Small cell lung cancer with peripheral neuropathy as the first symptom:Two case reports

BACKGROUND Small cell lung cancer(SCLC)is the most malignant type of lung cancer.Even in the latent period and early stage of the tumor,SCLC is prone to produce distant metastases with complex and diverse clinical manifestations.SCLC is most closely related to paraneoplastic syndrome,and some cases present as paraneoplastic peripheral neuropathy(PPN).PPN in SCLC appears early,lacks specificity,and often occurs before diagnosis of the primary tumor.It is easy to be misdiagnosed as a primary disease of the nervous system,leading to missed diagnosis and delayed diagnosis and treatment.CASE SUMMARY This paper reports two cases of SCLC with limb weakness as the first symptom.The first symptoms of one patient were rash,limb weakness,and abnormal electromyography.The patient was repeatedly referred to the hospital for limb weakness and rash for>1 year,during which time,treatment with hormones and immunosuppressants did not lead to significant improvement,and the condition gradually aggravated.The patient was later diagnosed with SCLC,and the dyskinesia did not worsen as the dermatomyositis improved after antineoplastic and hormone therapy.The second case presented with limb numbness and weakness as the first symptom,but the patient did not pay attention to it.Later,the patient was diagnosed with SCLC after facial edema caused by tumor thrombus invading the vein.However,he was diagnosed with extensive SCLC and died 1 year after diagnosis.CONCLUSION The two cases had PPN and abnormal electromyography,highlighting its correlation with early clinical indicators of SCLC.

Physical exercise reverses immuno-cold tumor microenvironment via inhibiting SQLE in non-small cell lung cancer

Dear Editor,Physical exercise has been shown to be associated with reduced cancer incidence and cancer-associated mortality[1,2],but the underlying mechanisms are obscure.Immunometabolic regulation has emerged as one of the most prominent mechanisms explaining the effects of exercise on cancer[1,2].Physical exercise primarily lowers blood cholesterol and triglycerides,and protects against cardiovascular diseases[3].However,whether physical exercise can modulate cholesterol metabolism in tumor cells is currently unknown.

Stage Ⅳ non-small cell lung cancer with multiple metastases to the small intestine leading to intussusception: A case report

BACKGROUND Gastrointestinal tract metastasis from lung cancer is rare and compared to small cell lung cancer(SCLC),non-SCLC(NSCLC)is even less likely to metastasize in this manner.Additionally,small intestinal tumors can also present with diverse complications,some of which require urgent intervention.CASE SUMMARY In this report,we detail a unique case of stage IV lung cancer,where the presence of small intestine tumors led to intussusception.Subsequent to a small intestine resection,pathology confirmed that all three tumors within the small intestine were metastases from adenocarcinoma of the lung.The postoperative follow-up period extended beyond 14 mo.CONCLUSION In patients with stage IV NSCLC,local tumor control can be achieved with various treatments.However,if small intestinal metastasis occurs,surgical intervention remains necessary,as it may improve survival.

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.

Immunological features of EGFR-mutant non-small cell lung cancer and clinical practice:a narrative review

Immune checkpoint inhibitors(ICIs)have significantly improved outcomes for patients with advanced driver-negative non-small cell lung cancer(NSCLC).However,targeted therapy remains the preferred treatment for advanced driver-positive NSCLC,including cases with epidermal growth factor receptor(EGFR)mutations.Con-sidering the variability in EGFR-mutant NSCLC,including expression levels of programmed cell death ligand 1(PD-L1),tumor mutation burden(TMB),and other immunological features,the application of immunotherapy in this group is still a subject of investigation.Therefore,we have summarized and analyzed the immunological characteristics and regulatory mechanisms of different EGFR mutations in NSCLC,as well as the current clinical application of immunotherapy in the EGFR-mutant population,to provide a reference for future research.

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.

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.

Non-platinum doublets versus single agents in non-small cell lung cancer （NSCLC） patients with elderly age and/or poor performance status： a meta-analysis

Objective： The aim of the study was to compare the efficacies and toxicities of non-platinum doublets （doublets group） with a non-platinum single agent （single-agent group） in previously untreated advanced non-small cell lung cancer （NSCLC） patients with elderly age and/or poor performance status （PS）. Methods： The PubMed database was screened. Subsequently, the hazard ratios （HRs） for overall survival （OS） and progression-free survival （PFS）, relative risks （RRs） for overall response rate （ORR） and one-year survival, and odds ratios （ORs） for the different types of toxicities were pooled using the Review Manager 5.0 package. Results： This study comprised of 1427 patients enrolled in four randomized controlled trials. The pooled HR showed that the doublet group could increase ORR （P = 0.002） with no heterogeneity （P = 0.64）, and might improve OS （P = 0.01 / P = 0.06） with heterogeneity （P 0.001）. There was no significant difference in PFS （P = 0.16） and one-year survival （P = 0.25） between two treatment groups. The doublet group led to more grade 3/4 neutropenia and thrombocytopenia than the single-agent group （P = 0.02 and P = 0.000, respectively）. The incidences of grade 3/4 anemia, vomiting, mucositis, constipation, diarrhea, neurotoxicity, allergy, and fatigue between the two treatment groups were insignificant. Conclusion： Except for neutropenia and thrombocytopenia, the non-platinum doublets could increase ORR, and might improve OS for NSCLC patients with elderly age and/or poor PS without addition of more side effects; however, the doublets showed an increased rate of neutropenia and thrombocytopenia. The addition of doublets may not improve PFS and one-year survival.

Expressions and significance of Survivin,MDR1 and MRP in non-small cell lung cancer (NSCLC)

Objective： To investigate the expressions and significance of Survivin, MDR1 and MRP in non-small cell lung cancer （NSCLC）. Methods： Immunohistochemical staining was used to detect the expressions of Survivin, MDR1 and MRP. The correlation between the results was assessed and the impact of Survivin on prognoses was also examined. Results： Survivin was expressed in 78% tissues from NSCLC patients but not found in tissues from control patients （P 〈 0.05）. The expression of Survivin was related to the tissue differentiation stage and lymph nodes metastasis of lung cancer. The mean survival time was shorter in patients with Survivin-expression than those who not. There was a significant correlation between MDR1 and Survivin （P 〈 0.05）, whereas no close correlation was found between MRP and Survivin. Conclusion： （1） Survivin is of critical importance in the development of NSCLC, thus may provide an novel therapeutic target for lung cancer; （2） MDR1 and MRP present in tissues from lung cancer synergistically with Survivin, which might be involved in turnout resistance.

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.

Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases:A case report

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.

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.

Immunotherapy for Small Cell Lung Cancer

Small cell lung cancer (SCLC) is a poorly differentiated, highly malignant neuroendocrine tumor characterized by rapid growth, aggressiveness, and easy recurrence. It is usually found in late clinical stage and the opportunity for surgery is lost. Therefore, surgery is often not used in clinical treatment. Although it is sensitive to chemoradiotherapy, it has a high recurrence rate and lacks effective treatment methods at present. Following chemotherapy and radiotherapy, immunotherapy for small cell lung cancer has become the mainstream research direction. Immunotherapy is profoundly changing the approach to cancer treatment due to its tolerable safety profile, sustained treatment response due to the production of immune memory, and effectiveness in a broad patient population. Immunotherapy for small cell lung cancer is one of the effective treatment methods for small cell lung cancer, and relevant studies are not rare, but there are still shortcomings such as intolerance of side effects and inaccurate evaluation of treatment timing. This article reviews the history of immunotherapy, the mechanism of action of immunodrugs, and the current immunodrugs used in the first-line treatment of extensive small cell lung cancer.

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.

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.

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.

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.

Activation of Toll-like receptors signaling in non-small cell lung cancer cell line induced by tumor-associated macrophages

Background： Inflammation is often linked with the progress and poor outcome of lung cancer. The understanding of the relationship between tumor-associated macrophages （TAMs） and lung cancer cells involves in the underlying mechanism of inflammatory cytokine production. Toll-like receptors （TLRs） are engaged in promoting the production of pro-inflammatory cytokines and play an important role in tumor immunology. Methods： To investigate the mechanisms by which TAMs influence the production of pro-inflammatory cytoldnes in lung cancer cells, we established an in vitro coculture system using TAMs and human non- small cell lung cancer （NSCLC） cell line SPC-A1. Levels of interleukin （IL）-113, IL-6 and IL-8 in SPC-A1 were evaluated by RT-PCR and cytometric bead array assay after being cocultured with TAMs. Expression changes of TLRs and TLRs signaling pathway proteins in SPC-Al were further confirmed by RT-PCR and western blot. The level changes of IL-1β, IL-6 and IL-8 in SPC-Al were also detected after the stimulation of TLRs agonists. Results： We found that the phenotype markers of TAMs were highly expressed after stimulating human monocyte cell line THP-1 by phorbol-12-myristate-β-acetate （PMA）. Higher mRNA and supernate secretion levels of IL-1β, IL-6 and IL-8 were detected in SPC-A1 after being eocultured with TAMs. We also found that TLR1, TLR6 and TLR7 were up-regulated in SPC-A1 in the coculture system with TAMs. Meanwhile, TLRs signaling pathway proteins were also significantly activated. Moreover, pre-treatment with agonist ligands for TLR1, TLR6 and TLR7 could dramatically promote inductions of IL-1β, IL-6 and IL-8. Conclusions： These findings demonstrated that TAMs may enhance IL-1β, IL-6 and IL-8 expressions via TLRs signaling pathway. We conclude that TAMs contribute to maintain the inflammation microenvironment and ultimately promote the development and progression of lung cancer.

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.