Heterogeneity and prognosis of programmed cell death-ligand 1 expression in the circulating tumor cells of non-small cell lung cancer.

Due to tumor heterogeneity, the consistency of programmed cell death-ligand 1 (PD-L1) expression between circulating tumor cells (CTCs) and tissue is controversial. This study aimed to establish a method for detecting CTC PD-L1 expression and exploring the impact of the same on the prognosis of lung cancer. In 32 patients with non-small cell lung cancer, lung cancer cells in the blood were enriched using CD326 immunomagnetic beads. Goat anti-mouse polyclonal CD326 antibody stained the epithelial lung cancer cells and anti-PD-L1 antibody was used to detect the expression of CTC PD-L1. The DAKO Link 48 automatic staining device detected the expression in lung cancer tissue. The consistency of PD-L1 expression was analyzed in lung cancer tissue and CTCs. The effect of plasma interferon gamma, tumor necrosis factor alpha, and interleukin-2 on PD-L1 expression and prognosis was analyzed. The number of CTCs detected in patients was 1-36, with a median of 2. There was no significant difference in PD-L1 expression fractions between CTCs and paired tumor tissue (p>0.05). The correlation coefficient was 0.20. Regardless of lung cancer tissue or CTCs, there was no statistically significant difference in the blood cytokine levels between the two groups with positive or negative PD-L1 expression (p>0.05). There was no correlation between CTCs and PD-L1 in 23 untreated patients. The expression of PD-L1 in CTCs and lung cancer tissue is heterogeneous and unaffected by the peripheral cytokines' levels. PD-L1 expression has no correlation between CTCs and tissues and is not related to prognosis.

Endoscopic Partial Plantar Fasciotomy via 2 Medial Portals vs Mini-Open Procedure for Refractory Plantar Fasciitis.

BACKGROUND: The treatment of plantar fasciitis may require surgical intervention in patients with ineffective response to conservative treatment. There is a lack of evidence regarding the differences in clinical outcomes between the endoscopic and the mini-open procedures. The purpose of this study was to compare the clinical outcomes of the endoscopic partial plantar fasciotomy via 2 medial portals with mini-open partial plantar fasciotomy for treating refractory plantar fasciitis. METHODS: A retrospective analysis was carried out on 62 patients with refractory plantar fasciitis from January 2015 to July 2017. Thirty-three patients received endoscopic partial plantar fasciotomy, while the other 29 received mini-open procedure by patient preference. Two medial portals were used in the endoscopic group while single mini-medial method was used in the open group. All patients were followed up for 24 months. The pain visual analog scale (VAS), the American Orthopaedic Foot & Ankle Society (AOFAS) score, the calcaneodynia score (CS), and the 36-item Short Form Health Survey questionnaire (SF-36) were employed to evaluate the clinical outcomes of the 2 groups. RESULTS: There was increase in the functional scores (eg, VAS, AOFAS, CS, and SF-36) in both groups recorded at 3 months, 6 months, 1 year, and 2 years after surgery. The patients in the endoscopic group had better VAS, AOFAS, CS, and SF-36 scores at 3 months after the surgery compared with those of the open group. During the 6-month follow-up, although the 2 groups showed similar VAS and AOFAS, the CS and SF-36 scores of the endoscopic group were significantly higher than those of the open group. During the 1-year and 2-year follow-ups, the endoscopic group gained equivalent VAS, AOFAS, CS, and SF-36 scores compared with those of the open group. The recurrence rate was similar in both groups. Moreover, the patients in the endoscopic group achieved earlier recovery in comparison to those in the open group. CONCLUSION: For refractory plantar fasciitis, endoscopic partial plantar fasciotomy via 2 medial portals produced better short-term and equivalent long-term subjective outcomes than the mini-open surgery. LEVEL OF EVIDENCE: Level II, comparative study.

Icotinib as Adjuvant Treatment for Stage II-IIIA Lung Adenocarcinoma Patients with EGFR Mutation (ICWIP Study): Study Protocol for a Randomised Controlled Trial.

The efficacy and possible role of epidermal growth factor receptor tyrosine kinase inhibitors in treating early-stage non-small-cell lung cancer have yet to be established. Therefore, we aimed to explore the efficacy and safety of icotinib in completely resected EGFR-mutant stage II-IIIA lung adenocarcinoma patients who underwent standard chemotherapy. This is a randomised, double-blinded, placebo-controlled, multicentre, Phase III trial. A total of 124 patients aged 18-75 years who qualified the inclusion criteria were recruited. These patients were randomised (1:1) to receive either icotinib (125 mg 3 times per day) or placebo (the same dosage and frequency) for 36 months, followed by a further 36 months of observational window. The primary endpoint is disease-free survival (DFS), while the secondary endpoints are overall survival, 3-year and 5-year DFS, safety and tolerability of the medication, and health-related quality-of-life. Analyses will be conducted in a full analysis set and a per-protocol set as well. To our knowledge, the present study is the first randomised, double-blinded, placebo-controlled, multicenter trial designed to explore efficacy and safety of icotonib in this population. The results obtained in the near future may provide potential guidance in clinical practice. Trial Registration: This trial was registered on www.ClinicalTrail.gov as NCT02125240.

miR-30b and miR-30c expression predicted response to tyrosine kinase inhibitors as first line treatment in non-small cell lung cancer.

BACKGROUND: Aberrantly expressed microRNAs are a hallmark of cancer, and microRNA expression profiling is associated with tumor progression and response to chemotherapy, suggesting their potential application as prognostic and predictive biomarkers. The role of microRNAs in lung cancer remains elusive. It has been recently reported that epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (MET) tyrosine kinase can regulate expression of specific microRNAs including miR-30b, miR-30c, miR-221, miR-222, miR-103 and miR-203, and induce tumorigenesis and gefitinib resistance in lung cancers. We intend to study the role of miR-30b and miR-30c expression in predicting response to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). METHODS: We have therefore retrospectively examined expression of miR-30b miR-30c in 41 formalin fixed paraffin embedded tissue samples from NSCLC patients when TKIs were used as first line therapy. RESULTS: We found a significant correlation between expression of miR-30b and miR-30c. Furthermore, miR-30b and miR-30c expression correlated with short-term response. Kaplan-Meier analysis further revealed that the expression of miR-30b and miR-30c predicted progression free survival and the overall survival rate in the examined cohort. CONCLUSION: Our study identified miR-30b and miR-30c as useful prognostic predictors in NSCLC patients who underwent first line treatment with TKIs.

[Clinical observation of icotinib hydrochloride for patients with advanced non-small cell lung cancer].

OBJECTIVE: To explore the efficacy and side effects of icotinib hydrochloride in the treatment of patients with advanced non-small cell lung cancer (NSCLC). METHODS: The efficacy and side effects of icotinib hydrochloride in treatment of 59 cases with stage IV NSCIC and followed-up from March 2009 to January 2012 were retrospectively analyzed. RESULTS: Twenty seven patients (45.8%) showed partial response (PR), 17 patients (28.8%) achieved SD, and 15 (25.4%) had progressive disease. The objective response rate (ORR) was 45.8% (27/59), and disease control rate (DCR) was 74.6% (44/59). Among the 23 patients with EGFR mutation, ORR was 73.9% (17/23), and DCR was 95.7% (22/23). Thirty six patients (61.0%) achieved remission of symptoms to varying degrees. The main symptoms relieved were cough, asthmatic suffocating, pain and hoarseness. The major adverse events were mild skin rash (35.6%) and diarrhea (15.3%). Others were dry skin, nausea and stomach problems. The efficacy of icotinib hydrochloride were related to the ECOG performance status, smoking history, EGFR mutation and rash significantly (P < 0.05). CONCLUSIONS: Monotherapy with icotinib hydrochloride is effective and tolerable for patients with advanced NSCLC, especially with EGFR mutation.

The bone morphogenetic protein antagonist Gremlin is overexpressed in human malignant mesothelioma.

Gremlin is a member of the bone morphogenetic protein (BMP) antagonist family and its antagonistic effect is likely through direct binding to BMP proteins. As an antagonist of BMP, Gremlin plays a role in regulating organogenesis, body patterning and tissue differentiation. Recent studies have shown a deregulation of Gremlin in several types of human cancers. However, the role of Gremlin in human malignant mesothelioma (MM) is still unknown. In this study, we investigated the expression of Gremlin in human MM. We found that Gremlin mRNA and protein were both overexpressed in the majority of primary MM tissue samples that we examined. We also observed high level expression of the Gremlin gene in 4 of the 6 MM cell lines. Consistently, we found that the Gremlin promoter activity was significantly elevated in those MM cell lines expressing the Gremlin gene. On the other hand, no activity of the Gremlin promoter was detected in the two MM cell lines lacking Gremlin expression. Moreover, to examine the functional significance of the Gremlin overexpression in MM, we used shRNA to knock down Gremlin expression in MM cell lines expressing Gremlin and found that inhibition of Gremlin expression significantly suppressed proliferation of those MM cells. Taken together, our results suggest that the BMP antagonist Gremlin is overexpressed in MM and that aberrant activation of Gremlin may play a critical role in the tumorigenesis of human MM.

[Efficacy and safety of palonosetron versus tropisetron in the prevention of highly emetogenic chemotherapy-induced acute and delayed vomiting in Chinese cancer patients].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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 (P > 0.05), 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. CONCLUSION: With a high safety profile, palonosetron is an effective agent for the prevention of acute and delayed chemotherapy-induced nausea and vomiting.

[PAH sources in road runoff system in Beijing].

In this study, road runoff, rainwater, ground sediment and roadside tree water samples were collected from three types of roads in Beijing in 2006. The samples were analyzed for polycyclic aromatic hydrocarbons (PAHs). The average PAH concentrations in each media in May-June were generally higher than those in July-August. Factor analysis indicated that PAHs in road runoff were mainly from ground sediment, and rainwater and roadside tree water also had certain influence to road runoff. Multiple regression analysis indicated that PAHs in ground sediment and road runoff mainly come from vehicular emission at the vehicle way and branch road, and at the bicycle way, the contributions of vehicular emission and coal combustion were equal. PAHs in rain were mainly from coal/oil combustion, and PAHs in roadside tree water were dominated by vehicular emission source.

[Concentration characteristics and influencing factors of atmospheric polycyclic aromatic hydrocarbons in TSP in the southeastern suburb of Beijing, China].

ATSP samples were collected at three sampling sites in the southeastern suburb of Beijing from March, 2005 to January, 2006. The samples were analyzed for TSP and sixteen PAHs. The concentrations and seasonal changes of TSP and sixteen PAHs were illustrated. Concentrations of sigma 16PAHs range from 0.29 - 1 184.48 ng/m3, and the average value is 239.44 ng/m3. Partial correlation analysis was applied to investigate the influence of meteorological parameters (temperature, wind speed, air pressure and relative humidity) and air pollution indexes (SO2, NO2 and PM10) on PAHs concentrations. Finally, quantitative estimation equations between PAHs and meteorological parameters and air pollution indexes were put forward by applying stepwise linear regression method, and the equations are sigma 16PAHs = 572.56 - 23.18 t and sigma 16PAHs = 5.99 SO2, respectively. Concentration of PAHs could be estimated using temperature or API of SO2.

[Combined effects of genetic polymorphisms in cytochrome P450s and GSTM1 on lung cancer susceptibility].

OBJECTIVE: To investigate the relationship between the gene polymorphism of metabolizing enzymes and the genetic susceptibility to lung cancer as well as to study the synergistic effects between smoking and the genes. METHODS: Peripheral blood samples were collected from 279 patients with primary lung cancer and 684 age-, nationality-, and native place-matched controls, including patients with benign diseases and healthy volunteers. PCR-RELP was used to detect the distribution of CYP1A1, 2D6, 2E1, and GSTM1 genotypes. The correlation of these genes with the sensibility to lung cancer was analyzed. RESULTS: The CYP1A1 variant allele frequency of the lung cancer group was 67.4%, significantly higher than that of the control group (55.7%, P = 0.001). GSTM1-null genotype was found to be associated with lung cancer (OR = 1.58, P = 0.002). The risk of lung cancer in the individuals carrying GSTM1-null genotype and CYP1A1 (w/m, m/m) genotype was 2.75 times that of the individuals not carrying these genotypes (P < 0.01). There were no significant differences in the frequencies of CYP2D6 and CYP2E1 genotypes between these two groups. In the heavy smokers GSTM1-null, CYP1A1, CYP2D6, and CYP2E1 genotypes increased the risk of lung cancer by 5.71 - 11.67 times (P = 0.000). CONCLUSION: The individuals who carry GSTM1-null genotype and CYP1A1 (m) genotype have an increase risk of lung cancer. The combined effect of I phase metabolizing enzymes and II phase metabolizing enzymes is observed. In heavy smokers the polymorphism of GSTM1 and CYPs affects the susceptibility to lung cancer.

[Correlation between the mRNA levels of carcinoembryonic antigen and cytokeratin 19 in peripheral blood with staging, treatment response and prognosis in patients with lung cancer].

OBJECTIVE: To investigate the expression of carcinoembryonic antigen (CEA) and cytokeratin19 (CK19) mRNAs in peripheral blood of patients with lung cancer and their correlation with staging, treatment response and prognosis. METHODS: CEA and CK19 mRNAs in peripheral blood were detected by Taq Man reverse transcriptase-polymerase chain reaction (RT-PCR) in 78 patients with lung cancer before and after treatment, 30 patients with benign lung diseases and 30 healthy subjects. Serum CEA and CYFRA21-1 levels were also measured by enzyme linked immunosorbent assay (ELISA) in the 78 patients with lung cancer before treatment. The patients were followed for 2 years. RESULTS: The positive rates of CEA mRNA and CK19 mRNA in patients with lung cancer were 69.2% (54/78) and 62.8% (49/78), respectively, which were significantly higher than those in patients with benign lung diseases and the healthy controls (P < 0.01). The positive rate of CEA mRNA was the highest in adenocarcinoma, while the positive rate of CK19 mRNA was the highest in squamous cell carcinoma. There was no statistically significant difference among different stages (P > 0.05), The positive rates of CEA mRNA and CK19 mRNA were higher than those of serum CEA and CYFRA21-1. The positive rates of CEA mRNA and CK19 mRNA decreased significantly after surgical operation, but there was no significant change after chemotherapy. The median survival time (MST) for patients with a positive CEA mRNA before chemotherapy was shorter than those with a negative CEA mRNA (8.5 month and 11.7 month, respectively). The MST for patients with a positive CK19 mRNA before chemotherapy was shorter than those with a negative CK19 mRNA (8.9 month and 12.3 month, respectively). The rate of relapse and metastasis was higher in patients (29.4%) with a positive CEA mRNA preoperatively than those with a negative CEA mRNA (7.7%). The rate of relapse and metastasis was also higher in patients with a positive CK19 mRNA preoperatively (18.8%) as compared to those with a negative PCR result (7.1%). CONCLUSIONS: CEA and CK19 mRNAs can be used as markers in the detection of tumor micrometastases in lung cancer, and in evaluating surgical response and prognosis. The results suggest that the gene markers are better than the serum ones, and therefore may be useful for the early diagnosis of lung cancer.