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The objective of this study was to evaluate the preventive effects of oral administration of lansoprazole on acute exacerbation of chronic obstructive pulmonary disease ( COPD). Patients with COPD in groups C and D in the stable phase were stratified into a group with neither gastroesophageal reflux nor lansoprazole therapy (group A) and a group subjected to oral lansoprazole therapy (group B1) and a group not subjected to oral lansoprazole therapy (group B2). The frequency scale for the symptoms of gastroesophageal reflux disease ( FSSG) questionnaire, COPD assessment test (CAT) questionnaire, pulmonary function test and the 6-minute walk test were applied; in addition, arterial blood gas, white blood cell ( WBC), hs- CRP, liver function and the levels of IL-1β, IL-6, IL-8, TNF-α and GM- CSF in sputum were monitored during follow-up. In the 12-month follow-up period, the frequency of exacerbation in group B2 was statistically higher than that in groups A and B1 ( P < 0.05). After a 3-month follow-up, the score of groups A and B1 in the FSSG questionnaire was significantly lower than that of group B2 ( P < 0.05). After the 1-year follow-up, the CAT score, FEV1, 6-min walk test, the total number of WBC, hs- CRP, alanine aminotransferase, aspartate aminotransferase, pH of the arterial blood, PaO2, Pa CO2 and the levels of IL-1β, IL-6, IL-8, TNF-α and GM- CSF in the sputum were statistically different in group B2 compared with groups A and B1 ( P < 0.05). Oral lansoprazole therapy decreased the frequency of acute exacerbation of COPD by alleviating gastroesophageal reflux and lowering the levels of IL-1β, IL-6, IL-8, TNF-α and GM- CSF in the sputum. [ABSTRACT FROM AUTHOR]

Background To explore the efficacy and safety of crizotinib versus platinum-based double agent chemotherapy as the first-line treatment in patients with advanced anaplastic lymphoma kinase (ALK)-positive lung adenocarcinoma. Method We retrospectively analyzed data from 19 patients with advanced ALK-positive lung adenocarcinoma who had received no previous systemic treatment for advanced disease. Seven patients received oral crizotinib at a dose of 250 mg twice daily; 12 patients were administered standard chemotherapy (pemetrexed, paclitaxel, vinorelbine or gemcitabine plus either cisplatin or carboplatin) every three weeks for up to six cycles. The primary endpoint was overall response rate ( ORR), disease control rate ( DCR), and safety. Results The ORR was significantly higher with crizotinib than with chemotherapy (83.3% in the crizotinib vs. 25.0% in the chemotherapy group, P < 0.05); the DCRs were 100% and 75%, respectively ( P < 0.05). The common adverse events associated with crizotinib were visual abnormality and diarrhea, whereas those associated with chemotherapy were neutropenia and nausea. In the crizotinib group, liver aminotransferase elevation (adverse events grade 3 or 4) occurred in one patient (14.3%). In the chemotherapy group, the same grade neutropenia adverse event occurred in two patients (16.6%). The incidence of treatment-related grade 3 or 4 adverse events was similar in both groups. Compared with chemotherapy, crizotinib was associated with a greater reduction in lung cancer symptoms and a greater improvement in quality of life. Conclusion As a first-line treatment, crizotinib was superior to platinum-based double chemotherapy in patients with previously untreated advanced ALK-positive lung adenocarcinoma. Therefore, crizotinib is an optimal therapy as a first-line treatment in these patients. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is the deadliest and most common type of primary brain tumor in adults with a grim prognosis despite multimodal treatments. Dendritic cell (DC)-based immunotherapy has emerged as a promising therapeutic modality for GBM, whose efficacy is nonetheless fundamentally undermined by GBM-induced immunosuppression. Inducing emission of damage associated molecular patterns (DAMPs) is a highly effective strategy to subvert tumor-associated immunosuppression. The present work was carried out to explore the idea of subverting the GBM immunosuppressive microenvironment through DC-mediated delivery of doxorubicin-polyglycerol-nanodiamond composites (Nano-DOX), a potent DAMPs inducer demonstrated by our previous study, and thereby eliciting enhanced DC-driven anti-GBM immune response. In the in-vitro work on human cell models, Nano-DOX-loaded DC were shown to be functionally viable and release cargo drug to co-cultured GBM cells (GC). Nano-DOX-treated GC displayed not only profuse DAMPs emission but also antigen release. Enhanced activation and acquisition and presentation of GC-derived antigen were then demonstrated in DC in co-culture with GC and Nano-DOX. Consistently, co-culture with GC and Nano-DOX also activated mouse bone marrow-derived DC (mDC) which in turn stimulated mouse spleen-derived lymphocytes which ultimately suppressed co-cultured GC. Next, athymic mice bearing orthotopic human GBM xenografts were intravenously injected with Nano-DOX-loaded mDC and, 48 h later, spleen-derived lymphocytes. The presence of Nano-DOX, DAMPs emission and enhanced infiltration and activation of mDC and lymphocytes were detected in the GBM xenografts. Taken together, our results demonstrate the efficacy of DC-mediated delivery of Nano-DOX to stimulate GC immunogenicity and elicit anti-cancer immune response in the GBM. By this work, we present a novel approach with great application potential to subverting the GBM immunosuppressive microenvironment and to anti-GBM immunotherapy. Investigation has also been conducted probing the mechanisms by which Nano-DOX stimulates GC immunogenicity, which is described in a follow-up paper. [ABSTRACT FROM AUTHOR]

Background To evaluate the efficacy and safety of Icotinib - an orally administered, highly potent selective inhibitor of epidermal growth factor receptor ( EGFR) and its active mutations, in the treatment of patients with advanced non-small cell lung cancer ( NSCLC). Methods A total of 101 patients with stage IIIb/ IV NSCLC were treated with 125 mg Icotinib three times a day until disease progression or intolerable toxicity. Response rate was evaluated using response evaluation criteria in solid tumors and progression-free survival ( PFS) was collected. Results The overall response rate ( ORR) and disease control rate ( DCR) were 37.6% (38/101) and 79.2% (80/101), respectively. The median PFS was 6.5 months. Multivariate analysis showed that female gender ( P = 0.048, 95% confidence interval [ CI] 1.010-6.016) and occurrence of rash ( P = 0.002, 95% CI 1.667-9.809) were the independent predictive factors for ORR, while a performance status ( PS) score of 0-1 ( P = 0.001, 95% CI 0.024-0.402) and rash ( P = 0.042, 95% CI 1.089-76.557) were the independent predictive factors for DCR. In addition, PS scores of 0-1 ( P < 0.001, 95% CI 0.135-0.509), and non-smoking ( P = 0.017, 95% CI 0.342-0.900) were found to be independent influencing factors for PFS. Moreover, patients with EGFR mutations had better PFS than patients with wild type EGFR, while patients with EGFR exon 19 deletion had better survival than those with EGFR exon 21 mutation. The most common adverse effects of Icotinib were rash (35.6%) and diarrhea (17.8%), which was tolerable. Conclusion Treatment of stage IIIb/ IV NSCLC patients with Icotinib was effective and tolerable, specifically in patients with EGFR mutation. [ABSTRACT FROM AUTHOR]

Background Epidermal growth factor receptor-tyrosine kinase inhibitors ( EGFR-TKIs) effectively treat advanced non-small cell lung cancer with EGFR-mutation. However, most patients develop acquired resistance without effective therapy subsequent to EGFR-TKI failure. We evaluated the efficacy of subsequent treatment strategies for EGFR-TKI resistance. Methods We retrospectively analyzed 240 patients with advanced lung adenocarcinoma with EGFR-TKI failure and following subsequent treatment. According to the first subsequent strategies after EGFR- TKI failure, patients were divided into groups of EGFR-TKI continuation (21 cases), EGFR-TKI continuation with chemotherapy (23 cases), chemotherapy alone (143 cases), and best supportive care ( BSC) (53 cases). Results Except for 53 cases of BSC, the disease control rates ( DCR) of the remaining 187 patients in the EGFR-TKI continuation, EGFR-TKI continuation with chemotherapy, and chemotherapy alone groups were 66.7%, 73.9%, and 44.8%, respectively. The median post-progression progression-free survival ( PFS) for the three groups was 3.0, 3.3, and 2.0 months, respectively. The DCR for the EGFR-TKI continuation with chemotherapy group was significantly higher than the chemotherapy alone group ( P = 0.006). The post-progression PFS of the EGFR-TKI continuation with chemotherapy group was significantly longer than the chemotherapy alone group ( P = 0.037). The median overall survival in the EGFR-TKI continuation, EGFR-TKI continuation with chemotherapy, chemotherapy alone, and BSC groups were 6.9, 11.6, 8.8, and 0.9 months, respectively. Compared to the BSC group, all groups achieved a survival benefit ( P < 0.001). Conclusions EGFR-TKI continuation with chemotherapy could provide benefits for patients with acquired resistance to EGFR-TKI. [ABSTRACT FROM AUTHOR]

[Display omitted] • Two heptamannosylated β-cyclodextrin derivatives (CD-Man7 and C 3 -CD-Man7) were synthesized. • Multivalent mannose ligands induced macrophages to differentiate into the M2 phenotype. • Both CD-Man7 and CD-Man-NPs could reduce the inflammatory response in wound tissue and accelerate wound healing. Macrophages have high plasticity and heterogeneity, and can suppress or mediate inflammation, depending on their cytokine secretion and phenotype. Regulating macrophage polarization into its M2 phenotype has a remarkable effect on inflammatory inhibition, inducing the regeneration of injured tissues. Here, we synthesized two heptamannosylated β-cyclodextrin derivatives (CD-Man7 and C 3 -CD-Man7) and demonstrated that their multivalent mannose ligands could induce M2 macrophage polarization to accelerate wound healing. Unlike hydrophilic CD-Man7, amphiphilic C 3 -CD-Man7 can self-assemble to form nanoparticles (CD-Man-NPs) in aqueous solution. Further, in vitro results confirmed that multivalent mannose ligands of either CD-Man7 or CD-Man-NPs stimulated RAW264.7 macrophages to differentiate into the M2 phenotype, which promoted fibroblast migration via a paracrine mechanism. In vivo results confirmed that both CD-Man7 and CD-Man-NPs reduced the inflammatory response in wound tissue and accelerated wound healing. The present study demonstrates multivalent effects of CD-Man7 and CD-Man-NPs on M2 macrophage polarization, indicating the therapeutic potential of these β-cyclodextrin glycoconjugates in the treatment of inflammatory diseases and wound healing. [ABSTRACT FROM AUTHOR]