Analysis and Review of Downregulated Actin Cytoskeletal Proteins in Non-Small Cell Lung Cancer

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.

Pang Fuwan Uses Yao Medicine to Observe the Therapeutic Effects on the Physical and Mental Symptoms of Patients with Advanced Non-Small Cell Lung Cancer

Objective: Investigate the efficacy and safety of Yao Medicine in the treatment of advanced non-small-cell lung carcinoma, and explore the best therapeutic measure for clinical benefit. Methods: From July 2020 to July 2022, 84 patients with advanced non-small-cell lung carcinoma were selected and randomly divided into the Observation Group and control group, and the control group was treated with routine Western medicine, with 42 cases in each group. The activity of daily living (ADL) was assessed before and after treatment, meanwhile, the self-rating depression scale (SDS) and self-rating anxiety SAS (SAS) were used to assess the improvement of a bad mood, and quality of life SF-36 was used to assess the quality of life, to judge the efficacy and safety. Results: The effective rate of observation group was 91.67%. The effective rate of the control group was 76.19%. The effective rate of the observation group was significantly higher than that of the control group (P 0.05). There were no significant differences in the scores of SDS, SAS and quality of life between the two groups before treatment (P > 0.05), and after treatment, the scores of SDS, SAS and quality of life in the two groups were compared with those in the control group (P > 0.05), the scores of VAS, SDS and SAS decreased significantly, while ESCV, angle of straight leg elevation, ADL, physiological score, emotional score, social score and health status score increased significantly, the difference was statistically significant (P 0.05). Conclusion: Yao Medicine can improve the psychosomatic symptoms of patients with advanced non-small-cell lung carcinoma better, with better efficacy and higher safety.

Efficacy and Safety of Primary Radiotherapy in Combination with EGFR-TKIs for Non-Small Cell Lung Cancer Harboring EGFR Mutation

Objective: To evaluate the efficacy and safety of EGFR-TKI with the radiotherapy in EGFR mutant metastatic NSCLC. Methods: Retrospective analysis of 72 patients with stage IV lung cancer with EGFR-sensitive mutation. Patients in the A group were treated with the first-generation EGFR-TKI (Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor) combined with radiotherapy for primary tumors (34 cases). The B group was treated with the first-generation EGFR-TKI alone until the disease progressed (38 cases). PFS, OS, pulmonary infection and hematological toxicity during treatment were commented in both groups. Results: The objective remission rate was 47.1% (16/34) in the A group and 21.1% (8/38) in the B group. There was a significant difference between the two groups. There was no significant difference in hematological toxicity between the A group and the B group. There were 10 patients (29.4%) with degree II pulmonary infection in the A group and 3 patients (7.9%) in the B group. The difference between the two groups was statistically significant, suggesting that the incidence of pneumonia in the A group was higher than that in the B group. The median PFS (Progression-Free Survival)) and OS (Overall Survival) of the A group were significantly longer than those of the B group (16.5 months vs 9 months) and the median OS (36 months vs 19 months). The PFS and OS in the A group were significantly longer than those in the B group. Conclusion: EGFR-TKI combined with primary radiotherapy can significantly prolong the drug resistance time of EGFR mutant metastatic NSCLC.

Clinical Biomarkers and Prognosis in Taiwan Residents Patients with Non-Small Cell Lung Cancer (NSCLC)

Introduction: Lung cancer is the leading cause of cancer death worldwide with poor survival rates. However, the prognostic factors for survival of patients with lung cancer are not well-established. In this study, we examined the impact of routine laboratory biomarkers and traditional factors on survival of patients with non-small cell lung cancer (NSCLC). Method: Secondary data analysis was conducted from a retrospective study of 404 patients with newly diag-nosed lung cancer in 2005-2007 in Taiwan. There were eight routine laboratory biomarkers and eight traditional factors investigated in the analyses. Cox proportional hazards model was used to assess the hazard ratios for the association between risk factors and patient overall survival. The Kaplan-Meier method was used to compare survival curves for each prognostic indicator. Results: High WBC counts (HR = 1.798, 95%CI: 1.225 - 2.639), low Hgb level (HR = 1.437, 95%CI: 1.085 - 1.903), and low serum albumin level (HR = 2.049, 95%CI: 1.376 - 3.052) were significant laboratory prognostic biomarkers for poor NSCLC survival. Additionally we confirmed the traditional prognostic factors for poor overall survival among NSCLC patients, including older age, comorbidity conditions, advanced cancer stage, and non-surgical treatment. Conclusions: This study identified three available laboratory biomarkers, high WBC counts, low Hgb level, and low serum albumin level, to be significant prognostic factors for poorer overall survival in NSCLC patients. Further prognostic evaluation studies are warranted to compare different ethnic groups on the prognostic values of these clinical parameters in NSCLC survival outcomes. These identified prognostic biomarkers should be included in early risk screening of hospitalized lung cancer patient population.

A Clinic-Epidemilogical Study of Cases of Locally Advanced Non Small Cell Lung Cancer (NSCLC) That Received Radiotherapy at NCI Cairo in the Period from 2001-2010

Purpose: This work was to study the clinic-epidemiological characteristics of patients with locally advanced NCSLC and to analyze their prognostic factors and also the results of different treatment modalities for local control and their effect on overall survival (OAS). Materials and Methods: This is a retrospective study including 121 patients with primary locally advanced NSCLC diagnosed between 2001 and 2010 at the radiotherapy department , National Cancer Institute, Cairo University, Egypt. Results: The study showed significant correlation between the tumor size 60, moderately differentiated tumors G2 and treatment outcomes;better locoregional control and better survival rates. On the opposite side poorly differentiated tumors G3, tumor size > 7 cm had the worst locoregional control and survival rates. The study also showed significant statistical correlation between treatment modality, locoregional control and survival rates. Patients who were treated by either concommitent chemo-radiotherapy or sequential chemo-radiotherapy had better local control compared to other patients who were treated by radical radiotherapy, and they also had the best survival rates among all the other treatment groups. The average 6 months OAS rates for all studied patients were 60.3% while 12 months survival rates were 38.8%. The median OAS was 7 months. Conclusions: From the present study, we concluded that concomitant chemo-radiotherapy is the treatment of choice for locally advanced non small cell lung cancer;also we concluded that better performance status and higher hemoglobin levels have better treatment outcome in these cases.

Single nucleotide polymorphisms of MAGE-A3 gene and its clinical implications in Chinese patients with non-small cell lung cancer(NSCLC)

Background： Available study revealed advanced tumors have a higher expression rate of MAGE-A3 gene which has a lot of single nucleotide polymorphism（SNP） loci with polymorphisms. This study aimed to analyze the allele frequency of SNP loci in MAGE-A3 gene and investigate the relationship between MAGE-A3 gene polymorphisms and clinical factors.Methods： Tumor samples of a cohort of 191 NSCLC patients were collected. EGFR m RNA expression were detected by q RT-PCR. SNPs in whole length of MAGE-A3 gene were detected by direct sequencing. Frequencies of the SNPs were correlated to gene expression, mutation status of EGFR and clinical factors.Results： Sequencing analysis confirmed that allele frequencies of genotypes on SNP loci rs5970360, rs5925210, rs5970361, rs5925211 and rs35123853 were CC（0.681）/CT（0.319）, CC（0.660）/CG（0.340）, CC（0.681）/CA（0.319）, AA（0.984）/AT（0.016） and GG（1.000）/GA（0.000）, respectively, which were different from the frequencies and genotypes of MAGE-A3 in SNP database. Chi-square tests showed the EGFR mR NA expression level had significant correlation with the genotypes of SNP loci rs5970360 and rs5925210. But all frequencies of each MAGE-A3 SNPs were not found significantly different between EGFR mutant and wild type patients. MAGE-A3 gene polymorphisms had no significant effects on survival of NSCLC patients.Conclusions： Chinese patients with NSCLC had different SNP patterns of MAGE-A3 in comparison with those in international SNP database. These MAGE-A3 SNP loci might have not prognostic significance. MAGE-A3 SNP loci rs5970360 and rs5925210 might be predictive for EGFR m RNA expression levels and helpful to the selection of patients for epidermal growth factor receptor（EGFR） targeted immunotherapy.

Impact of Cardiac Dose on Overall Survival in Lung Stereotactic Body Radiotherapy (SBRT) Compared to Conventionally Fractionated Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer (LA-NSCLC)

Purpose: To examine possible association between heart irradiation and Overall Survival (OS) in lung SBRT patients and to compare observed associations with cardiac toxicity models previously derived in LA-NSCLC patient studies. Materials and Methods: 197 Patients treated with lung SBRT at Mayo Clinic Arizona were selected for this IRB-approved study. Multivariate Cox model with Akaike Information Criterion (AIC) was used to select patient specific covariates associated with OS. Heart dosimetry was represented by VD indices, which is a percentage of volume exposed to dose D or greater. Multivariate Cox models with patient specific covariates and single VD index per model was used to find a range of doses which were predictive for OS. A digital subdivision of the heart was further used to determine the spatial distribution of doses which were predictive for OS. A coarse subdivision divided heart into 4 segments, while the fine subdivision divided heart into 64 segments. Knowledge constrained Fused Lasso operator was used to derive a more complete model which correlated heart dosimetry with OS. Results of statistical analysis were compared to predictions of a model of cardiac toxicity in LA-NSCLC patients. Results: Higher age (p < 0.001), higher stage (p < 0.001) and squamous cell histology (p = 0.001) were associated with reduced OS. Whole heart DVH analysis did not reveal associations between heart irradiation and reduced OS. Coarse subdivision of the heart into four segments revealed that the irradiation of two inferior segments of the heart with low doses was associated with reduced OS, V2Gy in the right-inferior segment (HR = 1.012/1%, p = 0.02), and V1Gy in the left-inferior segment (HR = 1.01/1%, p = 0.04). Maximum dose in the right-inferior segment of the heart was also associated with reduced OS (HR = 1.02/Gy, p = 0.02). Fine subdivision of the heart into 64 segments revealed that approximately 25% of heart volume in the inferior part of the heart (15/64 segments), when irradiated to doses in the 1 Gy - 5 Gy range, were predictive for reduced OS (HR = 1.01/1%, p = 0.01). A previously derived model of cardiac toxicity in LA-NSCLC patients did not predict a reduction of OS due to heart irradiation in lung SBRT patients, because of relatively low doses to the heart in most lung SBRT patients. Conclusions: Doses lower than 5 Gy in the inferior segments of the heart may be associated with reduced overall survival in patients treated for lung lesions with SBRT. Stage and histology of the disease, as well as patients’ age, were also associated with overall survival. Comparisons of cardiac toxicity patterns in LA-NSCLC patients and lung SBRT patients suggest different etiology of cardiac toxicity in the two groups.

A Prospective Study of the Effect of Different Palliative Radiotherapy Fractionation Schedules on Tumor Response and Toxicity in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients

Background: The optimal dose of palliative radiotherapy (RT) in symptomatic advanced lung cancer is unclear. Patients and methods: Patients with advanced NSCLC who were indicated for thoracic palliative RT with age up to 65 y and Performance Status (PS) 0 - 2 and no significant cardiac or lung co-morbidities were randomized into two fractionation arms: arm A: 30 Gy/10 over 2 weeks and arm B: 27 Gy/6 over 3 weeks (2 fractions per week) using 2 anterior posterior (AP-PA) fields in both arms. Primary end points were symptomatic and radiological tumor response, respiratory functions assessment. Secondary end point was toxicity. Results: From December 2014 to October 2015, 40 patients were randomized, 20 patients in each arm. There was statistically insignificant higher symptomatic improvement in arm B. Four weeks after treatment, 12 out of 40 patients (30%), 6 patients in each arm, had radiological Partial Response (PR) of the primary thoracic lesion without significant difference between the two arms. There was a tendency for improvement in the post treatment mean Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1) in each arm without statistical significance. There were no reported skin reactions or esophagitis in both arms up to 4 weeks after treatment. Eleven out of the 40 patients (27.5%), 6 in arm B and 5 in arm A, had radiological signs of radiation pneumonitis without significant difference between both arms. Conclusion: The two RT fractionation schedules showed equal efficacy in terms of symptoms relief, radiological response of the primary thoracic tumor, respiratory functions and toxicity. Thus the 27 Gy/6 fractionation arm appears preferable compared to 30 Gy/10 arm to minimize the patients’ visits and load on the machines.

Improvement of Quality of Life with Shenfu Injection (参附注射液) in Non Small Cell Lung Cancer Patients Treated with Gemcitabine plus Cisplatin Regimen

Objective： To observe the effect of Shenfu injection （参附注射液, SFI） in treating non small cell lung cancer （NSCLC） patients on quality of life with gemcitabine （GEM） plus cisplatin （GP） regimen. Methods： Thirty-four patients were ready to receive GP regimen chemotherapy for treating NSCLC disease, according to lot-drawing, they were divided into SFI pre-treatment group （18 cases） and SFI post-treatment group （ 16 cases）. SFI pre-treatment group： During the first treatment course, chemotherapy was begun with SFI 60 ml, intravenous dripping on the 3rd day, once daily, consecutively for 10 days; on the 1st day, GP regimen （GEM 1250 mg/m^2 , intravenous dripping, on the 1st and 8th day; cisplatin 70 mg/m^2 on the 2nd day; 21 days as one cycle） was carried out; in the second treatment course GP regimen was merely given to serve as the self-control. SFI post-treatment group： the medicament sequence order was reversed from that of pre-treatment group. Using dual international quality of life （QOL） scores, the effect of SFI on the patients＂ QOL was observed through randomized self pre- and post- crossover control. Results： The QOL in the 34 patients after being treated by SFI in combination with GP chemotherapy regimen in one group, and GP chemotherapy regimen alone in the other, was improved in different degrees, with significant difference （P〈0.01）; comparision of SFI combined with GP chemotherapy regimen with GP chemotherapy alone showed that QOL in patients was significantly different （P〈0.01）. Conclusion： SFI could improve QOL in patients with NSCLC who were treated with GP regimen.

Efficacy and safety evaluation of icotinib in patients with advanced non-small cell lung cancer

Objective： To evaluate the efficacy and safety of icotinib hydrochloride in patients with advanced non-small cell lung cancer （NSCLC）. Methods： A total of 89 patients with stage IIIB or IV NSCLC received icotinib at a dose of 125 mg administered 3 times a day. Icotinib treatment was continued until disease progression or development of unacceptable toxicity. Results： A total of 89 patients were assessable. In patients treated with icotinib, the overall response rate （RR） was 36.0% （32/89）, and the disease control rate （DCR） was 69.7% （62/89）. RR and DCR were significantly improved in patients with adenocarcinoma versus non-adenocarcinoma （P〈0.05）. The symptom improvement rate was 57.3% （51/89）, and the main symptoms improved were cough, pain, chest distress, dyspnea, and Eastern Cooperative Oncology Group performance status. The main toxic effects were rash [30/89 （33.7%）] and diarrhea [15/89 （16.9%）]. The level of toxicity was typically low. Conclusions： The use of icofinib hydrochloride in the treatment of advanced NSCLC is efficacious and safe, and its toxic effects are tolerable.

Nab-paclitaxel(abraxane)-based chemotherapy to treat elderly patients with advanced non-small-cell lung cancer:a single center,randomized and open-label clinical trial

Background： The purpose of this study is to evaluate the clinical efficacy and safety of abraxane-based chemotherapy with/without nedaplatin in elderly patients with non-small-cell lung cancer （NSCLC）. Materials and methods： From October 2009 to January 2013, 48 elderly patients （≥65 years） with NSCLC were investigated in this clinical trial. The patients were randomized and equally allocated into arms A and AP- （A） abraxane （130 mg/m2, days 1, 8）; （B） abraxane ＋ nedaplatin （20 mg/m2 days 1-3, q3w）. The parameters of objective response rate （ORR）, disease control rate （DCR）, progression-free survival （PFS）, overall survival （OS） and side effects were evaluated between two arms. Results： Over 80% of the patients completed four cycles of chemotherapy. The total ORR was 21.3 %, DCR was 55.3%, PFS 4.5 months and OS 12.6 months. No significant difference was found between arms A and AP in terms of ORR （16.7% vs. 26.1%, P=0.665） or DCR （55.3% vs. 56.5%, P=0.871）. The median PFS in arm A was 3.3 months [25-75% confidence interval （CI）： 3.1-7.2] and 5.5 months （25-75% CI： 3.2-7.0） in arm AP with no statistical significance （P=0.640）. The median OS in arm A was 12.6 months （25-75% CI： 5.7-26.2） and 15.1 months （25-75% CI： 6.4-35.3） in arm AP with no statistical significance （P=0.770）. The side effects were mainly grade 1-2. The incidence of grade 3-4 toxicities was 29.1% in arm A and 62.5% in arm AP with a statistical significance （P=0.020）. Conclusions： Compared with combined therapy, abraxane alone chemotherapy was beneficial for elderly NSCLC patients with better tolerability and less adverse events, whereas did not significantly differ in terms of ORR, DCR, PFS or OS.

Identification of plasma microRNA-21 as a biomarker for early detection and chemosensitivity of non-small cell lung cancer

Studies have shown cell-free microRNA(miRNA) circulating in the serum and plasma with specific expression in cancer,indicating the potential of using miRNAs as biomarkers for cancer diagnosis and therapy.This study was to investigate whether plasma miRNA-21(miR-21) can be used as a biomarker for the early detection of non-small cell lung cancer(NSCLC) and to explore its association with clinicopathologic features and sensitivity to platinum-based chemotherapy.We used real-time RT-PCR to investigate the expression of miR-21 in the plasma of 63 NSCLC patients and 30 healthy controls and correlated the findings with early diagnosis,pathologic parameters,and treatment.Thirty-five patients(stages IIIB and IV) were evaluable for chemotherapeutic responses:11 had partial response(PR);24 had stable and progressive disease(SD+PD).Plasma miR-21 was significantly higher in NSCLC patients than in age-and sex-matched controls(P<0.001).miR-21 was related to TNM stage(P<0.001),but not related to age,sex,smoking status,histological classification,lymph node status,and metastasis(all P>0.05).This marker yielded a receiver operating characteristic(ROC) curve area of 0.775(95% CI:0.681-0.868) with 76.2% sensitivity and 70.0% specificity.Importantly,miR-21 plasma levels in PR samples were several folds lower than that in SD plus PD samples(P=0.049),and were close to that in healthy controls(P=0.130).Plasma miR-21 can serve as a circulating tumor biomarker for the early diagnosis of NSCLC and is related to the sensitivity to platinum-base chemotherapy.

Pharmacogenomics of EGFR-targeted therapies in non-small cell lung cancer:EGFR and beyond

Commonly observed aberrations in epidermal growth factor receptor(EGFR) signaling have led to the development of EGFR-targeted therapies for various cancers,including non-small cell lung cancer(NSCLC).EGFR mutations and overexpression have further been shown to modulate sensitivity to these EGFR-targeted therapies in NSCLC and several other types of cancers.However,it is clear that mutations and/or genetic variations in EGFR alone cannot explain all of the variability in the responses of patients with NSCLC to EGFR-targeted therapies.For instance,in addition to EGFR genotype,genetic variations in other members of the signaling pathway downstream of EGFR or variations in parallel receptor tyrosine kinase(RTK) pathways are now recognized to have a significant impact on the efficacy of certain EGFR-targeted therapies.In this review,we highlight the mutations and genetic variations in such genes downstream of EGFR and in parallel RTK pathways.Specifically,the directional effects of these pharmacogenetic factors are discussed with a focus on two commonly prescribed EGFR inhibitors:cetuximab and erlotinib.The results of this comprehensive review can be used to optimize the treatment of NSCLC with EGFR inhibitors.Furthermore,they may provide the rationale for the design of subsequent combination therapies that involve the inhibition of EGFR.

Shenqi Fuzheng injection combined with GP chemotherapy in the treatment of advanced non-small cell lung cancer： a meta-analysis

Objective： To evaluate the clinical efficacy of Shenqi Fuzheng injection combined with gemcitabine plus cisplatin（GP） in the treatment of advanced non-small cell lung cancer （NSCLC）. Methods： we performed a systematicsearch in the electronic databases such as Cochrane Library, Pubmed, Embase, Chinese Journal Full-text Database,Chinese Biomedical Literature Database, Chinese Science and Technology Periodical Full-text Database andWanfang Database up to 30 January 2017. Randomized controlled trials （RCT） of Shenqi Fuzheng Injectioncombined with GP chemotherapy in the treatment of advanced NSCLC were searched, and all the RCTs wereconducted on methodological quality assessment. Data extraction and data analysis were according to standards ofCochrane systematic review. Results： Eight trials were included including a total of 701 patients. Meta-analysisresults： Shenqi Fuzheng injection combined with GP chemotherapy could significantly improve the functionalstatus of patients with NSCLC （OR = 3.44, 95% CI [2.26, 5.25], P 〈 0.0001） and clinical treatment efficacy （OR =（OR = 0.31, 95%CI [0.20, 0.47], P 〈 0.0001. The rate of leukopenia （OR = .31, 95%CI [0.20,0.47], P 〈 0.0001）,thrombocytopenia （OR = 0.58, 95%CI [0.37, 0.91], P = 0.020）, hemoglobin decline （（OR = 0.31, 95%CI [0.16,0.59], P = 0.0004） and incidence of gastrointestinal reactions （OR = 0.58,P 〈 0.05） could be reduced. Conclusion：Shenqi Fuzheng injection combined with GP chemotherapy in the treatment of advanced NSCLC obtainedsignificantly clinical efficacy. The quality of the literature incorporated is low, the conclusion requires high-qualityresearch to further prove.

PTEN and Ki67 expression is associated with clinicopathologic features of non-small cell lung cancer

Phosphatase and tensin homolog deleted on chromosome 10（PTEN） and the proliferating antigen Ki67 have been widely studied in several tumors.However,their role as indicator in non-small cell lung cancer（NSCLC）remains unknown.Here,we investigated the expression of PTEN and Ki67 in NSCLC tissues and paired normal lung tissues to identify whether these proteins are associated with lung cancer development and survival.Immunohistochemistry for PTEN and Ki67 was performed on 67 lung cancer tissues and 41 paired adjacent normal lung tissues to detect the expression of these two proteins.The expression of PTEN in NSCLC tissues（32.8%） was significantly lower than that in normal tissues（82.9%,P 〈 0.05）.In contrast,the expression of Ki67 in NSCLC tissues（76.1%） was significantly higher than that in normal tissues（27.3%,P 〈 0.05）.Expression of both PTEN and Ki67 were strongly associated with tumor histology,clinical stage,lymph node metastasis,differentiation and4-year postoperative survival rate（P 〈 0.05）.However,PTEN expression was negatively correlated with Ki67 expression（r =-0.279,P 〈 0.05）.In conclusion,low PTEN expression and Ki67 overexpression are associated with malignant invasion and lymph node metastasis of NSCLC.These proteins may serve as diagnostic and prognostic biomarkers of NSCLC.

Prognostic assessment of apoptotic gene polymorphisms in non-small cell lung cancer in Chinese

Apoptosis plays a key role in inhibiting tumor growth, progression and resistance to anti-tumor therapy. We hypothesized that genetic variants in apoptotic genes may affect the prognosis of lung cancer. To test this hypoth- esis, we selected 38 potentially functional single nucleotide polymorphisms （SNPs） from 12 genes （BAX, BCL2, BID, CASP3, CASP6, CASP7, CASPS, CASP9, CASPIO, FAS, FASLG and MCL1） involved in apoptosis to assess their prognostic significance in lung cancer in a Chinese case cohort with 568 non-small cell lung cancer （NSCLC） patients. Thirty-five SNPs passing quality control underwent association analyses, 11 of which were shown to be significantly associated with NSCLC survival （P 〈 0.05）. After Cox stepwise regression analyses, 3 SNPs were independently associated with the outcome of NSCLC （BID rs8190315： P = 0.003; CASP9 rs4645981： P = 0.007 and FAS rs1800682： P = 0.016）. A favorable survival of NSCLC was significantly associated with the genotypes of BID rs8190315 AG/GG （adjusted HR = 0.65, 95% CI： 0.49-0.88）, CASP9 rs4645981 AA （HR = 0.22, 95% CI： 0.07-0.69） and FAS rs1800682 GG （adjusted HR = 0.67, 95% CI： 0.46-0.97）. Time-dependent receptor operation curve （ROC） analysis revealed that the area under curve （AUC） at year 5 was significantly increased from 0.762 to 0.819 after adding the risk score of these 3 SNPs to the clinical risk score. The remaining 32 SNPs were not sig- nificantly associated with NSCLC prognosis after adjustment for these 3 SNPs. These findings indicate that BID rs8190315, CASP9 rs4645981 and FAS rs1800682 polymorphisms in the apoptotic pathway may be involved in the prognosis of NSCLC in the Chinese population.

Nedaplatin/Gemcitabine Versus Carboplatin/Gemcitabine in Treatment of Advanced Non-small Cell Lung Cancer: A Randomized Clinical Trial

Objective： To evaluate the efficacy and safety of nedaplatin/gemcitabine （NG） and carboplatin/gemcitabine （CG） in the management of untreated advanced non-small cell lung cancer （NSCLC）. Methods： Sixty-two patients with previously untreated advanced NSCLC were recruited between June 2006 and November 2007. Subjects were randomly assigned to the NG arm （n=30） and the CG arm （n=32）. Only patients （24 and 25 in the NG and CG arms, respectively） who completed 〉2 chemotherapy cycles were included in the data analysis. The primary outcome measure was the objective response rate （ORR）. The secondary outcome measures included progression-free survival （PFS）, overall survival （OS） and adverse events. Results： There were no statistically significant differences in the efficacy measures （ORR, P=0.305; median PFS, P=0.298, median OS, P=0.961） or in the major adverse events （grade 3/4 neutropenia, P=0.666; grade 3/4 anemia, P=0.263; grade 3/4 thrombocytopenia, P=0.222） between the two treatment arms. However, there was a trend towards higher ORR （37.5% vs. 24.0%）, longer PFS （6.0 vs. 5.0 months）, and less adverse events in the NG arm. Conclusion： NG regimen seems to be superior over CG regimen for advance NSCLS, but further investigation is needed to validate this superiority.

Clinical characteristics and response to tyrosine kinase inhibitors of patients with non-small cell lung cancer harboring uncommon epidermal growth factor receptor mutations

Objective： To investigate the clinical features of patients with non-small cell lung cancer（NSCLC） harboring uncommon epidermal growth factor receptor（EGFR） mutations, and the treatment outcomes of EGFR tyrosine kinase inhibitors（TKIs） in these patients.Methods： We retrospectively analyzed the data of 128 NSCLC patients pathologically diagnosed with uncommon EGFR mutation in the Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences ＆ Peking Union Medical College and Beijing Hospital from January 2010 to December 2015, including 40 advanced patients who received EGFR-TKI.Results： Among the total 128 patients, 11 patients were non-adenocarcinoma, including squamous carcinoma（3.9%）, adenosquamous carcinoma（2.3%）, large cell carcinoma（0.8%）, and composite neuroendocrine carcinoma（1.6%）. Single mutations accounted for 75.0%（96/128）, including G719X（29.7%）, S768I（18.0%）, 20 exon insertion（13.3%）, L861Q（12.5%）, De novo T790M（0.8%）, and T725（0.8%）. Thirty-two patients harbored complex mutations. Forty advanced patients received EGFR-TKI, the objective response rate（ORR） was 20.0%,the disease control rate（DCR） was 85.0%, and the progression-free survival（PFS） was 6.4 [95% confidence interval（95% CI）, 4.8–7.9] months. The exploratory analysis of tumor response and PFS in 33 patients with G719X/S768I/L861 Q subtypes showed that ORR was 21.2%（7/33）, the DCR was 93.9%（31/33）, and PFS was 7.6（95% CI, 5.8–9.4） months. Patients with exon 20 insertion mutation and De novo T790 M experienced rapid disease progression with PFS no more than 2.7 months.Conclusions： Uncommon EGFR-mutant NSCLCs are heterogeneous, EGFR-TKIs can have different efficacy in this specific subtype, and thus further individual assessment is required for each case.

Therapeutic management options for stage Ⅲ non-small cell lung cancer

Lung cancer is the leading cause of cancer death worldwide.Majority of newly diagnosed lung cancers are non-small cell lung cancer(NSCLC), of which up to half are considered locally advanced at the time of diagnosis.Patients with locally advanced stage Ⅲ NSCLC consists of a heterogeneous population, making management for these patients complex.Surgery has long been the preferred local treatment for patients with resectable disease.For select patients, multimodality therapy involving systemic and radiation therapies in addition to surgery improves treatment outcomes compared to surgery alone.For patients with unresectable disease, concurrent chemoradiation is the preferred treatment.More recently, research into different chemotherapy agents, targeted therapies, radiation fractionation schedules, intensity-modulated radiotherapy, and proton therapy have shown promise to improve treatment outcomes and quality of life.The array of treatment approaches for locally advanced NSCLC is large and constantly evolving.An updated review of past and current literature for the roles of surgery, chemotherapeutic agents, radiation therapy, and targeted therapy for stage Ⅲ NSCLC patients are presented.

A Preliminary Analysis of Non-small Cell Lung Cancer Biomarkers in Serum

To identify potential serum biomarkers that could be used to discriminate lung cancers from normal. Methods Proteomic spectra of twenty-eight serum samples from patients with non-small cell lung cancer and twelve from normal individuals were generated by SELDI (Surfaced Enhanced Laser Desorption/Ionization) Mass Spectrometry. Anion-exchange columns were used to fractionate the sera into 6 designated pH groups. Two different types of protein chip arrays, IMAC-Cu and WCX2, were employed. Samples were examined in PBSII Protein Chip Reader (Ciphergen Biosystem Inc) and the discriminatory profiling between cancer and normal samples was analyzed with Biomarker Pattern software. Results Five distinct potential lung cancer biomarkers with higher sensitivity and specificity were found, with four common biomarkers in both IMAC-Cu and WCX2 chip; the remaining biomarker occurred only in WCX2 chip. Two biomarkers were up-regulated while three biomarkers were down-regulated in the serum samples from patients with non-small cell lung cancer. The sensitivities provided by the individual biomarkers were 75%-96.43% and specificities were 75%-100%. Conclusions The preliminary results suggest that serum is a capable resource for detecting specific non-small cell lung cancer biomarkers. SELDI mass spectrometry is a useful tool for the detection and identification of new potential biomarker of non-small cell lung cancer in serum.