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Objective To analyze the clinical characteristics and influencing factors of non-small cell lung cancer (NSCLC) patients with chronic obstructive pulmonary disease (COPD) in Hubei province, and to provide a theoretical basis for the diagnosis and treatment of NSCLC patients with COPD. Methods A total of 246 NSCLC patients admitted to our hospital from 2018 to 2020 were selected and divided into control group (without COPD, n=125) and observation group (with COPD, n=121) according to COPD. The clinical characteristics of chest pain, hemoptysis, emasculation, atelectasis and pleural effusion were compared between the two groups. The values of FEV1/FVC, RV/TLC and DLCO in the two groups were measured by pulmonary function detector. The age, gender, smoking, smoking history, proportion of lung squamous cell carcinoma, TNM stage and other clinical data of all subjects were analyzed by self-made survey scale of our hospital. Univariate analysis and logistic regression were used to analyze the risk factors of COPD in NSCLC patients. Results Among 246 NSCLC patients, 121 patients (49.19%) were complicated with COPD, including 76 males and 45 females, and there was a statistical difference between the two groups (χ2=4.891, P>0.05). The average age of the observation group (61.02±4.82) was significantly higher than that of the control group (59.76±4.73) (t=2.069, P0.05). Male (OR=2.982), smoking history (OR=2.623) and lung squamous cell carcinoma (OR=3.147) were risk factors for COPD in NSCLC patients (P<0.05). Conclusions NSCLC patients with COPD are more common in male smokers in Hubei Province, often accompanied by pleural effusion , severe hemoptysis and other symptoms , and their lung function is decreased. Early detection and standardized treatment of COPD in the treatment of NSCLC can improve the prognosis of patients.
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ObjectiveTo explore the mechanism of Buzhong Yiqitang-containing serum in alleviating the cisplatin resistance in human non-small cell lung cancer （A549/DDP） cells via regulating the nuclear factor E2-related factor 2 （Nrf2）/reactive oxygen species （ROS） signaling pathway. MethodThe serum containing Buzhong Yiqitang was prepared and A549/DDP cells were cultured and randomly grouped： blank （10% blank serum）， cisplatin （10% blank serum+20 mg·L-1 cisplatin）， Buzhong Yiqitang （10% Buzhong Yiqitang-containing serum+20 mg·L-1 cisplatin）， ML385 （10% blank serum+5 μmol·L-1 ML385+20 mg·L-1 cisplatin）， Buzhong Yiqitang+ML385 （10% Buzhong Yiqitang-containing serum+5 μmol·L-1 ML385+20 mg·L-1 cisplatin）， tertiary butylhydroquinone （TBHQ） （10% blank serum+5 μmol·L-1 TBHQ+20 mg·L-1 cisplatin）， and Buzhong Yiqitang+TBHQ （10% Buzhong Yiqitang-containing serum+5 μmol·L-1 TBHQ+20 mg·L-1 cisplatin）. The median inhibitory concentration （IC50） of cisplatin in each group was determined by the cell counting kit-8 （CCK-8） method and the resistance index （RI） was calculated. The apoptosis rate was detected by flow cytometry. The ROS content of each group was determined with the DCFH-DA fluorescence probe. Western blot was employed to determine the protein levels of Nrf2， cleaved cysteinyl aspartate-specific protease-3 （cleaved Caspase-3）， cytochrome C （Cyt C）， and B-cell lymphoma-2 （Bcl-2）. ResultCompared with those in the cisplatin group， the IC50 and RI of A549/DDP cells to cisplatin in Buzhong Yiqitang， ML385， and Buzhong Yiqitang+ML385 groups decreased （P˂0.05）. Compared with the blank group， the cisplatin， Buzhong Yiqitang， ML385， and Buzhong Yiqitang+ML385 groups showed increased apoptosis rate of A549/DDP cells （P˂0.05）. Compared with the blank group， cisplatin promoted the expression of Nrf2 （P˂0.05）. Compared with the cisplatin group， Buzhong Yiqitang， ML385， and Buzhong Yiqitang+ML385 inhibited the expression of Nrf2 （P<0.05）， elevated the ROS level （P˂0.05）， up-regulated the protein levels of cleaved Caspase-3 and Cyt C， and down-regulated the protein level of Bcl-2 （P<0.05）， which were the most significant in the Buzhong Yiqitang+ML385 group. Compared with the cisplatin group， the TBHQ group showed increased IC50 and RI of cisplatin （P<0.05）， decreased apoptosis rate of A549/DDP cells （P<0.05）， up-regulated protein levels of Nrf2 and Bcl-2 （P<0.05）， lowered level of ROS （P˂0.05）， and down-regulated protein levels of cleaved Caspase-3 and Cyt C （P<0.05）. Compared with the TBHQ group， Buzhong Yiqitang+TBHQ decreased the IC50 and RI of cisplatin in A549/DDP cells （P<0.05）， increased the apoptosis rate （P<0.05）， down-regulated the protein levels of Nrf2 and Bcl-2 （P<0.05）， increased ROS （P˂0.05）， and up-regulated the protein levels of cleaved Caspase-3 and Cyt C （P<0.05）. ConclusionBuzhong Yiqitang induced apoptosis by inhibiting Nrf2/ROS pathway to alleviate cisplatin resistance in A549/DDP cells.
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El cáncer de pulmón es la neoplasia maligna que causa mayor mortalidad en el mundo. Dentro de los factores pronósticos de esta entidad, se encuentran el índice neutrófilo-linfocito y el índice plaquetas-linfocito, parámetros hematológicos que se utilizan para evaluar la inflamación y la respuesta inmunitaria en el cuerpo humano. Se realizó una revisión bibliográfica con el objetivo de exponer el valor que presentan el índice neutrófilo-linfocito y el índice plaquetas-linfocito como herramientas pronósticas del cáncer de pulmón, teniendo en cuenta la evidencia científica publicada hasta el momento. Se estudiaron 46 artículos, 28 de los cuales resultaron seleccionados para la elaboración de la investigación. Se emplearon como criterios de selección la calidad de los estudios, el nivel de actualización sobre el tema en cuestión, así como la fiabilidad de la fuente. Se usaron los recursos disponibles en la red Infomed para la selección de la información, entre ellos: PubMed, SciELO, EBSCO, Cumed, LILACS y Scopus, además de Medline, Academic Search Premier y MedicLatina. Se expuso el valor que presentan el índice neutrófilo-linfocito y el índice plaquetas-linfocito como herramientas pronósticas del cáncer de pulmón de células no pequeñas, en todos los estadios y con modalidades terapéuticas diferentes.
Lung cancer is the malignant neoplasm that causes higher mortality in the world. Among the prognostic factors of this entity are the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio, hematological parameters that are used to assess inflammation and the immune response in the human body. A bibliographic review was carried out with the objective of exposing the value of the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as a prognostic tool for lung cancer, taking into account the scientific evidence published to date. A total of 46 articles were studied, of which 28 were selected for the development of the research. The quality of the studies, the level of updating on the subject in question, as well as the reliability of the source was used as selection criteria. The resources available in the Infomed network were used to select the information, including PubMed, SciELO and EBSCO, Cumed, LILACS and Scopus, as well as Medline, Academic Search Premier and MedicLatina databases. The value of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as a prognostic tool in non-small cell lung cancer at all stages and with different therapeutic modalities was exposed.
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Resumen El carcinoma tipo-linfoepitelioma pulmonar es una variante rara de carcinoma de células no pequeñas de pulmón, representa aproximadamente 0.7% de todos los casos. Está usualmente asociado con la infección por el virus de Epstein-Barr y es más prevalente en el Sureste de Asia; sin embargo, es extremadamente raro en Améri ca Latina. Informamos el caso de un hombre de 65 años de edad con un carcinoma tipo-linfoepitelioma pulmo nar, que se presentó con tos, disnea y pérdida de peso. La TAC de tórax mostró nódulo mal definido localizado en el pulmón derecho. Se realizó biopsia transtorácica de la lesión, y el estudio microscópico reveló células gran des poligonales dispuestas en mantos, infiltrados por abundantes linfocitos y células plasmáticas, alrededor del intersticio. Las células neoplásicas fueron positivas para citoqueratina 5/6 y p63, y negativas para Napsina A y el factor de transcripción tiroideo 1 (TTF-1). La expre sión de PD-L1 fue positivo (aproximadamente 100%) por inmunohistoquímica; así como el núcleo de las células neoplásicas mediante hibridación in situ para el RNA codificado por el virus de Epstein-Barr (EBER-ISH). El paciente recibió seis ciclos de un esquema combinado de quimioterapia basado en platino (gencitabina/cisplatino) más durvalumab. Presentó progresión de la enfermedad y finalmente murió 9 meses después del diagnóstico.
Abstract Pulmonary lymphoepithelioma-like carcinoma is a rare type of non-small cell lung cancer, it accounts for approximately 0.7% of all cases. It is usually associated with Epstein-Barr virus infection and is more prevalent in Southeast Asia; however, it is extremely rare in Latin America. We present a 65-year-old man with a primary pulmonary lymphoepithelioma-like carcinoma, who presented with cough, dyspnoea and weight loss. Com puter tomographic scan of the thorax showed a nodule localized in the right lung. A transthoracic biopsy of the lung lesion was made and the microscopic obser vation revealed large polygonal cells that proliferated in a nest pattern with infiltration by lymphocytes and plasma cells around the interstitium. The tumour cells were positive for citokeratin 5/6 and p63, and negative for Napsin A and thyroid transcription factor 1 (TTF-1). PD-L1 expression was positive (approximately 100%) in the immunohistochemical study, and the nuclei of the tumour cells were positive for EBV-encoded small RNA in-situ hybridization (EBER-ISH). The patient underwent six cycles of platinum-based combination (gencitabine/ carboplatin) chemotherapy plus durvalumab. He pre sented progression of the disease and finally he died 9 months after diagnosis.
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Background: Curative thoracic radiotherapy (CTRT) with concurrent chemotherapy has been considered as standard treatment approach for stage-III non-small cell lung cancer (NSCLC). The hematological and esophageal toxicities that have been encountered during CTRT would affect the immunonutritional status of the patients. The aim of this study is to evaluate the prognostic value of the change in pre- and post-treatment prognostic nutritional index (PNI) in stage-III NSCLC patients. Methods: Eighty seven consecutive stage III NSCLC patients� data were collected. Pre-radiotherapy (RT) and post-RT PNI values were calculated and the impact of prognostic value of PNI change on overall survival (OS) was evaluated by univariate and multivariate Cox regression analyses. A cutoff value of PNI change was obtained by receiver operator characteristic (ROC) curve analysis. Results: The cutoff value was found to be a 22% decrease in PNI by ROC curve analysis in terms of effect on OS. The median OS of low and high PNI decrease groups were 22.5 and 16.5 months respectively (P = 0,001). In univariate and multivariate analyses PNI decrease of ? 22% was found to be an independent poor prognostic factor for OS (P = 0.012) and hazard ratio (95% confidence interval)= 2.05 (1.16�62). Conclusion: The PNI change would be a convenient parameter to assess the immunonutrition
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ObjectiveTo observe the effect of Feiyanning prescription （FYN） on cisplatin （DDP） resistance in non-small cell lung cancer （NSCLC） and explore the underlying mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the proliferation of A549 and A549/DDP （DDP-resistant） cells treated by DDP （0， 2.0， 4.0， 6.0， 8.0， 10.0 mg⋅L-1） and the proliferation of A549/DDP cells treated by FYN （0， 100， 200， 300， 400， 500， 600 mg⋅L-1）. Based on immunofluorescence staining and Western blot （WB）， the expression of epithelial mesenchymal transition （EMT）-related proteins in A549 and A549/DDP groups was observed. A549/DDP cells were classified into control group， FYN group （200 mg⋅L-1）， DDP group （6.0 mg⋅L-1）， and combination group ［FYN （200 mg⋅L-1） + DDP （6.0 mg⋅L-1）］ and respectively treated with corresponding drugs. Then， invasion ability of each group was examined by transwell assay， and the expression of EMT-related proteins in each group by WB. Moreover， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and immunofluorescence staining were separately applied to detect the mRNA and protein expression of drug resistance-related factors in each group， respectively. ResultCompared with A549 group， A549/DDP group showed high resistance to DDP （P<0.01）， low expression of E-cadherin， and high protein expression of Vimentin， N-cadherin， and Snail （P<0.05， P<0.01）. As compared with the control group， FYN inhibited the proliferation of A549/DDP cells in a concentration-dependent manner （P<0.01）， and the FYN group， DDP group， and combination group demonstrated low invasion ability （P<0.01）. In addition， the invasion ability in the combination group was particularly lower than that in the DDP group （P<0.01）. The expression of E-cadherin protein was higher and the protein expression of N-cadherin， Vimentin， and Snail was lower in the in FYN group than in the control group （P<0.01）. The protein expression of E-cadherin， N-cadherin， and Vimentin was lower and the expression of Snail was higher in the DDP group than in the control group （P<0.05，P<0.01）. The protein expression of E-cadherin， N-cadherin， Vimentin， and Snail in the combination group decreased as compared with that in the control group （P<0.01）. Compared with the DDP alone， the combination raised the expression of E-cadherin and lowered the protein expression of N-cadherin， Vimentin， and Snail （P<0.01）. The protein and mRNA expression of lung resistance-related protein （LRP） and multidrug resistance 1 （MDR1） was lower and the protein and mRNA expression of topoisomerase Ⅱα （TOPO Ⅱα） was higher in the FYN group than in the control group （P<0.01）. The protein and mRNA expression of LRP， MDR1， and TOPO Ⅱα was higher in the DDP group than in the control group （P<0.01）. The expression of LRP protein and mRNA showed no significant variation， but the protein and mRNA expression of MDR1 and TOPO Ⅱα increased in the combination group compared with those in the control group （P<0.01）. Compared with the DDP group， FYN group and combination group showed low protein and mRNA expression of LRP and MDR1 and high protein and mRNA expression of TOPO Ⅱα （P<0.01）. Compared with FYN， the combination elevated the protein and mRNA expression of LRP， MDR1， and TOPO Ⅱα （P<0.01）. ConclusionFYN prescription can reverse the DDP resistance of NSCLC by modulating EMT.
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@#Objective To systematically evaluate the efficacy of neoadjuvant chemoradiotherapy or chemotherapy followed by surgery versus definitive chemoradiation in stage ⅢA-N2 non-small cell lung cancer (NSCLC). Methods We searched PubMed, EMbase, Web of Science and The Cochrane Library to collect clinical studies on the efficacy comparison between neoadjuvant chemoradiotherapy or chemotherapy followed by surgery and definitive chemoradiation in stage ⅢA-N2 NSCLC from inception to September 2022. The meta-analysis was performed by using RevMan 5.3 software. Results A total of 9 studies (3 randomized controlled trials and 6 retrospective cohort studies) with 12 801 patients were included. The results of meta-analysis showed that there was no statistical difference in the progression-free survival rate between the inductive treatment followed by surgery (including lobectomy and pneumonectomy) and definitive chemoradiation (HR=0.99, 95%CI 0.86-1.15, P=0.91). Compared with definitive chemoradiation, the overall survival (OS) rate in the inductive treatment followed by surgery (including lobectomy and pneumonectomy) was lower (HR=1.24, 95%CI 1.09-1.42, P=0.001), while the OS rate in the inductive treatment followed by lobectomy was higher (HR=0.55, 95%CI 0.51-0.61, P<0.000 01). And the local recurrence rate in the inductive treatment followed by surgery was reduced (OR=0.44, 95%CI 0.36-0.55, P<0.000 01). Conclusion Neoadjuvant chemoradiotherapy or chemotherapy followed by lobectomy is superior to definitive chemoradiation in OS and it has a lower local recurrence rate, so lobectomy should be one of the multidisciplinary treatments for selected ⅢA-N2 NSCLC patients.
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@#Objective To systematically evaluate the clinical efficacy and adverse reactions of paclitaxel and carboplatin with or without bevacizumab in the treatment of non-small cell lung cancer (NSCLC). Methods The databases including PubMed, The Cochrane Library, EMbase, CNKI, Wanfang Data, VIP and CBM were searched from inception to October 2022 to collect randomized controlled trials of the clinical efficacy of paclitaxel and carboplatin with or without bevacizumab for the treatment of NSCLC. RevMan 5.4 software was used for meta-analysis. Results Eight randomized controlled trials were enrolled, involving a total of 1 724 patients. Meta-analysis showed that for the treatment of NSCLC, the disease control rate, overall response rate, 1-year survival rate, and 2-year survival rate were higher in the trial group (paclitaxel and carboplatin combined with bevacizumab) than those in the control group (paclitaxel and carboplatin) (P<0.05); however, the incidences of the adverse reactions, such as leukopenia, hemorrhage, proteinuria and hypertension, etc, were higher in the trial group than those in the control group (P<0.05). There were no statistical differences between the trial group and the control group in the incidences of fatigue, thrombocytopenia, neutropenia or hyponatremia, etc (P>0.05). In addition, the median progression-free survival and overall survival were longer in the trial group than those in the control group. Conclusion For the treatment of NSCLC, paclitaxel and carboplatin combined with bevacizumab is superior in terms of disease control, overall response and prolonging patient survival, etc, but will be associated with more adverse reactions.
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@#Objective To compare and analyze the therapeutic effects of robot-assisted lobectomy and segmentectomy for stage ⅠA non-small cell lung cancer with a diameter≤2 cm. Methods A total of 181 patients with pathologically confirmed stage ⅠA non-small cell lung cancer (diameter≤2 cm) who underwent robot-assisted lobectomy and segmentectomy in our hospital from 2018 to 2021 were included. There were 74 males and 107 females with an average age of 57.50±10.60 years. They were divided into two groups according to the surgical procedure: a segmentectomy group (85 patients) and a lobectomy group (96 patients). Results There was no statistically significant difference between the two groups in terms of clinical data such as age, gender, smoking history, basic disease, pathological type, tumour diameter, operative time, postoperative 24 h drainage volume and overall complications (P>0.05). The intraoperative blood loss (33.88±16.26 mL vs. 39.27±19.48 mL, P=0.046), groups of dissected lymph nodes (4.76±1.19 vs. 5.52±1.46, P=0.000), number of dissected lymph nodes (14.81±7.23 vs. 18.06±7.70, P=0.004) and postoperative 72 h drainage volume (561.65±225.31 mL vs. 649.84±324.34 mL, P=0.037) of patients in the segmentectomy were less than those in the lobectomy group. The chest drainage time (5.49±3.92 d vs. 7.60±4.96 d, P=0.002) and postoperative hospital stay time (7.47±4.16 d vs. 9.67±5.50 d, P=0.003) were shorter than those in the lobectomy group. There was no conversion to thoracotomy or perioperative death in the two groups. The postoperative follow-up rate was 100.0% with a longest follow-up time of 48 months. The 3-year recurrence-free survival rates of the segmentectomy group and lobectomy group were 87.7% and 92.4%, respectively (P=0.465). Conclusion The da Vinci robot-assisted lobectomy and segmentectomy are safe and feasible surgical procedures for patients with stage ⅠA non-small cell lung cancer (diameter≤2 cm), with a similar 3-year recurrence-free survival rate. The lobectomy group has more lymph nodes dissected, while the segmentectomy group is superior to the lobectomy group in terms of intraoperative blood loss, postoperative 72 h chest drainage volume, chest drainage time and postoperative hospitalization time.
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In non-small cell lung cancer(NSCLC),the heterogeneity promotes drug resistance,and the restricted expression of programmed death-ligand 1(PD-L1)limits the immunotherapy benefits.Based on the mechanisms related to translation regulation and the association with PD-L1 of methyltransferase-like 3(METTL3),the novel small-molecule inhibitor STM2457 is assumed to be useful for the treat-ment of NSCLC.We evaluated the efficacy of STM2457 in vivo and in vitro and confirmed the effects of its inhibition on disease progression.Next,we explored the effect of STM2457 on METTL3 and revealed its effects on the inhibition of catalytic activity and upregulation of METTL3 protein expression.Importantly,we described the genome-wide characteristics of multiple omics data ac-quired from RNA sequencing,ribosome profiling,and methylated RNA immunoprecipitation sequencing data under STM2457 treatment or METTL3 knockout.We also constructed a model for the regulation of the translation of METTL3 and PD-L1.Finally,we found PD-Ll upregulation by STM2457 in vivo and in vitro.In conclusion,STM2457 is a potential novel suppressor based on its inhibitory effect on tumor progression and may be able to overcome the heterogeneity based on its impact on the translatome.Furthermore,it can improve the immunotherapy outcomes based on PD-L1 upregulation in NSCLC.
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Lung cancer is one of the malignant tumors with the highest morbidity and mortality. Epidermal growth factor receptor is expressed in the majority of non-small cell lung cancer tumor cells, making it possible to give these patients more precise and targeted therapies. The mechanisms of abnormal EGFR regulation are closely related to the efficacy of targeted therapy and the occurrence of drug resistance. Therefore, this review will review the expression mechanism of EGFR in NSCLC and the acquired drug resistance of epidermal growth factor receptor tyrosine kinase inhibitor after treatment of NSCLC.
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OBJECTIVE To investigate the synergistic effect of triptolide （TPL） combined with epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKI） gefitinib on EGFR-mutated non-small cell lung cancer （NSCLC） cells and its potential mechanism. METHODS Human NSCLC cell lines H1975 （EGFR T790M/L858R mutated drug-resistant cell lines） and H1299 （EGFR wild-type non-drug-resistant cell lines） were cultured in vitro. MTT method was used to detect cell activity， and the effect of combined medication was evaluated by the combination index （CI）. The H1975 cells were divided into blank group， low- concentration and high-concentration groups of TPL （5 nmol/L or 15 nmol/L）， gefitinib group （2 μmol/L）， low-concentration and high-concentration groups of TPL+gefitinib （5 nmol/L TPL+2 μmol/L gefitinib， 15 nmol/L TPL+2 μmol/L gefitinib）. Flow cytometry was used to detect the apoptosis of H1975 cells and the distribution of the cell cycle. Molecular docking studies were used to predict the binding ability of TPL to EGFR. The expressions of phosphatidylinositol 3 kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） pathway and autophagy-related proteins [microtubule-associated protein 1 light chain 3α （MAP1LC3A）， MAP1LC3B] in H1975 cells were detected by flow cytometry. RESULTS TPL had a strong inhibitory effect on the proliferation of H1975 and H1299 cells in a time-dependent and dose-dependent manner. Forty-eight hours treatment of 5 or 15 nmol/L TPL combined with gefitinib had a synergistic inhibitory effect on the proliferation of H1975 cells （CI＜1）， while there was no synergistic inhibitory effect on H1299 cells （CI＞1）. Compared with the blank group， the apoptosis rate and the proportion of H1975 cells at G0/G1 phase were increased significantly in administration groups， while the proportions of cells at S phase and G2/M phase （except for several TPL groups） were decreased significantly， and the combination group had better effects （P＜0.05）. Molecular docking studies showed that the hydroxyl radical of TPL could form hydrogen bonds with the Thr854 residue of the product encoded by EGFR T790M/L858R mutation. Compared with the blank group， the expressions of pathway-related proteins were down-regulated significantly in administration groups， while those of autophagy-related proteins were up-regulated significantly， and the combination group had better effects （P＜0.05）. CONCLUSIONS TPL combined with gefitinib can synergically inhibit the proliferation activity of EGFR-mutated NSCLC cells， the mechanism of which may be related to the down-regulation of PI3K/Akt/ mTOR pathway and induction of autophagy.
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Ferroptosis is a novel regulatory cell death characterized by iron dependence and mainly caused by the accumulation of lipid peroxides and reactive oxygen species in the cell. This process plays an important role in the development of many malignancies, and has been extensively studied in lung cancer, especially in antitumor therapy. In recent years, the role of ferroptosis in tumor immunotherapy has been gradually explored. Studies showed that targeting ferroptosis can improve the therapeutic efficacy of antitumor immunotherapy. In addition, immunotherapy and ferroptosis can work synergistically to enhance the effectiveness of antitumor therapy, suggesting a potential relationship between ferroptosis and immunotherapy and the possible reversal of immune drug resistance. This study aims to elucidate the characteristics of ferroptosis, and the role and potential clinical applications of ferroptosis in the antitumor immunotherapy of advanced non-small cell lung cancer. We also explore the role of some nanomaterials that target the onset of tumor ferroptosis in facilitating immunotherapy.
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Objective To investigate the effect of imatinib on the growth of A549 non-small cell lung cancer transplanted tumors and the expression of PDGFB and PDGFRβ proteins in tumor tissues and stroma in nude mice and to explore the underlying tumor suppression mechanism. Methods A transplantation tumor model of A549 non-small cell lung cancer was established in nude mice. The mice were then randomly divided into four groups: control group (0.9%NaCl), low-dose imatinib group (50 mg/(kg·d)), medium-dose imatinib group (100 mg/(kg·d)), and high-dose imatinib group (200 mg/(kg·d)). The effect of different concentrations of imatinib administered by continuous gavage on tumor growth was observed for 28 days. HE staining was performed to observe the pathological changes of tumor tissues. The expression of PDGF/PDGFR pathway-related proteins and the phosphorylation levels of AKT and ERK1/2 proteins in tumor tissues were detected by Western blot analysis. Double immunofluorescence staining was used to detect the expression of PDGFB and PDGFRβ proteins in the tumor stroma. Results Imatinib inhibited the growth of A549 non-small cell lung cancer cells in nude mice, suppressed the expression of PDGFB in tumor tissues, and decreased the phosphorylation levels of PDGFRβ, AKT, and ERK1/2. The expression of PDGFB and PDGFRβ in tumor stromal fibroblasts of the administered group was significantly lower than that of the control group. Conclusion Imatinib exhibits a pronounced inhibitory effect on A549 xenografts of nude mice with non-small cell lung cancer, and its antitumor mechanism may involve the downregulation of PDGFB and PDGFRβ expression in tumor stromal fibroblasts.
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A large proportion of patients with non-small cell lung cancer (NSCLC) are diagnosed with metastatic and incurable advanced lung cancer at the time of discovery, so these patients are given no surgical opportunity and have a low 5-year survival rate. In the era of immunotherapy, many kinds of immune checkpoint inhibitors (ICIs) have been approved as the first/second-line treatment for patients with advanced NSCLC with negative driving genes and have been combined with radiotherapy as an important treatment strategy for patients with advanced NSCLC. The innovative strategy of combining radiotherapy and immunotherapy has shown feasibility as supported by practical evidence in clinical research. A preclinical experiment of observing the immune mechanism at the molecular and cellular levels preliminarily revealed the interaction among tumor, radiation, and immune system. This paper briefly reviews the progress of combined radiotherapy and immunotherapy in the treatment of advanced NSCLC with negative drvier genes.
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OBJECTIVE@#To investigate the role of myosin heavy chain 9 (MYH9) in regulation of cell proliferation, apoptosis, and cisplatin sensitivity of non-small cell lung cancer (NSCLC).@*METHODS@#Six NSCLC cell lines (A549, H1299, H1975, SPCA1, H322, and H460) and a normal bronchial epithelial cell line (16HBE) were examined for MYH9 expression using Western blotting. Immunohistochemical staining was used to detect MYH9 expression in a tissue microarray containing 49 NSCLC and 43 adjacent tissue specimens. MYH9 knockout cell models were established in H1299 and H1975 cells using CRISPR/Cas9 technology, and the changes in cell proliferation cell were assessed using cell counting kit-8 (CCK8) and clone formation assays; Western blotting and flow cytometry were used to detect apoptosis of the cell models, and cisplatin sensitivity of the cells was evaluated using IC50 assay. The growth of tumor xenografts derived from NSCLC with or without MYH9 knockout was observed in nude mice.@*RESULTS@#MYH9 expression was significantly upregulated in NSCLC (P < 0.001), and the patients with high MYH9 expression had a significantly shorter survival time (P=0.023). In cultured NSCLC cells, MYH9 knockout obviously inhibited cell proliferation (P < 0.001), promoted cell apoptosis (P < 0.05), and increased their chemosensitivity of cisplatin. In the tumor-bearing mouse models, the NSCLC cells with MYH9 knockout showed a significantly lower growth rate (P < 0.05). Western blotting showed that MYH9 knockout inactivated the AKT/c- Myc axis (P < 0.05) to inhibit the expression of BCL2- like protein 1 (P < 0.05), promoted the expression of BH3- interacting domain death agonist and the apoptosis regulator BAX (P < 0.05), and activated apoptosis-related proteins caspase-3 and caspase-9 (P < 0.05).@*CONCLUSION@#High expression of MYH9 contributes to NSCLC progression by inhibiting cell apoptosis via activating the AKT/c-Myc axis.
Subject(s)
Animals , Humans , Mice , Apoptosis , Carcinoma, Non-Small-Cell Lung/metabolism , Cell Line, Tumor , Cell Proliferation , Cisplatin/pharmacology , Cytoskeletal Proteins/metabolism , Lung Neoplasms/metabolism , Mice, Nude , Myosin Heavy Chains/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal TransductionABSTRACT
Lung cancer is considered as the leading cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for about 85% of primary lung cancer. Owing to the improved utilization of medical technological level and the popularization of health examinations, the detection rate of early-stage NSCLC is gradually increasing. The main treatment modalities for early-stage NSCLC are surgical resection and adjuvant chemotherapy. Platinum-based chemotherapy is recommended as the standard postoperative adjuvant treatment for patients with completely resected stageⅡ-ⅢA NSCLC. However, adjuvant therapy remains a controversial option in stageⅠB NSCLC. This review focuses on postoperative adjuvant therapy such as adjuvant chemotherapy, targeted therapy, and immunotherapy for completely resected stageⅠB NSCLC. Moreover, the biomarkers and prognostic factors of high-risk patients are discussed.
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Objective To systematically evaluate the effect of sequence of pulmonary artery and vein transection in thoracoscopic lobectomy on the efficacy and safety of patients with non-small cell lung cancer. Methods PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, Wanfang, VIP and CBM databases were searched for the researches on The post-operative efficacy of pulmonary arteriovenous and pulmonary vein resection sequence in thoracoscopic lobectomy for non-small cell lung cancer. The retrieval time is from the database construction to May 2022. Meta-analysis was performed using RevMan 5.4 software. Results Eight articles were included, including 3 randomized controlled studies and 5 cohort studies, with a total of 1810 patients. Meta-analysis results showed that: The operative time (MD=13.34, 95%CI(7.36, 19.32), P < 0.0001) and intraoperative blood loss (MD=45.29, 95%CI(40.24, 50.35), P < 0.0001) in the group with priority pulmonary vein resection were significantly higher than those in the group with priority pulmonary vein resection. The difference was statistically significant. However, the benefits of OS (HR=1.34, 95%CI (1.12, 1.60), P=0.001) and DFS (HR=1.44, 95%CI(1.18, 1.76), P=0.0003) in the group of priority pulmonary vein transection were significantly better than those in the group of priority pulmonary artery transection, with statistically significant differences. Conclusion Priority pulmonary vein transection during thoracoscopic lobectomy effectively improved patients' OS and DFS, resulting in higher survival benefit for patients with non-small cell lung cancer, but intraoperative bleeding and operation time are more than those with priority pulmonary artery transection.
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With the discovery of lung cancer targets and drug development, targeted therapy has improved the clinical prognosis of non-small cell lung cancer (NSCLC) with driver gene mutations. Immune checkpoint inhibitors (ICIs) have shown good efficacy in driver gene-negative NSCLC. Although some patients with driver gene mutations benefited significantly from the corresponding targeted therapy, they did not respond well to immunotherapy. In most clinical trials and daily practice, patients with NSCLC and driver gene mutations such as EGFR and ALK are excluded or only account for a minority of patients. Applying immunotherapy to patients with driver gene mutations, selecting the best treatment regimens among targeted therapy, chemotherapy, and immunotherapy, and formulating the optimal treatment strategy are crucial to improve the prognosis of patients with advanced NSCLC and driver gene mutations. This paper reviews the characteristics of tumor immune microenvironment with different driver gene mutations and the application of immunotherapy for patients with NSCLC and different driver gene mutations.
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Objective To investigate the biological role of LINC01614 in non-small cell lung cancer A549 cells and its drug resistance-related mechanism. Methods The CRISPR/Cas9 technology was used to construct the A549 cell model with knockdown of LINC01614. Transcriptome sequencing was performed on A549 cells knocked down with LINC01614. We validated the transcriptomic differential genes MCAM and ABCC3 at the gene level and MCAM at the protein level, detected the IC50 changes of A549 cells after knockdown of LINC01614 under the effect of different concentrations of cisplatin, and detected the effect of knockdown of LINC01614 on the migration ability of A549 cells. Results Of the 2 713 DEGs after knockdown of LINC01614, a total of 1 626 genes were up-regulated and 1, 087 genes were down-regulated. GO analysis showed that DEGs were associated with intracellular signaling, cell adhesion, and so on. Meanwhile, the KEGG analysis showed that DEGs were associated with the Wnt signaling pathway, TGF-β signaling pathway, and Rap1 signaling pathway. Selection of drug resistance-associated gene ABCC3 from DEGs for validation with MCAM: qRT-PCR results showed that knockdown of LINC01614 significantly down-regulated the expression of MCAM (P<0.05) and upregulated the expression of ABCC3 on A549 cells (P<0.05). After knockdown of LINC01614, the protein expression of MCAM, was significantly decreased in A549 cells (P<0.05); the IC50 of A549 cells to cisplatin was significantly increased (P<0.05); and the scratch healing rate of A549 cells was also significantly decreased (P<0.05). Conclusion LINC01614 may be associated with the proliferation, invasion, and apoptotic pathways of A549 cells. In addition, LINC01614 may exert its migration ability through MCAM and chemoresistance to cisplatin through ABCC3.