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Banking of perinatal mesenchymal stem/stromal cells for stem cellbased personalized medicine over lifetime:Matters arising

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World Journal of Stem Cells 2023年第4期15卷 105-119页

作者： Cheng-Hai Li Jing Zhao Hong-Yan Zhang Bin Wang Stem Cell Program of Clinical Research Center People’s Hospital of Zhengzhou University and Henan Provincial People’s HospitalZhengzhou 450003Henan ProvinceChina Department of Clinical Laboratory People’s Hospital of Zhengzhou University and Henan Provincial People’s HospitalZhengzhou 450003Henan ProvinceChina Department of Pharmacy Fuwai Central China Cardiovascular HospitalZhengzhou 450000Henan ProvinceChina Department of Neurosurgery People’s Hospital of Zhengzhou University and Henan Provincial People’s HospitalZhengzhou 450003Henan ProvinceChina

Mesenchymal stromal/stem cells(MSCs)are currently applied in regenerative medicine and tissue engineering.Numerous clinical studies have indicated that MSCs from different tissue sources can provide therapeutic benefits for patients.MSCs derived from either human adult or perinatal tissues have their own unique advantages in their medical practices.Usually,clinical studies are conducted by using of cultured MSCs after thawing or short-term cryopreserved-then-thawed MSCs prior to administration for the treatment of a wide range of diseases and medical disorders.Currently,cryogenically banking perinatal MSCs for potential personalized medicine for later use in lifetime has raised growing interest in China as well as in many other countries.Meanwhile,this has led to questions regarding the availability,stability,consistency,multipotency,and therapeutic efficiency of the potential perinatal MSC-derived therapeutic products after longterm cryostorage.This opinion review does not minimize any therapeutic benefit of perinatal MSCs in many diseases after short-term cryopreservation.This article mainly describes what is known about banking perinatal MSCs in China and,importantly,it is to recognize the limitation and uncertainty of the perinatal MSCs stored in cryobanks for stem cell medical treatments in whole life.This article also provides several recommendations for banking of perinatal MSCs for potentially future personalized medicine,albeit it is impossible to anticipate whether the donor will benefit from banked MSCs during her/his lifetime.

关键词： Mesenchymal stromal/stem cells Adult mesenchymal stromal/stem cells Perinatal mesenchymal stromal/stem cells Perinatal tissue Stem cell bank personalized medicine

personalized medicine in non-small cell lung cancer: a review from a pharmacogenomics perspective

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Acta Pharmaceutica Sinica B 2018年第4期8卷 530-538页

作者： Wenxiao Jiang Guiqing Cai Peter C.Hu Yue Wang Department of Genetics and Genomic Sciences Icahn School of Medicine at Mount Sinai The University of Texas MD Anderson Cancer Center Department of Molecular and Human Genetics Baylor College of Medicine

Non-small cell lung cancer is a prevalent and rapidly-expanding challenge to modern medicine. While generalized medicine with traditional chemotherapy yielded comparatively poor response rates and treatment results, the cornerstone of personalized medicine using genetic profiling to direct treatment has exalted the successes seen in the field and raised the standard for patient treatment in lung and other cancers. Here, we discuss the current state and advances in the field of personalized medicine for lung cancer, reviewing several of the mutation-targeting strategies that are approved for clinical use and how they are guided by patient genetic information. These classes include inhibitors of tyrosine kinase(TKI), anaplastic lymphoma kinase(ALK), and monoclonal antibodies. Selecting from these treatment plans and determining the optimal dosage requires in-depth genetic guidance with consideration towards not only the underlying target genes but also other factors such as individual metabolic capability and presence of resistance-conferring mutations both directly on the target gene and along its cascade(s).Finally, we provide our viewpoints on the future of personalized medicine in lung cancer, including target-based drug combination, mutation-guided drug design and the necessity for data of population genetics, to provide rough guidance on treating patients who are unable to get genetic testing.

关键词： personalized medicine Non-small cell lung cancer Pharmacogenomics Tyrosine kinase Anaplastic lymphoma kinase Inhibitor Monoclonal antibody

personalized medicine of non-gene-specific chemotherapies for non-small cell lung cancer

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Acta Pharmaceutica Sinica B 2021年第11期11卷 3406-3416页

作者： Wenxiao Jiang Guiqing Cai Peter Hu Yue Wang Otogenetics Corp. AtlantaGA 30360USA Quest Diagnostics San Juan CapistranoCA 92675USA The University of Texas MD Anderson Cancer Center HoustonTX 77030USA Department of Molecular and Human Genetics Baylor College of MedicineHoustonTX 77030USA

Non-small cell lung cancer is recognized as the deadliest cancer across the globe.In some areas,it is more common in women than even breast and cervical cancer.Its rise,vaulted by smoking habits and increasing air pollution,has garnered much attention and resource in the medical field.The first lung cancer treatments were developed more than half a century ago.Unfortunately,many of the earlier chemotherapies often did more harm than good,especially when they were used to treat genetically unsuitable patients.With the introduction of personalized medicine,physicians are increasingly aware of when,how,and in whom,to use certain anti-cancer agents.Drugs such as tyrosine kinase inhibitors,anaplastic lymphoma kinase inhibitors,and monoclonal antibodies possess limited utility because they target specific oncogenic mutations,but other drugs that target mechanisms universal to all cancers do not.In this review,we discuss many of these non-oncogene-targeting anti-cancer agents including DNA replication inhibitors(i.e.,alkylating agents and topoisomerase inhibitors)and cytoskeletal function inhibitors to highlight their application in the setting of personalized medicine as well as their limitations and resistance factors.

关键词： Non-small cell lung cancer personalized medicine Pharmacogenomics Pharmacogenetics Drug resistance Vinca alkaloids Toxoids DNA replication inhibitors

Frequency of and reasons behind non-listing in adult patients referred for liver transplantation: Results from a retrospective study

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World Journal of Transplantation 2024年第2期14卷 99-106页

作者： Marco Biolato Luca Miele Giuseppe Marrone Claudia Tarli Antonio Liguori Rosaria Calia Giovanni Addolorato Salvatore Agnes Antonio Gasbarrini Maurizio Pompili Antonio Grieco Department of Medical and Surgical Sciences CEMADFondazione Policlinico Universitario Agostino Gemelli IRCCSRome 00168Italy Department of Translational medicine and Surgery Catholic University of Sacred HeartRome 00168Italy

BACKGROUND Few studies have evaluated the frequency of and the reasons behind the refusal of listing liver transplantation candidates.AIM To assess the ineligibility rate for liver transplantation and its motivations.METHODS A single-center retrospective study was conducted on adult patients which entailed a formal multidisciplinary assessment for liver transplantation eligibility.The predictors for listing were evaluated using multivariable logistic regression.RESULTS In our center,314 patients underwent multidisciplinary work-up before liver transplantation enlisting over a three-year period.The most frequent reasons for transplant evaluation were decompensated cirrhosis(51.6%)and hepatocellular carcinoma(35.7%).The non-listing rate was 53.8%and the transplant rate was 34.4%for the whole cohort.Two hundred and five motivations for ineligibility were collected.The most common contraindications were psychological(9.3%),cardiovascular(6.8%),and surgical(5.9%).Inappropriate or premature referral accounted for 76(37.1%)cases.On multivariable analysis,a referral from another hospital(OR:2.113;95%CI:1.259–3.548)served as an independent predictor of non-listing.CONCLUSION A non-listing decision occurred in half of our cohort and was based on an inappropriate or premature referral in one case out of three.The referral from another hospital was taken as a strong predictor of non-listing.

关键词： Controindication Eligibility Evaluation Referral personalized medicine

personalized medicine approach to osteoporosis management in women: integrating genetics, pharmacogenomics, and precision treatments

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Clinical Research Communications 2023年第3期6卷 22-29页

作者： Seyi Samson Enitan Esther Ngozi Adejumo John Osaigbovoh Imaralu Ayodele Ademola Adelakun Oluwakemi Anike Ladipo Comfort Bosede Enitan Department of Medical Laboratory Science Babcock UniversityIlishan-Remo 121103Nigeria Department of Gynaecology and Obstetrics Babcock University Teaching HospitalIlishan-Remo 121103Nigeria Department of Chemical Pathology Babcock University Teaching HospitalIlishan-Remo 121103Nigeria

Osteoporosis has emerged as a significant health issue among postmenopausal women.Addressing this concern necessitates a multifaceted approach encompassing genetics,pharmacogenomics,bone turnover markers,lifestyle factors,concurrent medical conditions,biomarkers,and advanced imaging techniques.Nonetheless,challenges in terms of cost-effectiveness and ethical considerations do exist.Fortunately,the convergence of technological progress and research endeavors offers a promising trajectory.The integration of genetic testing and pharmacogenomics into clinical practice holds substantial potential.This integration empowers healthcare professionals to forecast treatment responses and pinpoint individuals with elevated susceptibility,thereby enabling the implementation of tailored and efficacious interventions that optimize outcomes–personalized medicine.Given the intricate nature of osteoporosis,personalized strategies stand to greatly benefit women grappling with this condition.Further research and collaborative efforts are imperative to propel advancements within this domain,paving the way for further breakthroughs.

关键词： osteoporosis management personalized medicine pharmacogenomics women

Spastin and alsin protein interactome analyses begin to reveal key canonical pathways and suggest novel druggable targets

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Neural Regeneration Research 2025年第3期20卷 725-739页

作者： Benjamin R.Helmold Angela Ahrens Zachary Fitzgerald P.Hande Ozdinler Department of Neurology Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Center for Molecular Innovation and Drug Discovery Center for Developmental TherapeuticsChemistry of Life Processes InstituteNorthwestern UniversityEvanstonILUSA Mesulam Center for Cognitive Neurology and Alzheimer’s Disease Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Feinberg School of medicine Les Turner ALS Center at Northwestern UniversityChicagoILUSA

Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.

关键词： ALS2 alsin amyotrophic lateral sclerosis hereditary spastic paraplegia neurodegenerative diseases personalized medicine precision medicine protein interactome protein-protein interactions SPAST spastin

Pharmacomicrobiomics： a novel route towards personalized medicine？

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Protein & Cell 2018年第5期9卷 432-445页

作者： Marwah Doestzada Arnau Vich Vila Alexandra Zhernakova Debby P.Y. Koonen Rinse K. Weersma Daan J. TOUW Folkert Kuipers Cisca Wijmenga Jingyuan Fu Departments of Genetics University Medical Center Groningen PO Box 30001 9700 RB Groningen The Netherlands Departments of Paediatrics University Medical Center Groningen PO Box 30001 9700 RB Groningen The Netherlands Departments of Gastroenterology & Hepatology University Medical Center Groningen PO Box 30001 9700 RB Groningen The Netherlands Departments of Clinical Pharmacy & Pharmacology University Medical Center Groningen PO Box 30001 9700 RB Groningen The Netherlands Departments of Laboratory medicine University Medical Center Groningen PO Box 30001 9700 RB Groningen The Netherlands K.G. Jebsen Coeliac Disease Research Centre Department of Immunology University of Oslo P.O. Box 1072 Blindern 0316 Oslo Norway

Inter-individual heterogeneity in drug response is a serious problem that affects the patient＇s wellbeing and poses enormous clinical and financial burdens on a societal level. Pharmacogenomics has been at the forefront of research into the impact of individual genetic background on drug response variability or drug toxicity, and recently the gut microbiome, which has also been called the second genome, has been recog- nized as an important player in this respect. Moreover, the microbiome is a very attractive target for improving drug efficacy and safety due to the opportunities to manipulate its composition. Pharmacomicrobiomics is an emerging field that investigates the interplay of microbiome variation and drugs response and disposi- tion （absorption, distribution, metabolism and excretion）. In this review, we provide a historical overview and examine current state-of-the-art knowledge on the complex interactions between gut microbiome, host and drugs. We argue that combining pharmacogenomics and pharmacomicrobiomics will provide an important foundation for making major advances in personalized medicine.

关键词： gut microbiome drug metabolism personalized medicine

Exploitation of Gene Expression and Cancer Biomarkers in Paving the Path to Era of personalized medicine

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Genomics, Proteomics & Bioinformatics 2017年第4期15卷 220-235页

作者： Hala Fawzy Mohamed Kamel Hiba Saeed A.Bagader Al-Amodi Biochemistry Department Faculty of Medicine Umm AL-Qura University Medical Biochemistry Department Faculty of Medicine Ain Shams University

Cancer therapy agents have been used extensively as cytotoxic drugs against tissue or organ of a specific type of cancer. With the better understanding of molecular mcchanislns undcrlying carcinogenesis and cellular events during cancer progression and metastasis, it is now possible to use targeted therapy for these molecular events. Targeted therapy is able to identify cancer patients with dissimilar genetic defects at cellular level for the same cancer type and consequently requires individualized approach for treatment. Cancer therapy begins to shill steadily from the tra- ditional approach of ＂one regimen for all patients＂ to a more individualized approach, through which each patient will be treated specifically according to their specific genetic defects. personalized medicine accordingly requires identification of indicators or markers that guide in the decision mak- ing of such therapy to the chosen patients for more effective therapy. Cancer biomarkcrs are fre- quently used in clinical practice for diagnosis and prognosis, as well as identification ol responsive patients and prediction of treatment response of cancer patient. The rapid breakthrough and development of microarray and sequencing technologies is probably the main tool for paving the way toward ＂individualized biomarker-driven cancer therapy＂ or ＂personalized medicine＂. In this review, we aim to provide an updated knowledge and overview of the currcnt landscape of cancer biomarkers and their role in personalized medicine, emphasizing the impact of gcnomics Oil the implementation of new potential targeted therapies and development of novel cancer biomarkers in improving the outcome of cancer therapy.

关键词： personalized medicine Gene expression Targeted therapy Predictive biomarkers Prognostic biomarkers

Organoid models of gastrointestinal Neoplasms:Origin,current status and future applications in personalized medicine

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Genes & Diseases 2018年第4期5卷 323-330页

作者： Yi Pan Shuliang Zhao Zhijun Cao Division of Gastroenterology and Hepatology Key Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai Institute of Digestive Disease145 Middle Shandong RoadShanghai200001China

The in vitro organoid model is a major technological breakthrough that has been established as an important tool in many basic biological and clinical applications.This near-physiological 3D culture system accurately models various biological processes,including tissue renewal,stem cell/niche functions and tissue responses to drugs,mutations or damage.Organoids have the potential value of being an accurate model for disease predictions or drug screening applications and to identify the ideal treatment for that patient.Carcinogenesis can be modeled by mutating specific cancer genes in wild-type organoids;and patient-derived organoids provide an important resource in the development of personalized cancer treatment.Organoids from cancer patients could be used to identify the ideal treatment for a specific patient by growing matched healthy and diseased organoids from human cancer patients which additionally enables clinical screens for drug combinations.Organoids could also provide autologous cells ordin the futuredtissue for transplantation.In this review,we discuss the current advances,challenges and potential applications of this technique in gastrointestinal neoplasms.

关键词： Gastrointestinal neoplasms Intestinal stem cells Living biobanks personalized medicine Stem cell niches Wnt signaling