Sang-heng Kok - Academia.edu (original) (raw)

Papers by Sang-heng Kok

Journal of the Formosan Medical Association = Taiwan yi zhi, Jan 6, 2015

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. This study evaluated whe... more Vascular endothelial growth factor (VEGF) is a potent angiogenic factor. This study evaluated whether the VEGF mRNA level in oral squamous cell carcinoma (OSCC) tissue could be a biomarker to predict the progression and prognosis of OSCCs in Taiwan. This study used quantitative real-time reverse transcription-polymerase chain reaction (quantitative RT-PCR) to detect the VEGF mRNA levels in 60 OSCC specimens. Threshold cycle (CT) was defined as the PCR cycle number needed to generate a predetermined amount of DNA (threshold). The relative amount of tissue VEGF mRNA, standardized against the amount of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA, was expressed as ΔCT = (VEGF CT - GAPDH CT). For a chosen threshold, a smaller starting copy number of mRNA results in a higher CT value. Thus, the lower the ΔCT, the greater the copy number of VEGF mRNA in tissues. The lower mean VEGF mRNA ΔCT value was significantly associated with OSCCs with larger tumor size (p = 0.040), positive...

The International journal of oral & maxillofacial implants

The aim of this prospective clinical study was to assess the risk factors associated with failure... more The aim of this prospective clinical study was to assess the risk factors associated with failure of mini-implants used for orthodontic anchorage. A total of 140 mini-implants in 44 patients, including 48 miniplates and 92 freestanding miniscrews, were examined in the study. A variety of orthodontic loads were applied. The majority of implants were placed in the posterior maxilla (104/140), and the next most common location was the posterior mandible (34/140). A cumulative survival rate of 89% (125/140) was found by Kaplan-Meier analysis. There was no significant difference in the survival rate between miniplates and freestanding miniscrews, but miniplates were used in more hazardous situations. The Cox proportional-hazards regression model identified anatomic location and peri-implant soft tissue character as 2 independent prognostic indicators. The estimated relative risk of implant failure in the posterior mandible was 1.101 (95% confidence interval, 0.942 to 1.301; P = .046). Th...

Because of its close proximity to teeth and periodontium, gingival squamous cell carcinoma (SCC) ... more Because of its close proximity to teeth and periodontium, gingival squamous cell carcinoma (SCC) can sometimes mimic tooth-related benign inflammatory conditions, resulting in misdiagnosis. In this study we report a case of gingival SCC that mimicked a dentoalveolar abscess of endodontic origin in its early presentation. The course and treatment of this case is discussed and a brief review of the literature is presented. Because many patients with gingival SCC visit dentists as their initial professional contact, it is hoped that the case can serve as a reminder for dentists to keep the possibility of carcinoma in mind when examining intraoral lesions. (J Endod 2007;33:177-180)

Oral squamous cell carcinoma (OSCC) is common in many Asian countries. The immunopathogenesis of ... more Oral squamous cell carcinoma (OSCC) is common in many Asian countries. The immunopathogenesis of OSCC is unclear. The authors analyzed the lymphocyte subtypes and surface activation markers in healthy Taiwanese people (n = 130) and patients with OSCC (n = 97)/oral leukoplakia (OL, n = 28) using flow cytometry. Univariate analysis found an elevation in the percentage of CD56+ NK cells, CD4+/CD69+ T cells, CD19+/CD69+ B cells and CD56+/CD69+ NK cells in OSCC patients relative to healthy people. The CD19+ and CD19+/CD25+ lymphocyte subtypes decreased in OSCC patients. CD56+ NK cells increased in OL patients. CD56+/CD69+ NK cells were elevated in recurrent and advanced OSCC. Multivariate analysis revealed an increase in CD56+ NK and CD19+/CD69+ cells in OL patients relative to controls. CD19+ B cells declined during progression from OL to OSCC. Betel quid chewing, alcohol, smoking, tumour location and staging showed little effect on lymphocyte subtypes. These results suggest that alterations and activation of NK cells, T and B cells are important and associated with disease status in oral carcinogenesis.

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 2006

The purpose of this prospective randomized study was to investigate the manifestations and effici... more The purpose of this prospective randomized study was to investigate the manifestations and efficiency of mandibular block (MB) using a standardized method. In this study, 123 patients requiring MB were randomly assigned to receive MB using a repeated measures design. Mandibular block was administered in each patient by using 2.1 mL of 2% lidocaine with 1:100 000 epinephrine for the inferior alveolar nerve, lingual nerve, and/or buccal nerve. Clinical parameters including the electric pulp test and test for soft tissue sensation using a sharp dental explorer were assessed on both the operated side and contralateral side before and 5, 10, and 15 minutes after injection, and at the end of surgical procedure. Results of the test of the contralateral tooth served as the control group. No response to the electric pulp test at a maximum output (80 readings) was used as the criterion for pulpal anesthesia. Results obtained with electric pulp test and sharp explorer test were not significantly different during various intervals on the contralateral side, indicating the reliability of this standardized method for assessing MB. The MB technique achieved a high rate of subjective numbness (100%) according to the perception of the patients of overall numbness and lip numbness. Overall anesthetic success rates of pulpal anesthesia were 5.7% for the central incisor, 38.2% for the canine, 55.3% for the first premolar, and 90.2% for the first molar. No significant difference was found in the efficiency of anesthesia related to sex or age of the patients. A slower onset of pulpal anesthesia after MB was found for the anterior teeth than for the posterior teeth. This study suggests that the use of a standardized method might produce a clearer and more comprehensive evaluation of the efficiency and manifestations of MB. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;102:462-68)

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 2005

The aim of the study was to examine the expressions of p53 and proliferating cell nuclear antigen... more The aim of the study was to examine the expressions of p53 and proliferating cell nuclear antigen (PCNA) in oral lichen planus (OLP) in relation to its clinical behavior and the patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; oral habits. Immunohistochemical study was carried out to investigate the expressions of p53 and PCNA in 56 OLP specimens. The results were correlated with the clinical behavior of the disease and the patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; oral habits. The expression rates were further compared with those of normal oral mucosa (NOM), epithelial hyperkeratosis (EH), epithelial dysplasia (ED), and squamous cell carcinoma (SCC). The staining rate of p53 (28.6%) and PCNA labeling index (LI) (27.6 +/- 8.8%) in OLP were similar to those in EH ( P = .868, .074, respectively), but higher than those of NOM and lower than those of ED and SCC (all P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05). In OLP, no significant correlations were found between p53 or PCNA expression and the patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; age, gender, lesion duration, location, size, number of site, presence of pain, presence of local irritant, and the habits of alcohol drinking and cigarette smoking (all P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; .05). In addition, the mean PCNA LI of p53+ cases was close to that of p53- cases (P = .38). However, the staining rate of p53 in OLP was higher in areca quid (AQ) chewers compared to abstainers (P = .001), and the mean PCNA LI in atrophic cases was higher than that in hypertrophic cases (P = .029). Interestingly, the staining rate of p53 and mean PCNA LI were significantly increased in AQ chewers with atrophic OLP (100%, 36.7% +/- 9.0%, respectively), which were similar to those in ED and SCC (all P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; .05). Although this study could not confirm the precancerous nature of OLP by the relatively low p53 and PCNA expression, the results do suggest that atrophic form OLP and patients with AQ chewing habit may have a higher disease activity in view of higher expression rates of p53 and PCNA in the lesions.

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 2004

Objectives. The aim of the study was to investigate the effectiveness of an educational program o... more Objectives. The aim of the study was to investigate the effectiveness of an educational program on the reduction of the incidence of wrong-site tooth extraction at the outpatient department of a university hospital in Taiwan. Study design. Data collected from cases of wrong-site tooth extraction during 1996 to 1998 were used to develop a specific educational intervention that was implemented from 1999 to 2001. The annual incidence of erroneous extraction was compared between the preintervention and intervention periods. The factors contributing to wrong tooth extraction were also analyzed. Results. The annual incidence rates of erroneous extraction from 1996 to 1998 were 0.026%, 0.025%, and 0.046%, respectively. During the intervention period from 1999 to 2001, wrong-site tooth extraction did not occur at the department. There was a significant difference in the incidence of erroneous extraction between the preintervention and intervention periods (P\.01). Cognitive failure was the most frequent form of active failure responsible for wrong-site tooth extraction, whereas communication and training were found to be major latent factors contributing to these errors. Conclusions. Our results suggest the effectiveness of an educational program comprising case-based materials, information feedback, and clinical guidelines in reducing the incidence of wrong-site tooth extraction.

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontology, 2007

Objectives. Incisional biopsy is accepted by most clinicians as a dependable way of assessing the... more Objectives. Incisional biopsy is accepted by most clinicians as a dependable way of assessing the nature of oral leukoplakia (OL). The aim of the present study was to investigate its reliability and analyze risk factors associated with underdiagnosis from incisional biopsy. Study design. A cross-sectional retrospective study was conducted in 242 patients with a clinical diagnosis of OL. The discrepancy between provisional diagnosis (from incisional biopsy) and definitive diagnosis (from resection specimen) was analyzed and correlated with clinical variables. Patients who had incisional biopsy taken from a single location and those who received multiple-site biopsies were analyzed separately. Results. In the 200 cases receiving single-site biopsy, the agreement rate between provisional and definitive diagnoses was only 56%, and underdiagnosis from incisional biopsy was noted in 29.5% of patients. Underdiagnosis rate in the 42 patients receiving multiple-site biopsies was significantly lower (11.9%; P Ͻ .05). The rate of unexpected carcinoma in resection specimen was also significantly lower in the multiple-biopsy patients than in the single-biopsy patients (2.4% vs. 12.0%; P Ͻ .05). For the single-biopsy group, multivariate analysis revealed that clinical appearance significantly influenced the risk of underdiagnosis and unexpected carcinoma (both P Ͻ .05). Compared with homogeneous lesions, nonhomogeneous OL were more prone to be underdiagnosed (adjusted odds ratio [AOR] 2.36, 95% confidence interval [CI] 1.16-4.82) and have carcinoma undetected by incisional specimen (AOR 15.94, 95% CI 2.09-121.72).

Oral Oncology, 2002

There are about 600 million betel quid (BQ) chewers in the world. BQ chewing is the major risk fa... more 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 mg/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 mM, a copper chelator) and 1,10-phenanthroline (50, 100 mM, a lipid permeable iron chelator), lacked preventive effects. Specific reactive oxygen species scavengers such as dimethylsulfoxide (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 ANinduced 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. #

Oral Oncology, 2009

Esculetin has been shown to selectively induce tumor apoptosis in several types of cancers and is... more Esculetin has been shown to selectively induce tumor apoptosis in several types of cancers and is regarded as a promising chemotherapeutic agent. In this study, we showed that esculetin significantly suppressed the growth of oral cancer SAS cells in a dose-dependent manner. DNA content flow cytometry and TUNEL assay revealed that esculetin induced cell cycle arrest and apoptosis. Western blotting showed esculetin increased DR5 protein expression and activated caspase-8, which differed from previous studies conducted in other cell types. Furthermore, treatment with esculetin significantly increased TRAIL-induced apoptosis in SAS cells and the TRAIL-sensitizing effect was blocked by DR5/Fc chimera protein. Our results indicate that esculetin enhances TRAIL-induced apoptosis primarily through upregulation of DR5. Combination of esculetin and TRAIL may be a novel treatment strategy for oral cancers.

Journal of Surgical Oncology, 2005

Surgery is the only effective treatment able to improve survival of patients with hilar cholangio... more Surgery is the only effective treatment able to improve survival of patients with hilar cholangiocarcinoma (CCA). However, the significance of prognostic factors on overall survival is still debated. We evaluated early and long-term outcomes of patients resected for hilar cholangiocarcinoma over a 3-year period to determine the role of prognostic factors and their effect on overall survival. Medical records of patients with hilar CCA who underwent resection between January 2001 and December 2004 were retrospectively reviewed. Univariate and multivariate analysis was performed to identify prognostic factors associated with survival. Thirty-two of 45 patients underwent surgical resection with curative intent. Morbidity was 24.4 per cent; perioperative mortality was 0 per cent. Overall median survival was 22.3 months. Well-differentiated tumor grading and R0 resection were independently associated with better survival at multivariate analysis. Aggressive surgery, including biliary resection combined with major hepatectomy, is a safe procedure with low morbidity and mortality in a tertiary referral hepatobiliary center. The main aim of an aggressive surgical approach is to obtain a microscopic margin-negative resection, which is associated with better prognosis. Another important prognostic factor is tumor grading, which is independently associated with survival.

Journal of Oral Pathology and Medicine, 2002

Background: Adenomatous polyposis coli (APC) gene mutations have been demonstrated not only in co... more Background: Adenomatous polyposis coli (APC) gene mutations have been demonstrated not only in colorectal tumors but also in a variety of human cancers. Methods: To elucidate the possible roles of APC gene mutations in oral squamous cell carcinomas (OSCCs), we examined 40 untreated human primary OSCCs using polymerase chain reac-tion±single strand conformation polymorphism (PCR±SSCP) and DNA sequencing assays. Results: By screening nearly one-half of the coding region (codons 279±1673, including the MCR) of the APC gene, ®ve missense mutations and a 1-base pair deletion were detected in ®ve (12.5%) tumors, resulting in ®ve amino-acid substitutions or a truncation of the APC protein. All patients with APC mutations were both areca quid chewers and tobacco smokers (P 0.049). Conclusions: These results suggest that APC mutations may also contribute to the carcinogenesis of at least some OSCCs in Taiwan, especially for the users of areca quid and tobacco.

Journal of Oral Pathology and Medicine, 2001

MDM2 (murine double minute gene 2) overexpression has been implicated in the pathogenesis of huma... more 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 (Pϭ0.032). 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.

Journal of Oral Pathology and Medicine, 1997

Loss of heterozygosity (LOH) at adenomatous polyposis coli (APC) and mutated in colon cancer (MCC... more 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%) ...

Journal of Oral and Maxillofacial Surgery, 1999

International Journal of Radiation Oncology*Biology*Physics, 2006

To develop a clinical staging system for maxillary osteoradionecrosis (ORN) in irradiated nasopha... more To develop a clinical staging system for maxillary osteoradionecrosis (ORN) in irradiated nasopharyngeal carcinoma (NPC) patients. The data of maxillary ORN cases among 1,758 irradiated NPC patients were analyzed. A staging system based on the degrees of bone exposure (E), infection (I), and bleeding (B) was developed. Correlations between various clinical parameters and stages of maxillary ORN and relationships between treatment modalities and outcomes at each stage were evaluated. Cumulative success of treatment and risk factors that affect treatment outcomes were analyzed. The incidence of maxillary ORN was 2.7% (48/1,758). TNM stage of NPC (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), radiation dose (p = 0.029), and tooth extraction (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) appeared to have significant influences on disease severity. Success rates between conservative therapy and surgical treatment were not significantly different for Stage I ORN but differed significantly for Stage II (p = 0.013) and Stage III (p = 0.008) lesions. Grade 3 infection and bleeding significantly jeopardized treatment success (p = 0.043 and 0.015, respectively). The risk ratios of treatment failure for Grade 3 infection and bleeding were 2.523 (p = 0.034) and 3.141 (p = 0.027), respectively. More serious maxillary ORN tended to occur in cases with more advanced NPC, higher radiation dose, and history of tooth extraction. Surgical treatment was usually required in Stage II and III ORN. The grades of infection and bleeding are important factors in guidance of treatment and prediction of outcomes.

Head & Neck, 2011

The management of bisphosphonate-related osteonecrosis of the jaws (BRONJ) is challenging and con... more The management of bisphosphonate-related osteonecrosis of the jaws (BRONJ) is challenging and controversial. At present, there is no established medication treatment for the disease. A 78-year-old osteoporotic woman with osteonecrosis of the mandible related to alendronate therapy was referred for treatment. The disease was unresponsive to conservative therapy, including antibacterial mouth rinse, antibiotics, and minor surgical debridement. Teriparatide, a human recombinant pararthyroid hormone peptide 1-34, was then used for treatment. The oral mucosa completely regrew, and pain subsided 4 weeks after the initiation of teriparatide administration. Progressive bone regeneration was found during and after the 6-month period of teriparatide therapy. Our case demonstrated that teriparatide can be an important adjuvant in the management of advanced BRONJ and should be considered prior to major resection with reconstruction. Its true value in the treatment of BRONJ for noncancer patients with osteoporosis warrants future studies.

Head & Neck, 2010

Background. Cysteine-rich 61 (Cyr61 [CCN1]) has disparate functions in tumorigenesis that are dep... more Background. Cysteine-rich 61 (Cyr61 [CCN1]) has disparate functions in tumorigenesis that are dependent on the cell types. The aim of the study was to investigate its role in the growth of oral squamous cell carcinoma (SCC).

British Journal of Oral and Maxillofacial Surgery, 2005

Mucormycosis is an invasive and potentially lethal infection caused primarily by fungi of the ord... more Mucormycosis is an invasive and potentially lethal infection caused primarily by fungi of the order mucorales. An ulcer or extraction in the mouth can be the port of fungal invasion, particularly when the patient is immunocompromised. Early recognition and aggressive treatment have reduced the mortality and morbidity. We present a case of oral mucormycosis with extensive maxillary osteonecrosis that is of interest because the patient ignored the initial warning signs and was rescued from the fulminating stage by thorough debridement and medical treatment.