Biomedical subjects

Khee Chee Soo

Publications and source records attributed to Khee Chee Soo.

28 records · Page 2Linked to original sources

PubMed2003

A combined comparative genomic hybridization and expression microarray analysis of gastric cancer reveals novel molecular subtypes.

Comparative genomic hybridization (CGH), microsatellite instability (MSI) assays, and expression microarrays were used to molecularly subclassify a common set of gastric tumor samples. We identified a number of novel genomic aberrations associated with gastric cancer and discovered that gastric tumors could be grouped by their expression profiles into three broad classes: "tumorigenic," "reactive," and "gastric-like." Patients with gastric-like tumors exhibited a significantly better overall survival than patients belonging to the other two classes (P < 0.05). A novel supervised learning methodology for multiclass prediction was used to identify optimal predictor gene sets that accurately predicted the class of an unknown tumor sample. These predictor sets may prove useful in the development of new diagnostic applications for gastric cancer staging and prognostication.

Adenocarcinoma↗

PubMed2003

Optimal excitation-emission wavelengths for autofluorescence diagnosis of bladder tumors.

Tissue autofluorescence depends on endogenous fluorophores in the tissue, which undergo a change associated with malignant transformation. This change can be detected as an alteration in the spectral profile and intensity of autofluorescence. Our purpose was to determine the optimal excitation and emission wavelengths for autofluorescence diagnosis of bladder cancer. A total of 52 bladder tissue specimens were obtained from 25 patients undergoing mucosal biopsies or surgical resections of bladder tumors. Light-induced autofluorescence measurements were performed to study the spectroscopic differences between normal and malignant bladder tissue. Fluorescence excitation wavelengths varying from 220 to 500 nm were used to induce tissue autofluorescence, and emission spectra were measured in the 280-700 nm range. These spectra were then combined to construct 2-dimensional fluorescence excitation-emission matrices (EEMs). Significant changes in fluorescence intensity of EEMs were observed between normal and tumor bladder tissues, the most marked differences being at the excitation wavelengths of 280 and 330 nm. The diagnostic algorithm based on the combination of the fluorescence peak intensity ratios of I(350)/I(470) at 280 nm excitation and I(390)/I(470) at 330 nm excitation yielded a sensitivity of 100% [95% confidence interval (CI) 0.95-1.0] and specificity of 100% (95% CI 0.90-1.0). The results of the present fluorescence EEM study demonstrate that autofluorescence spectroscopy can distinguish malignant from normal bladder tissue and that excitation wavelengths of 280 and 330 nm are the most significant for differentiation between normal and malignant bladder mucosae with a high degree of diagnostic accuracy.

Aged↗

PubMed2003

A study of 5-aminolevulinic acid and its methyl ester used in in vitro and in vivo systems of human bladder cancer.

The use of 5-aminolevulinic acid and its esters to induce endogenous porphyrins for the purpose of detection of epithelial cancers is being studied extensively in many centres around the world. The challenge is to prepare an efficacious formulation for the purpose of cancer detection. Photodynamic diagnosis of cancer using 5-aminolevulinic acid (ALA) and its ester derivatives is being actively investigated. In this study, we compared ALA with ALA methyl ester (AME) derivative in terms of PpIX fluorescence intensity in in vitro and in vivo systems of bladder carcinoma. For the in vivo system consisting of RT112 xenografts, the modes of drug administration compared were intravenous administration and topical application. The Karl Storz fluorescence endoscopy system was used to obtain macroscopic fluorescence images. The macroscopic images were further analysed for fluorescence intensity distribution. For the intravenous administration, over all time points studied (1, 3, 6 h), AME-PpIX fluorescence was lower than ALA-PpIX fluorescence and was cleared at a faster rate than the ALA-PpIX when administered intravenously. Topical application with two different polymers, Gantrez and Polyvinyl pyrrolidone (PVP) which are fast releasing polymers was found to be comparable in inducing PpIX fluorescence. Topical AME-PpIX fluorescence was found to be comparable with ALA-PpIX fluorescence. The results of this study suggest that the AME can also be used as a good diagnostic agent.

Administration, Topical↗

PubMed2003

Macro-microscopic fluorescence of human bladder cancer using hypericin fluorescence cystoscopy and laser confocal microscopy.

The early detection of carcinoma is very essential for the diagnosis and prognosis of a bladder cancer patient. In this study we have investigated the use of hypericin as a fluorescent tumour marker and laser confocal microscopy as a diagnostic tool to aid the diagnosis of such cancers. Both cellular and clinical studies have been conducted. In the cellular studies, we have compared two bladder cell lines for the uptake and sub-cellular localization of hypericin. It was found that there was a rapid uptake and clearance of hypericin and significant localization in mitochondria and lysosomes. The study also revealed that there was a time-dependent increase in fluorescence intensity in bladder cells. The optimum localization was found to be 2-4 h post drug incubation. In the clinical study, consisting of 30 patients, both white light and fluorescence cystoscopy were performed after hypericin instillation. Biopsies taken from fluorescing regions were imaged using the confocal microscope. The order of fluorescence was detected to be as follows: normal < inflammation < grade 1 < grade 2 < CIS < grade 3. It was also found that the fluorescence intensity increased with the stage of the disease thereby enabling the determination of the degree of invasiveness of cancer. This enables the use of hypericin as a prognostic marker and laser confocal microscopy as a tool to aid in diagnosis of bladder cancer.

Anthracenes↗

PubMed2003

Novel photodynamic diagnosis of bladder cancer: ex vivo fluorescence cytology using hypericin.

In this study we have evaluated the use of hypericin ex vivo urine fluorescence cytology as a non-invasive method for detecting early bladder cancers. To date this is the first study reported using this technique with hypericin. Urine samples from patients with early bladder cancers were processed for fluorescence cytology by incubation with hypericin, a novel photosensitizer. Normal urine samples incubated with hypericin served as normal controls. Laser confocal microscopy and spectroscopy was used to detect the fluorescence in the exfoliated low-grade urothelial tumor cells. Fluorescence cytology was considered positive if hypericin fluorescence of the low-grade urothelial tumor cells was detected to be stronger (>8.5 times) compared to the baseline fluorescence established for normal urine samples. Automated analysis for an objective reproducible outcome appears possible. The possibility of detection of malignant urothelial cells in early cancer makes ex vivo fluorescence cytology promising for routine diagnostic screening.

Anthracenes↗

PubMed2002

Detection of squamous cell carcinomas and pre-cancerous lesions in the oral cavity by quantification of 5-aminolevulinic acid induced fluorescence endoscopic images.

BACKGROUND AND OBJECTIVES: Studies of 5-aminolevulinic acid-induced protoporphyrin IX fluorescence have shown a sensitivity of 95-100% for oral cancer diagnosis, but the specificity is only about 50-60%. Here, we explore the applicability of quantifying PPIX fluorescence images to improve the diagnostic specificity and detect early oral lesions. STUDY DESIGN/MATERIALS AND METHODS: PPIX Fluorescence endoscopy and imaging were performed on 28 patients with a known or suspected premalignant or malignant oral cavity lesion. A total of 70 biopsies were taken from the tissue sites imaged for histological analysis. The red-to-blue and red-to-green intensity ratios were calculated from the fluorescence images to correlate with histology. RESULTS: Suspicious lesions display bright reddish fluorescence, while normal mucosas exhibit blue color background in the fluorescence images. The red-to-blue and red-to-green intensity ratios of malignant tissues are larger than those of benign tissues. Combining the two ratio diagnostic algorithms yields a sensitivity and specificity of 95% and 97%, respectively, exceeding each diagnostic algorithm alone for discriminating malignant tissue from benign tissue. CONCLUSIONS: Quantifying PPIX fluorescence endoscopic images combined with the ratio diagnostic algorithms developed in this study has the potential to significantly improve the noninvasive diagnosis of oral cavity lesions in vivo.

Adult↗

PubMed2002

A comparison of protoporphyrin IX and protoporphyrin IX dimethyl ester as a photosensitizer in poorly differentiated human nasopharyngeal carcinoma cells.

Protoporphyrin IX dimethyl ester (PME), a dimethyl esterification of protoporphyrin IX (PpIX), exhibits higher intracellular uptake into NPC/CNE2 cells, a poorly differentiated human nasopharyngeal carcinoma, than does PpIX. Phototoxicity studies reveal PME to be a more potent photosensitizer than is PpIX, at the early and late incubation time points. Correlating phototoxicity with subcellular localization indicates that PME is a more potent photosensitizer when its primary target of photodamage is mitochondria. Also, additional targeting of lysosome enhances phototoxicity.

Apoptosis↗

PubMed2002

Detection of neoplasms in the oral cavity by digitized endoscopic imaging of 5-aminolevulinic acid-induced protoporphyrin IX fluorescence.

Studies of 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PPIX) fluorescence have shown a sensitivity of 95-100% for oral cancer diagnosis, but the specificity is only about 50-60%. To improve the diagnostic specificity, a 5-ALA mediated digitized fluorescence endoscopic imaging system was built in this study to enable the on-line image acquisition, analysis and fluorescence quantification for the early detection of neoplasms in the oral cavity. PPIX fluorescence endoscopy and fluorescence image quantification were performed on 16 patients with known or suspected premalignant or malignant lesions in the oral cavity. Preliminary data from the head and neck clinical trials show that the red-to-blue intensity ratio of malignant tissue is larger than that of benign tissue. By applying the intensity ratio as a diagnostic algorithm, both high specificity and sensitivity can be achieved for discriminating malignant tissue from benign tissue, and the capability of classifying different histopathological stages of oral lesions has also been demonstrated. It was found that the red fluorescence intensity distribution in the lesion area could also be obtained to better understand the situation of PPIX accumulations in the tissues. Our initial results indicate that the digitized endoscopic imaging system combined with the fluorescence image quantification method and the ratio diagnostic algorithm developed in this study has the potential to significantly improve the non-invasive diagnosis of early oral neoplasms in vivo.

Adult↗

PubMed2002

Macro-microscopic fluorescence imaging of human NPC xenografts in a murine model using topical vs intravenous administration of 5-aminolevulinic acid.

The use of 5-aminolevulinic acid to induce endogenous porphyrins for the purpose of detection of epithelial cancers is being studied extensively in many centres around the world. The challenge is to prepare an efficacious formulation of 5-ALA for the purpose of cancer detection. In this study, we compared two formulations of topical 5-ALA applications with intravenous administration in NPC/CNE-2 xenografts on balb/c nude mice. One of the formulations was a gantrez muco-adhesive patch and the other was a polyvinyl-pyrolidone muco-adhesive patch. The Karl Storz fluorescence endoscopy system was used to obtain macroscopic fluorescence images. Microscopic fluorescence imaging was done by laser confocal microscopy. The macroscopic images were further analysed for fluorescence intensity distribution. It was found that between the two formulations of topical application of 5-ALA; there was very little difference in the fluorescence biodistribution. When the topical applications were compared with the intravenous administration, the tumour to normal differential in biodistribution was significantly higher with the topical application compared to the intravenous application.

Administration, Topical↗

PubMedDate not supplied

An evaluation of exogenous application of protoporphyrin IX and its dimethyl ester as a photodynamic diagnostic agent in poorly differentiated human nasopharyngeal carcinoma.

5-Aminolevulinic acid and its esterified analogues have been under much investigation to enhance the endogenous production of protoporphyrin IX (PpIX) in tumor cells. However, in this work, we studied the in vitro and in vivo efficacy of exogenously administered PpIX and its esterified analogue, PpIX dimethyl ester (PME), in poorly differentiated human nasopharyngeal carcinoma (NPC/CNE-2) as a photodynamic diagnostic (PDD) agent. NPC/CNE-2 at its earliest time, 1 h after incubation with PME in in vitro studies, has exhibited 64% (P <0.01) higher tumor to normal cell (T/N) fluorescence ratio than with PpIX. In an in vivo mouse xenograft model, comparable photosensitizer concentration in tumor after intravenous administration was observed at 1-3 h time points, but at 9 h, PME had 31% (P=0.05) greater concentration in tumor compared with PpIX. In addition, by constituting PME and PpIX in different topical gel composites, of which, PME gel composition of 8:2 Plasdone and Gantrez resulted in the highest T/N ratio at 6 h after application (34%; P <0.05) in comparison with other gel composites. Evaluation of PME and PpIX constituted in the delivery vehicles investigated showed comparable selectivity for tumor at 1-3 h, thus neither photosensitizer is more efficient than the other for PDD at the early time points; however, beyond 6 h, PME had higher selectivity for tumor compared with PpIX. Thus, further investigation is warranted to improve the drug delivery vehicle for greater tumor selectivity at a shorter incubation time.

Aged↗