in relation to EGFR (23.8 vs. 8.5%), TP53 (30.2 vs. 46.9%) and STK11 (1.6 vs. 12.3%) mutations (all p < 0.05). The different clinicopathological features and mutation profiles in Asian and white patients may explain the superior outcome following atezolizumab treatment in Asian patients with NSCLC. The results of this study have important implications for further studies on racial disparities in relation to immunotherapy. 相似文献
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Vicky C. Chang Michelle Cotterchio Susan J. Bondy Joanne Kotsopoulos 《International journal of cancer. Journal international du cancer》2020,147(5):1354-1373
Iron has been suggested to contribute to breast cancer development through oxidative stress generation. Our study investigated associations between iron intake and breast cancer risk, overall and by menopausal and estrogen receptor/progesterone receptor (ER/PR) status, and modification by oxidative stress-related genetic polymorphisms (MnSOD, GSTM1 and GSTT1). A population-based case–control study (3,030 cases and 3,402 controls) was conducted in Ontario, Canada. Iron intake (total, dietary, supplemental, heme, nonheme) was assessed using a validated food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from multivariable logistic regression models. Interactions between iron intake and genotypes were assessed among 1,696 cases and 1,761 controls providing DNA. Overall, no associations were observed between iron intake and breast cancer risk. Among premenopausal women, total, dietary and dietary nonheme iron were positively associated with ER–/PR– breast cancer risk (all ptrend < 0.05). Among postmenopausal women, supplemental iron was associated with reduced breast cancer risk (OR>18 vs. 0 mg/day = 0.68, 95% CI: 0.51–0.91), and dietary heme iron was associated with an increased risk, particularly the ER–/PR– subtype (ORhighest vs. lowest quintile = 1.69, 95% CI: 1.16–2.47; ptrend = 0.02). Furthermore, GSTT1 and combined GSTM1/GSTT1 polymorphisms modified some of the associations. For example, higher dietary iron was most strongly associated with increased breast cancer risk among women with GSTT1 deletion or GSTM1/GSTT1 double deletions (pinteraction < 0.05). Findings suggest that iron intake may have different effects on breast cancer risk according to menopausal and hormone receptor status, as well as genotypes affecting antioxidant capacity. 相似文献
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Qingyang Xiao Yitian Zhou Stefan Winter Florian Büttner Elke Schaeffeler Matthias Schwab Volker M. Lauschke 《International journal of cancer. Journal international du cancer》2020,146(9):2475-2487
Multidrug resistance due to facilitated drug efflux mediated by ATP-binding cassette (ABC) transporters is a main cause for failure of cancer therapy. Genetic polymorphisms in ABC genes affect the disposition of chemotherapeutics and constitute important biomarkers for therapeutic response and toxicity. Here we correlated germline variability in ABC transporters with disease-specific survival (DSS) in 960 breast cancer (BRCA), 314 clear cell renal cell carcinoma and 325 hepatocellular carcinoma patients. We find that variant burden in ABCC1 is a strong predictor of DSS in BRCA patients, whereas candidate polymorphisms are not associated with DSS. This association is highly drug-specific for subgroups treated with the MRP1 substrates cyclophosphamide (log-rank p = 0.0011) and doxorubicin (log-rank p = 0.0088) independent of age and tumor stage, whereas no association was found in individuals treated with tamoxifen (log-rank p = 0.13). Structural mapping of significant variants revealed multiple variants at residues involved in protein stability, cofactor stabilization or substrate binding. Our results demonstrate that BRCA patients with high variant burden in ABCC1 are less prone to respond appropriately to pharmacological therapy with MRP1 substrates, thus incentivizing the consideration of genomic germline data for precision cancer medicine. 相似文献
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While the goals of genetic counseling for cystic fibrosis – delivering relevant information on the risk of recurrence and nondirectional support of couples at risk in their reproductive choices – have not changed fundamentally, the practice has evolved considerably in the last decade, growing more complex to face new challenges but also proving more effective. Many factors have contributed to this evolution: technical progress in the exploration of the genome (new generation sequencing) and in reproductive medicine, but also societal developments promoting access to genetic information and the professionalization of genetic counselors in France. The prospect of expanded pre-conception screening of at-risk couples makes genetic counselors major actors not only in medical care centers, but also in modern society by contributing to genetic education among citizens.© 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved. 相似文献