BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastas...BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.展开更多
Actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties ...Actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties of NSCLC proteins is a potential alternative for developing treatment strategies. Towards this, 35 downregulated actin cytoskeletal proteins on NSCLC prognosis and treatment were studied by examining their protein-protein interactions, gene ontology enrichment terms, and signaling pathways. Using PubMed, various proteins in NSCLC were identified. The protein-protein interactions and functional associations of these proteins were examined using the STRING database. The focal adhesion signaling pathway was selected from all available KEGG and Wiki pathways because of its role in regulating gene expression, facilitating cell movement and reproduction, and significantly impacting NSCLC. The protein-protein interaction network of the 35 downregulated actin cytoskeleton proteins revealed that ACTG1, ACTR2, ACTR3, ANXA2, ARPC4, FLNA, TLN1, CALD1, MYL6, MYH9, MYH10, TPM1, TPM3, TPM4, PFN1, IQGAP1, MSN, and ZXY exhibited the highest number of interactions. Whereas HSPB1, CTNNA1, KRT17, KRT7, FLNB, SEPT2, and TUBA1B displayed medium interactions, while UTRN, TUBA1B, and DUSP23 had relatively fewer interactions. It was discovered that focal adhesions are critical in connecting membrane receptors with the actin cytoskeleton. In addition, protein kinases, phosphatases, and adapter proteins were identified as key signaling molecules in this process, greatly influencing cell shape, motility, and gene expression. Our analysis shows that the focal adhesion pathway plays a crucial role in NSCLC and is essential for developing effective treatment strategies and improving patient outcomes.展开更多
BACKGROUND Combined small cell lung cancer(C-SCLC) is a special subtype of small cell lung cancer that is relatively rare, aggressive, and prone to early metastasis and has a poor prognosis. Currently, there are limit...BACKGROUND Combined small cell lung cancer(C-SCLC) is a special subtype of small cell lung cancer that is relatively rare, aggressive, and prone to early metastasis and has a poor prognosis. Currently, there are limited studies on C-SCLC, and there is no uniform standard treatment, especially for extensive C-SCLC, which still faces great challenges. In recent years, the development and progress of immunotherapy have provided more possibilities for the treatment of C-SCLC. We used immunotherapy combined with first-line chemotherapy to treat extensive-stage C-SCLC to explore its antitumor activity and safety.CASE SUMMARY We report a case of C-SCLC that presented early with adrenal, rib, and mediastinal lymph node metastases. The patient received carboplatin and etoposide with concurrent initiation of envafolimab. After 6 cycles of chemotherapy, the lung lesion was significantly reduced, and the comprehensive efficacy evaluation showed a partial response. No serious drug-related adverse events occurred during the treatment, and the drug regimen was well tolerated.CONCLUSION Envafolimab combined with carboplatin and etoposide in the treatment of extensive-stage C-SCLC has preliminary antitumor activity and good safety and tolerability.展开更多
Small cell lung cancer is an invasive neuroendocrine carcinoma with early metastasis potential. It tends to grow rapidly and metastasize early, with the majority of patients diagnosed as advanced stage small cell lung...Small cell lung cancer is an invasive neuroendocrine carcinoma with early metastasis potential. It tends to grow rapidly and metastasize early, with the majority of patients diagnosed as advanced stage small cell lung cancer (ES-SCLC). Systemic treatment consisting of platinum drugs and etoposide chemotherapy is the main treatment method, although the objective effective rate of this combination is 60% - 80%. However, most SCLC patients experience disease progression shortly after initial treatment, with a median overall survival of 10 months. There are few second-line treatment drugs available, and immunotherapy using checkpoint inhibitors has completely changed the treatment of many cancer types. Adding immune checkpoint inhibitors (ICI) to conventional chemotherapy as first-line treatment can improve the survival rate of widespread small cell lung cancer (ES-SCLC), but so far, there are no definitive factors to determine patients who are more likely to benefit from immunotherapy. This review summarizes the results of immunotherapy trials for small cell lung cancer. And a review was conducted on the predictive factors of these trials, with special emphasis on the expression of PD-L1 in small cell lung cancer to determine its clinical value.展开更多
Small Cell Lung Cancer (SCLC) is a low-differentiated neuroendocrine tumor with rapid growth, early metastasis and sensitivity to radiotherapy and chemotherapy. It is highly recurrence rate. And there is lacking effec...Small Cell Lung Cancer (SCLC) is a low-differentiated neuroendocrine tumor with rapid growth, early metastasis and sensitivity to radiotherapy and chemotherapy. It is highly recurrence rate. And there is lacking effective treatment now. As an active research direction at present, anti-angiogenic drugs are not only widely used in non-small cell lung cancer and other tumors, but also have certain effects in small cell lung cancer combined with chemotherapy. As one of the effective treatment methods for small cell lung cancer, related research is not rare, but there is still inadequacy, such as side effects can not be tolerated, and the timing of treatment can not be accurately assessed. This article will briefly describe the research progress of anti-angiogenic drugs combined with chemotherapy in the first-line treatment of extensive small cell lung cancer.展开更多
Thoracic radiotherapy(TRT)is one of the main treatments in limited-stage small cell lung cancer(LS-SCLC).Hyperfractionated TRT(45 Gy,1.5 Gy twice daily)has been the standard of care(SOC)since Turrisi and colleagues pu...Thoracic radiotherapy(TRT)is one of the main treatments in limited-stage small cell lung cancer(LS-SCLC).Hyperfractionated TRT(45 Gy,1.5 Gy twice daily)has been the standard of care(SOC)since Turrisi and colleagues published the results of their clinical trial in 1999.Two meta-analyses have demonstrated the benefits of concurrent chemotherapy and TRT in terms of intrathoracic disease control at 2 years and 3-year overall survival(OS).The phase 2 trial by Grønberg et al(2016)comparing once-daily hypofractionated TRT to twice-daily hyperfractionated TRT in LS-SCLC found similar outcomes in both groups in terms of response rate,progression-free survival(PFS),grade 3-4 adverse effects,and OS.The CONVERT trial,published in 2017,failed to demonstrate the superiority of the conventional scheme(once-daily TRT)vs twice-daily radiotherapy,despite the application of modern radiotherapy techniques and a quality assurance programme,thus confirming the twice-daily hyperfractionated regimen as the SOC.At the 2020 American Society of Clinical Oncology(ASCO)annual meeting,Grønberg et al reported preliminary findings from a phase 2 trial comparing two different TRT dose regimens(45 Gy vs 60 Gy),both administered twice daily.Those data demonstrated a marked improvement in 2-year survival rates in the high dose arm(70.2%vs 46.1%,P=0.002),despite similar objective response rates and PFS outcomes.Those findings provide a new treatment alternative to consider:Hyperfractionated,high-dose TRT.However,the results of that trial will need to be validated in a large,randomized phase 3 study.The results of the phase 2 CALCG 30610 trial will help to clarify the optimal dose and regimen.The potential role of upfront immunotherapy,which early data suggest may improve OS,also needs to be determined.展开更多
Lung cancer is a global health concern as the leading cause of cancer related mortality worldwide.Small cell lung cancer(SCLC)poses a formidable challenge to the treating physicians with the worst prognosis among all ...Lung cancer is a global health concern as the leading cause of cancer related mortality worldwide.Small cell lung cancer(SCLC)poses a formidable challenge to the treating physicians with the worst prognosis among all lung cancers.However,limited stage SCLC(LS-SCLC)has a relatively better outcome with multimodality management.Efforts have been focused on optimal integration of treatment modalities to achieve an improved therapeutic ratio for patients with LS-SCLC.While chemotherapy and thoracic radiation therapy(TRT)are primary components of initial management for LS-SCLC,there is no consensus on optimal timing of TRT.Within this context,we herein provide a concise overview of current evidence and future prospects regarding the optimal timing of thoracic irradiation for LS-SCLC in light of the literature.展开更多
To better understand the outcomes of small cell lung cancer(SCLC),we examined the clinical features and prognostic factors of SCLC in this study.A total of 148 patients who were diagnosed as having SCLC between Januar...To better understand the outcomes of small cell lung cancer(SCLC),we examined the clinical features and prognostic factors of SCLC in this study.A total of 148 patients who were diagnosed as having SCLC between January 2009 and December 2013 in Cancer Center of Union Hospital,Wuhan,China,were enrolled and their clinical features and prognostic factors were retrospectively analyzed.Log-rank test and Cox regression model were employed for analysis of prognostic factors.The 1-and 2-year overall survival(OS) rates were 59.7% and 25.7%,respectively,for limited disease(LD) patients whose median survival time(MST) was 16 months.The 1-and 2-year OS rates were 29.5% and 5.3%,respectively,for extensive disease(ED) patients whose MST was 10 months.The univariate analysis and multivariate analysis revealed that age,tumor stage,serum CEA and Ki-67 antigen were significantly correlated to the outcomes of SCLC,and they were significant prognostic factors for SCLC.展开更多
With the development of molecular pathology, many types of epidermal growth factor receptor(EGFR) mutations have been identified. The efficacy of EGFR tyrosine kinase inhibitors(EGFR-TKIs) in non-small cell lung cance...With the development of molecular pathology, many types of epidermal growth factor receptor(EGFR) mutations have been identified. The efficacy of EGFR tyrosine kinase inhibitors(EGFR-TKIs) in non-small cell lung cancer(NSCLC) patients with different types of EGFR mutations, especially in patients with single rare mutations or complex mutations(co-occurrence of two or more different mutations), has not been fully understood. This study aimed to examine the efficacy of EGFR-TKIs in NSCLC patients with different types of EGFR mutations. Clinical data of 809 NSCLC patients who harbored different types of EGFR mutations and treated from January 2012 to October 2016 at Renmin Hospital and Zhongnan Hospital, Wuhan, were retrospectively reviewed. The clinical characteristics of these patients and the efficacy of EGFR-TKIs were analyzed. Among these patients, 377 patients had only the EGFR del-19 mutation, 362 patients the EGFR L858R mutation in exon 21, 33 patients single rare mutations and 37 patients complex mutations. Among these 809 patients, 239 patients were treated with EGFR-TKIs. In all the 239 patients, the disease control rate(DCR) was 93.7% with two patients(0.2%) achieving complete response(CR), the median progression free survival(PFS) was 13.0 months(95% confidence interval [CI], 11.6–14.4 months), and the median overall survival(OS) was 55.0 months(95% CI, 26.3–83.7 months). Subgroup analysis revealed that the DCR in patients harboring single rare or complex mutations of EGFR was significantly lower than in those with del-19 or L858 R mutation(P<0.001). Patients with classic mutations(del-19 and/or L858 R mutations) demonstrated longer PFS(P<0.001) and OS(P=0.017) than those with uncommon mutations(single rare and/or complex mutations). Furthermore, the patients with single rare mutations had shorter median OS than in those with other mutations. Multivariate Cox regression analysis identified that the type of EGFR mutations was an independent risk factor for PFS(hazard ratio [HR]=0.308, 95% CI, 0.191–0.494, P<0.001) and OS(HR=0.221, 95% CI, 0.101–0.480, P<0.001). The results suggest that the single rare or complex EGFR mutations confer inferior efficacy of EGFR-TKIs treatment to the classic mutations. The prognosis of the single rare EGFR mutations is depressing. EGFR-TKIs may be not a good choice for NSCLC patients with single rare mutations of EGFR. Further studies in these patients with uncommon mutations(especially for the patients with single rare mutations) are needed to determine a better precision treatment.展开更多
Gefitinib is used as a first-line treatment for advanced non-small cell lung cancer(NSCLC).Unfortunately,most NSCLC patients inevitably develop gefitinib resistance during treatment.In addition to EGFR mutation status...Gefitinib is used as a first-line treatment for advanced non-small cell lung cancer(NSCLC).Unfortunately,most NSCLC patients inevitably develop gefitinib resistance during treatment.In addition to EGFR mutation status,the mechanisms involved are largely unknown.In this study,we showed that mi R-124,a tumor suppressor,was significantly down-regulated in gefitinib-resistant NSCLC patients and cell lines compared with gefitinib-sensitive patients and cell lines.In addition,the mi R-124 depletion induced gefitinib resistance,and mi R-124 overexpression sensitized gefitinib-resistant cells to gefitinib.Mechanistic analysis revealed that mi R-124 decreased SNAI2 and STAT3 expression by directly targeting their 3'UTRs and that knocking down SNAI2 or STAT3 partly reversed the gefitinib resistance induced by mi R-124 depletion.Our data demonstrate that the mi R-124 plays a new critical role in acquired resistance to gefitinib and that the manipulation of mi R-124 might provide a therapeutic strategy for reversing acquired gefitinib resistance.展开更多
Objective: Adjuvant chemotherapy(AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer(NSCLC); however, few studies have reported the correlation between the time to...Objective: Adjuvant chemotherapy(AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer(NSCLC); however, few studies have reported the correlation between the time to initiation of AC(TTAC) and survival in NSCLC patients.Methods: The clinical data of 925 NSCLC patients who received curative resection and post-operative AC at the Cancer Hospital of Chinese Academy of Medical Sciences between 2003 and 2013 were retrospectively analyzed.TTAC was measured from the date of surgery to the initiation of AC. Disease-free survival(DFS) was defined as the duration from surgery to the time of tumor recurrence or last follow-up evaluation. The optimal cut-off value of TTAC was determined by maximally selected log-rank statistics. The DFS curve was estimated using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to identify risk factors independently associated with DFS. Propensity score matching(PSM) was performed for survival analysis using the match data.Results: The optimal discriminating cut-off value of TTAC was set at d 35 after curative resection based on which the patients were assigned into two groups: group A(≤35 d) and group B(>35 d). There was no significant difference in the DFS between the two groups(P=0.246), indicating that the TTAC is not an independent prognostic factor for DFS. A further comparison continued to show no significant difference in the DFS among 258 PSM pairs(P=0.283).Conclusions: There was no significant correlation between the TTAC and DFS in NSCLC patients. Studies with larger samples are needed to further verify this conclusion.展开更多
Objective: To identify clinical and pathologic factors that were associated with the survival of stage IB upper lobe non-small cell lung cancer (NSCLC) patients. Methods: A retrospective study of 147 subjects who had ...Objective: To identify clinical and pathologic factors that were associated with the survival of stage IB upper lobe non-small cell lung cancer (NSCLC) patients. Methods: A retrospective study of 147 subjects who had undergone curative resection for stage IB upper lobe NSCLC was performed. Patients who had received any adjuvant or neo-adjuvant chemotherapy were excluded. Survival function curves were estimated using the Kaplan-Meier procedure. Crude and adjusted hazard ratios (HRs) of potential prognostic factors were estimated using Cox proportional hazards models. Results: Five factors, including age, tumor size, histologic grade of differentiation, number of removed superior mediastinal lymph node stations and presence of visceral pleura invasion, were significantly and independently associated with mortality risk. Adjusted HRs were 2.6 [95% confidence interval (95% CI): 1.1?6.5] and 4.6 (95% CI: 1.9?11) for those aged 58?68 years and those >68 years, respectively, relative to those aged <58 years. HRs for those with poorly and moderately differentiated tumors were 6.4 (95% CI: 2.3?18) and 1.4 (95% CI: 0.7?2.8), respectively. HRs for those with tumor size 3.1?5 cm and >5 cm (vs ?3.0 cm) were 2.3 (95% CI: 1.1?4.9) and 4.3 (95% CI: 1.9?10), respectively. The presence of visceral pleura invasion also increased the risk of mortality (HR=4.0, 95% CI: 1.3?12). Conclusion: Advanced age, larger tumor size, poorly differentiated histology, smaller number of removed superior mediastinal lymph node stations, and presence of visceral pleura invasion were associated with poor survival of surgically treated stage IB upper lobe NSCLC patients.展开更多
Objective:Metastasis is one of the key causes of high mortality in lung cancer.Aberrant DNA methylation is a common event in metastatic lung cancer.We aimed to identify new epigenetic regulation of metastasis-associat...Objective:Metastasis is one of the key causes of high mortality in lung cancer.Aberrant DNA methylation is a common event in metastatic lung cancer.We aimed to identify new epigenetic regulation of metastasis-associated genes and characterize their effects on lung cancer progression.Methods:We screened genes associated with non-small cell lung cancer(NSCLC)metastasis by integrating datasets from the Gene Expression Omnibus(GEO)database.We obtained epigenetic-regulated candidate genes by analyzing the expression profile of demethylation genes.By overlapping analysis,epigenetically modulated metastasis-associated genes were obtained.Kaplan-Meier plotter(KM plotter)was utilized to assess the overall survival(OS)of stomatin in lung cancer.Immunohistochemistry(IHC)was conducted to determine the association between stomatin and metastasis-associated clinical indicators.Both in vitro and in vivo assays were performed to investigate the potential role of stomatin in metastasis.The regulation mechanisms of transforming growth factorβ1(TGFβ1)on stomatin were determined by Sequenom MassARRAY quantitative methylation and western blot assays.Results:A series of bioinformatic analyses revealed stomatin as the metastasis-associated gene regulated by DNA methylation.The KM plotter analysis showed a positive association between stomatin and the OS of lung cancer.IHC analysis indicated that the decreased stomatin expression is linked with advanced TNM stage.Loss-and gainof-function experiments displayed that stomatin could inhibit the migration and invasion of NSCLC cells.Furthermore,TGFβ1 repressed stomatin expression during epithelial-to-mesenchymal transition(EMT).The negative correlation between stomatin and TGFβ1 was also validated in advanced stage III lung tumor samples.The underlying mechanism by which TGFβ1 inhibits stomatin is due in part to DNA methylation.Conclusions:Our results suggest that stomatin may be a target for epigenetic regulation and can be used to prevent metastatic diseases.展开更多
In recent years, the incidence of lung adenocarcinoma has been increasing, </span><span style="font-family:Verdana;">and now it has become the largest type of non-small cell lung cancer (NSCLC)&l...In recent years, the incidence of lung adenocarcinoma has been increasing, </span><span style="font-family:Verdana;">and now it has become the largest type of non-small cell lung cancer (NSCLC)</span><span style="font-family:Verdana;">. Currently, treatment of advanced NSCLC consists of several modalities: systemic chemotherapy, local radiation therapy, and targeted therapy (including most recently immunotherapy). In the past decade, the discovery of new mo</span><span style="font-family:Verdana;">lecular subtypes, the search for tumor driver gene mutations, the developmen</span><span style="font-family:Verdana;">t </span><span style="font-family:Verdana;">of targeted molecular targeted drugs, or targeted therapy to suppress tumor angioge</span><span style="font-family:Verdana;">nesis and regulate tumor immune response have been the main directio</span><span style="font-family:Verdana;">ns of NSCLC research and clinical diagnosis and treatment. At present, platinum-based chemotherapy is widely used in NSCLC patients clini</span><span style="font-family:Verdana;">cally. Platinum-based chemotherapy drugs can effectively prolong the survival time of patients and improve their quality of life, but the incidence of adverse reactions is still high. Therefore, it is necessary to find a drug that can improve the efficacy of patients and reduce the adverse reactions of platinum chemotherapy drugs to NSCLC patients.展开更多
OBJECTIVE Identification of novel autophagy inhibitors for the combinational treatment of non-small cell lung cancer(NSCLC).METHODS MTT assay and annexin V/PI staining assay were used to evaluate the cell proliferatio...OBJECTIVE Identification of novel autophagy inhibitors for the combinational treatment of non-small cell lung cancer(NSCLC).METHODS MTT assay and annexin V/PI staining assay were used to evaluate the cell proliferation and apoptosis,respectively.Immunofluorescence staining and cathepsin activity assay were used to detect autophagy.Small interfering RNA was performed to silence the genes and Western blot assay was used to evaluate the protein express levels.Xenograft experiments were applied for in vivo evaluation.RESULTS Cepharanthine,a natural compound,increased LC3-II expression and GFP-LC3 puncta formation in NSCLC NCI-H1975 cells.Numerous yellow puncta were observed in cepharanthine-treated cells with m RFP-EGFP-LC3 transfection.Co-staining of GFP-LC3 with LysoT racker red or LAMP1 antibody suggested that cepharanthine inhibits autophagosomes-lysosomes fusion.Moreover,cepharanthine attenuated the lysosomal cathepsins maturation.We also confirmed that dacomitinib induced cytoprotective autophagy.Combined treatment with cepharanthine increased the anti-cancer effects of dacomitinib in vitro and in vivo.Besides,cepharanthine could not enhance the anti-cancer effect of dacomitinib in autophagy deficient cells.CONCLUSION Cepharanthine might be further developed as a promising autophagic inhibitor,and combined treatment cepharanthine with dacomitinib could pose as an effective strategy for NSCLC treatment.展开更多
Background: We have developed a new next-generation intrapleural hyperthermic chemotherapy (IPHC) for non-small cell lung cancer with dissemination, which is a hybrid chemotherapy combined with oral S-1 medication plu...Background: We have developed a new next-generation intrapleural hyperthermic chemotherapy (IPHC) for non-small cell lung cancer with dissemination, which is a hybrid chemotherapy combined with oral S-1 medication plus conventional cisplatin-based IPHC. We now report the preliminary feasibility and outcome of quality of life (QOL) regarding this hybrid IPHC. Methods: The patient was a 76-year-old male with a 2-cm nodule in the left upper lobe. After partial resection by video-assisted thoracic surgery (VATS), which was diagnosed with advanced pulmonary adenocarcinoma with intrapleural dissemination. We initially performed two regimens of systemic chemotherapy, S-1 (day 1 - 21, 100 mg 2X/day) + CDDP (day 8, 60 mg/m<sup>2</sup>) and S-1 (day 1 - 14,100 mg 2X/day) + CBDCA (day 1, AUC 5). The regimen of next-generation IPHC is oral S-1 medication (day 1 - 21, 100 mg/day) + intrapleural hyperthermic perfusion of cisplatin (200 mg/m<sup>2</sup>) with VATS (day 8,43°C, 2 hours). Adverse outcomes, QOL, and pleural effusion were assessed in three regimens. To investigate the outcomes of the QOL, the European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30 and QLQ-LC13), the QOL questionnaire for cancer patients treated with anticancer drugs (QOL-ACD), the Cancer Dyspnea Score (CDS), and the St. George’s Respiratory Questionnaire (SGRQ) were used. Results: During the IPHC treatment course, grade 3 neutropenia, anemia, and diarrhea were observed. The physical function after IPHC became worse compared to that before the IPHC. Fatigue during chemotherapy (CBDCA+S-1) was more pronounced than that during the IPHC. Nausea, vomiting, and diarrhea during the IPHC were prevalent than those of chemotherapy. The overall QOL after the IPHC was improved compared to that before the IPHC. Regarding before and after the IPHC, the physical function after the IPHC became worse compared to that before the IPHC, on the other hand, the global QOL before and after the IPHC had not dramatically changed. Pleural effusion was controlled after the IPHC for more than 1 year. Conclusion: The first case of a clinical trial of the next-generation IPHC showed grade 3 adverse events. However, it was an acceptable feasibility compared to the usual platinum doublet chemotherapy. The effectiveness of the IPHC allowed the patient to obtain a good control of the pleural effusion and preserved the patient’s QOL.展开更多
Obojective Non-small-cell lung cancer(NSCLC)is a common malignancy.pN2 NSCLC,with pathologically confirmed ipsilateral mediastinal/subcarinal nodes metastasis,has been known as a very heterogeneous subgroup in terms o...Obojective Non-small-cell lung cancer(NSCLC)is a common malignancy.pN2 NSCLC,with pathologically confirmed ipsilateral mediastinal/subcarinal nodes metastasis,has been known as a very heterogeneous subgroup in terms of its anatomical,biological and patient characteristics.Prognostic factors based on patient characteristics were not well determined yet in this subgroup,and there is currently no standard treatment recommendation for these heterogeneous pN2 subjects.Apparent disagreements and inconsistency exist in study reports concerning the prognostic significance of certain factors in pN2 NSCLC,especially regarding to the issue about whether skip N2 metastasis benefit from surgery.Methods We therefore performed this comprehensive summary of the published literatures to draw a more precise and less uncertain conclusion.After a comprehensive literature search,a total of 73 studies involving 23,773 subjects were included according to eligibility criteria.Results As expected,most of the investigated factors,such as old age,male,advanced pathological T stage,advanced clinical N stage,multiple N2 stations,extended surgical resection(pneumonectomy),and incomplete resection,but not post-operation treatment(eg.chemotherapy and radiotherapy)were significantly associated with poor survival.However,skip N2 metastasis was favourable prognostic factors in operable pN2 NSCLC subjects.Other factors(histological type and primary tumour side)were neutral in terms of association with overall survival.We highlighted a number of important prognostic factors for pN2 NSCLC patients.Particularly,patients with skip N2 disease benefit from surgery.Conclusion Our findings could be used as reference information for decision-making in clinical practice and future study design.展开更多
<strong>Objective:</strong> To analyze various immune cytokines (NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-a, IFN-r) and peripheral blood of patients with non-small cell lung cancer (NSCLC) at different ti...<strong>Objective:</strong> To analyze various immune cytokines (NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-a, IFN-r) and peripheral blood of patients with non-small cell lung cancer (NSCLC) at different times after chemotherapy. Changes in CD4+, CD8+, Th17 and IgG, IgM, and IgA levels. <strong>Methods:</strong> A total of 118 NSCLC patients who attended the Oncology Department of the Affiliated Hospital of Chengde Medical College from September 2018 to September 2021 were selected as the research objects, and the patients were analyzed at different time points (before chemotherapy, after the first chemotherapy, and after the second chemotherapy). The effects of NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-A, IFN-r, CD4+, CD8+ Th17, IgG, IgM and IgA levels in peripheral blood at different time points (before chemotherapy, after the first chemotherapy and after the second chemotherapy) were analyzed. The changes of NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-A, IFN-r and the levels of CD4+, CD8+ Th17, IgG, IgM and IgA in peripheral blood were compared at each time point. <strong>Results:</strong> NKG2D, IL-12, IL-15, IL-18, TNF-a, IFN-r gradually decreased before chemotherapy, one week after chemotherapy, and two weeks after chemotherapy, the difference was statistically significant, but DC cells were not significant Variety. CD4+ and CD8+ both increased significantly, and the levels of Th17, IgG, IgM, and IgA gradually decreased. <strong>Conclusion:</strong> In the course of chemotherapy, all immune factors except DC cells were significantly decreased compared with those before chemotherapy, and the decrease of immune factors except DC cells was positively correlated with the length of chemotherapy cycle. If additional immunotherapy is needed, it should be carried out in the early stage of chemotherapy.展开更多
Small cell lung cancer(SCLC)is a high-grade neuroendocrine(NE)cancer characterized by high circulating tumor-cell burden and early extensive metastasis.Considering the complexity of SCLC genes and the immune microenvi...Small cell lung cancer(SCLC)is a high-grade neuroendocrine(NE)cancer characterized by high circulating tumor-cell burden and early extensive metastasis.Considering the complexity of SCLC genes and the immune microenvironment,their unique molecular heterogeneity profiles have been continuously explored.The understanding of SCLC subtypes has recently changed from traditional"classical"and"variant"types to"NE"and"non-NE"phenotypes and to the subtypes defined by major transcriptional regulators,which indicates the gradual revelation of high intratumoral heterogeneity and plasticity characteristics of SCLCs.Advances in genomics as well as the development of single-cell sequencing analysis and new preclinical models have helped investigators gain many new insights into SCLCs and the development of targeted therapy and immunotherapy strategies.This article provides an overview of changes in molecular typing,tumor heterogeneity,and plasticity and that of advances in the precise treatment of different subtypes of SCLC.展开更多
The treatment of small cell lung cancer(SCLC)is a challenge for all specialists involved.New treatments have been added to the therapeutic armamentarium in recent months,but efforts must continue to improve both survi...The treatment of small cell lung cancer(SCLC)is a challenge for all specialists involved.New treatments have been added to the therapeutic armamentarium in recent months,but efforts must continue to improve both survival and quality of life.Advances in surgery and radiotherapy have resulted in prolonged survival times and fewer complications,while more careful patient selection has led to increased staging accuracy.Developments in the field of systemic therapy have resulted in changes to clinical guidelines and the management of patients with advanced disease,mainly with the introduction of immunotherapy.In this article,we describe recent improvements in the management of patients with SCLC,review current treatments,and discuss future lines of research.展开更多
基金Yu-Qing Xia Famous Old Chinese Medicine Heritage Workshop of“3+3”Project of Traditional Chinese Medicine Heritage in Beijing,Jing Zhong Yi Ke Zi(2021),No.73National Natural Science Foundation of China,No.81973640+1 种基金Nursery Program of Wangjing Hospital,Chinese Academy of Traditional Chinese Medicine,No.WJYY-YJKT-2022-05China Academy of Traditional Chinese Medicine Wangjing Hospital High-Level Chinese Medicine Hospital Construction Project Chinese Medicine Clinical Evidence-Based Research:The Evidence-Based Research of Electrothermal Acupuncture for Relieving Cancer-Related Fatigue in Patients With Malignant Tumor,No.WYYY-XZKT-2023-20.
文摘BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.
文摘Actin, a highly conserved protein, plays a dominant role in Non-small cell lung cancer (NSCLC). Late diagnosis and the aggressive nature of NSCLC pose a significant threat. Studying the clinic pathological properties of NSCLC proteins is a potential alternative for developing treatment strategies. Towards this, 35 downregulated actin cytoskeletal proteins on NSCLC prognosis and treatment were studied by examining their protein-protein interactions, gene ontology enrichment terms, and signaling pathways. Using PubMed, various proteins in NSCLC were identified. The protein-protein interactions and functional associations of these proteins were examined using the STRING database. The focal adhesion signaling pathway was selected from all available KEGG and Wiki pathways because of its role in regulating gene expression, facilitating cell movement and reproduction, and significantly impacting NSCLC. The protein-protein interaction network of the 35 downregulated actin cytoskeleton proteins revealed that ACTG1, ACTR2, ACTR3, ANXA2, ARPC4, FLNA, TLN1, CALD1, MYL6, MYH9, MYH10, TPM1, TPM3, TPM4, PFN1, IQGAP1, MSN, and ZXY exhibited the highest number of interactions. Whereas HSPB1, CTNNA1, KRT17, KRT7, FLNB, SEPT2, and TUBA1B displayed medium interactions, while UTRN, TUBA1B, and DUSP23 had relatively fewer interactions. It was discovered that focal adhesions are critical in connecting membrane receptors with the actin cytoskeleton. In addition, protein kinases, phosphatases, and adapter proteins were identified as key signaling molecules in this process, greatly influencing cell shape, motility, and gene expression. Our analysis shows that the focal adhesion pathway plays a crucial role in NSCLC and is essential for developing effective treatment strategies and improving patient outcomes.
基金Supported by the Foundation of Science and Technology Bureau of Dalian,No. 2021JJ13SN70。
文摘BACKGROUND Combined small cell lung cancer(C-SCLC) is a special subtype of small cell lung cancer that is relatively rare, aggressive, and prone to early metastasis and has a poor prognosis. Currently, there are limited studies on C-SCLC, and there is no uniform standard treatment, especially for extensive C-SCLC, which still faces great challenges. In recent years, the development and progress of immunotherapy have provided more possibilities for the treatment of C-SCLC. We used immunotherapy combined with first-line chemotherapy to treat extensive-stage C-SCLC to explore its antitumor activity and safety.CASE SUMMARY We report a case of C-SCLC that presented early with adrenal, rib, and mediastinal lymph node metastases. The patient received carboplatin and etoposide with concurrent initiation of envafolimab. After 6 cycles of chemotherapy, the lung lesion was significantly reduced, and the comprehensive efficacy evaluation showed a partial response. No serious drug-related adverse events occurred during the treatment, and the drug regimen was well tolerated.CONCLUSION Envafolimab combined with carboplatin and etoposide in the treatment of extensive-stage C-SCLC has preliminary antitumor activity and good safety and tolerability.
文摘Small cell lung cancer is an invasive neuroendocrine carcinoma with early metastasis potential. It tends to grow rapidly and metastasize early, with the majority of patients diagnosed as advanced stage small cell lung cancer (ES-SCLC). Systemic treatment consisting of platinum drugs and etoposide chemotherapy is the main treatment method, although the objective effective rate of this combination is 60% - 80%. However, most SCLC patients experience disease progression shortly after initial treatment, with a median overall survival of 10 months. There are few second-line treatment drugs available, and immunotherapy using checkpoint inhibitors has completely changed the treatment of many cancer types. Adding immune checkpoint inhibitors (ICI) to conventional chemotherapy as first-line treatment can improve the survival rate of widespread small cell lung cancer (ES-SCLC), but so far, there are no definitive factors to determine patients who are more likely to benefit from immunotherapy. This review summarizes the results of immunotherapy trials for small cell lung cancer. And a review was conducted on the predictive factors of these trials, with special emphasis on the expression of PD-L1 in small cell lung cancer to determine its clinical value.
文摘Small Cell Lung Cancer (SCLC) is a low-differentiated neuroendocrine tumor with rapid growth, early metastasis and sensitivity to radiotherapy and chemotherapy. It is highly recurrence rate. And there is lacking effective treatment now. As an active research direction at present, anti-angiogenic drugs are not only widely used in non-small cell lung cancer and other tumors, but also have certain effects in small cell lung cancer combined with chemotherapy. As one of the effective treatment methods for small cell lung cancer, related research is not rare, but there is still inadequacy, such as side effects can not be tolerated, and the timing of treatment can not be accurately assessed. This article will briefly describe the research progress of anti-angiogenic drugs combined with chemotherapy in the first-line treatment of extensive small cell lung cancer.
文摘Thoracic radiotherapy(TRT)is one of the main treatments in limited-stage small cell lung cancer(LS-SCLC).Hyperfractionated TRT(45 Gy,1.5 Gy twice daily)has been the standard of care(SOC)since Turrisi and colleagues published the results of their clinical trial in 1999.Two meta-analyses have demonstrated the benefits of concurrent chemotherapy and TRT in terms of intrathoracic disease control at 2 years and 3-year overall survival(OS).The phase 2 trial by Grønberg et al(2016)comparing once-daily hypofractionated TRT to twice-daily hyperfractionated TRT in LS-SCLC found similar outcomes in both groups in terms of response rate,progression-free survival(PFS),grade 3-4 adverse effects,and OS.The CONVERT trial,published in 2017,failed to demonstrate the superiority of the conventional scheme(once-daily TRT)vs twice-daily radiotherapy,despite the application of modern radiotherapy techniques and a quality assurance programme,thus confirming the twice-daily hyperfractionated regimen as the SOC.At the 2020 American Society of Clinical Oncology(ASCO)annual meeting,Grønberg et al reported preliminary findings from a phase 2 trial comparing two different TRT dose regimens(45 Gy vs 60 Gy),both administered twice daily.Those data demonstrated a marked improvement in 2-year survival rates in the high dose arm(70.2%vs 46.1%,P=0.002),despite similar objective response rates and PFS outcomes.Those findings provide a new treatment alternative to consider:Hyperfractionated,high-dose TRT.However,the results of that trial will need to be validated in a large,randomized phase 3 study.The results of the phase 2 CALCG 30610 trial will help to clarify the optimal dose and regimen.The potential role of upfront immunotherapy,which early data suggest may improve OS,also needs to be determined.
文摘Lung cancer is a global health concern as the leading cause of cancer related mortality worldwide.Small cell lung cancer(SCLC)poses a formidable challenge to the treating physicians with the worst prognosis among all lung cancers.However,limited stage SCLC(LS-SCLC)has a relatively better outcome with multimodality management.Efforts have been focused on optimal integration of treatment modalities to achieve an improved therapeutic ratio for patients with LS-SCLC.While chemotherapy and thoracic radiation therapy(TRT)are primary components of initial management for LS-SCLC,there is no consensus on optimal timing of TRT.Within this context,we herein provide a concise overview of current evidence and future prospects regarding the optimal timing of thoracic irradiation for LS-SCLC in light of the literature.
基金supported by the National Natural Science Foundation of China(No.81172595 and No.81573090)
文摘To better understand the outcomes of small cell lung cancer(SCLC),we examined the clinical features and prognostic factors of SCLC in this study.A total of 148 patients who were diagnosed as having SCLC between January 2009 and December 2013 in Cancer Center of Union Hospital,Wuhan,China,were enrolled and their clinical features and prognostic factors were retrospectively analyzed.Log-rank test and Cox regression model were employed for analysis of prognostic factors.The 1-and 2-year overall survival(OS) rates were 59.7% and 25.7%,respectively,for limited disease(LD) patients whose median survival time(MST) was 16 months.The 1-and 2-year OS rates were 29.5% and 5.3%,respectively,for extensive disease(ED) patients whose MST was 10 months.The univariate analysis and multivariate analysis revealed that age,tumor stage,serum CEA and Ki-67 antigen were significantly correlated to the outcomes of SCLC,and they were significant prognostic factors for SCLC.
基金supported by grants from the National Natural Science Foundation of China(No.81372407)Health and Family Planning Scientific Research Project of Hubei Province(No.WJ2017Q007)
文摘With the development of molecular pathology, many types of epidermal growth factor receptor(EGFR) mutations have been identified. The efficacy of EGFR tyrosine kinase inhibitors(EGFR-TKIs) in non-small cell lung cancer(NSCLC) patients with different types of EGFR mutations, especially in patients with single rare mutations or complex mutations(co-occurrence of two or more different mutations), has not been fully understood. This study aimed to examine the efficacy of EGFR-TKIs in NSCLC patients with different types of EGFR mutations. Clinical data of 809 NSCLC patients who harbored different types of EGFR mutations and treated from January 2012 to October 2016 at Renmin Hospital and Zhongnan Hospital, Wuhan, were retrospectively reviewed. The clinical characteristics of these patients and the efficacy of EGFR-TKIs were analyzed. Among these patients, 377 patients had only the EGFR del-19 mutation, 362 patients the EGFR L858R mutation in exon 21, 33 patients single rare mutations and 37 patients complex mutations. Among these 809 patients, 239 patients were treated with EGFR-TKIs. In all the 239 patients, the disease control rate(DCR) was 93.7% with two patients(0.2%) achieving complete response(CR), the median progression free survival(PFS) was 13.0 months(95% confidence interval [CI], 11.6–14.4 months), and the median overall survival(OS) was 55.0 months(95% CI, 26.3–83.7 months). Subgroup analysis revealed that the DCR in patients harboring single rare or complex mutations of EGFR was significantly lower than in those with del-19 or L858 R mutation(P<0.001). Patients with classic mutations(del-19 and/or L858 R mutations) demonstrated longer PFS(P<0.001) and OS(P=0.017) than those with uncommon mutations(single rare and/or complex mutations). Furthermore, the patients with single rare mutations had shorter median OS than in those with other mutations. Multivariate Cox regression analysis identified that the type of EGFR mutations was an independent risk factor for PFS(hazard ratio [HR]=0.308, 95% CI, 0.191–0.494, P<0.001) and OS(HR=0.221, 95% CI, 0.101–0.480, P<0.001). The results suggest that the single rare or complex EGFR mutations confer inferior efficacy of EGFR-TKIs treatment to the classic mutations. The prognosis of the single rare EGFR mutations is depressing. EGFR-TKIs may be not a good choice for NSCLC patients with single rare mutations of EGFR. Further studies in these patients with uncommon mutations(especially for the patients with single rare mutations) are needed to determine a better precision treatment.
基金supported by the grants from National Natural Science Foundation of China(No.81301899 and 81372662)Wu Jie Ping Medical Foundation(No.320.6750.1239)the Special Funds for Major State Basic Research Program of China(973 Program)(No.2009CB521802)
文摘Gefitinib is used as a first-line treatment for advanced non-small cell lung cancer(NSCLC).Unfortunately,most NSCLC patients inevitably develop gefitinib resistance during treatment.In addition to EGFR mutation status,the mechanisms involved are largely unknown.In this study,we showed that mi R-124,a tumor suppressor,was significantly down-regulated in gefitinib-resistant NSCLC patients and cell lines compared with gefitinib-sensitive patients and cell lines.In addition,the mi R-124 depletion induced gefitinib resistance,and mi R-124 overexpression sensitized gefitinib-resistant cells to gefitinib.Mechanistic analysis revealed that mi R-124 decreased SNAI2 and STAT3 expression by directly targeting their 3'UTRs and that knocking down SNAI2 or STAT3 partly reversed the gefitinib resistance induced by mi R-124 depletion.Our data demonstrate that the mi R-124 plays a new critical role in acquired resistance to gefitinib and that the manipulation of mi R-124 might provide a therapeutic strategy for reversing acquired gefitinib resistance.
文摘Objective: Adjuvant chemotherapy(AC) after curative resection is known to improve the survival of patients with non-small cell lung cancer(NSCLC); however, few studies have reported the correlation between the time to initiation of AC(TTAC) and survival in NSCLC patients.Methods: The clinical data of 925 NSCLC patients who received curative resection and post-operative AC at the Cancer Hospital of Chinese Academy of Medical Sciences between 2003 and 2013 were retrospectively analyzed.TTAC was measured from the date of surgery to the initiation of AC. Disease-free survival(DFS) was defined as the duration from surgery to the time of tumor recurrence or last follow-up evaluation. The optimal cut-off value of TTAC was determined by maximally selected log-rank statistics. The DFS curve was estimated using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to identify risk factors independently associated with DFS. Propensity score matching(PSM) was performed for survival analysis using the match data.Results: The optimal discriminating cut-off value of TTAC was set at d 35 after curative resection based on which the patients were assigned into two groups: group A(≤35 d) and group B(>35 d). There was no significant difference in the DFS between the two groups(P=0.246), indicating that the TTAC is not an independent prognostic factor for DFS. A further comparison continued to show no significant difference in the DFS among 258 PSM pairs(P=0.283).Conclusions: There was no significant correlation between the TTAC and DFS in NSCLC patients. Studies with larger samples are needed to further verify this conclusion.
文摘Objective: To identify clinical and pathologic factors that were associated with the survival of stage IB upper lobe non-small cell lung cancer (NSCLC) patients. Methods: A retrospective study of 147 subjects who had undergone curative resection for stage IB upper lobe NSCLC was performed. Patients who had received any adjuvant or neo-adjuvant chemotherapy were excluded. Survival function curves were estimated using the Kaplan-Meier procedure. Crude and adjusted hazard ratios (HRs) of potential prognostic factors were estimated using Cox proportional hazards models. Results: Five factors, including age, tumor size, histologic grade of differentiation, number of removed superior mediastinal lymph node stations and presence of visceral pleura invasion, were significantly and independently associated with mortality risk. Adjusted HRs were 2.6 [95% confidence interval (95% CI): 1.1?6.5] and 4.6 (95% CI: 1.9?11) for those aged 58?68 years and those >68 years, respectively, relative to those aged <58 years. HRs for those with poorly and moderately differentiated tumors were 6.4 (95% CI: 2.3?18) and 1.4 (95% CI: 0.7?2.8), respectively. HRs for those with tumor size 3.1?5 cm and >5 cm (vs ?3.0 cm) were 2.3 (95% CI: 1.1?4.9) and 4.3 (95% CI: 1.9?10), respectively. The presence of visceral pleura invasion also increased the risk of mortality (HR=4.0, 95% CI: 1.3?12). Conclusion: Advanced age, larger tumor size, poorly differentiated histology, smaller number of removed superior mediastinal lymph node stations, and presence of visceral pleura invasion were associated with poor survival of surgically treated stage IB upper lobe NSCLC patients.
基金supported by the National Natural Science Foundation of China (No. 81602576, 81802872)National Key Research and Development Program of China (No. 2016YFA0201503)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS) (No. 2016I2M-1-007, 2018-I2M-1-002)
文摘Objective:Metastasis is one of the key causes of high mortality in lung cancer.Aberrant DNA methylation is a common event in metastatic lung cancer.We aimed to identify new epigenetic regulation of metastasis-associated genes and characterize their effects on lung cancer progression.Methods:We screened genes associated with non-small cell lung cancer(NSCLC)metastasis by integrating datasets from the Gene Expression Omnibus(GEO)database.We obtained epigenetic-regulated candidate genes by analyzing the expression profile of demethylation genes.By overlapping analysis,epigenetically modulated metastasis-associated genes were obtained.Kaplan-Meier plotter(KM plotter)was utilized to assess the overall survival(OS)of stomatin in lung cancer.Immunohistochemistry(IHC)was conducted to determine the association between stomatin and metastasis-associated clinical indicators.Both in vitro and in vivo assays were performed to investigate the potential role of stomatin in metastasis.The regulation mechanisms of transforming growth factorβ1(TGFβ1)on stomatin were determined by Sequenom MassARRAY quantitative methylation and western blot assays.Results:A series of bioinformatic analyses revealed stomatin as the metastasis-associated gene regulated by DNA methylation.The KM plotter analysis showed a positive association between stomatin and the OS of lung cancer.IHC analysis indicated that the decreased stomatin expression is linked with advanced TNM stage.Loss-and gainof-function experiments displayed that stomatin could inhibit the migration and invasion of NSCLC cells.Furthermore,TGFβ1 repressed stomatin expression during epithelial-to-mesenchymal transition(EMT).The negative correlation between stomatin and TGFβ1 was also validated in advanced stage III lung tumor samples.The underlying mechanism by which TGFβ1 inhibits stomatin is due in part to DNA methylation.Conclusions:Our results suggest that stomatin may be a target for epigenetic regulation and can be used to prevent metastatic diseases.
文摘In recent years, the incidence of lung adenocarcinoma has been increasing, </span><span style="font-family:Verdana;">and now it has become the largest type of non-small cell lung cancer (NSCLC)</span><span style="font-family:Verdana;">. Currently, treatment of advanced NSCLC consists of several modalities: systemic chemotherapy, local radiation therapy, and targeted therapy (including most recently immunotherapy). In the past decade, the discovery of new mo</span><span style="font-family:Verdana;">lecular subtypes, the search for tumor driver gene mutations, the developmen</span><span style="font-family:Verdana;">t </span><span style="font-family:Verdana;">of targeted molecular targeted drugs, or targeted therapy to suppress tumor angioge</span><span style="font-family:Verdana;">nesis and regulate tumor immune response have been the main directio</span><span style="font-family:Verdana;">ns of NSCLC research and clinical diagnosis and treatment. At present, platinum-based chemotherapy is widely used in NSCLC patients clini</span><span style="font-family:Verdana;">cally. Platinum-based chemotherapy drugs can effectively prolong the survival time of patients and improve their quality of life, but the incidence of adverse reactions is still high. Therefore, it is necessary to find a drug that can improve the efficacy of patients and reduce the adverse reactions of platinum chemotherapy drugs to NSCLC patients.
基金supported by Science and Technology Development Fund,Macao S.A.R(FDCT)(024/2016/A1)Research Fund of University of Macao(MYRG2015-00091-ICMS-QRCM and MYRG2015-00101-ICMS-QRCM)
文摘OBJECTIVE Identification of novel autophagy inhibitors for the combinational treatment of non-small cell lung cancer(NSCLC).METHODS MTT assay and annexin V/PI staining assay were used to evaluate the cell proliferation and apoptosis,respectively.Immunofluorescence staining and cathepsin activity assay were used to detect autophagy.Small interfering RNA was performed to silence the genes and Western blot assay was used to evaluate the protein express levels.Xenograft experiments were applied for in vivo evaluation.RESULTS Cepharanthine,a natural compound,increased LC3-II expression and GFP-LC3 puncta formation in NSCLC NCI-H1975 cells.Numerous yellow puncta were observed in cepharanthine-treated cells with m RFP-EGFP-LC3 transfection.Co-staining of GFP-LC3 with LysoT racker red or LAMP1 antibody suggested that cepharanthine inhibits autophagosomes-lysosomes fusion.Moreover,cepharanthine attenuated the lysosomal cathepsins maturation.We also confirmed that dacomitinib induced cytoprotective autophagy.Combined treatment with cepharanthine increased the anti-cancer effects of dacomitinib in vitro and in vivo.Besides,cepharanthine could not enhance the anti-cancer effect of dacomitinib in autophagy deficient cells.CONCLUSION Cepharanthine might be further developed as a promising autophagic inhibitor,and combined treatment cepharanthine with dacomitinib could pose as an effective strategy for NSCLC treatment.
文摘Background: We have developed a new next-generation intrapleural hyperthermic chemotherapy (IPHC) for non-small cell lung cancer with dissemination, which is a hybrid chemotherapy combined with oral S-1 medication plus conventional cisplatin-based IPHC. We now report the preliminary feasibility and outcome of quality of life (QOL) regarding this hybrid IPHC. Methods: The patient was a 76-year-old male with a 2-cm nodule in the left upper lobe. After partial resection by video-assisted thoracic surgery (VATS), which was diagnosed with advanced pulmonary adenocarcinoma with intrapleural dissemination. We initially performed two regimens of systemic chemotherapy, S-1 (day 1 - 21, 100 mg 2X/day) + CDDP (day 8, 60 mg/m<sup>2</sup>) and S-1 (day 1 - 14,100 mg 2X/day) + CBDCA (day 1, AUC 5). The regimen of next-generation IPHC is oral S-1 medication (day 1 - 21, 100 mg/day) + intrapleural hyperthermic perfusion of cisplatin (200 mg/m<sup>2</sup>) with VATS (day 8,43°C, 2 hours). Adverse outcomes, QOL, and pleural effusion were assessed in three regimens. To investigate the outcomes of the QOL, the European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30 and QLQ-LC13), the QOL questionnaire for cancer patients treated with anticancer drugs (QOL-ACD), the Cancer Dyspnea Score (CDS), and the St. George’s Respiratory Questionnaire (SGRQ) were used. Results: During the IPHC treatment course, grade 3 neutropenia, anemia, and diarrhea were observed. The physical function after IPHC became worse compared to that before the IPHC. Fatigue during chemotherapy (CBDCA+S-1) was more pronounced than that during the IPHC. Nausea, vomiting, and diarrhea during the IPHC were prevalent than those of chemotherapy. The overall QOL after the IPHC was improved compared to that before the IPHC. Regarding before and after the IPHC, the physical function after the IPHC became worse compared to that before the IPHC, on the other hand, the global QOL before and after the IPHC had not dramatically changed. Pleural effusion was controlled after the IPHC for more than 1 year. Conclusion: The first case of a clinical trial of the next-generation IPHC showed grade 3 adverse events. However, it was an acceptable feasibility compared to the usual platinum doublet chemotherapy. The effectiveness of the IPHC allowed the patient to obtain a good control of the pleural effusion and preserved the patient’s QOL.
基金grants from the National Basic Research Program of China(973 ProgramNo.2012CB720605)the Zhongnan Hospital of Wuhan University Science,Technology and Innovation Seed Fund(No.znpy2016046).
文摘Obojective Non-small-cell lung cancer(NSCLC)is a common malignancy.pN2 NSCLC,with pathologically confirmed ipsilateral mediastinal/subcarinal nodes metastasis,has been known as a very heterogeneous subgroup in terms of its anatomical,biological and patient characteristics.Prognostic factors based on patient characteristics were not well determined yet in this subgroup,and there is currently no standard treatment recommendation for these heterogeneous pN2 subjects.Apparent disagreements and inconsistency exist in study reports concerning the prognostic significance of certain factors in pN2 NSCLC,especially regarding to the issue about whether skip N2 metastasis benefit from surgery.Methods We therefore performed this comprehensive summary of the published literatures to draw a more precise and less uncertain conclusion.After a comprehensive literature search,a total of 73 studies involving 23,773 subjects were included according to eligibility criteria.Results As expected,most of the investigated factors,such as old age,male,advanced pathological T stage,advanced clinical N stage,multiple N2 stations,extended surgical resection(pneumonectomy),and incomplete resection,but not post-operation treatment(eg.chemotherapy and radiotherapy)were significantly associated with poor survival.However,skip N2 metastasis was favourable prognostic factors in operable pN2 NSCLC subjects.Other factors(histological type and primary tumour side)were neutral in terms of association with overall survival.We highlighted a number of important prognostic factors for pN2 NSCLC patients.Particularly,patients with skip N2 disease benefit from surgery.Conclusion Our findings could be used as reference information for decision-making in clinical practice and future study design.
文摘<strong>Objective:</strong> To analyze various immune cytokines (NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-a, IFN-r) and peripheral blood of patients with non-small cell lung cancer (NSCLC) at different times after chemotherapy. Changes in CD4+, CD8+, Th17 and IgG, IgM, and IgA levels. <strong>Methods:</strong> A total of 118 NSCLC patients who attended the Oncology Department of the Affiliated Hospital of Chengde Medical College from September 2018 to September 2021 were selected as the research objects, and the patients were analyzed at different time points (before chemotherapy, after the first chemotherapy, and after the second chemotherapy). The effects of NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-A, IFN-r, CD4+, CD8+ Th17, IgG, IgM and IgA levels in peripheral blood at different time points (before chemotherapy, after the first chemotherapy and after the second chemotherapy) were analyzed. The changes of NKG2D, IL-12, IL-15, IL-18, DC cells, TNF-A, IFN-r and the levels of CD4+, CD8+ Th17, IgG, IgM and IgA in peripheral blood were compared at each time point. <strong>Results:</strong> NKG2D, IL-12, IL-15, IL-18, TNF-a, IFN-r gradually decreased before chemotherapy, one week after chemotherapy, and two weeks after chemotherapy, the difference was statistically significant, but DC cells were not significant Variety. CD4+ and CD8+ both increased significantly, and the levels of Th17, IgG, IgM, and IgA gradually decreased. <strong>Conclusion:</strong> In the course of chemotherapy, all immune factors except DC cells were significantly decreased compared with those before chemotherapy, and the decrease of immune factors except DC cells was positively correlated with the length of chemotherapy cycle. If additional immunotherapy is needed, it should be carried out in the early stage of chemotherapy.
基金supported by grants from Jilin Provincial Key Laboratory of Biological Therapy(No.20170622011JC)Jilin Provincial Science and Technology Department(No.20190303146SF)Jilin Province Finance Department(No.2018SCZWSZX-010)。
文摘Small cell lung cancer(SCLC)is a high-grade neuroendocrine(NE)cancer characterized by high circulating tumor-cell burden and early extensive metastasis.Considering the complexity of SCLC genes and the immune microenvironment,their unique molecular heterogeneity profiles have been continuously explored.The understanding of SCLC subtypes has recently changed from traditional"classical"and"variant"types to"NE"and"non-NE"phenotypes and to the subtypes defined by major transcriptional regulators,which indicates the gradual revelation of high intratumoral heterogeneity and plasticity characteristics of SCLCs.Advances in genomics as well as the development of single-cell sequencing analysis and new preclinical models have helped investigators gain many new insights into SCLCs and the development of targeted therapy and immunotherapy strategies.This article provides an overview of changes in molecular typing,tumor heterogeneity,and plasticity and that of advances in the precise treatment of different subtypes of SCLC.
文摘The treatment of small cell lung cancer(SCLC)is a challenge for all specialists involved.New treatments have been added to the therapeutic armamentarium in recent months,but efforts must continue to improve both survival and quality of life.Advances in surgery and radiotherapy have resulted in prolonged survival times and fewer complications,while more careful patient selection has led to increased staging accuracy.Developments in the field of systemic therapy have resulted in changes to clinical guidelines and the management of patients with advanced disease,mainly with the introduction of immunotherapy.In this article,we describe recent improvements in the management of patients with SCLC,review current treatments,and discuss future lines of research.
