In recent years, series of driver genes, such as EGFR, KRAS/NRAS, BRAF, PIK3CA, ALK and ROS1 and so on, have been found in non-small cell lung cancer (NSCLC) one after another with the development of molecular detecting technology. Targeted drugs bring benefits for these NSCLC patients with driver gene variations. However, some NSCLC did not have any known driver gene variations; we called it pan-negative lung cancer. In this paper, we summarize the concept, clinical pathological characteristics, the epidemiological characteristics, treatment and prognosis of pan-negative NSCLC.
Carcinoma, Non-Small-Cell Lung ; diagnosis ; drug therapy ; genetics ; pathology ; Humans ; Lung Neoplasms ; diagnosis ; drug therapy ; genetics ; pathology ; Mutation ; Prognosis

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrous interstitial lung disease of unknown etiology. IPF is also considered to be among the independent risk factors for lung cancer, increasing the risk of lung cancer by 7% and 20%. The incidence of IPF complicated with lung cancer, especially non-small cell lung cancer (NSCLC), is increasing gradually, but there is no consensus on unified management and treatment. IPF and NSCLC have similar pathological features. Both appear in the surrounding area of the lung. In pathients with IPF complicated with NSCLC, NSCLC often develops from the honeycomb region of IPF, but the mechanism of NSCLC induced by IPF remains unclear. In addition, IPF and NSCLC have similar genetic, molecular and cellular processes and common signal transduction pathways. The universal signal pathways targeting IPF and NSCLC will become potential therapeutic drugs for IPF complicated with NSCLC. This article examines the main molecular mechanisms involved in IPF and NSCLC and the research progress of drugs under development targeting these signal pathways.
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Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Idiopathic Pulmonary Fibrosis/drug therapy* ; Lung Neoplasms/genetics* ; Lung/pathology* ; Signal Transduction

BACKGROUND: Immune checkpoint inhibitors (ICIs) improved survival of partial patients with lung squamous cell carcinoma (LUSC). However, it was still insufficient of data in older patients. This study aimed to investigate the efficacy and toxicity of immunotherapy in patients with LUSC in Chinese population of real world. METHODS: A total of 185 LUSC patients underwent pathological diagnosis were involved from January 2018 to January 2022. Patients were divided into elderly group (age ≥70 years) and younger group (age <70 years). The efficacy of mono-immunotherapy or combined with chemotherapy to chemotherapy in first-line treatment was compared. The expression of programmed cell death ligand 1 (PD-L1) and tumor mutational burden (TMB) were evaluated. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to evaluate the efficacy, and Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 was used to evaluate immune-related adverse. Kaplan-Meier and Log-rank test was performed. Cox regression was used in prognostic analysis. RESULTS: Combined therapy acquired significantly higher overall response rate (ORR) compared with chemotherapy alone in elderly group (P<0.05), and also in younger group, despite the difference was not significant (P>0.05). The median progression-free survival (mPFS) and median overall survival (mOS) in elderly group were similar with younger group (P>0.05). Both combined group and immunology alone demonstrated prolonged mPFS in first-line compared with chemotherapy in elderly group. And combined group demonstrated significantly prolonged mPFS compared with chemotherapy in younger group (P<0.01). There was no difference of mOS between different regimes in two groups. Elderly LUSC patients had higher PD-L1 positive rate (≥1%) and similar TMB compared with younger group. There was no relationship between mPFS and mOS with the expression of PD-L1 and TMB. Immunology combined with chemotherapy demonstrated better mPFS compared to chemotherapy in first-line therapy with TMB-High (P<0.05), and inferior mPFS with TMB-Low despite the difference was not significant (P>0.05). Cox regression model demonstrated that clinical stage was an independent predictor and prognostic factor. The incidence of immune-related adverse was 58.0% (51/88) and grade 3 or above 25.0% (22/88). The most common grade 3 adverse events were rash, immune-associated pneumonia, and fatigue. CONCLUSIONS Immunology combined with chemotherapy increased ORR, mPFS and mOS of Chinese patients with LUSC in first-line therapy compared with chemotherapy. There was no difference of efficacy and adverse effects rate between elderly group and younger group. The adverse effects of immunology in elderly patients with LUSC were controllable.
Aged ; B7-H1 Antigen/analysis* ; Biomarkers, Tumor ; Carcinoma, Non-Small-Cell Lung/pathology* ; Carcinoma, Squamous Cell/drug therapy* ; China ; Humans ; Lung/pathology* ; Lung Neoplasms/pathology*

Non-small cell lung cancer (NSCLC) with oncogenic driver mutations was previously deemed " forbidden territory" for immunotherapy. With the growing understanding of the impact of target drugs on the immune microenvironment and the continuous generation of clinical evidence, immunotherapy is expected to bring new hope for the NSCLC patients with oncogenic driver mutations. An expert panel of medical oncology, respiratory medicine and pathology organized by the Society of Cancer Precision Medicine of Chinese Anti-Cancer Association and Expert Group on Lung Cancer of Chinese Medical Journal conducted an in-depth discussion on current evidence of immune microenvironment and clinical studies and formulated a Chinese expert consensus on immunotherapy for advanced NSCLC with oncogenic driver mutations by combining with clinical experience. This expert consensus aims to provide guidance for Chinese clinicians on immunotherapy in NSCLC with oncogenic driver mutations.
Humans ; Lung Neoplasms/pathology* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Consensus ; Immunotherapy ; Carcinogenesis ; Mutation ; China ; Tumor Microenvironment

Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; surgery ; therapy ; China ; Consensus ; Expert Testimony ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; surgery ; therapy ; Neoplasm Staging ; Thoracic Surgery

Lung cancer is one of the most important malignant tumors in the world. The morbidity and mortality rank the first in all kinds of cancer. Long non-coding RNA (lncRNA) is at least 200 nt long and has no protein coding capacity. It plays an important role in the epigenetic regulation, cell cycle regulation, the regulation of cell differentiation, and many other life activities. The studies indicate that dysregulation of lncRNAs in non-small cell lung cancer (NSCLC) tissue and blood circulation is associated with the occurrence and development of cancer. The lncRNAs play an significant role in proliferation, differentiation, migration and apoptosis of the tumor cells. Explore the potential mechanism between lncRNAs and NSCLC is beneficial for the early diagnosis, target therpy and improve prognosis. Therefore, the study aims to demonstrate the latest studies on the lncRNAs related to occurence, diagnosis, therpy and prognosis of NSCLC. It can help to deeply understanding of lncRNA, and provide new ideas for the prevention of NSCLC.
Carcinogenesis ; genetics ; Carcinoma, Non-Small-Cell Lung ; diagnosis ; drug therapy ; genetics ; pathology ; Humans ; Molecular Targeted Therapy ; RNA, Long Noncoding ; genetics

BACKGROUNDThe prognosis of R1-resection at the bronchial stump in patients with non-small cell lung cancer (NSCLC) remains unclear. This study intends to identify the prognostic factors and to optimize treatments for these patients under update conditions.

METHODSThe data of 124 NSCLC patients who underwent R1-resection at the bronchial stump was reviewed. There were 41 patients in the surgery group (S), 21 in the postoperative radiotherapy (PORT) group (S+R), 30 in the postoperative chemotherapy (POCT) group (S+C), and 32 in the PORT plus POCT group (S+R+C). The constitute proportion in different groups was tested using the χ(2) method, univariate analysis was performed using the Kaplan-Meier and log-rank method, and multivariate analysis was done using the Cox hazard regression with entry factors including age, sex, pathological type and stage, classification of the residual disease, and treatment procedure. The process was performed stepwise backward with a maximum iteration of 20 and an entry possibility of 0.05 as well as an excluded possibility of 0.10 at each step.

RESULTSIn univariate analysis, survival was more favorable for patients with squamous cell carcinoma, early pathological T or N stage, and chemotherapy or radiotherapy. There was no significant difference in the survival for patients with different types of the residual disease, except for the difference between patients with carcinoma in situ and lymphangiosis carcinomatosa (P = 0.030). The survival for patients receiving chemoradiotherapy was superior to that for those undergoing surgery alone (P = 0.016). In multivariate analysis, the pathological type (HR 2.51, 95% CI 1.59 to 3.96, P = 0.000), pathological T (HR 1.29, 95% CI 1.04 to 1.60, P = 0.021) or N stage (HR 2.04, 95% CI 1.40 to 2.98, P = 0.000), and chemotherapy (HR 0.24, 95% CI 0.13 to 0.43, P = 0.000) were independent prognostic factors.

CONCLUSIONPatients with squamous cell carcinoma, early pathological T or N stage, or receiving chemotherapy had a more favorable prognosis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; radiotherapy ; surgery ; Female ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Male ; Middle Aged ; Prognosis

OBJECTIVETo evaluate the efficacy and safety of domestic Gemcitabine in the treatment of patients with stage IIIB approximately IV non-small cell lung cancer (NSCLC).

METHODS124 NSCLC patients were randomized into three groups: Group A: single drug group, 40 cases, gemcitabine 1 000 mg/m(2) + NS 100 ml or 200 ml was infused within 30 approximately 60 minutes on D1, 8 and 15, with 28 days taken as one cycle. Group B: combined treatment group, 36 cases, in addition to the above protocol, cisplatin 30 mg/m(2) was infused within 60 approximately 120 min, on D1, 2 and 3. Group C: combined control group: 39 cases, the protocol applied was the same as group B except domestic gemcitabine being replaced by imported gemzar. The efficacy and side effects of treatment were evaluated after 8 weeks of treatment.

RESULTS115 patients could be evaluated for response rate. PR was observed in 9/40 (22.5%) of group A, 15/36 (41.6%) in group B and 15/39 (38.36%) in group C. There was no significant difference of PR rates between group B and group C (P = 0.552). 117 patients who received the second cycle of treatment were evaluated for toxicity. The incidence of grade III approximately IV nausea, vomiting and loss of appetite was much higher in group B. Hematological toxicity of groups B and C was higher than that of group A. There was no significant difference between groups B and C.

CONCLUSIONThe efficacy and incidence of side effects between domestic gemcitabine and the imported gemzar are similar.

Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Deoxycytidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Female ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Neoplasm Staging

Angiogenesis Inhibitors ; pharmacology ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; blood supply ; pathology ; Humans ; Lung Neoplasms ; blood supply ; pathology ; Neovascularization, Pathologic ; drug therapy ; therapy ; Societies, Medical

BACKGROUNDLumiracoxib is a highly selective cyclooxygenase-2 (COX-2) inhibitor with antiinflammatory, analgesic and antipyretic activities comparable with class specific drugs, but with much improved gastrointestinal safety. No studies have examined lumiracoxib for antitumorigenic activity on human nonsmall cell lung cancer cell lines in vitro or its possible molecular mechanisms.

METHODSThe antiproliferative effect of lumiracoxib alone or combined with docetaxol on A549 and NCI-H460 lines was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Drug-drug interactions were analyzed using the coefficient of drug interaction (CDI) to characterize the interactions as synergism, additivity or antagonism. Morphological changes were observed by acridine orange fluorescent staining. Extent of apoptosis was determined by flow cytometry.

RESULTSLumiracoxib (15 - 240 micromol/L) has an inhibitory effect on the proliferation of A549 and NCI-H460 cell lines in concentration- and time-dependent manners with the IC50 values of 2597 micromol/L and 833 micromol/L, respectively. The synergistic effect was prominent when lumiracoxib (15 - 240 micromol/L) was combined with docetaxol (0.2 - 2 micromol/L) (CDI < 1). Fluorescent staining showed that lumiracoxib could induce apoptosis in A549 and NCI-H460 cells. Lumiracoxib treatment also caused an increase of the sub-G1 fraction in each cell line and resulted in an increase of G0/G1-phase cells and a decrease of S-phase cells.

CONCLUSIONSLumiracoxib had antiproliferative effect on the human nonsmall cell lung cancer cell lines A549 and NCI-H460 and had a significant synergy with docetaxol, which may be related to apoptotic induction and cell cycle arrest.

Apoptosis ; drug effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclooxygenase 2 Inhibitors ; pharmacology ; Diclofenac ; analogs & derivatives ; pharmacology ; Humans ; Lung Neoplasms ; drug therapy ; pathology ; Taxoids ; pharmacology