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As one of the most malignant tumors worldwide, lung cancer, fueled by metastasis, has shown rising mortality rates. However, effective clinical strategies aimed at preventing metastasis are lacking owing to its dynamic multi-step, complicated, and progressive nature. Immunotherapy has shown promise in treating cancer metastasis by reversing the immunosuppressive network of the tumor microenvironment. However, drug resistance inevitably develops due to inadequate delivery of immunostimulants and an uncontrolled immune response. Consequently, adverse effects occur, such as autoimmunity, from the non-specific immune activation and non-specific inflammation in off-target organs. Nanocarriers that improve drug solubility, permeability, stability, bioavailability, as well as sustained, controlled, and targeted delivery can effectively overcome drug resistance and enhance the therapeutic effect while reducing adverse effects. In particular, nanomedicine-based immunotherapy can be utilized to target tumor metastasis, presenting a promising therapeutic strategy for lung cancer. Nanotechnology strategies that boost the immunotherapy effect are classified based on the metastatic cascade related to the tumor immune microenvironment; the breaking away of primary tumors, circulating tumor cell dissemination, and premetastatic niche formation cause distant secondary site colonization. In this review, we focus on the opportunities and challenges of integrating immunotherapy with nanoparticle formulation to establish nanotechnology-based immunotherapy by modulating the tumor microenvironment for preclinical and clinical applications in the management of patients with metastatic lung cancer. We also discuss prospects for the emerging field and the clinical translation potential of these techniques.
الموضوعات
Humans , Lung Neoplasms/therapy , Tumor Microenvironment , Neoplasms/drug therapy , Immunotherapy/methodsالملخص
Lung cancer is the malignant tumor with the highest morbidity and mortality in China. Non-small cell lung cancer (NSCLC) is the main pathological subtype of lung cancer. On April 13, 2023, the National Comprehensive Cancer Network (NCCN) released the third edition of the 2023 NCCN Oncology Clinical Practice Guidelines: Non-small Cell Lung Cancer, which reflects the latest advances in international lung cancer research. This article will interpret the main updated contents of the new edition of the guidelines, and compare it with the third edition of the NCCN guidelines in 2022, so as to provide references about the diagnosis and treatment of NSCLC for clinical medical personnel in China. .
الموضوعات
Humans , Carcinoma, Non-Small-Cell Lung , China , Lung Neoplasms , Thoraxالملخص
Metastasis is the leading cause of cancer-related death. Despite extensive treatment, the prognosis for patients with metastatic cancer remains poor. In addition to conventional surgical resection, radiotherapy, immunotherapy, chemotherapy, and targeted therapy, various nanobiomaterials have attracted attention for their enhanced antitumor performance and low off-target effects. However, nanomedicines exhibit certain limitations in clinical applications, such as rapid clearance from the body, low biological stability, and poor targeting ability. Biomimetic methods utilize the natural biomembrane to mimic or hybridize nanoparticles and circumvent some of these limitations. Considering the involvement of immune cells in the tumor microenvironment of the metastatic cascade, biomimetic methods using immune cell membranes have been proposed with unique tumor-homing ability and high biocompatibility. In this review, we explore the impact of immune cells on various processes of tumor metastasis. Furthermore, we summarize the synthesis and applications of immune cell membrane-based nanocarriers increasing therapeutic efficacy against cancer metastases via immune evasion, prolonged circulation, enhanced tumor accumulation, and immunosuppression of the tumor microenvironment. Moreover, we describe the prospects and existing challenges in clinical translation.
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Surgery is the standard treatment for resectable non-small cell lung cancer (NSCLC). Neoadjuvant and adjuvant therapy have been widely used for preventing recurrence and metastasis. Immune checkpoint inhibitors (ICIs) have brought long-term survival benefits in advanced NSCLC and showed higher downstage rates and pathological remission in the neoadjuvant setting. Predictive biomarkers are of great significance to identify the beneficiaries of neoadjuvant ICIs. At present, the biomarkers are still inconclusive. We summarized the clinical trials of neoadjuvant immune checkpoint inhibitors that have been disclosed so far, and reviewed the progress of the biomarkers associated with those trials. .
الموضوعات
Humans , Biomarkers , Carcinoma, Non-Small-Cell Lung/drug therapy , Immune Checkpoint Inhibitors , Lung Neoplasms/drug therapy , Neoadjuvant Therapyالملخص
ObjectiveTo analyze the relationship between mental health status and coping styles among village poverty alleviation cadres in Leshan City, and to provide references for the improvement of mental health and coping styles of them. MethodsA cluster random sampling method was used to select 6 of the 11 districts and counties in Leshan City, and all the village poverty alleviation cadres in the selected areas were evaluated through the psychological cloud CT system. A total of 700 cadres participated in the questionnaire evaluation, and were assessed using Symptom Checklist 90 (SCL-90) and Coping Style Questionnaire (CSQ). Results①A total of 207 (35.9%) village poverty alleviation cadres factor scored above 2, and 92 (15.9%) cadres scored above 200. ②There was a statistically significant difference in SCL-90 obsessive-compulsive symptom factor score and other factor score between different poverty alleviation time groups (P<0.05 or 0.01), and the factor score of SCL-90 obsessive-compulsive symptom showed significant difference among village poverty-alleviation cadres of different genders (P<0.05). ③The scores of problem-solving factor in CSQ showed significant differences among village poverty alleviation cadres of different genders and different ages (P<0.01). ④Correlation analysis showed that the scores of each dimension and total score of SCL-90 of village poverty alleviation cadres in Leshan City were positively correlated with the score of self-blame factor in CSQ (r=0.423~0.521, P<0.01). ConclusionThe village poverty alleviation cadres of female and with a working length of less than 90 days or more than 360 days are at high risk of obsessive-compulsive symptoms, while the cadres of male and aged over 41 years adopt mature coping styles. Furthermore, the immature coping style of cadres will lead to serious mental health problems.
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Small cell lung cancer (SCLC), as a pathological type with high malignancy, presents a high risk of early brain metastasis. Prophylactic cranial irradiation (PCI) can reduce the risk of brain metastasis in patients with SCLC, however, the incidence of brain structural and functional damage caused by PCI is high, and their clinical symptoms are not typical. The existing treatment methods can relieve some clinical symptoms, but can not effectively reverse the process of brain injury, which reduces the survival benefit of patients. In-depth understanding the mechanisms of PCI neurotoxicity and exploring effective strategies for ptevention and treatment are of great value in improving prognosis of SCLC.
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Small cell lung cancer (SCLC) is the most malignant lung cancer with the highest mortality. At present, the first-line standard treatment is still based on Etoposide and Platinum chemotherapy. However, for SCLC that progresses after first-line therapy, the treatment options are still very limited. Since the molecular mechanism of first-line drug resistance of SCLC is still unclear, and the precision medicine strategy after first-line drug resistance is still in the pre-clinical stage. The proportion of secondary biopsy and genetic testing is very low after the progress of first-line treatment of SCLC. In this study, we report a case of a middle-aged woman who was first diagnosed with SCLC. Adenocarcinoma with sensitive gene mutations and repeated changes of small cell carcinoma were detected by multiple biopsies during the course of the disease, suggesting that the patient may be a special subtype of SCLC - mixed SCLC (M-SCLC). In this case, the patient has been treated with radiotherapy and chemotherapy, immunotherapy and targeted therapy successively, and the survival time has reached 2 years and 8 months. Through the case report and literature review retrospectively, this study aimed to explore the part patients may start to present hybrid histopathologic types or tissue type change after treatment of SCLC. Biopsy pathologic histology and genetic testing is necessary after disease progression to look for potential therapeutic targets, so as to give precise treatment based on molecular markers detection results and provide the patient with the benefit of survival for as long as possible. .
الموضوعات
Female , Humans , Middle Aged , Adenocarcinoma of Lung , Etoposide , Lung Neoplasms/genetics , Retrospective Studies , Small Cell Lung Carcinoma/geneticsالملخص
BACKGROUND@#Bronchial sleeve lobectomy is essential surgical approach to treat centralized lung cancer. It is the best reflected the principle of lung cancer surgery, "remove tumor completely while minimize pulmonary function loss". Bronchial pleural fistula (BPF) is not common but very severe complication of bronchial sleeve lobectomy, that is usually fatal. Present article is to explore clinical effect on prevention of bronchial pleural fistula (BPF) in bronchial sleeve lobectomy, by wrapping brachial anastomosis with pedicled pericardial fat flap.@*METHODS@#Clinical data of 39 non-small cell lung cancer (NSCLC) patients who underwent surgical resection during January 2016 to May 2019 in Lung Cancer Center of West China Hospital, Sichuan University were collected and retrospectively analyzed. All of the patients underwent bronchial sleeve lobectomy and a brachial anastomosis wrapping with pedicled pericardial fat flap.@*RESULTS@#All patients recovered well and were discharged within 6 d-14 d after operation. No BPF occurred, nor other severe complications, such as reoperation needing intrathoracic bleeding, several pneumonia and respiratory failure, and life threatening cardiac arrhythmia. Only one patient (1/39) had several anastomotic stenosis and consequential atelectasis of residual lung in operative side 6 months after surgery.@*CONCLUSIONS@#Wrapping bronchial anastomosis with pedicled pericardial fat flap in bronchial lobectomy for centralized NSCLC is a simple and effective approach to prevent BPF, thus safety of the operation could be significantly improved.
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BACKGROUND@#Mortality of lung cancer can be decreased by early screening effectively. However, consistent and proficient standards & methods have not been established in China. This study was based on pulmonary nodules/lung cancer comprehensive management platform established by West China Hospital, Sichuan University. Early screening of pulmonary nodules was integrated into standard healthcare of lung cancer system, aiming to improve survivals of lung cancer patients.@*METHODS@#Three cohorts were established: healthy populations, pulmonary nodules cohort and lung cancer patients cohort, and related clinical data will be collected and analyzed. Preliminary plan includes verifying effect of pulmonary nodules screening module.@*RESULTS@#Pulmonary nodules screening was performed in 2,836 employers (>40 years old) of West China Hospital. Lung cancers were diagnosed in 66 participants, all receiving surgery to remove the lesions. 65 of them were with early stage diseases, 1 with lung cancer and brain metastasis.@*CONCLUSIONS@#Proficient screening, follow-up and healthcare can be achieved via pulmonary nodules/lung cancer comprehensive management mode, which will be extended all over west China region in future.
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N6-methyladenosine is one of the most prevalent mRNA modification in eukaryotes. The regulation of this pervasive mark is a dynamic and reversible process. m⁶A RNA methylation is catalyzed by m⁶A writers, removed by m⁶A erasers and recognized by m⁶A readers, thereby regulating multiple RNA processes including alternative splicing, nuclear export, degradation and translation. Accumulated evidence suggests that m⁶A modification plays a crucial role in the pathogenic mechanism and malignant progression in non-small cell lung cancer (NSCLC), including cell survival, proliferation, migration, invasion, tumor metastasis and drug resistance. Moreover, the expression of m⁶A and its related proteins are dysregulated in clinical samples and circulating tumor cells (CTCs) of lung cancer patients, indicating that m⁶A modification may serve as a novel potential biomarker for the diagnosis and prognosis of lung cancer. In this review, by summarizing a great number of recent reports related to m⁶A's function and its modulators, we aim to provide a new insight on the early diagnosis and drug development in NSCLC therapy. .
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BACKGROUND@#The aim of this study is to systematically evaluate the efficacy and adverse effects of Lobaplatin and Cisplatin in the treatment of malignant pleural effusion.@*METHODS@#The databases of Medline (PubMed), Embase, Web of Science, Cochrane, Wanfang, CNKI and VIP were retrieved so as to search the studies about the randomized controlled clinical trials (RCT) that compared the Lobaplatin and Cisplatin for malignant pleural effusion. The main outcome indicators include objective response rate, complete response, partial response, nephrotoxicity, chest pain, gastrointestinal reaction, myelosuppression, fever response and hepatotoxicity. Relative risk was used as the effect size, which was expressed as 95% confidence interval. The meta-analysis was performed using Stata 14.0 statistical software.@*RESULTS@#A total of 12 RCTs and 720 MPE patients were included. The results showed that the ORR (RR=1.27, 95%CI: 1.15-1.40, P<0.001), CR (RR=1.39, 95%CI: 1.09-1.78, P=0.007), PR (RR=1.21, 95%CI: 1.02-1.42, P=0.026) in LBP thoracic perfusion chemotherapy were significantly higher than those in DDP thoracic perfusion chemotherapy. The incidence of nephrotoxicity (RR=0.31, 95%CI: 0.13-0.71, P=0.005) and gastrointestinal reactions (RR=0.44, 95%CI: 0.31-0.62, P<0.001) in the LBP group were significantly lower than those in DDP group.@*CONCLUSIONS@#Compared with DDP pleural perfusion chemotherapy, the ORR, CR and PR of LBP pleural perfusion chemotherapy for MPE are significantly better than DDP, and its nephrotoxicity and gastrointestinal reactions are remarkably lower than DDP.
الموضوعات
Humans , Antineoplastic Agents , Therapeutic Uses , Cisplatin , Therapeutic Uses , Cyclobutanes , Therapeutic Uses , Organoplatinum Compounds , Therapeutic Uses , Pleural Effusion, Malignant , Drug Therapy , Randomized Controlled Trials as Topicالملخص
BACKGROUND@#It has been proven that CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated 9) system was the modern gene-editing technology through the constitutive expression of nucleases Cas9 in the mammalian, which binds to the specific site in the genome mediated by single-guide RNA (sgRNA) at desired genomic loci. The aim of this study is that the animal model of EZH2 gene knockout was constructed using CRISPR/Cas9 technology.@*METHODS@#In this study, we designed two single-guide RNAs targeting the Exon3 and Exon4 of EZH2 gene. Then, their gene-targeting efficiency were detected by SURVEYOR assay. The lentivirus was perfused into the lungs of mice by using a bronchial tube and detected by immunohistochemistry and qRT-PCR.@*RESULTS@#The experimental results of NIH-3T3 cells verify that the designed sgEZH2 can efficiently effect the cleavage of target DNA by Cas9 in vitro. The immunohistochemistry and qRT-PCR results showed that the EZH2 expression in experimental group was significantly decreased in the mouse lung tissue.@*CONCLUSIONS@#The study successfully designed two sgRNA which can play a knock-out EZH2 function. An EZH2 knockout animal model was successfully constructed by CRISPR/Cas9 system, and it will be an effective animal model for studying the functions and mechanisms of EZH2.
الموضوعات
Animals , Female , Humans , Male , Mice , CRISPR-Cas Systems , Enhancer of Zeste Homolog 2 Protein , Genetics , Metabolism , Gene Knockout Techniques , Gene Targeting , Lung Neoplasms , Genetics , Metabolism , Mice, Inbred C57BL , Mice, Knockoutالملخص
BACKGROUND@#Lung cancer is the leading cause of cancer-related death in China. The results from a randomized controlled trial using annual low-dose computed tomography (LDCT) in specific high-risk groups demonstrated a 20% reduction in lung cancer mortality. The aim of tihs study is to establish the China National lung cancer screening guidelines for clinical practice.@*METHODS@#The China lung cancer early detection and treatment expert group (CLCEDTEG) established the China National Lung Cancer Screening Guideline with multidisciplinary representation including 4 thoracic surgeons, 4 thoracic radiologists, 2 medical oncologists, 2 pulmonologists, 2 pathologist, and 2 epidemiologist. Members have engaged in interdisciplinary collaborations regarding lung cancer screening and clinical care of patients with at risk for lung cancer. The expert group reviewed the literature, including screening trials in the United States and Europe and China, and discussed local best clinical practices in the China. A consensus-based guidelines, China National Lung Cancer Screening Guideline (CNLCSG), was recommended by CLCEDTEG appointed by the National Health and Family Planning Commission, based on results of the National Lung Screening Trial, systematic review of evidence related to LDCT screening, and protocol of lung cancer screening program conducted in rural China.@*RESULTS@#Annual lung cancer screening with LDCT is recommended for high risk individuals aged 50-74 years who have at least a 20 pack-year smoking history and who currently smoke or have quit within the past five years. Individualized decision making should be conducted before LDCT screening. LDCT screening also represents an opportunity to educate patients as to the health risks of smoking; thus, education should be integrated into the screening process in order to assist smoking cessation.@*CONCLUSIONS@#A lung cancer screening guideline is recommended for the high-risk population in China. Additional research , including LDCT combined with biomarkers, is needed to optimize the approach to low-dose CT screening in the future.
الموضوعات
Aged , Female , Humans , Male , Middle Aged , China , Epidemiology , Early Detection of Cancer , Lung Neoplasms , Diagnostic Imaging , Epidemiology , Mass Screening , Patient Selection , Practice Guidelines as Topic , Radiation Dosage , Risk , Rural Population , Tomography, Spiral Computedالملخص
[ ABSTRACT ] AIM: To characterize the phenotypic and genetic features of a patient with Lowe syndrome. METHODS:The clinical data and the MRI of a ten-month-old patient were analyzed.At the same time, all exons of the OCRL gene of the patient and his parents were amplified and Sanger-sequenced.RESULTS:Clinical analysis revealed that the patient has abnormal vision, nystagmus, congenital cataract, hypotonia, proteinuria, hematuria and psychomotor retar-dation.MRI showed white matter myelination delay, bilateral frontal and temporal dysplasia, and subarachnoid cavity en-largement.The results of PCR and Sanger sequencing detected a de novo mutation, NM_000276.3: c.1280-1281delTT (p.Cys428Hisfs*2), a deletion causing a frame shift.To our knowledge, this mutation in OCRL gene has not been repor-ted previously.CONCLUSION:The clinical manifestations suggested a phenotype of Lowe syndrome, and molecular ge-netic testing confirmed the diagnosis.The novel de novo mutation enriches the OCRL mutation spectrum.
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Objective To evaluate the standardization of Meta-analyses on nephropathy published in Chinese journals.Methods By searching in WANFANG,VIP,CNKI databases and Chinese Biomedical Literature Database(CBM) as well as related Chinese journals,eligible Meta-analyses were enrolled and analyzed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statement and the MOOSE (Meta-analysis of Observational Studies in Epidemiology) Checklist.Results A total of 217 Meta-analyses were enrolled with 166 on randomized controlled trials (RCT) and 51 on observational studies.Based on the PRSIMA Statement,of the 166 Meta-analyses on RCT,51.8%(86 papers) were found with the complete research hypothesis,13.9% (23) with the literature screening flow chart,15.7% (26) with the subgroup analysis,53.0% (88) with the publication bias analysis and 28.3% (47) with the sensitivity analysis.According to the MOOSE Checklist,of the 51 Meta-analyses on observational studies,only 9.8% (5) had done the statistical stability calculation,54.9% (28) with the outlook of application,45.1% (23) with the limitation of the study,2.0% (1) with the quantitative analysis on potential bias and 17.6% (9) with the suggestion for future studies.Conclusions Unclear hypothesis,limited methodological description,lack of in-depth analysis on heterogeneity and bias are the common defects in Meta-analyses published in Chinese journals on nephrology.
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Objective To explore the dysfunction of dendritic cells (DC) related to TGFβ reversed after blocking the TGFβ signal pathway by recombinant adenovirus vector encoding for Smad7.Methods Smad7 by recombinant adenovirus vector was transfected into dendritic cells.Expression of immunologic phenotypes was detected by FCM,and CTL activity induced by DC was compared.Results The DC modified with Smad7 still expressed high adhesiveness factor related to maturation even if existing exogenous TGFβ1,which was significant statistically compared with DC transfected with control adenoviral vector (P <0.01).Even if existing exogenous TGFβ1,the DC modified with Smad7 pulsed with soluble antigen associated with Lewis pulmonary carcinoma could still induce potent CTL activity against Lewis pulmonary carcinoma,which showed significant difference with DC-Ad-c (P <0.01).Conclusion The inhibitory effects on function of DC of TGFβ may be reversed by blocking the Smad signal of TGFβ pathway.
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<p><b>UNLABELLED</b>BACKGROUND AND OBJECTIVE Telomerase and CYFRA21-1 may be positively expressed in malignant pleural effusion, but the sensitivity and specificity of single tumor marker were low. The aim of this study is to investigate the diagnostic value of combining determination of telomerase activity and CYFRA21-1 levels in differentiating benign from malignant pleural effusion caused by lung cancer.</p><p><b>METHODS</b>80 patients with malignant and 50 patients with benign pleural effusion were enrolled into this study. The telomerase activity in pleural effusion was tested by means of telomeric repeat amplification protocal-PCR-ELISA (TRAP-PCR-ELISA) and CYFRA21-1 levels were tested by the EIA method. All the results were analyzed by the statistical method.</p><p><b>RESULTS</b>The levels of telomerase and CYFRA21-1 in malignant pleural effusion was significantly higher than that in benign one (t = 17.252 and t = 13.951, P < 0.001). The sensitivity of telomerase activity testing for diagnosing malignant pleural effusion was 71.3%; the specificity was 86.0% and the overall accuracy was 76.9%. The sensitivity of CYFRA 21-1 testing was 60.0%, the specificity was 78.0% and the overall accuracy was 66.9%. The sensitivity of the combined testing was 90.0%, the specificity was 76.0% and the overall accuracy was 86.9%. The sensitivity and the overall accuracy of combined testing were higher than those of telomerase and CYFRA21-1 testing single (chi2 = 9.002 and chi2 = 19.201, P < 0.01; chi2 = 4.389 and chi2 = 14.647, P < 0.05).</p><p><b>CONCLUSION</b>The combined testing oftelomerase with CYFRA21-1 can increase the sensitivity and overall accuracy of differential diagnosis of benign and malignant pleural effusion diagnosis.</p>
الموضوعات
Aged , Female , Humans , Male , Middle Aged , Antigens, Neoplasm , Diagnosis, Differential , Keratin-19 , Pleural Effusion , Diagnosis , Pleural Effusion, Malignant , Diagnosis , Telomerase , Metabolismالملخص
<p><b>BACKGROUND AND OBJECTIVE</b>It has been proven that close relation was existed between XPD polymorphism G312A and lung cancer risk. However, some of the results are not consistent. The aim of this study is to explore the impact of DNA repair gene XPD polymorphism G312A on lung cancer risk.</p><p><b>METHODS</b>The literatures eligible from PUBMED, EMBASE, CNKI and WANGFANG database were enrolled in the meta-analysis. Heterogeneity among combined studies was assessed. The pooled OR and 95%CI were calculated. The sensitivity analysis and the publication bias were evaluated by RevMan 5.0 and STATA 11.0.</p><p><b>RESULTS</b>There were 6554 cases and 8322 controls from 18 studies included in the meta-analysis. In total, individuals with 312A allele and 312AA genotype showed increased lung cancer risk (A vs. G: OR = 1.06, 95% CI: 1.00-1.12; AA vs. AG+GG: OR = 1.20, 95% CI: 1.06-1.36; AA vs. GG: OR = 1.19, 95% CI: 1.04-1.36). In Asians, individuals with 312AA genotype showed 6.15 fold and 6.20 fold increased lung cancer risk in recessive genetic model and homogenous contrast respectively (AA vs. AG+GG: OR = 7.15, 95% CI: 1.90-26.94; AA vs. GG: OR = 7.20, 95% CI: 1.91-27.15). In Caucasians, individuals with 312AA genotype showed a 15% increased lung cancer risk (OR = 1.15, 95% CI: 1.01-1.31).</p><p><b>CONCLUSION</b>XPD 312A allele is risk allele for lung cancer. Individuals with AA genotype have higher risk of lung cancer, especially in Asians.</p>
الموضوعات
Humans , Genotype , Lung Neoplasms , Genetics , Odds Ratio , Polymorphism, Genetic , Xeroderma Pigmentosum Group D Protein , Geneticsالملخص
<p><b>BACKGROUND AND OBJECTIVE</b>Glutathione S-transferase M1 (GSTM1) is an important phase II metabolic enzyme gene which involves metabolism of various carcinogens in human body. Many studies showed that GSTM1 genetic polymorphism was associated with lung cancer risk. The aim of this study is to investigate the relationship between GSTM1 genetic polymorphism and lung cancer risk among Han nationality population in Tianjin district.</p><p><b>METHODS</b>GSTM1 genetic polymorphism was detected by melting curve analysis of SYBR green I real-time PCR assay. Two hundred and sixty-five histological confirmed lung cancer patients and 307 health controls were recruited in this case-control study and the relationship between GSTM1 genetic polymorphism and lung cancer riskwas investigated.</p><p><b>RESULTS</b>(1) The frequency of the GSTMI(-) in lung cancer and control groups was 56.6% and 57.0% respectively, and no significant difference was found between the distribution of the GSTM1 (-) genotype in the two groups (chi2 = 0.831, P = 0.362). (2) When considered the GSTM1(+) genotype as reference, there was no overall statistically increased lung cancer risk for carriers with the GSTM1(-) genotype adjusted by age, gender and smoking status (OR = 0.840, 95% CI: 0.578-1.221, P = 0.362). (3) The frequency of the GSTM1(-) genotype for squamous cell carcinoma, adenocarcinoma, SCLC and other histological types was 65.8%, 48.5%, 47.8% and 52.2% respectively, compared with the control group, no statistically increased lung cancer risk was observed (P > 0.05).</p><p><b>CONCLUSION</b>No evidence is found between GSTMI genetic polymorphism and lung cancer risk among Han nationality population in Tianjin district.</p>
الموضوعات
Adult , Aged , Female , Humans , Male , Middle Aged , Genotype , Glutathione Transferase , Genetics , Lung Neoplasms , Genetics , Organic Chemicals , Polymerase Chain Reaction , Methods , Polymorphism, Genetic , Riskالملخص
<p><b>BACKGROUND AND OBJECTIVE</b>It has been reported that defective expression of TGFBR3 was found in non-small cell lung cancer (NSCLC). However, its molecular mechanisms remain unclear. The aim of this study is to investigate expression of TGFBR3 in NSCLC cell lines and normal human bronchial epithelial cell (HBEpiC), and to explore potential molecular mechanisms underlying inactivation of TGFBR3 gene.</p><p><b>METHODS</b>Western blot was performed to determine the expression of TGFBR3 in HBEpiC and NSCLC cell lines. Automatic image analysis was carried out to estimate relative expression of TGFBR3 protein. We screened for mutation of the promoter region of TGFBR3 gene using DNA direct sequencing. Bisulfite-sodium modification sequencing was used to detect the methylation status of TGFBR3 promoter.</p><p><b>RESULTS</b>TGFBR3 protein level was abnormally reduced in NSCLC cell lines as compared with HBEpiC. There was significant difference in TGFBR3 expression between the highly metastatic cell line 95D and non-metastatic cell lines, including LTEP-alpha-2, A549 and NCI-H460. No mutation and methylation was found in upstream sites -165 to -75 of the proximal promoter of TGFBR3 in HBEpiC and NSCLC cell lines. Hypermethylation was shown in upstream sites -314 to -199 of the distal promoter of TGFBR3 in HBEpiC and NSCLC cell lines.</p><p><b>CONCLUSION</b>Reduced expression of TGFBR3 was observed in NSCLC cell lines, especially in 95D, suggesting that TGFBR3 might play an important role in development and progression of NSCLC and correlate with NSCLC invasion and migration. The methylation event occurring at TGFBR3 promoter is not a major cause for reduction of TGFBR3 expression.</p>