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Genome and clonal hematopoiesis stability contrasts with immune,cfDNA,mitochondrial,and telomere length changes during short duration spaceflight

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Precision clinical Medicine 2024年第1期7卷 1-13页

作者： J.Sebastian Garcia-Medina Karolina Sienkiewicz S.Anand Narayanan Eliah G.Overbey Kirill Grigorev Krista A.Ryon Marissa Burke Jacqueline Proszynski Braden Tierney caleb M.Schmidt Nuria Mencia-Trinchant Remi Klotz Veronica Ortiz Jonathan Foox christopher chin Deena Najjar Irina Matei Irenaeus chan carlos cruchaga Ashley Kleinman JangKeun Kim Alexander Lucaci conor Loy Omary Mzava Iwijn De Vlaminck Anvita Singaraju Lynn E.Taylor Julian c.Schmidt Michael A.Schmidt Kelly Blease Juan Moreno Andrew Boddicker Junhua Zhao Bryan Lajoie Andrew Altomare Semyon Kruglyak Shawn Levy Min Yu Duane c.Hassane Susan M.Bailey Kelly Bolton Jaime Mateus christopher E.Mason department of Physiology and Biophysics Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud institute for computational Biomedicine Weill Cornell MedicineNew YorkNY 10021USA department of Immunology Weill Cornell MedicineCornell UniversityNew YorkNY 10021USA department of Stem cell Biology and Regenerative Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Space Exploration Technologies corporation HawthomeCA 90250USA Sovaris Aerospace BoulderCO 80302USA Advanced Pattern Analysis&Human Performance Group BoulderCO 80302USA children's cancer and Blood Foundation Laboratories Departments of Pediatrics and Cell and Developmental BiologyDrukier Institute for Children's HealthMeyer Cancer CenterWeill Cornell MedicineNew YorkNY 10021USA Meyer cancer center Weill Cornell MedicineNew YorkNY 10065USA department of Nutrition and Integrative Physiology Florida State UniversityTallahasseeFL 32306USA department of Systems Engineering Colorado State UniversityFort CollinsCO 80523USA Element Biosciences San DiegoCA 10055USA department of Environmental and Radiological Health Sciences Colorado State UniversityFort CollinsCO 80523USA cell and Molecular Biology Program Colorado State UniversityFort CollinsCO 80523USA BioAstra Inc New YorkNYUSA Washington University St Louis oncology Division St.LouisMO 63100USA Meinig School of Biomedical Engineering Cornell UniversityIthacaNY 14853USA The Feil Family Brain and Mind research institute Weill Cornell MedicineNY 10021USA WorldQuant Initiative for Quantitative Prediction Weill Cornell MedicineNew YorkNY 10021USA

Background The Inspiration4(I4)mission,the first all-civilian orbital flight mission,investigated the physiological effects of short-duration spaceflight through a multi-omic *** advances,there remains much to learn about human adaptation to spaceflight's unique challenges,including microgravity,immune system perturbations,and radiation *** To provide a detailed genetics analysis of the mission,we collected dried blood spots pre-,during,and post-flight for DNA *** length was measured by quantitative PcR,while whole genome and cfDNA sequencing provided insight into genomic stability and immune adaptations.A robust bioinformatic pipeline was used for data analysis,including variant calling to assess mutational *** Telomere elongation occurred during spaceflight and shortened after return to ***-free DNA analysis revealed increased immune cell signatures *** significant clonal hematopoiesis of indeterminate potential(cHIP)or whole-genome instability was *** long-term gene expression changes across immune cells suggested cellular adaptations to the space environment persisting months *** Our findings provide valuable insights into the physiological consequences of short-duration spaceflight,with telomere dynamics and immune cell gene expression adapting to spaceflight and persisting after return to *** sequencing data will serve as a reference point for studying the early development of cHIP in astronauts,an understudied phenomenon as previous studies have focused on career *** study will serve as a reference point for future commercial and non-commercial spaceflight,low Earth orbit(LEO)missions,and deep-space exploration.

关键词： genomes clonal hematopoiesis stability immune mitochondria ribosomes spaceflight

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大肠癌相关新基因ST13单克隆抗体的制备及生物学特性鉴定

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实用肿瘤杂志 2001年第5期16卷 304-306页

作者：邵吉民郑树彭佳萍浙江大学医学院基础医学系浙江杭州310031 浙江大学肿瘤研究所浙江杭州310009

目的　研制抗 ST13蛋白单克隆抗体 ,建立检测方法 ,探讨 ST13基因的生物学特性。方法　按淋巴细胞杂交瘤技术制备抗 ST13蛋白单克隆抗体 ,并以亲和层析法纯化单抗 ,将此单抗作探针用 Western- Blot和免疫组化检测标本。结果　获得 3个抗... 详细信息

目的　研制抗 ST13蛋白单克隆抗体 ,建立检测方法 ,探讨 ST13基因的生物学特性。方法　按淋巴细胞杂交瘤技术制备抗 ST13蛋白单克隆抗体 ,并以亲和层析法纯化单抗 ,将此单抗作探针用 Western- Blot和免疫组化检测标本。结果　获得 3个抗 ST13蛋白单抗的杂交瘤细胞株 ,杂交瘤细胞培养上清和腹水中单抗的 EL ISA效价为 10 4～ 10 5。以 ST13单抗作 Westerb- Blot和免疫组化证实该单抗具有高度特异性 ,可用于检测组织表达的ST13蛋白。结论　制备了具有高度特异性和高效价的抗 ST13蛋白单抗 ;建立了 Western- Blot及免疫组化检测组织表达的 ST13蛋白的方法。

关键词：结直肠肿瘤 ST13基因免疫印迹法大肠癌单克隆抗体免疫组织化学

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Plasma Epstein-Barr virus DNA as a biomarker for nasopharyngeal carcinoma

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chinese Journal of cancer 2014年第12期33卷 598-603页

作者： K.c.Allen chan Li Ka Shing institute of Health Sciences The Chinese University of Hong Kong department of chemical Pathology The Chinese University of Hong Kong Prince of Wales Hospital State Key Laboratory in oncology in South china Sir Y.K. Pao Centre for Cancer The Chinese University of Hong Kong Prince of Wales Hospital

Nasopharyngeal carcinoma(NPc)is common in southern china and Southeast ***-Barr virus(EBV)infection is an important etiology for NPc,and EBV genome can be detected in almost all tumor tissues of NPc in this *** EBV DNA,when quantitatively analyzed using real-time polymerase chain reaction(PcR),has been developed as a biomarker for *** this review,the different clinical applications of plasma EBV DNA in the management of NPc,including screening,monitoring,and prognostication,are *** addition,the biological issues of circulating EBV DNA,including the molecular nature and clearance kinetics,are also explored.

关键词：病毒DNA 生物标志物鼻咽癌等离子体聚合酶链反应东南亚地区 EBV 中国南部

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DNA Damage Response Inhibitor and Anti-PD-L1 Therapy for Prostate cancer: Development of Predictive Biomarkers

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Engineering 2022年第5期8卷 12-15页

作者： chuandong Geng Timothy c.Thompson department of Genitourinary Medical oncology The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA

*** Although androgen receptor biosynthesis and signaling inhibi-tors have significantly improved outcomes in patients with castra-tion-resistant prostate cancer(cRPc),there is still a dearth of effective treatment op... 详细信息

关键词： cancer Therapy patients

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Improved hemostasis with major hepatic resection in the current surgical era

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Hepatobiliary & Pancreatic Diseases International 2019年第5期18卷 439-445页

作者： christopher W Mangieri Matthew A Strode Bradley c Bandera department of Surgery Dwight D. Eisenhower Army Medical Center(DDEAMC)Fort GordonGA 30809USA department of Surgical oncology Roswell Park Cancer InstituteBuffaloNY 14203USA

Background: Major hepatic resection, predominantly performed for oncologic intent, is a complex procedure with the potential for severe intraoperative hemorrhage. The current surgical era has the ability to improve hemostasis throughout the performance of major hepatic resections which decreases blood transfusions and the detrimental effects associated with transfusion. We evaluated hemostasis and outcomes in the current surgical era of performing hepatic resections. Methods: Utilizing the American college of Surgeons (AcS) National Surgical Quality Improvement Program (NSQIP) database all major hepatic resections performed between 2012 and 2016 were analyzed in regards to hemostasis. Hemostasis was evaluated by the need for and magnitude of blood transfusions. Additional perioperative variables (including operative time, length of hospital stay, and mortality rates) were analyzed to assess for outcomes with hemostasis. The NSQIP results were compared to previous publications involving major hepatic resections to detect improvement in hemostasis and outcomes in the current surgical era. Results: A total of 22777 major hepatic resections met the inclusion criteria for analysis in the NSQIP database. An additional 21198 cases were compiled within the selected publications for comparative analysis. The transfusion rate in the current surgical era was 13.3% versus 38.7% in the previous era ( P = 0.0001). When a transfusion was required in the current surgical era there was a two-fold reduction in the number of units transfused (1.5 U vs. 3.8 U, P = 0.0001). Statistically significant improvements in operative time and length of hospital stay were presented within the current surgical era ( P = 0.0001). When a transfusion was required there was an increased relative risk score of 7 for mortality (4.9% vs. 0.7%, P = 0.0001), however, improvement in mortality rates did not reach statistical significance across surgical eras (1.3% vs. 4.0%, P = 0.0001). conclusions: The cond

关键词： Major hepatic resection Improved hemostasis Improved outcomes

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cDc7 inhibition impairs neuroendocrine transformation in lung and prostate tumors through MYc degradation

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3519-3532页

作者： Alvaro Quintanal-Villalonga Kenta Kawasaki Esther Redin Fathema Uddin Swanand Rakhade Vidushi Durani Amin Sabet Moniquetta Shafer Wouter R.Karthaus Samir Zaidi Yingqian A.Zhan Parvathy Manoj Harsha Sridhar Dennis Kinyua Hong Zhong Barbara P.Mello Metamia ciampricotti Umesh K.Bhanot Irina Linkov Juan Qiu Radhika A.Patel colm Morrsey Sanjoy Mehta Jesse Barnes Michael c.Haffner Nichlas D.Socci Richard P.Koche Elisa de Stanchina Sonia Molina-Pinelo Sohrab Salehi Helena A.Yu Joseph M.chan charles M.Rudin department of Medicine Thoracic Oncology ServiceMemorial Sloan Kettering Cancer CenterNew YorkNYUSA cancer Biology and Genetics Program Sloan Kettering InstituteMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Vagelos college of Physicians and Surgeons Columbia UniversityNew YorkNYUSA Weill cornell Graduate School of Medical Sciences Weill Cornell MedicineNew YorkNYUA Human oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNYUSA center for Epigenetics research Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Pathology core Facilty Department of Pathology and Laboratory MedicineMSKCCNew YorkNYUSA Antitumor Assessment core Memorial Sloan Kettering Cancer CenterNew YorkNYUSA Divisionsof Human Biology and clinical research Fred Hutchinon Cancer CenterSeattleWAUSA Deparmentof Urology University of WashingtonSeattleWAUSA Gene Editing&Screening core Facility Memorial Sloan Kettering cancer center New YorkNYUSA department of Laboratory Medicine and Pathology University of WashingtonSeattleWAUSA Bioinfomatics coreFacility Memorial Soan Kettering Cancer CenterNew YorkNYUSA institute of Biomedicine of Seille(Bis) HURCSCUniversidad de SevillaSevilleSpain computational oncology Department of Epidemiology and BiostatisticsMemorial Sloan Kettering Cancer CenterNew YorkNYUSA Well cornell Medical college New York NYUSA Present address:Swiss institute for Experimental cancer research(ISREc) School of Life SciencesEPFLLausanneSwitzerland

Neuroendocrine(NE)transformation is a mechanism of resistance to targeted therapy in lung and prostate adenocarcinomas leading to poor *** to date,even if patients at high risk of transformation can be identified by the occurrence of Tumor Protein P53(TP53)and Retinoblastoma Transcriptional corepressor 1(RB1)mutations in their tumors,no therapeutic strategies are available to prevent or delay histological *** of the cell cycle kinase cell Division cycle 7(cDc7)occurred in tumors during the initial steps of NE transformation,already after TP53/RB1 co-inactivation,leading to induced sensitivity to the cDc7 inhibitor ***7 inhibition suppressed NE transdifferentiation and extended response to targeted therapy in in vivo models of NE transformation by inducing the proteasome-mediated degradation of the MYc Proto-Oncogen(MYc),implicated in stemness and histological *** overexpression of a degradation-resistant MYc isoform reestablished the NE transformation phenotype observed on targeted therapy,even in the presence of ***7 inhibition also markedly extended response to standard cytotoxics(cisplatin,irinotecan)in lung and prostate small cell carcinoma *** results nominate cDc7 inhibition as a therapeutic strategy to constrain lineage plasticity,as well as to effectively treat NE tumors de novo or after *** simurosertib clinical efficacy trials are ongoing,this concept could be readily translated for patients at risk oftransformation.

关键词： tumors markedly transformation

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4’,5,7-三羟基异黄酮对Balb/c 3T3小鼠成纤维细胞恶性转化的抑制作用

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实用肿瘤杂志 1999年第2期14卷 78-81页

作者：春洪袁守军陈晓光韩锐中国医学科学院中国协和医科大学药物研究所

目的４’，５，７－三羟基异黄酮（ｇｅｎｉｓｔｅｉｎ）与多种肿瘤的低发生风险呈正相关，此文旨在探讨这一化合物的癌化学预防作用。方法用３－ＭＣＡ和ＴＰＡ诱导Ｂａｌｂ／ｃ３Ｔ３细胞，建立体外二阶段转化模型，用这一模型来观察... 详细信息

目的４’，５，７－三羟基异黄酮（ｇｅｎｉｓｔｅｉｎ）与多种肿瘤的低发生风险呈正相关，此文旨在探讨这一化合物的癌化学预防作用。方法用３－ＭＣＡ和ＴＰＡ诱导Ｂａｌｂ／ｃ３Ｔ３细胞，建立体外二阶段转化模型，用这一模型来观察ｇｅｎｉｓｔｅｉｎ对Ｂａｌｂ／ｃ３Ｔ３－Ａ３１小鼠成纤维细胞恶性转化的影响。结果在对细胞没有明显细胞毒作用的浓度下，ｇｅｎｉｓｔｅｉｎ明显抑制细胞的恶性转化。机理研究表明，ｇｅｎｉｓｔｅｉｎ抑制ＴＰＡ刺激的鸟氨酸脱羧酶基因的表达，但其抗氧化作用较弱。结论ｇｅｎｉｓｔｅｉｎ具有良好的癌化学预防作用，其作用与抑制ＴＰＡ的生长刺激以及促癌作用有关。

关键词：成纤维细胞实验肿瘤预防控制三羟基异黄酮

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Emerging molecular targets and therapy for cholangiocarcinoma

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World Journal of Gastrointestinal oncology 2017年第7期9卷 268-280页

作者： Hamzeh Kayhanian Elizabeth c Smyth chiara Braconi department of Gastrointestinal oncology Royal Marsden Hospital London and Surrey SM2 5PT institute of cancer research London and Surrey SM2 5PT

cholangiocarcinoma(ccA) is a rare cancer arising from the biliary tree with a poor prognosis and limited therapeutic options. Recent large scale molecular characterisation studies have identified recurrent genetic alterations in ccA which may be amenable to therapeutic targeting. In this review we explore the genomic landscape of ccA and examine results from trials of molecularly targeted agents and immunotherapy in this disease. challenges in ccA diagnosis, treatment and trial design are discussed and we reflect on future directions which may lead to improved outcomes for ccA patients.

关键词： cholangiocarcinoma Biliary tract cancer Targeted therapy immunotherapy Mutation Molecular Microenvironment Stroma MiRNA

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Nicotine-induced upregulation of antioxidant protein Prx 1 in oral squamous cell carcinoma

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chinese Science Bulletin 2013年第16期58卷 1912-1918页

作者： ZHAO YanHua ZHANG Min YAN Fei cASTO Bruce c TANG XiaoFei Division of Oral Pathology Beijing Institute of Dental Research School of Stomatology Capital Medical University Division of Medical oncology Department of Internal Medicine Ohio State University College of Medicine and Comprehensive Cancer Center Division of Environmental Health Sciences Ohio State University College of Public Health

Nicotine is a source of exogenous oxidative stress, which is associated with the pathogenesis of numerous diseases including oral squamous cell carcinoma (OScc), whereas an antioxidant protein, peroxiredoxin 1 (Prx 1), plays an important role in the modulation of this condition. This study was to investigate the association between Prx 1 and tobacco-induced oxidative stress. The expression of Prx 1 and GST in OScc Tca8113 cells, which were pre-treated with nicotine, was determined. In the present study, MTT assay, reactive oxygen species (ROS) assay, RT-PcR and Western blot analyses, respectively, were conducted to assess cell viability, ROS level, and expression level of Prx 1 and GST in nicotine-treated Tca8113 cells. Nuclear factor kappa B (NF- B) expression was detected by immuno-fluorescence. Our results showed the growth of Tca8113 cells was increased in a dose-dependent manner when cells were treated with nicotine at concentrations from 0.1 to 10 mol/L, but the proliferation of the cells decreased at 100 mol/L. ROS levels increased in all groups treated with nicotine at concentrations of 0.1, 1, 10, or 100 mol/L for 24h. Prx 1 and GST mRNA and protein expression were up-regulated in cells treated with nicotine for the same time at different concentrations or at the same concentration for different times (Pcated from cytoplasm to nucleus, the expression of NF- B was increased in nucleus. These results suggest that up-regulation of Prx1 expression appears to be associated with tobacco-induced oxidative stress, which may play an important role in the pathogenesis of OScc.

关键词：鳞状细胞癌蛋白表达抗氧化剂尼古丁口腔诱导氧化应激 RT-PcR

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Functional expression of gap junction gene cx43 and the myogenic differentiation of rhabdomyosarcoma cells

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Science china chemistry 1995年第3期38卷 305-312页

作者：林仲翔张志谦韩亚玲 c.c.G.Naus K.R.Yu H.Holtzer department of cell Biology Beijing Medical School of Oncology Beijing Institute for Cancer ResearchBeijing 100034 China department of Anatomy University of Western Ontorio London ON N6A5C1Canada department of cell and Developmental Biology University of Pennsylvania PA19104 USA

Rhabdomyosarcoma (RD) cells express low levels of the gap junction protein connexin 43 (cx43), and its mRNA, and display very weak gap junctional intercellular communication (GJIc) as detected by cx43 immunofluorescence, slot-blot and dye-transfer methods. These cells grow rapidly and show aberrant and incomplete myogenic differentiation. To investigate the role of gap junctions in these cells, the expression of cx43 with relation to cell growth and myogenic differentiation in RD single-cell subclones-RDL3 and RDL6 is studied. The subclone RDL3 grows slowly and displays better myogenic differentiation. The expression of cx43, its mRNA and the GJIc in RDL3 is comparable to that in normal myoblasts. Another subclone RDL6 which grows rapidly, but is poorly differentiated, expresses very low levels of cx43 and its mRNA, and very weak GJIc. By using the calcium phosphate precipitate transfection technique, a full-length cDNA-encoding cx43 and a pSV2neo have been introduced into the RDL6 cells. Several stably transfected clones have been obtained. A stable cx43-transfectant clone RDL6/c4 expresses high level of cx43 and its mRNA, and results in dramatic increase of GJIc. These cells grow slowly but display the enhanced myogenic differentiation. A correlation between the down-regulation of cx43 gene expression and a reduced expression of myogenic differentiation in RD cells is demonstrated. Forced expression of cx43 not only inhibits cell growth but also correlates with the improved myogenic differentiation of RD cells.

关键词： connexin 43 gap junctional intercellular communication rhabdomyosarcoma myogenic differentiation single-cell clone cell transfection.

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