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High-definition Fourier Transform Infrared (FT-IR) Spectroscopic Imaging of Human Tissue Sections towards Improving Pathology
Published on: January 21, 2015
Observation of molecular changes of a necrotic tissue from a murine carcinoma by Fourier-transform infrared
Tetsushi Yamada1, Norio Miyoshi, Toru Ogawa
1Department of Dentistry and Oral Surgery, Fukui Medical University, Matsuoka, Fukui 910-1193, Japan.
Purpose:
Our purpose is to develop infrared (IR) microspectroscopy as a new optical diagnostic tool to support conventional lightscopic techniques in investigating the viability of carcinoma tissues and to develop its use in the evaluation of the early effects of anticancer therapy by monitoring the IR spectra in the necrotic area.
Experimental Design:
We evaluated the tissue which amassed for 4 weeks after the isotransplantation of mouse squamous cell carcinoma into the thigh of mice. The borders of the necrotic area of frozen tissue specimens were investigated by Fourier-transform IR microspectroscopy and conventional histological staining.
Results:
A significantly higher accumulation of cholesterol was observed in the necrotic tissue of a carcinoma. The mechanism of this phenomenon is hitherto unrecognized. We proposed that the accumulated cholesterol may lie extracellularly as a result of the ruptured plasma and internal membranes after the swelling of the necrotic cells brought on by hypoxia. The analysis of the secondary structure of protein revealed that the amounts of beta-sheet increased significantly in striking contrast to the decreasing amounts of alpha-helix in a necrotic area of a carcinoma. It is plausible that this structural conversion of protein was because of lipid-autooxidation products, such as cholesterol oxide but not cholesterol itself, which possesses cell toxicity and could be generated in a necrotic area.
Conclusions:
We conclude that it will be possible to evaluate the efficacy of the clinical treatment of carcinoma by monitoring subtle biological changes of cholesterol absorbance in the early stage of necrosis because of anticancer treatment.
Insights
Infrared (IR) microspectroscopy detects increased cholesterol and altered protein structures in necrotic carcinoma tissue. This technique may help evaluate early anticancer treatment effects by monitoring these changes in early necrosis.
Area of Science:
- Biomedical Optics
- Cancer Research
- Spectroscopy
Background:
- Conventional light microscopy has limitations in assessing carcinoma tissue viability.
- Early detection of therapeutic effects in cancer treatment is crucial.
Purpose of the Study:
- To establish infrared (IR) microspectroscopy as an optical diagnostic tool for carcinoma tissue viability.
- To evaluate early anticancer therapy effects by monitoring IR spectra in necrotic areas.
Main Methods:
- Fourier-transform IR microspectroscopy and histological staining were used.
- Mouse squamous cell carcinoma tissues, 4 weeks post-transplantation, were analyzed.
- Borders of necrotic areas in frozen tissue specimens were investigated.
Main Results:
- Significantly higher cholesterol accumulation was observed in necrotic carcinoma tissue.
- Protein analysis revealed increased beta-sheet and decreased alpha-helix structures in necrotic areas.
- Hypoxia-induced cell swelling and membrane rupture are proposed mechanisms for cholesterol accumulation.
Conclusions:
- IR microspectroscopy can monitor subtle biological changes in cholesterol absorbance during early necrosis.
- This method shows potential for evaluating the efficacy of clinical carcinoma treatments.