RESUMO
BACKGROUND: Oxaliplatin is a crucial chemotherapy drug that plays an important role in colorectal cancer and oral cancer treatment. However, the molecular mechanism of oxaliplatin in killing tongue squamous cell cancer cells is still unknown. This paper investigates the mechanism of by which oxaliplatin regulates tongue squamous cell carcinoma Tca8113 cell survival and death. MATERIAL AND METHODS: Tca8113 was treated with 1 µmol/L oxaliplatin for 24 h. Tca8113 cell proliferation and apoptosis were determined by MTT method and flow cytometry, respectively. Western blot was applied to detect receptor-interacting protein kinase 1 (RIP1) level. Tca8113 was transfected with siRNA RIP1 and then treated with 1 µmol/L oxaliplatin, and the cell apoptosis was detected. RESULTS: We found that 1 µmol/L oxaliplatin could inhibit Tca8113 cell growth (cell survival rate was 19.3%), reduce mitochondrial membrane potential (reduce 82.3%) and phosphatidylserine eversion (positive rate was 62.7%), and activate caspase-3 (increased 2.6 times). We also found that 1 µmol/L oxaliplatin treatment could increase RIP1 expression in Tca8113 cells. Cell apoptosis rate increased after siRNA RIP1 and 1 µmol/L oxaliplatin treatment (apoptosis rate was 90.2%). CONCLUSIONS: Down-regulating RIP1 promotes oxaliplatin induced Tca8113 cells apoptosis.
Assuntos
Antineoplásicos/química , Apoptose , Regulação Neoplásica da Expressão Gênica , Compostos Organoplatínicos/química , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Carcinoma de Células Escamosas/patologia , Caspase 3/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células , Sobrevivência Celular , Regulação para Baixo , Citometria de Fluxo , Humanos , Potencial da Membrana Mitocondrial , Potenciais da Membrana , Oxaliplatina , Fosfatidilserinas/química , RNA Interferente Pequeno/metabolismo , Neoplasias da Língua/patologia , TransfecçãoRESUMO
Acute myeloid leukemia (AML) is a hematological tumor in which progress T helper (Th) subsets including Th22, Th17, and Th1 cells play a pivotal role. However, the role of T helper (Th) subsets in the immune pathogenesis of AML remains unclear. Here, we investigated frequencies of Th22, Th17, pure Th17, and Th1 cells in the peripheral blood (PB) of AML patients. We demonstrated that Th22, Th17, and pure Th17 in newly-diagnosed (ND) and non-complete remission (Non-CR) AML patients and plasma IL-22 in ND AML patients were significantly increased. Retinoid-related orphan receptor C (RORC) expression was significantly elevated in CR and Non-CR AML patients. However, Th1 in ND AML patients and IL-17 in ND, Non-CR or CR AML patients was significantly decreased compared with controls. Moreover, Th22 and IL-22 showed positive correlation with pure Th17, but Th22 showed negative correlation with Th1 in ND AML patients. RORC showed positive correlation with Th22 and approximately positive correlation with pure Th17 in Non-CR patients. PB blast cell showed positive correlation with Th22 and negative correlation with Th1 in ND AML patients. Our results indicate that Th22 and pure Th17 cells conjointly contribute to the pathogenesis of AML and might be promising novel clinical index for AML.
Assuntos
Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/imunologia , Contagem de Linfócitos , Subpopulações de Linfócitos T/imunologia , Células Th17/imunologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Casos e Controles , Citocinas/sangue , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Imunofenotipagem , Interleucinas/sangue , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Indução de Remissão , Subpopulações de Linfócitos T/metabolismo , Células Th1/imunologia , Células Th17/metabolismo , Adulto Jovem , Interleucina 22RESUMO
Linezolid is commonly used for the treatment of drug-resistant Gram-positive bacterial infection. This study aimed to evaluate the efficacy and safety of linezolid in treating Gram-positive bacterial infection in the elderly from January 2010 to December 2012. Total 40 elderly patients (>60 years old) with Gram-positive bacterial infection were treated with linezolid and their demographic and clinical data were collected and analyzed. Among the 40 patients, 31 patients (77.5 %) were cured. Linezolid caused little adverse effects on liver and renal function. The main adverse effect was thrombocytopenia and its incidence was significantly associated with baseline platelet count and the duration of treatment (P < 0.05). Logistic regression analysis showed that the baseline platelet count <200 × 10(6)/mL, but not the age, the sex, the length of hospital stay, baseline levels of hemoglobin, alanine aminotransferase, or creatinine clearance rate was significantly associated with linezolid-induced thrombocytopenia. In conclusion, linezolid is effective to cure Gram-positive bacterial infection in the elderly and causes little adverse effects on liver and renal function. Timely monitoring of baseline platelet count may be helpful to guide the use of linezolid to avoid the occurrence of thrombocytopenia.
RESUMO
In patients with intrathoracic neoplasms, low forced expiratory volume (FEV1) can preclude surgical treatment. Here, we present a case of a giant solitary fibroma of the pleura (SFTP) successfully treated by surgical removal in spite of low FEV1. A 39-year-old male patient was referred to our hospital with dyspnoea and chest distress. Computed tomography (CT) showed a large mass in the left chest. Spirometry showed FEV1 1.4 L (39% of the expected value). Computed tomography scan-guided transcutaneous aspiration biopsy was performed on the patient, and microscopic examination of the specimen revealed spindle tumor cells with a background of abundant collagen. Complete surgical resection was accomplished. The tumor was large and encapsulated. It measured 28 cm × 20 cm × 18 cm. The definitive diagnosis obtained by histopathology after resection was benign SFTP. The patient felt no dyspnoea at discharge. Surgical treatment of SFTP should be considered even in patients with a huge tumor and with increased post-operative risk.
RESUMO
Tumor angiogenesis plays important roles in the pathogenesis and prognosis of lung cancer. Both vascular endothelial growth factor (VEGF) and Dll4/Notch pathways are critical for angiogenesis, whereas their relationship under hypoxia in lung cancer remains unknown. Thus, in the present study, we evaluated the expression of VEGF and Dll4/Notch signaling molecules, and assessed their association with the microvessel density (CD31) and hypoxia (HIF1a) in lung cancer and normal lung tissues using immunohistochemical and Real-time RT-PCR techniques. Then, we investigated the biological function of Dll4 by transfecting Dll4 into HUVECs. In lung cancer tissues, Notch pathway molecules (HES1) and VEGF pathway molecules (VEGFR1 and VEGFR2) were significantly up-regulated, while the ratio of VEGFR1/VEGFR2 was decreased. CD31 and HIF1a were also found to be elevated in lung cancer. VEGFR1 was negatively correlated with Notch1 while positively correlated with Dll4. CD31 was positively correlated with HIF1a but negatively correlated with VEGFR1. Moreover, HIF1a was nearly positively correlated with HES1 in lung cancer tissues. After transfection, Dll4, Notch1 and VEGFR1 were up-regulated while VEGF and VEGFR2 were down-regulated in Dll4-transfected HUVECs compared with controls. Also, our findings suggest that the expression of VEGF and VEGFR2 increased gradually with the disease progression of lung cancer. In summary, VEGF and Notch signaling pathway molecules were overexpressed in lung cancer, which positively correlates with hypoxia (HIF1a) and angiogenesis (CD31). There might be a negative feedback loop between VEGF and Dll4/Notch signaling pathway in lung tumor angiogenesis.
Assuntos
Adenocarcinoma/metabolismo , Carcinoma de Células Escamosas/metabolismo , Hipóxia/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neoplasias Pulmonares/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Proteínas de Ligação ao Cálcio , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Células Cultivadas , Progressão da Doença , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Receptores Notch/genética , Estudos Retrospectivos , Fatores de Transcrição HES-1 , Veias Umbilicais/metabolismo , Veias Umbilicais/patologia , Regulação para Cima , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
AIMS AND BACKGROUND: To study the inhibitory effect of p21WAF1/CIP1 activation by saRNA on the growth of human pancreatic cancer cells PANC-1 in vitro and in vivo. METHODS AND STUDY DESIGN: A dsRNA (dsP21) targeting the p21WAF1/CIP1 gene promoter at position-322 relative to the transcription start site was transfected into PANC-1 cells. Expression of mRNA and protein was evaluated by semiquantitative RT-PCR and Western blotting. Proliferation of PANC-1 cells was measured by the MTT method, and the apoptosis rate was detected by flow cytometry. PANC-1 cells were transplanted subcutaneously in nude mice, and the inhibitory effect of dsP21 on tumor growth was observed. RESULTS: The introduction of dsP21 was shown to efficiently up-regulate expression of the p21WAF1/CIP1 gene in PANC-1 cells according to the results of RT-PCR and Western blotting (P <0.01, compared with controls). The inhibitory effect on cell proliferation was confirmed by the MTT test (P <0.05, compared with controls). The apoptosis rate of PANC-1 cells treated with dsP21 was significantly higher than that of the control cells (P <0.01). Our experimental data showed that dsP21-mediated up-regulation of p21 expression exerted an apparent growth inhibitory effect on PANC-1 cells in vivo. CONCLUSIONS: dsP21 targeting the p21WAF1/CIP1 gene promoter can specifically up-regulate expression of the p21WAF1/CIP1 gene in PANC-1 cells. It therefore has a substantially inhibitory effect on cell proliferation in vitro and in vivo and can be used as a new method and material for the gene therapy of pancreatic cancer.
Assuntos
Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , RNA Interferente Pequeno/metabolismo , Animais , Apoptose , Western Blotting , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Neoplasias Pancreáticas/genética , Regiões Promotoras Genéticas/genética , RNA Interferente Pequeno/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Regulação para Cima , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
T-helper (Th) 22 and Th17 cells are implicated in the pathogenesis of autoimmune diseases. However, the role of Th22 cells in the pathophysiology of immune thrombocytopenia (ITP) remains unclear. Th22, Th17 and Th1 cells in both ITP patients and healthy controls were examined by flow cytometry. Plasma interleukin-22 (IL-22) level was measured by enzyme linked immunosorbent assay (ELISA). Signal transducers and activators of transcription 3 (STAT-3) and transcription factor RAR-related organ receptor C (RORC) messenger RNA (mRNA) expressions were examined by quantitative reverse transcription polymerase chain reaction (RT-PCR). Th22 cells, Th17 cells, Th1 cells and plasma IL-22 were significantly higher in ITP patients than in healthy controls. Moreover, Th22 cells showed a positive correlation with the levels of plasma IL-22 as well as Th17 and Th1 cells in ITP patients. Significant up-regulations of both STAT-3 and RORC transcription factors were also observed. Additionally, the percentage of Th22 cells was higher in autoantibody-negative ITP patients than in autoantibody-positive patients. Our results demonstrate a possible role of Th22 cells in ITP, and thus, the blockade of IL-22 may be a reasonable therapeutic strategy for ITP.
Assuntos
Autoimunidade , Plaquetas/imunologia , Linfócitos T Auxiliares-Indutores/patologia , Células Th17/patologia , Trombocitopenia/patologia , Adolescente , Adulto , Idoso , Autoanticorpos/imunologia , Plaquetas/patologia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucinas/sangue , Interleucinas/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/sangue , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/imunologia , Contagem de Plaquetas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT3/sangue , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Células Th17/imunologia , Trombocitopenia/sangue , Trombocitopenia/imunologia , Regulação para Cima , Interleucina 22RESUMO
PURPOSE: The objective of this study was to investigate the mechanism of MAb225 regulating radiosensitivity of Tca8113 cells. METHODS: Tca8113 cells were treated with MAb225 of different concentrations. The apoptosis rate was analysed by FCM and bi-fluorescence stain, the repair of DNA damage after radiation was analysed by single cell gel electrophoresis, cells redistribution in each phase of cell cycle was analysed by FCM, and GSH level of cell were assessed by spectrophotometer. RESULTS: Radiation alone (6 Gy) and MAb225 alone (0.5 microg/ml) produced a 2-fold induction of apoptosis respectively, whereas exposure to MAb225 (0.5 microg/ml) combination with 6 Gy of radiation induced apoptosis 5-6 fold, compared to untreated controls (F test). The length of comet tail of cells which treated with MAb225 was significantly longer than that of the control cells (t test, P<0.05). The percentage of cells in S phase was significantly decreased in MAb225 treated cells. Intracellular GSH level of MAb225 treated cells was significantly lower than that of untreated cells (t test, P<0.05). CONCLUSION: MAb225 increased the radiosensitivity of Tca8113 cells by enhancing radiation-induced apoptosis, downregulating S phase percentage, inhibiting DNA repair after radiation and decreasing GSH level.