RESUMO
Cisplatin (DPP), a clinically potent antineoplastic agent, is limited by its severe adverse effects. The aim of this study was to investigate the effect of oligogalacturonides (OGA) and DDP on human lung cancer A549 cells. The combined use of OGA and DDP had a synergistic effect on the growth inhibition of A549 cells, changed the cell cycle distribution, and enhanced apoptotic response, especially in sequential combination treatment group of DDP 12 h + OGA 12 h. Western blot analyses showed that the combination treatment of OGA and DDP upregulated Bax, p53, and Caspase-3 and downregulated Bcl-2 proteins. More importantly, DDP-induced toxicity was attenuated by OGA and DDP combination treatment in normal HEK293 cells. Our data suggests that the combined use of OGA from natural sources and DDP could be an important new adjuvant therapy for lung cancer as well as offer important insights for reducing kidney toxicity of DDP and delaying the development of DDP resistance.
Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Oligossacarídeos/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Células HEK293 , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
Familial aggregation of hepatocellular carcinoma (HCC), the third leading cause of cancer death worldwide, has shown to be a common phenomenon. We investigated the association between the genetic background and HCC familial aggregation. Serum samples were collected from HCC family members and normal control family members for screening the differentially expressed protein peaks with the approach of surface-enhanced laser desorption ionization time-of-flight mass spectrometry. Potential genetically associated protein peaks were selected and further identified by matrix assisted laser desorption ionization-time of flight mass spectrometry. A panel of six protein peaks (m/z 6432.94, 8478.35, 9381.91, 17284.67, 17418.34, and 18111.04) were speculated to reflect the genetic susceptibility of HCC familial aggregation. Three of them (m/z 6432.94, 8478.35, and 9381.91) were selected to identify as the candidate proteins. Nine identified proteins, including mostly apolipoprotein family (ApoA1, ApoA2, ApoC3, ApoE) and serum amyloid A protein (SAA), were found overexpressed in the multiple HCC cases family members. The comparative proteomic profiles have suggested that genetic factors ought to be taken into account for familial aggregation of HCC.
Assuntos
Carcinoma Hepatocelular/genética , Predisposição Genética para Doença/genética , Neoplasias Hepáticas/genética , Adulto , Carcinoma Hepatocelular/sangue , Feminino , Humanos , Lactente , Neoplasias Hepáticas/sangue , Masculino , Linhagem , Proteômica/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , TranscriptomaRESUMO
OBJECTIVE: To explore the clinicopathological correlation between CD4(+) T lymphocyte count and superficial lymphadenopathy HIV/AIDS patients. METHODS: A total of 1066 HIV/AIDS patients were included in this study. The incidence of superficial lymphadenopathy, peripheral blood CD4(+) T lymphocyte counts and histological features of superficial lymphadenopathy were analyzed. RESULTS: Among 1066 patients, 126 cases (11.8%) presented with superficial lymphadenopathy. Of the 126 cases, there were 69 cases with CD4(+) T lymphocyte counts < 100/µl and clinical diagnoses including tuberculosis (37 cases), reactive hyperplasia (8 cases), AIDS-related lymphadenopathy (18 cases), penicillium diseases (12 cases), fungal infection (5 cases) and non-tuberculous mycobacterial infection (1 case). Twenty-six cases had CD4(+) T lymphocyte counts between 100/µl to 200/µl and clinical diagnosis including tuberculosis (12 cases), reactive hyperplasia (8 cases), AIDS-related lymphadenopathy(6 cases), penicillium disease (2 cases) and non-Hodgkin lymphoma (1 case). Twenty-nine cases had CD4(+) T lymphocyte counts > 200/µl and clinical diagnoses including tuberculosis (11 cases), reactive hyperplasia (12 cases), AIDS-related lymphadenopathy (3 cases), Penicillium diseases (1 case) and non-Hodgkin lymphoma (4 cases). The CD4(+) T lymphocyte counts among patients with tuberculosis, AIDS-related lymphadenopathy and Penicillium diseases were significantly different (χ(2) = 8.861, P = 0.012). A significant correlation between the incidence of superficial lymphadenopathy and CD4(+) T lymphocyte counts was found (χ(2) = 375.41, P = 0.000). CONCLUSIONS: The most common cause of superficial lymphadenopathy in HIV/AIDS patients is tuberculosis, followed by lymph node reactive hyperplasia, AIDS-related lymphadenopathy and Penicillium disease. Low CD4(+) T lymphocyte count correlates with an increased incidence of superficial lymphadenopathy and the risk of opportunity infection. Therefore, determination of peripheral blood CD4(+) T lymphocyte count should become an integral marker for the early diagnosis and treatment of superficial lymphadenopathy in HIV/AIDS patients.
Assuntos
Complexo Relacionado com a AIDS/sangue , Síndrome da Imunodeficiência Adquirida/sangue , Contagem de Linfócito CD4 , Infecções por HIV/sangue , Complexo Relacionado com a AIDS/complicações , Complexo Relacionado com a AIDS/patologia , Infecções Oportunistas Relacionadas com a AIDS/sangue , Infecções Oportunistas Relacionadas com a AIDS/complicações , Infecções Oportunistas Relacionadas com a AIDS/patologia , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Infecções por HIV/complicações , Infecções por HIV/patologia , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Tuberculose/sangue , Tuberculose/complicações , Tuberculose/patologia , Adulto JovemRESUMO
Hyperthermal stress and resulting free radical generation is known to impair endurance capacity and immune cell redistribution during prolonged exercise. Caffeic acid phenethyl ester (CAPE), a phenolic compound purified from propolis, has many biological and pharmacological activities including antioxidation. To examine whether CAPE has protective effect against hyperthermal stress in athletes, we isolated peripheral blood mononuclear cells (MNC) from competitive cyclists and assessed their response to hyperthermia with or without CAPE pretreatment. We found that pretreatment of cyclists' MNC with CAPE (0, 1, 2, 4 microg/mL) reversed or reduced hyperthermia-induced survival inhibition, necrosis, superoxide production, glutathione depletion, and intracellular superoxide burst in a dose-dependent manner. These results suggest that CAPE may enhance the hyperthermal tolerance in immune mononuclear cells of competitive cyclists.
Assuntos
Antioxidantes/farmacologia , Ácidos Cafeicos/farmacologia , Temperatura Alta/efeitos adversos , Leucócitos Mononucleares/efeitos dos fármacos , Álcool Feniletílico/análogos & derivados , Aptidão Física/fisiologia , Estresse Fisiológico/efeitos dos fármacos , Ciclismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Teste de Esforço , Glutationa/análise , Humanos , Técnicas In Vitro , Leucócitos Mononucleares/patologia , Masculino , Necrose/prevenção & controle , Álcool Feniletílico/farmacologia , Própole/química , Superóxidos/análiseRESUMO
DNA screening for LDL receptor mutations was performed in 170 unrelated hyperlipidemic Chinese patients and two clinically diagnosed familial hypercholesterolemia patients. Two deletions (Del e3-5 and Del e6-8), eight point mutations (W-18X, D69N, R94H, E207K, C308Y, I402T, A410T, and A696G), and two polymorphisms (A370T and I602V) were identified. Of these mutations, C308Y and Del e6-8 were found in homozygosity, and D69N and C308Y were seen in unrelated patients. The effects of mutations on LDL receptor function were characterized in COS-7 cells. The LDL receptor level and activity were close to those of wild type in A696G transfected cells. A novel intermediate protein and reduction of LDL receptor activity were seen in D69N transfected cells. For R94H, E207K, C308Y, I402T, and A410T mutations, only approximately 20-64% of normal receptor activities were seen. Conversely, Del e3-5 and Del e6-8 lead to defective proteins with approximately 0-13% activity. Most of the mutant receptors were localized intracellularly, with a staining pattern resembling that of the endoplasmic reticulum and Golgi apparatus (D69N, R94H, E207K, C308Y, and I402T) or endosome/lysosome (A410T and Del e6-8). Molecular analysis of the LDL receptor gene will clearly identify the cause of the patient's hyperlipidemia and allow appropriate early treatment as well as antenatal and family studies.