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Bronchoalveolar lavage fluid assessment facilitates precision medicine for lung cancer

Cancer Biology & medicine 2024年第3期21卷 230-251页

作者： Hantao Zhang Dan Deng Shujun Li Jing Ren Wei Huang Dan Liu Weiya Wang Department of Pathology West China HospitalSichuan UniversityChengdu 610000China West China Biobank West China HospitalSichuan UniversityChengdu 610000China Department of Respiratory and Critical Care medicine Clinical Research Center for Respiratory DiseaseWest China HospitalSichuan UniversityChengdu 610000China

Lung cancer is the most common and fatal malignant disease worldwide and has the highest mortality rate among tumor-related causes of death.Early diagnosis and precision medicine can significantly improve the survival rate and prognosis of lung cancer patients.At present,the clinical diagnosis of lung cancer is challenging due to a lack of effective non-invasive detection methods and biomarkers,and treatment is primarily hindered by drug resistance and high tumor heterogeneity.Liquid biopsy is a method for detecting circulating biomarkers in the blood and other body fluids containing genetic information from primary tumor tissues.Bronchoalveolar lavage fluid(BALF)is a potential liquid biopsy medium that is rich in a variety of bioactive substances and cell components.BALF contains information on the key characteristics of tumors,including the tumor subtype,gene mutation type,and tumor environment,thus BALF may be used as a diagnostic supplement to lung biopsy.In this review,the current research on BALF in the diagnosis,treatment,and prognosis of lung cancer is summarized.The advantages and disadvantages of different components of BALF,including cells,cell-free DNA,extracellular vesicles,and micro RNA are introduced.In particular,the great potential of extracellular vesicles in precision diagnosis and detection of drug-resistant for lung cancer is highlighted.In addition,the performance of liquid biopsies with different body fluid sources in lung cancer detection are compared to facilitate more selective studies involving BALF,thereby promoting the application of BALF for precision medicine in lung cancer patients in the future.

关键词： Lung cancer bronchoalveolar lavage fluid extracellular vesicles liquid biopsy precision medicine

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Hepatitis B virus genotypes in precision medicine of hepatitis Brelated hepatocellular carcinoma:Where we are now

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1097-1103页

作者： Caecilia H C Sukowati Sri Jayanti Turyadi Turyadi David H Muljono Claudio Tiribelli Eijkman Research Center for Molecular Biology Research Organization for HealthNational Research and Innovation Agency of IndonesiaJakarta 10340Indonesia Liver Cancer Unit Fondazione Italiana Fegato ONLUSTrieste 34149Italy Faculty of medicine Hasanuddin UniversityMakassar 90245South SulawesiIndonesia Faculty of medicine and Health University of SydneySydney 2050Australia

Hepatitis B virus(HBV)infection is a major player in chronic hepatitis B that may lead to the development of hepatocellular carcinoma(HCC).HBV genetics are diverse where it is classified into at least 9 genotypes(A to I)and 1 putative genotype(J),each with specific geographical distribution and possible different clinical outcomes in the patient.This diversity may be associated with the precision medicine for HBV-related HCC and the success of therapeutical approaches against HCC,related to different pathogenicity of the virus and host response.This Editorial discusses recent updates on whether the classification of HBV genetic diversity is still valid in terms of viral oncogenicity to the HCC and its precision medicine,in addition to the recent advances in cellular and molecular biology technologies.

关键词： Hepatitis B virus Hepatocellular carcinoma Genotypes Pathogenesis precision medicine

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Re-evaluating the role of pelvic radiation in the age of modern precision medicine and systemic therapy

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World Journal of Clinical Oncology 2024年第1期15卷 1-4页

作者： Tao-Wei Ke Yu-Min Liao Sheng-Chi Chang Che-Hung Lin William Tzu-Liang Chen Ji-An Liang Chun-Ru Chien Department of Colorectal Surgery China Medical University HospitalTaichung 40402Taiwan School of Chinese medicine College of Chinese MedicineChina Medical UniversityTaichung 40402Taiwan Division of Hematology and Oncology Department of Internal MedicineChina Medical University HospitalTaichung 40402Taiwan Department of Colorectal Surgery China Medical University Hsinchu HospitalHsinchu 30272Taiwan School of medicine College of MedicineChina Medical UniversityTaichung 40402Taiwan Department of Radiation Oncology China Medical University HospitalTaichung 40402Taiwan

The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials such as FOWARC(J Clin Oncol 2019;37:3223-3233),NCT04165772(N Engl J Med 2022;386:2363-2376),and PROSPECT(N Engl J Med 2023;389:322-334).In this review,we comprehensively assess these pivotal trials and offer additional insights into the evolving role of pelvic radiation in contemporary oncology.

关键词： Radiotherapy Locally advanced stage rectal cancer precision medicine Systemic therapy Clinical trial

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Integrating disulfidptosis-related long noncoding RNAs in colorectal cancer prognosis:A path to precision medicine

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World Journal of Clinical Oncology 2024年第5期15卷 664-666页

作者： Shi-Yan Zhang Department of Clinical Laboratory Fuding HospitalFujian University of Traditional Chinese MedicineFuding 355200Fujian ProvinceChina

This commentary explores the burgeoning field of disulfidptosis-related long noncoding RNAs(lncRNAs)in the prognosis and therapeutic targeting of colorectal cancer(CRC).By evaluating recent research,including the pivotal study"Predicting colorectal cancer prognosis based on long noncoding RNAs of disulfidptosis genes"by Wang et al,this analysis underscores the critical role of lncRNAs in deciphering the molecular complexities of CRC.Highlighting the innovative methodologies and significant findings,I discuss the implications for patient survival,therapeutic response,and the potential of lncRNAs as biomarkers for precision medicine.The integration of bioinformatics,clinical databases,and molecular biology in these studies offers a promising avenue for advancing CRC treatment strategies and improving patient outcomes.

关键词： Colorectal cancer Disulfidptosis Long noncoding RNAs Prognosis precision medicine

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Push forward LC-MS-based therapeutic drug monitoring and pharmacometabolomics for anti-tuberculosis precision dosing and comprehensive clinical management

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Journal of Pharmaceutical Analysis 2024年第1期14卷 16-38页

作者： Nguyen Quang Thu Nguyen Tran Nam Tien Nguyen Thi Hai Yen Thuc-Huy Duong Nguyen Phuoc Long Huy Truong Nguyen Department of Pharmacology and PharmacoGenomics Research Center Inje University College of MedicineBusan47392Republic of Korea Department of Chemistry University of EducationHo Chi Minh City700000Viet Nam Faculty of Pharmacy Ton Duc Thang UniversityHo Chi Minh City700000Viet Nam

The spread of tuberculosis(TB),especially multidrug-resistant TB and extensively drug-resistant TB,has strongly motivated the research and development of new anti-TB drugs.New strategies to facilitate drug combinations,including pharmacokinetics-guided dose optimization and toxicology studies of first-and second-line anti-TB drugs have also been introduced and recommended.Liquid chromatography-mass spectrometry(LC-MS)has arguably become the gold standard in the analysis of both endo-and exo-genous compounds.This technique has been applied successfully not only for therapeutic drug monitoring(TDM)but also for pharmacometabolomics analysis.TDM improves the effectiveness of treatment,reduces adverse drug reactions,and the likelihood of drug resistance development in TB patients by determining dosage regimens that produce concentrations within the therapeutic target window.Based on TDM,the dose would be optimized individually to achieve favorable outcomes.Pharmacometabolomics is essential in generating and validating hypotheses regarding the metabolism of anti-TB drugs,aiding in the discovery of potential biomarkers for TB diagnostics,treatment monitoring,and outcome evaluation.This article highlighted the current progresses in TDM of anti-TB drugs based on LC-MS bioassay in the last two decades.Besides,we discussed the advantages and disadvantages of this technique in practical use.The pressing need for non-invasive sampling approaches and stability studies of anti-TB drugs was highlighted.Lastly,we provided perspectives on the prospects of combining LC-MS-based TDM and pharmacometabolomics with other advanced strategies(pharmacometrics,drug and vaccine developments,machine learning/artificial intelligence,among others)to encapsulate in an all-inclusive approach to improve treatment outcomes of TB patients.

关键词： Tuberculosis Therapeutic drug monitoring LC-MS MIPD Pharmacometabolomics precision medicine

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precision medicine in chronic obstructive pulmonary disease

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Chinese Medical Journal 2022年第10期135卷 1156-1162页

作者： David M.G.Halpin University of Exeter Medical School College of Medicine and HealthUniversity of ExeterExeterUK.

Over the last 20 years, it has become possible to use a precision medicine approach to the management of chronic obstructive pulmonary disease (COPD). Clinical and physiological features as well as a blood biomarker can be used to target treatments to patients most likely to benefit and avoid treatment in patients less likely to benefit. Future advances in a precision medicine approach to COPD will depend on more precise characterization of individual patients, possibly using quantitative imaging, new physiological techniques, novel biomarkers and genetic profiling. precision medicine has led to significant improvements in the management of COPD and clinicians should use all available information to optimize the treatment of individual patients.

关键词： Chronic obstructive pulmonary disease(COPD) precision medicine Biomarkers Microbiome Comorbidity

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Developing risk models and subtypes of autophagy-associated LncRNAs for enhanced prognostic prediction and precision in therapeutic approaches for liver cancer patients

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Oncology Research 2024年第4期32卷 703-716页

作者： LU ZHANG JINGUO CHU YUSHAN YU Department of General Practice The First Affiliated Hospital of Ningbo UniversityNingboChina

Background:Limited research has been conducted on the influence of autophagy-associated long non-coding RNAs(ARLncRNAs)on the prognosis of hepatocellular carcinoma(HCC).Methods:We analyzed 371 HCC samples from TCGA,identifying expression networks of ARLncRNAs using autophagy-related genes.Screening for prognostically relevant ARLncRNAs involved univariate Cox regression,Lasso regression,and multivariate Cox regression.A Nomogram was further employed to assess the reliability of Riskscore,calculated from the signatures of screened ARLncRNAs,in predicting outcomes.Additionally,we compared drug sensitivities in patient groups with differing risk levels and investigated potential biological pathways through enrichment analysis,using consensus clustering to identify subgroups related to ARLncRNAs.Results:The screening process identified 27 ARLncRNAs,with 13 being associated with HCC prognosis.Consequently,a set of signatures comprising 8 ARLncRNAs was successfully constructed as independent prognostic factors for HCC.Patients in the high-risk group showed very poor prognoses in most clinical categories.The Riskscore was closely related to immune cell scores,such as macrophages,and the DEGs between different groups were implicated in metabolism,cell cycle,and mitotic processes.Notably,high-risk group patients demonstrated a significantly lower IC50 for Paclitaxel,suggesting that Paclitaxel could be an ideal treatment for those at elevated risk for HCC.We further identified C2 as the Paclitaxel subtype,where patients exhibited higher Riskscores,reduced survival rates,and more severe clinical progression.Conclusion:The 8 signatures based on ARLncRNAs present novel targets for prognostic prediction in HCC.The drug candidate Paclitaxel may effectively treat HCC by impacting ARLncRNAs expression.With the identification of ARLncRNAsrelated isoforms,these results provide valuable insights for clinical exploration of autophagy mechanisms in HCC pathogenesis and offer potential avenues for precision medicine.

关键词： Autophagy Hepatocellular carcinoma(HCC) Prognosis precision medicine Paclitaxel

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precision medicine in inflammatory bowel disease:Individualizing the use of biologics and small molecule therapies

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World Journal of Gastroenterology 2023年第10期29卷 1539-1550页

作者： Eric Cheah James Guoxian Huang Department of Gastroenterology and Clinical Nutrition The Royal Children's Hospital MelbourneParkvilleVIC 3052Australia Department of Paediatrics Khoo Teck Puat-National University Children's Medical InstituteNational University Health SystemSingapore 119228Singapore Department of Paediatrics Yong Loo Lin School of MedicineNational University of SingaporeSingapore 119228Singapore

The advent of biologics and small molecules in inflammatory bowel disease(IBD)has marked a significant turning point in the prognosis of IBD,decreasing the rates of corticosteroid dependence,hospitalizations and improving overall quality of life.The introduction of biosimilars has also increased affordability and enhanced access to these otherwise costly targeted therapies.Biologics do not yet represent a complete panacea:A subset of patients do not respond to first-line anti-tumor necrosis factor(TNF)-alpha agents or may subsequently demonstrate a secondary loss of response.Patients who fail to respond to anti-TNF agents typically have a poorer response rate to second-line biologics.It is uncertain which patient would benefit from a different sequencing of biologics or even a combination of biologic agents.The introduction of newer classes of biologics and small molecules may provide alternative therapeutic targets for patients with refractory disease.This review examines the therapeutic ceiling in current treatment strategies of IBD and the potential paradigm shifts in the future.

关键词： precision medicine Therapeutic ceiling Inflammatory bowel disease Biologics Small molecules

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precision medicine via the integration of phenotype-genotype information in neonatal genome project

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Fundamental Research 2022年第6期2卷 873-884页

作者： Xinran Dong Tiantian Xiao Bin Chen Yulan Lu Wenhao Zhou Center for Molecular medicine Children's Hospital of Fudan UniversityNational Children's Medical CenterShanghai 201102China Division of Neonatology Children's Hospital of Fudan UniversityNational Children's Medical CenterShanghai 201102China Department of Neonatology Chengdu Women's and Children's Central HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 610066China

The explosion of next-generation sequencing(NGS)has enabled the widespread use of genomic data in precision medicine.Currently,several neonatal genome projects have emerged to explore the advantages of NGS to diagnose or screen for rare genetic disorders.These projects have made remarkable achievements,but still the genome data could be further explored with the assistance of phenotype collection.In contrast,longitudinal birth cohorts are great examples to record and apply phenotypic information in clinical studies starting at the neonatal period,especially the trajectory analyses for health development or disease progression.It is obvious that efficient integration of genotype and phenotype benefits not only the clinical management of rare genetic disorders but also the risk assessment of complex diseases.Here,we first summarize the recent neonatal genome projects as well as some longitudinal birth cohorts.Then,we propose two simplified strategies by integrating genotypic and phenotypic information in precision medicine based on current studies.Finally,research collaborations,sociological issues,and future perspectives are discussed.How to maximize neonatal genomic information to benefit the pediatric population remains an area in need of more research and effort.

关键词： Neonatal genome project Rare genetic disorders precision medicine Genotype and phenotype integration Longitudinal birth cohort

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Status of precision medicine approaches to traumatic brain injury

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Neural Regeneration Research 2022年第10期17卷 2166-2171页

作者： Sahithi Reddi Smita Thakker-Varia Janet Alder Anna O.Giarratana Department of Neuroscience and Cell Biology Rutgers Robert Wood Johnson Medical SchoolPiscatawayNJUSA

Traumatic brain injury(TBI)is a serious condition in which trauma to the head causes damage to the brain,leading to a disruption in brain function.This is a significant health issue worldwide,with around 69 million people suffering from TBI each year.Immediately following the trauma,damage occurs in the acute phase of injury that leads to the primary outcomes of the TBI.In the hours-to-days that follow,secondary damage can also occur,leading to chronic outcomes.TBIs can range in severity from mild to severe,and can be complicated by the fact that some individuals sustain multiple TBIs,a risk factor for worse long-term outcomes.Although our knowledge about the pathophysiology of TBI has increased in recent years,unfortunately this has not been translated into effective clinical therapies.The U.S.Food and Drug Administration has yet to approve any drugs for the treatment of TBI;current clinical treatment guidelines merely offer supportive care.Outcomes between individuals greatly vary,which makes the treatment for TBI so challenging.A blow of similar force can have only mild,primary outcomes in one individual and yet cause severe,chronic outcomes in another.One of the reasons that have been proposed for this differential response to TBI is the underlying genetic differences across the population.Due to this,many researchers have begun to investigate the possibility of using precision medicine techniques to address TBI treatment.In this review,we will discuss the research detailing the identification of genetic risk factors for worse outcomes after TBI,and the work investigating personalized treatments for these higher-risk individuals.We highlight the need for further research into the identification of higher-risk individuals and the development of personalized therapies for TBI.

关键词： apolipoprotein E biomarkers brain injury brain-derived neurotrophic factor clinical trials personalized treatments precision medicine tau translational research traumatic brain injury

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