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Biomedical subjects

S H Kok

Publications and source records attributed to S H Kok.

At least 19 recordsLinked to original sources
PubMed2003

Comparisons of norcantharidin cytotoxic effects on oral cancer cells and normal buccal keratinocytes.

Norcantharidin (NCTD) is the demethylated analogue of cantharidin. In this study, multi-parameter assessments of morphological alterations, clonogenic efficiency, cell growth curves, DNA synthesis, and DNA strand break were employed to determine and compare the cytotoxic effects of NCTD on oral cancer KB cell line and normal buccal keratinocytes. The results showed NCTD induced significant cytotoxicity in KB cells after 24 h of exposure. Normal buccal keratinocytes were more resistant to NCTD induced cytotoxicity. The IC(50) of 24 h NCTD treatment for KB and keratinocytes were 15.06 and 216.29 microg/ml, respectively with a keratinocyte/KB selective index of 14.36. Anoikis and membrane blebbing, morphological characterization of apoptosis, were observed in about 90% of KB cells after exposure to 100 microg/ml of NCTD for 24 h compared to about 30% in keratinocytes. In addition, inhibition of colony formation was noted in KB cells even when exposed to low concentration of drug (5 microg/ml) for a short period of time (6 h). NCTD inhibited subsequent cell proliferation in KB but growth of normal keratinocytes was retarded only temporarily. NCTD inhibited DNA synthesis in both KB and normal keratinocytes. However, keratinocytes were more sensitive to DNA synthesis inhibition by low dose of NCTD. Significant DNA strand break was noted in KB cells only after cell viability was reduced to less than 60% of the control. In comparison, normal keratinocytes were resistant to NCTD induced DNA strand break. These results indicated KB cells were more sensitive to NCTD induced cytotoxicity compared to normal keratinocytes. NCTD may be of value in treating oral cancers. The underlying mechanisms of the differential actions of NCTD on these two cell types are worthy of further investigations.

Bridged Bicyclo Compounds, Heterocyclic↗
PubMed2002

Prevention of the areca nut extract-induced unscheduled DNA synthesis of gingival keratinocytes by vitamin C and thiol compounds.

There are about 600 million betel quid (BQ) chewers in the world. BQ chewing is the major risk factor of oral cancer in India, Taiwan, South Africa and numerous other countries. Areca nut (AN) extract, the main component of BQ, exerts cytotoxicity and genotoxicity to several types of cells. In the present study, AN extract induced the unscheduled DNA synthesis (UDS) of gingival keratinocytes (GK). Vitamin C, at concentration of 50 and 200 microg/ml prevented the AN-induced UDS by 41 and 56%, respectively. Glutathione (GSH, 1-3 mM) and N-acetyl-L-cysteine (NAC, 1-3 mM) also protected the AN-induced UDS by 89-100 and 76-90%. These preventive effects were not due to cytotoxicity as analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. Deferoxamine (20 and 30 mM), an iron chelator and a free radical scavenger, also prevented AN extract induced UDS of GK by 30-55%. On the contrary, banthocuproine (50-200 microM, a copper chelator) and 1,10-phenanthroline (50, 100 microM, a lipid permeable iron chelator), lacked preventive effects. Specific reactive oxygen species scavengers such as dimethyl-sulfoxide (2%), mannitol (10-20 mM), dimethylthiourea (10-20 mM), pyruvate (10 mM), catalase (200 and 400 U/ml), and superoxide dismutase (50 and 200 U/ml) also lacked these preventive effects. Moreover, higher concentrations of H(2)O(2) (0.5-1 mM) inhibited the basal levels of UDS by 19-37%. Interestingly, NAC, GSH, Vitamin C and deferoxamine cannot prevent the AN-induced morphological changes of GK at similar concentrations. These results reveal that AN extract-induced UDS of GK is associated with free radical reactions. Possibly different ingredients of AN is responsible for genotoxicity and cytotoxicity. Vitamin C, GSH and NAC may be potentially used in the future for chemoprevention of BQ chewing related oral mucosal lesions.

Antioxidants↗
PubMed2002

Repair of oroantral communications in the third molar region by random palatal flap.

Various palatal flap procedures based on the greater palatine vessels have been advocated for the repair of oroantral communications (OACs). However, when the defect is located in the third molar region, difficulty is encountered in using the palatal flap because rotation is hindered by the vascular pedicle. In this study, we used random palatal flaps to repair OACs in the third molar area in 21 patients. The vascular pedicles were ligated and severed in all cases in order to evaluate whether it was necessary to preserve the greater palatine vessels when using the palatal rotation flap (PRF). The repair was successful in 16 cases (76.2%). The length/width ratio of the flap was the most important factor determining the outcome. The ratios were 2.23 +/- 0.12 and 2.40 +/- 0.14 in the success and failure groups, respectively and their difference was statistically significant (P<0.05). Other clinical parameters such as age, gender, antral infection, tooth displacement into the sinus and duration of the communication had no influence on the outcome (P>0.05). The study showed that the PRF with the appropriate length/width ratio can safely be used in a random fashion. This provided another option in the repair of oroantral communications of difficult locations such as in the tuberosity area.

Age Factors↗
PubMed2001

MDM2 expression in areca quid chewing-associated oral squamous cell carcinomas in Taiwan.

MDM2 (murine double minute gene 2) overexpression has been implicated in the pathogenesis of human tumors via inhibition of the p53 tumor suppressor protein. To investigate the potential involvement of MDM2 overexpression in the pathogenesis of oral squamous cell carcinomas (SCCs) in Taiwan, we examined the expression of MDM2 protein and its relationship to p53 protein levels in 52 oral SCCs using antibodies to MDM2 and p53. Of the 52 patients, 36 (69 %) had tumors with positive MDM2 nuclear staining and 32 (61%) had tumors with p53 nuclear staining. Co-expression of MDM2 protein and p53 was detected in 25 (48%) cases; and 9 (17%) tumors showed neither MDM2 protein nor p53 staining. A significant correlation was observed between MDM2 protein and p53 expression in 38 cases with an areca quid (AQ) chewing habit (P=0.032). No significant correlation was found between the degree of MDM2 protein staining and the patients' ages, sex, cancer location, clinical staging, primary tumor TNM status or histological differentiation of SCC at the time of initial presentation. Kaplan-Meier analysis showed that either MDM2 protein expression or co-expression of p53 and MDM2 protein did not relate significantly to patient overall survival. Nevertheless, the high prevalence of MDM2 protein overexpression found in this study suggest that MDM2 may also participate in the carcinogenesis of AQ chewing-associated oral SCCs in Taiwan.

Adult↗
PubMed2001

Phase, compositional, and morphological changes of human dentin after Nd:YAG laser treatment.

Although techniques for repairing root fracture have been proposed, the prognosis is generally poor. If the fusion of a root fracture by laser is possible, it will offer an alternative to extraction. Our group has attempted to use lasers to fuse a low melting-point bioactive glass to fractured dentin. This report is focused on the phase, compositional, and morphological changes observed by means of X-ray diffractometer, Fourier transforming infrared spectroscopy, and scanning electron microscopy-energy dispersive X-ray spectroscopy in human dentin after exposure to Nd:YAG laser. The irradiation energies were from 150 mJ/ pulse-10 pps-4 s to 150 mJ/pulse-30 pps-4 s. After exposure to Nd:YAG laser, dentin showed four peaks on the X-ray diffractometer that corresponding to a-tricalcium phosphate (TCP) and beta-TCP at 20 = 30.78 degrees/34.21 degrees and 32.47 degrees/33.05 degrees, respectively. The peaks of a-TCP and beta-TCP gradually increased in intensity with the elevation of irradiation energy. In Fourier transforming infrared analysis, two absorption bands at 2200 cm(-1) and 2015 cm(-1) could be traced on dentin treated by Nd:YAG laser with the irradiation energies beyond 150 mJ/pulse-10 pps-4 s. The energy dispersive X-ray results showed that the calcium/phosphorus ratios of the irradiated area proportionally increased with the elevation of irradiation energy. The laser energies of 150 mJ/ pulse-30 pps-4 s and 150 mJ/pulse-20 pps-4 s could result in the a-TCP formation and collagen breakdown. However, the formation of glass-like melted substances without a-TCP at the irradiated site was induced by the energy output of 150 mJ/ pulse-10 pps-4 s. Scanning electron micrographs also revealed that the laser energy of 150 mJ/ pulse-10 pps-4 s was sufficient to prompt melting and recrystallization of dentin crystals without cracking. Therefore, we suggest that the irradiation energy of Nd:YAG laser used to fuse a low melting-point bioactive glass to dentin is 150 mJ/ pulse-10 pps-4 s.

Aluminum Silicates↗
PubMed2000

Treatment of tooth fracture by medium energy CO2 laser and DP-bioactive glass paste: compositional, structural, and phase changes of DP-bioglass paste after irradiation by CO2 laser.

Nowadays, fractured teeth are difficult to treat effectively. Currently, root fractures are usually treated by root amputation, hemisection or tooth extraction. If the fusion of tooth fracture by laser were possible, it would offer a different therapy to repair fracture teeth. We tried to use a developed DP-bioactive glass paste to fuse or bridge the tooth crack line by a medium energy continuous-wave CO2 laser. The study is divided into three parts: (1) The compositional and structure changes in tooth enamel and dentin after laser treatment; (2) The phase transformation and recrystallization of DP-bioactive paste during exposure to the CO2 laser; (3) The thermal interactions and bridge mechanism between DP-bioactive glass paste and enamel/dentin when they are subjected to CO2 laser. The present report will focus on the second part that will examine the changes of laser-exposed DP-bioactive glass paste by means of X-ray diffractometer (XRD), Fourier transforming infrared spectroscopy (FTIR), differential thermal analysis/thermogravimetric analysis (DTA/TGA), and scanning electron microscopy (SEM). From the study, we could find that the temperature increase due to laser irradiation is greater than 900 degrees C and that the DP-bioactive glass paste could be melted in a short period of time after irradiation. In the study, we successfully developed a DP-bioactive glass paste which could form a melting glass within seconds after exposure to a medium energy density continuous-wave CO2 laser. The paste will be used in the near future to bridge the enamel or dentin surface crack by the continuous-wave CO2 laser.

Carbon Dioxide↗
PubMed2000

Induction of the c-jun protooncogene expression by areca nut extract and arecoline on oral mucosal fibroblasts.

To investigate the mechanisms of areca quid (AQ)-induced carcinogenesis, expression of c-fos and c-jun protooncogenes was examined in human oral mucosal fibroblasts after exposure to areca nut extracts (ANE) or arecoline. We found that treatment of cells with 200 microg/ml ANE or 10 microg/ml arecoline for 1 h induced about three-fold increase in c-jun mRNA levels. This increase was transient and the level of c-jun mRNAs returned rapidly to control levels thereafter. However, ANE and arecoline did not induce c-fos mRNA expression at detectable levels. During AQ chewing, oral mucosal cells are continuously stimulated by ANE and arecoline. Persistent induction of the c-jun protooncogene by ANE and arecoline may be one of the mechanisms in the carcinogenesis of oral squamous cell carcinoma in Taiwan. Furthermore, we observed that pre-incubation of cells with either N-acetyl-cysteine [a glutathione (GSH) precursor] or L-buthionine-S,R-sulfoximine (a specific inhibitor of GSH biosynthesis) had a minimal effect on arecoline-induced c-jun expression. Therefore, arecoline-induced c-jun expression is independent of GSH depletion.

Areca↗
PubMed2000

Treatment of tooth fracture by medium energy CO2 laser and DP-bioactive glass paste: thermal behavior and phase transformation of human tooth enamel and dentin after irradiation by CO2 laser.

Acute trauma or trauma associated with occlusal disharmony can produce tooth crack or fracture. Although several methods are proposed to treat the defect, however, the prognosis is generally poor. If the fusion of a tooth fracture by laser is possible it will offer an alternative to extraction or at least serve as an adjunctive treatment in the reconstruction. The responses of soft tissues to lasers of different wavelengths are fairly well known, but the reactions of hard tissues are still to be understood. The purpose of this research was to study the feasibility of using a medium energy continuous-wave CO(2) laser and a low melting-point bioactive glass to fuse or bridge tooth fractures. The present report is focused on the first part of the research, the analysis of changes in laser-irradiated human tooth enamel/dentin by means of X-ray diffractometer (XRD), Fourier-transforming infrared spectroscopy (FTIR), differential thermal analysis/thermogravimetric analysis (DTA/TGA), and scanning electron microscopy (SEM). After CO(2) laser irradiation, there were no marked changes in the X-ray diffraction pattern of the enamel when compared to that before laser treatment. However, a small peak belonging to alpha-TCP appeared at the position of 2theta=30.78 degrees C. After being treated with CO(2) laser, the dentin showed much sharper peaks on the diffraction patterns because of grain growth and better crystallinity. alpha-TCP and beta-TCP were identified after laser treatment. In the FTIR analysis, an HPO(4)(-2) absorption band was noted before laser treatment disappeared after the irradiation. No significant change in the absorption band of HPO(4)(-2) was found on the FTIR curves of enamel after laser treatment. The results of DTA/TGA indicated that loss of water and organic materials occurred in both enamel and dentin after laser treatment. Under SEM, melting and resolidification occurred in both enamel and dentin by medium energy of CO(2) laser. This implies that using a continuous-wave CO(2) laser of medium energy density to fuse a low melting-point bioactive glass to the enamel/dentin is possible. We believe these phase changes and thermal data can make a useful guide for future studies on the thermal interaction and bridging mechanism between the bioactive glass and enamel/dentin under CO(2) laser irradiation.

Journal Article↗
PubMed1999

Infrequent p53 mutations in patients with areca quid chewing-associated oral squamous cell carcinomas in Taiwan.

Mutations in the conserved regions (exons 5-9) of the p53 gene were investigated in 37 untreated human primary oral squamous cell carcinomas (SCCs) using polymerase chain reaction-single strand conformation polymorphism and DNA sequencing analyses. P53 mutations were detected in 2 of 37 (5.4%) oral SCC cases. One tumor sample (case 23) showed a mis-sense point mutation at codon 177, changing CCC to CTC, which resulted in a substitution of proline to leucine in the p53 protein. The other tumor (case 33) had a point mutation at codon 266, changing GGA to AGA and causing a substitution of glycine to arginine in the p53 protein. These two patients with p53 mutations did not have an areca quid chewing habit. These results suggest that mutations in the p53 gene may not play a role in the pathogenesis of human oral SCCs in Taiwan. Recently, we have shown that positive p53 staining was observed in 47 of 81 (58%) cases of oral SCC. The discrepancies between positive p53 protein staining and the low prevalence of p53 mutation in oral SCCs indicate that other mechanism(s) are involved in p53 overexpression.

Adult↗
PubMed1998

Expression of CD44s, CD44v5, CD44v6 and CD44v7-8 in betel quid chewing-associated oral premalignant lesions and squamous cell carcinomas in Taiwan.

Aberrant expression of the cell surface adhesion molecule CD44 and its variant forms has been shown to be associated with the invasive and metastatic potential of cancer cells, and with poor prognosis in several types of cancers. Expression of CD44 standard (CD44s) and variant (CD44v) forms in oral squamous cell carcinoma (SCC), epithelial dysplasia (ED), epithelial hyperkeratosis (EH) and normal buccal mucosa (NBM) have been examined using antibodies to CD44s, CD44v5, CD44v6 and CD44v7-8. Positive CD44s, CD44v5, CD44v6 and CD44v7-8 staining was detected in all the specimens from NBM, EH and ED. Positive staining of CD44s, CD44v5, CD44v6 or CD44v7-8 was detected in 55 (88.7%), 48 (77.4%), 59 (95.2%) and 22 (35.5%) of the 62 SCC specimens, respectively. The positive staining of CD44v7-8 in oral SCC was significantly less than that in NBM (P<0.01). No significant correlation was found between CD44v7-8 expression and daily or total consumption of betel quids or cigarettes by the SCC patients. The 5-year survival rate for patients with CD44v7-8-positive tumours was significantly higher than that for the CD44v7-8-negative group (P<0.03). These results indicate that loss of CD44v7-8 expression may be a valuable factor for determining prognosis in oral SCC patients.

Adult↗
PubMed1997

Loss of heterozygosity of APC and MCC genes in oral squamous cell carcinomas in Taiwan.

Loss of heterozygosity (LOH) at adenomatous polyposis coli (APC) and mutated in colon cancer (MCC) genes was investigated in 37 untreated human primary oral squamous cell carcinomas (SCCs) using the polymerase chain reaction. LOH was observed in 14 of 26 (53.8%) heterozygous (informative) patients at APC and 9 of 13 (69.2%) heterozygous patients at MCC> Homozygous deletion of MCC was detected in one patient. Of the 37 patients, 29 were informative at APC or MCC or both; LOH at APC and/or MCC was detected in 68.9% (20/29) of the cases. Ten cases were informative for both genes; LOH at both loci was found in only three of these cases. LOH at the APC and/or MCC was found in both early and advanced stages of oral SCCs. No significant correlation was observed between LOH at the APC and/or MCC locus and the patients' tobacco/betel quid consumption, tumour location, TNM status, or histological differentiation. These results suggest that LOH at the APC and/or MCC may be an early event and may play a role in the pathogenesis of human oral SCCs in Taiwan.

Carcinoma, Squamous Cell↗
PubMed1990

Histologic reactions to a newly developed calcium phosphate cement implanted in the periapical and periodontal tissues.

A newly developed calcium phosphate cement (CPC), basically composed of tetracalcium phosphate, Ca4(PO4)2O and dicalcium phosphate dihydrate, CaHPO4.2H2O or anhydrous calcium phosphate, CaHPO4, was tested in this study. When combined with water, the cement hardens and produces hydroxylapatite resembling the principal mineral of teeth and bones. Therefore, the CPC should be highly compatible with the body. However, before its clinical application in dentistry, the biocompatibility of CPC in the potential environments of implantation needs confirmation. Eight monkeys were used in our study to test the material in the periapical and marginal periodontal regions. Surgically created periodontal defects were implanted with CPC and hydroxylapatite (HA) (Calcitite 4060). In another application, CPC was pushed into the periapical areas via overfilling of the root canals. Sargenti N2 served as the control material in the periapical test. Generally, only a limited inflammatory response to CPC was found after 6 weeks of implantation in the periodontal area. In the 16-week specimens, the adverse reaction was negligible, and bone regeneration was marked and directly surrounding the CPC. The bone formation activity and biocompatibility in general were found to be even better in the periapical region. The results suggest that the CPC may have a good potential in future clinical applications, although many issues remain to be investigated.

Animals↗