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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
H. sinensis mycelium inhibits epithelial-mesenchymal transition by inactivating
Li Lu, Haiyan Zhu, Hailin Wang, Huaping Liang, Yayi Hou, Huan Dou
《医学前沿(英文)》 2021年 第15卷 第2期 页码 313-329 doi: 10.1007/s11684-020-0737-1
关键词: epithelial−mesenchymal transition H. sinensis mycelium midkine pulmonary fibrosis
Lihui WANG, Lianhong LI, Shen LV, Shujun FAN, Li ZHAN, Bo WANG, Zhong ZHANG
《医学前沿(英文)》 2009年 第3卷 第2期 页码 164-170 doi: 10.1007/s11684-009-0038-1
关键词: epithelial-mesenchymal transition vascular endothelial cell growth factor matrix metalloproteinase-9 cyclooxygenase-2 higher microvascular density breast cancer
Non-genetic mechanisms of diabetic nephropathy
null
《医学前沿(英文)》 2017年 第11卷 第3期 页码 319-332 doi: 10.1007/s11684-017-0569-9
Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetes mellitus patients and is characterized by thickened glomerular basement membrane, increased extracellular matrix formation, and podocyte loss. These phenomena lead to proteinuria and altered glomerular filtration rate, that is, the rate initially increases but progressively decreases. DN has become the leading cause of end-stage renal disease. Its prevalence shows a rapid growth trend and causes heavy social and economic burden in many countries. However, this disease is multifactorial, and its mechanism is poorly understood due to the complex pathogenesis of DN. In this review, we highlight the new molecular insights about the pathogenesis of DN from the aspects of immune inflammation response, epithelial–mesenchymal transition, apoptosis and mitochondrial damage, epigenetics, and podocyte–endothelial communication. This work offers groundwork for understanding the initiation and progression of DN, as well as provides ideas for developing new prevention and treatment measures.
关键词: diabetic nephropathy immune inflammatory response epithelial–mesenchymal transition apoptosis mitochondrial damage epigenetics podocyte–endothelial communication
Zhao DING, Zhishui CHEN, Xilin CHEN, Ming CAI, Hui GUO, Nianqiao GONG
《医学前沿(英文)》 2009年 第3卷 第2期 页码 204-210 doi: 10.1007/s11684-009-0039-0
关键词: anti-ERK2 renal transplantation epithelial mesenchymal transition chronic allograft nephropathy
Mesenchymal stem cells and immune disorders: from basic science to clinical transition
Shihua Wang, Rongjia Zhu, Hongling Li, Jing Li, Qin Han, Robert Chunhua Zhao
《医学前沿(英文)》 2019年 第13卷 第2期 页码 138-151 doi: 10.1007/s11684-018-0627-y
关键词: mesenchymal stem cell clinical transition immune disorders
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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
Comparison of human nasal epithelial cells grown as explant outgrowth cultures or dissociated tissue
null
《医学前沿(英文)》 2013年 第7卷 第4期 页码 486-491 doi: 10.1007/s11684-013-0287-x
The purpose of this study was to compare cell growth characteristics, ciliated cell differentiation, and function of human nasal epithelial cells established as explant outgrowth cultures or dissociated tissue cultures. Human nasal mucosa of the uncinate process was obtained by endoscopy and epithelial cell cultures were established by explant outgrowth or dissociated tissue culture methods. Epithelial cell growth characteristics were observed by inverted phase contrast microscopy. Ciliated cell differentiation was detected by β-tubulin IV and ZO-1 immunocytochemistry. Basal and ATP-stimulated ciliary beat frequency (CBF) was measured using a high-speed digital microscopic imaging system. Both the explant and dissociated tissue cultures established as monolayers with tight junctions and differentiated cell composition, with both types of cultures comprising ciliated and non-ciliated epithelial cells. Fibroblasts were also frequently found in explant cultures but rarely seen in dissociated tissue cultures. In both culture systems, the highest ciliated cell density appeared at 7th–10th culture day and declined with time, with the lifespan of ciliated cells ranging from 14 to 21 days. Overall, 10% of the cells in explant cultures and 20% of the cells in the dissociated tissue cultures were ciliated. These two cultures demonstrated similar ciliary beat frequency values at baseline (7.78±1.99 Hz and 7.91±2.52 Hz, respectively) and reacted equivalently following stimulation with 100 μM ATP. The results of this study indicate that both the explant outgrowth and dissociated tissue culture techniques are suitable for growing well-differentiated nasal ciliated and non-ciliated cells, which have growth characteristics and ciliary activity similar to those of nasal epithelial cells in vivo.
关键词: ciliated cells ciliary beat frequency dissociated tissue culture explant culture nasal epithelial cells
null
《医学前沿(英文)》 2011年 第5卷 第1期 页码 33-39 doi: 10.1007/s11684-011-0114-1
Adult stem cells hold great promise for wound healing and tissue regeneration. Mesenchymal stem cells (MSCs), for example, have been shown to play a role in tissue repair. Research has shown that endogenous bone marrow MSCs or exogenously delivered MSCs migrate to the sites of injury and participate in the repair process. The precise mechanisms underlying migration of MSCs into the injured tissue are still not fully understood, although multiple signaling pathways and molecules were reported, including both chemoattractive factors and endogenous electric fields at wounds. This review will briefly summarize the regulatory facors and signaling transduction pathways involved in migration of MSCs. A better understanding of the molecular mechanisms involved in the migration of MSCs will help us to develop new stem cell-based therapeutic strategies in regenerative medicine.
关键词: mesenchymal stem cells migration molecular mechanisms signaling pathway
null
《医学前沿(英文)》 2014年 第8卷 第1期 页码 91-95 doi: 10.1007/s11684-014-0305-7
A total of 251 patients with epithelial ovarian cancer (EOC) treated between 2002 and 2008 was retrospectively analyzed to investigate the long-term outcomes and prognostic factors of these patients, particularly those who underwent primary debulking surgery followed by platinum-based chemotherapy. Clinico-pathological parameters, including progression-free survival (PFS) and overall survival (OS), were also analyzed. The median follow-up period from the end of initial treatment to June 2010 was 58 months. The three-year PFS rate was 61.7% for International Federation of Gynecology and Obstetrics (FIGO) I–II, 19.9% for FIGO III–IV, and 33.9% for all stages. By comparison, the five-year PFS rate was 44.6% for FIGO I–II, 17.7% for FIGO III–IV, and 28.3% for all stages. The three-year OS rate was 67.9% for FIGO I–II, 41.7% for FIGO III–IV, and 50.2% for all stages. The five-year OS rate was 52.7% for FIGO I–II, 30.8% for FIGO III–IV, and 39.2% for all stages. Univariate analysis revealed that advanced FIGO stage, serum CA125, and suboptimal debulking were significant factors affecting PFS and OS. In multivariate analysis, PFS was significantly influenced by FIGO stage and suboptimal debulking. However, OS was significantly influenced by advanced FIGO stage only. Our study confirms the efficacy of surgery followed by platinum-based chemotherapy for EOC. FIGO stage is considered as one of the most reliable predictors of the prognosis of patients with EOC.
关键词: ovarian carcinoma prognostic factors surgery chemotherapy survival
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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
null
《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
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
《医学前沿(英文)》 2023年 第17卷 第4期 页码 781-795 doi: 10.1007/s11684-023-0986-x
关键词: dry eye disease glycolytic reprogramming pyroptosis inflammation 2-DG
Transplantation of placenta-derived mesenchymal stem cells in type 2 diabetes: a pilot study
null
《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
Epithelial-to-mesenchymal transition in cancer: complexity and opportunities
Yun Zhang, Robert A. Weinberg
期刊论文
H. sinensis mycelium inhibits epithelial-mesenchymal transition by inactivating
Li Lu, Haiyan Zhu, Hailin Wang, Huaping Liang, Yayi Hou, Huan Dou
期刊论文
Lymphatic metastasis is related to the epithelial-mesenchymal transition and expressions of VEGF, MMP
Lihui WANG, Lianhong LI, Shen LV, Shujun FAN, Li ZHAN, Bo WANG, Zhong ZHANG
期刊论文
Adenovirus-mediated antisense ERK2 gene therapy ameliorates chronic allograft nephropathy in a rat model
Zhao DING, Zhishui CHEN, Xilin CHEN, Ming CAI, Hui GUO, Nianqiao GONG
期刊论文
Mesenchymal stem cells and immune disorders: from basic science to clinical transition
Shihua Wang, Rongjia Zhu, Hongling Li, Jing Li, Qin Han, Robert Chunhua Zhao
期刊论文
Umbilical cord-derived mesenchymal stem cells: strategies, challenges, and potential for cutaneous regeneration
null
期刊论文
Comparison of human nasal epithelial cells grown as explant outgrowth cultures or dissociated tissue
null
期刊论文
Regulatory factors of mesenchymal stem cell migration into injured tissues and their signal transduction
null
期刊论文
Clinical outcomes and prognostic factors of patients with epithelial ovarian cancer subjected to first-line
null
期刊论文
Implantation of human umbilical cord mesenchymal stem cells for ischemic stroke: perspectives and challenges
null
期刊论文
Capacity of human umbilical cord-derived mesenchymal stem cells to differentiate into sweat gland-like
null
期刊论文
Mesenchymal stem cells hold promise for regenerative medicine
Shihua Wang, Xuebin Qu, Robert Chunhua Zhao
期刊论文
Hyperosmolarity promotes macrophage pyroptosis by driving the glycolytic reprogramming of corneal epithelial
期刊论文