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Objective: Oral squamous cell carcinoma (OSCC) is the most common cancer in oral and maxillofacial tissue. This study aimed to investigate the expression of SLC3A2 in human OSCC tissues and its regulatory roles in OSCC. Methods: The expression of SLC3A2 in human OSCC tissues was assessed using immunohistochemistry. The proliferation, migration, and invasion of oral squamous cells were evaluated after knockdown of SLC3A2. Results: The expression of SLC3A2 in OSCC was higher than that in normal oral epithelial cells. SLC3A2 had higher expression levels in OSCC tissues than that in adjacent normal tissues. Upregulation of SLC3A2 was associated with advanced stages and poor survival of OSCC patients. In vitro experiments showed that knocking down of SLC3A2 was associated with reduced migration, invasion, and proliferation, but increased apoptosis of OSCC cells. Conclusion: SLC3A2 exerted a harmful effect on OSCC patients by increasing migration, invasion and proliferation, and decreasing apoptosis. [ABSTRACT FROM AUTHOR]

Background: This study aimed to elucidate the correlation between gene amplification, protein expression of receptor tyrosine kinase, and prognosis of patients with oral squamous cell carcinoma (OSCC) using immunohistochemistry (IHC) and next-generation sequencing data.Methods: We evaluated data pertaining to 208 patients with OSCC using IHC for epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET).Results: High expressions of EGFR and MET were detected in 60 and 41 patients, respectively. We evaluated the association of clinicopathological variables with high expressions of EGFR and/or MET. Distant metastasis was found in 9 of 41 patients (22.0%) and 6 of 15 patients (40.0%) with high expression of MET and high co-expressions of EGFR and MET, respectively; statistically significant differences were detected in both high expression of MET (P = .003) and high co-expressions of EGFR and MET (P = 3.41 × 10-5 ). The cumulative 5-year survival rate of patients with high and low expressions of EGFR or MET was approximately 65% and 85%, respectively. Conversely, among cases with high expressions of EGFR or MET, there was no additional decrease in the survival rate of patients harboring TP53 mutations. Moreover, the survival rate of patients with high co-expression of both EGFR and MET was very poor (22.0%) (P < 1.0 × 10-9 ).Conclusion: Our findings suggest that evaluation of protein expressions of EGFR and MET may facilitate prognostic assessment of patients with OSCC; in addition, patients with OSCC should be screened for enrollment in clinical trials of combination therapy with EGFR and MET inhibitors. [ABSTRACT FROM AUTHOR]

Objective: To investigate possible associations between disease-specific survival (DSS) of oral cancer and single nucleotide polymorphisms (SNPs) in transforming growth factor beta receptor 1 (TGFBR1).Methods: Using iPLEX Sequenom MassARRAY platform, three SNPs in TGFBR1 gene were genotyped in 356 newly diagnosed patients with histologically confirmed primary oral cancer. Demographic and clinical information of all cases were obtained from face-to-face interviews and electronic medical records, and telephone interviews were carried out every 6 months to timely gain follow-up data. Univariate and multivariate Cox proportional hazards model were used to assess the association between the polymorphisms of tagging loci and DSS of oral cancer.Results: TGFBR1 rs33438 polymorphism was protective against death of oral cancer in codominant (AG vs AA: HR = 0.55, 95% CI = 0.35-0.88) and dominant (GG + AG vs AA: HR = 0.57, 95% CI = 0.38-0.87) models. Moreover, better DSS was particularly significant in radiotherapy patients who carrying GG + AG genotype. There also existed a positive multiplicative interaction on DSS between the polymorphism of TGFBR1 rs334348 and radiotherapy (P = .001). Not any associations between TGFBR1 rs334354 or rs3739798 polymorphism and DSS were observed.Conclusions: This preliminary prospective study suggests that polymorphism of TGFBR1 rs334348 may act as a potentially independent factor and novel genetic biomarker to predict oral cancer DSS especially for patients with radiotherapy. A much more extensive investigation will need to confirm our findings. [ABSTRACT FROM AUTHOR]

Background: MLL2 (mixed-lineage leukemia 2) is recognized as an essential role in regulating histone 3 lysine 4 tri-methylation (H3K4me3) in mammalian cells. It is frequently mutated to promote developmental diseases and tumor initiation. However, the expression pattern of MLL2 and its clinical significance for patients with early-stage oral squamous cell carcinoma (OSCC) remain totally unknown.Methods: Eighty-five samples of primary early-stage OSCC were enrolled in this retrospective study, and immunohistochemistry (IHC) was performed to detect the spatial pattern of MLL2. The diagnostic and prognostic value of MLL2 were assessed.Results: MLL2 was widely expressed in tumor cells (TCs), fibroblast-like cells (FLCs), and tumor-infiltrating lymphocytes (TILs), both in tumor center and invasive tumor front, and showed no distributive heterogeneity. Moreover, regardless of cell types and microlocalization, patients with high expressed MLL2 had increased depth invasion of tumor (DOI). Besides, upregulation of MLL2TC and MLL2TIL in tumor center were both associated with poor differentiation, but showed no correlation with tumor growth with comparable Ki-67 levels. Prognostic analysis indicated that early-stage OSCC patients with enhanced MLL2TIL in invasive tumor front were susceptible to occur postoperative metastasis and recurrence. Indeed, patients with higher expressed MLL2TIL showed shorter overall survival (OS) and disease-free survival (DFS), and MLL2TIL in invasive tumor front was an independent risk factor of DFS.Conclusion: TIL-derived MLL2 in invasive tumor front was an independent prognostic factor of DFS for early-stage OSCC patients. [ABSTRACT FROM AUTHOR]

Background: ADAR1 is an enzymatic protein, which catalyzes a RNA editing reaction by converting Adenosine to Inosine, and its expression has been found to be dysregulated in many cancer types. The aim of this study was to analyze the expression of ADAR1 in oral squamous cells carcinoma.Methods: In order to analyze the ADAR1 mRNA expression, data from The Cancer Genome Atlas (TCGA) database were downloaded and analyzed. In addition, immunohistochemistry analysis was performed on an institutional database including 46 samples of oral squamous cell carcinoma in a tissue microarray (TMA).Results: No statistically significant correlation linked the mRNA ADAR1 expression to any clinic-pathological variables in the TCGA database. Immunohistochemistry analysis of ADAR1 showed different expressions between normal mucosa and tumor tissue. Focusing on the subcellular localization, the nuclear expression of ADAR1 correlated with higher grading of differentiation (ρ = 0.442; P-value = 0.002); the general expression of ADAR1 either in cytoplasm or in nuclei, correlated with the Gender of patients (Cytoplasm expression: ρ = -0.295; P-value = 0.049; while for nuclear expression: ρ = +0.374; P = 0.011); cytosol expression resulted to be an independent protective prognostic factor (HR = 0.047; C.I. 95% 0.007-0.321; P-value = 0.002).Conclusion: Higher expression of ADAR1 into the cytoplasm resulted to be an independent prognostic factor. In order to understand ADAR1 role in cancer, further studies should be performed, in bigger cohort and under a bio-molecular point of view. [ABSTRACT FROM AUTHOR]

Background: Availability of reliable methods distinguishing high-risk recurrent tumours from regressive tumours prior to surgery could help in better management of the disease. This study was aimed to estimate pre-surgical serum CD44 concentration and assess the possibility of using it as a non-invasive prognostic tool in oral cancer.Methods: ELISA was performed on pre-surgical serum samples from 64 primary oral cancer patients and 16 healthy individuals to estimate soluble CD44 levels. Immunohistochemistry was performed on parallel 64 solid tumours and 10 recurrent tumours. All patients clinically followed up for median period of 19.2 months and obtained prognostic information correlated with CD44 concentration in serum as well as in tumours.Results: Serum CD44 concentration was found significantly high in patients as compared to healthy individuals (P < .001) and also in patients whose disease locally recurred as compared to those did not recur (P = 0026). High serum CD44 concentration inversely affected on patients survival (P = .032). CD44v6 staining intensity was detected significantly high in recurrent tumours as compared to primary tumours (P < .001), and it also correlated with poor survival (P < .001). Furthermore, in combination, patients with increased CD44 concentration in serum and CD44v6 expression in tumours significantly correlated with local recurrence (P < .001) and poor survival (P < .001).Conclusion: Our data suggest that the ELISA-based estimation of pre-surgical serum CD44 concentration could be a non-invasive reliable method distinguishing high-risk recurrent tumours which can further assist in post-surgery treatment planning. [ABSTRACT FROM AUTHOR]

Background: Oral squamous cell carcinoma (OSCC) is a cancer of the oral cavity that is a major health problem in India. There is an urgent need to identify biomarkers that have prognostic significance. We studied HIF-1α levels as well as single-nucleotide polymorphism of HIF-1α gene in cancer and healthy controls.Methods: Fifty newly diagnosed OSCC patients and 50 age and sex-matched healthy control were included in the study. Serum concentrations of HIF-1α were measured by sandwich ELISA; whereas HIF-1α gene polymorphism study was performed using restriction enzyme digestion by HpH I.Results: The major genotype observed was CC genotype in both control (84%) and patients (86%) followed by CT genotype (control 16%, cases 14%). CT genotype led to more aggressive tumors. On subgroup analysis based on prognosis, the median overall survival of patients who were treatment responders was 488 days (16.2 months) and that of the patients with progressive disease was 365 days (12.1 months). The patients who expired during the study observation period had median survival of 330 days (11 months).Conclusion: Our study showed that CT genotype for C1772T polymorphism of HIF-1α predisposes to aggressive tumor phenotype in patients with OSCC. Moreover, patients with CT genotype had poor survival rate as compared to CC genotype. A cut-off value of 460 pg/mL of HIF-1α can help to segregate patients with OSCC from healthy controls. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is the commonest subtype of oral cancer, mainly affecting older patients. It used to be a rare disease among individuals younger than 40 years, but recently increased incidences in this age group are being reported worldwide. The pathogenesis of OSCC affecting young patients remains controversial, and the well-known etiological factors for oral cancer, tobacco, and alcohol use are believed to play a minor role in the carcinogenesis of the neoplasm, suggesting that the etiology and the molecular basis of OSCC may differ between younger and older patients. Although several molecular markers and chromosomal abnormalities have been demonstrated to differ between both groups, most of the studies have failed to find significant differences. Moreover, divergent results have also been obtained regarding the presence of high-risk human papillomavirus infection in OSCC of young patients. Given these contradictory results and the limited methodological approaches of the majority of the studies, the exact difference between both age groups remains to be fully established. In this review, we evaluate the available data to establish the current evidence that might support the hypothesis that the molecular basis of OSCC in young patients (especially those under 40 years) differ from the older patients. [ABSTRACT FROM AUTHOR]

Objectives: Late-stage diagnosis is one of the major confounders for poor prognosis of patients with oral cancer owing to lack of a biomarker to diagnose this disease at an early stage. Moreover, till date, invasive biopsies are the only option to assess disease occurrence and progression in this malignancy. Thus, this study aims to identify and assess potential salivary markers in OSCC patients in order to open newer avenues in the field of non-invasive biopsies.Methodology: Bioinformatic-based analysis was performed to identify potential biomarkers that could be assessed in OSCC patients. The expression patterns of CD44v and its genetic and epigenetic modulators were assessed in saliva of OSCC patients, leukoplakia, and controls using real-time and methylation-specific PCR. Statistical analysis was conducted to understand the significance of these markers in terms of their clinical relevance.Results: CD44v/SYNE1/miR34a axis was identified using bioinformatic analysis, and the expression profile of these markers was assessed in saliva of OSCC patients. CD44v6 and CD44v10 demonstrated a significantly increased expression, whereas SYNE1 and miR34a depicted a significantly decreased expression in OSCC patients. Statistical analysis suggested a probable role of CD44v6, SYNE1, and miR34a in early stages of the malignancy, whereas a strong association was observed between CD44v6, CD44v10, and miR34a expression with locoregional aggressiveness and histopathological conditions.Conclusion: Collectively, these findings suggested a plausible role of CD44v/SYNE1/miR34a axis as non-invasive salivary biomarkers to diagnose this disease at an early stage and predict the early onset of metastasis. [ABSTRACT FROM AUTHOR]

Background: The aim was to explore the immunophenotype of neutrophils and lymphocytes and the inflammatory mediators in patients with oral squamous cell carcinoma, comparing with controls; and to associate with clinicopathological data.Methods: Blood was collected from 13 patients and 13 controls. The immunophenotype of neutrophils (CD66b, CD16, CD11a, arginase-1), T lymphocytes (CD4, CD8) and the intracellular cytokine production (IL-10, TNF, IFN-γ) was evaluated by flow cytometry. Plasma concentration of sVCAM-1, sTNF-RI, sTNF-RII, and IL-1β was measured by ELISA. MPO, Lipocalin-2/NGAL, sICAM-1, and p-selectin were quantified by Luminex assay. The excised tumors were submitted to immunohistochemistry for neutrophils (CD66b) and lymphocytes (CD3, CD4, CD8). Association with clinical data was explored. P values <.05 were considered significant.Results: Patients presented higher percentage of neutrophils and lower lymphocytes, resulting a higher neutrophil/lymphocyte ratio than controls. They also presented higher percentage of neutrophils expressing CD66b+ , CD66b+ Arginase-1+ , CD66b+ IL10+ , CD66b+ TNF+ , CD66b+ Arginase-1+ IL-10+ , and lower CD66b+ CD16+ CD11a+ and CD66b+ Arginase-1+ TNF+ . CD66b+ neutrophils were detected in all tumors, with a CD66b+ /CD3+ ratio of 0.40. Patients showed higher concentration of plasmatic sVCAM-1 and lower Lipocalin-2/NGAL. Patients with good outcome presented lower percentage of neutrophils, higher percentage of lymphocytes, and lower NLR than patients who died.Conclusion: The amount and immunophenotype of neutrophils and lymphocytes differ between patients and healthy individuals, with a pro-tumorigenic profile of neutrophils. As these cells also get within tumor microenvironment, they possibly exert systemic and local functions in cancer pathogenesis. The association of neutrophil count with outcome corroborates recent studies and this merits further investigation for applicability as a prognosticator. [ABSTRACT FROM AUTHOR]

Background: Platelet-derived growth factors alpha (PDGFA) is a tyrosine kinase receptor activator which is known to be amplified in the malignancies, and their expression levels are correlated to tumor progression and reduced overall survival. The expression of PDGFRA is different among the tumors and normal tissues; furthermore, their expression level is site specific. Under a physiological condition, PDGFRA and its ligand are expressed in distinct cell populations and activated in a paracrine manner. Nevertheless, heterodimer characteristic of PDGFRA allows it to be trans-activated by non-specific ligands or via autocrine manner. The future of cancer therapy can be based on PDGFRA receptor blockade and therefore warrants further investigation to determine the differing expression of PDGFRA between controls and patients with oral squamous cell carcinoma (OSCC).Methods: We performed a case-control study of 111 patients with newly diagnosed tongue squamous cell carcinoma and 111 control subjects without a cancer diagnosis, matched for age and gender, to evaluate the association between PDGFRA expression levels in oral mucosa. We then performed smoking stratification in each cohort. Independent t test analysis was applied for case-control comparisons.Results: Mean value of PDGFRA mRNA level (-ΔCt) for normal cohort is -30.242, whereas mean value of PDGFRA mRNA level for patients with OSCC is -11.516. PDGFRA mRNA level (-ΔCt) was significantly higher in oral cancer cohort, P<.001. Smokers have a significantly higher PDGFRA mRNA expression in comparison with non-smokers (P=.002) among the non-cancer group. Likewise, this trend is observed in cancer cohort too, P=.044.Conclusion: PDGFRA expression is significantly higher in oral cancer cohort with or without the establishment of tobacco risk factor. [ABSTRACT FROM AUTHOR]

Background: Lymph node metastasis in oral squamous cell carcinoma (OSCC) is a well-known independent prognostic factor. However, the identification of occult tumour cells within the lymph nodes has remained a challenge for the pathologist as well as the clinician.Objective: The aim of this study was to determine the prevalence of micrometastasis and isolated tumour cells (ITCs) in pathologically staged N0 OSCC of the tongue and buccal mucosa and to assess its correlation with vascular endothelial growth factor C, (VEGF-C) expression in the primary tumour.Methods: Thirty-four cases of N0 OSCC comprising of 17 cases each from the tongue and buccal mucosa were evaluated by immunohistochemistry for VEGF-C expression. The corresponding lymph nodes from levels I and II were pathologically examined and cross-detected for micrometastasis and ITCs with desmoglein 3 (DSG3).Results: The prevalence of micrometastasis and ITCs in OSCC of the tongue and buccal mucosa was 23.5% and 17.6%, respectively. A total of 12 out of 151 lymph nodes contained micrometastatic tumour foci and ITCs. A higher expression of VEGF-C in the primary tumour was associated with a greater probability for the occurrence of micrometastasis and ITCs in the lymph nodes.Conclusion: High expression of VEGF-C in the primary tumour may be a good determinant for detection of occult tumour cells in the lymph nodes of OSCC cases. [ABSTRACT FROM AUTHOR]

Background: THBS1 (thrombospondin-1) is the extracellular matrix (ECM) protein that affects diverse cellular activities. It constitutes the tumor stroma, but the role of THBS1 in oral squamous cell carcinoma (OSCC) development is unclear. The aim of this study was to clarify the relevance of THBS1 in the pathogenesis of OSCC.Materials and Methods: The expression of THBS1 was examined in 44 OSCC by immunohistochemical analysis and in 43 OSCC by cDNA microarray analysis. Cell culture experiments were conducted using human OSCC cell lines HSC3 and HO1N1 and mouse fibroblast ST2 cells to examine the effect of TGFB1 on THBS1 expression, and the effect of THBS1 on cellular behaviors.Results: THBS1 was specifically induced in the tumor microenvironment of OSCC. THBS1 appeared to be produced mainly by the stromal cells, but also by OSCC cells. TGFB1 stimulated THBS1 expression in ST2, primary fibroblasts, and the OSCC cells. THBS1 promoted migration and invasion of HSC3 and HO1N1 in transwell migration assays. THBS1 stimulated the expression of MMP3 (matrix metalloprotease 3), MMP9, MMP11, and MMP13 in ST2 cells and MMP3, MMP11, and MMP13 in HO1N1 cells. The RGD peptide suppressed the THBS1-stimulated migration and upregulation of MMP11 and MMP13.Conclusions: THBS1 is a tumor-specific ECM protein that is induced by TGFB1 and promotes migration of cancer cells and stimulates the expression of MMPs partly through the integrin signaling, thereby favoring OSCC invasion. [ABSTRACT FROM AUTHOR]

Background: Few studies have focused on the relationship between Helicobacter pylori (H. pylori) infection and oral diseases. In this study, we explored the correlation between H. pylori infection and oral squamous cell carcinoma (OSCC).Methods: A total of 68 patients with OSCC and 104 age- and sex- matched healthy control subjects were retrospectively enrolled in this study. The H. pylori immunoglobin (Ig) G antibodies in serum were detected by enzyme-linked immunosorbent assay (ELISA) method to assess the status of H. pylori infection of our study sample. Polymerase chain reaction (PCR) was also employed using H. pylori genus-specific 16S rRNA primers in fasting blood, and OSCC specimens were analyzed by histochemical stain of each enrolled subject. The strength of correlation between H. pylori and the development of OSCC was estimated by Spearman's correlation coefficient.Results: According to the three methods for detecting prevalence of H. pylori infection in the patients with OSCC, it was statistically lower than that in the healthy controls (35.3% vs. 54.8%, P = 0.012). An inverse correlation was observed between H. pylori infection and OSCC development (Spearman's correlation coefficient = -0.191, P = 0.012). In stratification analysis, we also found a statistical association between H. pylori infection and OSCC in the subpopulation with age ≥ 60 years (P = 0.037).Conclusion: Our findings suggested that H. pylori infection may be negatively related to OSCC. A reverse association of H. pylori infection with OSCC risk in the subpopulation with age ≥ 60 years was also found. [ABSTRACT FROM AUTHOR]

Background While the protective role of antioxidant nutrients against cancer is well established, data on Asian diets in patients with oral cancer are meagre. Methods A total of 1029 subjects over 30 years of age were investigated on their dietary practices in the Sabaragamuwa province (Sri Lanka) in 2006-07. Data collection tools were an interviewer-administered questionnaire, a three-day food diary and an examination of the oral cavity. Subjects identified with Oral Potentially Malignant Disorders ( OPMD) and disease-free controls were analysed in a case-control fashion. Among the OPMDs, those with leukoplakia were separately considered. A further subgroup analysis was undertaken for β-carotene-rich foods. The analysis was stratified by portions of fruit/vegetables consumed as five or more portions and two or more portions daily. Results A low BMI (<18.5) was a significant independent risk factor for the development of OPMD. More than half of both cases and controls consumed less than two portions of fruit/vegetables per day and only 20 subjects consumed more than five portions per day. Intake of more than two portions per day of β-carotene-containing fruits/vegetables significantly reduced the risk of having an OPMD and leukoplakia ( OR = 0.5; 95% CI, 0.3-0.9). The significant differences observed with BMI and fruits/vegetables were attenuated when adjusted for betel quid chewing, smoking and alcohol use. Conclusions This study discloses prevailing under-nutrition in this rural population with very low daily consumption of fruit/vegetables. Cancer preventive properties in their diets are limited and are swamped by the known carcinogenic agents associated with use of betel quid, tobacco and alcohol. [ABSTRACT FROM AUTHOR]

Introduction Functional polymorphisms ( SNPs) of the vascular endothelial growth factor ( VEGF) are associated with the incidence of oral squamous cell carcinoma ( OSCC). An impact of VEGF- SNPs on prognosis of OSCC patients seems possible. Therefore, correlations between prognostic parameters of OSCC patients and five VEGF- SNPs were determined. Materials and Methods In a retrospective long-term study, in 113 OSCC patients that underwent curative resections, five VEGF- SNPs (−1154 G/A, +405 G/C, +936 C/T, −2578 C/A, and −460 C/T) were analyzed. Associations between SNPs and prognosis (incidence of local recurrent disease, second cancer, metastases, death, total disease-free survival) were examined. Results After a mean follow-up time of 57.6 months, 32 patients had local recurrences; 15 patients had second cancer, 15 patients metastases, and 23 patients died. The mean disease-free survival was 43.1 months. A significant increased incidence of OSCC in smokers with the VEGF −2578 A/C and −460 C/T SNP was seen (each P < 0.0001). In univariate analysis, patients with advanced OSCCs ( T > 2 or N > 0) together with the −1154 A/A allele had a significant worse survival and a worse disease-free survival (both P < 0.04). The same was seen for the +405 G/G SNP (both P = 0.002). In multivariate analysis, only the negative influence of the +405 G/G SNP on survival in advanced OSCCs ( T > 2) could be confirmed ( P = 0.002). Discussion Possible reciprocal interactions between smoking and VEGF- SNP function were observed. Multivariate analysis confirmed the VEGF +405 G/G genotype to be associated with poor survival in advanced OSCCs; a further use of this haplotype as biomarker has to be discussed. [ABSTRACT FROM AUTHOR]

Objectives Production of carcinogenic acetaldehyde by Candida has been suggested to contribute to epithelial dysplasia and oral carcinogenesis. Oral lichen planus ( OLP), oral lichenoid lesion ( OLL) and oral leukoplakia ( OL) are potentially carcinogenic oral diseases where colonisation by Candida is common, but acetaldehyde production by Candida has not been studied. Study Design Acetaldehyde production in ethanol (11 mM), glucose (100 mM), ethanol-glucose (11 mM and 100 mM) or red wine (1200 mM ethanol) incubation by Candida albicans from patients with OLL ( n = 6), OLP ( n = 16), OL ( n = 6) and controls ( n = 6) was measured by gas chromatography. Participants completed a questionnaire regarding their smoking habits and alcohol consumption. Results All Candida albicans isolates produced potentially carcinogenic levels of acetaldehyde (>100 μM) in all incubations containing ethanol. The control group isolates produced the highest acetaldehyde levels. Isolates from smokers produced more acetaldehyde in all incubations than those from non-smokers. The difference was significant in ethanol-glucose incubation. Isolates from patients who were both smokers and drinkers produced the highest amounts when incubated in ethanol, ethanol-glucose and wine. Conclusions Candida albicans isolated from potentially carcinogenic oral diseases can produce mutagenic amounts of acetaldehyde. Cigarette smoking and alcohol consumption may favour adaptational changes resulting in the upregulation of candidal acetaldehyde metabolism. [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2011) : 61-66 Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in folate metabolism. Two common polymorphisms associated with MTHFR gene - C677T and A1298C - influence the thermolabile nature and activity of the enzyme. This study aimed to investigate the role of MTHFR polymorphisms on oral cancer susceptibility and its potential impact on the prognostic outcome. Oral cancer cases and controls were genotyped using PCR-RFLP technique for MTHFR C677T and A1298C polymorphisms. Disease susceptibility analysed using regression analysis. The association between clinical outcomes and the polymorphisms were analysed using univariate and multivariate model. The 677CT+TT genotype showed a significant three-fold reduction in oral cancer risk (RR-0.35, p-0.009). 1298CC genotype showed decreased cancer risk when compared to AA+AC genotype (RR-0.55, p-0.062). When prognostic significance of MTHFR polymorphism was evaluated, 677CT+TT patients showed improved survival than the CC individuals (RR = 0.56, P = 0.378). The 1298 CC and AC+CC showed an increased risk for treatment failure and poor survival when compared with the wild AA genotype (HR = 4.27, P = 0.001). Here we observed MTHFR C677T to influence oral cancer susceptibility, while A1298C polymorphism associated with patient prognosis. Our data support MTHFR polymorphism to be an independent prognostic marker in oral carcinoma. [ABSTRACT FROM AUTHOR]

To investigate the mechanism whereby serum dipeptidyl peptidase (DPP) IV activity in oral cancer patients is decreased, we examined the expression of cell surface DPP IV, also known as CD2b, in cultured peripheral blood T lymphocytes of these patients and (he amounts of DPP IV released into culture medium: values were compared with those found in healthy subjects. When peripheral blood T lymphocytes were cultured in the presence of phytohaemagglutinin, concanavalin A and/or interleukin-2. the proliferative response and expression of CD26 (DPP IV) in their plasma membranes were greatly diminished in oral cancer patients as compared with those in healthy subjects. In addition. DPP IV activity in lymphocyte culture medium was reduced more in oral cancer patients than in healthy subjects. indicating decreased shedding of DPP IV from activated T lymphocytes in the patients. Based on these findings, it is suggested that suppression of DPP IV expression in peripheral blood T lymphocytes is one of the important factors involved in the mechanism of decrease of serum DPP IV activity in oral cancer patients. [ABSTRACT FROM AUTHOR]

To investigate the mechanism of decrease of serum DPP IV activity in oral cancer patients, we analyzed the expression of DPP IV in peripheral blood T lymphocytes of oral cancer patients and healthy subjects. Consequently, serum DPP IV activity was found to correlate significantly with the number of peripheral blood lymphocytes (PBL), T lymphocytes and CD26 (identified as DPP IV)+ T lymphocytes in healthy subjects, and the number of PBL and CD26+ T lymphocytes in cancer patients. However, the numbers of PBL and T lymphocytes were significantly less in cancer patients than in healthy subjects. Although the number of CD26+ T lymphocytes was somewhat greater in cancer patients than in healthy subjects, serum DPP IV activity was significantly lower in cancer patients. DPP IV activity and amount of CD26 in T lymphocyte plasma membranes were much less in cancer patients than in healthy subjects. These findings suggest that a decrease in the number of T lymphocytes and the small amount of DPP IV in their plasma membrane may contribute to the decrease of serum DPP IV activity in cancer patients. [ABSTRACT FROM AUTHOR]

An editorial is presented which addresses the potential need to rethink the guidelines for follow-up medical studies for oral squamous cell carcinoma (OSCC) cancer patients, and it mentions the goal of early detection of second primary disease, distant metastasis, and disease recurrences. According to the article, OSCC patients who participate in follow-up studies should receive benefits such as improved quality of life and chance of cure. Patient anxiety is mentioned.