RESUMO
INTRODUCTION: There are emerging but inconsistent evidences about anti-epileptic drugs (AEDs) as radio- or chemo-sensitizers to improve survival in glioblastoma patients. We conducted a nationwide population-based study to evaluate the impact of concurrent AED during post-operative chemo-radiotherapy on outcome. MATERIAL AND METHODS: A total of 1057 glioblastoma patients were identified by National Health Insurance Research Database and Cancer Registry in 2008-2015. Eligible criteria included those receiving surgery, adjuvant radiotherapy and temozolomide, and without other cancer diagnoses. Survival between patients taking concurrent AED for 14 days or more during chemo-radiotherapy (AED group) and those who did not (non-AED group) were compared, and subgroup analyses for those with valproic acid (VPA), levetiracetam (LEV), or phenytoin were performed. Multivariate analyses were used to adjust for confounding factors. RESULTS: There were 642 patients in the AED group, whereas 415 in the non-AED group. The demographic data was balanced except trend of more patients in the AED group had previous drug history of AEDs (22.6% vs. 18%, P 0.078). Overall, the AED group had significantly increased risk of mortality (HR = 1.18, P 0.016) compared to the non-AED group. Besides, an adverse dose-dependent relationship on survival was also demonstrated in the AED group (HR = 1.118, P 0.0003). In subgroup analyses, the significant detrimental effect was demonstrated in VPA group (HR = 1.29,P 0.0002), but not in LEV (HR = 1.18, P 0.079) and phenytoin (HR = 0.98, P 0.862). CONCLUSIONS: Improved survival was not observed in patients with concurrent AEDs during chemo-radiotherapy. Our real-world data did not support prophylactic use of AEDs for glioblastoma patients.
Assuntos
Anticonvulsivantes , Neoplasias Encefálicas , Glioblastoma , Humanos , Feminino , Anticonvulsivantes/uso terapêutico , Masculino , Glioblastoma/mortalidade , Glioblastoma/terapia , Pessoa de Meia-Idade , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Idoso , Quimiorradioterapia Adjuvante/métodos , Quimiorradioterapia Adjuvante/estatística & dados numéricos , Adulto , Estudos de Coortes , Fenitoína/uso terapêutico , Fenitoína/administração & dosagem , Sistema de Registros/estatística & dados numéricos , Levetiracetam/uso terapêutico , Ácido Valproico/uso terapêuticoRESUMO
BACKGROUND: This study aimed to investigate skin condition, quality of life, and psychological impact of breast cancer patients after radiation therapy. We designed and administered a questionnaire to breast cancer survivors for better understanding the skin sequelae after radiation therapy. METHODS: This study performed an anonymous online survey. Invitation join was posted in Facebook groups for Breast Cancer. Content of the questionnaire included basic information and a three-point scale on the degree of skin dryness, sweating, hotness sensation, itchy sensation, presence of pigment deposition, history of severe skin disorder, psychological impact, and quality of life after radiotherapy. Categorical variables were summarized using counts and percentages, and then Mantel-Haenszel chi-square tests, multiple correspondence analysis, Wald chi-square statistics, and logistic regression analyses were performed; P < 0.05 was considered statistically significant. RESULTS: In total, 421 breast cancer survivors completed the questionnaire. Among them, 331 (78.62%) reported rarely sweating; 340 (80.76%) reported dry skin; 184 (43.71%) reported itchy skin in addition to dry skin; 336 (79.81%) had severe or mild skin color deposition; and 76 (18.05%) had eczema or contact dermatitis. Dry skin problems were caused by absent sweating and skin dryness in the irradiated skin area, post-RT severe skin disorders, and skin color deposition. Compared with patients sweating normally in the radiation field, patients with absent sweating and hotness sensation in the radiation field had a higher risk of depression. CONCLUSIONS: This study showed that breast cancer patients after whole breast radiotherapy may experience skin dryness, hypersensitivity and hyper pigmentation in the irradiated skin area. These "radiation-irritated skin" lesions may induce depressive psychological status and impact the quality of life in breast cancer patients after whole breast radiotherapy.
Assuntos
Neoplasias da Mama/complicações , Neoplasias da Mama/radioterapia , Hiperpigmentação/etiologia , Qualidade de Vida/psicologia , Pele/patologia , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários , VoluntáriosRESUMO
BACKGROUND/AIM: The present study aimed at evaluating the contribution of IL-4 promoter T-1099G (rs2243248), C-589T (rs2243250), C-33T (rs2070874) genotypes to the risk of breast cancer in Taiwanese. MATERIALS AND METHODS: A total of 1232 breast cancer patients and 1232 age-matched controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS: Genotypic frequencies of IL-4 rs2243248, rs2243250 and rs2070874 were not differentially distributed between case and control groups. Consistently, there was no difference in the distribution of allelic frequencies among patients and controls. CONCLUSION: IL-4 rs2243248, rs2243250 and rs2070874 do not confer breast cancer susceptibility in Taiwanese.
Assuntos
Neoplasias da Mama/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Interleucina-4/genética , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Alelos , Povo Asiático/genética , Neoplasias da Mama/epidemiologia , Feminino , Frequência do Gene , Genótipo , Humanos , Pessoa de Meia-Idade , Razão de Chances , Regiões Promotoras Genéticas , Medição de Risco , TaiwanRESUMO
BACKGROUND/AIM: Etomidate, an intravenous anesthetic, has been shown to have anticancer effects, including induction of cell-cycle arrest and apoptosis. However, to our knowledge, there are no reports about the anti-metastasis effects of etomidate on A549 human lung adenocarcinoma cells. MATERIALS AND METHODS: The cell viability, cell adhesion, gelatin zymography assay, transwell migration and invasion assay, and western blotting analysis were used to investigate the effects of etomidate on A549 cells. RESULTS: In our study, etomidate showed low cytotoxicity, inhibited cell adhesion, and suppressed the migration and invasion in A549 cells. The activity of matrix metallopeptidase 2 (MMP2) was reduced by 48 h treatment of etomidate. Results of western blotting analysis indicated that etomidate down-regulated the expression of protein kinase C, MMP7, MMP1, MMP9, and p-p-38, but up-regulated that of RAS, phosphoinositide 3-kinase, and phosphor-extracellular-signal related kinase after 24 and 48 h treatment, in A549 cells. CONCLUSION: Etomidate suppressed the migration and invasion of lung adenocarcinoma A549 cells via inhibiting the expression of MMP1, MMP2, MMP7 and MMP9, and provides potential therapeutic targets for lung cancer treatment.
Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Etomidato/farmacologia , Metaloendopeptidases/genética , Invasividade Neoplásica/genética , Células A549 , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Apoptose/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas de Neoplasias/genéticaRESUMO
Lung cancer has a very high prevalence of brain metastasis, which results in a poor clinical outcome. Up-regulation of a disintegrin and metalloproteinase 9 (ADAM9) in lung cancer cells is correlated with metastasis to the brain. However, the molecular mechanism underlying this correlation remains to be elucidated. Since angiogenesis is an essential step for brain metastasis, microarray experiments were used to explore ADAM9-regulated genes that function in vascular remodeling. The results showed that the expression levels of vascular endothelial growth factor A (VEGFA), angiopoietin-2 (ANGPT2), and tissue plasminogen activator (PLAT) were suppressed in ADAM9-silenced cells, which in turn leads to decreases in angiogenesis, vascular remodeling, and tumor growth in vivo. Furthermore, simultaneous high expression of ADAM9 and VEGFA or of ADAM9 and ANGPT2 was correlated with poor prognosis in a clinical dataset. These findings suggest that ADAM9 promotes tumorigenesis through vascular remodeling, particularly by increasing the function of VEGFA, ANGPT2, and PLAT.
Assuntos
Proteínas ADAM/genética , Angiopoietina-2/genética , Neoplasias Pulmonares/genética , Proteínas de Membrana/genética , Ativador de Plasminogênio Tecidual/genética , Fator A de Crescimento do Endotélio Vascular/genética , Remodelação Vascular/genética , Células A549 , Proteínas ADAM/metabolismo , Angiopoietina-2/metabolismo , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundário , Linhagem Celular , Linhagem Celular Tumoral , Células Cultivadas , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Ativador de Plasminogênio Tecidual/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
ent-13-Hydroxykaur-16-ene-19-N-butylureide (6) was one of 33 synthesized C-4-substituted steviol derivatives that were evaluated for their effects on hepatitis B virus (HBV) surface antigen (HBsAg) secretion. The IC50 (16.9 µM) and SI (57.7) values for inhibiting HBV DNA replication of compound 6 were greater than those of the reference compound, lamivudine (3-TC; IC50: 107.5 µM; SI: 22.0). Thus, the anti-HBV mechanism of 6 was investigated, and it specifically inhibited viral gene expression and reduced viral DNA levels, as well as potently attenuated all of the viral promoter activity of HBV-expressing Huh7 cells. Examination of cellular signaling pathways found that 6 inhibited the activities of the nuclear factor (NF)-κB- and activator protein (AP)-1 element-containing promoters, but had no effects on AP-2 or interferon-stimulated response element (ISRE)-containing promoters in HBV-expressing cells. Meanwhile, it significantly eliminated NF-κB and extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling-related protein levels and inhibited their phosphorylation in HBV-transfected Huh7 cells. The inhibitory potency of 6 against HBV DNA replication was reversed by cotransfecting the NF-κB p65 expression plasmid. Using the MAPK-specific activator anisomycin also reversed the inhibitory effect of 6 on viral DNA replication. The present findings suggest that the anti-HBV mechanism of 6 is partly mediated through the NF-κB and MAPK signaling pathways.
Assuntos
Diterpenos do Tipo Caurano/síntese química , Diterpenos do Tipo Caurano/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , DNA Viral/efeitos dos fármacos , Diterpenos do Tipo Caurano/classificação , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estrutura Molecular , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Fator de Transcrição AP-1/metabolismo , Replicação Viral/efeitos dos fármacosRESUMO
Various sedative agents, including dexmedetomidine (dex), induce immunosuppression, and enhance infection progression. However, there was no information on how anesthetic affects local and systemic cellular immune function. We conducted this study to examine the impact of dex on the differentiation and function of immune cells at site of inflammation and in peripheral blood during endotoxemia of mice. In BALB/c mice with and without endotoxemia, we evaluated the influence of two dosages of 5 and 50 mcg/kg/h intravenous dex on immune cells: including number of T cells (CD3), B cells (CD19), natural killer cells (CD8a), monocytes (CD11b), and macrophages (Mac-3) in peripheral blood, the activities of macrophages in peripheral blood and in peritoneal lavage, and proliferation of B and T cells and of natural killer cells activity in the spleen. Endotoxemia increased the number of CD3 T cells, CD 19 B cells and macrophages in the peripheral blood, augmented macrophage activity in the peritoneum, and increased T cell proliferation and natural killer cell activity in the spleen. Further administration of 5 mcg/kg/h dex attenuated systemic increase in number of T cells, B cells, and macrophages during endotoxemia and 50 mcg/kg/h dex significantly attenuated the increase in activity of macrophages in the peripheral blood during endotoxemia. In the peritoneum, however, 5 mcg/kg/h dex preserved and 50 mcg/kg/h dexmedetomidine enhanced the activity of macrophages during endotoxemia. Increased in proliferation of T cells in spleen during endotoxemia was attenuated by both doses of dex. Last, 50 mcg/kg/h dex enhanced natural killer cells activity during endotoxemia. While preserving the effects of endotoxemia on macrophage's activity in the infection site and natural killer cell's activity in the spleen, dex decreased systemic fulminant immune reaction in endotoxemia, by attenuating the augmented response in the number of T cells, B cells and macrophages, activity of macrophages in the peripheral blood, and proliferation of T cells in spleen during endotoxemia.
Assuntos
Dexmedetomidina/farmacologia , Hipnóticos e Sedativos/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Animais , Linfócitos B/citologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Proliferação de Células/efeitos dos fármacos , Endotoxemia/metabolismo , Endotoxemia/patologia , Escherichia coli/metabolismo , Células Matadoras Naturais/citologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Lipopolissacarídeos/toxicidade , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Monócitos/citologia , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Fagocitose/efeitos dos fármacos , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
BACKGROUND: This study investigated the incidence and patient- and treatment-related risk factors related to pneumonia acquired during radiotherapy (PNRT) in head and neck cancer (HNC) patients. METHODS: Using the universal insurance claims data, 15,894 total HNC patients between 1998 and 2007 were included in this analysis. PNRT was defined as the occurrence of pneumonia within 90 days of the commencement of radiotherapy. Information also included some demographic characteristics, treatment-related factors, and comorbidities. Appropriate statistical tests were performed to assess the difference between patients with and those without PNRT. A logistic regression was used to estimate the odds ratio (OR) of PNRT among the variables examined. RESULTS: In total, 772 patients (4.86%) were identified with PNRT as the case group, whereas 15,122 subjects of the same cancer without PNRT formed the control group. Of patients with PNRT, 632 (81.9%) were hospitalized with a mean length of stay of 25.9 days. Results from the multiple logistic regression showed that an older age and certain comorbidities were associated with an increased risk of PNRT. Patients with cancer of the tongue, buccal mucosa, oropharynx, and hypopharynx/larynx were at particularly higher risk (OR = 1.28, 1.28, 1.67, and 1.74, respectively). Compared to radiotherapy alone, concurrent chemoradiotherapy had no effect on the PNRT. Patients in the PNRT group had higher overall medical costs and length of stay. CONCLUSION: The incidence of PNRT in HNC patients receiving radiotherapy was approximately 5%. Notably, an older age, certain comorbidities, and certain specific tumor sites were associated with an increased risk.