nystatin-a1 and Lung-Neoplasms

Topics: Administration, Oral; Aged; Antifungal Agents; Candidiasis, Oral; Diagnosis, Differential; Drug Eruptions; Humans; Lung Neoplasms; Male; Nystatin; Suspensions

Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a major limitation for its clinical use. The mechanisms of TRAIL resistance have been mostly studied in the context of cell lines that are intrinsically resistant to TRAIL. However, little is known about the molecular alterations that contribute to the development of acquired resistance during treatment with TRAIL. In this study, we established H460R, an isogenic cell line with acquired TRAIL resistance, from the TRAIL‑sensitive human lung cancer cell line H460 to investigate the mechanisms of acquired resistance. The acquired TRAIL‑resistant H460R cells remained sensitive to cisplatin. The mRNA and protein expression levels of death receptor 4 (DR4) and death receptor 5 (DR5) were not altered in either of the TRAIL-treated cell lines. Nevertheless, tests in which the DR4 or DR5 gene was overexpressed or silenced suggest that death receptor expression is necessary but not sufficient for TRAIL‑induced apoptosis. Compared with parental TRAIL-sensitive H460 cells, H460R cells showed a decreased TRAIL-induced translocation of DR4/DR5 into lipid rafts. Further studies showed that nystatin partially prevented lipid raft aggregation and DR4 and DR5 clustering and reduced apoptosis in H460 cells again. Analysis of apoptotic molecules showed that more pro-caspase-8, FADD, caspase-3 and Bid, but less cFLIP in H460 cells than in H460R cells. Our findings suggest that the lack of death receptor redistribution negatively impacts DISC assembly in lipid rafts, which at least partially leads to the development of acquired resistance to TRAIL in H460R cells.

Topics: Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cisplatin; Death Domain Receptor Signaling Adaptor Proteins; Drug Resistance, Neoplasm; Humans; Lung Neoplasms; Membrane Microdomains; Nystatin; Receptors, TNF-Related Apoptosis-Inducing Ligand; Recombinant Proteins; TNF-Related Apoptosis-Inducing Ligand

Topics: Administration, Oral; Amoxicillin; Anti-Bacterial Agents; Antifungal Agents; Drug Eruptions; Drug Hypersensitivity; Erythema; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mycoses; Nystatin; Opportunistic Infections; Patch Tests; Time Factors; Tooth Diseases; Withholding Treatment

The condensation of 6-amino-2-thiouracil 1 with aromatic aldehydes afforded azomethine derivatives 3a,b. The formed azomethines underwent [4+2] cycloaddition with enaminones 4a-c and enaminonitrile 9 to form the corresponding condensed pyrimidines 8a-f and 11a,b, respectively. On the other hand, the interaction of 3a,b with acetylene derivatives 12a,b, 14 afforded the corresponding pyrido[2,3-d]pyrimidines 13a-d and 16a,b, respectively. The newly synthesized 2-azadiene 18 reacted with ortho-aminophenol and ortho-aminothiophenol 19a,b to yield the amidines 21a,b. The in vitro antimicrobial activity of some of the newly synthesized compounds was examined. All the tested compounds proved to be active as antibacterial and antifungal agents. Also the in vivo antitumor activity of compounds 8a, 11b, 13a,d, and 16b against lung (H460) and liver (HEPG2) carcinoma cells was examined. Compounds 8a, 16b showed moderate activity against lung carcinoma cell line (H460).

Topics: Antifungal Agents; Antineoplastic Agents; Drug Screening Assays, Antitumor; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Liver Neoplasms; Lung Neoplasms; Microbial Sensitivity Tests; Molecular Structure; Pyrimidines; Structure-Activity Relationship; Thiouracil; Tumor Cells, Cultured

Bioassay-guided fractionation of the organic extract from a culture of Phomopsis longicolla, an endophytic fungus of the endangered mint Dicerandra frutescens, led to the isolation of dicerandrols A, B, and C. Extensive NMR and HRFABMS experiments were used to identify these new yellow antibiotic and cytotoxic compounds as 2,2'-dimeric tetrahydroxanthones.

Topics: Antibiotics, Antineoplastic; Ascomycota; Bacillus subtilis; Colonic Neoplasms; Florida; Geotrichum; Humans; Lamiaceae; Lung Neoplasms; Magnetic Resonance Spectroscopy; Molecular Structure; Saccharomyces cerevisiae; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet; Staphylococcus aureus; Stereoisomerism; Tumor Cells, Cultured; Xanthenes; Xanthones

Of 12 cell lines derived from human lung cancers, only Calu-3 cells showed high transepithelial resistance (Rte) and increases in short-circuit current (Isc) in response to mediators. Calu-3 cells formed polarized monolayers with tight junctions and Rte of approximately 100 omega.cm2. Baseline Isc was approximately 35 microA/cm2 and was increased by approximately 75 microA/cm2 on elevation of intracellular adenosine 3',5'-cyclic monophosphate (cAMP) by isoproterenol. Flux studies showed that the increase in Isc was due to Cl- secretion. Forskolin and permeant analogues of cAMP also increased Isc. Consistent with the presence of cAMP-dependent Cl- secretion, immunoprecipitation demonstrated the presence of the cystic fibrosis transmembrane conductance regulator (CFTR). Bradykinin, methacholine, trypsin, and histamine all transiently (15-30 s) elevated Isc, probably by increasing intracellular Ca concentration. Experiments in which the basolateral membrane was permeabilized with nystatin indicated that CFTR was substantially activated under baseline conditions and that Ca-activated Cl- channels were absent from the apical membrane. We anticipate that Calu-3 cells will prove useful in the study of Cl- secretion and other functions of human airway epithelial cells.

Topics: Bradykinin; Bumetanide; Calcimycin; Cell Line; Cell Membrane; Cell Membrane Permeability; Chloride Channels; Chlorides; Colforsin; Cyclic AMP; Cystic Fibrosis Transmembrane Conductance Regulator; Cytoplasmic Granules; Desmosomes; Epithelium; Histamine; Humans; Intercellular Junctions; Isoproterenol; Kinetics; Lung Neoplasms; Membrane Proteins; Methacholine Chloride; Microscopy, Electron; Nystatin; Ouabain; Sodium; Trypsin; Tumor Cells, Cultured

Topics: Aged; Candidiasis; Diagnosis, Differential; Diagnostic Errors; Geotrichosis; Humans; Lung Diseases, Fungal; Lung Neoplasms; Male; Mycoses; Nystatin

Topics: Candidiasis; Complement Fixation Tests; Hemagglutination Tests; Humans; Intestinal Neoplasms; Lung Neoplasms; Male; Nystatin; Pneumonectomy

Topics: Candida albicans; Candidiasis; Candidiasis, Oral; Deglutition Disorders; Esophagitis; Esophagoscopy; Humans; Lung Neoplasms; Nystatin; Oxytetracycline; Penicillins; Speech Disorders; Vocal Cord Paralysis