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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.
Metabolism and immunity in breast cancer
Deyu Zhang, Xiaojie Xu, Qinong Ye
《医学前沿(英文)》 2021年 第15卷 第2期 页码 178-207 doi: 10.1007/s11684-020-0793-6
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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
Determination of telomerase activity in stem cells and non-stem cells of breast cancer
LI Zhi, HE Yanli, ZHANG Jiahua, ZHANG Jinghui, HUANG Tao
《医学前沿(英文)》 2007年 第1卷 第3期 页码 294-298 doi: 10.1007/s11684-007-0056-9
Porcine pluripotent stem cells: progress, challenges and prospects
Jianyong HAN, Yi-Liang MIAO, Jinlian HUA, Yan LI, Xue ZHANG, Jilong ZHOU, Na LI, Ying ZHANG, Jinying ZHANG, Zhonghua LIU
《农业科学与工程前沿(英文)》 2019年 第6卷 第1期 页码 8-27 doi: 10.15302/J-FASE-2018233
Pluripotent stem cells (PSCs) are characterized by their capacity for high self-renewal and multiple differentiation potential and include embryonic stem cells, embryonic germ cells and induced PSCs. PSCs provide a very suitable model for the studies of human diseases, drugs screening, regenerative medicine and developmental biology research. Pigs are considered as an ideal model for preclinical development of human xenotransplantation, therapeutic approaches and regenerative medicine because of their size and physiological similarity to humans. However, lack of knowledge about the derivation, characterization and pluripotency mechanisms of porcine PSCs hinders progress in these biotechnologies. In this review, we discuss the latest progress on porcine PSCs generation, evaluation criteria for pluripotency, the scientific and technical questions arising from these studies. We also introduce our perspectives on porcine PSC research, in the hope of providing new ideas for generating naive porcine PSCs and animal breeding.
关键词: embryonic germ cells embryonic stem cells induced pluripotent stem cells pigs pluripotent stem cells
The past, present and future of bovine pluripotent stem cells: a brief overview
Xiuchun TIAN
《农业科学与工程前沿(英文)》 2019年 第6卷 第1期 页码 3-7 doi: 10.15302/J-FASE-2018247
Although the pursuit of bovine embryonic stem cells started more than 26 years ago for the purpose of gene-targeting, true pluripotent stem cells in this economically important species are still elusive. With the rapid advances in genome-editing and cloning using homologously recombined somatic cells, the need for pluripotent stem cells for precise genetic modification in any species became questionable. With the pig being the better model for human regenerative biology, the identification of the commonalities and uniqueness of the pluripotency circuitry across mammalian species may be the main objective for studying pluripotent stem cells in the bovine.
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《医学前沿(英文)》 2012年 第6卷 第1期 页码 41-47 doi: 10.1007/s11684-012-0175-9
Umbilical cord mesenchymal stem cells (MSCs) are a unique, accessible, and non-controversial source of early stem cells that can be readily manipulated. As the most common pluripotent cell, bone marrow-derived MSCs display limitations with the progress of stem cell therapy. By contrast, umbilical cord-derived cells, which have plentiful resources, are more accessible. However, several uncertain aspects, such as the effect of donor selection or culture conditions, long-term therapeutic effects, product consistency, and potential tumorigenicity, are the bottleneck in this clinical therapy. MSCs are predicted to undergo an unprecedented development in clinical treatment when a generally acknowledged criterion emerges. In the current paper, we highlight the application of umbilical cord-derived MSCs in skin therapies based on our previous studies, as well as the achievements of our peers in this field. This paper focuses on the strategies, challenges, and potential of this novel therapy.
关键词: umbilical cord mesenchymal stem cells cutaneous regeneration
Mesenchymal stem cells hold promise for regenerative medicine
Shihua Wang, Xuebin Qu, Robert Chunhua Zhao
《医学前沿(英文)》 2011年 第5卷 第4期 页码 372-378 doi: 10.1007/s11684-011-0164-4
关键词: mesenchymal stem cells differentiation immunomodulation regenerative medicine
Highlights for special issue on “Large Animal Stem Cells”
Jianyong HAN
《农业科学与工程前沿(英文)》 2019年 第6卷 第1期 页码 1-2 doi: 10.15302/J-FASE-2019251
GID complex regulates the differentiation of neural stem cells by destabilizing TET2
《医学前沿(英文)》 doi: 10.1007/s11684-023-1007-9
关键词: TET2 GID complex neural stem cells differentiation of neurons
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《医学前沿(英文)》 2015年 第9卷 第1期 页码 20-29 doi: 10.1007/s11684-014-0371-x
Ischemic stroke is a focal cerebral insult that often leads to many adverse neurological complications severely affecting the quality of life. The prevalence of stroke is increasing throughout the world, while the efficacy of current pharmacological therapies remains unclear. As a neuroregenerative therapy, the implantation of human umbilical cord mesenchymal stem cells (hUC-MSCs) has shown great possibility to restore function after stroke. This review article provides an update role of hUC-MSCs implantation in the treatment of ischemic stroke. With the unique “immunosuppressive and immunoprivilege” property, hUC-MSCs are advised to be an important candidate for allogeneic cell treatment. Nevertheless, most of the treatments are still at primary stage and not clinically feasible at the current time. Several uncertain problems, such as culture conditions, allograft rejection, and potential tumorigenicity, are the choke points in this cellular therapy. More preclinical researches and clinical studies are needed before hUC-MSCs implantation can be used as a routinely applied clinical therapy.
关键词: cellular therapy transplantation human umbilical cord mesenchymal stem cells ischemic stroke
Tumor growth and metastasis can be inhibited by maintaining genomic stability in cancer cells
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《医学前沿(英文)》 2015年 第9卷 第1期 页码 57-62 doi: 10.1007/s11684-015-0389-8
The existence of cancer stem cells, stem-like cancer cells (SLCCs), or tumor-initiating cells is considered as the cause of tumor formation and recurrence, indicating the importance of studying novel therapy that targets SLCCs. The origin of SLCCs is controversial because of two competing hypotheses: SLCCs are either transformed from tissue adult stem cells or dedifferentiated from transformed progenitor cells. Our previous research demonstrates that SLCCs are inducible by increasing genomic instability in cancer cells. In this study, to block the emergence of SLCCs, aminoethyl isothiourea (AET), a compound that clears free radicals and is used to protect patients from radioactive exposure, was used as an agent that maintains genomic stability in combination with mitomycin C (MMC), a commonly used chemotherapeutic drug that damages DNA. Using a rabbit tumor model with VX2 hepatic carcinoma, we found that MMC alone increased lung metastases and disadvantaged survival outcome, but the combination of MMC and AET reversed this effect and even prolonged overall survival. Moreover, in a VX2 xenograft model by immunocompromised mice, MMC alone enriched tumor-initiating cells, but the administration of MMC in combination with AET eliminated tumor cells effectively. Furthermore, MMC alone enhanced genomic instability, but MMC combined with AET attenuated the extent of genomic instability in primary VX2 tumor tissue. Taken together, our data suggest that the genomic protector AET can inhibit the induction of SLCCs, and this combination treatment by AET and cytotoxic agents should be considered as a promising strategy for future clinical evaluation.
关键词: rabbit VX2 liver tumor mitomycin C AET stem-like cancer cells genomic instability
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《医学前沿(英文)》 2013年 第7卷 第3期 页码 345-353 doi: 10.1007/s11684-013-0282-2
Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) possess various advantageous properties, including self-renewal, extended proliferation potential, multi-lineage differentiation potential and capacity for differentiating into sweat gland-like cells in certain conditions. However, little is known about the effect of clinical-grade culture conditions on these properties and on the differentiative potential of hUC-MSCs. In this study, we sought to investigate the properties of hUC-MSCs expanded with animal serum free culture media (ASFCM) in order to determine their potential for differentiation into sweat gland-like cells. We found that primary cultures of hUC-MSCs could be established with ASFCM. Moreover, cells cultured in ASFCM showed vigorous proliferation comparable to those of cells grown in classical culture conditions containing fetal bovine serum (FBS). Morphology of hUC-MSCs cultured in ASFCM was comparable to those of cells grown under classical culture conditions, and hUC-MSCs grown in both of the two culture conditions tested showed the typical antigen profile of MSCs—positive for CD29, CD44, CD90, and CD105, and negative for CD34 and CD45, as expected. Chromosomal aberration assay revealed that the cells were stable after long-term culture under both culture conditions. Like normal cultured MSCs, hUC-MSCs induced under ASFCM conditions exhibited expression of the same markers (CEA, CK14 and CK19) and developmental genes (EDA and EDAR) that are characteristic of normal sweat gland cells. Taken together, our findings indicate that the classical culture medium used to differentiate hUC-MSCs into sweat gland-like cells can be replaced safely by ASFCM for clinical purposes.
关键词: umbilical cord mesenchymal stem cells sweat gland preclinical
Reprogramming of the pig primordial germ cells into pluripotent stem cells: a brief review
Qijing LEI, Qin PAN, Shuai YU, Na LI, Shulin CHEN, Kuldip SIDHU, Jinlian HUA
《农业科学与工程前沿(英文)》 2019年 第6卷 第1期 页码 28-32 doi: 10.15302/J-FASE-2018222
Primordial germ cells (PGCs) are regarded as unipotent cells that can produce only either spermatogonia or oocytes. However, PGCs can be converted into the pluripotent state by first dedifferentiation to embryonic germ cells and then by reprogramming to induce them to become pluripotent stem cells (iPSCs). These two stages can be completely implemented with mouse cells. However, authentic porcine iPSCs have not been established. Here, we discuss recent advances in the stem cell field for obtaining iPSCs from PGCs. This knowledge will provide some clues which will contribute to the regulation of reprogramming to pluripotency in farm species.
关键词: pig pluripotent stem cells primordial germ cells reprogramming
Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study
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《医学前沿(英文)》 2011年 第5卷 第1期 页码 94-100 doi: 10.1007/s11684-011-0116-z
Mesenchymal stem cells (MSC) have been used in clinical trials for severe diabetes, a chronic disease with high morbidity and mortality. Bone marrow is the traditional source of human MSC, but human term placenta appears to be an alternative and more readily available source. Here, the therapeutic effect of human placenta-derived MSC (PD-MSC) was studied in type 2 diabetes patients with longer duration, islet cell dysfunction, high insulin doses as well as poor glycemic control in order to evaluate the safety, efficacy and feasibility of PD-MSC treatment in type 2 diabetes (T2D). Ten patients with T2D received three intravenous infusions of PDSC, with one month interval of infusion. The total number of PDSC for each patient was (1.22–1.51) × 106/kg, with an average of 1.35 × 106/kg. All of the patients were followed up after therapy for at least 3 months. A daily mean dose of insulin used in 10 patients was decreased from 63.7?±?18.7 to 34.7?±?13.4 IU (P<0.01), and the C-peptide level was increased from 4.1?±?3.7 ng/mL to 5.6?±?3.8 ng/mL (P<0.05) respectively after therapy. In 4 of 10 responders their insulin doses reduced more than 50% after infusion. The mean levels of insulin and C-peptide at each time point in a total of 10 patients was higher after treatment (P<0.05). No fever, chills, liver damage and other side effects were reported. The renal function and cardiac function were improved after infusion. The results obtained from this pilot clinical trial indicate that transplantation of PD-MSC represents a simple, safe and effective therapeutic approach for T2D patients with islet cell dysfunction. Further large-scale, randomized and well-controlled clinical studies will be required to substantiate these observations.
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
Determination of telomerase activity in stem cells and non-stem cells of breast cancer
LI Zhi, HE Yanli, ZHANG Jiahua, ZHANG Jinghui, HUANG Tao
期刊论文
Porcine pluripotent stem cells: progress, challenges and prospects
Jianyong HAN, Yi-Liang MIAO, Jinlian HUA, Yan LI, Xue ZHANG, Jilong ZHOU, Na LI, Ying ZHANG, Jinying ZHANG, Zhonghua LIU
期刊论文
Umbilical cord-derived mesenchymal stem cells: strategies, challenges, and potential for cutaneous regeneration
null
期刊论文
Mesenchymal stem cells hold promise for regenerative medicine
Shihua Wang, Xuebin Qu, Robert Chunhua Zhao
期刊论文
Implantation of human umbilical cord mesenchymal stem cells for ischemic stroke: perspectives and challenges
null
期刊论文
Tumor growth and metastasis can be inhibited by maintaining genomic stability in cancer cells
null
期刊论文
Capacity of human umbilical cord-derived mesenchymal stem cells to differentiate into sweat gland-likecells: a preclinical study
null
期刊论文
Reprogramming of the pig primordial germ cells into pluripotent stem cells: a brief review
Qijing LEI, Qin PAN, Shuai YU, Na LI, Shulin CHEN, Kuldip SIDHU, Jinlian HUA
期刊论文