Precision Clinical Medicine最新文献_第9页

Future directions for screening and treatment in congenital hearing loss. 先天性听力损失筛查和治疗的未来方向。

IF 5.1 4区医学

Precision Clinical Medicine Pub Date : 2020-09-01 Epub Date: 2020-07-16 DOI: 10.1093/pcmedi/pbaa025

Ryan K Thorpe, Richard J H Smith

引用次数: 0

Recent advancements in PARP inhibitors-based targeted cancer therapy. 基于PARP抑制剂的靶向癌症治疗的最新进展。

IF 5.3 4区医学

Precision Clinical Medicine Pub Date : 2020-09-01 Epub Date: 2020-08-31 DOI: 10.1093/pcmedi/pbaa030

Ping Zhou, Justin Wang, Daniel Mishail, Cun-Yu Wang

{"title":"Recent advancements in PARP inhibitors-based targeted cancer therapy.","authors":"Ping Zhou, Justin Wang, Daniel Mishail, Cun-Yu Wang","doi":"10.1093/pcmedi/pbaa030","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa030","url":null,"abstract":"Poly(ADP-ribose) polymerase inhibitors (PARPi) are a new class of agents with unparalleled clinical achievement for driving synthetic lethality in BRCA-deficient cancers. Recent FDA approval of PARPi has motivated clinical trials centered around the optimization of PARPi-associated therapies in a variety of BRCA-deficient cancers. This review highlights recent advancements in understanding the molecular mechanisms of PARP 'trapping' and synthetic lethality. Particular attention is placed on the potential extension of PARPi therapies from BRCA-deficient patients to populations with other homologous recombination-deficient backgrounds, and common characteristics of PARPi and non-homologous end-joining have been elucidated. The synergistic antitumor effect of combining PARPi with various immune checkpoint blockades has been explored to evaluate the potential of combination therapy in attaining greater therapeutic outcome. This has shed light onto the differing classifications of PARPi as well as the factors that result in altered PARPi activity. Lastly, acquired chemoresistance is a crucial issue for clinical application of PARPi. The molecular mechanisms underlying PARPi resistance and potential overcoming strategies are discussed.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"3 3","pages":"187-201"},"PeriodicalIF":5.3,"publicationDate":"2020-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbaa030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38429051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 25

Calling for a united action to defeat COVID-19. 呼吁采取联合行动击败 COVID-19。

IF 5.1 4区医学

Precision Clinical Medicine Pub Date : 2020-09-01 Epub Date: 2020-08-06 DOI: 10.1093/pcmedi/pbaa027

Madison Overby, Qinqin Pu, Xiawei Wei, Min Wu

引用次数: 0

Recent advances of deep learning in psychiatric disorders 深度学习在精神疾病研究中的最新进展

IF 5.3 4区医学

Precision Clinical Medicine Pub Date : 2020-08-28 DOI: 10.1093/pcmedi/pbaa029

Lu Chen, C. Xia, Huaiqiang Sun

引用次数: 13

Whole-exome sequencing in a patient with synchronous triple primary malignancies involving lung cancer: a case report 全外显子组测序患者同步三重原发性恶性肿瘤合并肺癌:一个病例报告

IF 5.3 4区医学

Precision Clinical Medicine Pub Date : 2020-06-05 DOI: 10.1093/pcmedi/pbaa019

Dan Li, M. Yu, P. Zhou, Jie Yang, Yongsheng Wang

{"title":"Whole-exome sequencing in a patient with synchronous triple primary malignancies involving lung cancer: a case report","authors":"Dan Li, M. Yu, P. Zhou, Jie Yang, Yongsheng Wang","doi":"10.1093/pcmedi/pbaa019","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa019","url":null,"abstract":"Abstract The incidence of multiple primary malignancies (MPMs) has been increasing rapidly in recent years, however, the genetic pathogenesis is largely unknown on account of rare cases, especially for those patients who are diagnosed with three or more tumors. Under these circumstances, whole-exome sequencing (WES) may help to provide more comprehensive genomic information and guidance to proper therapeutic strategies. Here, we presented a rare case of a 66-year-old Chinese male patient who was diagnosed with synchronous triple primary malignancies: esophageal squamous cell carcinoma (ESCC), lung adenocarcinoma (LA), and hepatocellular carcinoma (HCC). Tumors were surgically removed within 3 months. WES was performed when the patient suffered from cancer recurrence and tumor-specific neoantigens were predicted. Each tumor displayed a distinct somatic mutation profile, providing direct evidence of independent origins. No shared driver gene mutation or neoantigen was detected among the three tumors. Two germline alterations of cancer susceptibility genes—SPINK1 c.194 + 2T>C and JAK3 c.425G>A were identified. This case is the first report of synchronous primary triple cancers covering the esophagus, lung, and liver. Our findings highlight the complexities of MPMs that even when under identical germline genetic backgrounds, the occurrence of MPMs can be a random event and driven by distinct somatic gene mutations. Synchronous multiple primary cancers that originated from different organs may not have common therapeutic gene targets, and it can be difficult to find a treatment to cover all the tumors.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"73 1","pages":"306 - 310"},"PeriodicalIF":5.3,"publicationDate":"2020-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83565510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Can the personalized medicine approach contribute in controlling tuberculosis in general and India in particular? 个体化医疗方法能否有助于控制结核病，特别是在印度?

IF 5.3 4区医学

Precision Clinical Medicine Pub Date : 2020-06-04 DOI: 10.1093/pcmedi/pbaa021

Nikhat Khan, Aparup Das

引用次数: 4

Improved gastrointestinal health for irritable bowel syndrome with metagenome-guided interventions. 宏基因组引导干预改善肠易激综合征胃肠道健康

IF 5.3 4区医学

Precision Clinical Medicine Pub Date : 2020-06-01 Epub Date: 2020-04-29 DOI: 10.1093/pcmedi/pbaa013

Cem Meydan, Ebrahim Afshinnekoo, Nate Rickard, Guy Daniels, Laura Kunces, Theresa Hardy, Loukia Lili, Sarah Pesce, Paul Jacobson, Christopher E Mason, Joel Dudley, Bodi Zhang

{"title":"Improved gastrointestinal health for irritable bowel syndrome with metagenome-guided interventions.","authors":"Cem Meydan, Ebrahim Afshinnekoo, Nate Rickard, Guy Daniels, Laura Kunces, Theresa Hardy, Loukia Lili, Sarah Pesce, Paul Jacobson, Christopher E Mason, Joel Dudley, Bodi Zhang","doi":"10.1093/pcmedi/pbaa013","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa013","url":null,"abstract":"Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal disorder worldwide, and the most common reason for referral to gastroenterology clinics. However, the pathophysiology is still not fully understood and consequently current management guidelines are very symptom-specific, leading to mixed results. Here we present a study of 88 individuals with IBS who had baseline sequencing of their gut microbiome (stool samples), received targeted interventions that included dietary, supplement, prebiotic/probiotic, and lifestyle recommendations for a 30-day period, and a follow-up sequencing of their gut microbiome. The study's objectives were to demonstrate unique metagenomic signatures across the IBS phenotypes and to validate whether metagenomic-guided interventions could lead to improvement of symptom scores in individuals with IBS. Enrolled subjects also completed a baseline and post-intervention questionnaire that assessed their symptom scores. The average symptom score of an individual with IBS at baseline was 160 and at the endpoint of the study the average symptom score of the cohort was 100.9. The mixed IBS subtype showed the most significant reduction in symptom scores across the different subtypes (average decrease by 102 points, P = 0.005). The metagenomics analysis reveals shifts in the microbiome post-intervention that have been cross-validated with the literature as being associated with improvement of IBS symptoms. Given the complex nature of IBS, further studies with larger sample sizes, more targeted analyses, and a broader population cohort are needed to explore these results further.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"3 2","pages":"136-146"},"PeriodicalIF":5.3,"publicationDate":"2020-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbaa013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38170632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Double contrast-enhanced ultrasonography of a small intestinal neuroendocrine tumor: a case report of a recommendable imaging modality 小肠神经内分泌肿瘤的双重超声造影:推荐的成像方式1例报告

IF 5.3 4区医学

Precision Clinical Medicine Pub Date : 2020-04-17 DOI: 10.1093/pcmedi/pbaa011

Jie-ying Zhao, H. Zhuang, Yuan Luo, M. Su, M. Xiong, Yu-ting Wu

引用次数: 0

RNA-based therapies in animal models of Leber congenital amaurosis causing blindness Leber先天性黑朦致盲动物模型的rna治疗

IF 5.3 4区医学

Precision Clinical Medicine Pub Date : 2020-03-12 DOI: 10.1093/pcmedi/pbaa009

Xia Wang, Xianghong Shan, K. Gregory-Evans, C. Gregory-Evans

{"title":"RNA-based therapies in animal models of Leber congenital amaurosis causing blindness","authors":"Xia Wang, Xianghong Shan, K. Gregory-Evans, C. Gregory-Evans","doi":"10.1093/pcmedi/pbaa009","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa009","url":null,"abstract":"Abstract Leber congenital amaurosis (LCA) is a severe, genetically heterogeneous recessive eye disease in which ~ 35% of gene mutations are in-frame nonsense mutations coding for loss-of-function premature termination codons (PTCs) in mRNA. Nonsense suppression therapy allows read-through of PTCs leading to production of full-length protein. A limitation of nonsense suppression is that nonsense-mediated decay (NMD) degrades PTC-containing RNA transcripts. The purpose of this study was to determine whether inhibition of NMD could improve nonsense suppression efficacy in vivo. Using a high-throughput approach in the recessive cep290 zebrafish model of LCA (cep290;Q1223X), we first tested the NMD inhibitor Amlexanox in combination with the nonsense suppression drug Ataluren. We observed reduced retinal cell death and improved visual function. With these positive data, we next investigated whether this strategy was also applicable across species in two mammalian models: Rd12 (rpe65;R44X) and Rd3 (rd3;R107X) mouse models of LCA. In the Rd12 model, cell death was reduced, RPE65 protein was produced, and in vivo visual function testing was improved. We establish for the first time that the mechanism of action of Amlexanox in Rd12 retina was through reduced UPF1 phosphorylation. In the Rd3 model, however, no beneficial effect was observed with Ataluren alone or in combination with Amlexanox. This variation in response establishes that some forms of nonsense mutation LCA can be targeted by RNA therapies, but that this needs to be verified for each genotype. The implementation of precision medicine by identifying better responders to specific drugs is essential for development of validated retinal therapies.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"181 1","pages":"113 - 126"},"PeriodicalIF":5.3,"publicationDate":"2020-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74545740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Clinical applications of exosome membrane proteins. 外泌体膜蛋白的临床应用。

IF 5.3 4区医学

Precision Clinical Medicine Pub Date : 2020-03-01 Epub Date: 2020-02-24 DOI: 10.1093/pcmedi/pbaa007

Qian Hu, Hang Su, Juan Li, Christopher Lyon, Wenfu Tang, Meihua Wan, Tony Ye Hu

{"title":"Clinical applications of exosome membrane proteins.","authors":"Qian Hu, Hang Su, Juan Li, Christopher Lyon, Wenfu Tang, Meihua Wan, Tony Ye Hu","doi":"10.1093/pcmedi/pbaa007","DOIUrl":"https://doi.org/10.1093/pcmedi/pbaa007","url":null,"abstract":"Extracellular vesicles (EVs) are small membranous particles that can mediate cell-to-cell communication and which are divided into at least three categories according to their subcellular origin and size: exosomes, microvesicles, and apoptotic bodies. Exosomes are the smallest (30-150 nm) of these EVs, and play an important role in EV-mediated cell-to-cell interactions, by transferring proteins, nucleic acids and, lipids from their parental cells to adjacent or distant cells to alter their phenotypes. Most exosome studies in the past two decades have focused on their nucleic acid composition and their transfer of mRNAs and microRNAs to neighboring cells. However, exosomes also carry specific membrane proteins that can identify the physiological and pathological states of their parental cells or indicate their preferential target cells or tissues. Exosome membrane protein expression can also be directly employed or modified to allow exosomes to serve as drug delivery systems and therapeutic platforms, including in targeted therapy approaches. This review will briefly summarize information on exosome membrane proteins components and their role in exosome-cell interactions, including proteins associated with specific cell-interactions and diseases, and the potential for using exosome membrane proteins in therapeutic targeting approaches.","PeriodicalId":33608,"journal":{"name":"Precision Clinical Medicine","volume":"3 1","pages":"54-66"},"PeriodicalIF":5.3,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/pcmedi/pbaa007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37808778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 88