Association of single nucleotide polymorphisms in cell cycle regulatory genes with oral cancer susceptibility.

Alterations in the regulation of the cell cycle are strongly linked to tumorigenesis, so genetic variants in genes critical to control of the cycle are good candidates to have their association with susceptibility to oral cancer assessed. In this hospital-based, case-control study of 445 patients who had been newly-diagnosed with oral cancer and 449 unaffected controls, we used a multigenic approach to examine the associations among a panel of 10 selected polymorphisms in the pathway of the cell cycle that were possibly susceptible to oral cancer. Six of 9 single nucleotide polymorphisms in the cell cycle showed significant risks for oral cancer, the highest risk being evident for p27 (rs34329; Odds ratio 3.

Accumulation of inactive p53 protein in oral squamous cell carcinoma: stabilization by protein interaction.

Our previous study showed that p53 protein is accumulated in >60% of cases of oral squamous cell carcinoma (OSCC) and its overexpression is related to poor prognosis. However, the mechanism behind this is still elusive. The present study attempts to dissect p53 alterations at various levels from gene to function in tumor biopsies to understand whether molecular alterations have any relationship with the accumulation of p53 protein in OSCC.

Influence of methylenetetrahydrofolate reductase polymorphisms in oral cancer patients.

Background: 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.

Differential roles of p16INK4A and p14ARF genes in prognosis of oral carcinoma.

Background: Oral cancer patients are found to have poor clinical outcome and high disease recurrence rate, in spite of an aggressive treatment regimen. The inactivation of INK4A/ARF loci is reported to be second to p53 inactivation in human cancers. The purpose of this study was to assess the prognostic significance of the molecular aberrations in the INK4A locus for effective identification of aggressive oral carcinoma cases needing alternate therapy.

CCND1 polymorphisms (A870G and C1722G) modulate its protein expression and survival in oral carcinoma.

Cyclin D1 is an essential regulator of the G1 phase of the cell cycle progression and plays an important role in the transition of the cell from the G1 phase to the S phase of the cell cycle. Overexpression of cyclin D1 is a frequently observed feature of human cancers of diverse histological origin. Recently, we have reported overexpression of cyclin D1 in oral carcinoma.

H-Ras mutation modulates the expression of major cell cycle regulatory proteins and disease prognosis in oral carcinoma.

Activating mutations of the Ras is a moderately frequent event in oral carcinogenesis in Indian patients. Ras pathway has essential roles in regulation of various phases of the cell cycle, especially at G1 phase. Despite a large body of in vitro evidence, the multidimensional interaction between mutated Ras pathway and G1 cell cycle regulatory proteins in tumours in vivo is poorly determined.

Carcinoma of tongue and the buccal mucosa represent different biological subentities of the oral carcinoma.

Purpose: Clinico-epidemiological studies show that the behaviour of the tongue cancer is different from the cancer originating at other sites of the oral cavity. However, studies identifying the reason for such difference are lacking in the literature.

Methods: In the present study, we have attempted to see whether any difference existed in the cell cycle regulatory mechanism of these tumours by comparing immunohistochemically the expression of major cell cycle regulatory proteins in 147 buccal and 94 tongue carcinoma (anterior two-third of tongue) prospectively.

Influence of single nucleotide polymorphisms in H-Ras and cyclin D1 genes on oral cancer susceptibility.

Although tobacco usage and alcohol consumption are the major risk factors for oral cancer, there are individual variations in genetic susceptibility to oral cancer. The Ras pathway plays an important role in oral carcinogenesis. High percentage of Ras mutation in oral carcinoma was reported from India.

Phenotypic alterations in Rb pathway have more prognostic influence than p53 pathway proteins in oral carcinoma.

The two well-defined pathways that are shown to be prominently altered in a variety of cancers are the cell cycle regulatory pathways led by either p53 or Rb genes. The present study is undertaken to find the pathway that is more altered in oral carcinoma at protein level, with special emphasis on its prognostic significance. The expression pattern of key molecules of the Rb and p53 pathways, such as Rb, cyclin D1, CDK4, p16, p53, p21 and Bcl-2 and the proliferative marker PCNA were analysed in 348 oral carcinoma specimens by immunohistochemical technique.

p53, p16 and cyclin D1: molecular determinants of radiotherapy treatment response in oral carcinoma.

Management of oral cancer by radiotherapy has witnessed promising advances in the past few years, with patient-tailored radio fractionation regimens. Different fractionation schedules, conventional and altered regimes, have been used in curative radiotherapy. Although contribution of biological markers on radio response has been evaluated, its unique influence on various radio fractionation schemes has not been accounted so far.

Genetic polymorphism of CYP1A1, GSTM1 and GSTT1 genes in Indian oral cancer.

Oral cancer ranks first among all cancers in males and is the third most common among females in India. Tobacco-derived carcinogens are involved in the development of oral cancer. Environment-gene interaction in oral carcinogenesis is well demonstrated by phase I and II enzymes that are involved in the metabolism of carcinogens.

De novo programmed cell death in oral cancer.

Aim: The importance of programmed cell death or apoptosis in the maintenance of tissue homoeostasis and the pathogenesis of oral cancer was analysed in relation to apoptosis regulatory proteins, tissue proliferation and tumour histology.

Methods And Results: The extent of apoptosis was defined by morphological criteria and the TUNEL (terminal deoxy nucleotidyl transferase-mediated dUTP biotin nick end labelling) assay. p53, bax, bcl-2 and cyclin D1 expression was evaluated by immunocytochemistry.

Angiogenesis during tumor progression in the oral cavity is related to reduced apoptosis and high tumor cell proliferation.

Angiogenesis, the growth of new blood vessels, is believed to aid tumor progression and metastasis. Tumor progression is also influenced by the extent of proliferation and apoptosis. This study, therefore, analyzed in lesions of the oral cavity, the significance of angiogenesis in relation to apoptosis, expression of apoptosis regulatory p53, bax and bcl-2 proteins as well as tissue proliferation defined by cyclin D1 expression.

Serum levels of copper, zinc, iron and ceruplasmin in oral leukoplakia and squamous cell carcinoma.

Trace elements have been extensively studied in recent years to assess whether they have any modifying effects in the etiology of cancer. In the present study serum levels of copper, zinc, ceruloplasmin, total iron and total protein were estimated in 92 patients with oral leukoplakia and squamous cell carcinoma and 45 age and sex matched controls. Copper was significantly increased in oral leukoplakia and cancer in both sexes.

Telomerase activity in premalignant and malignant lesions of human oral mucosa.

Recent studies have demonstrated a strong association between carcinogenesis and re-activation of telomerase in various human tumors. In the present study, we have analyzed the telomerase activity in 105 oral mucosal samples, including normal mucosa and premalignant and malignant lesions, by using the telomeric repeat amplification protocol assay. The telomerase activity was detected in normal oral squamous epithelium and in 75% of the oral leukoplakias and oral carcinomas.

Expression of programmed cell death regulatory p53 and bcl-2 proteins in oral lesions.

With the ultimate goal of characterizing the molecular pathogenesis of oral cancer, the most predominant malignancy in India, immunocytochemical evaluation of p53 and bcl-2 proteins was carried out in hypeplastic oral mucosa, dysplastic oral mucosa and invasive oral cancer. All subjects gave a similar and almost uniform history of prolonged use of betal quid and tobacco. Expression of p53 was insignificant while bcl-2 was absent in hyperplastic leukoplakia lesions.

Ultrastructural analysis of the adjacent epithelium of oral squamous cell carcinoma.

Fifteen biopsies of the immediate adjacent epithelium of oral squamous cell carcinoma were examined under light and electron microscopy. Light microscopic examination of one micron thick sections revealed that the majority of lesions (67%) had hyperplastic or mildly dysplastic epithelium while the remaining (33%) had moderate to severe dysplasia. Ultrastructural observations showed that all these lesions had subcellular alterations similar to those seen in frank malignant oral tissue, particularly in the lower half of the epithelium.

Human papillomaviruses in 91 oral cancers from Indian betel quid chewers--high prevalence and multiplicity of infections.

India has one of the world's highest incidences of oral cancer. The habit of chewing betel quid is widespread and is suspected to play a role in the etiology of this disease. Studies in many other countries have also pointed to a role for human papilloma-viruses (HPVs) in the etiology of some oral cancers.

Scanning electron microscopy of different types of oral leukoplakia: comparison with normal and malignant oral mucosa.

The present study analysed surface architecture of normal, premalignant and malignant oral mucosa using scanning electron microscopy to evaluate its role in early diagnosis of potentially malignant oral lesions. The surface ultrastructure of the buccal mucosa in tobacco chewers showed variations from that of non-chewers. Homogenous leukoplakia demonstrated well-defined intercellular junctions and the microrugal surface pattern as seen in normal mucosa.

Expression of galactoside-specific endogenous lectins and their ligands in human oral squamous cell carcinoma.

Human endogenous lectins have a wide spectrum of biological functions. The present study analyses the expression of beta-galactoside specific and N-acetyl-D-galactosamine specific endogenous lectins in oral squamous cell carcinomas using biotinylated neoglycoproteins. The expression pattern of beta-galactosyl-containing glycoconjugates or ligands of beta-galactoside specific lectins in these tissues was also studied using an endogenous biotinylated lectin, the human 14-kDa lectin.

Alterations in expression of basement membrane proteins during tumour progression in oral mucosa.

Expression of three basement membrane proteins--collagen IV, laminin and fibronectin--was studied in normal, hyperplastic, dysplastic and neoplastic conditions of the oral mucosa using immunohistochemistry. Collagen IV and laminin exhibited similar staining patterns, while fibronectin showed a different pattern of expression. The expression of collagen IV and laminin also demonstrated an inverse correlation between staining intensity, thickness and basement membrane continuity in various stages of tumour progression.

Immunohistochemical localization of epidermal growth-factor and its receptor in normal, premalignant and malignant oral-mucosa.

An important growth factor involved in epithelial carcinogenesis is the epidermal growth factor (EGF). The present study analyze the expression pattern of EGF and its receptor (EGFR) in different stages of tumour progression in oral mucosa (normal epithelium, non-dysplastic and dysplastic leukoplakias and carcinomas). Alterations in expression pattern of EGFR was not significant in the various tissues from normal mucosa to malignancy.

Immunoregulation of T-lymphocytes by autologous serum in oral-cancer.

Autologous sera from 130 patients with squamous cell carcinoma of the buccal mucosa were evaluated for its immunoregulatory effect on the different sheep erythrocyte resetting populations of the patients. All the T cell populations were significantly reduced in oral cancer patients. The patient sera could be classified into blockers (0.

CD2 related immunoregulation in oral cancer.

Sera from 93 patients with carcinoma of the buccal mucosa were analysed for its regulatory effect on CD2 antigen expression using anti CD2 monoclonal antibodies and sheep erythrocyte rosetting assay. The sera from 55.5% of the patients showed an inhibitory effect (blocker sera) while sera from 44.

Ultrastructure of oral squamous cell carcinoma: a comparative analysis of different histological types.

Twenty-five oral carcinomas and five normal oral epithelial specimens were studied using light and electron microscopy. All histological types (well differentiated squamous cell carcinoma, moderately differentiated squamous cell carcinoma, poorly differentiated squamous cell carcinoma, verrucous carcinoma and spindle cell carcinoma) were seen in the study sample. In addition, 1 case of carcinoma in situ was also present.