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1.
Exp Cell Res ; 380(1): 9-19, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-30951707

RESUMO

Chordoma is a rare, slow-growing tumor thought to arise from remnants of embryonic notochord associated with an aggressive outcome. Cancer stem-like cells (CSCs) are related to tumorigenesis, recurrence, and resistance in cancers. Therefore, chordoma CSCs are possible targets for chordoma treatment. In this study, dysregulated miRNAs were determined in chordoma CSCs and identified their role in chordoma. Dysregulated miRNAs were determined via miRNA microarray and validated through qPCR. miRNAs were transiently transfected to the chordoma cell lines and their roles in proliferation, apoptosis, migration and invasion capacities and stem-like properties were identified. Finally, a relationship between clinicopathological features and dysregulated miRNAs has been evaluated among 21 chordoma patients. CD133+CD15+ cells exhibited CSC phenotype with increased CSC- and Epithelial-Mesenchymal Transition (EMT)-related gene expression, invasion, migration, tumorosphere- and colony-forming abilities. In addition, WNT5A, TGF-α, BTG2 and MYCBP genes involved in CSC-related pathways, were targets of miR-140-3p, miR-148a-3p, miR-210-5p and miR-574-5p, respectively. Transfection of CSC-related miRNAs also increased migration and invasion along with stem cell phenotype. Finally, we determined that miR-140-3p and miR-148a-3p expressions correlated with Ki67 while miR-140-3p and TGF-α expressions were correlated with p53. Moreover, MYCBP expression was positively correlated with tumor volume, and metastasis was associated with the expression of miR-210-5p and TGF-α in our patient cohort. Through these findings, we conclude that chordoma CSCs have distinctive miRNA profile, which can regulate stem-like properties of chordoma CSCs.


Assuntos
Cordoma/genética , MicroRNAs/genética , Idoso , Carcinogênese/genética , Movimento Celular/genética , Proliferação de Células/genética , Cordoma/patologia , Proteínas de Ligação a DNA/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Antígeno Ki-67/genética , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Metástase Neoplásica , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fatores de Transcrição/genética , Fator de Crescimento Transformador alfa/genética , Proteína Supressora de Tumor p53/genética
2.
Adv Exp Med Biol ; 1247: 125-134, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31749136

RESUMO

Cancer has an increasing death rate over the world population without discriminating between the industrial and developing countries. Complexity of cancer such as ability of cancer cells to develop resistance to drugs or differential behavior of sub-types and different responses from the patients indicate the continuous need for research and development of new anticancer drugs, new formulations of drug combinations and treatment strategies. Not too surprisingly nature itself, is often the largest territorial reservoir as a source for this type of research and development. Speaking of plant variety, more than 1000 plants have already been identified to produce agents with anticancer activities. In this review, a panel of plant derived anti-cancer agents will be reiterated in terms of their mechanism of action in treatment of disease.


Assuntos
Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Ciclo Celular/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Humanos , Neoplasias/patologia
3.
Exp Cell Res ; 352(2): 393-402, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28232116

RESUMO

Cell lines established from tumors are the most commonly used models in cancer research, and their use in recent years has enabled a greater understanding of the biology of cancer and the means to develop effective treatment strategies. Astroblastomas are uncommon neuroepithelial tumors of glial origin, predominantly affecting young people, mainly teenagers and children, predominantly females. To date, only a single study has reported that astroblastomas contain a large number of neural stem-like cells, which had only a partial proliferation capacity and differentiation. Our objective was to establish an astroblastoma cell line to investigate the presence of astroblastic cells and cancer stem-like cells. The migratory and invasion abilities of the cells were quantified with invasion and migration assays and compared to a glioblastoma cell line. The presence of stem cells was detected with surface-marker analysis by using flow cytometry, and measuring the differentiation ability with a differentiation assay and the self-renewal capacity with a sphere-forming assay. These characteristics may determine whether this novel cell line is a model for astroblastomas that may have stem-cell characteristics. With this novel cell line, scientists can investigate the molecular pathways underlying astroblastomas and develop new therapeutic strategies for patients with these tumors.


Assuntos
Técnicas de Cultura de Células/métodos , Neoplasias Neuroepiteliomatosas/patologia , Células-Tronco Neoplásicas/citologia , Linhagem Celular Tumoral , Separação Celular/métodos , Humanos , Masculino , Células-Tronco Neoplásicas/fisiologia , Esferoides Celulares/citologia , Esferoides Celulares/fisiologia , Células Tumorais Cultivadas , Adulto Jovem
4.
In Vivo ; 33(6): 1921-1927, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31662520

RESUMO

BACKGROUND/AIM: Cumulus cells (CCs) originate from the membrane granulosa cells and surround oocytes during follicle maturation. CCs produce high levels of hyaluronan that targets CD44, which is a major tumorigenic marker. This study aimed to investigate whether CCs have a role in cell therapy by targeting CD44 in pancreatic cancer cells. MATERIALS AND METHODS: CCs were isolated from the oocytes and incubated in a hypoxic environment. BxPC-3 pancreatic cancer cells were treated with CC conditioned media for three days. RESULTS: Conditioned media of CC cells incubated in hypoxic conditions caused a 25% reduction in the viability of BxPC-3 cells. Expression of anti-apoptotic genes was down-regulated, while that of pro-apoptotic genes was upregulated. An increased number of BxPC-3 cells exhibited increased levels of reactive oxygen species and arrested in the synthesis (S) phase of the cell cycle. CONCLUSION: CCs conditioned medium induced apoptosis of pancreatic cancer cells.


Assuntos
Células do Cúmulo/citologia , Apoptose/fisiologia , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Terapia Baseada em Transplante de Células e Tecidos , Células do Cúmulo/metabolismo , Regulação para Baixo/fisiologia , Perfilação da Expressão Gênica/métodos , Humanos , Receptores de Hialuronatos/metabolismo , Oócitos/citologia , Oócitos/metabolismo , Neoplasias Pancreáticas/metabolismo
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