Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts

Odontogenic keratocyst(OKC)is a common jaw cyst with a high recurrence rate.OKC combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin syndrome.Moreover,OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw cysts.Because of the different prognosis,differential diagnosis of several cysts can contribute to clinical management.We collected 519 cases,comprising a total of 2157 hematoxylin and eosinstained images,to develop digital pathology-based artificial intelligence(AI)models for the diagnosis and prognosis of OKC.The Inception_v3 neural network was utilized to train and test models developed from patch-level images.Finally,whole slide imagelevel AI models were developed by integrating deep learning-generated pathology features with several machine learning algorithms.The AI models showed great performance in the diagnosis(AUC=0.935,95%CI:0.898–0.973)and prognosis(AUC=0.840,95%CI:0.751–0.930)of OKC.The advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide model.Furthermore,the study investigates the correlation between AI features generated by deep learning and pathological findings,highlighting the interpretative potential of AI models in the pathology.Here,we have developed the robust diagnostic and prognostic models for OKC.The AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.

Management of Mandibular Fractures in Children in Ivory Coast: Experience of the Stomatology and Maxillofacial Surgery Department at the University Hospital of Cocody from 2000 to 2019

Introduction: Mandibular fractures in children are becoming increasingly common. Treatment of these fractures is difficult due to their anatomical and physiological complexity. Therefore, there is a need for well-codified management. Our main aim was to develop a decision algorithm for the management of mandibular fractures in children based on our experience. Materials and Methods: This was a retrospective descriptive study carried out in the Department of Stomatology and Maxillofacial Surgery at the University Hospital of Cocody over a period of 20 years (2000-2019). Results: We enrolled 58 patients. The mean age of the patients was 9.35 ± 2.3 years with a sex ratio of 2.22. Traffic accidents were the main cause of mandibular fractures (60.35%). Condylar fractures were the most common (46.87%). Treatment was orthopedic in 45.76% of cases, mixed (orthopedic and surgical) in 24.14% and surgical in 5.17%. Patients were followed up weekly for 1 month, then monthly for 6 months and annually for 3 years, with panoramic radiographs of the maxilla starting at 21 days. We observed 2 cases of complications: temporomandibular ankylosis and gingival stomatitis. Conclusion: Mandibular fractures are common in children. Management is difficult due to anatomical and physiological peculiarities. The choice of treatment depends on several criteria.

Novel insights on oral squamous cell carcinoma management using long non-coding RNAs

Oral squamous cell carcinoma(OSCC)is one of the most prevalent forms of head and neck squamous cell carcinomas(HNSCC)with a poor overall survival rate(about 50%),particularly in cases of metastasis.RNA-based cancer biomarkers are a relatively advanced concept,and non-coding RNAs currently have shown promising roles in the detection and treatment of various malignancies.This review underlines the function of long non-coding RNAs(lncRNAs)in the OSCC and its subsequent clinical implications.LncRNAs,a class of non-coding RNAs,are larger than 200 nucleotides and resemble mRNA in numerous ways.However,unlike mRNA,lncRNA regulates multiple druggable and non-druggable signaling molecules through simultaneous interaction with DNA,RNA,proteins,or microRNAs depending on concentration and localization in cells.Upregulation of oncogenic lncRNAs and downregulation of tumor suppressor lncRNAs are evident in OSCC tissues and body fluids such as blood and saliva indicating their potential as valuable biomarkers.Targeted inhibition of candidate oncogenic lncRNAs or overexpression of tumor suppressor lncRNAs showed potential therapeutic roles in in-vivo animal models.The types of lncRNAs that are expressed differentially in OSCC tissue and bodily fluids have been systematically documented with specificity and sensitivity.This review thoroughly discusses the biological functions of such lncRNAs in OSCC cell survival,proliferation,invasion,migration,metastasis,angiogenesis,metabolism,epigenetic modification,tumor immune microenvironment,and drug resistance.Subsequently,we addressed the diagnostic and therapeutic importance of lncRNAs in OSCC pre-clinical and clinical systems,providing details on ongoing research and outlining potential future directions for advancements in this field.In essence,this review could be a valuable resource by offering comprehensive and current insights into lncRNAs in OSCC for researchers in fundamental and clinical domains.

Classificatory updates in verrucous and cuniculatum carcinomas:Insights from the 5^(th) edition of WHO-IARC head and neck tumor classification

The International Agency for Research on Cancer(IARC)and World Health Organization(WHO)collaboratively produce the'WHO Blue Books'essential tools standardizing the diagnostic process for human cancers.Regular updates in this classification accommodate emerging molecular discoveries,advances in immunohistochemical techniques,and evolving clinical insights.The 5th edition of the WHO/IARC classification of head and neck tumors refines the'Oral Cavity and Mobile Tongue'chapter,including sections for non-neoplastic lesions,epithelial tumors,and tumors of uncertain histogenesis.Notably,the epithelial tumors section is rearranged by tumor behavior,starting with benign squamous papillomas and progressing through potentially malignant oral disorders to oral squamous cell carcinoma(OSCC).The section on OSCC reflects recent information on epidemiology,pathogenesis,and histological prognostic factors.Noteworthy is the specific categorization of verrucous carcinoma(VC)and carcinoma cuniculatum(CC),both associated with the oral cavity and distinct in clinical and histologic characteristics.This classification adjustment emphasizes the oral cavity as their predominant site in the head and neck.Designating specific sections for VC and CC aims to provide comprehensive insights into these unique subtypes,elucidating their clinical features,distinct histological characteristics,prevalence,significance,and clinical relevance.By categorizing these subtypes into specific sections,the 5th edition of the WHO classification aims to provide a more nuanced and detailed account,enhancing our understanding of these specific variants within the broader spectrum of head and neck tumors.

Characterization of tumors of jaw:Additive value of contrast enhancement and dual-energy computed tomography

BACKGROUND Currently,the differentiation of jaw tumors is mainly based on the lesion’s morphology rather than the enhancement characteristics,which are important in the differentiation of neoplasms across the body.There is a paucity of literature on the enhancement characteristics of jaw tumors.This is mainly because,even though computed tomography(CT)is used to evaluate these lesions,they are often imaged without intravenous contrast.This study hypothesised that the enhancement characteristics of the solid component of jaw tumors can aid in the differentiation of these lesions in addition to their morphology by dual-energy CT,therefore improving the ability to differentiate between various pathologies.AIM To evaluate the role of contrast enhancement and dual-energy quantitative parameters in CT in the differentiation of jaw tumors.METHODS Fifty-seven patients with jaw tumors underwent contrast-enhanced dual-energy CT.Morphological analysis of the tumor,including the enhancing solid component,was done,followed by quantitative analysis of iodine concentration(IC),water concentration(WC),HU,and normalized IC.The study population was divided into four subgroups based on histopathological analysis-central giant cell granuloma(CGCG),ameloblastoma,odontogenic keratocyst(OKC),and other jaw tumors.A one-way ANOVA test for parametric variables and the Kruskal-Wallis test for nonparametric variables were used.If significant differences were found,a series of independent t-tests or Mann-Whitney U tests were used.RESULTS Ameloblastoma was the most common pathology(n=20),followed by CGCG(n=11)and OKC.CGCG showed a higher mean concentration of all quantitative parameters than ameloblastomas(P<0.05).An IC threshold of 31.35×100μg/cm^(3) had the maximum sensitivity(81.8%)and specificity(65%).Between ameloblastomas and OKC,the former showed a higher mean concentration of all quantitative parameters(P<0.001),however when comparing unilocular ameloblastomas with OKCs,the latter showed significantly higher WC.Also,ameloblastoma had a higher IC and lower WC compared to“other jaw tumors”group.CONCLUSION Enhancement characteristics of solid components combined with dual-energy parameters offer a more precise way to differentiate between jaw tumors.

Prevalence of Taurodontism in a Tertiary Hospital in Ghana

Background: Taurodontism is one of the most significant deviations from the normal tooth morphology affecting the molars in both primary and permanent dentition. Taurodontism refers to the Enlargement of the pulp chamber, resulting in its bifurcation pushed toward the apex of a tooth’s root. This study evaluated the prevalence of Taurodontism from radiographs taken at the University of Ghana Dental School Oral Radiology Unit from January 2017 to December 2022. Methodology: In this cross-sectional study, panoramic and periapical radiographs of 1000 randomly selected patients who visited the Oral Radiology Unit from January 2017 to December 2022. Radiographs were evaluated for apically displaced pulp chamber. Data was statistically evaluated, and the chi-square test was employed to assess the prevalence of taurodontism in the upper and lower jaws (p Results: Taurodontism was found in 171 radiographs giving it a prevalence of 17.1% of which 57% (98 radiographs) were from females and 43% (73 radiographs) were from males. This finding was not significant (p > 0.05). Taurodontism occurred more in the maxilla (289 teeth, 80.7%) compared to the mandible molars (186 teeth, 64.3%) giving it a ratio of 1.6:1. This finding was highly significant (p Conclusion: Taurodontism is relatively common in the Ghanaian population affecting more females compared to males according to this study. Further studies using a large sample need to be carried out to determine its incidence in the general community.

Journey of Immunohistochemistry in General and Oral Pathology:A Review on its Applications and Updates

Immunohistochemistry is a technique with an interesting journey.It is one of the well-established and reliable technique in modern pathology and it is extremely useful in diagnosis of sinister pathologies with perplexing histopathology.Not only does it enhance the diagnostic abilities of a pathologist,but it also has a huge prognostic potential,a great aid in establishing stage of malignancies,determines phenotypic expressions of lymphoid neoplasms and monitors treatment progress and response to therapy.By employing and integrating the basics of varied branches like immunology,histology,microscopy and hematology,it has emerged as a magnificent tool over last few decades,saving pathologists and patients from the impact of serious diseases inflicting the human body.Furthermore,it has contributed immensely to all aspects of diseases related to oral cavity as well.This review has been thus taken to highlight the wide applications of this technique in General and Oral Pathology with an update.

Loss of oral mucosal stem cell markers in oral submucous fibrosis and their reactivation in malignant transformation

The integrity of the basal stem cell layer is critical for epithelial homoeostasis.In this paper,we review the expression of oral mucosal stem cell markers(OM-SCMs)in oral submucous fibrosis(OSF),oral potentially malignant disorders(OPMDs)and oral squamous cell carcinoma(OSCC)to understand the role of basal cells in potentiating cancer stem cell behaviour in OSF.While the loss of basal cell clonogenicity triggers epithelial atrophy in OSF,the transition of the epithelium from atrophic to hyperplastic and eventually neoplastic involves the reactivation of basal stemness.The vacillating expression patterns of OM-SCMs confirm the role of keratins 5,14,19,CD44,β1-integrin,p63,sex-determining region Y box(SOX2),octamer-binding transcription factor 4(Oct-4),c-MYC,B-cell-specific Moloney murine leukaemia virus integration site 1(Bmi-1)and aldehyde dehydrogenase 1(ALDH1)in OSF,OPMDs and OSCC.The downregulation of OM-SCMs in the atrophic epithelium of OSF and their upregulation during malignant transformation are illustrated with relevant literature in this review.

Intraoperative imaging of oral-maxillofacial lesions using optical coherence tomography

Histopathological examination is still the gold standard for diagnoses of oral-maxillofacial lesions,but it is invasive and time-consuming.Optical coherence tomography(OCT)provides a kind of noninvasive,label-free,real-time and high-resolution imaging technology.In this study,in order to assess the feasibility of OCT in oral clinical application,fresh excised tissue specimens from 59 patients undergoing oral-maxillofacial surgery were imaged in detail by using a benchtop sweptsource OCT system.It is shown that different lesions or tissues can be obviously distinguished based on their different microstructural features in OCT images,and the features are similar to those of their corresponding histopathological images.It is proven that OCT has great feasibility and potential as a diagnostic aid for surgeons in oral medicine.

Identification of oral squamous cell carcinoma in optical coherence tomography images based on texture features

Surgical excision is an effective treatment for oral squamous cell carcinoma(OSCC),but exact intraoperative differentiation OSCC from the normal tissue is the first premise.As a noninvasive imaging technique,optical coherence tomography(OCT)has the nearly same resolution as the histopathological examination,whose images contain rich information to assist surgeons to make clinical decisions.We extracted kinds of texture features from OCT images obtained by a home-made swept-source OCT system in this paper,and studied the identification of OSCC based on different combinations of texture features and machine learning classifiers.It was demonstrated that different combinations had different accuracies,among which the combination of texture features,gray level co-occurrence matrix(GLCM),Laws'texture measnres(LM),and center symmetric auto-correlation(CSAC),and SVM as the classifier,had the optimal comprehensive identification effect,whose accuracy was 94.1%.It was proven that it is feasible to distinguish OSCC based on texture features in OCT images,and it has great potential in helping surgeons make rapid and accurate decisions in oral clinical practice.

Role of angiogenesis in oral squamous cell carcinoma development and metastasis: an immunohistochemical study

Although a few studies have shown that vascularity is increased from normal mucosa to dysplasia to carcinoma suggesting that disease progression in the oral mucosa is accompanied by angiogenesis. The role in lymph node metastasis in oral squamous cell carcinoma （OSCC） is equivocal. Role of angiogenesis in OSCC development and metastasis is evaluated in this study. This retrospective study of 50 samples consisted of 9 normal buccal mucosa, 22 leukoplakias, and 19 OSCC. Polyclonal antibodies to von-Willebrand factor were used to highlight the microvessels. Images were captured and morphometric image analysis was done for microvessel density （MVD）, area, and perimeter. Highest, as well as mean values of these three parameters were compared. MVD and perimeter, but not area, are significantly different between normal mucosa and OSCC, and leukoplakia and OSCC. There were no differences between normal mucosa and leukoplakia. MVD, area, and perimeter were not significantly different between the OSCC with and without lymph node metastasis. The highest and mean values of MVD are significantly correlated. In the development of OSCC, angiogenic phenotypic change occurs in carcinomas rather than in the pre-cancerous stage, and quantification of angiogenesis in OSCC does not predict the risk of lymph node metastasis.

Dynamic role of myofibroblasts in oral lesions

Fibroblasts are the most abundant cellular components of connective tissue. They possess phenotypical heterogenicity and may be present in the form of smooth muscle cells or myofibroblasts(MFs). MFs are spindle-shaped cells with stress fibres and welldeveloped fibronexus,and they display α-smooth muscle actin immunohistochemically and smoothmuscle myofilaments ultrastructurally. MFs play a crucial role in physiological and pathological processes. Derived from various sources,they play pivotal roles not only by synthesizing and producing extracellular matrix components,such as other connective tissue cells,but also are involved in force production. In the tissue remodelling phase of wound closure,integrinmediated interactions between MFs and type I collagen result in scar tissue formation. The tumour stroma in oral cancer actively recruits various cell types into the tumour mass,where they act as different sources of MFs. This article reviews the importance of MFs and its role in pathological processes such as wound healing,odontogenic cysts and tumours,salivary gland tumours,oral preneoplasia,and oral squamous cell carcinoma. Research oriented on blocking the transdifferentiation of fibroblasts into MFs can facilitate the development of noninvasive therapeutic strategies for the treatment of fibrosis and/or cancer.

Oral and maxillofacial pain as the first sign of metastasis of an occult primary tumour:A fifteen-year retrospective study

BACKGROUND Metastatic adenocarcinoma of the jaw(MAJ)is a rare disease that accounts for 1%-3%of all oral and maxillofacial malignant tumours.Oral and maxillofacial pain may be the first symptom of metastatic spread of an occult primary tumour.Therefore,early identification of oral and maxillofacial pain by dental professionals is critical.AIM To explore the clinical and computerized tomography(CT)features of MAJ with oral and maxillofacial pain as the first symptom.METHODS The medical records of all patients who were treated in our hospital between January 2006 and February 2020,and diagnosed with MAJ with oral and maxillofacial pain as the first symptom,were reviewed retrospectively.Clinical data were collected on age,sex,medical history,clinical manifestations,site of metastasis,and site of the primary lesion.CT features were analysed in detail,and a radiological classification scheme comprising five types:Osteolytic,osteoblastic,mixed,cystic,and alveolar bone resorption was proposed.RESULTS The primary sites of MAJ were the lungs(n=6),liver(n=4),kidneys(n=2),prostate(n=1),and gastric cardia(n=1).Five tumours were classified as the osteolytic type,all with a permeative margin(100%,P<0.05),and three were classified as the mixed type,mostly with a moth-eaten margin(80%,P<0.05).The cystic(n=3)and alveolar bone resorption(n=1)types had geographic margins,and the osteoblastic type(n=1)had sclerotic margins.Moreover,nine tumours showed periosteal reaction and five showed a localised soft tissue mass,while the occurrence of jaw expansion was relatively rare.CONCLUSION MAJ has complex clinical and CT features.Oral and maxillofacial pain may be the first sign of a primary tumour affecting other sites.

Effect of lead on IL-8 production and cell proliferation in human oral keratinocytes

Objective:To investigate the effect of lead on the production of IL-8 and cell proliferation in normal human oral keratinocytes（NHKs）.Methods:NHKs were prepared as outgrowths from normal human buccal mucosa.The cells were treated with three concentrations of lead glutamate(4.5×10-5M,4.5×10-6M and 4.5×10-7M).NHKs grown in glutamic acid were used as control.The amounts of IL-8 secreted in the culture supernatants were evaluated at 12 and 24 h using enzyme-linked immunospecific assay（ELISA）.Cell proliferation was determined by the MTT colorimetric assay.Three cultures were used for each experiment,and three independent experiments were performed.Analysis of variance and Duncan’s multiple range tests were used for statistical analysis.Results:An elevation of IL-8 in culture supernatants of NHKs treated with lead at all concentrations at 12 and 24 h after exposure in a dose-dependent manner was revealed.A significant increase in cell numbers was observed only at 24 h exposed to 4.5×10- 5M lead glutamate.Conclusions:The capacity of NHKs,to secrete IL-8,enhanced by lead glutamate,is demonstrated here.Induction of cell proliferation is revealed only after exposure to high lead concentration.The elevation of secreted IL-8 is a probable initial sign for the acute inflammatory response and may be involved in the pathogenesis of lead stomatitis.

Characteristics of benign lymphoadenosis of oral mucosa

AIM: To investigate the pathological characteristics and carcinogenesis mechanism of benign lymphoadenosis of oral mucosa (BLOM).METHODS: The expressions of Ki-67, CD34 and apoptosis were evaluated by immunohistochemical SP staining in 64 paraffin-embedded tissue samples. Of them, 9 were from BLOM with dysplasia, 15 from BLOM without dysplasia,15 from oral squamous cell carcinoma (OSCC), 15 from oral precancerosis, and 10 from normal tissues. Cell proliferation, apoptosis and angiogenesis of tissue samples were also analyzed.RESULTS: The expression of Ki-67 in BLOM with dysplasia,oral precancerosis and OSCC was significantly higher than in BLOM without dysplasia and normal mucosa. The microvascular density (MVD) in BLOM with and without dysplasia, oral precancerosis, and OSCC was significantly higher than in normal mucosa. Apoptosis in BLOM and oral precancerosis was significantly higher than in OSCC and normal mucosa.CONCLUSION: Benign lymphoadenosis of oral mucosa has potentialities of cancerization.

Effect of PAIP1 on the metastatic potential and prognostic significance in oral squamous cell carcinoma

Poly Adenylate Binding Protein Interacting protein 1(PAIP1) plays a critical role in translation initiation and is associated with the several cancer types. However, its function and clinical significance have not yet been described in oral squamous cell carcinoma(OSCC) and its associated features like lymph node metastasis(LNM). Here, we used the data available from Gene Expression Omnibus(GEO), The Cancer Genome Atlas(TCGA), and Clinical Proteomic Tumor Analysis Consortium(CPTAC) to analyze PAIP1 expression in oral cancer. The publicly available data suggests that PAIP1 mRNA and protein levels were increased in OSCC. The high PAIP1 expression was more evident in samples with advanced stage, LNM, and worse pattern of invasion. Moreover, the in vitro experiments revealed that PAIP1 knockdown attenuated colony forming, the aggressiveness of OSCC cell lines, decreasing MMP9 activity and SRC phosphorylation. Importantly, we found a correlation between PAIP1 and pSRC through the analysis of the IHC scores and CPTAC data in patient samples. Our findings suggest that PAIP1 could be an independent prognostic factor in OSCC with LNM and a suitable therapeutic target to improve OSCC patient outcomes.

Quality of life and oral potentially malignant disorders: Critical appraisal and prospects

Quality of life(QoL) is a vital and often required health outcome measure that is relevant to patient care. A healthy oral cavity enables person to perform daily activities without any limitations. However, any disturbance may result in impaired QoL. The oral health-remains an essential element of people's health and well-being. In recent years, the tradition of clinical practice and research has been changed by incorporating QoL assessment, as it helps in assessment of patients' needs and monitoring treatment responses. Oral potentially malignant disorders(OPMDs) are a group of chronic disorders including oral leukoplakia(OL), oral lichen planus and oral submucous fibrosis(OSF). It is evident that patients with OPMDs experience significant health-related symptoms, functional limitations and psycho-social impairment, compromising their Qo L. Moreover, the worsening of Qo L has been associated with advanced stages of OPMDs. Despite of increasing number of OPMD cases in recent decades, limited literature is available regarding QoL in this population. Although, there is higher prevalence of habit-related OPMDs, particularly OSF and OL in Southern Asian countries, only a few studies have been performed in these populations. Moreover, these studies administered generic Qo L instruments, which offer less sensitivity to clinical changes. However, condition-specific instruments are more sensitive and allows better measurement of QoL. As the impacts of different conditions on OHRQoL may vary, the development and validation of a QoL instrument specific to each clinical entity of OPMDs is currently needed.

Cytomorphological Analysis of Keratinocytes in Oral Smears from Tobacco Users and Oral Squamous Cell Carcinoma Lesions—A Histochemical Approach

Aim To analyse the cytomorphological features of kerati- nocytes in smears obtained from the oral mucosa of tobacco users and from oral squamous cell carcinoma lesions. Methodology Oral smears were obtained from clinically, normal appearing mucosa of oral squamous cell carcinoma patients （n=20） and from the mucosa of smokers （n=20）, and apparently healthy individuals （n=20） were used as controls. The smears were histochemically stained and cytomorphological assessment of the keratinocytes was carried out. One-way ANOVA （Analysis of Variance） was used for comparing the parameters among multiple groups and Tukey-HSD test was used to compare the mean values between groups. Results The mean nuclear area of keratinocytes from the mucosa of tobacco users was 46 ± 2.57 and that of the oral squamous cell carcinoma lesion was 81.54±4.31. While there was a significant （P=0.001） reduction in the cellular area of keratinocytes from oral squamous cell carcinoma lesion when compared with those from oral smears of tobacco users. Conclusion Cytomorphometric analysis of keratinocytes can serve as a useful adjunct in the early diagnosis of oral squamous cell carcinomas.

The Apoptotic Effect of the Methanol Extract of <i>Polygonum cuspidatum</i>through Up-Regulation Death Receptor 5 and CHOP in HSC-2 Human Oral Cancer Cells

Polygonum cuspidatum is used as a traditional medicinal herb for the therapy of various diseases including several types of cancers. In the present study, we focused on addressing the anti-cancer activity and molecular mechanism of methanol extract of Polygonum cuspidatum (MEPC) in HSC-2 human oral cancer cells. The effect of MEPC on oral cancer cells was estimated by 3-(4,5-dimethylthiazol-20yl)-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium (MTS) assay, 4’-6-diamidino-2-phenylindole (DAPI) staining and Western blot analysis. MEPC inhibited the cell viability and induced apoptosis through the induction of death receptor (DR) 5. MEPC also increased the expression of C/EBP homologous protein/growth arrest and the DNA damage-inducible gene 153 (CHOP), a transcription factor induced by ER stress. Thus, we concluded that the induction of CHOP leading to DR5 up-regulation is required for the anti-cancer activity of MEPC in HSC-2 cells and MEPC may be a promising drug candidate for oral cancer.

Chemotherapeutic Effect of Withaferin A in Human Oral Cancer Cells

Withaferin A (WA) is a bioactive compound derived from a medicinal plant Withania somnifera and has potential therapeutic effects against various types of cancers. The purpose of this study is to investigate an apoptotic effect of WA and identify its molecular target in HSC-3 and HSC-4 human oral cancer cell lines using Trypan blue exclusion assay, DAPI staining and western blotting. WA inhibited cell viability and induced apoptosis in a concentration- or time-dependent manner, as evidenced by induction of nuclear condensation and fragmentation, activation of caspase 3 and poly (ADP-ribose) polymerase (PARP) cleavage. WA-induced apoptosis was partly diminished by Z-VAD, a pancaspase inhibitor. WA also increased Bim and Bax protein in HSC-3 and HSC-4 cells, respectively. These results suggest that WA may be a potential chemotherapeutic drug candidate against human oral cancer.