Gastric cancer secreted miR-214-3p inhibits the anti-angiogenesis effect of apatinib by suppressing ferroptosis in vascular endothelial cells.

Different from necrosis, apoptosis, autophagy and other forms of cell death, ferroptosis is a mechanism that catalyzes lipid peroxidation of polyunsaturated fatty acids under the action of iron divalent or lipoxygenase, leading to cell death. Apatinib is currently used in the third-line standard treatment of advanced gastric cancer, targeting the anti-angiogenesis pathway. However, Apatinib-mediated ferroptosis in vascular endothelial cells has not been reported yet. Tumor-secreted exosomes can be taken up into target cells to regulate tumor development, but the mechanism related to vascular endothelial cell ferroptosis has not yet been discovered. Here, we show that exosomes secreted by gastric cancer cells carry miR-214-3p into vascular endothelial cells and directly target zinc finger protein A20 to negatively regulate ACSL4, a key enzyme of lipid peroxidation during ferroptosis, thereby inhibiting ferroptosis in vascular endothelial cells and reducing the efficiency of Apatinib. In conclusion, inhibition of miR-214-3p can increase the sensitivity of vascular endothelial cells to Apatinib, thereby promoting the antiangiogenic effect of Apatinib, suggesting a potential combination therapy for advanced gastric cancer.

[The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study].

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

Association of oxidative stress and Kashin-Beck disease integrated Meta and Bioinformatics analysis.

OBJECTIVE: To explore the association between oxidative stress (OS) and Kashin-Beck disease (KBD). METHODS: Terms associated with "KBD" and "OS" were searched in the six different databases up to October 2021. Stata 14.0 was used to pool the means and standard deviations using random-effect or fixed-effect model. The differentially expressed genes in the articular chondrocytes of KBD were identified, the OS related genes were identified by blasting with the GeneCards. The KEGG pathway and gene ontology enrichment analysis was conducted using STRING. RESULTS: The pooled SMD and 95% CI showed hair selenium (-4.59; -6.99, -2.19), blood selenium (-1.65; -2.86, -0.44) and glutathione peroxidases (-4.15; -6.97, -1.33) levels were decreased in KBD, whereas the malondialdehyde (1.12; 0.60, 1.64), nitric oxide (2.29; 1.31, 3.27), nitric oxide synthase (1.07; 0.81, 1.33) and inducible nitric oxide synthase (1.69; 0.62, 2.77) were increased compared with external controls. Meanwhile, hair selenium (-2.71; -5.32, -0.10) and glutathione peroxidases (-1.00; -1.78, -0.22) in KBD were decreased, whereas the malondialdehyde (1.42; 1.04, 1.80), nitric oxide (3.08; 1.93, 4.22) and inducible nitric oxide synthase (0.81; 0.00, 1.61) were elevated compared with internal controls. Enrichment analysis revealed apoptosis was significantly correlated with KBD. The significant biological processes revealed OS induced the release of cytochrome c from mitochondria. The cellular component of OS located in the mitochondrial outer membrane. CONCLUSIONS: The OS levels in KBD were significantly increased because of selenium deficiency, OS mainly occurred in mitochondrial outer membrane, released of cytochrome c from mitochondria, and induced apoptotic signaling pathway.

[Correlation between nUGT1A1 gene polymorphisms and adverse events of irinotecan plus S-1 for patients with recurrent or metastatic esophageal squamous cell carcinoma: a prospective, open-label, randomized controlled trial (ESWN 01)].

Objective: To investigate the correlation between UGT1A1 polymorphisms and the irinotecan plus S-1 regimen-induced toxicities in Chinese advanced esophageal squamous cell carcinoma (ESCC) patients. Methods: A total of 46 recurrent or metastatic ESCC patients selected from ESWN 01 trial were randomly assigned to irinotecan plus S-1 group [intravenous infusion of irinotecan (160 mg/m(2)) on day 1 and oral S-1 (80-120 mg) on days 1-10, repeated every 14 days]. Peripheral venous blood at baseline was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6 and UGT1A1*28 were analyzed by polymerase chain reaction (PCR) amplification. Irinotecan plus S-1 regimen-induced toxicities of patients with different UGT1A1 polymorphisms were observed. The correlation between UGT1A1 polymorphisms and the adverse effects was analyzed. Results: Among the 46 patients, the numbers of UGT1A1*6 wild type genotype (GG), mutant heterozygote (GA) and mutant homozygote (AA) were 30, 15 and 1, while those with UGT1A1*28 wild type genotype (TA6/6), mutant heterozygote (TA6/7) and mutant homozygote (TA7/7) were 36, 8 and 2, respectively. Only one patient with UGT1A1*6 AA genotype occurred grade 3 diarrhea, while one of the 2 patients with UGT1A1*28 TA7/7 genotype occurred grade 4 diarrhea. No neutropenia was observed in the patient with UGT1A1*6 AA genotype, however, both of the two patients with UGT1A1*28 TA7/7 genotype occurred grade 3-4 neutropenia. Patients with UGT1A1*28 genetic polymorphism (TA 6/7 or TA7/7) had a higher response rate compared with wild-type TA6/6 carriers. (55.6% versus 26.5%). Conclusions: The homozygous genotype of UGT1A1*6 AA and UGT1A1*28 TA7/7 are rare (<5%) in Chinese ESCC population. Not all homozygous AA and TA7/7 carriers occur severe dose limited toxicities (DLT) when treated with irinotecan (160 mg/m(2)) plus S-1 regimen for 2 weeks. However, it's still necessary torigorously observe the occurrence of severe diarrhea and neutropenia in patients with UGT1A1*6 AA and UGT1A1*28 TA7/7 and adjust the dose timely.

[Value of serum parathyroid hormone in the diagnosis of primary aldosteronism].

Objective: To explore the value of serum parathyroid hormone (PTH) in the diagnosis of primary aldosteronism (PA) and to investigate an optimal cut-off of serum PTH to distinguish PA from nonfunctional adrenal tumor (NFA). Methods: The clinical data of patients with adrenal incidentaloma in Chinese PLA General Hospital from January 1, 2017 to December 31, 2019 were collected. The data of PA and NFA by clinical characteristics and evaluation on endocrine function were retrospectively analyzed. The logistic regression model was used to find the potential risk factors of elevated PTH. The receiver operating characteristic(ROC) curve was used to evaluate the efficacy of PTH in diagnosis of PA and to explore the best cut-off value. Results: A total of 773 patients were included. There were 356 PA patients (203 males, 57.0%), aged (50±11) years and 417 NFA patients (219 males, 52.5%), aged (51±12) years. The serum PTH level in patients with PA was significantly higher than that in patients with NFA [63.1 (48.4, 80.3) ng/L vs 41.7 (34.1, 51.7) ng/L, P<0.05], as well as the proportion of patients with elevated PTH level (47.8% vs 7.2%, P<0.05). Logistic regression analysis showed that having PA and deficiency of Vitamin D were risk factors for PTH elevation (both P<0.05). The ROC curve showed that the best cut-off value of PTH for the diagnosis of PA in patients with vitamin D deficiency was 56.44 ng/L, with a sensitivity of 66.5% and a specificity of 83.0%, and that in patients with normal vitamin D was 48.81 ng/L, with a sensitivity of 70.5% and a specificity of 72.6%. Conclusions: Patients with PA tend to show increased levels of serum PTH compared with NFA patients. The level of serum PTH can be used as one of the valuable indexes in screening of PA.

[Analysis of sugammadex for antagonistic neuromuscular block in patients with radical resection of lung cancer under thoracoscope].

Objective: To investigate the efficacy and safety of sugammadex for antagonistic neuromuscular block in patients with radical resection of lung cancer under thoracoscope. Methods: One hundred patients undergoing radical resection of lung cancer under thoracoscope in Affiliated Cancer Hospital of Zhengzhou University from March to September in 2019, were randomly divided into control group (group C) and sugammadex group (group S). All patients were anaesthetized (induced and maintained) with intravenous target-controlled infusion of propofol and remifentanil, and intermittent intravenous injection of the neuromuscular block of rocuronium. During the operation, the bispectral index (BIS) was used to monitor the depth of anesthesia, and the neuromuscular block was assessed with TOF. Single-lung mechanical ventilation and double-lumen endotracheal intubation were carried out, and patient-controlled analgesia after operation were enforced. Patients in group C received neostigmine (2 mg) combined with atropine (0.5-1.0 mg) after thoracic closure, while patients in group S received sugammadex (2 mg/kg) at TOF count (≥2) after thoracic closure, and then double-lumen endotracheal tubes were extubated according to extubation indications. At these time points: T(0) (immediate before anesthesia induction), T(1) (immediate before tracheal intubation), T(2) (immediately after thoracic closure), T(3) (1 h after operation), T(4) (6 h after operation), T(5) (24 h after operation), T(6)(48 h after operation), the heart rate(HR) and mean arterial pressure (MAP) were recorded, QT interval (V3 ECG) were measured and calculated, indicators of liver function [alanine transaminase (ALT), aspartate transaminase(AST)], renal function [blood urea nitrogen (BUN), creatinine (Cre)] and clotting function [thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB)] were detected. The duration of operation, postoperative conditions within 48 hours after operation(the time of tracheal tube extubation, respiratory suppression/dysfunction, allergy, nausea and vomiting, itching of skin, abnormal sensation), pathological types and the postoperative hospital stay were recorded. Results: There were no significant differences of the age, sex ratio, body mass index (BMI), American Society of Anesthesiologists (ASA) grading ratio, duration of operation, pathological types and the postoperative hospital stay, HR, MAP and QT interval between two groups (all P>0.05). There were no remarkable differences of the levels of serum histamine, ALT, AST, BUN, Cre, TT, PT, APTT and FIB before and after administration of neuromuscular blockade antagonists (neostigmine or Sugammadex) in the same group patients (all P>0.05), also no significant differences between group C and group S at the same time points (all P>0.05). Average time of tracheal tube extubation in group S [(3.7±1.3) min] was sharply shorter than that in group C [(14.5±4.4) min, t=2.266, P<0.05)]. There were no patients with allergy, skin itching, sensory abnormality in these two groups. There were no significant difference of the incidence of postoperative nausea and vomiting between these two groups. There were 5 patients with respiratory depression in group C and no respiratory depression patient in group S, the difference was statistically significant between these two groups (χ(2)=5.263, P<0.05). Conclusion: Sugammadex is effective for antagonizing the neuromuscular blockade of rocuronium in patients with radical resection of lung cancer under thoracoscope, and can shorten the time of tracheal tube extubation after surgery.

[Prognosis factors analysis of 56 cases of non-Hodgkin's lymphoma originating from the nasopharynx].

Objective:To investigate the prognosis of non-Hodgkin's lymphoma originating from the nasopharynx.Method:The clinical data of 56 patients with a primary diagnosis of non-Hodgkin's lymphoma originating from the nasopharynx treated between January 2010 and December 2015 were studied.The association between clinical parameters and survival rate was evaluated by Kaplan-Meier method and Cox regression model.Result:The 1,3,5-year overall survival were 91.1%, 73.1%,and 49.6% respectively.Single factor analysis displayed that age,Ann-Arbor staging,iactate dehydrogenase,combined with B symptoms at the time of diagnosis,international prognostic index and the expression level of Ki-67 were related to the prognosis factors.Multivariate analysis showed that the international prognostic index greater than or equal to 2 points and the positive rate of Ki-67 greater than or equal to 60% were the independent risk factors for the prognosis of non-Hodgkin's lymphoma originating from the nasopharynx.Conclusion:International prognostic index and the expression level of Ki-67 may be independent prognostic factors for non-Hodgkin's lymphoma originating from the nasopharynx.

Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemo-refractory gastric cancer treated with toripalimab, a PD-1 antibody in phase Ib/II clinical trial NCT02915432.

BACKGROUND: High tumor mutational burden (TMB-H) is correlated with enhanced objective response rate (ORR) and progression-free survival (PFS) for certain cancers receiving immunotherapy. This study aimed to investigate the safety and efficacy of toripalimab, a humanized programmed death-1 (PD-1) antibody, in advanced gastric cancer (AGC), and the predictive survival benefit of TMB and PD-L1. PATIENTS AND METHODS: We reported on the AGC cohort of phase Ib/II trial evaluating the safety and activity of toripalimab in patients with AGC, oesophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma. In cohort 1, 58 chemo-refractory AGC patients received toripalimab (3 mg/kg d1, Q2W) as a monotherapy. In cohort 2, 18 chemotherapy-naive AGC patients received toripalimab (360 mg d1, Q3W) with oxaliplatin 130 mg/m2 qd, d1, capecitabine 1000 mg/m2 b.i.d., d1-d14, Q3W as first-line treatment. Primary end point was ORR. Biomarkers such as PD-L1 and TMB were evaluated for correlation with clinical efficacy. RESULTS: In cohort 1, the ORR was 12.1% and the disease control rate (DCR) was 39.7%. Median PFS was 1.9 months and median OS was 4.8 months. The TMB-H group showed significant superior OS than the TMB-L group [14.6 versus 4.0 months, HR = 0.48 (96% CI 0.24-0.96), P = 0.038], while PD-L1 overexpression did not correlate with significant survival benefit. A 77.6% of patients experienced at least one treatment-related adverse event (TRAE), and 22.4% of patients experienced a grade 3 or higher TRAE. In cohort 2, the ORR was 66.7% and the DCR was 88.9%. A 94.4% of patients experienced at least one TRAE and 38.9% of patients experienced grade 3 or higher TRAEs. CONCLUSIONS: Toripalimab has demonstrated a manageable safety profile and promising antitumor activity in AGC patients, especially in combination with XELOX. High TMB may be a predictive marker for OS of AGC patients receiving toripalimab as a single agent. TRIAL REGISTRATION: ClinicalTrials.gov NCT02915432.

Potential of piperine in modulation of voltage-gated K+ current and its influences on cell cycle arrest and apoptosis in human prostate cancer cells.

OBJECTIVE: Piperine is an attractive therapeutic alkaloid from black pepper that exhibits a broad spectrum of pharmacological properties over various pathological disorders including cancer. Voltage-gated K+ channels (KV) play an important role in regulating cancer cell proliferation and are considered as potential targets for the treatment of cancer. However, there is a paucity of information with regard to the implication of piperine in KV associated anticancer activities on human prostate cancer cells LNCaP and PC-3 cells. Therefore, the primary objective of the present study was to elucidate the anticancer action of piperine that might be mediated via voltage-gated K+ current (IK) blockade. PATIENTS AND METHODS: Whole-cell patch clamp was used to record the modulatory effects of piperine on IK expressed in LNCaP and PC-3 cells. Moreover, the anticancer activity of piperine was evaluated by MTT assay, flow cytometry and live/dead assay. RESULTS: Piperine significantly inhibited IK in a dose-dependent manner with an effective IC50 dose 39.91 µM in LNCaP and 49.45 µM in PC-3 cells. Also, piperine induced a positive shift in the relative activation curve in both cells. Blockade of IK by piperine exerted G0/G1 phase cell cycle arrest that led to inhibition of cell proliferation and induced apoptosis in a dose-dependent manner. CONCLUSIONS: We showed that the anticancer effects of piperine are directly correlated with the blockade of IK in LNCaP and PC-3 cells. The study also confirmed that IK inhibition by piperine might be responsible for its anticancer activities in prostate cancer cells.

[CD23 on B cells determines Breg-facilitated IL-10 secretion as well as activation of T cells].

Objective:To explore whether or not the IL-10 mediated by Bregs modulate the secreting T cells activation by the anti-CD23 antibody, to find a new target for the treatment of allergic rhinitis. Method:The rat model of allergic rhinitis was established. Anti-CD23 antibody was used to observe the behavioral changes, passive skin allergen test, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, immunofluorescence and flow cytometry serological indicators, systemic and nasal mucosa. Result:Compared with the blank control group, allergic rhinitis group rats sneezing, flexible nose, runny nose, subcutaneous mass increases;The levels of IL-10, IFN-γ and Bregs in blood decreased, the levels of IL-4, CD23+ B cells and CD4+ T cells increased;Nasal mucosa CD23 fluorescence intensity increased, CD19 and IL-10 fluorescence intensity decreased. Compared with the allergic rhinitis group, the number of sneezing, the frequency of nasal flexion, the symptoms of runny nose and the subcutaneous mass in the antibody intervention group were significantly improved;The levels of IL-10 in the blood, IFN-γ, the percentage of Bregs cells in whole blood increased, the levels of IL-4, CD23+ B cells and CD4+ T cells decreased;Nasal mucosa CD23 fluorescence intensity decreased, CD19 and IL-10 fluorescence intensity increased. There is little difference between the two routes of administration. Conclusion:The enhanced expression of CD23 on B cells is involved in the development of allergic rhinitis. The anti-CD23 antibody may control the symptoms and signs of allergic rhinitis. There is no significant difference between subcutaneous administration and improved nasal-drip way. As the preferred method of anti-CD23 antibody application, anti-CD23 is expected to become a new method to control and treat allergic rhinitis. Anti-CD23 antibodies can exert a therapeutic effect by T cell activation,which rely on the Bregs-mediated secretion of IL-10.

Prognostic significance of the T2 substage in patients with esophageal squamous cell carcinoma.

The invasion of the muscularis propria is defined as T2 stage in esophageal squamous cell carcinoma. Evidence is lacking regarding whether the T2 substage based on anatomy may serve as a prognostic indicator. This study aims to confirm the prognostic value of the T2 substage. The clinicopathological characteristics of 120 patients who had pathologically verified T2 tumors between 2006 and 2011 at the Tianjin Medical University Cancer Institute and Hospital were retrospectively studied. Based on the invasion depth, tumors that had penetrated the circular muscle layer were defined as T2a, while T2b disease referred to those that had invaded the longitudinal muscle layer. Factors potentially related to survival were analyzed with univariate and multivariate analyses. The logistic regression model was used to examine the factors associated with lymph node metastasis. To verify the prognostic value of the T2 substage further, patients with T1b and T3 stage disease during the same period were selected for comparisons. The univariate and multivariate analyses demonstrated that the T2 substage and N stage were independent prognostic factors. The T2 substage was highly relevant to lymph node metastasis in the logistic regression model (P = 0.044). When T1b and T3 was considered, the survival of T2a patients was closer to that of T1b patients, while the survival of T2b patients was closer to that of T3 disease (P = 0.000). The T2 substage was an independent prognostic factor. Patients with T2a tumors displayed a favorable survival, while the prognosis of T2b patients was closer to that of T3 patients.

[The expression and role of PLUNC, TLR2 and NF-κB in nasal polyps].

Objective:To investigate the expression of palate, lung, nasal epithelium clone (PLUNC), Tolllike receptor 2 (TLR-2) and nuclear factor-Kappa B (NF-κB) in nasal polyps tissues and normal inferior turbinate mucosa. To analysethe correlation of their expression and to provide a new treatment of nasal polyps.Method:The specimens were divided into two groups: nasal polyps tissues group (n = 46) and normal inferior turbinate mucosa group (n = 19). EOS and others inflammatory cells was detected by HE staining. performing immunohistochemistry, we investigated the expression and distribution of PLUNC, TLR2 and NF-κB. Meanwhile we evaluated the positive expression and correlation of PLUNC, TLR2 and NF-κB between experimental group and control group. All data were processed by using SPSS 21.0 software.Result:EOS infiltration was significantly higher than the control group (P< 0.05). The expression level of PLUNC in experimental group is significantly lower, there is a statistical significance (P< 0. 05). The expression of TLR2 and NF-κB in experimental group is obviously higher than the control group, with statistical significance (P< 0.05). Spearman correlation analysia showed that PLUNC in experimental group is negatively correlated with TLR2 and NF-κB (r= －0.675, r= －0.550, P< 0.05). TLR2 is positively correlated with NF-κB (r= 0.540, P< 0.05). EOS infiltration degree positive correlation with TLR2 and NF-κB exist (r= 0.417, r= 0.470, P< 0.05), degree negative correlation with PLUNC exist (r= －0.859, P< 0.05).Conclusion:PLUNC expression in nasal polyps is lower than the normal inferior turbinate group. TLR2 and NF-κB expression in nasal polyps are higher than the normal inferior turbinate group.suggesting that the formation of nasal nolyps may be associated with lower natural immunity and the existing of infectious agents.

[The clinical features and prognosis analysis of adenoid cystic carcinoma in nasal cavity and paranasal sinus].

Objective:To investigate the clinical features and prognosis of adenoid cystic carcinoma (ACC) in nasal cavity and sinus. Method:67 patients with ACC were recruited interview in our department from 2007 to 2017. The association between clinical parameters and survival were evaluated by statistical analysis. Result:The 1-, 5- and 10- overall survival were 95%, 79%, 67%, and the 1-, 3- and 5-year recurrence rate were 5%, 7%, 9%, respectively. Simple factor analysis displays that age, the location of the tumour, clinical stages, sex, the interval time between starting symptoms to diagnosis time, the expression quantity of Ki-67 were related to the prognosis, and the latter three and surgical margin were also influential factors of distant metastasis after treatment. Multi-factors analysis revealed that sex, the interval time between starting symptoms to diagnosis time, the expression quantity of Ki-67 were significant factors for prognosis, and the latter two and surgical margin were influential factors of distant metastasis after treatment. Conclusion:The sex and the interval time between starting symptoms to diagnosis time and Ki-67 may be independent prognostic factors for ACC. The interval time between starting symptoms to diagnosis time and Ki-67 level may be independent factors of distant metastasis after treatment. Patients with long interval time between starting symptoms to diagnosis time and high expression of Ki-67 may have a higher risk of recurrence and mortality, which need reexamination of cycle-time reduction. The surgical margin is influential factor of distant metastasis, but not for the patients' prognosis.

[Efficacy and prognostic factors of 178 advanced non-small lung cancer patients undergoing different second-line chemotherapeutic regimens].

OBJECTIVE: The purpose of this study is to explore the efficacy and predictors of second-line chemotherpy in advanced non-small cell lung cancer patients and suggest optimal protocols suitable for differently characterized patients. METHODS: The clinical data of 178 advanced NSCLC patients second-line-treated in Tianjin Cancer Hospital from 2009.1.1 to 2013.12.31 were retrospectively analyzed. According to the different second-line treatments, the patients were divided into standard mono-drug therapy group (46 cases), endostar combined with standard mono-drug therapy group (42 cases), and platinum-based doublet chemotherapy group (90 cases). Kaplan-Meier and Log-rank analyses were used to estimate and compare the survival rates in the groups, and Cox's hazard regression model was used to determine the prognostic factors. Chi-square test was used to analyze the differences among different groups. RESULTS: The median progression-free survivals (mPFS) were 50 days, 54 days, and 79 days (P=0.042) for the standard mono-drug therapy group, endostar combined with standard mono-drug therapy group, and platinum-based doublet chemotherapy group, respectively. The differences between the mono-drug therapy group and doublet chemotherapy group were statistically significant (P=0.011). The disease control rate (DCR) for each group was 26.1%, 47.6% and 46.7% (P=0.041), and the DCR were statistically significantly different between the mono-drug therapy group and doublet chemotherapy group (P=0.016), and between the mono-drug therapy group and endostar combined with standard mono-drug therapy group (P=0.041). The overall response rate (ORR) for each group was 2.2%, 0, and 4.4% (P>0.05 for all). Multivariate analysis showed that the period from the begining of first-line to second-line chemotherapy (progression-free time), base-line clinical stage, neuron specific enolase (NSE) before second-line therapy, the cycles of second-line chemotherapy and the response to second-line therapy were independent predictors for PFS (P<0.005 for all). Subgroup analysis indicated that the patients obtained more clinical benefit from doublet chemotherapy rather than mono-drug therapy, with following factors: age<60 years, paclitaxel plus cisplatin for first-line treatment, chemotherapy cycles ≤4, CR, PR and SD for response, progression time within 3-6 months from the begining of first-line to second-line chemotherapy, performance status score≤1 at the begining of second-line therapy, Ⅳ stage, and mild leukopenia (P<0.05 for all). The patients whose progression-free survival time within 3-6 months from the begining of the first-line to second-line chemotherapy got more clinical benefit from endostar combined with standard mono-drug chemotherapy than mono-drug therapy (P=0.006). CONCLUSIONS: The period from the begining of first-line to second-line chemotherapy, base-line TNM stage, NSE before second-line chemotherapy, the cycles of second-line chemotherapy and the response to second-line therapy were independent predictors for PFS. Platinum-based doublet chemotherapy and endostar plus standard second-line regimen can improve the efficacy in some characterized advanced NSCLC as compared with the patients by standard mono-drug therapy, wherein the platinum-based chemotherapy revealed the best efficacy.

CXCL10/CXCR3 overexpression as a biomarker of poor prognosis in patients with stage II colorectal cancer.

The CXCL10/CXCR3 axis of inflammatory mediators is one of the most important groups of chemokine axes, which has been proven to be a lymphocyte-associated metastasis mediator in several tumors. The term inflammatory adhesions refers to tumors found to be attached to the surrouding tissues during surgery, although no cancer cell infiltration is later identified on pathological examination. The aim of the present study was to investigate the clinical characteristics of stage II colorectal cancer (CRC) and determine the correlation between the CXCL10/CXCR3 axis, inflammatory adhesions and prognosis. Clinicohistopathological data were collected from 401 CRC patients who had undergone R0 resection. Statistical analysis was performed with SPSS 17.0 software. Immunohistochemistry (IHC) was applied to measure the expression of CXCL10 and CXCR3 in 71 recurrent CRC patients, 72 non-recurrent CRC patients and 10 samples from normal peritumoral tissues, all retrieved from the Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. Inflammatory adhesions, tumor location and size and the number of high-risk factors for reccurrence were more significantly associated with overall survival (OS) rather than disease-free survival in all the patients as determined by the log-rank and Cox's regression hazard analysis. Further analysis demonstrated that only the presence of inflammatory adhesions (P=0.025) was associated with the OS of recurrent patients. Patients with recurrence exhibited higher CXCR3 (P<0.001) and CXCL10 (P<0.001) expression compared with non-recurrent patients, as determined by IHC. The correlation between clinicopathological variables, CXCL10/CXCR3 expression and survival was also analyzed: Inflammatory adhesions and general tumor type (ulcerated vs. elevated) exhibited a significant correlation with CXCR3; however, the expression of CXCL10 was not significantly correlated with tumor location, histological type, size, gender, or preoperative carcinoembryonic antigen and hemoglobin levels. Furthermore, patients exhibiting a high expression of CXCR3 presented with a higher risk of relapse; among those, patients with inflammatory adhesions always exhibited worse survival. However, no such association was identified for CXCL10 expression. In conclusion, CXCR3 expression may be used as a prognostic marker and may contribute to the prediction of clinical outcome in stage II CRC patients.

[A case report of myoepithelial carcinoma in the nasal septum].

Summary To explore the clinical features and treatment methods of myoepithelial carcinoma in the nasal septum.Myoepithelial carcinoma occurs in malignant epithelial tumors of the parotid region,from the nasal septum is more rare.The clinical feature of myoepithelial carcinoma in the nasal septum was atypical .The patients is mainly characterized by nasal obstruction,CT of tumor invasion nasal septum,on the right of the sinuses and lamina papyracea; pathology examination showed CK,S-100 protein and vimentin were positive,eventually,diagnosed with nasal septum myoepithelial carcinoma.

[Childhood nasal lymphoma:two cases report and literature review].

Here we report two childhood lymphoma cases,which present with a nasal cavity associated with obstructive symptoms and intermittence pyrexia.Application of antibiotic can temporarily alleviate these symptoms but it can not cure this disease radically.Computed tomography of nasopharynx showed inferior turbinate hypertrophy and absence of obvious specific manifestation.The examination of blood and marrow cells did not find any abnormity.The precision diagnostic evaluation is biopsy of clinically involved mass.The definitive pathological diagnosis is NK/T cell lymphoma.The two younger children patients have shorter course of disease,lacking typical cinical presentation and auxiliary examination of it.We should be vigilant whether a child having nasal obstruction and pyrexia is probably NK/T cell lymphoma or not.

Addition of bevacizumab to chemotherapy in patients with ovarian cancer: a systematic review and meta-analysis of randomized trials.

BACKGROUND: This systematic review and meta-analysis analyzed randomized controlled trials (RCTs) assessing the efficacy and tolerance of incorporating bevacizumab into chemotherapy in patients with advanced ovarian cancer. METHODS: MEDLINE, Web of Science, EMBASE and the Cochrane Central Register of Controlled Trials were reviewed for RCTs evaluating add-on bevacizumab in advanced ovarian cancer. Progression-free survival (PFS), overall survival (OS), objective response rate and adverse events were obtained from RCTs comparing first- and second-line bevacizumab plus chemotherapy with chemotherapy alone for advanced ovarian cancer. Meta-analyses were performed to determine hazard ratios for time-to-event variables and odds ratios for dichotomous outcomes using random-effects or fixed-effects model based on the heterogeneity of included studies. RESULTS: Four RCTs, including 4246 patients, were identified and analyzed. Two trials, GOG218 and ICON7, assessing bevacizumab in first-line chemotherapy, found that bevacizumab significantly extended PFS (HR 0.82; 95% CI 0.75-0.89) and OS (HR 0.86; 95% CI 0.75-0.99). The other two trials, OCEANS and AURELIA, analyzing second-line bevacizumab, found that this agent extended PFS (HR 0.48; 95% CI 0.41-0.57), but did not enhance OS (HR 0.93; 95% CI 0.78-1.12). The most common adverse events associated with bevacizumab included hypertension, proteinuria and gastrointestinal perforation. CONCLUSION: The addition of bevacizumab to chemotherapy followed by bevacizumab significantly improved PFS and OS in frontline setting and PFS in recurrent settings compared with that of chemotherapy alone in patients with advanced ovarian cancer.