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1.
J Photochem Photobiol B ; 148: 82-87, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25900553

RESUMO

Multidrug resistance (MDR) refers to the ability of cancer cells to develop cross resistance to a range of anticancer drugs which are structurally and functionally unrelated. P-glycoprotein (P-gp) is the best studied MDR phenotype in photodynamic therapy (PDT) treated cells. Our pervious study demonstrated that FosPeg® mediated PDT is effective to NPC cell line models. In this in vitro study, the expression of MDR1 gene and its product P-gp in undifferentiated, poorly differentiated and well differentiated human nasopharyngeal carcinoma (NPC) cells were investigated. The influence of P-gp efflux activities on photosensitizer FosPeg® was also examined. Regardless of the differentiation status, PDT tested NPC cell lines all expressed P-gp protein. Results indicated that FosPeg® photoactivation could heighten the expression of MDR1 gene and P-gp transporter protein in a dose dependent manner. Up to 2-fold increase of P-gp protein expression were seen in NPC cells after FosPeg® mediated PDT. Interestingly, our finding demonstrated that FosPeg® mediated PDT efficiency is independent to the MDR1 gene and P-gp protein expression in NPC cells. FosPeg® itself is not the substrate of P-gp transporter protein and no efflux of FosPeg® were observed in NPC cells. Therefore, the PDT efficiency would not be affected even though FosPeg® mediated PDT could induce MDR1 gene and P-gp protein expression in NPC cells. FosPeg® mediated PDT could be a potential therapeutic approach for MDR cancer patients.


Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Lipossomos/farmacologia , Mesoporfirinas/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Carcinoma , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Luz , Lipossomos/química , Lipossomos/uso terapêutico , Mesoporfirinas/química , Mesoporfirinas/uso terapêutico , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/uso terapêutico , RNA Mensageiro/metabolismo
2.
J Photochem Photobiol B ; 127: 114-22, 2013 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-24013466

RESUMO

Nasopharyngeal carcinoma (NPC) is one of the top ten cancers highly prevalent in Hong Kong and South China. Epstein-Barr virus (EBV) infection contributes to the tumorigenesis of NPC through the expression of different viral proteins. Among these, Latent Membrane Protein 1(LMP1) is the major oncoprotein expressed by EBV. Foscan® (Biolitec AG), m-tetrahydroxyphenylchlorin (mTHPC)-based photosensitizing drug, has been used in the photodynamic therapy (PDT) for head and neck cancers. FosPeg® (Biolitec AG) is a new formulation of mTHPC contained in PEGylated liposomes with optimized distribution properties. In this in vitro study, the potential of FosPeg®-PDT on human EBV positive NPC cell (c666-1) and EBV negative cells (HK1 and CNE2) were investigated. Effects of FosPeg®-PDT on the expression of EBV BART miRNAs (EBV miRNA BART 1-5p, BART 16, and BART 17-5p), LMP1 mRNA and proteins on c666-1 cells were also elucidated. The killing efficacy of FosPeg®-PDT on NPC cells were determined by MTT assay after LED activation. Effects of FosPeg®-PDT on the expression of LMP1 mRNA and protein were examined by real time PCR and western blot analysis. FosPeg®-PDT demonstrated its antitumor effect on c666-1 cells in a drug and light dose dependent manner. LD30, LD50 and LD70 were achieved by applying LED activation (3J/cm(2)) at 4h post incubated cells with 0.05µg/ml, 0.07µg/ml and 0.3µg/ml FosPeg®, respectively. Up-regulation of both LMP1 mRNA and protein were observed after FosPeg®-PDT in a dose dependent manner. FosPeg®-PDT exerted antitumor effect on c666-1 cells through up-regulation of LMP1 protein. Understanding the mechanism of FosPeg®-PDT may help to develop better strategies for the treatment of NPC.


Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Herpesvirus Humano 4/genética , Mesoporfirinas/farmacologia , MicroRNAs/genética , Neoplasias Nasofaríngeas/patologia , Fotoquimioterapia , Proteínas da Matriz Viral/metabolismo , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Linhagem Celular Tumoral , Química Farmacêutica , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Herpesvirus Humano 4/fisiologia , Humanos , Espaço Intracelular/efeitos dos fármacos , Espaço Intracelular/metabolismo , Espaço Intracelular/efeitos da radiação , Lipossomos , Mesoporfirinas/administração & dosagem , Mesoporfirinas/química , Mesoporfirinas/metabolismo , Mesoporfirinas/uso terapêutico , Neoplasias Nasofaríngeas/virologia , Polietilenoglicóis/química , RNA Viral/genética , Proteínas da Matriz Viral/genética
3.
Mol Cell Neurosci ; 36(3): 416-24, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17889554

RESUMO

Tissue damage in the CNS is critically influenced by the adaptive immune system. Primary oligodendrocyte damage (by overexpression of PLP) leads to low-grade inflammation of high pathological impact, which is mediated by CD8+ T cells. To yield further insight into pathogenesis and nature of immune responses in myelin mutated mice, we here apply a detailed immunological characterization of CD8+ T cells in PLP-transgenic and aged wild type mice. We provide evidence that T effector cells accumulate in the CNS of PLP-transgenic and wild-type mice and show a higher level of activation in mutant mice, indicated by surface markers and clonal expansions, as demonstrated by T cell receptor CDR3-spectratype analysis. Vbeta-Jbeta similarities suggest specificity against a common antigen, albeit we could not find specific responses against myelin-antigen-derived peptides. The association of primary oligodendrocyte damage with secondary expansions of pathogenic cells underlines the role of adaptive immune reactions in neurodegenerative and neuroinflammatory diseases.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Sistema Nervoso Central/imunologia , Doenças Desmielinizantes/imunologia , Sistema Imunitário/imunologia , Bainha de Mielina/imunologia , Animais , Autoimunidade/genética , Autoimunidade/imunologia , Antígenos CD8/imunologia , Proliferação de Células , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/fisiopatologia , Células Clonais/imunologia , Doenças Desmielinizantes/genética , Doenças Desmielinizantes/fisiopatologia , Sistema Imunitário/fisiopatologia , Imunidade Inata/genética , Imunidade Inata/imunologia , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes Neurológicos , Camundongos Transgênicos , Bainha de Mielina/genética , Bainha de Mielina/metabolismo , Oligodendroglia/imunologia , Oligodendroglia/metabolismo , Oligodendroglia/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
4.
Tohoku J Exp Med ; 178(3): 339-44, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8727716

RESUMO

The clinical and pathological features of an apparently unique case of an endometrial cyst of the uterus are reported. The cyst was located within the myometrium of a 16-year-old woman suffering from dysmenorrhea. After excision of the cyst, patient's symptoms improved. On histological examination, the cyst most closely resembled an adenomyotic cyst.


Assuntos
Cistos/patologia , Endometriose/patologia , Doenças Uterinas/patologia , Adolescente , Cistos/diagnóstico , Cistos/cirurgia , Diagnóstico Diferencial , Endometriose/diagnóstico , Endometriose/cirurgia , Endométrio/patologia , Feminino , Humanos , Laparoscopia , Imageamento por Ressonância Magnética , Menorragia/etiologia , Menorragia/patologia , Doenças Uterinas/diagnóstico , Doenças Uterinas/cirurgia
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