Efficacy and safety of second-line camrelizumab combined with apatinib and chemotherapy in patients with advanced lung adenocarcinoma: A prospective, open-label, multicentric study.

OBJECTIVES: Camrelizumab (a programmed cell death protein 1 inhibitor) and apatinib (an angiogenesis inhibitor) are considered as potential treatments for advanced lung adenocarcinoma (LUAD). This study aimed to evaluate the efficacy and safety of second-line camrelizumab combined with apatinib and chemotherapy (albumin-bound paclitaxel, docetaxel, or pemetrexed) in patients with advanced LUAD. METHODS: Twenty-nine patients with advanced LUAD underwent second-line camrelizumab combined with apatinib and chemotherapy were enrolled in this prospective, open-label, multicentric study. Follow-up with a median duration of 18.0 months was conducted. RESULTS: There were 0 (0.0 %), 11 (37.9 %), 14 (48.4 %), and 3 (10.3 %) patients achieving complete response, partial response, stable disease, and progressive disease, respectively. Meanwhile, treatment response was not evaluated in 1 (3.4 %) patient. The objective response and disease control rates were 37.9 % and 86.3 %, respectively. In terms of survival, the median (95 % confidence interval) progression-free survival (PFS) was 11.1 (5.2-17.0) months, with 1-year and 2-year PFS rates of 40.4 % and 20.5 %, respectively. The median overall survival (OS) was not reached; the 1-year and 2-year OS rates were 72.0 % and 64.8 %, respectively. Current treatment cycles ≥ 8 were associated with better PFS and OS (both P < 0.001). In addition, 21 (72.4 %) patients experienced at least one treatment-emergent adverse event (TEAE), which was mostly of grade I and II. The most commonly occurring TEAE was leukopenia (17.2 %), liver dysfunction (17.2 %), hypothyroidism (13.8 %), hand-foot syndrome (13.8 %), and thrombocytopenia (13.8 %). CONCLUSION: Second-line camrelizumab combined apatinib and chemotherapy might serve as a potential treatment with acceptable safety in patients with advanced LUAD.

Central nervous system efficacy of rezivertinib (BPI-7711) in advanced NSCLC patients with EGFR T790M mutation: A pooled analysis of two clinical studies.

BACKGROUND: Rezivertinib (BPI-7711) is a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) which revealed the systematic and central nervous system (CNS) antitumor activities for EGFR T790M-mutated advanced NSCLC in previous clinical studies and is further analyzed here. METHODS: Eligible patients from the previous phase I and phase IIb studies of rezivertinib were included for pooled analysis. Post-progressive patients who received a prescribed dosage (≥180 mg) of rezivertinib orally once daily were included in full analysis set (FAS), while those with stable, asymptomatic CNS lesions, including measurable and non-measurable ones at baseline were included in CNS full analysis set (cFAS). Patients with measurable CNS lesions were included in CNS evaluable for response set (cEFR). BICR-assessed CNS objective response rate (CNS-ORR), CNS disease control rate (CNS-DCR), CNS duration of response (CNS-DoR), CNS progression-free survival (CNS-PFS), and CNS depth of response (CNS-DepOR) were evaluated. RESULTS: 355 patients were included in FAS, among whom 150 and 45 patients were included in cFAS and cEFR. This pooled analysis showed the CNS-ORR was 32.0% (48/150; 95% CI: 24.6-40.1%) and the CNS-DCR was 42.0% (63/150; 95% CI: 34.0-50.3%) in cFAS, while that in cEFR were 68.9% (31/45; 95% CI: 53.4-81.8%) and 100% (45/45; 95% CI: 92.1-100.0%). In cEFR, the median CNS-DepOR and the mean of CNS-DepOR were -52.0% (range: -100.0 to 16.1%) and -46.8% (95% CI: -55.5 to -38.1%). In cFAS, the median CNS-DoR and CNS-PFS were 13.8 (95% CI: 9.6-not calculable [NC]) and 16.5 (95% CI: 13.7-NC) months. CONCLUSIONS: Rezivertinib demonstrated encouraging clinical CNS efficacy among advanced NSCLC patients with EGFR T790M mutation and CNS metastases.

Efficacy and Safety of Denosumab Biosimilar QL1206 Versus Denosumab in Patients with Bone Metastases from Solid Tumors: A Randomized Phase III Trial.

BACKGROUND: Denosumab has been approved for the treatment of bone metastases from solid tumors. QL1206 is the first denosumab biosimilar and needs to be compared with denosumab in a phase III trial. OBJECTIVE: This phase III trial aims to compare the efficacy, safety, and pharmacokinetics between QL1206 and denosumab in patients with bone metastases from solid tumors. METHODS: This randomized, double-blind, phase III trial was conducted in 51 centers in China. Patients aged 18-80 years, with solid tumors and bone metastases, and an Eastern Cooperative Oncology Group performance status of 0-2 were eligible. This study was divided into a 13-week double-blind period, a 40-week open-label period, and a 20-week safety follow-up period. In the double-blind period, patients were randomly assigned (1:1) to receive three doses of QL1206 or denosumab (120 mg subcutaneously every 4 weeks, each). Randomization was stratified by tumor types, previous skeletal-related events, and current systemic anti-tumor therapy. In the open-label period, up to ten doses of QL1206 could be given in both groups. The primary endpoint was percentage change in urinary N-telopeptide/creatinine ratio (uNTX/uCr) from baseline to Week 13. Equivalence margins were ± 0.135. Secondary endpoints included percentage change in uNTX/uCr at Week 25 and 53, percentage change in serum bone-specific alkaline phosphatase at Week 13, 25, and 53, and time to on-study skeletal-related events. The safety profile was evaluated based on adverse events and immunogenicity. RESULTS: From September 2019 to January 2021, in the full analysis set, 717 patients were randomly assigned to receive QL1206 (n = 357) or denosumab (n = 360). Median percentage changes in uNTX/uCr at Week 13 in two groups were - 75.2% and - 75.8%, respectively. Least-squares mean difference in the natural log-transformed ratio of uNTX/uCr at Week 13 to baseline between the two groups was 0.012 (90% confidence interval - 0.078 to 0.103), within the equivalence margins. There were no differences in the secondary endpoints between the two groups (all p > 0.05). Adverse events, immunogenicity, and pharmacokinetics were similar in the two groups. CONCLUSIONS: Denosumab biosimilar QL1206 had promising efficacy, tolerable safety, and pharmacokinetics equivalent to denosumab and could benefit patients with bone metastases from solid tumors. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04550949, retrospectively registered on 16 September, 2020.

Efficacy and Safety of Rezivertinib (BPI-7711) in Patients With Locally Advanced or Metastatic/Recurrent EGFR T790M-Mutated NSCLC: A Phase 2b Study.

INTRODUCTION: Rezivertinib (BPI-7711) is a novel third-generation EGFR tyrosine kinase inhibitor (TKI) targeting both EGFR-sensitizing mutations and EGFR T790M mutation. This study aimed to evaluate the efficacy and safety of rezivertinib in patients with locally advanced or metastatic/recurrent EGFR T790M-mutated NSCLC. METHODS: Patients with locally advanced or metastatic/recurrent NSCLC with confirmed EGFR T790M mutation who progressed after first-/second-generation EGFR TKI therapy or primary EGFR T790M mutation were enrolled. Patients received rezivertinib at 180 mg orally once daily until disease progression, unacceptable toxicity, or withdrawal of consent. The primary end point was objective response rate (ORR) assessed by blinded independent central review per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included disease control rate (DCR), duration of response, progression-free survival (PFS), overall survival, and safety. This study is registered with Clinical Trials.gov (NCT03812809). RESULTS: A total of 226 patients were enrolled from July 5, 2019, to January 22, 2020. By the data cutoff date on January 24, 2022, the median duration of follow-up was 23.3 months (95% confidence interval [CI]: 22.8-24.0). The ORR by blinded independent central review was 64.6% (95% CI: 58.0%-70.8%), and DCR was 89.8% (95% CI: 85.1%-93.4%). The median duration of response was 12.5 months (95% CI: 10.0-13.9), and median PFS was 12.2 months (95% CI: 9.6-13.9). The median overall survival was 23.9 months (95% CI: 20.0-not calculated [NC]). Among 91 (40.3%) patients with central nervous system (CNS) metastases, the median CNS PFS was 16.6 months (95% CI: 11.1-NC). In 29 patients with more than or equal to one brain target lesion at baseline, the CNS ORR and CNS DCR were 69.0% (95% CI: 49.2%-84.7%) and 100% (95% CI: 88.1%-100%), respectively. Time to progression of CNS was 16.5 months (95% CI: 9.7-NC). Of 226 patients, 188 (83.2%) had at least one treatment-related adverse event, whereas grade more than or equal to 3 occurred in 45 (19.9%) patients. No interstitial lung disease was reported. CONCLUSIONS: Rezivertinib was found to have promising efficacy and favorable safety profile for patients with locally advanced or metastatic/recurrent NSCLC with EGFR T790M mutation.

Prognostic values of inflammatory indexes in bevacizumab-treated patients with advanced non-small-cell lung cancer.

Purpose: Inflammatory indexes, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII) and lymphocyte-to-monocyte ratio (LMR), have been confirmed as prognostic factors in multiple manigances. However, the prognostic value of these parameters in bevacizumab-treated non-small-cell lung cancer (NSCLC) is still not clear. Methods: We retrospectively studied 119 patients with advanced NSCLC who received bevacizumab treatment. The associations of pretreatment NLR, PLR, SII and LMR with progression-free survival (PFS) and overall survival (OS) were analyzed. Results & Conclusion: The median PFS and OS of patients with high baseline NLR, PLR and SII and low LMR were significantly decreased than those of patients with low baseline NLR, PLR and SII and high LMR. Multivariable analysis indicated that high baseline SII was independently related with inferior prognosis, and baseline LMR was an independent predictor for OS.

Influence of concomitant gastric acid suppressants use on the survival of patients with non-small cell lung cancer treated with programmed death-1/ligand-1 inhibitors: A meta-analysis.

INTRODUCTION: Influence of concomitant use of gastric acid suppressants (GAS) on survival of non-small cell lung cancer (NSCLC) patients receiving programmed death-1/ligand-1 (PD-1/PD-L1) inhibitors has rarely been comprehensively evaluated. A meta-analysis was performed to systematically evaluate the effect of concomitant GAS in NSCLC patients receiving PD-1/PD-L1inhibitors. METHODS: Relevant observational studies were identified by search of Medline, Embase, and Web of Science databases from inception to May 26, 2022. A random-effect model which incorporates the possible between-study heterogeneity was used to combine the results. RESULTS: Ten retrospective and one prospective cohort studies including 5892 patients were patients were included. Influence of concomitant proton pump inhibitors (PPIs) was evaluated in ten studies, and influence of GAS, including PPIs or histamine type-2 receptor antagonists were evaluated in one study. Pooled results showed that concomitant use of GAS was associated with worse progression-free survival (PFS, adjusted hazard ratio [HR]: 1.32, 95% confidence interval [CI]: 1.20 to 1.45, P < 0.001; I2 = 0%) and overall survival (OS, adjusted HR: 1.36, 95% CI: 1.26 to 1.48, P < 0.001; I2 = 0%) in NSCLC patients taking PD-1/PD-L1inhibitors. Subgroup analyses indicated that the association between concomitant use of GAS and poor survival in NSCLC patients taking PD-L1inhibitors was consistent in univariate and multivariate studies (P values for subgroup difference both > 0.05 for PFS and OS). CONCLUSIONS: The meta-analysis by summarizing the up-to-date literatures showed that use of GAS, primarily PPIs, may be associated with poor survival outcomes in patients with NSCLC receiving PD-1/PD-L1inhibitors.

Updated Overall Survival Data and Predictive Biomarkers of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC in the Phase 3 ORIENT-11 Study.

INTRODUCTION: Sintilimab plus chemotherapy significantly prolonged progression-free survival (PFS) compared with chemotherapy alone in nonsquamous NSCLC in the ORIENT-11 study. Updated overall survival (OS) and PFS data and corresponding biomarker analyses are reported here. METHODS: In this study, a total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC were assigned to sintilimab plus chemotherapy combination treatment (combo) group or placebo plus chemotherapy treatment group. The patients were stratified by programmed death-ligand 1 (PD-L1) expression levels. Immune signature profiles from tumor RNA sequencing and PD-L1 immunohistochemistry were correlated with clinical outcome to identify predictive biomarkers. RESULTS: As of January 2021, with median follow-up of 22.9 months, median OS was significantly improved in the combo group compared with the placebo plus chemotherapy treatment group (not reached versus 16.8 mo; hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.45-0.79, p = 0.0003). High or medium immune cell infiltration was strongly associated with improved PFS in the combo group, in contrast to absent or low immune cell infiltration, which suggests that chemotherapy could not prime "immune deserts" to obtain benefit from programmed cell death protein-1 inhibition. In particular, high major histocompatibility complex (MHC) class II presentation pathway expression was significantly correlated with prolonged PFS (HR = 0.32, 95% CI: 0.19-0.54, p < 0.0001) and OS (HR = 0.36, 95% CI: 0.20-0.64, p = 0.0005) in the combo group. Importantly, patients with low or absent PD-L1 but high MHC class II expression could still benefit from the combo treatment. In contrast, MHC class I antigen presentation pathway was less relevant in this combination setting. CONCLUSIONS: The addition of sintilimab to chemotherapy resulted to significantly longer OS in nonsquamous NSCLC. Expression of MHC class II antigen presentation pathway could identify patients benefiting most from this combination.

Bevacizumab biosimilar LY01008 compared with bevacizumab (Avastin) as first-line treatment for Chinese patients with unresectable, metastatic, or recurrent non-squamous non-small-cell lung cancer: A multicenter, randomized, double-blinded, phase III trial.

BACKGROUND: Previous studies have demonstrated the preclinical pharmacological and toxicological consistency, and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab (Avastin). This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC). METHODS: Stage IIIB-IV NSCLC patients with evaluable lesions, good physical status, and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin (combined treatment) for 4-6 cycles, followed by maintenance monotherapy with LY01008 until disease progression, intolerable toxicity, or death. The primary endpoint was objective response rate (ORR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by independent radiological review committees (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. This study was registered in ClinicalTrials.gov (NCT03533127). RESULTS: Between December 15th , 2017, and May 15th , 2019, a total of 649 patients were randomized to the LY01008 (n = 324) or Avastin (n = 325) group. As of September 25th , 2019 for primary endpoint analysis, 589 patients received ORR evaluation, with a median number of combined treatment cycles of 5 (range 1-6) and median duration of treatment of 3.0 (range 0.0-5.1) months. ORR of response-evaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%, respectively. The stratified ORR ratio was 0.91 (90% CI 0.80-1.04, within the prespecified equivalence margin of 0.75-1.33). Up to May 15th , 2020, with a median follow-up of 13.6 (range 0.8-28.4) months, no notable differences in DCR, median DoR, median PFS, median OS, and 1-year OS rate were observed between the LY01008 and Avastin groups. There were no clinically meaningful differences in safety and immunogenicity across treatment groups. CONCLUSIONS: LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC. LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable, metastatic, or recurrent non-squamous NSCLC patients in the first-line setting.

Equivalent efficacy study of QL1101 and bevacizumab on untreated advanced non-squamous non-small cell lung cancer patients: a phase 3 randomized, double-blind clinical trial.

OBJECTIVE: This phase 3 study aimed to test equivalence in efficacy and safety for QL1101, a bevacizumab analogue in Chinese patients with untreated locally advanced non-squamous non-small cell lung cancer (NSCLC). METHODS: Eligible patients were randomly assigned 1:1 to receive carboplatin and paclitaxel in combination with either QL1101 or bevacizumab, 15 mg/kg every 3-week for 6 cycles. This was followed by maintenance treatment with single agent QL1101 every 3-week. The primary end-point was objective response rate (ORR), with secondary end-points being progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs). RESULTS: Of 675 patients, 535 eligible patients were randomized to the QL1101 group (n = 269) and bevacizumab group (n = 266). ORRs were 52.8% and 56.8%, respectively, for the QL1101 and bevacizumab groups, with an ORR hazard ratio 0.93 (95% confidence interval: 0.8-0131.1). The PFS, OS, DCR, and AEs were comparable between the 2 groups, which remained the same after stratification according to epidermal growth factor receptor mutation or smoking history. CONCLUSIONS: QL1101 showed similar efficacy and safety profiles as compared to bevacizumab among Chinese patients with untreated locally advanced non-squamous NSCLC.

The efficiency and safety of immune checkpoint inhibitors in the treatment of small cell lung cancer: a meta-analysis.

BACKGROUND: Small cell lung cancer (SCLC) is highly invasive and fatal, sensitive to chemotherapy and radiotherapy but prone to relapse, with a poor overall survival rate. It is particularly urgent for SCLC patients to receive effective follow-up treatment. In the past 20 years, there has been no breakthrough in clinical treatment of SCLC. Currently, clinical studies on immunotherapy for SCLC with extensive stage disease (ED) have achieved good efficacy, bringing new hope for the treatment of small-cell lung cancer. PD-1 inhibitors used to treat small cell lung cancer include Pembrolizumab and Nivolumab. PD-L1 inhibitors mainly include Atezolizumab and Durvalumab. Other PD-1/PD-L1 inhibitors, such as Avelumab, are currently being tried for SCLC and the results have not yet been published. This study is to evaluate the efficacy and safety of immunotherapy in patients with ED SCLC. METHODS: A literature search of the PubMed, Embase, and Cochrane Library databases were performed. Two reviewers independently screened the literature, extracted the data, and evaluated the risk of bias of the included studies. RevMan 5.3 software was used for meta-analysis. RESULTS: Four studies involving 1,981 patients with ED SCLC were included. Both overall survival (OS) [hazard ratio (HR) =0.80, 95% confidence interval (CI) (0.68, 0.95), P=0.009] and progression-free survival (PFS) [HR =0.82, 95% CI (0.75, 0.90), P<0.00001] were longer in the immunotherapy group than in the chemotherapy group. The incidence of total treatment-related adverse events in the immunotherapy group were lower than those in the chemotherapy group [relative risk (RR) =1.050, 95% CI (1.010, 1.080), P=0.007], and the differences were statistically significant. CONCLUSIONS: Immunotherapy has better efficacy and safety than chemotherapy for the treatment of ED SCLC.

Activity and Safety of Geptanolimab (GB226) for Patients with Unresectable, Recurrent, or Metastatic Alveolar Soft Part Sarcoma: A Phase II, Single-arm Study.

PURPOSE: Patients with alveolar soft part sarcoma (ASPS) are rare and have few treatment options. We assessed the activity of geptanolimab (GB226), a fully humanized programmed cell death protein 1 antibody, for patients with unresectable, recurrent, or metastatic ASPS. PATIENTS AND METHODS: We conducted this multicenter, single-arm, phase II study (Gxplore-005, NCT03623581) in patients aged 18-75 years who had unresectable, recurrent, or metastatic ASPS at 11 sites in China. Patients received intravenous geptanolimab (3 mg/kg) every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed by independent review committee (IRC) per RECIST 1.1 in the full analysis set population. RESULTS: Between September 6, 2018 and March 6, 2019, we enrolled and treated 37 patients with 23 (62.2%) having received prior systemic treatment. Fourteen [37.8%; 95% confidence interval (CI), 22.5-55.2] of 37 patients had an objective response assessed by IRC with a 6-month duration of response rate of 91.7%. Median progression-free survival was 6.9 months (95% CI, 5.0-not reached) and disease control was achieved in 32 (86.5%; 95% CI, 71.2-95.5) patients. Three of 37 patients reported grade 3 treatment-related adverse events (TRAEs), including anemia, hypophysitis, and proteinuria [one each (2.7%)]. No grade 4 TRAEs were observed. Two (5.4%) patients discontinued treatment due to TRAEs (one with hypophysitis and one with Mobitz type I atrioventricular block). The baseline percentage of CD4+ T cells was adversely associated with patient response (P = 0.031). CONCLUSIONS: Geptanolimab has clinically meaningful activity and a manageable safety profile in unresectable, recurrent, or metastatic ASPS.

Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT anti-PD-1-11).

INTRODUCTION: Sintilimab, an anti-programmed death 1 antibody, plus pemetrexed and platinum had revealed promising efficacy for nonsquamous NSCLC in a phase 1b study. We conducted a randomized, double-blind, phase 3 study to compare the efficacy and safety of sintilimab with placebo, both in combination with such chemotherapy (ClinicalTrials.gov: NCT03607539). METHODS: A total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC without sensitizing EGFR or anaplastic lymphoma kinase genomic aberration were randomized (2:1 ratio) to receive either sintilimab 200 mg or placebo plus pemetrexed and platinum once every 3 weeks for four cycles, followed by sintilimab or placebo plus pemetrexed therapy. Crossover or treatment beyond disease progression was allowed. The primary end point was progression-free survival (PFS) as judged by an independent radiographic review committee. RESULTS: As of November 15, 2019, the median follow-up was 8.9 months. The median PFS was significantly longer in the sintilimab-combination group than that in the placebo-combination group (8.9 versus 5.0 mo; hazard ratio, 0.482, 95% confidence interval [CI]: 0.362-0.643; p < 0.00001). The confirmed objective response rate was 51.9% (95% CI: 45.7%-58.0%) in the sintilimab-combination group and 29.8% (95% CI: 22.1%-38.4%) in placebo-combination group. The incidence of grade 3 or higher adverse events was 61.7% in sintilimab-combination group and 58.8% in placebo-combination group. CONCLUSIONS: In Chinese patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC, the addition of sintilimab to chemotherapy with pemetrexed and platinum resulted in considerably longer PFS than with chemotherapy alone with manageable safety profiles.

Downregulation of NEAT1 Suppresses Cell Proliferation, Migration, and Invasion in NSCLC Via Sponging miR-153-3p.

Background: Long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) has been reported to play a promotive role in nonsmall cell lung cancer (NSCLC) progression through microRNAs (miRNAs). However, the exact influence and mechanism of NEAT1 were unsatisfied. Methods: Quantitative real-time polymerase chain reaction was applied to examine the expression of NEAT1 and miR-153-3p. The cell proliferation ability, apoptosis rate, migration, and invasion were measured by Cell Counting Kit-8 (CCK8) assay, flow cytometry, and transwell assay, respectively. The epithelial-mesenchymal transition process and Wnt/ß-catenin signaling pathway were verified by Western blot. The interaction between NEAT1 and miR-153-3p was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Results: These data showed that NEAT1 is highly expressed in NSCLC tissues and cell lines. Knockdown of NEAT1 suppresses cell proliferation, invasion, migration, and induces the cell apoptosis in NSCLC cell lines. At the same time, NEAT1 directly interacts with miR-153-3p in NSCLC. In addition, upregulation of miR-153-3p inhibits the cell progression, and miR-153-3p inhibitor recovers the inhibition effect of si-NEAT1 in NSCLC cell lines. Subsequently, si-NEAT1 inhibits Wnt/ß-catenin signaling pathway, which is reactivated by miR-153-3p inhibitor. Conclusions: Knockdown of NEAT1 could suppress cell proliferation, migration, and invasion of NSCLC while promoting cell apoptosis through sponging miR-153-3p.

The expression and the role of PIWI like RNA-mediated gene silencing 3 (PIWIL3) in lung cell line.

BACKGROUND: To determine the expression and role of PIWI-like RNA-mediated gene silencing 3 (PIWIL3) in human lung cancer. METHODS: Immunohistochemistry was performed to measure the expression of PIWIL3 in 30 of pairs lung cancer and corresponding paracancer tissues. Quantitative PCR (qPCR) was conducted to analyze the expression of PIWIL3 in four breast cancer cell lines. siRNA was used to silence PIWIL3 in the lung cancer cells (A549). Methylthiazoletetrazolium (MTT) proliferation assay and colony formation assay were conducted to detect the growth of A549 cells. Fluorescence-activated cell sorting (FACS) was performed to measure the apoptosis of A549 cells. Transwell migration assay and wound scratch healing assay were used to analyze the migration and invasion ability of A549 cells. SPSS 20.0 was used to analyze the data. RESULTS: The expression of PIWIL3 protein was higher in tumor tissues than that in paracancer tissues. In addition, PIWIL3 mRNA was highly expressed in all four lung cancer cell lines. Furthermore, RPS15A knockdown significantly suppressed cell proliferation (P<0.01), induced apoptosis (P<0.01) and inhibited metastasis (P<0.01) of A549 cells. CONCLUSIONS: PIWIL3 was highly expressed in lung cancer tissues and could promote the progression of lung cancer.

Effect of inhibiting ACAT-1 expression on the growth and metastasis of Lewis lung carcinoma.

Accumulating evidence suggests that acetyl-CoA acetryltransferase 1 (ACAT-1) may mediate tumor development and metastasis. However, the specific function served by ACAT-1 in lung cancer is not well understood. Therefore, the present study initially verified that ACAT-1 was overexpressed in Lewis lung carcinoma (LLC) tissues compared with non-LLC mice and that this overexpression promoted the proliferation, invasion and metastasis of these LLC samples. Western blotting, immunofluorescence microscopy and flow cytometry allowed the present study to determine that the ACAT-1 inhibitor avasimibe significantly reduced the expression of ACAT-1 in LLC compared with LLC cells that are not treated with avasimibe (P<0.05). A combination of Cell Counting Kit-8 and wound healing assays demonstrated that downregulating ACAT-1 expression sufficiently inhibited the proliferation of LLC cells. Avasimibe promoted LLC cell apoptosis as assessed by a Annexin V/propidium iodide double staining assay. Furthermore, avasimibe inhibited tumor growth in vivo and improved immune responses, with tissue biopsies from LLC model mice exhibiting higher levels of ACAT-1 compared with in healthy controls. Altogether, the results of the present study reveal that avasimibe may inhibit the progression of LLC by downregulating the expression of ACAT-1, which may thus be a potential novel therapeutic target for lung cancer treatment.

Comparison of case-based learning and traditional method in teaching postgraduate students of medical oncology.

Purpose: Case-based learning (CBL) is now used as a teaching strategy to promote clinical problem-solving ability. The purpose of this study was to determine whether CBL is superior to the traditional teaching method in teaching lung cancer curriculum to oncology students. Methods: This study was a randomized controlled trial, enrolled 80 first-year oncology postgraduates from Bengbu medical college in the past 3 years. They were randomized to divide into 2 groups, had courses with the same lung cancer contents and timing. The experimental group (n = 40) utilized the CBL method while the control group (n = 40) used the traditional lecture-based teaching method. A questionnaire was used to attain the students' learning satisfaction and self-efficacy of the course, and a post-study examination was used to assess end-of-course performance. Results: Complete data were obtained from participating students (n = 40 in CBL; n = 40 in traditional teaching). The CBL group performed significantly better in questionnaire and examination compared to traditional teaching groups. Students showed high levels of satisfaction and problem-solving ability in the CBL group. Conclusion: Compared with the traditional teaching method. The case teaching method is a more effective teaching method to improve the ability of problem-solving for graduate students in medical oncology.

Successful treatment of metastatic colorectal cancer with apatinib: report of two cases and literature review.

Apatinib, a novel small molecule tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor-2, was approved for metastatic gastric adenocarcinoma in China in Oct 2014. This is the first report on its use for advanced colorectal cancer as a kind of third-line therapy to date. Here we report two Chinese patients who presented with metastatic colorectal cancer who received apatinib 850 mg daily as a third-line therapy. Both the patients achieved favorable benefits in outcomes after the administration of apatinib. Patient 1 benefited 4 months progression-free survival and 11 months overall survival, while patient 2's progression-free survival was over 10 months. Both the patients presented hand-foot syndrome, and one of them suffered a slight impairment of liver function, mild elevated blood pressure, and proteinuria. But these adverse events were manageable with symptomatic treatment and dose reduction or a short-time drug withdrawal.

Survival analysis of patients with advanced non-small cell lung cancer receiving tyrosine kinase inhibitor (TKI) treatment: A multi-center retrospective study.

BACKGROUND: The study was conducted to assess differences in overall survival (OS) in patients with non-small cell lung cancer (NSCLC) receiving different treatment modalities of tyrosine kinase inhibitors (TKIs). METHODS: A total of 463 NSCLC patients receiving TKI treatment were included. OS was compared according to treatment timing in all patients, the elderly, and patients positive for EGFR mutations. RESULTS: One hundred and seventy two patients received TKIs as first-line treatment, 220 as second-line, and 67 as third-line. The results between the three groups were not statistically significant: the one, two, and three-year OS rates were: 55.3%, 22.3%, and 11.3% (first-line); 59.6%, 27.8%, and 14.9% (second-line); and 53.8%, 41.3%, and 29.5% (third-line), respectively (P = 0.095). Results between the three groups of elderly patients were also not statistically significant (P = 0.469). The one and two-year OS rates in EGFR mutation-positive patients receiving first-line treatment were 48% and 17.5%, respectively. The one, two, and three-year OS rates of patients receiving second-line treatment were: 54.2%, 30.3%, and 20.2%, respectively. There were no statistically significant differences between the groups with EGFR mutations receiving first-line or second-line treatment. Thirteen EGFR mutation-positive patients received third-line TKI treatment for a median duration of 7 months. Their one and two-year OS rates were 69.8% and 58.2%, respectively, which were higher than in the other two groups (P = 0.015). CONCLUSION: Three lines of TKI therapy can prolong survival in NSCLC patients. Elderly patients can benefit from TKI therapy. EGFR mutation-positive patients can benefit from second-line or third-line TKI therapy.

Apatinib in gastric carcinoma: A case report of partial response for first-line treatment in advanced disease.

Gastric cancer (GC) is the most common gastrointestinal malignant tumor, with a gradual increasing incidence throughout the world. Mostly GC is diagnosed in its late stage. To date, there is no usable standardized treatment regimen for patients with advanced GC. Apatinib mesylate, small-molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor (TKI), has been approved as third-line treatment for patients with advanced gastric adenocarcinoma in China, October, 2014. Till now, there is no case report about apatinib as first-line treatment for patients with advanced GC in literature. We present an 83-year-old Chinese man with advanced gastric adenocarcinoma, who received apatinib as first-line option and obtained clinical benefit within 2 weeks. The lung metastases disappeared completely and the liver metastases shrank significantly. The patient's progression-free survival was 163 days and overall survival was 201 days. This paper reviews and discusses apatinib as a new targeted drug for patients with advanced GC by comparison with other effective molecular-targeted therapy.

Metformin induces apoptosis via a mitochondria-mediated pathway in human breast cancer cells in vitro.

Breast cancer is the most commonly occurring cancer and second leading cause of mortality in women. Metformin is a widely prescribed anti-hyperglycemic drug, which is emerging as a potential cancer preventative and treatment agent. However, the mechanisms underlying the suppressive effects of metformin on cancer cell growth and the induction of cancer cell apoptosis are not fully elucidated. The present study aimed to identify the pathways regulated by metformin in two breast cancer cell lines, MDA-MB-231 and MDA-MB-435. Cells were treated with various concentrations of metformin and then evaluated with respect to viability, proliferation, adenosine triphosphate (ATP) and reactive oxygen species (ROS) levels, mitochondrial membrane potential (∆ψm), and the expression of anti- and pro-apoptotic proteins. Metformin caused apoptosis in a concentration- and time-dependent manner, and decreased cell viability and ATP production. Furthermore, metformin induced the generation of ROS and decreased the ∆ψm. Moreover, metformin downregulated the expression of the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and myeloid cell leukemia-1, and upregulated the expression of the pro-apoptotic BCL-2-associated X protein in MDA-MB-231 cells. These results demonstrate that the apoptotic and cytotoxic effects of metformin on breast cancer cells are mediated by the intrinsic mitochondria-mediated apoptosis pathway.