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Biomedical subjects

Shou-Yen Kao

Publications and source records attributed to Shou-Yen Kao.

17 recordsLinked to original sources

Segmental osteotomy to reposition multiple osseointegrated dental implants in the anterior maxilla in a trauma patient.

A 16-year-old young man had severe loss of alveolar bone and lost four teeth in the anterior maxilla because of traumatic injury in a traffic accident. To overcome the surgically compromised condition for implant rehabilitation, the deficient ridge was augmented by autogenous bone graft from the mandibular symphysis. The augmented ridge had much improvement in width but less in vertical height. Four implants were placed to gain initial osseointegration. Segmental osteotomy was performed to occlusally reposition the implants and bone for 5-mm in the anterior maxilla. After 2 years of clinical follow-up, the rehabilitation outcome is satisfactory and stable.

Adolescent↗

Use of methylene blue as a diagnostic aid in early detection of oral cancer and precancerous lesions.

We assessed the sensitivity, specificity, and positive and negative predictive value of methylene blue staining in the diagnosis of oral cancer in 58 patients. The sensitivity was 90%, the specificity 69%, positive predictive value 74%, and negative predictive value 87%. Because of the number of false negatives and false positives we recommend that the diagnosis should always be confirmed by histopathological examination of a biopsy specimen. Methylene blue staining may, however, be useful as a screening tool for oral cancer in large, high-risk groups in a similar way to the more expensive toluidine blue.

Carcinoma, Squamous Cell↗

Areca nut extract treatment down-regulates involucrin in normal human oral keratinocyte through P13K/AKT activation.

Areca (betel) is an important etiological factor linked to the high prevalence of oral carcinoma and other oral diseases in South Asians. Involucrin is a key component of the cornified envelop and a differentiation marker of keratinocyte. In this study, we found that 5 microg/ml non-toxic areca nut extract (ANE) treatment resulted in the 0.5-fold down-regulation of involucrin and disruption in involucrin distribution in normal human oral keratinocyte (NHOK). Progressive down-regulation of involucrin during oral carcinogenesis was noted. Activation of AKT by 1.7-fold and up-regulation of COX-2 by 2-fold were elicited following ANE treatment in NHOK. Treatment with PI3K/AKT blockers reverted the down-regulation of involucrin. ANE also down-regulated involucrin by 0.6-fold and disturbed both cornified envelope and cell aggregation in calcium-induced differentiated NHOK. However, such phenomena seemed to be independent from the ANE-associated COX-2 activation. The ANE-associated down-regulation of involucrin through AKT pathway could underlie the areca-associated epithelial pathogenesis.

Adult↗

A retrospective analysis of the stability and relapse of soft and hard tissue change after bilateral sagittal split osteotomy for mandibular setback of 64 Taiwanese patients.

PURPOSE: This study was an analysis of the soft and hard tissue changes of the facial profile after bilateral sagittal splitting osteotomy for mandibular setback of Taiwanese patients. PATIENTS AND METHODS: We collected pre- and postsurgical lateral cephalographs of 64 patients (28 males, 36 females) with skeletal Class III malocclusion who received combined orthodontic-surgical treatment with bilateral sagittal splitting osteotomy mandibular setback at Taipei Veterans General Hospital between 1994 and 2000. Nineteen cephalometric parameters of (14 linear, 4 angular, and the BS index) soft and hard tissues were measured at 1 week before treatment, and 2 months and 1 year after surgery, and analyzed by paired t test. RESULTS: Mean patient age was 20.0 +/- 1.6 years. The patients underwent an average of 7 mm mandibular setback at the osseous pogonion (Pog). Average setbacks at Pog and soft tissue pogonion (pog) were 5.54 mm and 4.85 mm, respectively, at 1 year after surgery. The setback ratio of Pog/pog was 1:0.88. The hard tissue relapse at Pog was 21% at 1 year after surgery. Improvement in prognathic profile was demonstrated by significant changes in the positions of Pog and pog, ANB angle, the distance from lower lip to esthetic line (E-L lip), and the BS index after surgery. However, compared with parameters obtained from a normal Taiwanese population, the cephalometric data of Pog, pog, and BS index still indicated mild prognathism. CONCLUSION: Although mandibular prognathism could be grossly improved by bilateral sagittal splitting osteotomy mandibular setback, a significant amount of relapse occurred within 1 year after surgery. The extent of the postoperatively preserved features showing mandibular prognathism should be a concern for both patients and physicians.

Adult↗

Frequent microsatellite alterations of chromosome locus 4q13.1 in oral squamous cell carcinomas.

BACKGROUND: Studies have revealed that losses of chromosome 4q24-25 regions are frequent in cancers including head and neck squamous cell carcinoma. Our previous comparative genomic hybridization analysis showed extensive losses of chromosome arm 4q in oral squamous cell carcinoma (OSCC). METHODS: To be more precise in mapping the potential regions of allelic losses and to understand the microsatellite instability (MSI) on 4q involving in oral pathogenesis, we performed allelotypings using eight polymorphic markers. Microsatellite analyses were first performed on 100 randomly selected controls to confirm the high informative rates of markers. Twenty OSCC tissues were microdissected from surgical specimens for microsatellite alterations (MA) analysis. RESULTS: MA was observed in 95% OSCC cases. The most eminently altered locus was 4q13.1 (75%), followed by 4q22.2 and 4q32.1 (55%). Allelic losses also occurred most frequently on these loci. Thirty-five percent cases had MA spanning 4q13.1 to 4q21.1. MSI occurred in 35% OSCC, at a lesser extent compared with allelic losses. The most common locus for MSI was 4q21.2 (20%). In addition, 4q MSI was significantly associated with the lymph node metastasis of OSCC (P = 0.01). So far, most tumor suppressor genes on 4q have not been specified. CONCLUSION: Our results were additive to previous findings and proposed novel scenario of suppressor loci located at 4q13.1-21.1 whose inactivation could be important for progression of OSCC.

Adult↗

A method using vestibulo-sulcoplasty combining a split-thickness skin graft and a palatal keratinized mucosa graft for peri-implant tissue secondary to oral cancer surgery.

Twelve patients presented with oral submucosal fibrosis and loss of keratinized gingiva in a compromised vestibule of a severely deficient mandibular edentulous ridge secondary to oral cancer surgery. They received implant rehabilitation with a total of 49 fixtures without major bone graft augmentation. To overcome vestibular compromise, soft tissue management consisting of simultaneous vestibulo-sulcoplasty, split-thickness skin graft (STSG), and palatal keratinized mucosa graft (KMG) was performed as a second stage when healing abutment was transferred to replace the cover screw of the dental implant. Postoperative follow-up of all patients consisted of clinical and radiographic examinations for an average of 4 years, revealing good stability of implant fixtures with a 91.8% success rate and generally healthy peri-implant tissue, the latter with an average sulcus depth of 2.9 +/- 0.6 mm. Satisfactory results were also demonstrated regarding improved morphology of the vestibule, cosmetics, and prosthetic functionality. Vestibulo-sulcoplasty combining STSG and palatal KMG offers a stable and convenient method for rebuilding peri-implant tissue without need for bone grafting in selected patients who have compromised atrophic ridges secondary to cancer surgery.

Alveolar Bone Loss↗

Outcomes of oral squamous cell carcinoma in Taiwan after surgical therapy: factors affecting survival.

PURPOSE: The study goal was to determine which clinical features correlated with 5-year survival in patients surgically treated for oral squamous cell carcinoma (OSCC) in Taiwan. PATIENTS AND METHODS: The records of 378 OSCC patients surgically treated with or without chemotherapy and radiotherapy were reviewed retrospectively. Their 5-year survival in relation to age, gender, tumor site, lymph node involvement, presence of distant metastasis, staging, differentiation, and risk factors, including betel quid (BQ) chewing, cigarette smoking, and alcohol consumption, was analyzed. RESULTS: The majority of the patients were men (male-to-female ratio, 5.87:1) with the mean age of 57.1 +/-11.7 years. Tumors occurred mainly at the buccal mucosa (BM) (100 of 378, 26.5%), gingiva (105 of 378, 27.8%), and tongue (103 of 378, 27.2%). Neck nodal metastasis occurred frequently at the floor of the mouth (in >60% of cases), followed by the gingiva (45.7%), buccal mucosa (34%), and tongue (20.4%), whereas early distant metastasis was rare (5.3%). There were 104 (27.5%) stage 1, 96 (25.4%) stage 2, 98 (25.9%) stage 3, and 80 (21.2%) stage 4 patients. OSCC at the BM and gingiva was most (and at the tongue least) associated with risk factors of BQ use and smoking. The 5-year survival was 75%, 65.6%, 49%, and 30% for patients with stage I, II, III, and IV, respectively. The size, nodal involvement, distant metastasis, staging, differentiation, and BQ use significantly affected the survival (P <.05, Kaplan-Meier analysis). BQ use also correlated most significantly with the younger age of occurrence of OSCC patients. CONCLUSIONS: Our data suggest that early treatment is the key to increasing the survival of OSCC patients. Periodic screening of high-risk populations for OSCC represents an urgent need in Taiwan.

Adult↗

The biphasic differential expression of the cellular membrane protein, caveolin-1, in oral carcinogenesis.

BACKGROUND: The increased expression of Cav-1 is seen in various cancers from prostate, esophagus, colon, breast and pancreas yet the information regarding the correlation between the expression of Cav-1 and oral cancer is blind. Thus, the expression profile of caveolin-1 (Cav-1) in oral carcinogenesis and the correlation to the clinicopathologic covariates are examined in this study. METHODS: Immunohistochemistry was used to detect Cav-1 expression in non-cancerous matched tissues (NCMT; n=12), and tissue from normal oral mucosa (NOM; n=12), oral pre-cancer lesions (OPL; n=17), primary oral squamous cell carcinoma (POSCC; n=47) and metastatic OSCC (MOSCC; n=8). The Cav-1 expression was correlated to the age, site, areca use, stage, size, nodal involvement, and differentiation stage. Western blot was used to confirm the specificity of antibody and to follow changes in Cav-1 expression. RESULTS: The Cav-1 immunoreactivity increased significantly from 8% in NOM and 17% in NCMT to 53% in OPL and 79% in POSCC. In addition, lymph node metastasis (LNM) was present in 62% of Cav-1(+) POSCCs, but only in 10% of Cav-1(-) POSCCs. Remarkably, only 38% of MOSCCs had Cav-1 immunoreactivity. CONCLUSION: An increased Cav-1 expression is seen in the stepwise carcinogenesis from NOM, NCMT, OPL to POSCC. The decrease in expression from the POSCC to MOSCC indicates the value to explore its biphasic functions in oral carcinogenesis. Whether Cav-1 is an important predictor or prognosis for survival still awaits the extension of clinical follow-up.

Adult↗

Multiple molecular alterations of FHIT in betel-associated oral carcinoma.

To determine the alterations of the FHIT (fragile histidine triad) gene in oral squamous cell carcinoma (OSCC), this study examined mutation, promoter methylation, mRNA transcription, and protein expression of FHIT in OSCC associated mostly with the use of betel and/or tobacco. Analyses of the coding exons (exons 5-9) identified a deletion of one base in intron 4 in one tumour and a deletion of exon 7 in two tumours. Using bisulphite genomic sequencing, 28% of the informative subjects exhibited promoter methylation. An aberrant FHIT transcript spanning from exon 3 to exon 10, which was verified by RT-PCR analysis, was identified in 36% of the OSCC subjects, 50% of the oral pre-invasive lesions, and 5% of the non-cancerous match tissue. An abnormal immunohistochemical level of Fhit was detected in 41% of OSCC subjects. A statistically significant association was found between aberrant transcription of the FHIT gene and an abnormal level of Fhit immunoreactivity. The results indicated that alteration of FHIT is a frequent occurrence in OSCC and thus suggests that the aberrance in FHIT transcription could be an early event of oral carcinogenesis.

Acid Anhydride Hydrolases↗

Regulation of IGFBP-5 expression during tumourigenesis and differentiation of oral keratinocytes.

To identify molecular events involved in the pathogenesis of oral squamous cell carcinoma (OSCC), genes differentially expressed in OSCC and non-cancerous matched tissue (NCMT) samples were analysed using a subtractive hybridization strategy. NCMT-enriching clones that have been linked to suppressor pathway in previous studies were subjected to advanced analyses. Complete absence of insulin-like growth factor binding protein-5 (IGFBP-5) expression at both the mRNA and the protein level was identified in nearly all (5/6) OSCC cell lines with the exception of the SCC25 cell line, which exhibited high IGFBP-5 expression. However, this protein is consistently present in cultured normal human oral keratinocytes (NHOKs). Immunohistochemistry revealed moderate to strong cytoplasmic immunoreactivity of IGFBP-5 in the stratum spinosum and stratum granulosum in the vast majority of NCMT samples. A remarkable reduction in IGFBP-5 immunoreactivity was detected in 56% (26/46) of OSCC samples, compared with the corresponding NCMT (p < 0.0001). Induction of differentiation in both NHOKs and SCC25 up-regulated IGFBP-5 expression. Administration of a green tea compound with anti-cancer properties, (-)-epigallocatechin 3-gallate, at a concentration of 5-20 micro g/ml also up-regulated IGFBP-5 expression in NHOKs in a dose-dependent manner. The findings suggest that IGFBP-5 may be an important factor in the differentiation of oral keratinocytes and that down-regulation of IGFBP-5 may be involved in the neoplastic transformation of oral keratinocytes.

Antineoplastic Agents↗

Genetic polymorphism of cytochrome P4501A1 and susceptibility to oral squamous cell carcinoma and oral precancer lesions associated with smoking/betel use.

BACKGROUND: The importance of the CYP1A1 polymorphisms at exon 7 (Ile/Val) and 3'-untranslated region (3'-UTR) has been controversial in oral squamous cell carcinoma (OSCC) or head and neck SCC (HNSCC) denoting the value of exploring the correlation between these polymorphisms and risk of betel/smoking associated OSCC. It is also important to evaluate the association between CYP1A1 polymorphisms and susceptibility of oral precancerous lesion (OPL) to confirm the findings in OSCC cases. METHODS: We examined polymorphic prevalence of CYP1A1 at exon 7 (Ile/Val) and 3'-UTR in 106 cases with OSCC, 60 cases with OPL, and 146 controls. DNA isolated from surgical specimens and whole blood was used for PCR-based genotyping. RESULTS: The prevalence of the CYP1A1 A/G genotype (Ile/Val) and G/G genotype (Val/Val) in exon 7 of cases with OSCC (79.2 and 7.6%) and OPL (68.3 and 10%) were significantly higher than in controls (53.4 and 1.4%) (P < 0.0001). The novelty of the present study is that we identified the onset age of OSCC in CYP1A1 A/G genotype to be significantly younger than that in A/A genotype (P < 0.01). No significant difference was seen between cases and controls regarding the polymorphisms at 3'-UTR. CONCLUSION: The findings indicate that the individuals with the CYP1A1 exon 7 containing G allele were at increased risk for OSCC and OPL.

Adolescent↗

The retinoic acid receptor-beta (RAR-beta) mRNA expression in the oral squamous cell carcinoma associated with betel quid use.

BACKGROUND: Within the abundant retinoids nuclear receptors, abnormally low expression of the RAR-beta has been shown to contribute to neoplastic progression in oral epithelium in western countries. Distinctly different risk factors contributing to oral squamous cell carcinoma (OSCC) in epidemiologically different societies denote the value of exploring the role of RAR-beta expression in OSCC associated with betel quid (BQ) use in our society. METHODS: We examined the cellular expression of RAR-beta using in situ hybridization (ISH) analysis on 38 pairs of surgical specimens of primary OSCC and non-cancerous matched tissues (NCMT) to correlate with their clinico-pathological features including age, sites of tumor, habit of BQ use, stage, size of primary tumor, lymph node metastasis, differentiation. RESULTS: Of all cases analyzed, BQ users were significantly younger than non-BQ users (51.2 +/- 2.1 vs. 60.2 +/- 2.6, P = 0.01). 52% OSCC of BQ users (13/25) and 23% OSCC of non-BQ users (3/13) exhibited the absence of RAR-beta expression. In 17 paired-samples from buccal mucosa (BM), most NCMT and less than half of OSCC exhibited RAR-beta expression (16/17, 94% vs. 8/17, 47%, P = 0.003). The RAR-beta expression was seen in the vast majority of the well-differentiated OSCC and in less than half of the moderately differentiated OSCC only (15/20, 75% vs. 7/18, 39%, P = 0.03). CONCLUSION: A correlation between the loss of RAR-beta expression and more advanced histopathological grade tumors was observed. This study also suggests that the loss of RAR-beta expression is significant in BM OSCC, which preferentially occurs in BQ users.

Adult↗

Reconstruction of the severely resorbed atrophic edentulous ridge of the maxilla and mandible for implant rehabilitation: report of a case.

We describe a case with a severely resorbed atrophic edentulous ridge in both the maxilla and mandible. The maxilla was reconstructed using a sinus-lifting procedure and onlay bone graft. The mandible was reconstructed by anterior osteotomy with an interpositional sandwich iliac bone graft at the symphysis area, subperiosteally with iliac bone chips mixed with hydroxylapatite bilaterally at the posterior atrophic ridge, and vestibuloplasty with a split thickness skin graft (STSG). After full-mouth implant rehabilitation, a 5-year follow-up of this case shows a satisfactory result.

Aged↗

Transpositioned flap vestibuloplasty combined with implant surgery in the severely resorbed atrophic edentulous ridge.

The use of transpositioned flap (lipswitch) vestibuloplasty combined with implant surgery in patients with severely resorbed atrophic edentulous ridges is reviewed. The cases of 17 patients with severely resorbed atrophic edentulous ridges at the mandible undergoing implant rehabilitation were reviewed. Lipswitch vestibuloplasty was followed immediately by the implant surgery. Postoperative follow-up consisted of clinical and radiographic examinations. Seventeen patients with atrophic ridges (12 class II and 5 class III) each had 2 implant fixtures placed in the mandible as abutments for a clip and bar overdenture. The average time of follow-up was 6 years. Before surgery, all patients had severely atrophic ridges with a compromised shallow vestibule of varying degrees. Satisfactory results were observed in regard to the immediate and long-term morphology of the vestibule, the health of the peri-implant tissue, the stability of implant fixtures, and the functionality of the prostheses. The lipswitch vestibuloplasty offers a safe and convenient method of surgical access for implant fixture installation, with the advantage of rebuilding the vestibule of a compromised atrophic ridge in the anterior mandible.

Atrophy↗

Rehabilitation of dental implants for the post-irradiated and marginally resected mandible in an oral cancer patient.

We describe a case with severely compromised edentulous ridge in the mandible, which previously received marginal resection and radiotherapy due to oral cancer at the mouth floor. Through careful evaluation, the patient had 30 dives of hyperbaric oxygen therapy (HBO) before implant surgery. The edentulous ridge was rehabilitated with 4 endosteal implant fixtures, and palatal mucosa grafting vestibulosulcoplasty. The case had been followed for 4 years with stability of bone and a satisfactory result of rehabilitation.

Combined Modality Therapy↗

In vitro growth inhibition by indomethacin on human oral squamous cell carcinoma lines synergistically suppressed by all-trans retinoic acid correlating to apoptosis.

BACKGROUND: Indomethacin, an NSAID capable of inhibiting the effect of both cyclooxygenase and lipooxygenase, has been reported to repress the growth of breast cancer, skin cancer and head & neck cancer, etc. Inhibition in the some cell lines of oral squamous cell carcinoma (OSCC) has also been reported. The purpose of this study was primarily to explore the cellular response of human OSCC lines after indomethacin or retinoic acid (RA) treatment and its correlation to apoptosis phenomenon. METHODS: Five human OSCC cell lines--KB, SCC15, SCC25, OEC-M1 and OC2--were used for this in vitro study. By direct cell number counting, the cellular response was observed under incremental indomethacin concentrations of 50 microM, 100 microM, 200 microM and 400 microM, in order to select the most appropriate concentration for further study. Then 200 microM indomethacin and all-trans RA at 1 microM were used in the 2nd experiment to explore the intensity of their inhibitory effects individually and potential synergistic inhibition when exerted together. While in the 3rd part, TdT-mediated-dUTP nick-end labeling (TUNEL) method was used for in situ apoptosis assay to see if the apoptosis rate varied with these two agents. RESULTS: All 5 cell lines constantly showed growth suppression with positive dosage effect of indomethacin. Synergistic inhibition by combined treatment of indomethacin and RA was seen in RA responsive lines of SCC15 and SCC25, whereas other RA-resistant clones showed no synergism of this combined treatment. The in situ detection of apoptosis by TUNEL assay revealed a significantly higher ratio of apoptotic cells in the indomethacin/RA treated SCC15 and SCC25 than in controls. CONCLUSIONS: The study provides the value of further exploration on the mechanism of how indomethacin inhibiting cancer cell growth and how RA-sensitive OSCC cell lines are synergistically suppressed by conjoint treatment of RA and indomethacin. This study also highlights the value to see how the apoptotic pathway responds differently to the indomethacin/RA treatment.

Apoptosis↗