flavin-adenine-dinucleotide and Mouth-Neoplasms

The molecular basis of reduced autofluorescence in oral squamous cell carcinoma (OSCC) cells relative to normal cells has been speculated to be due to lower levels of free flavin adenine dinucleotide (FAD). This speculation, along with differences in the intrinsic optical properties of extracellular collagen, lies at the foundation of the design of currently-used clinical optical detection devices. Here, we report that free FAD levels may not account for differences in autofluorescence of OSCC cells, but that the differences relate to FAD as a co-factor for flavination. Autofluorescence from a 70 kDa flavoprotein, succinate dehydrogenase A (SDHA), was found to be responsible for changes in optical properties within the FAD spectral region, with lower levels of flavinated SDHA in OSCC cells. Since flavinated SDHA is required for functional complexation with succinate dehydrogenase B (SDHB), decreased SDHB levels were observed in human OSCC tissue relative to normal tissues. Accordingly, the metabolism of OSCC cells was found to be significantly altered relative to normal cells, revealing vulnerabilities for both diagnosis and targeted therapy. Optimizing non-invasive tools based on optical and metabolic signatures of cancers will enable more precise and early diagnosis leading to improved outcomes in patients.

Topics: Carcinoma, Squamous Cell; Electron Transport Complex II; Flavin-Adenine Dinucleotide; Humans; Mouth Neoplasms; Succinate Dehydrogenase

Long non-coding RNAs (lncRNAs) play critical roles in human cancers. HOXA11 anti-sense RNA (

Topics: Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Flavin-Adenine Dinucleotide; Genes, Homeobox; Glyceraldehyde-3-Phosphate Dehydrogenases; Homeodomain Proteins; Humans; Lactic Acid; Mice; MicroRNAs; Mouth Neoplasms; NAD; NAD(P)H Dehydrogenase (Quinone); Quinone Reductases; Quinones; RNA, Antisense; RNA, Long Noncoding; Squamous Cell Carcinoma of Head and Neck

Mortality of oral cancer is often due to late diagnosis. Effective non-invasive diagnostic techniques may increase the survival rate based on an earlier diagnosis.. We report on the application of the polarization gating technique for isolating weakly scattered and highly scattered components of fluorescence emission from the superficial and deeper layers of tissue due to intrinsic fluorophores NADH and FAD. The fluorescence polarization spectra were collected from 21 normal and 67 oral squamous cell carcinoma biopsy tissues. The tissues were excited at 350 nm and the fluorescence emission had two peaks corresponding to NADH, and FAD respectively. The spectra were analyzed using the polarization gating technique along with the spectral deconvolution method to derive the optical redox ratio from different layers of tissue. The fractional change in redox ratio between superficial and deeper layers of tissue exhibits excellent statistical significance (p<10

Topics: Carcinoma, Squamous Cell; Flavin-Adenine Dinucleotide; Mouth Neoplasms; NAD; Oxidation-Reduction; Signal Processing, Computer-Assisted; Spectrometry, Fluorescence

We created a two-channel autofluorescence test to detect oral cancer. The wavelengths 375 and 460 nm, with filters of 479 and 525 nm, were designed to excite and detect reduced-form nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) autofluorescence. Patients with oral cancer or with precancerous lesions, and a control group with healthy oral mucosae, were enrolled. The lesion in the autofluorescent image was the region of interest. The average intensity and heterogeneity of the NADH and FAD were calculated. The redox ratio [(NADH)/(NADH + FAD)] was also computed. A quadratic discriminant analysis (QDA) was used to compute boundaries based on sensitivity and specificity. We analyzed 49 oral cancer lesions, 34 precancerous lesions, and 77 healthy oral mucosae. A boundary (sensitivity: 0.974 and specificity: 0.898) between the oral cancer lesions and healthy oral mucosae was validated. Oral cancer and precancerous lesions were also differentiated from healthy oral mucosae (sensitivity: 0.919 and specificity: 0.755). The two-channel autofluorescence detection device and analyses of the intensity and heterogeneity of NADH, and of FAD, and the redox ratio combined with a QDA classifier can differentiate oral cancer and precancerous lesions from healthy oral mucosae.

Topics: Adult; Aged; Aged, 80 and over; Discriminant Analysis; Female; Flavin-Adenine Dinucleotide; Humans; Male; Middle Aged; Mouth Mucosa; Mouth Neoplasms; NAD; Sensitivity and Specificity; Spectrometry, Fluorescence; Young Adult

Metabolic imaging of the relative amounts of reduced NADH and FAD and the microenvironment of these metabolic electron carriers can be used to noninvasively monitor changes in metabolism, which is one of the hallmarks of carcinogenesis. This study combines cellular redox ratio, NADH and FAD lifetime, and subcellular morphology imaging in three dimensions to identify intrinsic sources of metabolic and structural contrast in vivo at the earliest stages of cancer development. There was a significant (P < 0.05) increase in the nuclear to cytoplasmic ratio (NCR) with depth within the epithelium in normal tissues; however, there was no significant change in NCR with depth in precancerous tissues. The redox ratio significantly decreased in the less differentiated basal epithelial cells compared with the more mature cells in the superficial layer of the normal stratified squamous epithelium, indicating an increase in metabolic activity in cells with increased NCR. However, the redox ratio was not significantly different between the superficial and basal cells in precancerous tissues. A significant decrease was observed in the contribution and lifetime of protein-bound NADH (averaged over the entire epithelium) in both low- and high-grade epithelial precancers compared with normal epithelial tissues. In addition, a significant increase in the protein-bound FAD lifetime and a decrease in the contribution of protein-bound FAD are observed in high-grade precancers only. Increased intracellular variability in the redox ratio, NADH, and FAD fluorescence lifetimes were observed in precancerous cells compared with normal cells.

Topics: Animals; Carcinoma; Cell Nucleus; Cricetinae; Cytoplasm; Flavin-Adenine Dinucleotide; Fluorescence; Microscopy, Fluorescence, Multiphoton; Mouth Neoplasms; NAD; Oxidation-Reduction; Precancerous Conditions; Tumor Cells, Cultured

Topics: Adult; Aged; Female; Flavin-Adenine Dinucleotide; Glossitis; Humans; Male; Middle Aged; Mouth Neoplasms; Radiation Injuries; Radiotherapy; Stomatitis