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1.
J Cell Mol Med ; 24(21): 12840-12847, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32945069

RESUMO

Tumour drug resistance is one of the most urgent issues faced by anti-tumour therapies. P-glycoprotein (P-gp) has been reported to be correlated with drug resistance. In this study, we aimed to study the synergistic effect of fluorouracil (5FU) and Ubenimex (UBE) on drug resistance in lung cancer. In this study, the tumour inhibitory role of 5FU and UBE was assessed in nude mice bearing A549 or A549/ADR. Real-time polymerase chain reaction, Western blot and immunohistochemical were performed to analyse the mRNA and protein expression of P-gp. TUNEL assay was used to evaluate the apoptosis of A549/ADR cells under 5FU and UBE treatment. MTT assay was performed to calculate the IC50 value of 5FU and UBE in A549 or A549/ADR. Combined administration of 5FU and UBE significantly inhibited the tumour growth of multidrug-resistant cell lines A549/ADR in nude mice by down-regulating the mRNA and protein expression of P-gp. The apoptosis of A549/ADR was remarkably elevated in nude mice treated with 5FU and UBE. The IC50 value of 5FU and UBE was dramatically declined in A549/ADR cells compared with that of 5FU or UBE alone. Combined treatment of 5FU and UBE remarkably enhanced the apoptosis of A549/ADR cells by enhancing the intracellular accumulation of the drugs. The results of this study demonstrated that UBE combined with fluorouracil attenuated multiple drug resistance and inhibited the expression of P-gp in lung cancer.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Fluoruracila/uso terapêutico , Leucina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Células A549 , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Animais , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fluoruracila/administração & dosagem , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Leucina/administração & dosagem , Leucina/farmacologia , Leucina/uso terapêutico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos Endogâmicos C57BL , Camundongos Nus , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
2.
J Thorac Dis ; 7(12): 2366-70, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26793361

RESUMO

Now, more and more complete video-assisted thoracoscopic surgery (cVATS) surgeons are capable of performing lobectomy by uniportal approach. However, concerns regarding the safety of uniportal procedures for complex cases such as neoadjuvant chemotherapy, bronchial sleeves or vascular reconstructions still remains. As experience with uniportal VATS has increased, its application toward more technically demanding operations has also expanded. This article describes a uniportal cVATS left upper lobectomy with partial pulmonary arterioplasty for lung cancer with calcified lymph nodes. In order to reduce the risk of bleeding, we looped the left main pulmonary artery and applied two-stage maneuvering for left upper lobe (LUL) bronchus, cut the bronchus at the distal end and close the stump using a stapler at the end, which are conducive to maximal safety.

3.
Zhonghua Jie He He Hu Xi Za Zhi ; 35(8): 596-600, 2012 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-23158008

RESUMO

OBJECTIVE: To study the association between single nucleotide polymorphisms (SNPs) of interleukin-22 (IL-22) gene and pulmonary tuberculosis. METHODS: From January 2009 to December 2010, clinical data of 479 patients with pulmonary tuberculosis in Shenzhen Third People's Hospital were collected. There were 212 males, and 267 females, aging from 18 to 69 (mean 36 ± 17) years, as well as 358 healthy controls (162 males and 196 females), aging from 18 to 60 (mean 34 ± 13) years. The genotype of SNPs (rs1182844, rs2227473, rs2227476, rs2227480, rs2227485, rs2227508) in IL-22 gene were determined with MassARRAY assay, after Hardy-Weinberg equilibrium test, and the allelic frequency and odds ratio were calculated. Peripheral blood mononuclear cells (PBMCs) from patients with different rs2227473 genotypes were stimulated with anti-CD3 and CD28, and then the IL-22 concentration in supernatant was determined with ELSIA. The SNP allelic frequencies between 2 groups were analyzed by chi-square and IL-22 concentration by t-test. RESULTS: The frequency of allele G of rs2227473 SNP was significantly higher in tuberculosis group than that in the control group (χ(2) = 7.448, P < 0.01, OR = 1.509, 95%CI= 1.121 - 2.030). The other 5 SNPs allele frequency were not statistically significant between the 2 groups (χ(2) = 0.528 - 3.571, all P > 0.05). The secretion of IL-22 was significantly lower in PBMCs with genotype GG of rs2227473 SNP as compared to that in the others (GA/AA) (t = 2.686, P < 0.01). CONCLUSIONS: The results suggested that the rs2227473 SNP in IL-22 was associated with the risk of pulmonary tuberculosis. The allele G was the risk factor of pulmonary tuberculosis. The SNP (rs2227473) may play an important role in the protective immune process against tuberculosis by affecting the IL-22 expression of PBMCs.


Assuntos
Predisposição Genética para Doença , Interleucinas/genética , Polimorfismo de Nucleotídeo Único , Tuberculose Pulmonar/genética , Adolescente , Adulto , Idoso , Alelos , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Interleucina 22
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