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1.
J Cancer Res Clin Oncol ; 145(8): 1949-1976, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31292714

RESUMO

PURPOSE: Efflux transporters of the adenosine triphosphate-binding cassette (ABC)-superfamily play an important role in the development of multidrug resistance (multidrug resistant; MDR) in cancer. The overexpression of these transporters can directly contribute to the failure of chemotherapeutic drugs. Several in vitro and in vivo models exist to screen for the efficacy of chemotherapeutic drugs against MDR cancer, specifically facilitated by efflux transporters. RESULTS: This article reviews a range of efflux transporter-based MDR models used to test the efficacy of compounds to overcome MDR in cancer. These models are classified as either in vitro or in vivo and are further categorised as the most basic, conventional models or more complex and advanced systems. Each model's origin, advantages and limitations, as well as specific efflux transporter-based MDR applications are discussed. Accordingly, future modifications to existing models or new research approaches are suggested to develop prototypes that closely resemble the true nature of multidrug resistant cancer in the human body. CONCLUSIONS: It is evident from this review that a combination of both in vitro and in vivo preclinical models can provide a better understanding of cancer itself, than using a single model only. However, there is still a clear lack of progression of these models from basic research to high-throughput clinical practice.


Assuntos
Transportadores de Cassetes de Ligação de ATP/fisiologia , Antineoplásicos/isolamento & purificação , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Modelos Biológicos , Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Transportadores de Cassetes de Ligação de ATP/genética , Antineoplásicos/farmacologia , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/genética , Técnicas de Cultura/métodos , Técnicas de Apoio para a Decisão , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Especificidade de Órgãos , Seleção de Pacientes
2.
Curr Pharm Des ; 25(20): 2208-2240, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31269881

RESUMO

The skin is the largest organ and functions as a barrier to protect the underlying tissues against the elements and pathogens, while also fulfilling many physiological roles and biochemical functions such as preventing excessive water loss. Skin disorders vary greatly in terms of origin, severity, symptoms and affect persons of all ages. Many plants have been used for medicinal purposes since ancient times including the treatment of skin disorders and diseases. Aloe represents one of the earliest medicinal plant species mentioned in antique scriptures and even in rock art dating back thousands of years. Different Aloe species and materials have been used in the prevention and treatment of skin related disorders. Aloe vera is the most commonly used Aloe species for medicinal purposes. Some of the most prominent skin related applications and disorders that Aloe materials have been investigated for are discussed in this paper, which include cosmetic, radiation, cancer, wound and antimicrobial applications. Both in vitro and in vivo studies are included in the discussions of this paper and comprehensive summaries of all these studies are given in tables in each section. Although some contradictory results were obtained among studies, certain Aloe materials have shown excellent efficacy and exhibited potential for the treatment of skin related disorders and cosmetic applications.

3.
Planta Med ; 85(13): 1114-1123, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31340396

RESUMO

The fruit from various pepper plants has been employed for the seasoning of food, as perfuming agents, and also as traditional medicines. Phytochemicals isolated from different pepper species have been found to modulate the pharmacokinetics of orally administered drugs. This study investigated the possibility to apply capsaicin and piperine (extracted alkaloids) as modulators for drug delivery across the nasal epithelium. Both a nasal epithelial cell line (RPMI 2650) and excised sheep nasal tissue were used as models to investigate the effects of the selected pepper compounds on drug permeation. FITC-dextran 4400 (MW 4400 Da) was used as a large molecular weight marker compound for paracellular transport, while rhodamine 123 was used as a marker compound that is a substrate for P-glycoprotein-mediated efflux. From the permeation results, it was clear that capsaicin inhibited P-glycoprotein efflux to a larger extent, while piperine showed drug permeation enhancement via other mechanisms. The cell cytotoxicity studies indicated that capsaicin was noncytotoxic up to a concentration of 200 µM and piperine up to a concentration of 500 µM as indicated by cell viability above 80%. The histological analysis of the excised nasal tissue and cultured RPMI 2650 cell layers indicated that some damage occurred after treatment with 200 µM capsaicin, but no changes were observed for piperine up to a concentration of 50 µM.


Assuntos
Alcaloides/uso terapêutico , Benzodioxóis/uso terapêutico , Capsaicina/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Mucosa Nasal/metabolismo , Veículos Farmacêuticos/uso terapêutico , Piperidinas/uso terapêutico , Alcamidas Poli-Insaturadas/uso terapêutico , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Alcaloides/farmacologia , Animais , Benzodioxóis/farmacologia , Capsaicina/farmacologia , Mucosa Nasal/efeitos dos fármacos , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Ovinos
4.
Cytometry A ; 2018 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-30240134

RESUMO

This study is aimed to reveal morphological and functional changes in multipotent mesenchymal stromal cells (MSCs) isolated from the rat bone marrow after: (i) activation of Toll-like receptors (TLRs) with teichoic acid (TA), (ii) impact on epidermal growth factor (EGF) receptors with activator EGF or inhibitor Herceptin, and (iii) treatment with DNA intercalator Cisplatin. According to our results, TA and EGF cause an increase in the synthesis of glycosaminoglycans, c-Myc content, and protein in the MSC cytoplasm. It was observed that the cell population in G0 phase decreased and the cell population in G1 phase increased, when compared with control. At the same time, the cell population with a higher nuclear-cytoplasmic ratio (NCR) in S and G2 phases also increased. This indicates the manifestation of the MSC mesenchymal phenotype, exhibiting indirect metabolic signs of the regenerative potential increase. In other experiments, Herceptin was shown to suppress only the stemness signs of MSCs, while Cisplatin seriously affected cell viability in general, reducing synthetic and proliferative activities and causing cell morphology disturbances.

5.
Oncol Lett ; 15(4): 5034-5042, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29552139

RESUMO

Transplantation of placenta-derived multipotent cells (PDMCs) is a promising treatment method for many diseases. However, the impact of PDMCs on colon cancer has not yet been studied. PDMCs were obtained from rat placentas by culturing tissue explants. Colon cancer was experimentally induced in male albino Wistar rats by administering 20 mg/kg dimethylhydrazine (DMH) once a week for 20 consecutive weeks. The administration of the PDMCs was performed at the 20th week after the first DMH injection. The number and size of each tumour lesion were calculated in the 5th week after transplantation. The tumour type was determined by standard histological methods. To study the engraftment of PDMCs in the body of rats, the cells were transduced with enhanced green fluorescent protein. Cell engraftment was determined by assessing the presence of EGFP by PCR and immunohistochemistry. Survival of all rats was monitored daily. Allogeneic transplantation of PDMCs to rats at middle phase of DMH-induced colon carcinogenesis did not significantly influence the number of neoplasms and the parameters of mean and total tumour area, but led to an increase in size of the most invasiveness tumours. Intravenous allogeneic transplantation of PDMCs reduced the survival rate of rats with colon cancer by 17 days. PDMCs from rats engrafted into tissues of the normal intestine, tumours, lungs, liver, and spleen of rats for five weeks after intravenous transplantation. These results suggest that intravenous allogeneic transplantation of PDMCs promotes colon cancer progression and has a negative impact on survival of rats.

6.
Exp Ther Med ; 14(3): 2135-2147, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28962134

RESUMO

Transplantation of placenta-derived multipotent cells (PDMCs) is a promising approach for cell therapy to treat inflammation-associated colon diseases. However, the effect of PDMCs on colon cancer cells remains unknown. The aim of the present study was to characterize PDMCs obtained from human (hPDMCs) and rat (rPDMCs) placentas and to evaluate their impact on colon cancer progression in rats. PDMCs were obtained from human and rat placentas by tissue explant culturing. Stemness- and trophoblast-related gene expression was studied using reverse transcription-polymerase chain reaction (RT-PCR), and surface markers and intracellular proteins were detected using flow cytometry and immunofluorescence, respectively. Experimental colon carcinogenesis was induced in male albino Wistar rats by injecting 20 mg/kg dimethylhydrazine (DMH) once a week for 20 consecutive weeks. The administration of rPDMCs and hPDMC was performed at week 22 after the initial DMH-injection. All animals were sacrificed through carbon dioxide asphyxiation at week 5 after cell transplantation. The number and size of each tumor lesion was calculated. The type of tumor was determined by standard histological methods. Cell engraftment was determined by PCR and immunofluorescence. Results demonstrated that rPDMCs possessed the immunophenotype and differentiation potential inherent in MSCs; however, hPDMCs exhibited a lower expression of cluster of differentiation 44 and did not express trophoblast-associated genes. The data of the present study indicated that PDMCs may engraft in different tissues but do not significantly affect DMH-induced tumor growth during short-term observations.

7.
Biomed Res Int ; 2015: 418752, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26347038

RESUMO

We have investigated the characteristics of human hematopoietic progenitor cells (HPCs) with the CD34(+)CD45(low)SSC(low) phenotype from full-term placental tissue (FTPT) as compared to cord blood (CB) and fetal liver (FL) cells. We demonstrated the presence of cell subpopulations at various stages of the differentiation with such immunophenotypes as CD34(+/low)CD45(low/-), CD34(++)CD45(low/-), CD34(+++)CD45(low/-), CD34(+/low)CD45(hi), and CD34(++)CD45(hi) in both first trimester placental tissue (FiTPT) and FTPT which implies their higher phenotypic heterogeneity compared to CB. HPCs of the FTPT origin expressed the CD90 antigen at a higher level compared to its expression by the CB HPCs and the CD133 antigen expression being at the same level in both cases. The HPCs compartment of FTPT versus CB contained higher number of myeloid and erythroid committed cells but lower number of myeloid and lymphoid ones compared to FL HPCs. HPCs of the FTPT and CB origin possess similar potentials for the multilineage differentiation in vitro and similar ratios of myeloid and erythroid progenitors among the committed cells. This observation suggests that the active hematopoiesis occurs in the FTPT. We obtained viable HPCs from cryopreserved placental tissue fragments allowing us to develop procedures for banking and testing of placenta-derived HPCs for clinical use.


Assuntos
Antígenos CD/biossíntese , Sangue Fetal , Feto , Células-Tronco Hematopoéticas , Fígado , Placenta , Adulto , Diferenciação Celular , Feminino , Sangue Fetal/citologia , Sangue Fetal/metabolismo , Feto/citologia , Feto/metabolismo , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Humanos , Fígado/citologia , Fígado/metabolismo , Especificidade de Órgãos , Placenta/citologia , Placenta/metabolismo , Gravidez
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