RESUMO
BACKGROUND: Programmed cell death-1 (PD-1) and programmed cell death ligand-1(PD-L1) inhibitor therapy have been approved for the treatment of many cancers, although their incidence of some side effects was high. We aim to fully investigate the incidence risk of PD-1/PD-L1 inhibitors-related pneumonia and diarrhea in NSCLC patients, as well as treatment-related deaths. METHODS: PubMed, Medline, Cochrane Library, and Clinical trials.gov databases were searched up to Sep 17, 2020, for clinical trials of PD-1 inhibitors and PD-L1 inhibitors in the treatment of NSCLC. Randomized controlled trials and their references were screened. RESULTS: Seventeen trials were included in our meta-analysis, including 11,363 patients. PD-1/PD-L1 inhibitors significantly increased the risk of developing all-grade and high-grade (grade ≥ 3) pneumonia (risk ratio [RR] = 2.28; 95% CI: 1.39-3.76; P < 0.01; RR = 2.38; 95% CI: 1.72-3.29; P < 0.01, respectively). The use of PD-1/PD-L1 inhibitor did not increase the risk of developing all-grade and high-grade diarrhea (RR = 0.79; 95% CI: 0.62-1.01; P = 0.06; RR = 0.96; 95% CI: 0.70-1.31; P = 0.78, respectively). There was no significant difference between the rate of death in PD-1 and PD-L1 inhibitors (P = 0.079). CONCLUSION: These data suggest that PD-1/PD-L1 inhibitors significantly increase the risk of all-grade and high-grade pneumonia in NSCLC patients and PD-1/PD-L1 monotherapy increases the risk of all-grade pneumonia in NSCLC patients compared to PD-1/PD-L1 inhibitor combination regimens. Physicians should pay more attention to NSCLC patients who treated with PD-1/PD-L1 inhibitors.
Assuntos
Antineoplásicos/efeitos adversos , Antígeno B7-H1/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Antineoplásicos/uso terapêutico , Diarreia/induzido quimicamente , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Incidência , Gravidade do Paciente , Pneumonia/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Xeroderma pigmentosum, complementation group C (XPC) is an accessory recognition gene involved in the nucleotide excision repair (NER) pathway, which is activated during the initial DNA damage recognition stage. It participates in the regulation of DNA damageinduced proliferation and apoptosis. Emerging evidence demonstrates that upregulation of XPC increases the resistance of several tumor cell types to cytotoxic drugs. In addition, it can predict poor patient outcome for nonsmall cell lung cancer (NSCLC). However, the mechanisms linking upregulation of XPC and drug resistance in lung cancer are still unclear. In the present study, we aimed to confirm whether XPC was involved in the reversal of the cisplatin (DDP) resistance in drugresistant A549/DDP lung adenocarcinoma cells. RTPCR and western blot assays were used to examine XPC mRNA and protein expression levels. Cell viability was assessed by CCK8 assay. The knockdown of XPC was achieved in A549/DDP cells using siRNA, whereas cell proliferation and apoptosis were assessed by wound healing assay and ï¬ow cytometric analysis, respectively. The median inhibitory concentration (IC50) value of DDP was assessed by CCK8 assay. Western blot assays were conducted for the examination of caspase9/3, Bax and Bcl2 protein levels, whereas the activation of the PI3K/Akt/mTOR signaling pathway was investigated in XPCknockdown cells. High expression of XPC was noted in A549/DDP cells compared with that in A549 cells, which was associated with DDP resistance. XPC silencing significantly inhibited A549/DDP cell proliferation and increased the induction of apoptosis. In addition, XPC knockdown decreased the expression levels of the Akt/mTOR signaling proteins and the expression of their downstream mediator. The data of the present study revealed that XPC inhibition rescued DDP resistance in lung adenocarcinoma cells, which was dependent on the Akt/mTOR signaling pathway. Collectively, XPC may be considered a new strategy for curing DDPresistant lung cancer and may improve the efficacy of conventional chemotherapy.
Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Cisplatino/farmacologia , Proteínas de Ligação a DNA/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/tratamento farmacológico , Células A549 , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Cisplatino/uso terapêutico , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/genética , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Concentração Inibidora 50 , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Regulação para CimaRESUMO
We created a two-channel autofluorescence test to detect oral cancer. The wavelengths 375 and 460 nm, with filters of 479 and 525 nm, were designed to excite and detect reduced-form nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) autofluorescence. Patients with oral cancer or with precancerous lesions, and a control group with healthy oral mucosae, were enrolled. The lesion in the autofluorescent image was the region of interest. The average intensity and heterogeneity of the NADH and FAD were calculated. The redox ratio [(NADH)/(NADH + FAD)] was also computed. A quadratic discriminant analysis (QDA) was used to compute boundaries based on sensitivity and specificity. We analyzed 49 oral cancer lesions, 34 precancerous lesions, and 77 healthy oral mucosae. A boundary (sensitivity: 0.974 and specificity: 0.898) between the oral cancer lesions and healthy oral mucosae was validated. Oral cancer and precancerous lesions were also differentiated from healthy oral mucosae (sensitivity: 0.919 and specificity: 0.755). The two-channel autofluorescence detection device and analyses of the intensity and heterogeneity of NADH, and of FAD, and the redox ratio combined with a QDA classifier can differentiate oral cancer and precancerous lesions from healthy oral mucosae.
Assuntos
Neoplasias Bucais/diagnóstico por imagem , Espectrometria de Fluorescência/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Discriminante , Feminino , Flavina-Adenina Dinucleotídeo/análise , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/diagnóstico por imagem , NAD/metabolismo , Sensibilidade e Especificidade , Adulto JovemRESUMO
Transfer RNA selenocysteine 1 associated protein 1 (Trnau1ap) serves an essential role in the synthesis of selenoproteins, which have critical functions in numerous biological processes. Selenium deficiency results in a variety of diseases, including cardiac disease. However, the mechanisms underlying myocardial injury induced by selenium deficiency remain unclear. The present study examined the effects of Trnau1ap under and overexpression in cardiomyocytelike H9c2 cells, by transfection with small interfering RNA and an overexpression plasmid, respectively. Expression levels of glutathione peroxidase, thioredoxin reductase and selenoprotein K were decreased in Trnau1apunderexpressing cells, and increased in Trnau1apoverexpressing cells. Using MTT, proliferating cell nuclear antigen, annexin V and caspase3 activity assays, it was demonstrated that reducing Trnau1ap expression levels inhibited the proliferation of H9c2 cells and induced apoptosis. Conversely, increasing Trnau1ap expression levels promoted cell growth. Western blot analysis revealed that the phosphoinositide 3kinase/protein kinase B signaling pathway was activated in Trnau1apunderexpressing cells. Furthermore, the apoptotic pathway was activated in these cells, evidenced by relatively greater expression levels of Bcell lymphoma (Bcl2)associated X protein and reduced expression levels of Bcl2. Taken together, these findings suggest that Trnau1ap serves a key role in the proliferation and apoptosis of H9c2 cells. The present study provides insight into the underlying mechanisms of myocardial injury induced by selenium deficiency.