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Real-world performance analysis of a novel computational method in the precision oncology of pediatric tumors

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World Journal of Pediatrics 2023年第10期19卷 992-1008页

作者： Barbara Vodicska Júlia Déri Dóra Tihanyi Edit Várkondi EnikőKispéter Róbert Dóczi Dóra Lakatos Anna Dirner Mátyás Vidermann Péter Filotás Réka Szalkai-Dénes István Szegedi katalin Bartyik Krisztina Míta Gábor Réka Simon Péter Hauser György Péter Csongor Kiss Miklós Garami István Peták Oncompass Medicine Hungary Kft Retek Str.34Budapest 1024Hungary Division of Pediatric Hematology-Oncology Department of PediatricsFaculty of MedicineUniversity of DebrecenDebrecenHungary Department of Pediatrics Albert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Onco-Hematology Department Velkey LászlóPaediatric Health CentreMiskolcHungary Department of Paediatrics Semmelweis UniversityBudapestHungary Onco-Hematology Department Heim Pál Children’s HospitalBudapestHungary Department of Pharmacology and Pharmacotherapy Semmelweis UniversityBudapestHungary Department of Pharmaceutical Sciences University of Illinois at ChicagoChicagoUSA Genomate Health CambridgeMAUSA

Background The utility of routine extensive molecular profiling of pediatric tumors is a matter of debate due to the high number of genetic alterations of unknown significance or low evidence and the lack of standardized and personalized decision support *** drug assignment(DDA)is a novel computational method to prioritize treatment options by aggregating numerous evidence-based associations between multiple drivers,targets,and targeted *** has been validated to improve personalized treatment decisions based on the outcome data of adult patients treated in the SHIVA01 clinical *** aim of this study was to evaluate the utility of DDA in pediatric *** Between 2017 and 2020,103 high-risk pediatric cancer patients(ram,and samples from 100 patients were eligible for further *** or blood samples were analyzed by whole-exome(WES)or targeted panel sequencing and other molecular diagnostic modalities and processed by a software system using the DDA algorithm for therapeutic decision ***,a molecular tumor board(MTB)evaluated the results to provide therapy *** Of the 100 cases with comprehensive molecular diagnostic data,88 yielded WES and 12 panel sequencing *** identified matching off-label targeted treatment options(actionability)in 72/100 cases(72%),while 57/100(57%)showed potential drug *** reached 88%(29/33)by 2020 due to the continuous updates of the evidence *** approved the clinical use of a DDA-top-listed treatment in 56 of 72 actionable cases(78%).The approved therapies had significantly higher aggregated evidence levels(AELs)than dismissed *** of WES results for targeted panels missed important mutations affecting therapy *** DDA is a promising approach to overcome challenges associated with the interpretation of extensive molecular profiling in the routine car

关键词： Computational decision support Pediatric tumors Precision oncology Tumor board

Increased duodenal expression of mi R-146a and-155 in pediatric Crohn's disease

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World Journal of Gastroenterology 2016年第26期22卷 6027-6035页

作者： Dániel Szucs Nóra Judit Béres Réka Rokonay Kriszta Boros katalin Borka Zoltán Kiss András Arató Attila J Szabó ádám Vannay Erna Sziksz Csaba Bereczki Gábor Veres Department of Pediatrics and Pediatric Health Care Center University of Szeged H-6725 Szeged Hungary 1st Department of Pediatrics Semmelweis University H-1083 Budapest Hungary 2nd Department of Pathology Semmelweis University H-1091 Budapest Hungary 1st Department of Pediatrics Semmelweis University and MTA-SE Pediatrics and Nephrology Research Group H-1083 Budapest Hungary

AIM: To evaluate the role of microRNA (miR)-146a, -155 and -122 in the duodenal mucosa of pediatric patients with Crohn’s disease (CD) and the effect of transforming growth factor-β (TGF-β) on these miRs in duodenal epithelial and fibroblast ***: Formalin-fixed, paraffin-embedded biopsies derived from the macroscopically inflamed (CD inflamed: n = 10) and intact (CD intact: n = 10) duodenal mucosa of pediatric CD patients and control children (C: n = 10) were examined. Expression of miR-146a, -155 and -122 was determined by real-time polymerase-chain reaction (PCR). The expression of the above miRs was investigated in recombinant human TGF-β (1 nmol/L, 24 h) or vehicle treated small intestinal epithelial cells (CCL-241) and primary duodenal fibroblast cells derived from healthy children as ***: Expression of miR-146a was significantly higher in the inflamed duodenal mucosa compared to the intact duodenal mucosa of children with CD (CD inflamed: 3.21 ± 0.50 vs CD intact: 0.62 ± 0.26, P ≤ 0.01) and to the control group (CD inflamed: 3.21 ± 0.50 vs C: 1.00 ± 0.33, P ≤ 0.05). The expression of miR-155 was significantly increased in the inflamed region of the duodenum compared to the control group (CD inflamed: 4.87 ± 1.02 vs Control: 1.00 ± 0.40, P ≤ 0.001). The expression of miR-122 was unchanged in the inflamed or intact mucosa of CD patients compared to controls. TGF-β treatment significantly decreased the expression of miR-155 in small intestinal epithelial cells (TGF-β: 0.7 ± 0.083 vs Control: 1 ± 0.09, P ≤ 0.05) and also the expression of miR-146a (TGF-β: 0.67 ± 0.04 vs Control: 1 ± 0.15, P ≤ 0.01) and miR-155 (TGF-β: 0.72 ± 0.09 vs Control: 1 ± 0.06, P ≤ 0.05) in primary duodenal fibroblasts compared to corresponding vehicle treated control

关键词： Inflammatory bowel disease Crohn’ s disease Pediatric MicroRNAs Transforming growth factor-β

Identification of IL11ra and MELK amplification in gastric cancer by comprehensive genomic profiling of gastric cancer cell lines

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World Journal of Gastroenterology 2016年第43期22卷 9506-9514页

作者： Danielle Queiroz Calcagno Sylvia Santomi Takeno Carolina Oliveira Gigek Mariana Ferreira Leal Fernanda Wisnieski Elizabeth Suchi Chen Taíssa Maíra Thomaz Araújo Eleonidas moura.Lima Maria Isabel Melaragno Samia Demachki Paulo Pimentel Assumpcao Rommel Rodriguez Burbano Marília Cardoso Smith Disciplina de Genética Departamento de Morfologia e GenéticaUniversidade Federal de Sao Paulo Núcleo de Pesquisas em Oncologia Hospital Universitário Joao de Barros Barreto Departamento de Biologia Molecular Universidade Federal da Paraíba Disciplina de Gastroenterologia Cirúrgica Universidade Federal de Sao Paulo Departamento de Ortopedia e Traumatologia Universidade Federal de Sao Paulo

AIM To identify common copy number alterations on gastric cancer cell *** Four gastric cancer cell lines(ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array comparative genome hybridization. We also confirmed the results by fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone and quantitative real time PCR *** The amplification of 9p13.3 was detected in all cell lines by both methodologies. An increase in the copy number of 9p13.3 was also confirmed by fluorescence in situ hybridization analysis. Moreover, the interleukin 11 receptor alpha(IL11ra) and maternal embryonic leucine zipper kinase(MELK) genes, which are present in the 9p13.3 amplicon, revealed gains of the MELK gene in all the cell lines studied. Additionally, a gain in the copy number of IL11 ra and MELK was observed in 19.1%(13/68) and 55.9%(38/68) of primary gastric adenocarcinoma samples, respectively. CONCLUSION The characterization of a small gain region at 9p13.3 in gastric cancer cell lines and primary gastric adenocarcinoma samples has revealed MELK as a candidate target gene that is possibly related to the development of gastric cancer.

关键词： IL11ra Gastric cancer Genomic profiling MELK 9p13.3

The significance of midsummer movements of Autographa gamma： Implications for a mechanistic understanding of orientation behavior in a migrant moth

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Current Zoology 2013年第3期59卷 360-370页

作者： Jason W. CHAPMAN ka S. LIM Don R. REYNOLDS Department ofAgroEcology Rothamsted Research Harpenden Hertfordshire AL5 2JQ UK Environment and Sustainability Institute University of Exeter Penryn Cornwall TR10 9EZ UK Natural Resources Institute University of Greenwich Chatham Kent ME4 4TB UK

The silver Y moth Autographa gamma undertakes windbome spring and fall migrations between winter breeding re- gions around the Mediterranean and summer breeding regions in northern Europe. Flight behaviors facilitating these migrations include：（i） selection of seasonally-favorable tailwinds; （ii） flying at the altitude of the fastest winds; （iii） adopting flight headings that partially counteract crosswind drift; and （iv） seasonal reversal of preferred directions between spring and fall. In the UK, ra- dar measurements indicate that migratory activity is pronounced during the spring and fall, but is usually very low during mid- summer （July）. However, an atypically intense period of high-altitude flight was recorded during July 2006, and in this study we compare the flight behavior of A. gamma during these midsummer movements with the more typical spring and fall migrations. During July 2006, activity was most intense at significantly lower altitudes than occurred in spring or fall, and was not associated with the height of the fastest winds; consequently displacement speeds were significantly slower. The most striking difference was an absence of tailwind selectivity in July with windborne movements occurring on almost every night of the month and on tailwinds from all directions. Finally, orientation behavior was quantitatively different during July, with significantly greater dis- persion of flight headings and displacements than observed in spring and fall. We discuss mechanisms which could have caused these differences, and conclude that a lack of appropriate photopcriod cues during development of the summer generation resulted in randomly-oriented ＇dispersive＇ movements that were strikingly different from typical seasonal migrations .

关键词： Long-range migration Dispersal High-altitude flight Photoperiod Entomological radar Noctuid moths

Possible Roles of Diet in the Etiology of Rheumatoid Arthritis:A Systematic Review

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World Journal of Traditional Chinese Medicine 2016年第3期2卷 25-35页

作者： Chi Zhang ka-Miu Chan Ai-Ping Lu School of Chinese Medicine Hong Kong Baptist University Hong Kong Chinese Medicine Clinical study Center Hong Kong Baptist University Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical Sciences

Background:There is a growing interest in the possible role of diet in the prevention of rheumatoid arthritis(ra).However,the evidence for diet having a role in the etiology of ra is inconsistent,sometimes ***:To critically appraise the literature to pool the results of studies to clarify the relation between diet risk and ***:We performed a systematic review using guideline-recommended methodology to evaluate the association between pre-illness diet or diet pattern and the risk of subsequent ra ***:A total of 25 studies met the inclusion *** include 13 cohort studies,10 case-control studies and 2 nested case-control studies,with a total of 1279810 *** were new evidences of a protective effect of long term consumption of *** sodium intake was associated with an increased risk of *** intake has consistently been shown to have no effect on the development of *** diet pattern,Vitamin D intake,and the consumption of long-chain omega-3 acids were not associated with an increased/decreased risk of ra in every two *** were non-statistically significant association between ra and sugar-sweetened soda,red meat,vegetable and fruits in each single *** association between coffee,tea and ra was consistent,and here exists an inverse relationship between olive oil and *** to the heterogeneity of study designs and analyses,the results could not be ***:The results of this SR indicate that alcohol consumption and sodium intake may be associated with ra risk,especially evidence from recent *** of some discordant results,the debate continues on whether some other dietary intakes increase or decrease ra risk.

关键词： Diet Rheumatoid Arthritis Systematic review

基于线粒体DNA控制区序列的极边扁咽齿鱼群体遗传研究

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水产科学 2024年第1期43卷 79-87页

作者：杨濯羽杜岩岩卡伟焦文龙王太张艳萍达虎甘肃省水产研究所甘肃省冷水性鱼类种质资源与遗传育种重点实验室甘肃兰州730030 甘肃省计算中心甘肃兰州730030

极边扁咽齿鱼是黄河上游特有的裂腹鱼类,由于人类活动的加剧,使其野生数量急剧下降,近年来通过增殖放流的方式为野生资源量进行补充。为评价增殖放流过程中人工繁育群体对野生群体的种质资源的影响,笔者利用线粒体DNA控制区(D-loop)序... 详细信息

极边扁咽齿鱼是黄河上游特有的裂腹鱼类,由于人类活动的加剧,使其野生数量急剧下降,近年来通过增殖放流的方式为野生资源量进行补充。为评价增殖放流过程中人工繁育群体对野生群体的种质资源的影响,笔者利用线粒体DNA控制区(D-loop)序列来探究极边扁咽齿鱼野生和养殖的4个群体遗传多样性、遗传分化及遗传结构的差异。研究结果显示,4个群体均表现出了较高的单倍型多样性(0.950±0.011)和较低的核苷酸多样性(0.00987±0.00041),并且野生群体的单倍型数目、单倍型多样性指数、核苷酸多样性指数均高于人工繁育群体。遗传结构分析结果显示,野生群体与人工繁育群体之间已产生了一定的遗传分化。中性检验表明,2个野生群体可能经历过种群扩张事件。研究结果表明,极边扁咽齿鱼人工繁育群体可能受到亲本数量有限、人工选择等影响,遗传多样性略有降低,有必要定期开展增殖放流效果的评估,并采用科学的人工繁育方法,丰富极边扁咽齿鱼种群的遗传多样性。

关键词：极边扁咽齿鱼线粒体DNA控制区野生群体人工繁育群体遗传多样性

甘草对雷公藤治疗类风湿关节炎减毒增效的研究进展

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中华中医药学刊 2024年第10期42卷 139-143页

作者：林芳芳刘维卡玉秀岳青云陈婌娟顾庆香杨晓砚天津中医药大学第一附属医院天津300000 国家中医针灸临床医学研究中心天津300000 天津中医药大学研究生院天津300000

雷公藤是中医治疗风湿性疾病常用的中草药,对以类风湿关节炎(rheumatoid arthritis,ra)为主的风湿性疾病起到良好的治疗作用,但由于其存在的不良反应使得该药的使用受到限制。甘草是中医传统的解毒药物,以甘草对雷公藤治疗ra为例,通过... 详细信息

雷公藤是中医治疗风湿性疾病常用的中草药,对以类风湿关节炎(rheumatoid arthritis,ra)为主的风湿性疾病起到良好的治疗作用,但由于其存在的不良反应使得该药的使用受到限制。甘草是中医传统的解毒药物,以甘草对雷公藤治疗ra为例,通过对近些年的文献进行综述,发现甘草可以通过影响机体的应答以及影响药物在体内的代谢过程对雷公藤治疗ra起到减毒增效的作用。既往尚未有综述对这方面的内容进行讨论,希望通过综述,能为安全使用雷公藤及其相关制剂提供技术参考,为ra的发病机制研究提供理论依据,以及对复方的研究和新药的研发提供思路。

关键词：类风湿关节炎甘草雷公藤减毒增效研究进展

Comparative phytochemical analysis of Coffea benghalensis Roxb. Ex Schult, Coffea arabica L. and Coffea liberica Hiern

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Asian Pacific Journal of Tropical Medicine 2018年第8期11卷 480-485页

作者： éva Brigitta Patay ágnes Alberti Orsolya Csernák Szilvia Stranczinger Nóra Pap Department of Pharmacognosy Faculty of Pharmacy University of Pécs Department of Pharmacognosy Faculty of Pharmacy Semmelweis University Department of Plant Biology Faculty of Sciences University of Pécs

Objective: To make phytochemical studies of the leaf, pericarp and seed of Coffea benghalensis(C. Benghalensis) compared with those of the widely known Coffea arabica and Coffea liberica. Methods: The sample extracts were prepared by Soxhlet-extraction. Polyphenol content was analyzed by HPLC-ESI-MS/MS, the identification was carried out based on the retention time, UV and mass spectra of standards and literature data of the detected compounds. Results: Phenolic acids like caffeoylquinic acids, dicaffeoylquinic acids, feruloylquinic acids and coumaroylquinic acid, as well as mangiferin were detected as main constituents in all extracts. Procyanidin trimers were present exclusively in the leaves. In C. benghalensis, main constituents were 5-caffeoylquinic acid and 4-caffeoylquinic acid. Flavan-3-ols were described in all immature and mature pericarp and leaf extracts. Even though 4-feruloylquinic acid was described in both immature and mature seed, dicaffeoylquinic acids were identified only in the mature seed extracts. Mangiferin was present in the leaf, mature pericarp and seed. Conclusions: These analyses provide new chemotaxonomical data for the selected coffees, especially for C. benghalensis. Due to its high polyphenol content, our results indicate its significance of providing new data as a possible source for industry.

关键词： Coffee LC-MS Polyphenols Caffeoylquinic acids

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卵泡内和卵泡外轮流培养卵母细胞

内蒙古农牧学院学报 1988年第2期 89-92页

作者：卡毕拉内蒙古农牧学院畜牧系

当前在胚胎移植中,最大的问題是要从母牛取得尽可能多的胚胎。为要最大限度地提高优良母牛的繁殖率,取得较多的胚胎,仅仅通过超排处理是不够的。如果从卵巢的生长卵泡储库中取得卵母细胞,並在体外培养和受精,然后再移植到受体母牛,这是... 详细信息

当前在胚胎移植中,最大的问題是要从母牛取得尽可能多的胚胎。为要最大限度地提高优良母牛的繁殖率,取得较多的胚胎,仅仅通过超排处理是不够的。如果从卵巢的生长卵泡储库中取得卵母细胞,並在体外培养和受精,然后再移植到受体母牛,这是挖掘母牛繁殖潜力的很好途径。这对于那些存在繁殖障碍或患有疾病的优秀母畜,提供了生育后代的可能。对于研究卵细胞的发育,受精等方面,也很有重要意义。通过体外培养卵母细胞表明,在卵泡内培养卵母细胞时,其发育条件近似于母体环境,所以发育进行得较充分,能较完全的成熟。但成熟速度较泡外培养缓慢。为了解卵母细胞在卵泡内和卵泡外培养时的染色体形态改变情况,我们进行了泡內和泡外轮流培养卵母细胞的试验。

关键词：繁殖潜力闭锁卵泡隔离培养