RESUMO
The acquisition of metastasis potential is a critical point for malignant tumors. Melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) is a potential tumor suppress gene and frequently down-regulated in malignant tumors. It has been implicated that overexpression of MDA-7 led to proliferation inhibition in many types of human tumor. Invasion is an important process which is potential to promote tumor metastasis. However, the role and potential molecular mechanism of mda-7/IL-24 to inhibit the invasion of human melanoma cancer is not fully clear. In this report, we identified a solid role for mda-7/IL-24 in invasion inhibition of human melanoma cancer LiBr cells, including decreasing of adhesion and invasion in vitro, blocking cell cycle, down-regulating the expression of ICAM-1, MMP-2/9, CDK1, the phosphorylation of ERK and Akt, NF-kappaB and AP-1 transcription activity. Meanwhile, there was an increased expression of PTEN in mda-7/IL-24 over-expression LiBr cells. Our results demonstrated that mda-7/IL-24 is a potential invasion suppress gene, which inhibits the invasion of LiBr cells by the down-regulation of ICAM-1, MMP-2/9, PTEN, and CDK1 expression. The molecular pathways involved were the MAPK/ERK, PI3K-Akt, NF-kappaB, and AP-1. These findings suggest that mda-7/IL-24 may be used as a possible therapeutic strategy for human melanoma cancer.
Assuntos
Humanos , Proteína Quinase CDC2/genética , Linhagem Celular Tumoral , Movimento Celular , Regulação para Baixo , Pontos de Checagem da Fase G2 do Ciclo Celular , Molécula 1 de Adesão Intercelular/genética , Interleucinas/genética , Pontos de Checagem da Fase M do Ciclo Celular , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Melanoma/metabolismo , NF-kappa B/genética , PTEN Fosfo-Hidrolase/genética , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Fator de Transcrição AP-1/genética , Regulação para CimaRESUMO
<p><b>OBJECTIVE</b>To investigate the antiinflammatory activities of aqueous extract of Occimum gratissmium (OGE) with emphasis on expression of proinflammatory cytokines in Lipopolysaccharide (LPS)-stimulated epithelial cell BEAS-2B.</p><p><b>METHODS</b>Effects of OGE on cell viability were determined by MTT assay. mRNA expression were analyzed by and reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time PCR. Activation of kinase cascades was investigated by immunoblot. Intracellular reactive oxygen species (ROS) was analyzed by flow cytometry.</p><p><b>RESULTS</b>OGE (<200 μg/mL) treatment or pretreatment and following LPS exposure slightly affected viability of BEAS-2B cells. Increase of interleukin (IL)-6 and IL-8 and the elevated level of intracellular ROS in LPS-stimulated BEAS-2B cells were diminished by OGE pretreatment in a dose-dependent manner. OGE suppressed inflammatory response-associated mitogen-activated protein kinases (MAPKs) and Akt activation. Additionally, OGE pretreatment increased level of cellular inhibitor of κBα (IκBα) and inhibited nuclear translocation of nuclear factor kappa B (NF-κB).</p><p><b>CONCLUSION</b>These findings indicate that significant suppression of IL-6 and IL-8 expressions in LPS-stimulated BEAS-2B cells by OGE may be attributed to inhibiting activation of MAPKs and Akt and consequently suppressing nuclear translocation of NF-κB.</p>
Assuntos
Humanos , Núcleo Celular , Metabolismo , Sobrevivência Celular , Citosol , Metabolismo , Células Epiteliais , Metabolismo , Regulação da Expressão Gênica , Proteínas I-kappa B , Metabolismo , Interleucina-6 , Genética , Metabolismo , Interleucina-8 , Genética , Metabolismo , Espaço Intracelular , Metabolismo , Lipopolissacarídeos , Farmacologia , Proteínas Quinases Ativadas por Mitógeno , Metabolismo , Inibidor de NF-kappaB alfa , NF-kappa B , Metabolismo , Ocimum , Química , Fosforilação , Extratos Vegetais , Farmacologia , Transporte Proteico , Proteínas Proto-Oncogênicas c-akt , Metabolismo , RNA Mensageiro , Genética , Metabolismo , Espécies Reativas de Oxigênio , Metabolismo , Sistema Respiratório , Biologia Celular , ÁguaRESUMO
<p><b>BACKGROUND</b>Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is an emerging technique for the treatment of genital human papillomavirus (HPV)-induced benign and premalignant lesions. We report here in a case series of condyloma acuminata (CA) in pregnancy successfully treated with ALA-PDT.</p><p><b>METHODS</b>Five pregnant patients with CA received three to four times treatment respectively. Patients were followed up for 6 - 23 months after treatment.</p><p><b>RESULTS</b>The clearance rate of genital warts was 100%. No recurrence was found during the follow-up period. Major adverse events reported were mild erosion, pain, and local edema. All pregnancies resulted in healthy live births without delivery complications.</p><p><b>CONCLUSIONS</b>PDT with topical ALA seems to be safe and effective in the treatment of CA in pregnancy. It demonstrated high clearance rate of warts, was well-tolerated by patients, and showed no adverse effects on mothers or fetuses. ALA-PDT may be an ideal strategy of treatment for pregnant women with CA.</p>
Assuntos
Adulto , Feminino , Humanos , Gravidez , Ácido Aminolevulínico , Usos Terapêuticos , Condiloma Acuminado , Tratamento Farmacológico , Fotoquimioterapia , MétodosRESUMO
<p><b>OBJECTIVE</b>To investigate the expression of cannabinoid receptor 2 (CB2) in normal human skin and squamous cell carcinoma and analyze its relation with the tumorigenesis and development of squamous cell carcinoma.</p><p><b>METHODS</b>The expression of CB2 protein and mRNA levels were detected in normal human skin and squamous cell carcinoma using immunohistochemical staining and RT-PCR.</p><p><b>RESULTS</b>Both the normal skin and squamous cell carcinoma expressed CB2, which was localized mainly in the basal cell layer and prickle cell layer in human skin with low expressions in the subcutaneous tissue. The expression intensity of CB2 differed significantly between squamous cell carcinoma and normal human skin (P<0.05).</p><p><b>CONCLUSION</b>Squamous cell carcinoma over-expresses CB2 at both the protein and mRNA levels. High expression of CB2 in squamous cell carcinoma suggests an important role of CB2 in the tumorigenesis and development of squamous cell carcinoma.</p>
Assuntos
Feminino , Humanos , Masculino , Carcinoma de Células Escamosas , Metabolismo , RNA Mensageiro , Genética , Metabolismo , Receptor CB2 de Canabinoide , Genética , Metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele , Metabolismo , Neoplasias Cutâneas , MetabolismoRESUMO
Objective To assess efficacy and safety of oral brivudine 125 mg once daily versus 4 times daily in the treatment of herpes zoster.Methods A five-centre,randomized,double-blind,parallel- controlled study was performed on 226 patients with herpes zoster.Oral brivudine 125 mg was given once daily to 112 patients,and four times daily to 114 patients,both for 7 days.All patients were followed up for 3 weeks after the end of treatment.Results The time to the last formation of new vesicles was 3.88 days for the once daily group,and 3.79 days for the 4 times daily group,without significant differences between the two groups.There was also no significant difference between the two groups with respect to the time to total resolution of vesicles,time to first crusts,time to full crusting,time to first loss of crusts,time to full loss of crusts,time to first relief of pain,and time to complete relief of pain.Postherpetic neuralgia occurred in 34.5% of patients in the once daily group,and 30.4% of patients in the 4 times daily group.The incidence of treatment-related adverse events was 5.4% and 9.6%,in the once daily group and 4 times daily group, respectively.Conclusions Brivudine 125 mg once daily is equally effective,more convenient and safe in comparison with brivudine 125 mg 4 times daily for the treatment of herpes zoster.