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OBJECTIVES: To investigate the effect of Procyanidins (OPCs) on the autophagy of laryngeal cancer cell line TU686 and to explore the effect of OPCs on the chemosensitivity of laryngeal cancer cells to DDP in terms of autophagy and apoptosis. METHODS: CCK-8 was used to detected the effect of different concentrations of OPC and DDP on TU686 cell viability. Experimental grouping: Both kinds of cells were divided into CON group, DDP group, OPC group and MIX group. Annexin-V-FITC/PI double staining of flow cytometry was used to detect the effect of each experimental group on the apoptosis. Cell immunofluorescence staining was used to detect the formation of autophagy. Western blot was used to detect the expression of autophagy-related and apoptosis-related proteins. Autophagy inhibitors (3-MA) were used to study the effect of autophagy on apoptosis. RESULTS: The results of CCK-8 showed that TU686 cells were inhibited by OPC and DDP in a concentration-dependent manner for 24 hours. LC3-â ¡ protein staining showed that compared with CON group, DDP group and OPC group, MIX group significantly induced autophagy formation in TU686 cells (P<0.05). Flow cytometry showed that compared with CON group, apoptosis of TU686 cells was induced in DDP group, OPC group and MIX group. And the effect of MIX on apoptosis was significantly higher than that of OPC and DDP groups (P<0.05). After pretreatment with 3-MA, the apoptotic effect of OPC group and MIX group on TU686 cells was significantly decreased (P<0.05). Western blot results showed that the expression of LC3-â ¡ and Caspase-3 in DDP, OPC and MIX groups was significantly higher than that in CON group (P<0.05). In MIX group, the expression of LC3-â ¡ and Caspase-3 also had significant difference (P<0.05) compared with single drug group. After using 3-MA to inhibit autophagy, the expression of LC3-â ¡ was significantly decreased (P<0.05), and the expression of Caspase-3 was decreased along with LC3-â ¡, but the decrease of Caspase-3 expression was only significant in OPC and MIX group (P<0.05). CONCLUSIONS: OPC can induce autophagy in laryngeal carcinoma TU686 cells and promote its apoptosis, which in turn enhances sensitivity of laryngeal cancer cells to cisplatin chemotherapy.
Assuntos
Autofagia/efeitos dos fármacos , Cisplatino/farmacologia , Neoplasias Laríngeas/tratamento farmacológico , Proantocianidinas/farmacologia , Antineoplásicos , Apoptose , Proteínas Reguladoras de Apoptose , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , HumanosRESUMO
OBJECTIVE: To explore the efficacies of extended pelvic lymph node dissection (e-PLND) before or after radical cystectomy (RC). METHODS: From January 2003 to January 2013, a total of 107 patients underwent e-PLND plus RC. And their relevant clinical data were reviewed. Their median age was (62 ± 10) years. The e-PLND were divided into 10 regions and 6 groups according to the anatomic sites. Forty-seven (43.9%) underwent RC after e-PLND (group A) and 60 (56.1%) had RC before e-PLND (group B). Two groups were compared for operative duration, numbers of lymph nodes removed, metastatic rates of lymph node, dissected lymph node positive rates and operative complications. The results were analyzed with Chi-square or Student's test. RESULTS: Clinicopathological characteristics were comparable for two groups (P > 0.05). The mean operative durations of e-PLND were similar in both groups ( (83 ± 27) vs (78 ± 24) min , P > 0.05). The mean operative durations of RC were significantly shorter in group A than those in group B ( (79 ± 41) vs (113 ± 44) min, P < 0.01) . The mean number of lymph nodes removed (25.5 ± 9.7 vs 29.0 ± 8.4) and the mean number of lymph nodes removed at internal iliac (5.7 ± 2.9 vs 7.2 ± 3.5) and presacral (1.3 ± 1.1 vs 2.5 ± 1.6) regions were significantly fewer in group A than those in group B (all P < 0.05). The metastatic rates of lymph node (34.0% (16/47) vs 31.7% (19/60)), dissected lymph node positive rates (9.0% (108/1197) vs 7.5% (130/1743)) and operative complications (23.4% (11/47) vs 20.0% (12/60)) were similar in both groups (all P > 0.05). CONCLUSION: RC is performed preferably after e-PLND, and internal iliac and presacral area should be dissected for additional lymph nodes after RC.
Assuntos
Cistectomia/métodos , Excisão de Linfonodo , Pelve/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
UNLABELLED: To screen and analyze the apoptosis- and proliferation-related genes in human nasopharyngeal carcinoma (NPC). METHODS: According to gene ontology classification, the abnormal expressions of the genes related to cell apoptosis and proliferation were identified in the NPC gene chip data. The cell apoptosis- and proliferation-related genes expressed in each of the 3 stages, as defined by the tree model for the pathogenesis and progression of NPC, were screened, and with literature review, their distribution in the tree model were analyzed. RESULTS: Nineteen genes related to cell apoptosis were found in NPC, among which 9 were down-regulated (such as DNASE1L3) and located in the chromosome deletion regions, and 10 were up-regulated (such as DEDD) in the chromosome amplification regions. Twenty-one cell proliferation-related genes were identified, including 8 down-regulated genes (such as TUSC2) in the chromosome deletion regions and 13 up-regulated ones (such as EMP1) in the chromosome amplification regions. In the chromosome deletion regions, the down-regulated cell apoptosis-related genes participated mostly in inducing and regulating cell apoptosis, and the up-regulated cell proliferation-related genes in the chromosome amplification regions were mostly associated with the positive regulation of cell proliferation. CONCLUSION: NPC occurs possibly through two pathways by inhibiting cell apoptosis or by promoting excessive cell proliferation.
Assuntos
Apoptose/genética , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Proliferação de Células , Deleção Cromossômica , Regulação para Baixo , Perfilação da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Regulação para CimaRESUMO
Deleted in liver cancer-1 (DLC-1), encoding a Rho GTPase-activating protein (GAP), is considered as a promising candidate tumor suppressor gene in nasopharyngeal carcinoma (NPC). The single-nucleotide polymorphism (SNP) -29A/T upstream of ATG start codon was found when gene mutation profile of DLC-1 in NPC was analyzed. To evaluate the correlation between SNP -29A/T in the promoter region of DLC-1 gene and risk of NPC, a total of 521 samples from a Chinese population, including 320 healthy individuals and 201 NPC patients, were collected for SNP analysis by PCR-single-strand conformation polymorphism and sequencing. The differences in allele and genotype frequencies between NPC patients and controls were tested using logistic regression statistical method. No significant differences were found in allele or genotype frequencies between NPC patients and controls or among different NPC clinical stages. Hence, our data indicate that the SNP -29A/T of DLC-1 gene is not associated with NPC susceptibility.