acriflavine and Carcinoma--Squamous-Cell

Confocal laser endomicroscopy (CLE) is an imaging technique that uses miniaturized fiberoptic probes to allow real-time histological imaging of human tissue. An application of CLE in otorhinolaryngology has hardly been investigated so far. In our study, we analyzed the applicability of CLE to visualize cancerous and healthy tissue of the head and neck region. Formalin-fixed tissue specimens from 135 head and neck squamous cell carcinoma (HNSCC) patients and 50 healthy controls were investigated using CLE with and without topical application of acriflavine. Four head and neck surgeons, four pathologists, and four laymen evaluated the CLE images of the HNSCC cases regarding the tumor localization and its border to healthy tissue. The tumor localization and the tumor border were correctly identified in 97 % by the pathologists, 85 % by the head and neck surgeons, and 70 % by the laymen. The main difference in evaluation results was seen in the correct identification of the tumor site (p < 0.05), while there was no significant difference in the identification of the tumor border. CLE is a valuable tool for real-time histological imaging of HNSCCs. It can help to visualize the tumor border and, thereby, facilitate a more precise tumor surgery.

Topics: Acriflavine; Adult; Aged; Carcinoma, Squamous Cell; Female; Fluorescent Dyes; Head and Neck Neoplasms; Humans; Male; Microscopy, Confocal; Optical Imaging; Squamous Cell Carcinoma of Head and Neck

Fibered confocal fluorescence microscopy (FCFM) allows in vivo investigation of pulmonary microstructures. However, the bronchial epithelium can only be imaged using exogenous fluorophores. The objective of this study is to compare methylene blue (MB) and acriflavine genotoxicity and to assess FCFM performance for in vivo imaging of precancerous lesions.. Genotoxicity was assessed using the comet assay on both cultured human lymphocytes and NCI-H460 cells, which had been exposed to MB or acriflavine before being illuminated at 660 or 488 nm, respectively. FCFM was performed on precancerous lesions in the hamster cheek pouch model, following topical application of the fluorophores. FCFM data were analyzed according to histology.. No genotoxicity was found using 0.01% (w/v) MB after illumination at 660 nm for 2 and 15 min (5 mW). Acriflavine exposure (0.025%) led to DNA damages, increasing from 2 to 15 min of light exposure at 448 nm in both lymphocytes (83.4 to 88%, p = 0.021) and NCI H460 cell populations (79.9 to 84.6%, p = 0.045). In total, 11 invasive carcinoma, 24 reserve cell hyperplasia, and 17 dysplasia lesions were imaged using FCFM in vivo. With both fluorophores, the cellular density increased from hyperplasia to high-grade dysplasia (p < 0.05). With MB, the cellular diameter significantly decreased (48.9 to 13.9 μm) from hyperplasia to carcinoma (p < 0.05). In this model, a cut-off diameter of 30 μm enabled the diagnosis of high-grade lesions with a sensitivity of 94.7% and a specificity of 97%.. Methylene blue can be used safely to image precancerous lesions in vivo. This study does not support the use of acriflavine in humans.

Topics: Acriflavine; Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Cells, Cultured; Comet Assay; Epithelial Cells; Fluorescent Dyes; Humans; Intravital Microscopy; Lung; Lymphocytes; Mesocricetus; Methylene Blue; Microscopy, Confocal; Microscopy, Fluorescence; Mouth Mucosa; Mouth Neoplasms; Mutagenicity Tests; Optical Imaging; Precancerous Conditions

Confocal endomicroscopy is an emerging technique for intravital visualization of neoplastic lesions, but its use has so far been limited to the gastrointestinal (GI) tract. This study was designed to assess the feasibility of in vivo confocal endomicroscopy of different regions of the oropharyngeal mucosa and to evaluate different contrast agents. We examined five different regions of the human oropharynx in vivo, and images were collected in real time by using a confocal laser endoscope as formerly described for the GI tract. Additionally ex vivo specimens were examined using a topical contrast agent. Confocal scanning was performed at 488-nm illumination for excitation of exogenously applied fluorophores (topical acriflavine and intravenous fluorescein). Confocal endomicroscopy allowed for visualization of cellular and subcellular structures of the anterior human oropharyngeal region. Fluorescein staining yielded architectural details of the surface epithelium and also subepithelial layers. Images taken at increasing depth beneath the epithelium showed the mucosal capillary network. Acriflavine strongly contrasted the cell nuclei of the surface epithelium. The findings correlated well with the histology of biopsy specimens. This is the first report showing that the use of fluorescence confocal endomicroscopy represents a promising method to examine cellular details in vivo in different oropharyngeal regions in human.

Topics: Acriflavine; Adult; Biopsy; Capillaries; Carcinoma, Squamous Cell; Contrast Media; Endoscopes; Feasibility Studies; Female; Fluorescein; Humans; Male; Microscopy, Confocal; Mouth Mucosa; Mouth Neoplasms; Neoplasm Invasiveness; Oropharyngeal Neoplasms; Oropharynx; Sensitivity and Specificity; Video Recording

Antibiotics and small molecular enzyme inhibitors produced by micro-organisms are microbial secondary metabolites which have no obvious function in the growth of microorganisms. Involvement of plasmids in their biosyntheses has been studied and the structure of the microbial world where various compounds with widely varying structures have been found has been shown to be due to the presence of a great variety of plasmids. On the basis of this structure of microbial world, the author has found the microbial products which have various activities useful in treatment of cancer or in suppression of carcinogenesis. In this paper, the author reviewed his following studies: the plasmid involvement in biosyntheses of bioactive microbial secondary metabolites; the mechanism of therapeutic effect of bleomycin, and the development of useful analogs and derivatives of bleomycin and anthracyclic antibiotics; the screening method to find compounds affecting immune system, and the action of bestatin in enhancing delayed-type hypersensitivity and therapeutic effects of anticancer agents; enzyme inhibitors with potential utility in treatment or prevention of cancer.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Acriflavine; Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Bleomycin; Carcinoma, Squamous Cell; Chloramphenicol; Chromosome Mapping; Copper; DNA, Neoplasm; Enzyme Inhibitors; Genes; Hodgkin Disease; Immunity, Cellular; Neoplasms, Experimental; Plasmids; Skin Neoplasms; Streptomyces; Structure-Activity Relationship