PURPOSE: 83b1 is a novel quinoline derivative that has been shown to inhibit cancer growth in human esophageal squamous cell carcinoma (ESCC). This study was conducted to comprehensively evaluate the cytotoxic effects of 83b1 on a series of ESCC cell lines and investigate the mechanisms by which 83b1 suppresses cancer growth based on molecular docking analysis. MATERIALS AND METHODS: A series of ESCC and nontumor immortalized cell lines were exposed to 83b1 and cisplatin (CDDP) in a dose-dependent manner, and the cytotoxicity was examined by a MTS assay kit. Prediction of the molecular targets of 83b1 was conducted by molecular docking analysis. Expression of cyclooxygenase 2 (COX-2) mRNA and COX-2–derived prostaglandin E₂ (PGE₂) were measured by quantitative real-time polymerase chain reaction and enzymelinked immuno-sorbent assay, respectively. In vivo anti-tumor effect was determined using a nude mice xenografted model transplanted with an ESCC cell line, KYSE-450. RESULTS: 83b1 showed the significant anti-cancer effects on all ESCC cell lines compared to CDDP; however, 83b1 revealed much lower toxic effects on non-tumor cell lines than CDDP. The predicted molecular target of 83b1 is peroxisome proliferator-activated receptor delta (PPARδ), which is a widely known oncoprotein. Additionally the expression of COX-2 mRNA and COX-2–derived PGE2 were down-regulated by 83b1 in a dose-dependent manner in ESCC cell lines. Furthermore, 83b1 was shown to significantly reduce the tumor size in nude mice xenograft. CONCLUSION: The results of this study suggest that the potential anti-cancer effects of 83b1 on human esophageal cancers occur through the possible oncotarget, PPARδ, and down-regulation of the cancer related genes and molecules.
Animals ; Carcinoma, Squamous Cell* ; Cell Line ; Cisplatin ; Cyclooxygenase 2 ; Dinoprostone ; Down-Regulation* ; Epithelial Cells* ; Esophageal Neoplasms ; Heterografts ; Humans* ; Mice ; Mice, Nude ; Molecular Docking Simulation ; PPAR delta ; Quinolines ; Real-Time Polymerase Chain Reaction ; RNA, Messenger*

BACKGROUNDSevere acute respiratory syndrome is frequently complicated by respiratory failure requiring ventilatory support. We aimed to compare the efficacy of non-invasive ventilation against invasive mechanical ventilation treating respiratory failure in this disease.

METHODSRetrospective analysis was conducted on all respiratory failure patients identified from the Hong Kong Hospital Authority Severe Acute Respiratory Syndrome Database. Intubation rate, mortality and secondary outcome of a hospital utilizing non-invasive ventilation under standard infection control conditions (NIV Hospital) were compared against 13 hospitals using solely invasive ventilation (IMV Hospitals). Multiple logistic regression analyses with adjustments for confounding variables were performed to test for association between outcomes and hospital groups.

RESULTSBoth hospital groups had comparable demographics and clinical profiles, but NIV Hospital (42 patients) had higher lactate dehydrogenase ratio and worse radiographic score on admission and ribavirin-corticosteroid commencement. Compared to IMV Hospitals (451 patients), NIV Hospital had lower adjusted odds ratios for intubation (0.36, 95% CI 0.164 - 0.791, P = 0.011) and death (0.235, 95% CI 0.077 - 0.716, P = 0.011), and improved earlier after pulsed steroid rescue. There were no instances of transmission of severe acute respiratory syndrome among health care workers due to the use of non-invasive ventilation.

CONCLUSIONCompared to invasive mechanical ventilation, non-invasive ventilation as initial ventilatory support for acute respiratory failure in the presence of severe acute respiratory syndrome appeared to be associated with reduced intubation need and mortality.

Adolescent ; Adult ; Aged ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Respiration, Artificial ; Respiratory Insufficiency ; therapy ; Retrospective Studies ; Severe Acute Respiratory Syndrome ; complications ; therapy

We investigated the antineoplastic potentials of recombinant adenovirus containing wild-type p53 cDNA (Ad5CMV-p53) for malignant gliomas. In four human glioma cell lines (U-251 and LG expressing endogenous mutant p53, and U-87 and EFC-2 expressing wild-type p53) and two rat glioma cell lines (9L and C6, each expressing mutant and wild-type p53), gene transfer efficiency determined by X-gal staining and Western blotting was varied (10-99% at 10-500 multiplicity of infection, MOI). Growth inhibitory effect was drastic (>90% at 100 MOI) in U-251 cells and only moderate or minimal in other cell lines harboring wild-type p53 or low gene transfer efficiency. Ex vivo transduction of U-251 cells with Ad5CMV-p53 suppressed the in vivo tumorigenicity of the cells. Histopathologic examination for Ad5CMV-p53 toxicity to rat brains showed inflammatory reactions in half of the tested brains at 10(8) MOI. U-251 cells were inoculated intracerebrally in nude mice and injected Ad5CMV-p53 into the tumor, in which neither the tumor suppression nor the survival benefit was observed. In conclusion, heterogeneity of the cellular subpopulations of malignant glioma in p53 status, variable and insufficient gene delivery to tumor, and adenoviral toxicity to brain at higher doses may be limiting factors to be solved in developing adenovirus-p53 gene therapy for malignant gliomas.
Adenoviruses, Human ; Animal ; Brain Neoplasms/therapy* ; Cell Division ; Gene Therapy* ; Genetic Vectors ; Glioma/therapy* ; Human ; Mice ; Mice, Nude ; Protein p53/physiology ; Protein p53/genetics* ; Rats ; Tumor Cells, Cultured

We investigated the antineoplastic potentials of recombinant adenovirus containing wild-type p53 cDNA (Ad5CMV-p53) for malignant gliomas. In four human glioma cell lines (U-251 and LG expressing endogenous mutant p53, and U-87 and EFC-2 expressing wild-type p53) and two rat glioma cell lines (9L and C6, each expressing mutant and wild-type p53), gene transfer efficiency determined by X-gal staining and Western blotting was varied (10-99% at 10-500 multiplicity of infection, MOI). Growth inhibitory effect was drastic (>90% at 100 MOI) in U-251 cells and only moderate or minimal in other cell lines harboring wild-type p53 or low gene transfer efficiency. Ex vivo transduction of U-251 cells with Ad5CMV-p53 suppressed the in vivo tumorigenicity of the cells. Histopathologic examination for Ad5CMV-p53 toxicity to rat brains showed inflammatory reactions in half of the tested brains at 10(8) MOI. U-251 cells were inoculated intracerebrally in nude mice and injected Ad5CMV-p53 into the tumor, in which neither the tumor suppression nor the survival benefit was observed. In conclusion, heterogeneity of the cellular subpopulations of malignant glioma in p53 status, variable and insufficient gene delivery to tumor, and adenoviral toxicity to brain at higher doses may be limiting factors to be solved in developing adenovirus-p53 gene therapy for malignant gliomas.
Adenoviruses, Human ; Animal ; Brain Neoplasms/therapy* ; Cell Division ; Gene Therapy* ; Genetic Vectors ; Glioma/therapy* ; Human ; Mice ; Mice, Nude ; Protein p53/physiology ; Protein p53/genetics* ; Rats ; Tumor Cells, Cultured