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Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation EGFR tyrosine kinase inhibitor (TKI) with revealed activity against EGFR-sensitizing mutations and EGFR T790M mutation.Patients with locally advanced or metastatic NSCLC who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy were enrolled in this registrational phase 2 trial of aumolertinib at 110 mg orally once daily (NCT02981108). The primary end point was objective response rate (ORR) by independent central review.A total of 244 patients with EGFR T790M-positive NSCLC were enrolled. The ORR by independent central review was 68.9% (95% confidence interval [CI]: 62.6-74.6). The disease control rate was 93.4% (95% CI: 89.6-96.2). The median duration of response was 15.1 months (95% CI: 12.5-16.6). The median progression-free survival was 12.4 months (95% CI: 9.7-15.0). Among 23 patients with assessable central nervous system (CNS) metastases, the CNS-ORR and CNS-disease control rate were 60.9% (95% CI: 38.5-80.3) and 91.3% (95% CI: 72.0-98.9), respectively. The median CNS-duration of response was 12.5 months (95% CI: 5.6-not reached). Treatment-related adverse events of more than or equal to grade 3 occurred in 16.4% of the patients, with the most common being increased blood creatine phosphokinase level (7%) and increased alanine aminotransferase level (1.2%). The relative dose density of aumolertinib was 99.2% in this study.Aumolertinib is an effective and well-tolerated third-generation EGFR TKI for patients with EGFR T790M-positive advanced NSCLC after disease progression on first- and second-generation EGFR TKI therapy. On the basis of these findings, aumolertinib was approved in the People's Republic of China for patients positive for EGFR T790M NSCLC.

Summary Background Inhibition of vascular endothelial growth factor receptor (VEGFR) has shown antitumour activity in advanced hepatocellular carcinoma, but few studies of VEGFR inhibitors have been done in populations with a high prevalence of hepatitis B virus infection. The aim of this study was to evaluate the efficacy and safety of apatinib in patients with pretreated advanced hepatocellular carcinoma. Methods AHELP was a randomised, double-blind, placebo-controlled, phase 3 trial done at 31 hospitals in China, in patients (aged ≥18 years) with advanced hepatocellular carcinoma who had previously been refractory or intolerant to at least one line of systemic chemotherapy or targeted therapy. Patients were randomly assigned (2:1) to receive apatinib 750 mg or placebo orally once daily in 28-day treatment cycles. Group allocation was done with a central randomisation system, with a block size of six, and was stratified by Eastern Cooperative Oncology Group performance status, previous sorafenib treatment, and presence of vascular invasion or extrahepatic metastasis. The primary endpoint was overall survival, which was defined as time from randomisation to death from any cause, and was analysed in patients who were randomly assigned and received at least one dose of the study drug. Safety analyses were done in patients who received at least one dose of the study treatment and had post-dose safety assessments. This trial is registered with ClinicalTrials.gov , NCT02329860 . Findings Between April 1, 2014, and May 3, 2017, 400 eligible patients were randomly assigned to receive apatinib (n=267) or placebo (n=133). Seven patients (six in the apatinib group and one in the placebo group) did not receive study treatment and were excluded from efficacy analyses. Overall survival was significantly improved in the apatinib group compared with the placebo group (median 8·7 months [95% CI 7·5‒9·8] vs 6·8 months [5·7‒9·1]; hazard ratio 0·785 [95% CI 0·617‒0·998], p=0·048). 387 patients (257 in the apatinib group and 130 in the placebo group) had a safety assessment after study treatment and were included in safety analyses. The most common treatment-related adverse events of grade 3 or 4 were hypertension (71 [28%] patients in the apatinib group vs three [2%] in the placebo group), hand–foot syndrome (46 [18%] vs none), and decreased platelet count (34 [13%] vs one [1%]). 24 (9%) patients in the apatinib group and 13 (10%) in the placebo group died due to adverse events, but none of these deaths were deemed to be related to treatment by investigators. Interpretation Apatinib significantly improved overall survival in patients with pretreated advanced hepatocellular carcinoma compared with placebo, with a manageable safety profile. Funding Jiangsu Hengrui Medicine.

To explore a better treatment strategy for patients with advanced non‐small cell lung cancer harboring sensitive epidermal growth factor receptor mutations, a total of 271 patients were retrospectively analyzed. The patients were divided into two groups: the combination group (58 cases), which received concurrent icotinib, pemetrexed, and platinum treatment, and the sequential group (213 cases), which received the sequential pemetrexed and platinum therapy, followed by icotinib treatment. The primary end points were progression‐free survival (PFS) and PFS on the subsequent line of therapy (PFS2). PFS in the combination group was significantly higher compared with that in the sequential group (16.89 months vs. 9.90 months; p

By implementing dynamic circulating tumor DNA (ctDNA) analysis, we explored the impact of TP53 mutations on tumor evolution and resistance mechanisms to ensartinib in patients with ALK-positive NSCLC.In a multicenter phase 2 trial, patients with ALK-positive NSCLC who progressed on crizotinib were treated with ensartinib. Blood samples for ctDNA analysis were collected at baseline, cycle 3 day 1, and progression disease (PD) and analyzed with a 212-gene panel.A total of 440 samples were collected from 168 patients. Baseline TP53 mutations (20.2%) significantly correlated with inferior progression-free survival (4.2 mo versus 11.7 mo, p0.0001). Patients with TP53 mutations had higher mutation load than those without TP53 mutations at baseline (13.79 ± 3.72 versus 4.67 ± 0.39, p0.001). Although there was no significant difference in mutation load between these groups at cycle 3 day 1 (5.89 ± 2.25 versus 3.72 ± 0.62, p = 0.425), patients with mutated TP53 developed more mutations at PD (7.07 ± 1.25 versus 3.20 ± 0.33, p = 0.003). Frequency and abundance of secondary ALK mutations G1269A, G1202R, and E1210K increased markedly at PD than baseline. In patients without secondary ALK mutations, we identified ALK-independent resistance mechanisms including bypass signaling activation, downstream effector protein reactivation, epithelial-mesenchymal transformation, and epigenetic dysregulation.Our study highlighted the advantage of ctDNA analysis for monitoring tumor evolution. TP53 mutations promoted genetic evolution and accelerated occurrence of resistance. We also unveiled ALK-dependent resistance mechanisms, mainly by G1269A, G1202R, and E1210K mutations, and ALK-independent resistance mechanisms to ensartinib.

Background: FRESCO study demonstrated efficacy and safety of fruquintinib in metastatic colorectal cancer patients. Impact of prior targeted therapy (PTT) on efficacy and safety of fruquintinib was evaluated. Materials & methods: In this subgroup analysis of FRESCO trial, patients were divided into PTT and non-PTT subgroups, and efficacy and safety of fruquintinib were assessed, respectively. Results: In non-PTT subgroup, fruquintinib significantly prolonged overall survival (OS) and progression-free survival (PFS) of patients compared with placebo. In PTT subgroup, the median OS and PFS of patients in fruquintinib arm was significantly higher than those in placebo. Treatment-emergent adverse events (TEAEs) rates were similar in both subgroups. Conclusion: Fruquintinib demonstrated clinically meaningful improvement in OS, PFS, objective response rate, and disease control rate with manageable TEAEs in both subgroups. Clinical trial registration: NCT02314819 ( ClinicalTrials.gov )

Since the concept, DNA damage repair has been stated as a natural biological event, and research has increasingly revealed its strong association to tumors, aging, immunity, biochemical detection, and other factors. The discovery of abnormal DNA repair in cancers has been heralded as a paradigm shift in the treatment of malignancies. A poly (ADP-ribose) polymerase (PARP) activates poly (ADP-ribosylation) to repair single-strand DNA breaks after DNA damage. In some cancers, such as breast cancer and gastric cancer, a PARP inhibitor can target the DNA damage response pathway, prevent DNA repair, and induce homologous recombination deficiency (HRD) tumors to create the phenomena of synthetic lethality. Increasingly, clinical trials are being submitted to research the uses of PARP inhibitors in various types of cancers. Small cell lung cancer (SCLC) is a quickly growing malignancy with numerous therapeutic limitations and a dismal prognosis. Sequencing of mutant genes revealed multiple gene connections that may contribute to its carcinogenesis, indicating a viable study direction. Furthermore, the therapy of SCLC with PARP inhibitors has been further explored. The mechanism of PARP action, as well as the advancement of its preclinical and clinical applications in SCLC, will be discussed in this review.

Befotertinib (D-0316) is a novel, third-generation EGFR tyrosine kinase inhibitor (TKI). This study evaluated befotertinib in patients with locally advanced or metastatic NSCLC who developed an EGFR T790M mutation after progression on first- or second-generation EGFR TKI therapy.This was a single-arm, open-label, phase 2 study at 49 hospitals across mainland China. Patients with locally advanced or metastatic NSCLC harboring EGFR T790M mutations with disease progression after prior first- or second-generation EGFR TKI therapy received oral befotertinib of 50 mg (cohort A) or 75 to 100 mg (cohort B) once daily. The primary end point was objective response rate (ORR) assessed by an independent review committee in intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT03861156.A total of 176 patients and 290 patients were included in cohorts A (50 mg) and B (75-100 mg), respectively. At data cutoff (August 15, 2021), independent review committee-assessed ORR was 67.6% (95% confidence interval [CI]: 61.9%-72.9%) in cohort B. The investigator-assessed ORR was 54.0% (95% CI: 46.3%-61.5%) in cohort A and 65.9% (95% CI: 60.1%-71.3%) in cohort B. The median investigator-assessed progression-free survival was 11.0 (95% CI: 9.6-12.5) months in cohort A and 12.5 (95% CI: 11.1-13.8) months in cohort B. The median independent review committee-assessed progression-free survival in cohort B was 16.6 (95% CI: 15.0-not evaluable [NE]) months. The intracranial ORR was 26.7% (95% CI: 7.8%-55.1%) in cohort A by investigator assessment, while 57.1% (95% CI: 34.0%-78.2%) and 55.9% (95% CI: 37.9%-72.8%) in cohort B by investigator and independent review committee assessment, respectively. The median investigator-assessed intracranial progression-free survival was 16.5 (95% CI: 8.6-NE) months in cohort A, while the median intracranial progression-free survival was not evaluable in cohort B due to immature data regardless of investigator or independent review committee assessment. and NE (95% CI: 13.8-NE) in cohort B. The overall survival was immature. Grade 3 or higher treatment-related adverse events and treatment-related serious adverse events occurred in 20.5% and 11.4% of patients in cohort A and in 29.3% and 10.0% of patients in cohort B, respectively.Befotertinib of 75 to 100 mg has satisfying efficacy and manageable toxicity in patients with locally advanced or metastatic NSCLC harboring T790M mutation with resistance to first- or second-generation EGFR TKIs. A phase 3 randomized trial is underway (NCT04206072).

Aumolertinib (formerly almonertinib; HS-10296) is a novel third-generation epidermal growth factor receptor tyrosine kinase inhibitor approved in China. This double-blind phase III trial evaluated the efficacy and safety of aumolertinib compared with gefitinib as a first-line treatment for locally advanced or metastaticPatients at 53 sites in China were randomly assigned 1:1 to receive either aumolertinib (110 mg) or gefitinib (250 mg) once daily. The primary end point was progression-free survival (PFS) per investigator assessment.A total of 429 patients who were naïve to treatment for locally advanced or metastatic NSCLC were enrolled. PFS was significantly longer with aumolertinib compared with gefitinib (hazard ratio, 0.46; 95% CI, 0.36 to 0.60;Aumolertinib is a well-tolerated third-generation epidermal growth factor receptor tyrosine kinase inhibitor that could serve as a treatment option for

Imbalance of macrophage polarization plays an indispensable role in acute lung injury (ALI), which is considered as a promising target. Matrix metalloproteinase-9 (MMP-9) is expressed in the macrophage, and has a pivotal role in secreting inflammatory cytokines. We reported that saquinavir (SQV), a first-generation human immunodeficiency virus-protease inhibitor, restricted exaggerated inflammatory response. However, whether MMP-9 could regulate macrophage polarization and inhibit by SQV is still unknown. We focused on the important role of macrophage polarization in CLP (cecal ligation puncture)-mediated ALI and determined the ability of SQV to maintain M2 over M1 phenotype partially through the inhibition of MMP-9. We also performed a limited clinical study to determine if MMP-9 is a biomarker of sepsis. Lipopolysaccharide (LPS) increased MMP-9 expression and recombinant MMP-9 (rMMP-9) exacerbated LPS-mediated M1 switching. Small interfering RNA to MMP-9 inhibited LPS-mediated M1 phenotype and SQV inhibition of this switching was reversed with rMMP-9, suggesting an important role for MMP-9 in mediating LPS-induced M1 phenotype. MMP-9 messenger RNA levels in peripheral blood mononuclear cells of these 14 patients correlated with their clinical assessment. There was a significant dose-dependent decrease in mortality and ALI after CLP with SQV. SQV significantly inhibited LPS-mediated M1 phenotype and increased M2 phenotype in cultured RAW 264.7 and primary murine bone marrow-derived macrophages as well as lung macrophages from CLP-treated mice. This study supports an important role for MMP-9 in macrophage phenotypic switching and suggests that SQV-mediated inhibition of MMP-9 may be involved in suppressing ALI during systemic sepsis.

In FRESCO (Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer Patients) trial, fruquintinib demonstrated a statistically significant and clinically meaningful overall survival benefit in Chinese patients with metastatic colorectal cancer (mCRC). However, its safety profile, including adverse events of special interest (AESIs) and treatment-emergent adverse events (TEAEs) by age, sex, and body mass index (BMI), is not well known. The present analysis evaluated the safety profile and AESIs for fruquintinib in the FRESCO trial. In FRESCO, eligible Chinese patients were randomized (2:1) to receive fruquintinib (5 mg once daily for 3 weeks, followed by 1 week off in 28-day cycles) or placebo plus best supportive care. Treatment-related AESIs and time to first occurrence of AESIs were summarized. Treatment-related TEAEs by age, sex, and BMI were also summarized. A total of 266 patients (95.7%) in the fruquintinib group and 97 (70.8%) in the placebo group had at least one treatment-related TEAE; the mean relative dose intensity was 92% and 98%, respectively. In the fruquintinib group, the most common (in > 40% of patients) treatment-related AESIs were hypertension (55.4%), palmar-plantar erythrodysesthesia syndrome [known as hand-foot skin reaction (HFSR)] (49.3%), and proteinuria (42.1%). The most common treatment-related grade ≥ 3 AESIs (≥ 3% of patients) were hypertension (21.2%), HFSR (10.8%), and proteinuria (3.2%); the median time to onset of these events was 10, 21, and 20 days, respectively. Subgroup analysis by age, sex, and BMI revealed that the frequencies of treatment-related TEAEs were similar across all subgroups, and were consistent with the overall safety profile of fruquintinib. The most common treatment-related grade ≥ 3 AEs were hypertension, HFSR, and proteinuria. The treatment-related TEAE profile of fruquintinib in Chinese patents with mCRC was comparable among different subgroups and consistent with that reported in the overall population. Trial Registration: Clinical Trials identifier NCT02314819.

Triglycerides (TG) not only provide energy for infants but have important physiological functions. Understanding the composition and structure of TG in human milk is conducive to the development of infant formulas. In this study, TG species in human milk from 3 provincial capitals (Zhengzhou, Wuhan, and Harbin) in different regions of China were determined through C18 HPLC electrospray ionization tandem mass spectrometry (MS). The results showed that in human milk from these 3 regions, oleoyl-palmitoyl-linoleoylglycerol (OPL; 16.55, 19.20, and 18.67%, respectively) was more abundant than oleoyl-palmitoyl-oleoylglycerol (OPO; 10.08, 10.22, and 12.03%, respectively). Subsequently, regioisomeric and enantiomeric analysis of main TG in the human milk were performed on silver ion and chiral HPLC atmospheric pressure chemical ionization mass spectrometry (APCI)-MS, respectively. The results showed that rac-OPL (above 85%), rac-OPO (above 85%), rac-palmitoyl-oleoyl-oleoylglycerol (PPO; above 90%), and rac-OLaO (above 70%) were the main regioisomers of OPL, OPO, PPO, and lauroyl-oleoyl-oleoylglycerol (LaOO), respectively. The relative ratios of enantiomer pairs of rac-OPL (rac-OPL1 and rac-OPL2) were about 37 and 63%, respectively.

Supplemental Digital Content is available in the text., Objective: We aim to develop and validate an effective nomogram prognostic model for patients with typical lung carcinoid tumors using a large patient cohort from the Surveillance, Epidemiology, and End Results (SEER) database. Materials and Methods: Data from patients with typical lung carcinoid tumors between 2010 and 2015 were selected from the SEER database for retrospective analysis. Univariate and multivariate Cox analysis was performed to clarify independent prognostic factors. Next, a nomogram was formulated to predict the probability of 3- and 5-year overall survival (OS). Concordance indexes (c-index), receiver operating characteristic analysis and calibration curves were used to evaluate the model. Results: The selected patients were randomly divided into a training and a validation cohort. A nomogram was established based on the training cohort. Cox analysis results indicated that age, sex, T stage, N stage, surgery, and bone metastasis were independent variables for OS. All these factors, except surgery, were included in the nomogram model for predicting 3- and 5-year OS. The internally and externally validated c-indexes were 0.787 and 0.817, respectively. For the 3-year survival prediction, receiver operating characteristic analysis showed that the areas under the curve in the training and validation cohorts were 0.824 and 0.795, respectively. For the 5-year survival prediction, the area under the curve in the training and validation cohorts were 0.812 and 0.787, respectively. The calibration plots for probability of survival were in good agreement. Conclusion: The nomogram brings us closer to personalized medicine and the maximization of predictive accuracy in the prediction of OS in patients with typical lung carcinoid tumors.

Summary Background Ensartinib is a potent new-generation ALK inhibitor with high activity against a broad range of known crizotinib-resistant ALK mutations and CNS metastases. We aimed to assess the efficacy and safety of ensartinib in ALK-positive patients with non-small-cell lung cancer (NSCLC), in whom crizotinib therapy was unsuccessful. The associations between ensartinib efficacy and crizotinib-resistant mutations were also explored. Methods We did a single-arm, open-label, phase 2 study at 27 centres in China. Patients were aged 18 years or older, had stage IIIb or stage IV ALK-positive NSCLC that had progressed while they were on crizotinib therapy, an Eastern Cooperative Oncology Group performance status of 2 or less, had measurable disease, and had received fewer than three previous treatments. Patients with CNS metastases were included if these metastases were asymptomatic and did not require steroid therapy. All patients received 225 mg ensartinib orally once daily on a continuous dosing schedule. The primary outcome was the proportion of patients with an objective response according to the Response Evaluation Criteria in Solid Tumors (version 1.1), as assessed by an independent review committee in all patients who received at least one dose of ensartinib with no major violations of the inclusion criteria (ie, the full analysis set). Safety was assessed in all enrolled patients who received at least one dose of ensartinib. This trial was registered with ClinicalTrials.gov , NCT03215693 . Findings Between Sept 28, 2017, and April 11, 2018, 160 patients were enrolled and had at least one dose of ensartinib (safety analysis set). Four patients had inclusion violations and were excluded from the efficacy analysis, which thus included 156 patients (full analysis set). 97 (62%) patients in the full analysis set had brain metastases. 76 (52% [95% CI 43–60]) of 147 patients in the full analysis set, with responses that could be assessed by the independent review committee, had an objective response. 28 (70% [53–83]) of 40 patients with measurable brain metastases as assessed by the independent review committee had an intracranial objective response. 145 (91%) of 160 patients had at least one treatment-related adverse event, which were mostly grade 1 or 2. The most common treatment-related adverse events were rash (89 [56%]), increased alanine aminotransferase concentrations (74 [46%]), and increased aspartate aminotransferase concentrations (65 [41%]). Interpretation Ensartinib has activity and is well tolerated in patients with crizotinib-refractory, ALK-positive NSCLC, including those with brain metastases. The role of ensartinib in patients in whom other second-generation ALK inhibitors have been unsuccessful warrants further studies. Funding Betta Pharmaceuticals.

Background Clinical options for lung squamous carcinoma (LUSC) are still quite limited. Carcinogenesis is an exceedingly complicated process involving multi-level dysregulations. Therefore, only looking into one layer of genomic dysregulation is far from sufficient. Methods We identified differentially expressed genes with consistent upstream genetic or epigenetic dysregulations in LUSC. Random walk was adopted to identify genes significantly affected by upstream abnormalities. Expression differentiation and survival analysis were conducted for these significant genes, respectively. Prognostic power of selected gene was also tested in 102 male LUSC samples through immunohistochemistry assay. Results Twelve genes were successfully retrieved from biological network, including ERα (ESRS1), EGFR, AR, ATXN1, MAPK3, PRKACA, PRKCA, SMAD4, TP53, TRAF2, UBQLN4 and YWHAG, which were closely related to sex hormone signaling pathway. Survival analysis in public datasets indicated ERα was significantly associated with a poor overall survival (OS) in male LUSC. The result of our immunohistochemistry assay also demonstrated this correlation using R0 resected tumors (n = 102, HR: 2.152, 95% CI: 1.089–4.255, p = 0.024). Although disease-free survival (DFS) difference was non-significant (n = 102, p = 0.12), the tendency of distinction was straight-forward. Cox analysis indicated ERα was the only independent prognostic factor for male patients’ OS after R0 resection (HR = 2.152, p = 0.037). Conclusion ERα was significantly related to a poor prognosis in LUSC, especially for male patients after radical surgery, confirmed by our immunohistochemistry data.

Studies have shown that elevated serum lactate dehydrogenase (LDH) concentration can lead to poor prognosis in patients with small cell lung cancer and lung adenocarcinoma, but its relationship with the prognosis of patients with lung large-cell neuroendocrine carcinoma (L-LCNEC) is not clear. This study aims to explore the influence of L-LCNEC preoperative serum LDH concentration and postoperative LDH concentration change trend on the disease-free survival (DFS) of patients after surgery, so as to judge the clinical prognosis of L-LCNEC provides new ideas.Collected the clinical data. The receiver operating characteristic (ROC) curve was used to determine the optimal cut-off value, while the Kaplan-Meier and Cox proportional hazard model were used to analyze data.DFS was shortened in patients with high serum LDH concentration before operation and increased LDH concentration after operation (P0.001, P0.001). The preoperative LDH concentration and postoperative LDH concentration change trend were independent prognostic factors for patients (P0.001, P=0.037).Preoperative LDH concentration and its postoperative concentration change trend in patients with L-LCNEC are independent prognostic factors for DFS of patients.【中文题目：手术前后血清LDH浓度与大细胞神经内分泌 肺癌患者手术预后的相关性分析】 【中文摘要：背景与目的 血清乳酸脱氢酶（lactate dehydrogenase, LDH）浓度升高，会导致小细胞肺癌、肺腺癌患者预后不佳，但其与大细胞神经内分泌肺癌（lung large-cell neuroendocrine carcinoma, L-LCNEC）患者预后的关系并不清楚，本研究旨在探讨L-LCNEC患者术前血清LDH浓度、术后LDH浓度变化趋势对患者术后无病生存期（disease-free survival, DFS）的影响，从而为判断L-LCNEC的临床预后提供新的思路。方法 本研究共纳入49例L-LCNEC术后患者，通过医疗记录、电话随访获取患者的临床资料。应用受试者操作特征曲线确定术前LDH的最佳临界值。用Kaplan-Meier绘制生存曲线。应用Cox比例风险模型计算独立预后因素。结果 术前血清LDH最佳临界值分别为195.5 U/L。生存曲线显示，术前血清LDH高浓度、术后LDH浓度升高的患者术后DFS缩短（P0.001, P0.001）。多因素分析显示，术前LDH浓度、术后LDH浓度变化趋势是L-LCNEC患者术后DFS的独立预后因素（P0.001, P=0.037）。结论 L-LCNEC患者术前LDH浓度及其术后浓度变化趋势是患者DFS的独立预后因素，术前高浓度、术后浓度升高会导致患者DFS缩短，预后差，应及早进行干预治疗。】 【中文关键词：大细胞神经内分泌肺癌；乳酸脱氢酶；预后】.

To study the clinical significance of serum epidermal growth factor receptor (EGFR) gene mutation and serum tumor markers in the prediction of tyrosine kinase inhibitor (TKI) efficacy in patients with lung adenocarcinoma. Ninety patients with pathologically diagnosed lung adenocarcinoma were enrolled. Further, 51 out of 90 patients received the EGFR-TKI therapy, oral gefitinib. The correlations among serum EGFR gene mutations in exons 18–21, serum tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigen 24-2 (CA24-2), carbohydrate antigen 125, carbohydrate antigen 15-3 as well as carbohydrate antigen 19-9 (CA19-9) levels, and EGFR-TKI efficacy were determined. There was a high consistency of EGFR gene mutation rate between serum and tissue samples. The serum EGFR gene mutation rate in female patients or non-smokers was significantly higher than that in male patients or smokers, respectively. Serum CA19-9, CA24-2, and CEA levels were significantly correlated with serum EGFR mutation. After receiving gefitinib, the progression-free survivals (PFSs) of patients with high serum CEA level, high serum CA19-9 level, or serum EGFR gene mutation were significantly higher than those of normal patients, respectively. The PFSs were significantly prolonged in patients with EGFR gene mutation and high serum CEA level or patients with EGFR gene mutation and high serum CA19-9 level compared with those in patients with one abnormal biomarker and normal patients. Combined detection of EGFR gene mutations as well as CA19-9 and CEA levels in peripheral blood can predict the efficacy of EGFR-TKI in the treatment of patients with lung adenocarcinoma.

Purpose: The induced death signals following oncogene inhibition underlie clinical efficacy of molecular targeted therapies against human cancer, and defects of intact cell apoptosis machinery often lead to therapeutic failure. Despite potential importance, other forms of regulated cell death triggered by pharmacologic intervention have not been systematically characterized. Experimental Design: Pyroptotic cell death was assessed by immunoblot analysis, phase-contrast imaging, scanning electron microscopy, and flow cytometry. Tumor tissues of patients with lung cancer were analyzed using IHC. Functional impact of pyroptosis on drug response was investigated in cell lines and xenograft models. Results: We showed that diverse small-molecule inhibitors specifically targeting KRAS-, EGFR-, or ALK-driven lung cancer uniformly elicited robust pyroptotic cell death, in addition to simultaneously invoking cellular apoptosis. Upon drug treatment, the mitochondrial intrinsic apoptotic pathway was engaged and the mobilized caspase-3 protease cleaved and activated gasdermin E (GSDME, encoded by DFNA5), which permeabilized cytoplasmic membrane and executed cell-lytic pyroptosis. GSDME displayed ubiquitous expression in various lung cancer cell lines and clinical specimens, including KRAS-mutant, EGFR-altered, and ALK-rearranged adenocarcinomas. As a result, cooccurrence and interplay of apoptosis and pyroptosis were widespread in lung cancer cells, succumbing to genotype-matched regimens. We further demonstrated that pyroptotic cell death partially contributed to the drug response in a subset of cancer models. Conclusions: These results pinpoint GSDME-dependent pyroptosis as a previously unrecognized mechanism of action for molecular targeted agents to eradicate oncogene-addicted neoplastic cells, which may have important implications for the clinical development and optimal application of anticancer therapeutics.

Background: Gastric cancer (GC) is one of the top 10 malignant tumors worldwide and poses a great threat to human life and health, the prevention and treatment of which has become the focus and difficulty of medical research. With its unique advantages, traditional Chinese medicine (TCM) is widely used in the prevention and treatment of postoperative recurrence and metastasis of GC as well as the improvement of patients’ quality of life. The aim of this study is to elucidate the curative effect and the underlying mechanism of Yiqi Huayu Jiedu (YQHYJD) decoction. Methods/design: This is a prospective, multicenter, randomized controlled trial continuing 3 years. Two hundred ninety-eight eligible patients will be randomly divided into 2 groups, the chemotherapy combined with placebo and the chemotherapy combined with YQHYJD group at a ratio of 1:1. All patients will receive the treatment for 6 months and follow up for 3 years. The primary outcomes are disease-free survival, and 1-year, 2-year, 3-year progression-free survival rate, while the secondary outcomes are tumor makers, TCM syndrome score, quality of life score, overall chemotherapy completion rate, intestinal flora diversity test, immune function (T, B lymphocyte subsets and NK cells) test. The Security index includes blood, urine and stool routine, electrocardiogram, liver function (ALT), and renal function (BUN, Scr). All of these outcomes will be analyzed at the end of the trial. Discussion: This research will provide the valuable evidence for the efficacy and safety of Yiqi Huayu Jiedu decoction in postoperative GC. Furthermore, it will be helpful to form a higher level of evidence-based medical basis for TCM in the treatment of GC recurrence and metastasis. Trial registration: ChiCTR2000039038

Probiotics effectively regulated lipid metabolism and improved hyperlipidemia. The purpose of this study was to further evaluate the functions of lipid-lowering strains in vivo and elucidate the mechanism. The hyperlipidemia model was constructed using a high fat diet, and four lipid-lowering strains were selected for intervention. In the four strains, the strains Lactobacillus vaginalis FN3 (FN3) and Bifidobacterium animalis subsp. Lactis F1-7 (F1-7) reduced TG, TC and LDL and increased HDL. These two strains decreased TC and TC in the liver of high fat diet fed mice, and they increased total bile acids (TBA) in feces. F1-7 and FN3 reduced the mRNA levels of Farnesoid X Receptor (FXR), recombinant Fibroblast Growth Factor 15 (FGF 15) and Niemann-Pick C1-Like 1 (NPC1L1), and up-regulated the Liver X Receptor (LXR) mRNA level. They decreased the protein expressions of FXR and NPC1L1. In addition, F1-7 up-regulated the protein expression of cholesterol 7-alpha hydroxylase (CYP7A1). In summary, Bifidobacterium animalis subsp. Lactis F1-7 and Lactobacillus vaginalis FN3 could regulate bile acid metabolism by downregulating the FXR gene and reduce the absorption of exogenous cholesterol by regulating NPC1L1. F1-7 could also participate in the FXR/FGF15 pathway to improve hyperlipidemia, which showed better effects than FN3.

Preliminary reports suggested that presepsin was a powerful biomarker for sepsis in a general population. However, presepsin levels change with age. This study aimed to investigate the diagnostic and prognostic value of presepsin among elderly patients with sepsis in the intensive care unit (ICU).A total of 142 elderly patients were enrolled and assorted into three groups: non-infection, infection, and sepsis. Blood samples were collected on days 1, 3 and 7 during the first week of ICU stay for presepsin measurement. Diagnostic and prognostic utilities were tested by receiver operating characteristic, cutoff levels, Kaplan Meier survival curves and hazard ratios.The presepsin level on days 1 and 3 were significantly higher in sepsis compared with infection (P0.01) and non-infection (P0.01). The diagnostic area under the curve (AUC) of presepsin was comparable to that of procalcitonin (P0.05) and higher than that of C-reactive protein or interleukin 6 (P0.05) on days 1 and 3. In AUC and Kaplan-Meier survival curves, presepsin on day 3 showed a significant prognostic value for 30-day mortality but was not superior to other biomarkers.The presepsin level was significantly higher in elderly patients with sepsis compared with the non-infection and infection groups. Presepsin has a reliable early diagnostic ability for sepsis comparable to that of PCT. However, it cannot be defined as a perfect biomarker for prognosis of 30-day mortality in elderly patients. An overall and continual assessment of all the clinical indexes for sepsis during the course of the disease is necessary.

In recent years, lung cancer has become the leading cause of cancer-related deaths. There is increasing evidence that many lipids and lipid analogs are key regulators of tumorigenesis, and factors that affect blood lipid levels such as smoking, diet, and obesity may be associated with cancer risk. With the deepening of research on the relationship between lipids and tumorigenesis, exploring the correlation between blood lipids and lung cancer risk and prognosis has become a research hotspot. This article reviews the research progress of the relationship between blood lipid levels and the risk of lung cancer, blood lipid levels and the prognosis of lung cancer patients, and the adjustment of blood lipid drugs and the prevention and treatment of lung cancer. .【中文题目：血脂水平与肺癌风险及预后相关性的 研究进展】 【中文摘要：近年来，肺癌成为导致癌症相关死亡的主要原因。越来越多证据表明，许多脂类和脂类类似物是肿瘤发生的关键调节因子，吸烟、饮食及肥胖等影响血脂水平的因素可能与癌症的风险相关。目前随着脂质与肿瘤发生过程关系的研究逐渐深入，探索血脂与肺癌风险及预后相关性已成为研究的热点。本文就血脂水平与肺癌发病风险、血脂水平与肺癌患者预后相关性及调整血脂药物与防治肺癌方向的研究进展进行综述。 】 【中文关键词：肺肿瘤；血脂；预后】.

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).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.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; p0.00001). 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.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.

Background Large‐cell neuroendocrine carcinoma of the lung (LCNEC) and small‐cell lung carcinoma (SCLC) are neuroendocrine neoplasms. However, the underlying mechanisms of common and distinct genetic characteristics between LCNEC and SCLC are currently unclear. Herein, protein expression profiles and possible interactions with miRNAs were provided by integrated bioinformatics analysis, in order to explore core genes associated with tumorigenesis and prognosis in SCLC and LCNEC. Methods http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE1037 gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) in LCNEC and SCLC, as compared with normal lung tissues, were selected using the GEO2R online analyzer and Venn diagram software. Gene ontology (GO) analysis was performed using Database for Annotation, Visualization and Integrated Discovery. The biological pathway analysis was performed using the FunRich database. Subsequently, a protein–protein interaction (PPI) network of DEGs was generated using Search Tool for the Retrieval of Interacting Genes and displayed via Cytoscape software. The PPI network was analyzed by the Molecular Complex Detection app from Cytoscape, and 16 upregulated hub genes were selected. The Oncomine database was used to detect expression patterns of hub genes for validation. Furthermore, the biological pathways of these 16 hub genes were re‐analyzed, and potential interactions between these genes and miRNAs were explored via FunRich. Results A total of 384 DEGs were identified. A Venn diagram determined 88 common DEGs. The PPI network was constructed with 48 nodes and 221 protein pairs. Among them, 16 hub genes were extracted, 14 of which were upregulated in SCLC samples, as compared with normal lung specimens, and 10 were correlated with the cell cycle pathway. Furthermore, 57 target miRNAs for 8 hub genes were identified, among which 31 miRNAs were correlated with the progression of carcinoma, drug‐resistance, radio‐sensitivity, or autophagy in lung cancer. Conclusion This study provided effective biomarkers and novel therapeutic targets for diagnosis and prognosis of SCLC and LCNEC., Common and distinct features of DEGs of SCLC and LCNEC were identified by integrated bioinformatics methods. Genes related to the cell cycle pathway were discussed. Target miRNAs for hub genes were identified and discussed.

Direct quantification of exhausted T cells in human cancer is lacking, and its predictive value for checkpoint-based treatment remains poorly investigated. We sought to systematically characterize the pan-cancer landscape and molecular hallmarks of T-cell dysfunction for the purpose of precision immunotherapy. Here, we defined a transcriptional signature for T-cell exhaustion through analyzing differential gene expression between PD-1-high and PD-1-negative CD8+ T lymphocytes from primary non-small cell lung cancer (NSCLC), followed by positive correlation tests with PDCD1 in TCGA lung carcinomas. A 78-gene signature for exhausted CD8+ T cells (GET) was identified and validated to reflect dysfunctional immune state spanning different species and disease models. We discovered that GET estimation significantly correlated with intratumoral immune cytolytic activity (CYT) and T-cell-inflamed gene expression profile (GEP) across 30 solid tumor types. Miscellaneous tumor-intrinsic and -extrinsic properties, in particular leukocyte proportions, genomic abnormalities, specific mutational signatures, and signaling pathways, were notably associated with GET levels. Furthermore, higher GET expression predicted an increased likelihood of clinical response to immune checkpoint inhibitors. These findings highlight the interrelation between T-cell exhaustion and immune cytolytic activity at the pan-cancer scale. The resulting inflamed tumor microenvironment may further crosstalk with other molecular and clinicopathological factors, which should be properly considered during immunotherapy biomarker development. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Clear cell renal cell carcinoma (ccRCC) is a common malignancy of the genitourinary system and is associated with high mortality rates. However, the molecular mechanism of ccRCC pathogenesis is still unclear, which translates to few effective diagnostic and prognostic biomarkers. In this study, we conducted a bioinformatics analysis on three Gene Expression Omnibus datasets and identified 437 differentially expressed genes (DEGs) related to ccRCC development and prognosis, of which 311 and 126 genes are respectively down-regulated and up-regulated. The protein-protein interaction network of these DEGs consists of 395 nodes and 1872 interactions and 2 prominent modules. The Staphylococcus aureus infection and complement and coagulation cascades are significantly enriched in module 1 and are likely involved in ccRCC progression. Forty-two hub genes were screened, of which von Willebrand factor, TIMP metallopeptidase inhibitor 1, plasminogen, formimidoyltransferase cyclodeaminase, solute carrier family 34 member 1, hydroxyacid oxidase 2, alanine-glyoxylate aminotransferase 2, phosphoenolpyruvate carboxykinase 1, and 3-hydroxy-3-methylglutaryl-CoA synthase 2 are possibly related to the prognosis of ccRCC. The differential expression of all nine genes was confirmed by quantitative real-time polymerase chain reaction analysis of the ccRCC and normal renal tissues. These key genes are potential biomarkers for the diagnosis and prognosis of ccRCC and warrant further investigation.

Background In recent years, systemic chemotherapy and molecular targeted therapy have become standard first-line treatments for locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC). The objective of this survey was to investigate first-line anticancer treatment patterns and gene aberration test status of patients with advanced nonsquamous NSCLC in China. Methods Patients included in this study had unresectable Stage IIIB/IV nonsquamous NSCLC and were admitted during August 2015 to March 2016 into one of 12 tertiary hospitals throughout China for first-line anticancer treatment. Patient data (demographics, NSCLC histologic type, Eastern Cooperative Oncology Group [ECOG] Performance Status [PS], gene aberration test and results [if performed], and first-line anticancer treatment regimen) were extracted from medical charts and entered into Medical Record Abstraction Forms (MERAFs), which were collated for analysis. Results Overall, 1041 MERAFs were collected and data from 932 MERAFs were included for analysis. Patients with unresectable Stage IIIB/IV nonsquamous NSCLC had a median age of 59 years, 56.4% were male, 58.2% were never smokers, 95.0% had adenocarcinoma, and 92.9% had an ECOG PS ≤1. A total of 665 (71.4%) patients had gene aberration tests; 46.5% (309/665) had epidermal growth factor receptor (EGFR) gene mutations, 11.5% (48/416) had anaplastic lymphoma kinase (ALK) gene fusions, and 0.8% (1/128) had a c-ros oncogene 1 gene fusion. The most common first-line treatment regimen for unresectable Stage IIIB/IV nonsquamous NSCLC was chemotherapy (72.5%, 676/932), followed by tyrosine kinase inhibitors (TKIs; 26.1%, 243/932), and TKIs plus chemotherapy (1.4%, 13/932). Most chemotherapy regimens were platinum-doublet regimens (93.5%, 631/676) and pemetrexed was the most common nonplatinum chemotherapy-backbone agent (70.2%, 443/631) in platinum-doublet regimens. Most EGFR mutation-positive patients (66.3%, 205/309) were treated with EGFR-TKIs. Conclusions Findings from our survey of 12 tertiary hospitals throughout China showed an increased rate of gene aberration testing, compared with those rates reported in previous surveys, for patients with advanced nonsquamous NSCLC. In addition, pemetrexed/platinum-doublet chemotherapy was the predominant first-line chemotherapy regimen for this population. Most patients were treated based on their gene aberration test status and results. Electronic supplementary material The online version of this article (doi:10.1186/s12885-017-3451-x) contains supplementary material, which is available to authorized users.

// Hong-Bo Yang 1 , Meng Xing 1 , Lei-Na Ma 1 , Ling-Xin Feng 1 , Zhuang Yu 1 1 Oncology Department, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China Correspondence to: Zhuang Yu, email: yuzhuang2002@163.com Keywords: NLR, PLR, OS, clinicopathologic parameters, lung cancers Received: April 06, 2016 Accepted: August 10, 2016 Published: October 08, 2016 ABSTRACT Setting: For now, hematological markers of inflammatory response have emerged as prognostic factors for patients with cancer. Many articles have confirm that neutrophil to lymphocyte ratio(NLR) and platelet–lymphocyte ratio (PLR) are relate with poor prognosis in various types of tumors. Objective: To investigate the association between NLR/PLR and progression free survival (PFS), overall survival (OS) and clinicopathologic parameters in lung cancer patients. Design: We performed relevant searches in PubMed database, Google Scholar, Springer Link. We included retrospective cohort studies that reported hazard ratios with 95% confidence intervals for the NLR or PLR and PFS or OS. Results: Both high NLR ( P < 0.00001) and high PLR ( P = 0.01) were significantly predictive of poorer OS. It also demonstrated that elevated NLR predicted poorer PFS ( P = 0.0002). High NLR was significantly associated with deeper Invasive of tumor, ( P = 0.006) extensive lymph nodetastasis(N2–3) ( P = 0.01), poor differentiation ( P = 0.0002) and vascular invasion( P = 0.002).There was no evidence of publication bias. Subgroup analysis indicated that little evidence of heterogeneity. However, PLR has no prognostic significance for SCLC. Conclusions: We provides further evidence in support of elevated NLR and PLR were predictors of poor OS and PFS in patients with lung cancer. Given this, NLR and PLR may be markers to report treatment outcomes.

Background: Golgi protein 73 (GP73) is a potential serum marker for the diagnosis of hepatocellular carcinoma (HCC). However, the diagnostic value of GP73 for HCC remains controversy, and little is known about the relationship between serum GP73 concentration and clinical characteristics of HCC. This study was designed to analyze the clinical values of GP73 in diagnosing HCC and the relationship between GP73 level and clinical characteristics in HCC patients. Materials and Methods: In this study, a total of 443 serum samples including 180 patients with HCC, 61 patients with liver cirrhosis (LC), 99 chronic hepatitis patients, and 103 healthy individuals were enrolled from November 2011 to April 2013. Enzyme-linked immunosorbent assay and chemiluminescent immunoassay were used to detect the serum level of GP73 and other biomarkers. Results: GP73 level in HCC group was significantly higher than LC group, chronic hepatitis B group, and healthy control group. In HCC group, GP73 level significantly increased in patients with lymphatic metastasis; moreover, GP73 level in Child–Pugh Class B and C groups was statistically significantly higher than that in Child–Pugh Class A group (P < 0.05). The area under the receiver operating characteristic (AUROC) curve of GP73 and alpha-fetoprotein (AFP) was 0.840 and 0.718, respectively, when diagnosing HCC. Moreover, the AUROC curve by use of the combination of GP73 and AFP was 0.903. The differences among these three aspects were statistically significant (P < 0.05). Conclusion: GP73 was better than AFP for the diagnosis of HCC, and the expression of serum GP73 is related with the clinical characteristics of HCC patients.

Somatic KEAP1-NRF2 pathway alterations are frequently detected in both lung adenocarcinomas and squamous cell carcinomas. However, the biological characteristics and molecular subtypes of KEAP1/NRF2-mutant lung cancer remain largely undefined. Here, we performed a stepwise, integrative analytic and experimental interrogation of primary tumors and cancer cell lines harboring KEAP1 or NFE2L2 (encoding NRF2) gene mutations. First, we discovered that KEAP1/NRF2-mutant lung cancer presented APOBEC-mediated mutational signatures, impaired tumor angiogenesis, elevated hypoxic stress and deficient immune-cell infiltrates. Second, gene expression-based subtyping revealed three molecular subsets of KEAP1/NRF2-mutant lung adenocarcinomas and two molecular subsets of KEAP1/NRF2-mutant lung squamous cell carcinomas, each associated with distinguishing genetic, differentiation, immunological and clinicopathological properties. Third, single-sample prediction allowed for de novo identification of KEAP1/NRF2-active tumors within KEAP1/NRF2-wild-type samples. Our data demonstrate that KEAP1/NRF2-mutant lung cancer is a microenvironmentally distinct, biologically heterogeneous, and clinically underestimated disease. These new pathological and molecular insights may accelerate the development of efficacious therapeutic strategies against human malignancies featured by KEAP1-NRF2 pathway activation.

IMPORTANCE: Patients with metastatic colorectal cancer (CRC) have limited effective and tolerable treatment options. OBJECTIVE: To evaluate the efficacy and safety of oral fruquintinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, as third-line or later therapy in patients with metastatic CRC. DESIGN, SETTING, AND PARTICIPANTS: FRESCO (Fruquintinib Efficacy and Safety in 3+ Line Colorectal Cancer Patients) was a randomized, double-blind, placebo-controlled, multicenter (28 hospitals in China), phase 3 clinical trial. From December 2014 to May 2016, screening took place among 519 patients aged 18 to 75 years who had metastatic CRC that progressed after at least 2 lines of chemotherapy but had not received VEGFR inhibitor therapy; 416 met the eligibility criteria and were stratified by prior anti-VEGF therapy and K-ras status. The final date of follow-up was January 17, 2017. INTERVENTIONS: Patients were randomized in a 2:1 ratio to receive either fruquintinib, 5 mg (n = 278) or placebo (n = 138) orally, once daily for 21 days, followed by 7 days off in 28-day cycles, until disease progression, intolerable toxicity, or study withdrawal. MAIN OUTCOMES AND MEASURES: The primary end point was overall survival. Key secondary efficacy endpoints were progression-free survival (time from randomization to disease progression or death), objective response rate (confirmed complete or partial response), and disease control rate (complete or partial response, or stable disease recorded ≥8 weeks postrandomization). Duration of response was also assessed. Safety outcomes included treatment-emergent adverse events. RESULTS: Of the 416 randomized patients (mean age, 54.6 years; 161 [38.7%] women), 404 (97.1%) completed the trial. Median overall survival was significantly prolonged with fruquintinib compared with placebo (9.3 months [95% CI, 8.2-10.5] vs 6.6 months [95% CI, 5.9-8.1]); hazard ratio (HR) for death, 0.65 (95% CI, 0.51-0.83; P

Objectives This study investigated factors associated with (i) the likelihood of receiving a gene aberration test and (ii) the choice of treatment between chemotherapy and targeted therapy in patients with non-small cell lung cancer (NSCLC) in China. Materials and methods This cross-sectional study analyzed data previously extracted from the medical charts of patients with unresectable Stage IIIB/IV nonsquamous NSCLC discharged from one of 12 tertiary hospitals in China between August 2015 and March 2016. Logistic regressions were applied to investigate factors associated with receiving a gene aberration test and the treatment decision. Results Data from 932 patients were analyzed. Patients were less likely to have a gene aberration test if they had a histologic subtype other than adenocarcinoma or a hospital waiting time for test results of >5 days. Patients were more likely to receive tyrosine kinase inhibitor (TKI) treatment than chemotherapy if they had a positive result for epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase gene aberration testing. EGFR positive patients were more likely to receive TKI treatment than chemotherapy if they did not have insurance for TKI or pemetrexed treatment, and more likely to receive chemotherapy than TKI treatment if they had a waiting time for test results of >5 days. EGFR wild-type/unknown patients receiving chemotherapy were more likely to receive pemetrexed if they attended a hospital in a developed area or had insurance for pemetrexed. Conclusion In this real-world setting in China, the choice of first-line treatment for advanced NSCLC was appropriately guided by gene aberration testing for most patients. However, gene aberration testing and the treatment decision were influenced by practical factors such as hospital location, the waiting time for test results, and insurance coverage, which should be addressed to ensure optimal patient care.

The multifunctional RNA-binding protein CUGBP1 regulates multiple aspects of nuclear and cytoplasmic messenger RNA (mRNA) processing, including splicing, stabilization, and translation of mRNAs. Previous studies have shown that CUGBP1 is overexpressed in non-small-cell lung cancer (NSCLC) tissues, but the pathological functions of CUGBP1 in tumorigenesis and development are unknown. Here, we provide the first evidence demonstrating the clinicopathological significance of CUGBP1 in NSCLC. Using immunohistochemistry, the levels of CUGBP1 expression in NSCLC tissues and adjacent non-cancerous tissues were examined and determined to be associated with differentiation. Short hairpin RNA-induced downregulation of CUGBP1 promoted apoptosis and decreased proliferation in the A549 NSCLC cell line. Moreover, Western blot analysis indicated that the depletion of CUGBP1 increased the protein levels of cyclin D1, BAD, BAX, Jun D, and E-cadherin, while the cyclin B1 level decreased. Knockdown of CUGBP1 decreased β-catenin and vimentin levels and increased E-cadherin expression, suggesting that CUGBP1 may contribute significantly to epithelial to mesenchymal transition (EMT) progression. These results demonstrate the importance of CUGBP1 in the biological and pathological functions of NSCLC and indicate its potential as a therapeutic target for NSCLC.

The aim of the present study was to investigate the role of miR-124 in lung cancer and identify the potential predictive value of miR-124 in postoperative non-small cell lung cancer (NSCLC) patients. We detected miR-124 expression in A549, NCL-H460 and normal lung epithelial BEAS-2E cells and showed a significantly lower expression level of miR-124 in NSCLC cells than in BEAS-2E cells. Upregulation of miR-124 expression levels in both A549 and NCL-H460 cells by transfection with miR-124 mimics suppressed cell proliferation and induced apoptosis. Further investigation revealed that miR-124 bound directly to the 3' UTR region of STAT3, thereby inhibiting STAT3 expression. In addition, miR-124 levels detected in NSCLC tissues were lower than those in adjacent normal lung tissues, while the opposite was observed for STAT3. In NSCLC, the expression levels of miR-124 and STAT3 correlated significantly with the tumor node metastases (TNM) stage, differentiation grade and lymph node metastasis, while the levels of these molecules did not differ significantly by gender, age, location, smoking index, pleural invasion or pathological type. The expression level of miR-124 was significantly associated with disease-free survival (DFS) in both positive and negative lymph node groups. Furthermore, patients with low miR-124 or high STAT3 expression generally received a worse prognosis in terms of both overall survival (OS) and DFS. In conclusion, our findings suggest that miR-124 functions as a tumor suppressor by targeting STAT3, and that miR-124 may potentially serve as a useful biomarker for the prognosis of NSCLC patients.

In diagnosis of lung cancer, rapid distinction between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) tumors is very important. Serum markers, including lactate dehydrogenase (LDH), C-reactive protein (CRP), carcino-embryonic antigen (CEA), neurone specific enolase (NSE) and Cyfra21-1, are reported to reflect lung cancer characteristics. In this study classification of lung tumors was made based on biomarkers (measured in 120 NSCLC and 60 SCLC patients) by setting up optimal biomarker joint models with a powerful computerized tool - gene expression programming (GEP). GEP is a learning algorithm that combines the advantages of genetic programming (GP) and genetic algorithms (GA). It specifically focuses on relationships between variables in sets of data and then builds models to explain these relationships, and has been successfully used in formula finding and function mining. As a basis for defining a GEP environment for SCLC and NSCLC prediction, three explicit predictive models were constructed. CEA and NSE are frequently- used lung cancer markers in clinical trials, CRP, LDH and Cyfra21-1 have significant meaning in lung cancer, basis on CEA and NSE we set up three GEP models-GEP 1(CEA, NSE, Cyfra21-1), GEP2 (CEA, NSE, LDH), GEP3 (CEA, NSE, CRP). The best classification result of GEP gained when CEA, NSE and Cyfra21-1 were combined: 128 of 135 subjects in the training set and 40 of 45 subjects in the test set were classified correctly, the accuracy rate is 94.8% in training set; on collection of samples for testing, the accuracy rate is 88.9%. With GEP2, the accuracy was significantly decreased by 1.5% and 6.6% in training set and test set, in GEP3 was 0.82% and 4.45% respectively. Serum Cyfra21-1 is a useful and sensitive serum biomarker in discriminating between NSCLC and SCLC. GEP modeling is a promising and excellent tool in diagnosis of lung cancer.

Background Dulanermin is a recombinant soluble human Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) that activates apoptotic pathways by binding to proapoptotic death receptor (DR) 4 and DR5. The purpose of this study was to evaluate the efficacy and safety of dulanermin combined with vinorelbine and cisplatin (NP) as the first-line treatment for patients with advanced non-small-cell lung cancer (NSCLC). Experimental design Patients were randomly assigned to receive NP chemotherapy (vinorelbine 25 mg/m2 on days 1 and 8 and cisplatin 30 mg/m2 on days 2 to 4) for up to six cycles plus dulanermin (75 μg/kg on days 1 to 14) or placebo every three weeks until disease progression, intolerable toxicity, or withdrawal of consent. The primary end point was progression-free survival (PFS), and the secondary end points included objective response rate (ORR), overall survival (OS), and safety evaluation. Results Between October 2009 and June 2012, 452 untreated patients with stage IIIB to IV NSCLC were randomly assigned to receive dulanermin plus NP (n = 342) and placebo plus NP (n = 110). Median PFS was 6.4 months in the dulanermin arm versus 3.5 months in the placebo arm (hazard ratio (HR), 0.4034; 95% CI, 0.3181 to 0.5117, p

Toll-like receptor 4 (TLR4) is considered to play an important role in neuronal death in animal models and could be an important therapeutic target following traumatic brain injury (TBI). Resatorvid is a small molecule, commonly accepted to inhibit TLR4-mediated pathway. The purpose of this study was to investigate the neuroprotective effect of resatorvid after TBI. Our data revealed that inhibition of TLR4 by resatorvid attenuated the development of TBI in mouse model. And we found that resatorvid administration dramatically reduced neuronal apoptosis. To investigate the cellular mechanism, we evaluated the expression of transforming growth factor-β-activated kinase 1 (TAK1), which plays a crucial role in TLR4 signal transduction pathway and is activated by phosphorylation in response to TBI. In addition, enzyme-linked immunosorbent assay was used to determine the expression of tumor necrosis factor-α (TNF-α) and interlukin-1β (IL-1β) at 24h after injury. Our results showed that resatorvid treatment significantly reduced the protein levels of TAK1, p-TAK1, TNF-α, and IL-1β compared with vehicle treatment. Importantly, the delayed therapy (4h post injury) once daily consecutively for 5days ameliorated brain damage and improved neurological recovery, suggesting that this drug has a wide therapeutic time window. Clinically, we observed that TLR4 and TAK1 expression was significantly increased in human contusion specimens after TBI. These data provide an experimental rationale for the evaluation of TLR4 as a clinical target and therapeutic implication of resatorvid in human traumatic brain injury.

Background: This meta-analysis was performed to investigate the relationship between methylation of the P14 and O6-methylguanine-DNA methyltransferase (MGMT) genes and the risk of hepatocellular carcinoma (HCC). Materials and Methods: We searched PubMed, EMBASE, the Chinese Biomedical Database (CBM), and the China National Knowledge Infrastructure (CNKI) databases to identify relevant studies that analysed HCC tissues for P14 and MGMT gene methylation status; we then performed a meta-analysis. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to evaluate the association between gene methylation and the risk of HCC. Results: Ten studies that assessed P14 gene methylation in 630 HCC tumour tissues and nine studies analysing MGMT methylation in 497 HCC tumour tissues met our inclusion criteria. Our meta-analysis revealed that the rate of P14 methylation was significantly higher in HCCs than in adjacent tissues (OR 3.69, 95%CI 1.63-8.35, p=0.002), but there was no significant difference in MGMT methylation between HCC and adjacent tissues (OR 1.76, 95%CI 0.55-5.64, p=0.34). A subgroup analysis according to ethnicity revealed that P14 methylation was closely related to the risk of HCC in Chinese and Western individuals (Chinese, OR 7.74, 95%CI 1.36-44.04, p=0.021; Western, OR 3.60, 95%CI 1.49-8.69, p=0.004). Furthermore, MGMT methylation was not correlated with the risk of HCC in Chinese individuals (OR 2.42, 95%CI 0.76-7.73, p=0.134). The combined rate of P14 methylation was 35% (95%CI 24-48%) in HCC tumour tissues and 11% (95%CI 4-27%) in adjacent tissues, whereas the combined rate of MGMT methylation was 15% (95%CI 6-32%) in HCC and 10% (95%CI 4-22%) in adjacent tissues. Conclusions: These results suggest that the risk of HCC is related to P14 methylation, but not MGMT methylation. Therefore, P14 gene methylation may be a potential biomarker for the diagnosis of HCC.

Epidemiological studies show conflicting results regarding the link between serum triglyceride and the risk of prostate cancer and breast cancer. Therefore, we performed a meta-analysis of prospective studies to clarify this association. We searched PubMed, EMBASE, the Chinese Biomedical Database (CBM), and the China National Knowledge Infrastructure (CNKI) database to identify relevant prospective studies of the relationship between serum triglyceride and prostate cancer and breast cancer risk. Study-specific estimates adjusting for potential confounders were combined to evaluate a summary relative risks (RRs) and 95% confidence intervals (95% CIs) using a fixed- or random-effects model. A total of 11 prospective studies (619,410 subjects and 15,691 incident prostate cancer patients) and 8 prospective studies (590,878 subjects and 12,177 incident breast cancer patients) were respectively included in our meta-analysis to assess the associations of serum triglyceride with prostate cancer and breast cancer risk. The pooled adjusted RR estimates for prostate cancer and breast cancer for the highest versus the lowest exposure levels of serum triglycerides were 0.95 (95% CI: 0.87-1.04) and 0.94 (95% CI: 0.87-1.00), respectively. Additionally, a dose-response analysis revealed that serum levels of triglycerides were not associated with the risk of prostate cancer and breast cancer. We found that serum triglyceride was not related to the risk of prostate cancer and breast cancer.

Aims: To investigate the effect of Ginkgo biloba extract (EGb761) on cell proliferation and apoptosis in human colon cancer cells. Methods: Human colon cancer cell lines (HT-29) were cultured and incubated with various concentrations (0-320 mg/l) of EGb 761 solution for up to 72 h. Cell viability, cell apoptosis, cell cycle, expression of caspase-3, the mRNA levels of p53, and Bcl-2 were assessed. Results: EGb 761 inhibited the growth of HT-29 cells in a time-dose-dependent manner. At 80 and 320 mg/L, EGb 761 increased the number of cells in the G0/G1 phase and reduced cells in the G2/M and S phase. EGb 761 treatment also increased the apoptosis ratio of the HT-29 cells. EGb 761 treatment was associated with an increase in caspase-3 activities, reduction in bcl-2 mRNA expression and elevation in p53 mRNA expression. Conclusion: EGb 761 inhibits the progression of human colon cancer cells. Its therapeutic effect may be related to enhanced caspase-3 activities, up-regulation of p53 and down-regulation of bcl-2 genes.

A growing body of evidence suggests that inflammation plays a crucial role in cerebral aneurysm initiation, progression, and rupture. High-mobility group box 1 (HMGB1) is a non-histone nuclear protein that can serve as an alarmin to drive the pathogenesis of inflammatory disease. The purpose of this study was to investigate the expression of HMGB1 in the wall of ruptured and unruptured human cerebral aneurysms. Human cerebral aneurysms (25 ruptured and 16 unruptured) were immunohistochemically stained for HMGB1. As controls, four specimens of the middle cerebral arteries obtained at autopsy were also immunostained. Immunofluorescence double staining was used to determine HMGB1 cellular distribution. HMGB1 was nearly undetectable in the controls. All aneurysm tissues stained positive for HMGB1 monoclonal antibody, and expression of HMGB1 was more abundant in ruptured aneurysm tissue than unruptured aneurysms (p < 0.05). Furthermore, the expression of HMGB1 had no correlation with aneurysm size and time resected after the rupture. HMGB1 nuclear immunoreactivity was co-localized with immunoreactivity of CD3 in T lymphocytes, CD20 in B lymphocytes, CD68 in macrophages, α-SMA in smooth muscle cells, and CD31 in endothelial cells. Cytoplasmic HMGB1 localization was also detected in macrophages and T lymphocytes. Taken together, HMGB1 is expressed in the wall of human cerebral aneurysms and is more abundant in ruptured aneurysms than in unruptured ones. These data indicate a possible role of HMGB1 in the pathophysiology of human cerebral aneurysms.

CUGBP1, which is involved in posttranscriptional regulatory networks, may control cell growth, activation and differentiation. Meanwhile, CCAAT/enhancer-binding protein α (C/EBPα) acts as a basic leucine zipper transcription factor which controls differentiation-dependent gene expression and inhibits cell proliferation. To date, very little is known about the association between CUGBP 1 and C/EBPα in regulating cell proliferation and apoptosis in non-small cell lung cancer (NSCLC). CUGBP1 and C/EBPα mRNA expressions were analyzed in NSCLC tumor and adjacent normal tissues, and the relationship in clinicopathological parameters was evaluated. Knockdown of CUGBP1 and C/EBPα regulated by CUGBP1 in NSCLC cell line was identified by real-time PCR and Western blot. The effect of depletion of CUGBP1 was evaluated by MTT assay and Annexin/Propidium Iodide Apoptosis assay. CUGBP1 is highly expressed and expression of C/EBPα is low in NSCLC tissues. The correlation analysis revealed that there was negative correlation between the expression of CUGBP 1 and C/EBPα. Knockdown of CUGBP1 effectively silenced the expression of CUGBP1 and up-regulated C/EBPα. Also, suppression of CUGBP1 inhibits proliferation and induces apoptosis in A549 cells. These observations suggest that the first proof the overexpression of CUGBP1 in NSCLC contributes to tumorigenesis through down-regulation of C/EBPα. Knockdown of CUGBP1 or up-regulation C/EBPα might be a potential therapeutic approach for human non-small cell lung cancers.

A growing body of evidence suggests that inflammation actively participates in cerebral aneurysm initiation, progression, and rupture. The primary objective of this study was to assess the expression of NLR family, Pyrin-domain containing 3 (NLRP3) inflammasome in human cerebral aneurysms.Aneurysmal domes (19 ruptured and 17 unruptured) from patients undergoing surgical treatment for ruptured or unruptured cerebral aneurysms were analyzed. A control sample comprising 4 middle cerebral arteries was obtained from autopsy subjects. The expression of NLRP3, apoptotic speck-containing protein with a card (ASC), caspase-1, and interleukin (IL)-1β were assessed by immunohistochemistry. Immunofluorescence double staining was used to determine NLRP3, ASC, and caspase-1 cellular distribution.Expression of NLRP3, ASC, and caspase-1 were more abundant in ruptured aneurysm tissue than that in unruptured aneurysms, based on a semi-quantitative grading (P.05). IL-1β was also overexpressed in the ruptured cerebral aneurysms and associated with increased expression of NLRP3, ASC, and caspase-1 (P.05). Furthermore, NLRP3, ASC, and caspase-1 immunoreactivity were colocalized with immunoreactivity of CD3 in T lymphocytes and CD68 in macrophages.NLRP3 inflammasome was expressed in the wall of human cerebral aneurysms and was more abundant in ruptured aneurysms than in unruptured. This study raises the possibility that NLRP3 inflammasome may be involved in the pathogenesis of human intracranial aneurysms, and this requires further study.

Epidermal growth factor receptor (EGFR) and ErbB3 (HER3) play important roles in the regulation of cell proliferation, differentiation, anti-apoptosis and chemoresistance; however, their dysregulation in pemetrexed (PEM) resistance remains unclear. The aim of the present study was to clarify the relationship between PEM resistance and gene expression of EGFR and ErbB3, by establishing the PEM-resistant lung adenocarcinoma A549 cell line, A549/PEM. Compared with A549 cells, the A549/PEM cells were significantly more resistant to PEM (P=0.0024). The downregulation of S phase and arrest at G1 stage were detected in the A549/PEM cell line when compared to the A549 cells (P

To explore the invasiveness of papillary thyroid microcarcinoma(PTMC)with BRAF mutation.Totally 99 patients with PTMC with BRAF mutation were enrolled in this study, meanwhile another 97 patients with papillary thyroid carcinoma (PTC) (tumor size1 cm)with BRAF mutation were included as controls. The clinicopathologic factors including extrathyroidal invasion, multifocality, and distant metastasis were analyzed.The rates of extrathyroidal invasion and nodal metastasis in PTMC group were as high as 16.10% and 71.74%, respectively. In the PTMC group and PTC group,the extrathyroidal invasion rate was 16.10% and 39.18%, cervical lymph node metastasis rate was 71.74% and 91.75%, and distant metastasis rate was 1.01% and 9.28%, respectively. In the PTMC subgroups with tumor sizes ≤0.3 cm, 0.3-0.6 cm, and 0.6-1.0 cm, the cervical lymph node invasion rate was 60.00%, 72.50%, and 73.81%, the extrathyroidal invasion rate was 10.00%, 9.09%, and 24.44%, and the multifocality rate was 60.00%, 38.64%, and 57.78%, respectively. Univariate analysis showed that the tumor size was not significantly correlated with multifocality (Χ (2)=3.752, P=0.153), cervical lymph node metastasis (Χ (2) = 0.780,P = 0.677), extrathyroidal invasion (Χ (2) = 4.182, P = 0.124), and distant metastasis (Χ (2)=1.212, P = 0.545). While the BRAF group and PTC group were not significantly different in multifocality (Χ (2) = 1.742, P=0.187), they were significantly different in terms of extrathyroidal invasion (Χ (2) = 13.000, P = 0.000), nodal involvement (Χ (2) = 12.819, P = 0.000), and distant metastasis (Χ (2) = 5.316, P = 0.021). Multivariate analysis showed that nodal metastasis was independently associated with size1 cm (P=0.001) and extrathyroidal invasion (P=0.003).BRAF mutant PTMC manifests relative high extrathyroidal involvement and nodal metastasis, and the similar multifocality as BRAF mutant PTC. Radioactive iodine should be considered in PTMC with the presence of BRAF mutation combined with extrathyroidal invasion or nodal metastasis.

To report the results of a safety analysis from a phase II trial comparing administration of weekly paclitaxel plus S-1 (TS) versus paclitaxel plus 5-fluorouracil (5-FU)/calcium folinate (LV) (TLF) as first-line therapy for advanced gastric cancer.Patients (n = 240) with previously untreated advanced gastric cancer were randomly assigned to receive either TS or TLF in a 28-day cycle for six cycles.The clinical features of both sets of patients were similar, with the exception of the incidence of prior chemotherapy (P0·05). Most treatment-related adverse events occurred at similar rates in both treatment arms. However, patients receiving TS experienced an increase in all-grade especially grade 3/4 neutropenia, with an incidence of 43·7% in the TS arm and 16·3% in the TLF arm, respectively (P0·05). Other severe adverse events were infrequent and not significantly different between the groups.The safety and tolerance of weekly paclitaxel plus S-1 or 5-FU/LV is well in untreated advanced gastric cancer patients.

To evaluate the efficacy and safety of weekly paclitaxel combined with S-1 or fluorouracil in the first line treatment of advanced gastric carcinoma.Two hundred and forty patients with untreated advanced gastric carcinoma were randomized into two arms, patients in the experimental arm were given paclitaxel and S-1, while those in the control arm received paclitaxel and fluorouracil. The regimen of experimental arm was paclitaxel 60 mg/m(2) by intravenous infusion, day 1, 8, 15; S-1 80 - 120 mg/day given by oral administration, day 1 - 14. The regimen of control arm was fluorouracil 500 mg/m(2) by intravenous infusion continuously, day 1 - 5; CF 20 mg/m(2) by intravenous infusion, day 1 - 5. The regimens in both arms were repeated every 28 days. The efficacy and safety of both arms were assessed.Two hundred and twenty-eight patients were analyzed in the full analysis set, and 192 patients were analyzed in per-protocol set (experimental arm 100 patients, control arm 92 patients). The overall response rates of experimental and control arms were 50.0% and 28.3% (P = 0.002), and the disease control rates were 82.0% and 70.7% (P = 0.064), respectively. The primary endpoints of experimental arm were non-inferior to that of the control arm. The secondary endpoint of experimental arm in terms of median progression free survival was significantly better than that of control arm (5 months versus 4 months, P = 0.006). The experimental arm had a higher incidence of grade III-IV bone marrow suppression than the control arm, but the incidence of fever in both arms was not significantly different.Oral administration of S-1 is an alternative option of venous infusional fluorouracil. Weekly paclitaxel combined with S-1 is a safe regimen and has a promising efficacy.

Purpose This study aimed to compare the efficacy and toxicity of weekly paclitaxel plus S-1 with weekly paclitaxel plus 5-fluorouracil in treating advanced gastric cancer as first line regimen. The primary end-point was disease control rate (DCR). Methods Patients with advanced or recurrent gastric cancer were randomly assigned to an experimental arm or a control arm. The experimental arm’s dosage schedule was paclitaxel 60 mg/m2 (intravenous infusion) on days 1, 8 and 15 and S-1 80–120 mg/d (oral administration) on days 1–14. Control arm patients were given the same paclitaxel, combined with 5-fluorouracil 500 mg/m2 (continuous intravenous infusion) on days 1–5; and leucovorin 20 mg/m2 (intravenous infusion) on days 1–5. All schedules were repeated every 28 d. Results A total of 240 patients were enrolled and equally randomised into two arms. The overall response rate and DCR of the experimental arm was non-inferior to that of the control arm both in the per-protocol set and the full analysis set. The secondary end-point median progression-free survival (PFS) of the experimental and control arms was 153 and 129 d, with the hazard ratio of 0.641 (95% CI: 0.473–0.868, P = 0.004). The hazard ratio of the time to treatment failure of the two arms was 1.449 (95% CI: 0.705–2.980, P = 0.229). The six-month PFS rates of both arms were similar (31.3% versus 31.8%, P = 0.94). Cox regression analysis indicated that only treatment regimen and age were independent predictive factors for PFS. The most common adverse events were haematological and gastrointestinal. The rates of grade 3–4 adverse events were not significantly different between the two study arms and were mostly lower than 5%. Conclusion Weekly paclitaxel combined with S-1 is an active and well-tolerated regimen, supporting the view that S-1 can be an alternative for infusional 5-fluorouracil for advanced gastric cancer.

We conducted a case-control study in China to clarify the association between the XRCC1-Arg399Gln polymorphism and HCC risk.A total of 202 cases and 236 controls were selected from the the Affiliated Hospital of Qingdao University from May 2008 to May 2010. Assessment of the XRCC1-Arg399Gln polymorphism was based upon duplex polymerase-chain-reactions with the confronting-two-pair primer (PCR- CTPP) method. All analyses were performed using the STATA statistical package.A significant increase in risk was associated with the Arg/Gln genotype (adjusted OR 1.55, 95%CI=1.03-2.57) compared with Arg/ Arg. However, the Gln/Gln genotype had non-significant increased risk of HCC with adjusted OR (95%CI) of 1.34(0.67-2.38). There was also a significant increase with the Arg/Gln genotype among HCC patients above 50 years old (OR=1.95, 95% CI=1.14-3.57). Additionally, the risk of HCC was moderately increased in drinkers with Arg/Gln genotype compared with never drinkers, and the adjusted OR (95% CI) was 1.89 (1.13-3.45).This study demonstrated that a polymorphism in a DNA repair gene may influence the risk of HCC. The XRCC1 codon Arg/Gln was this associated with an increased risk of HCC, especially in patients above 50 years old and/or with a drinking habit.

To explore the efficacy and safety of palonosetron in the prevention of acute and delayed chemotherapy-induced nausea and vomiting after moderate to severe emetogenic chemotherapy.From November 2008 to November 2009, a multicenter, randomized, double-blind and self-crossover phase II clinical trial with a total planned enrollment of 160 patients was carried out to compare palonosetron (drug A) with tropisetron (drug B). The subjects were randomized divided into groups AB and BA. The dosing sequence in the group AB was drug A the first cycle and drug B the second cycle while the BA group was administered reversely. The efficacy was evaluated within a period of 5 days after cisplatin or adriamycin-based regimen chemotherapy. Adverse effects were assessed by CTCAE 3.0.Among 155 enrolled cases, 132 cases were assessable for efficacy. The complete control rate of acute chemotherapy-induced nausea and vomiting was 54.55% vs 51.52% for drug A vs drug B (P0.05), but that of delayed reaction was 53.03% vs 38.64% respectively. There were significant differences (P = 0.01). Meanwhile, the rate of adverse effects was 4.90% for investigational agent without severe adverse events. The main adverse reactions were headache and dizziness.With a high safety profile, palonosetron is an effective agent for the prevention of acute and delayed chemotherapy-induced nausea and vomiting.