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Somatic mutations of STK11 or KEAP1 are associated with poor clinical outcomes for advanced non-small-cell lung cancer (aNSCLC) patients receiving immune checkpoint inhibitors (ICIs), chemotherapy, or targeted therapy. Which treatment regimens work better for STK11 or KEAP1 mutated (SKmut) aNSCLC patients is unknown. In this study, the efficacy of atezolizumab versus docetaxel in SKmut aNSCLC was compared. A total of 157 SKmut aNSCLC patients were identified from POPLAR and OAK trials, who were tested by blood-based FoundationOne next-generation sequencing assay. Detailed clinical data and genetic alterations were collected. Two independent cohorts were used for biomarker validation (n = 30 and 20, respectively). Median overall survival was 7.3 months (95% confidence interval [CI], 4.8 to 9.9) in the atezolizumab group versus 5.8 months (95% CI, 4.4 to 7.2) in the docetaxel group (adjusted hazard ratio [HR] for death, 0.70; 95% CI, 0.49 to 0.99; P = .042). Among atezolizumab-treated patients, objective response rate, disease control rate, and durable clinical benefit were higher when blood tumor mutation burden (bTMB) and PD-L1 being higher (biomarker 1, n = 61) or with FAT3 mutation-positive tumors (biomarker 2, n = 83) than otherwise. The interactions for survival between these two biomarkers and treatments were significant, which were further validated in two independent cohorts. In SKmut patients with aNSCLC, atezolizumab was associated with significantly longer overall survival in comparison to docetaxel. Having FAT3 mutation or high TMB and PD-L1 expression potentially predict favorable response in SKmut patients receiving atezolizumab.

Summary In mammalian cells, histone deacetylase (HDAC) and Sirtuin (SIRT) are two families responsible for removing acetyl groups from acetylated proteins. Here, we describe protein deacetylation coupled with deacetylimination as a function of lysyl oxidase (LOX) family members. LOX-like 3 (Loxl3) associates with Stat3 in the nucleus to deacetylate and deacetyliminate Stat3 on multiple acetyl-lysine sites. Surprisingly, Loxl3 N-terminal scavenger receptor cysteine-rich (SRCR) repeats, rather than the C-terminal oxidase catalytic domain, represent the major deacetylase/deacetyliminase activity. Loxl3-mediated deacetylation/deacetylimination disrupts Stat3 dimerization, abolishes Stat3 transcription activity, and restricts cell proliferation. In Loxl3 −/− mice, Stat3 is constitutively acetylated and naive CD4 + T cells are potentiated in Th17/Treg cell differentiation. When overexpressed, the SRCR repeats from other LOX family members can catalyze protein deacetylation/deacetylimination. Thus, our findings delineate a hitherto-unknown mechanism of protein deacetylation and deacetylimination catalyzed by lysyl oxidases.

Background Severe malignant airway obstruction (SMAO) is a life-threatening form of non-small cell lung carcinoma (NSCLC). Objectives To determine the efficacy and safety of para -toluenesulfonamide (PTS) intratumoral injection in NSCLC-SMAO. Methods Ninety patients with NSCLC-SAO received repeated courses of PTS intratumoral injection until tumor sizes had reduced by 50% or greater. Primary endpoint was objective alleviation rate, assessed by chest computed tomography (CT) and bronchoscopy, at day 7 and 30 following final dosing. Secondary endpoints included airway obstruction, spirometry, quality-of-life and survival time. Results In full-analysis set ( N =88), using RECIST criteria, PTS treatment resulted in a significant objective alleviation rate [chest CT: 59.1% (95%CI: 48.1%–69.5%), bronchoscopy: 48.9% (95%CI: 38.1%–59.8%) at day 7; chest CT: 43.2% (95%CI: 32.7%–54.2%), bronchoscopy: 29.6% (95%CI: 20.3%–40.2%) at day 30]. There was a remarkable increase in FVC (mean difference: 0.35 liters, 95%CI: 0.16–0.53 liters), FEV 1 (mean difference: 0.27 liters, 95%CI: 0.07–0.48 liters), Baseline Dyspnea Index (mean difference: 64.8%, 95%CI: 53.9–74.7%) and Functional Assessment of Cancer Therapy-Lung Cancer Subscale (mean difference: 6·9, 95%CI: 3.8-9.9) at day 7 post-treatment. We noted significantly reduced prevalence of atelectasis (by 42.9%) and Eastern Cooperative Oncology Group physical performance scale (mean difference: 7.2, 95%CI: 3.9–10.5). Median survival time was 394 days in full-analysis set and 460 days in per-protocol set. Adverse events were reported in 64.0% of subjects. Seven severe adverse events (7.9%) were reported, of which three led to death (drug-related in one case). Conclusion PTS intratumoral injection is effective and well tolerated for palliative therapy of NSCLC-SMAO.

The notable clinical success of cancer immunotherapy using checkpoint blockade suggests that it is likely to form the foundation of curative therapy for many malignancies. However, checkpoint blockades do not achieve sustained clinical response in most patients and thus amounts of problems needed to be figured out. Regarding these challenges, the 2017 Chinese Lung Cancer Summit expert panel organized a forum on the 14th Chinese Lung Cancer Summit to formally discuss these controversies. Five consensuses finally were reached to guide the application of checkpoint blockades.

BaoHui Han,1 LuLu Yang,2 Xin Wang,3 LuanDi Yao2 1Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Lilly Suzhou Pharmaceutical Co. Ltd, Shanghai, People’s Republic of China; 3Asia Pacific Statistical Sciences, Lilly China Drug Development and Medical Affairs Centre, Shanghai, People’s Republic of China Abstract: Pemetrexed-based chemotherapy regimens (pem regimens) are the standard first-line treatment option in patients with non-squamous non–small cell lung cancer (NSCLC). The objective of this systematic review was to assess the efficacy of pemetrexed in the context of epidermal growth factor receptor (EGFR) mutation-positive NSCLC following the failure of EGFR–tyrosine kinase inhibitor (TKI) treatment. We searched biomedical literature databases (PubMed, EMBASE, and the Cochrane library) and conference proceedings for studies evaluating the efficacy of pemetrexed monotherapy or pemetrexed combined with platinum or any other chemotherapeutic agent in EGFR–mutation-positive NSCLC after EGFR-TKI failure. We extracted data of primary outcomes of interest (progression-free survival [PFS], overall survival [OS], and overall response rate [ORR]). The weighted median PFS, OS, and ORR were then calculated. Of 83 potentially relevant studies, eight (three randomized studies and five retrospective studies) were identified (involving 1,193 patients) and included in this systematic review, with 640 patients receiving pem regimens. The weighted median PFS, median OS, and ORR for patients treated with pem regimens were 5.09months, 15.91months, and 30.19%, respectively. Our systematic review results showed a favorable efficacy profile of pem regimens in NSCLC patients with EGFR mutation after EGFR–TKI failure. Keywords: pemetrexed, advanced non–small cell lung cancer, epidermal growth factor receptor, tyrosine kinase inhibitor&nbsp

Platinum-based chemotherapy is an important treatment for non-small cell lung cancer. However, the effectiveness of the treatment varies among the patients. We investigated the association between DNA polymorphisms of the autophagy pathway and responses of such treatment among 1004 Chinese patients. Ninety-nine SNPs located on 13 genes of the autophagy pathway were genotyped and assessed for their association with clinical benefit, progression-free survival (PFS) and overall survival (OS). The results showed that rs7953348 (GA) (P=0.017, OR: 0.67, 95%CI: 0.49-0.93) and rs12303764 (AC) (P=0.009, OR: 0.63, 95%CI: 0.45-0.89) at the ULK1 gene, and rs17742719 (CA) (P=0.002, OR: 1.83, 95%CI: 1.26-2.66), rs8003279 (AG) (P=0.006, OR: 1.65, 95%CI: 1.16~2.35) and rs1009647 (GA) (P=0.002, OR: 1.70, 95%CI: 1.22-2.37) at the ATG14 gene were associated with clinical benefit. Polymorphisms at rs7955890 (GA) (P=0.004, HR: 0.63; 95%CI: 0.46-0.86) and rs17032060 (GA) (P=0.006, HR: 0.65, 95%CI: 0.48-0.88) at the DRAM gene, and rs13082005 (GA) (P=0.012, HR: 1.27, 95%CI: 1.05-1.53) at the ATG3 gene were significantly associated with PFS. We also found that rs7953348 (GA) (P=0.011, HR: 0.74, 95%CI: 0.58-0.93) at the ULK1 gene and rs1864183 (GA) (P=0.016, HR: 0.42, 95%CI: 0.21-0.85) at the ATG10 gene were associated with OS. Thus, the study demonstrated that the autophagy pathway might play important role(s) in platinum-based chemotherapy. DNA polymorphisms in its component genes can potentially be predictors for clinical responses of platinum-based chemotherapy among the patients with non-small lung cancer.

Objective To investigate resistance and safety of HHPG–19K in treating non–small cell lung cancer patients. Methods A total of 30 cases were selected and randomly divided into 5 groups: three HHPG–19K groups of different dosage (60 μg/kg/day, 100 μg/kg/day, 200 μg/kg/day), positive control group (Filgrastim, namely G–CSF5 μg/kg/day) and negative control group. Safety indexes of 5 groups were observed and compared. Results All patients had adverse event (100%) in three HHPG–19K groups, and increased ALP, ALT and AST were main events. The degree was mild to moderate. There was no significant difference in the incidence of adverse event between dosage groups and positive control group no difference. But the incidence of negative control group was 13%, which was significantly lower than dosage groups and positive control group. Conclusions non–small cell lung cancer patients have satisfactory tolerance to HHPG–19K, and have no resistance. Besides, dosage at 100 μ g/kg is the most safe.

No standard therapy for pulmonary epithelioid hemangioendothelioma (PEH) has yet been established due to the rarity of the disease, the lack of clear standards for treatment and the partial-to-complete spontaneous regression. This report describes three cases of PHE manifested as bilateral intrapulmonary masses with an initial diagnosis conducted by thoracoscopic lung biopsy. These patients demonstrated a partial response to combination chemotherapy with carboplatin, paclitaxel, bevacizumab or endostar, and an improvement in clinical status. Furthermore, we reviewed the literature regarding such patients who received chemotherapy and immunotherapy; this indicated that patients with PEH demonstrated a good partial response to chemotherapy with carboplatin, paclitaxel, bevacizumab, thalidomide and α-interferon. Overall, combination chemotherapy regimens may hold therapeutic potential for the treatment of this rare disease.

A quantum gas of ultracold molecules, with long-range and anisotropic interactions, will enable a series of fundamental studies in physics and chemistry. In particular, samples of ground-state molecules at ultralow temperatures and high number densities will facilitate the explorations of a large number of many-body physical phenomena and applications in quantum information processing. However, due to the lack of efficiently cooling techniques such as laser cooling for atomic gases, high number densities for ultracold molecular samples are not readily attainable. Associating ultracold atoms to weakly bound dimer molecules via Feshbach resonance and subsequently transferring them to a wanted molecular ro-vibronic ground state by a stimulated Raman adiabatic passages (STIRAP) have proved to be an effective way in producing ideal ultracold molecular samples. As a typical illustration, in a recent study (2010 Nat. Phys. 6 265) Danzl et al. experimentally realized the preparation of Cs2 molecule into its ro-vibronic ground state via two different multi-level STIRAPs:one is based on a single conversion route and the others are based on a cascade-connected route (labeled by 4p-STIRAP and s-STIRAP, respectively). In this work, we present a theoretical study for these two STIRAP schemes, focusing on the differences in physical principle and realistic performance between them. On the one hand, according to the theoretical approach of quasi-dark eigenstates, we conclude that a highly efficient population transfer is achievable in both schemes. On the other hand, by systematically studying the influences of the relevant parameters, including the spontaneous decays and the detunings from the intermediate states, and the temporal sequence and the amplitude of the laser pulses, we disclose their respective advantages and weaknesses in the realistic implementation. We theoretically predict that for both schemes their maximal conversion efficiencies each can attain 0.97 as long as the spontaneous decays from the intermediate excited states are sufficiently suppressed. Yet considering the fact that the already implemented efficiency is only around 0.6 for both schemes, there is still room for optimization, e.g. using stable Rydberg energy levels in future experiment. Furthermore, the success of these two schemes can provide a new route to the controllable entanglement preparation, opening more applications in the fields of quantum logic gate and so on.

Objective: To evaluate the association of S100A4 levels with the prognosis of lung cancer (LC). Methods: The RevMan 5.0 software was utilized to perform literature retrieval, data collection, and statistical analysis according to its guidelines. Literature-based searching was guided to gather data, and the fixed-effect model was used to pool the hazard ratio (HR) in this study. Results: A total of 10 eligible studies that included 1364 LC patients were analyzed. About 72.6% of patients had positive expression of S100A4 according to the criteria defined by the authors. The HR of positive expression for overall survival (OS) was 1.30 times of that of negative expression in LC patients (HR=1.30, 95% confidence interval: 1.04 to 1.61, p=0.02). Conclusion: Patients with positive expression of S100A4 appear to have a poorer OS compared with those with negative expression of S100A4.

Introduction Since February 2013, a novel reassortant H7N9 virus associated with human deaths, but no apparent outbreaks in poultry and wild birds has emerged in eastern China. Objectives The potential reemergence of H7N9 during next year's influenza season demand a further understanding of this important disease. Methods Between March 1 and April 30, 2013, we obtained and analyzed clinical, epidemiologic and radiologic features, and virologic data from three laboratory‐confirmed patients of A H7N9 infection admitted in Shanghai Ruijin Hospital. Results All patients were middle to old aged (mean age 62 years) and overweight (mean body mass index 31) patients. Two patients were exposed to poultry directly or indirectly in food market. They presented with fever and rapidly progressive pneumonia that did not respond to antibiotics. Time between onset of symptoms and onset of respiratory failure (days) were 7–11 days. Two patients presented secondary invasive bacterial infections. All patients died on day 7 to day 86 after the onset of symptoms. Conclusions Cross species poultry‐to‐person transmission of this new reassortant avian influenza H7N9 virus can result in severe and fatal respiratory disease like acute respiratory distress syndrome (ARDS) in humans. Reduplicate chest imaging examination is suggested for risky patients with fever and dyspnea. Secondary invasive bacterial infections and pneumothorax can cause severe and fatal consequence. Old age, obesity and presence of comorbidity may be associated with increased mortality. Pulmonary fibrosis can be seen at late stage of the disease.

Sunitinib is an oral multitargeted tyrosine kinase inhibitor (TKI) exhibiting antiagiogenic and antitumor effects.To evaluate the efficacy and potential toxicity of sunitinib therapy in advanced non-small cell lung cancer (NSCLC) patients in China.From January 2009 to August 2011, 30 patients with stage IV NSCLC, who were pretreated with the epidermal growth factor receptor (EGFR)-TKIs and then received sunitinib, were retrospectively reviewed. Univariate and multivariate Cox proportional hazard regression analysis was performed to determine the potential prognostic risk factors influencing NSCLC survival.The median progression-free survival (PFS) and median overall survival (OS) of all 30 treated patients was 1.25 months [95% confidence interval (CI): 0.90-1.9 months] and 3.40 months (95% CI: 3.00-6.80 months), respectively. Cox regression analysis suggested that Eastern Cooperative Oncology Group (ECOG) performance status (PS) is predictive of both PFS (P=0.001) and OS (P0.001). Common adverse events (AEs) included hand-foot syndrome (53.3%), mucositis (40.0%), rash (36.7%) and diarrhea (33.3%).No sign of overall clinical benefits of sunitinib was detected in patients with pretreated EGFR-TKIs. Most patients suffered AEs from mild to moderate severity. ECOG PS is highly associated with PFS and OS rate. Further studies in NSCLC are required to determine whether sunitinib is beneficial nor not.

To evaluate real-time endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of intrapulmonary lesions.From October 2009 to November 2011, EBUS-TBNA was performed in 78 patients with parabrachial or parabronchial intrapulmonary lesions proved by CT scan. On-site cytological evaluation was not performed. Immunohistochemistry was applied to distinguish the type of malignant tumor when necessary.Sixty-five malignancies and 13 benign diseases were finally diagnosed in 78 intrapulmonary lesions, of which 62 malignancies and 13 benign diseases were distinguished by EBUS-TBNA, including 61 primary lung cancer (adenocarcinoma 36, squamous carcinoma 8, poorly-differentiated carcinoma 5, unknown type carcinoma 3, small cell carcinoma 9), one metastatic lung cancer, 7 pulmonary inflammation, 5 pulmonary tuberculosis and one fibrosis. There were 3 false negative cases which were diagnosed as pulmonary poorly-differentiated carcinoma, pulmonary sarcomatoid carcinoma and pulmonary lymphoma, respectively. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of EBUS-TBNA in distinguishing malignant from benign thoracic lesions was 95%, 100%, 81%, 100%, 96%, respectively. Immunohistochemistry was performed in 8 malignant tumors without definite type or origin, 5 primary lung cancer and one metastatic lung adenocarcinoma were further confirmed. Moderate bleeding from the puncture site during needle aspiration forming blood clot and obstructing the central airway was noted in 1 hypercoagulable subject.EBUS-TBNA is a minimally invasive, safe procedure with high sensitivity for distinguishing malignant from benign lesions. Immunohistochemistry can provide evidence for the definitive diagnosis of malignant lesions.

To analyze the efficacy and quality of life and safety for paclitaxel and carboplatin (TC) and TC combined with endostar in the treatment of advanced non-small cell lung cancer (NSCLC).This is a prospective, multicenter, randomized, double-blind, placebo-controlled clinical study. A total of 126 cases of untreated advanced NSCLC were enrolled in this study. There were 63 patients in the TC control arm and TC combined endostar arm, respectively. All enrolled patients were continuously followed-up for disease progression and death.The objective response rate (ORR) of TC combined with endostar arm was 39.3%, and that of TC control arm was 23.0%, P = 0.078. The progression-free survival rates for TC combined with endostar arm and TC control arm were 78.3% and 58.8%, respectively, in 24 weeks (P = 0.017). The hazard ratio for the risk of disease progression was 0.35 (95%CI 0.13 to 0.90, P = 0.030). The median time to progression (TTP) of the TC combined with endostar arm was 7.1 months and TC arm 6.3 months (P0.05). The follow-up results showed that the median survival time (mOS) of the TC + Endostar arm was 17.6 months; (95%CI 13.4 to 21.7 months), and the TC + placebo arm 15.8 months (95%CI 9.4 to 22.9 months) (P0.05). The quality of life scores (LCSS patient scale) after treatment of the TC combined with endostar arm was improved, and that of the TC group was improved after completion of two cycles and three cycles of treatment. The quality of life scores compared with baseline after the completion of one cycle treatment was significantly improved for both the TC combined with endostar arm (P = 0.028 and), and TC arm (P = 0.036). It Indicated that TC combined with endostar treatment improved the patient's quality of life in the early treatment. The difference of adverse and serious adverse event rates between the two groups was not significant (P0.05).Compared with TC alone treatmrnt, TC combined with endostar treatment can reduce the risk of disease progression at early time (24 weeks), increase the ORR, and can be used as first-line treatment for advanced NSCLC. The TC combined with endostar treatment has good safety and tolerability, improves the quality of life, and not increases serious adverse effects and toxicity for patients with advanced NSCLC.

To investigate the clinicopathological features of patients with lung cancers associated with epidermal growth factor receptor (EGFR) gene amplification and/or mutations.Mutations and amplification status of EGFR gene were detected by PCR-DNA sequencing and FISH, respectively, followed by subsequent clinicopathological correlative studies.Among 454 patients, the overall mutation rate of EGFR was 48.2% (219/454). The EGFR mutation rate in females was significantly higher than that of males, 59.6% (118/198) vs. 39.5% (101/256), P0.001. The mutation rate of EGFR gene of non-smokers was higher than that of smokers, 52.7% (147/279) vs. 41.4% (72/175), P=0.017. The mutation rate in patients with adenocarcinoma was higher than that in patients with other cancer types, 56.8% (193/340) vs. 22.8% (26/114), P0.05. Moreover, a significant difference of mutation rates among different subtypes of adenocarcinomas was found (P=0.001). Among 134 patients with available FISH analysis, no statistical significance of EGFR gene amplification was found in age, gender, histopathological types and subtypes of adenocarcinomas (P0.05). There was a significant correlation between EGFR mutation and its gene amplification (P=0.0005), although with poor consistency (P=0.275).EGFR gene mutations occur more frequently in females, non-smokers and patients with adenocarcinoma subtype. A significant variation of the mutation types exits among the subtypes of adenocarcinoma. The presence of EGFR amplification appears not related to age, gender, histopathological types of lung cancer and subtypes of adenocarcinoma. There is a significant correlation between EGFR mutations and its gene amplification (P=0.0005), although with poor consistency.

To assess the therapeutic efficacy of treating advanced non-small cell lung cancer (NSCLC) in the aged by Chinese medicine (CM) adopting the international questionnaire of quality of life (QOL).91 aged patients with advanced NSCLC were randomly assigned to three groups. There were 31 in the CM group (Group I), 30 in the chemotherapy group (Group II), and 30 in the CM and chemotherapy combination group (Group III). Oral administration of CM decoction and intravenous dripping of Chinese patent medicine was given to those in Group I. Patients in Group II received chemotherapeutic protocol alone. Patients in Group III received chemotherapeutic protocol while orally taking CM decoction. Twenty-eight days were taken as one therapeutic course, and two courses in total. Assessment was performed using European Organization for Research and Treatment of Lung Cancer Quality of Life Questionnaire LC-43 (EORTC QLQ-LC43) before treatment, the 10th day of the second therapeutic course, and the 28th day of the second therapeutic course, respectively.After two therapeutic courses of treatment, compared with Group II, better effects were obtained in Group I and Group III in the aspects of the physical function, roles function, emotional functions, social functions, general health state, and short breath, cough, fatigue, insomnia, poor appetite, and constipation (P0.05, P0.01).CM therapy could relieve the clinical symptoms of aged patients with advanced NSCLC and improve their QOL.

To evaluate the diagnostic yield and the safety of endobronchial ultrasound-guided transbronchial needle biopsy (EBUS-TBNA) in mediastinal and hilar lymph nodes and lung tumors.EBUS-TBNA was performed in 70 patients with thoracic masses or mediastinal-hilar lymphoadenopathy proved by CT scan.From July 2009 to January 2010, 70 patients were included in the study. EBUS-guided TBNA was performed to obtain samples from mediastinal and hilar lymph nodes (120 stations) and lung tumors (11 masses). In 46 cases of newly diagnosed lung cancer, 44 were confirmed by EBUS-TBNA without on site cytology assistance, with 2 false negative cases. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EBUS-TBNA in the diagnosis of lung cancer were 96%, 100%, 100%, 92% and 97% respectively. Non-caseous granuloma formed by epithelioid cells was found in EBUS-TBNA histological specimen from 5 out of 10 patients with clinically diagnosed sarcoidosis. TBNA cytological smear showed acid-fast bacilli and histology of the lymph node demonstrated coagulatory necrosis from 1 out of 4 tuberculous cases. The procedure was uneventful, and there were no complications.EBUS-TBNA is an effective and safe method for the diagnosis of bronchogenic carcinoma and unknown mediastinal-hilar lymphadenopathy.

To study the effects and possible mechanisms of the protein kinase C (PKC) inhibitor chelerythrine chloride (CH), combined with cisplatin (DDP) on human non-small cell lung cancer.The effect of CH, DDP and the combination on proliferation and apoptosis of human lung cancer cell line A549 were evaluated by MTT assay and flow cytometry respectively. The inhibitory effects of CH and DDP on neoplasia were verified on subcutaneous implanted tumor of nude mice. Implanted tumor models were constructed in nude mice using human lung adenocarcinoma cell line A549. Twenty-four BALB/c nude mice with implanted tumors were divided into 4 groups randomly: group CH, group DDP, group CH + DDP, and normal saline group (group NS), each with 5 mice. CH, DDP or NS were intraperitoneally injected into nude mice for 3 weeks (DDP or NS was injected once a week, CH was injected twice a week).CH inhibited A549 cell proliferation in a concentration-dependent pattern. When CH and DDP were combined, the inhibitory effect was enhanced in a synergistic or additive pattern. Both CH and DDP significantly increased the apoptosis of A549 cells, and this action was remarkably increased when DDP was combined with CH. CH and DDP inhibited the growth of subcutaneous implanted tumor in nude mice and the inhibitory rate of group CH + DDP (80.5%) was significantly higher than that of group CH (72.4%) or group DDP (64.3%) (t = 11.34, P0.01).CH combined with DDP shows significantly synergistic anti-tumor effects on non-small cell lung cancer cell line A549 and subcutaneous implanted tumor in nude mice, possibly by enhancement of growth inhibition and apoptosis induction on tumor cells.

To detect the cancer stem cells and to evaluate their prognostic implication in patients with lung adenocarcinoma.Three phenotypic markers of cancer stem cells (SP-C, CCSP and OCT4) in lung adenocarcinoma were detected by immunofluorecence staining. The correlation among the clinicopathological parameters and phenotypes of cancer stem cells as well as survival were analyzed by Cox proportional hazard method.Of the 57 cases, cancer stem cells were detected in 52, including OCT4(+) bronchioloalveolar stem cell (BASC) phenotype (SP-C(+) CCSP(+) OCT4(+)) in 40 cases and OCT4(-) BASC phenotype (SP-C(+) CCSP(+) OCT4(-)) in 12 cases. Statistical analysis revealed that the phenotype of cancer stem cells was related with the cellular differentiation, i.e. the OCT4(+) BASC phenotype occurred more frequently in the well-differentiated tumors, while the OCT4(-) BASC phenotype usually presented in most of the poorly-differentiated ones. Cox analysis showed that the OCT4(+) BASC phenotype was one of prognostic factors.The lung adenocarcinoma stem cells have phenotypic features of bronchioalveolar stem cells (SP-C(+) CCSP(+)). The expression of self-renewal regulatory gene OCT4 in these cells indicates an aggressive nature and unfavorable prognosis.

To evaluate the efficacy, median time to progression (TTP), quality of life and toxicity in the patients with advanced non-small cell lung cancer (NSCLC), treated with thalidomide plus vinorelbine and cisplatin (NP) or NP alone.Sixty six patients with advanced NSCLC were divided randomly into two groups, the trial and control groups. The trial group was treated with vinorelbine 25 approximately 30 mg/m(2) i.v. on D1 and D8, cisplatin 70 approximately 80 mg/m(2) i.v. on D1 (NP regimen), and thalidomide 200 mg orally and daily from D1. The control group received vinorelbine and cisplatin as above described.Of 66 assessable patients, the overall response rate was 51.5% in the trial group and 36.4% in the control group (P = 0.22). The median TTP was 6.0 months for the trial group, and 3.6 months for the control group (P0.001). The score of quality of life in trial group was higher than that in the control group, but no significant difference was observed between the two groups (P0.05). There were no significant differences in toxicities between the two groups (P0.05).NP regimen combined with thalidomide can significantly prolong the median time to tumor progression in patients with advanced NSCLC. Thalidomide may have a synergic activity with NP regimen without increased toxicities.

To analyze the incidence and profile of mutations in epidermal growth factor receptor (EGFR) in Chinese patients with non-small cell lung cancer (NSCLC).A total of 176 cases of NSCLC tissue was enrolled in this study, among which 123 normal lung samples were also included. The tissue DNA was extracted and the EGFR gene in exon 19 to 21 was subjected for PCR amplification and direct sequencing.The EGFR gene in exon 19-21 was of wild type in all normal lung tissues detected. Mutations were found in 57 cases of 176 lung cancer samples, with an incidence of 32. 4%. Mutations were mainly detected in the exon 19 (37/57 cases, 64. 9% ) and exon 21 (18/57 cases, 31. 6% ) , while that in the exon 20 was rare (2/57 cases, 3. 5% ). There were 7 types of EGFR mutation in the exon 19, resulting in the deletion of codon 746 to 753. A missense mutation was detected in exon 20, dealing with codon 789 to 793. The mutation in exon 21 belonged to the single missense substitution in codon 858. The EGFR mutations were more frequent in female patients than male ones, in adenocarcinoma and adenosquamous cell carcinoma versus cancer of other histologies.EGFR mutation is a tumor-specific somatic abnormality. Some one third of Chinese NSCLC tumors harbor EGFR mutations, especially in exons 19 and 21. These mutations are more frequently detected in female, adenocarcinoma and adenosquamous cell carcinoma.

To evaluate the effect of Feiji Recipe (FJR) on quality of life (QOL) of patients with non-small cell lung cancer (NSCLC).One hundred and two patients with NSCLC were randomly assigned into 2 groups. The 61 patients in the combined treated group were given FJR and chemotherapy and the 41 patients in the control group were treated with chemotherapy alone. They were observed for two treatment courses with QOL estimated by EORTC QLQ-C43 questionnaire and FACT-L questionnaire, the two international questionnaires as the tools for measurement, and referred to the traditional evaluating indexes of clinical efficiency.QOL in the combined treated group was improved after treatment with the improvement of scores in all domains, including functional and symptom sub-domain, while it in the control group deprived significantly, showing significant difference between the two groups (P0.05). Similar results were also shown in the evaluation of physical performance by Eastern Cooperative Oncology Group (ECOG) and Karnovfsky performance scoring. The gastrointestinal reaction and myelo-suppression were slighter in the combined treated group than those in the control group (P0.05), and no significant difference was shown between the response rate of the two groups (P0.05).FJR can improve QOL of patients with NSCLC, reduce the adverse reaction of chemotherapy, and improve patients' physical performance.

To clarify whether functionally competent dendritic cells (DC) can be generated from malignant pleural effusion in patients with lung cancer.Malignant effusion-associated monocytes were separated by adherence from malignant effusion-associated mononuclear cells and cultured in medium with granulocyte macrophage colony-stimulating factor (GM-CSF) plus interleukin 4 (IL-4). TNF-alpha was added for the last 24 h before culture termination. Cultured DC were identified by (1) using microscopy, scanning electron microscopy, and immunocytochemistry for the morphological features; (2) phenotypic markers; and (3) functional characteristics including a high stimulatory capacity to activate proliferation of lymphocyte in an allogeneic mixed leukocyte reaction and the ability to produce high levels of IFN-gamma.Cultured DC had the typical morphological features. The phenotype of DCs generated from effusion showed higher expression of CD(86) (84.6 +/- 6.1)%, HLA-DR (81.1 +/- 13.0)%, CD(40) (42.0 +/- 21.7)%, CD(1a) (20.0 +/- 9.5)% and lower expression of CD(14) (4.8 +/- 3.5)% than the control group. There was a significant difference in the stimulatory activity in allogeneic lymphocyte proliferation and the ability to produce high levels of IFN-gamma between DC derived from the malignant effusion and the control group.These findings suggest that DC can be generated from malignant pleural effusion, which might be a useful source of DC for immunotherapy.

To evaluate the relationship of micrometastatic cancer cells in the blood and prognosis of patients with non-small cell lung cancer (NSCLC).Blood samples were collected from peripheral vein perioperatively and from the pulmonary vein intraoperatively in NSCLC patients. Cancer cells were detected by flow cytometry, as described previously. The patients were followed up and analyzed statistically.Cancer cells in blood samples were detected in 20 of 58 patients (34.5%). Patients under 57 years of age or with stage III/IV lesions had higher positive findings than those over 57 years or with stage I/II lesions (P = 0.000 and 0.006, respectively). On the basis of 40 month follow-up data, the 2- and 3-year survival rates of patients with positive and negative results were 30.0% vs 20.0%, and 52.6% vs 50.0%, respectively. There was significant difference between the overall survival curves which favored patients with negative findings (P = 0.0291 and 0.0092, respectively).This study indicates that cancer cells can be detected in the blood perioperatively from NSCLC patients which means poor prognosis.

A number of studies had evaluated the benefit of neoadjuvant chemotherapy combined surgery on stage IIIa-IIIb NSCLC, survival benefit was found in several papers. We attempt to evaluate the survival and prognosis of cisplatinum-based schedule as peri-operative CT for resectable stage I-IIIa NSCLC.A prospective, randomized, multicenter study was conducted by Shanghai Lung Cancer Team (supported by Shanghai Branch of Discipline Foundation) since 1995-1997 for 211 cases of stage I-IIIa NSCLC with curative resection (99 stage I, 47 stage II, 65 stage III), age ofor= 75, KPSor= 80, staged by 1997 AJC TNM Criteria. They were randomized to be 103 cases with 1 - 2 cycles of pre-operative CT and 108 cases with no pre-operative CT, 2 - 4 cycles of post-operative CT were used for stage II and stage IIIa NSCLC, it was totally 4 cycles of MVP or MOP CT schedule each case. Follow-up team had been trained, the follow-up rate should beor= 95%, last follow-up date was March of 2002. Lobectomy was performed for most patients. Accumulated survival, log rank, MST, Cox uni-variance and multi-variance analyses were used as statistics for evaluation.The two arms were well balanced for baseline demographic and clinical characteristics (P0.05 for all). Stage I NSCLC had the best year-survival in whole patients. No statistical survival difference was found between the group with pre-op CT and with no pre-op CT, P = 0.074, 0.087 and 0.097, respectively, 5-year survival rates were of 31.98%:36.68%. In various stage, a statistical survival difference was only shown in stage IINSCLC, P = 0.042, 5-year survival rates and MST were worse in the group with pre-operation CT, 20%:65.2% and 24 months:48 months, respectively, but no difference was seen in stage I and stage IIIa NSCLC. Stage and post-operation CT were the only two meaningful parameters with statistical survival difference calculated by multi-variance analyses, P = 0.000 all, but no difference was found in others 4 parameters (age, sex, type and pre-operation CT). The response rate of pre-operation CT was of 50%. Though there was no statistical difference, the responders were with slightly better year-survival rates than MR + NR patients, 38.9% and 33.3%, respectively. In the cases with pathological "T" down stage and "T" unchanged after pre-operation CT had a better yr-survival rates than "T" up-stage, P = 0.03, 5-year survival rates were of 41.67%, 40.51% and 11.76%, respectively, thus, effective chemotherapy might be beneficial to survival. Besides, in the cases withor= 3 cycles of post-operation CT have better survival rates than less cycles.A prospective, randomized, multicenter peri-operation CT study for stage I-IIIa NSCLC conducted in Shanghai, China., it showed there had no benefit in survival between with pre-operation CT arm and with no pre-operation CT arm. In stage II NSCLC, pre-operation CT cases had a worse year-survival than with no pre-operation CT, P = 0.042, but no difference was seen in stage I and stage IIIa NSCLC. The responder of CT and "T" down stage, "T" unchanged had better survival rates than those of not response and "T" up-stage. From multivariate analyses, stage and post-operation CT were the two meaningful parameters to year-survival,or= 3 - 4 cycles of post-operation CT had a better statistical higher year-survival than less cycles. Nutrition, supportive treatment, immunity status and prevention of toxicity might be the next study worthy to conduct, for CT combined with OP.