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1.
Anticancer Drugs ; 28(8): 869-879, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28614092

RESUMO

Prostate cancer is the second most common cancer among men and the leading cause of death after lung cancer. Development of hormone-refractory disease is a crucial step for prostate cancer progression for which an effective treatment option is currently unavailable. Therefore, there is a need for new agents that can efficiently target cancer cells, decrease tumor growth, and thereby extend the survival of patients in late-stage castration-resistant prostate cancer. In the current study, a novel heterodinuclear copper(II)Mn(II) Schiff base complex combined with P85 was used to evaluate anticancer activity against prostate cancer in vitro and in vivo. Cell proliferation and cytotoxicity were evaluated by cell viability, gene, and protein expression assays in vitro. Results showed that the heterodinuclear copper(II)Mn(II) complex-P85 combination decreased cell proliferation by upregulating the apoptotic gene expressions and blocking the cell proliferation-related pathways. Tramp-C1-injected C57/B16 mice were used to mimic a prostate cancer model. Treatment combination of Schiff base complex and P85 significantly enhanced the cellular uptake of chemicals (by blocking the drug transporters and increased life time), suppressed tumor growth, and decreased tumor volume steadily over the course of the experiments. Overall, heterodinuclear copper(II)Mn(II) complex-P85 showed remarkable anticancer activity against prostate cancer in in vitro and in vivo.


Assuntos
Poloxaleno/farmacologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Bases de Schiff/farmacologia , Animais , Linhagem Celular Tumoral , Complexos de Coordenação/farmacologia , Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Neoplasias da Próstata/genética , Neoplasias de Próstata Resistentes à Castração/genética
2.
Prostate ; 76(15): 1454-63, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27338565

RESUMO

BACKGROUND: Prostate cancer which is the second most common cause of death among men has a high incidence in recent years. Current therapeutic regimens should be improved to overcome drug resistance. At the metastatic stage, tumors become refractory to established chemotherapeutic treatments and cause serious problems at the clinics. Development of new drug molecules that are able to transport through the membrane easily and kill tumor cells rapidly is of great interest. METHOD: In the current study, a novel Heterodinuclear copper(II)Mn(II) Schiff base complex combined with P85 was used for prostate cancer treatment in vivo. Tramp-C1 cells injected animals were subjected to chemotherapeutic formulation treatment and results were analyzed by toxicology analysis, tumor volume measurements, and histopathological analysis. 0.5 mg/kg Schiff base was selected and combined with 0.05% P85 according to the toxicology analysis showing the enzyme levels, blood parameters, and multiple organ toxicity. RESULTS: Results demonstrated that Heterodinuclear copper(II)Mn(II) complex-P85 combination decreased tumor formation and tumor volume steadily over the course of experiments. CONCLUSIONS: Overall, Heterodinuclear copper(II)Mn(II) complex-P85 exerted remarkable anti-cancer activity in vivo in C57/B16 mice. Prostate 76:1454-1463, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Adenocarcinoma/prevenção & controle , Poloxâmero/administração & dosagem , Neoplasias da Próstata/prevenção & controle , Bases de Schiff/administração & dosagem , Adenocarcinoma/patologia , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Progressão da Doença , Combinação de Medicamentos , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Poloxâmero/toxicidade , Neoplasias da Próstata/patologia , Bases de Schiff/toxicidade , Carga Tumoral
3.
Biol Trace Elem Res ; 162(1-3): 72-9, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25129136

RESUMO

After a disruption of skin integrity, the body produces an immediate response followed by a functional and comparable regeneration period, referred to as wound healing. Although normal wounds do not need much attention during the healing period, chronic (non-healing) wounds are the major challenge of current dermatological applications. Therefore, developing new, safe, and effective wound healing drugs has always been an attractive area of international research. In the current study, sodium pentaborate pentahydrate (NaB), pluronics (Plu; F68 and F127), and their combinations were investigated for their wound healing activities, using in vitro and in vivo approaches. The results revealed that NaB significantly increased migration capacity and superoxide dismutase activity in primary human fibroblasts. Combinations of optimized concentrations for pluronic block co-polymers further increased cell migration, and the messenger RNA (mRNA) expression levels of important growth factor and cytokines (vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-ß), and tumor necrosis factor alpha (TNF-α)). NaB containing hydrogel co-formulated with pluronics was also investigated for their wound healing activities using a full thickness wound model in rats. Macroscopic and histopathological analysis confirmed that wounds in combination gel-treated groups healed faster than those of control groups. NaB/Plu gel application was found to increase wound contraction and collagen deposition in the wound area. Therefore, our results suggest that NaB, and its pluronics combination, could be used in dermatological clinics and be a future solution for chronic wounds. However, further studies should be conducted to explore its exact action of mechanism and effects of this formulation on chronic wounds.


Assuntos
Boratos/uso terapêutico , Movimento Celular/efeitos dos fármacos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Poloxâmero/uso terapêutico , Cicatrização/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Fibroblastos/efeitos dos fármacos , Humanos , Masculino , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Pele/citologia , Pele/efeitos dos fármacos , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
4.
Curr Pharm Des ; 15(33): 3908-16, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19938343

RESUMO

Stem cell based therapies for cerebral ischemia (CI) utilize different cell sources including embryonic stem cells (ESCs), neural stem cells (NSCs), umbilical cord blood cells (UCBCs), mesenchymal stem cells (MSCs), and some immortalized cell lines. To date, experimental studies showed that all of these cell sources have been successful to some extent in attenuating the ischemic damage and improving functional recovery after brain injury. Bone marrow derived MSCs seem to be the most widely used and well characterized cell source, which can be also employed for autologous transplantation. Currently, there are two main theories behind the therapeutic effect of stem cell transplantation for treating CIs. The first concept is cell replacement theory in which transplanted stem cells differentiate into progenitor and specialized somatic cells to supersede dying cells. The other hypothesis is based on immuno-modulatory, neuro-protective and neuro-trophic abilities of stem cells which help reducing stroke size and increasing the recovery of behavioral functions. Recent studies focusing on alternative stem cell sources have revealed that dental stem cells (DSCs), including dental pulp stem cells (DPSCs) and dental follicle cells (DFCs) possess properties of MSCs and NSCs. They differentiate into neural linage cells and some other cell types such as osteocytes, adipocytes, chondrocytes, muscle cells and hepatocytes. This review is intended to examine stem cell therapy approaches for CI and emphasize potential use of DSCs as an alternative cell source for the treatment of brain ischemia.


Assuntos
Isquemia Encefálica/terapia , Transplante de Células-Tronco/métodos , Células-Tronco/metabolismo , Animais , Isquemia Encefálica/fisiopatologia , Diferenciação Celular , Polpa Dentária/citologia , Saco Dentário/citologia , Humanos
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