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Identification of cancer stem cells provides novel tumor models for drug discovery
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《医学前沿（英文）》 2012年 第6卷 第2期 页码 112-121 doi: 10.1007/s11684-012-0199-1
Cancer stem cells (CSCs) have received considerable attention from the research community since they were first reported in human acute myeloid leukemia 15 years ago. Accumulating evidence suggests that CSCs are responsible for tumor initiation and progression, drug resistance, and metastasis in both liquid and solid tumors. These findings lead to the development of novel compounds targeting CSC populations that is becoming increasingly important for eradicating CSCs in heterogeneous tumor masses and to cure the cancer. Since 2003, we have participated in CSC studies and encountered crucial early events in the field. This article reviews the history of CSC biology, clarifies the term and its definition, and further addresses the issue of how to utilize CSCs in therapeutic target discovery and drug development based on our substantial experience.
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《医学前沿（英文）》 2013年 第7卷 第4期 页码 462-476 doi: 10.1007/s11684-013-0270-6
Evaluating the effects of novel drugs on appropriate tumor models has become crucial for developing more effective therapies that target highly tumorigenic and drug-resistant cancer stem cell (CSC) populations. In this study, we demonstrate that a subset of cancer cells with CSC properties may be enriched into tumor spheroids under stem cell conditions from a non-small cell lung cancer cell line. Treating these CSC-like cells with gemcitabine alone and a combination of gemcitabine and the novel CHK1 inhibitor PF-00477736 revealed that PF-00477736 enhances the anti-proliferative effect of gemcitabine against both the parental and the CSC-like cell populations. However, the CSC-like cells exhibited resistance to gemcitabine-induced apoptosis. Collectively, the spheroid-forming CSC-like cells may serve as a model system for understanding the mechanism underlying the drug resistance of CSCs and for guiding the development of better therapies that can inhibit tumor growth and eradicate CSCs.
关键词： drug resistance cancer stem cell checkpoint kinase 1 (CHK1) PF-00477736 lung cancer tumorigenicity
Epithelial-to-mesenchymal transition in cancer: complexity and opportunities
Yun Zhang, Robert A. Weinberg
《医学前沿（英文）》 2018年 第12卷 第4期 页码 361-373 doi: 10.1007/s11684-018-0656-6
The cell-biological program termed the epithelial-to-mesenchymal transition (EMT) plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenchymal phenotypic axis. These cell states display distinctive cellular characteristics, including stemness, invasiveness, drug-resistance and the ability to form metastases at distant organs, and thereby contribute to cancer metastasis and relapse. Currently we still lack a coherent overview of the molecular and biochemical mechanisms inducing cells to enter various states along the epithelial-mesenchymal phenotypic spectrum. An improved understanding of the dynamic and plastic nature of the EMT program has the potential to yield novel therapies targeting this cellular program that may aid in the management of high-grade malignancies.
关键词： epithelial-to-mesenchymal transition cancer metastasis cancer stem cell
The unregulated commercialization of stem cell treatments: a global perspective
Douglas Sipp
《医学前沿（英文）》 2011年 第5卷 第4期 页码 348-355 doi: 10.1007/s11684-011-0150-x
关键词： stem cell tourism medical ethics stem cell policy and regulation alternative medicine
The regulatory sciences for stem cell-based medicinal products
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《医学前沿（英文）》 2014年 第8卷 第2期 页码 190-200 doi: 10.1007/s11684-014-0323-5
Over the past few years, several new achievements have been made from stem cell studies, many of which have moved up from preclinical stages to early, or from early to middle or late, stages thanks to relatively safe profile and preliminary evidence of effectiveness. Moreover, some stem cell-based products have been approved for marketing by different national regulatory authorities. However, many critical issues associated mainly with incomplete understanding of stem cell biology and the relevant risk factors, and lack of effective regulations still exist and need to be urgently addressed, especially in countries where establishment of appropriate regulatory system just commenced. More relevantly, the stem cell regulatory sciences need to be established or improved to more effectively evaluate quality, safety and efficacy of stem cell products, and for building up the appropriate regulatory framework. In this review, we summarize some new achievements in stem cell studies, especially the preclinical and clinical studies, the existing regulations, and the associated challenges, and we then propose some considerations for improving stem cell regulatory sciences with a goal of promoting the steadfast growth of the well-regulated stem cell therapies abreast of evolvement of stem cell sciences and technologies.
关键词： stem cell-based medicinal products (SCMPs) stem cell therapy (SCT) safety effectiveness standards guidelines regulatory science
Therapeutic potential of stem cell in liver regeneration
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《医学前沿（英文）》 2011年 第5卷 第1期 页码 26-32 doi: 10.1007/s11684-011-0107-0
Liver transplantation is the only life-saving procedure for patients with end-stage liver disease. However, its potential benefits are hampered by many disadvantages, such as the relative shortage of donors, operative risks, and high costs. These issues have prompted the search for new alternative therapies for irreversible liver disease. Stem cell therapy, with the ability for self-renewal and potential for multilineage differentiation, is a promising alternative approach. Several studies have demonstrated that transplantation of hepatic stem/progenitor cells or hepatocyte-like cells derived from multipotent stem cells leads to donor cell-mediated repopulation of the liver and improved survival rates in experimental models of liver disease. However, a registered clinical application based on stem cell technology will take at least an additional 5 to 10 years because of some limitations; e.g. the lack of suitable cell sources and risk of teratoma formation. This review summarizes the general understanding of the therapeutic potentials of stem cells in liver disease, including the sources, mechanisms, and delivery methods of hepatic stem cells in liver regeneration, and discusses some challenges for their therapeutic application.
Stem cell niches and endogenous electric fields in tissue repair
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《医学前沿（英文）》 2011年 第5卷 第1期 页码 40-44 doi: 10.1007/s11684-011-0108-z
Adult stem cells are responsible for homeostasis and repair of many tissues. Endogenous adult stem cells reside in certain regions of organs, known as the stem cell niche, which is recognized to have an important role in regulating tissue maintenance and repair. In wound healing and tissue repair, stem cells are mobilized and recruited to the site of wound, and participate in the repair process. Many regulatory factors are involved in the stem cell-based repair process, including stem cell niches and endogenous wound electric fields, which are present at wound tissues and proved to be important in guiding wound healing. Here we briefly review the role of stem cell niches and endogenous electric fields in tissue repair, and hypothesize that endogenous electric fields become part of stem cell niche in the wound site.
Transcriptomics and proteomics in stem cell research
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《医学前沿（英文）》 2014年 第8卷 第4期 页码 433-444 doi: 10.1007/s11684-014-0336-0
Stem cells are capable of self-renewal and differentiation, and the processes regulating these events are among the most comprehensively investigated topics in life sciences. In particular, the molecular mechanisms of the self-renewal, proliferation, and differentiation of stem cells have been extensively examined. Multi-omics integrative analysis, such as transcriptomics combined with proteomics, is one of the most promising approaches to the systemic investigation of stem cell biology. We reviewed the available information on stem cells by examining published results using transcriptomic and proteomic characterization of the different stem cell processes. Comprehensive understanding of these important processes can only be achieved using a systemic methodology, and employing such method will strengthen the study on stem cell biology and promote the clinical applications of stem cells.
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《医学前沿（英文）》 2013年 第7卷 第3期 页码 306-315 doi: 10.1007/s11684-013-0279-x
Allogeneic hematopoietic stem cell transplantation (HSCT) is one of the most effective options for hematological malignancies, and human leukocyte antigen-partially matched related donors (PMRDs) are a valuable option for HSCT. Several protocols (with or without ex vivo T-cell depletion (TCD)) have been established worldwide. TCD including CD34+positive selection and CD3/CD19 depletion has successfully overcome the human leukocyte antigen disparity. However, TCD is associated with prolonged immune deficiencies, increased risks of infectious complications, and high transplantation-related mortality. PMRD HSCT without ex vivo TCD is well developed, and numerous patients have benefitted from it. Here, we review the literature on PMRD HSCT.
关键词： partially matched related donor hematopoietic stem cell transplantation allogeneic
《医学前沿（英文）》 2022年 第16卷 第2期 页码 227-239 doi: 10.1007/s11684-021-0896-8
关键词： cannabidiol depression radial neural stem cells neurogenesis
In vivo imaging of hematopoietic stem cell development in the zebrafish
Panpan Zhang, Feng Liu
《医学前沿（英文）》 2011年 第5卷 第3期 页码 239-247 doi: 10.1007/s11684-011-0123-0
关键词：
hematopoietic stem cell
hematopoiesis
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《医学前沿（英文）》 2015年 第9卷 第4期 页码 412-420 doi: 10.1007/s11684-015-0423-x
Genetic mutations are considered to drive the development of acute myeloid leukemia (AML). With the rapid progress in sequencing technologies, many newly reported genes that are recurrently mutated in AML have been found to govern the initiation and relapse of AML. These findings suggest the need to distinguish the driver mutations, especially the most primitive single mutation, from the subsequent passenger mutations. Recent research on DNA methyltransferase 3A (DNMT3A) mutations provides the first proof-of-principle investigation on the identification of preleukemic stem cells (pre-LSCs) in AML patients. Although DNMT3A mutations alone may only transform hematopoietic stem cells into pre-LSCs without causing the full-blown leukemia, the function of this driver mutation appear to persist from AML initiation up to relapse. Therefore, identifying and targeting preleukemic mutations, such as DNMT3A mutations, in AML is a promising strategy for treatment and reduction of relapse risk.
关键词： preleukemic stem cell acute myeloid leukemia relapse DNMT3A
《医学前沿（英文）》 2021年 第15卷 第6期 页码 942-942 doi: 10.1007/s11684-021-0876-z
Stem cell gene therapy: the risks of insertional mutagenesis and approaches to minimize genotoxicity
Chuanfeng Wu, Cynthia E. Dunbar
《医学前沿（英文）》 2011年 第5卷 第4期 页码 356-371 doi: 10.1007/s11684-011-0159-1
关键词： gene therapy hematopoietic stem cells insertional mutagenesis genotoxicity induced pluripotent stem cell
The stem cell and tissue engineering research in Chinese ophthalmology
GE Jian, LIU Jingbo
《医学前沿（英文）》 2007年 第1卷 第1期 页码 6-10 doi: 10.1007/s11684-007-0002-x
关键词： available observable neuroregeneration protection function reconstruction
标题 作者 时间 类型 操作
Combined gemcitabine and CHK1 inhibitor treatment induces apoptosis resistance in cancer stem cell-likecells enriched with tumor spheroids from a non-small cell lung cancer cell line
null
期刊论文
Epithelial-to-mesenchymal transition in cancer: complexity and opportunities
Yun Zhang, Robert A. Weinberg
期刊论文
Advancement of human leukocyte antigen-partially matched related hematopoietic stem cell transplantation
null
期刊论文
Cannabidiol prevents depressive-like behaviors through the modulation of neural stem cell differentiation
期刊论文
Mutant DNA methylation regulators endow hematopoietic stem cells with the preleukemic stem cell property
null
期刊论文
Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancercell proliferation and
期刊论文
Stem cell gene therapy: the risks of insertional mutagenesis and approaches to minimize genotoxicity
Chuanfeng Wu, Cynthia E. Dunbar
期刊论文
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