جستجوی مقالات مرتبط با کلیدواژه "(self - renewal" در نشریات گروه "پزشکی"

According to the cancer stem cell (CSC) theory, a subpopulation of cells demonstrating stem-like cell properties is responsible for tumorigenicity, self-renewal capacity, therapy resistance, and recurrence. Due to CSCs’ resistance, it’s demanded to develop drugs having appropriate efficacy. Despite cisplatin is a potent antitumor agent widely used in the treatment of different cancers, its severe side effects and resistance remain a challenge in the clinic. Research has shown that platinum (IV) has considerably fewer side effects and drug resistance. In this study, toxicity and effectiveness of [Pt(dpyam)Cl4] where dpyam is 2,2'-dipyridylamine, as a platinum (IV) agent, has been investigated to find a reliable alternative for cisplatin. To this aim, cancer stem-like cells (CS-LCs) with CD44+/CD133+ phenotype were isolated from HT1080 cells. EJ138, HT1080, and its CS-LCs were selected to compare the effectiveness of Pt (IV) complex versus cisplatin. MTT, apoptosis, and cell cycle analysis were carried out to evaluate drug toxicity. Sphere and colony formation assays confirmed the potentiality of Pt (IV) complex and cisplatin to target stemness characteristics in CS-LCs. Although toxicity results were in favor of cisplatin, the anti-cancer activity of the synthesized Pt (IV) complex was also considerable. Regarding other studies that proposed high selective toxicity of Pt (IV), they could be a volunteer for additional improvements.

microRNAs (miRNAs) play important role in progression of tumorigenesis. They can target self-renewal and epithelial-mesenchymal transition (EMT) abilities in tumor cells, especially in cancer stem cells (CSCs). The objective of this study was to implement data mining to identify important miRNAs for targeting both self-renewal and EMT. We also aimed to evaluate these factors in mammospheres as model of breast cancer stem cells (BCSCs) and metastatic tumor tissues. In this experimental study, mammospheres were derived from MCF-7 cells and characterized for the CSCs properties. Then expression pattern of the selected miRNAs in spheroids were evaluated, using the breast tumor cells obtained from seven patients. Correlation of miRNAs with self-renewal and EMT candidate genes were assessed in mammospheres and metastatic tumors. The results showed that mammospheres represented more colonogenic and spheroid formation potential than MCF-7 cells (P<0.05). Additionally, they had enhanced migration and invasive capabilities. Our computational analyses determined that miR-200c and miR-30c could be candidates for targeting both stemness and EMT pathways. Expression level of miR-200c was reduced, while miR-30c expression level was enhanced in mammospheres, similar to the breast tumor tissues isolated from three patients with grade II/III who received neo-adjuvant treatment. Expression level of putative stem cell markers (OCT4, SOX2, c-MYC) and EMT-related genes (SNAIL1, CDH2, TWIST1/2) were also significantly increased in mammospheres and three indicated patients (P<0.05). Simultaneous down-regulation and up-regulation of respectively miR-200c and miR-30c might be signature of BCSC enrichment in patients post neo-adjuvant therapy. Therefore, targeting both miR-200c and miR-30c could be useful for developing new therapeutic approaches, against BCSCs.

Chronic myeloid leukemia (CML) is a myeloid clonal proliferation disease defining by the presence of the Philadelphia chromosome that shows the movement of BCR-ABL1. In this study, the critical role of the Musashi2-Numb axis in determining cell fate and relationship of the axis to important signaling pathways such as Hedgehog and Notch that are essential for self-renewal pathways in CML stem cells will be reviewed meticulously. In this review, a PubMed search using the keywords of Leukemia, signaling pathways, Musashi2-Numb was performed, and then we summarized different research works. Although tyrosine kinase inhibitors such as Imatinib significantly kill and remove the cell with BCR-ABL1 translocation, they are unable to target BCR-ABL1 leukemia stem cells. The main problem is stem cells resistance to Imatinib therapy. Therefore, the identification and control of downstream molecules/ signaling route of the BCR-ABL1 that are involved in the survival and self-renewal of leukemia stem cells can be an effective treatment strategy to eliminate leukemia stem cells, which supposed to be cured by Musashi2-Numb signaling pathway. The control of molecules /pathways downstream of the BCR-ABL1 and targeting Musashi2-Numb can be an effective therapeutic strategy for treatment of chronic leukemia stem cells. While Musashi2 is a poor prognostic marker in leukemia, in treatment and strategy, it has significant diagnostic value.

Spermatogonial stem cells (SSCs) are undifferentiated cells which are highly reproducible and expandable. Several studies have been conducted to reproduce these cells in culture. They used growth factors, hormones and different feeder cells to improve survival and proliferation of SSCs.
This study was conducted to evaluate the effects of follicular stimulating hormone (FSH) on gene expression of fibroblast growth factor (FGF2) and glial cell-derived neurotrophic factor (GDNF) in Sertoli cells.
Sertoli cells and SSCs were isolated from 3-5 month-old calves. Bovine testicular cells were cultured for 15 days with or without FSH. Identification of these cells was confirmed by immunocytochemistry analysis. Colony formation of SSCs was evaluated using an inverted microscope. The gene expression of FGF2 and GDNF and the gene markers bcl6b, thy-1, and C-kit were evaluated using the quantitative RT-PCR technique.
The results indicated that FSH increased colonization of SSCs. the expression of GDNF, FGF2, and markers of undifferentiated spermatogonia was increased following culture in control and FSH groups (p The results showed that FSH can increase the self-renewal of SSCs in vitro via upregulation of GDNF and FGF2 expression in Sertoli cells.

Embryonic stem cells (ESCs) are regulated by a gene regulatory circuitry composed of transcription factors, signaling pathways, metabolic mediators, and non-coding RNAs (ncRNAs). MicroRNAs (miRNAs) are short ncRNAs which play crucial roles in ESCs. Here, we explored the impact of miR-302b-3p on ESC self-renewal in the absence of leukemia inhibitory factor (LIF).
In this experimental study, ESCs were cultured in the presence of 15% fetal bovine serum (FBS) and induced to differentiate by LIF removal. miR-302b-3p overexpression was performed by transient transfection of mature miRNA mimics. Cell cycle profiling was done using propidium iodide (PI) staining followed by flow cytometry. miRNA expression was quantified using a miR-302b-3p-specific TaqMan assay. Data were analyzed using t test, and a P We observed that miR-302b-3p promoted the viability of both wild-type and LIF-withdrawn ESCs. It also increased ESC clonogenicity and alkaline phosphatase (AP) activity. The defective cell cycling of LIF-deprived ESCs was completely rescued by miR-302b-3p delivery. Moreover, miR-302b-3p inhibited the increased cell death rate induced by LIF removal.
miR-302b-3p, as a pluripotency-associated miRNA, promotes diverse features of ESC self-renewal in the absence of extrinsic LIF signals.

Hair follicle stem cells exist in different sites. Most of the hair follicle stem cells are reside in niche called bulge. Bulge region is located between the opening of sebaceous gland and the attachment site of the arrector pili muscle.
Data were collected using databases and resources of PubMed, Web of Science, Science Direct, Scopus, MEDLINE and their references from the earliest available published to identify English observational studies on hair follicle bulge region.
Bulge stem cells are pluripotent with high proliferative capacity. Specific markers allow the bulge cells to be isolated from mouse or human hair follicle. Stem cells isolated from bulge region are label retaining and slow cycling hence these cells are defined as label-retaining cells. Bulge cell populations, due to their plasticity nature are able to differentiate into distinct linage and could contribute in tissue regeneration.
The current review discuss about bulge stem cells characteristics and biology including their cycle, location, plasticity, specific markers and regenerative nature. Also the differences between mouse and human hair follicles are investigated.

Ecstasy, or 3, 4 (±) methylenedioxymethamphetamine (MDMA), is a potent neurotoxic drug. One of the mechanisms for its toxicity is the secondary release of glutamate. Mouse embryonic stem cells (mESCs) express only one glutamate receptor, the metabotropic glutamate receptor 5 (mGlu5), which is involved in the maintenance and self-renewal of mESCs. This study aims to investigate whether MDMA could influence self-renewal via the mGlu5 receptor in mESCs. In this expremental study, we used immunocytochemistry and reverse transcription-polymerase chain reaction (RT-PCR) to determine the presence of the mGlu5 receptor in mESCs. The expression of mGlu5 was evaluated after MDMA was added to mESCs throughout neural precursor cell formation as group 1 and during neural precursor cell differentiation as group 2. The stemness characteristic in treated mESCs by immunofluorescence and flow cytometry was studied. Finally, caspase activity was evaluated by fluorescence staining in the treated group. One-way ANOVA or repeated measure of ANOVA according to the experimental design was used for statistical analyses. In this study mGlu5 expression was shown in mESCs. In terms of neuronal differentiation, MDMA affected mGlu5 expression during neural precursor cell formation (group 1) and not during neural precursor differentiation (group 2). MDMA (450 μM) induced a significant increment in self-renewal properties in mESCs but did not reverse 2-methyl-6(phenylethynyl) pyridine (MPEP, 1 μM), a non-competitive selective mGlu5 antagonist. Fluorescence staining with anti-caspase 3 showed a significant increase in the number of apoptotic cells in the MDMA group. We observed a dual role for MDMA on mESCs: reduced proliferation and maintenance of self-renewal. The lack of decreasing stemness characteristic in presence of MPEP suggests that MDMA mediates its role through a different mechanism that requires further investigation. In conclusion, despite being toxic, MDMA maintains stemness characteristics.