Aldehyde dehydrogenase 1: Its key role in cell physiology and oral carcinogenesis.

Aldehyde dehydrogenase (ALDH), an aldehyde-metabolizing enzyme, is a cytosolic antioxidant. It performs many important physiological catalytic and non-catalytic functions in mammalian cells. Apart from physiological functions, like the biosynthesis of vital molecules, this NAD(P)+ substrate-dependent enzyme superfamily is primarily involved in catalyzing the oxidation of highly reactive exogenous and endogenous aldehydes to their respective carboxylic acids. Among ALDH isoenzymes, ALDH1 has gained much attention as a prominent stem cell marker, as it is associated with the maintenance of stemness and the differentiation of normal stem cells, in addition to involvement in oncogenic functions, like cell proliferation, anti-apoptosis and the reduction of oxidative stress in cancer stem cells (CSCs). In this context, the authors review the physiological functions of ALDH1 in normal cells, normal stem cells and CSCs, along with the discussion of the putative role of ALDH1 in oral carcinogenesis by commenting on its expression in normal oral mucosa cells, oral potentially malignant disorders (OPMDs), like leukoplakia and dysplastic lesions, and oral squamous cell carcinoma (OSCC).

Altered immunoexpression of SOX2, OCT4 and Nanog in the normal-appearing oral mucosa of tobacco users.

BACKGROUND: Tobacco use is causatively associated with various human cancers, including oral carcinoma. A number of pathways have been delineated to describe its etiopathological link with oral carcinogenesis, including alterations in the expression of stem cell markers. Embryonic stem cell markers, such as sex-determining region Y-box 2 (SOX2), octamer-binding protein 4 (OCT4) and homeobox protein Nanog, which are mainly involved in the maintenance of stemness and pluripotency, have been positively associated with the pathogenesis of oral potentially malignant disorders and oral cancers. In this context, we attempted to explore the subcellular impact of tobacco through examining the expression of these stem cell markers in normal and normal-appearing oral mucosa in non-tobacco users and tobacco users. OBJECTIVES: The aim of the study was to analyze the immunoexpression of SOX2, OCT4 and Nanog in the normal-appearing oral mucosa (NAOM) of tobacco users as compared to the normal oral mucosa (NOM) of non-tobacco users. MATERIAL AND METHODS: The tissue samples of tobacco users and non-tobacco users (n = 50 per group) were immunohistochemically stained to assess the expression of SOX2, OCT4 and Nanog. RESULTS: In the oral mucosa of non-tobacco users, a peculiar parabasal expression pattern of SOX2 and OCT4 was observed, whereas Nanog was non-reactive. The grade of inflammation was found to be a predictive variable influencing the expression of the 2 markers. In tobacco users, variables such as male gender, mixed habit and basilar hyperplasia significantly controlled the basilar and suprabasilar expression of SOX2, OCT4 and Nanog. The expression of SOX2 and OCT4 was higher in tobacco users; in particular, OCT4 positivity was significantly increased (p < 0.001) in comparison with non-tobacco users. CONCLUSIONS: The altered expression of the examined stem cell markers could be an indication of early molecular changes in NAOM under the influence of tobacco.

Identification of genetic instability in peripheral blood lymphocyte of oral squamous cell carcinoma patients assess by comet assay.

Context: Studies established that human cancer is principally a genetic disease; it arises as accumulation of a set of genetic changes. In the pathogenesis of cancer, genetic instability is the sequential event to a carcinogenic stimulus resulting in various genomic changes including DNA damage. Aims: To assess genetic instability, as susceptibility to DNA damage, we used single-cell gel electrophoresis (comet assay) to study double strand breaks in associated with the risk of oral squamous cell carcinoma (OSCC). Materials and Methods: We used comet assay to measure double strand break in individual peripheral blood lymphocytes from 50 individuals with OSCC and 30 healthy control subjects. All personal information was gathered from subjects including tobacco history. DNA damage was visualized as comet assay and quantified by movement of damaged strands as length of tail. Results: Study results of OSCC patients were observed in relation to clinical staging and histological grading of carcinoma. On the basis of clinical observation, cases were grouped in to Stage I, Stage II, Stage III and Stage IV. No stage I cases were in study sample. The mean DNA damage migration length was observed 4.600 ± 0.4613 µm in stage II, whereas in Stage III and Stage IV, it was observed to be 4.961 ± 0.5620 µm and 4.883 ± 0.410 µm, respectively. The DNA damage length in histological grades of squamous cell carcinoma patients in Grade I was 4.6437 ± 0.3061 µm and Grade II was 5.3533 ± 0.3831 µm. In comparison with control group and squamous cell carcinoma group, it was observed in the range of 0.02-0.36 µm and varied from 4.04 to 5.84 µm range, respectively. Thus, the results were statistically significant with the histological grading of OSCC. Statistical Analysis: Unpaired' test and "ANOVA" test are used for statistics. Statistical Analysis: Unpaired' test and "ANOVA" test are used for statistics. Conclusion: The amount of DNA strand breaks in peripheral lymphocytes are measured by comet assay which is associated with relative risk of OSCC.

Comparative evaluation of prevalence and phenotypic variations of Candida species in patients of oral lichen planus and oral lichenoid lesions with healthy individuals - A prospective microbiological study.

Context: Candida isolates might exaggerate the development and advancement of oral lichen planus (OLP) alone or together with other factors. There is a differing pathogenic potential of various Candida species. Since Candida species isolated from OLP and oral lichenoid lesions (OLL) have shown to be resistant to commonly used antifungal agents, identification of Candida species may play a pivotal role in its successful clinical management. Aim: The aim of the study was to evaluate and compare the prevalence and phenotypic variations of Candida species in patients of OLP and OLL with healthy controls. Subjects and Methods: This prospective microbiological study was conducted in the institution using indirect microscopic examination. The sample comprised of 40 clinicohistopathologically diagnosed cases of the study group (OLP and OLL) and 40 cases of control group (healthy individuals). Statistical Analysis Used: The data collected was statistically analyzed using the Chi-square test and Fisher's exact test with the SPSS 20.00 software. Results: The prevalence of Candida albicans was higher in the control group (28.10%) as compared to the study group (24.60%) and this difference was statistically significant. An increased frequency of non C. albicans species was seen in the study group, in decreasing order of Candida glabrata (40.70%), Candida tropicalis (22.20%), Candida krusei (22.20%) and Candida guilliermondii (3.70%), as compared to the control group. Conclusion: Non C. albicans species were the predominant pathogens associated with the study (OLP + OLL) group. It is important to identify the infecting strains of Candida because isolates of Candida species differ widely, both in their ability to cause infection and also in their susceptibility of resistance to antifungal agents. Thus, phenotypic speciation of Candida is emerging as a necessary trend to highlight the need of administering appropriate antifungal therapy.

Green Synthesis to Develop Iron-Nano Formulations and Its Toxicity Assays.

OBJECTIVES: In the past few years, herbal medicines have gained popularity over synthetic drugs because of their natural source and minimal side effects which has led to a tremendous growth of phytopharmaceuticals usage. With the development of nanotechnology, it provides alternative approaches to overcome several limitations using nano-formulations. In spite of considerable quantity of antianemic preparations with different iron forms available, currently additives are used and represented in modern pharmaceutical market. Iron deficiency anemia is a major global public health problem which particularly affects pregnant women, children and elderly persons. The situation is complicated because of disadvantages and drug side effects from existing antianemic medicines. There is a great demand for the development of new antianemic preparations. Green synthesis of iron oxide nanoparticles, possess high potential in this field. METHODS: Our study focuses on developing green synthesis of iron oxide nanoparticles (IONPs) of 10-50 nm with spherical shape where different dosages were used -1 mg/kg, 10 mg/kg and 100 mg/kg for exposure in Wistar albino female rats for 28 days. The toxicity was assessed using various parameters such as measurements of the rat body and organ mass, hematology, biochemical evaluation and histopathological examinations. RESULTS: No significant differences were observed in body and organ weights. Hematological indices also indicated no significant differences whereas biochemical factors showed increase in levels of direct bilirubin and globulin of medium as well as high dose and SGPT levels were increased only in high dose. The major organs (heart, kidney and liver) showed histopathological alterations in 10 and 100 mg/kg whereas brain showed only in 100 mg/kg. CONCLUSION: The toxicity of IONPs was found to be more significant when the concentration was increased; however, low doses can be used for further investigation as an antianemic preparation.

Comparative evaluation of staining efficacy of calcofluor white and acridine orange for detection of Candida species using fluorescence microscopy - A prospective microbiological study.

CONTEXT: Candida is a yeast-like fungus, and it causes candidiasis. Since it is commonly encountered in many cases, the need of the hour is for rapid and reliable method for identification of these fungi in tissue sections. AIM: The aim of this study was to evaluate and compare the staining efficacy of calcofluor white (CFW) and acridine orange (AO) for the detection of Candida species in formalin-fixed paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC) using fluorescence microscopy. SETTINGS AND DESIGN: Sample size comprised forty cases of OSCC. MATERIALS AND METHODS: Before tissue sampling, a swab of the area was taken, it was immediately inoculated on Sabouraud's dextrose agar media and germ tube test was performed for positive cultures for species identification. Tissue sections were obtained from cases of OSCC from the formalin-fixed paraffin-embedded tissue blocks of the same cases in which microbiological assessment was done at the time of tissue sampling, were stained with CFW and AO stain, respectively, and were examined using a fluorescent microscope. STATISTICAL ANALYSIS: Descriptive statistics were expressed in numbers and percentage. Independent t-test (unpaired t-test) and Chi-square test were used. P ≤0.05 was taken to be statistically significant. RESULTS: The mean number of microorganisms per high-power field stained by CFW and AO was 6.35 and 2.57, respectively, and a statistically significant difference (P ≤ 0.001) was observed. CFW compared to swab culture gave P = 0.018, which showed a statistically significant association. CONCLUSIONS: CFW is a better fluorescent stain when compared to AO to detect Candida species in tissue sections of OSCC cases.

SOX2, OCT4 and NANOG: The core embryonic stem cell pluripotency regulators in oral carcinogenesis.

Embryonic stem cells provide their major contribution to embryogenesis through formation of germ layers as they have pluripotency potential and capacity for self-renewal. Retention of pluripotency of these stem cells depends on expression/level of transcription factors, i.e., SOX2, OCT4 and NANOG. During organogenesis, the altered expression of the molecules also influences these stem cells to lose their pluripotency and turn toward the lineage selection. As the differentiation progresses, the maintenance of the somatic cells including the oral squamous cells also depends on differential expression of the transcription factors to some extent. Recently, many experimental and observational studies documented the significant contribution in carcinogenesis of various human cancers. In this review, we have attempted to summarize the evidences indicating about the putative role of these master pluripotency regulators in various phases of oral carcinogenesis i.e. initiation , progression and prognosis of oral squamous cell carcinoma.

Benign cementoblastoma involving left deciduous first molar: A case report and review of literature.

Cementoblastoma, a benign mesenchymal odontogenic neoplasm is derived from ectomesenchymal cells of the periodontium. Cementoblastomas associated with primary teeth are extremely rare as permanent mandibular first molars are mostly affected. Only 17 cases of those associated with deciduous dentition have been reported so far. The present case report describes a true cementoblastoma of an 8-year-old male child in relation to the left first primary mandibular molar along with emphasis on differential diagnosis.

Carotid Body Paraganglioma.

Carotid body paraganglioma (CBP) is a type neuroendocrine tumour arising from paraganglial chief cells of carotid body. Situated at the bifurcation of the common carotid artery, it constitutes 0.5% of all body tumours. Though CBP's is most common paraganglioma of head and neck it is a rare neoplasm and requires a thorough examination for a proper diagnosis and therapeutic management. Here, we present a case of 36 year old female patient with CBP in left side of the neck.

Adenosine Deaminase - a Novel Diagnostic and Prognostic Biomarker for Oral Squamous Cell Carcinoma.

BACKGROUND: The number of patients with oral cancer in India is increasing gradually (especially in younger people). Although the diagnostic modalities and therapeutic management of oral cancer are improving, the treatment outcome and prognosis of oral cancer remain poor. The absence of definite early warning symptoms for most head and neck cancers suggests that sensitive and specific biomarkers are likely to be important in screening for high-risk patients. AIMS: To analyze serum adenosine deaminase (ADA) levels in oral squamous cell carcinoma (OSCC) cases who reported to our institute. MATERIALS AND METHODS: A prospective study was performed on 100 histopathologically proven cases of OSCC (study group) and 100 normal healthy individuals (control group). Independent sample and one sample t-tests and one way ANOVA followed by Tuckey's POST HOC test were conducted for analysis. RESULTS: Statistically significant increase in serum ADA levels was observed in OSCC cases compared to the control group. Also serum ADA level increased significantly with the histopathological grade. CONCLUSIONS: Serum ADA levels in OSCC may be a useful diagnostic and prognostic biomarkers in clinical practice and our findings suggest that a large-scale study is warranted to confirm clinical utility as a prognostic and diagnostic biomarker.

Asymptomatic, blue, dome-shaped lesion on buccal mucosa.

An asymptomatic, blue, dome-shaped lesion on the buccal mucosa can include a plethora of entities clinically as well as histopathologically. Its clinical presentation may mimic reactive, developmental, benign or malignant conditions. This emphasizes the need on histopathological assessment of every docile looking lesion to explore its exact biological behavior.

Pagetoid polyostotic fibrous dysplasia.

Fibrous dysplasia (FD) is a benign skeletal lesion occurring due to mutation of Gs α gene and involves one or multiple bones. We present a case of a 30-year-old female patient, with a 1-year history of swelling under her right eye that had gradually increased in size. Extraoral examination revealed a diffuse swelling extending anteroposteriorly from preauricular region to nasolabial fold, frontonasal region and superoinferiorly from zygoma to body of mandible, causing ipsilateral proptosis and contralateral deviation of nose. Intraoral examination showed obliteration of right upper and lower buccal vestibule. CT disclosed expansile lytic lesions involving multiple skull bones, jaws, sternum, rib and thoracic vertebrae. Histopathology displayed broad and interconnected trabeculae connected to the host bone exhibiting reversal lines resembling the mosaic pattern of Paget's disease. These features suggested pagetoid polyostotic FD. The patient underwent cosmetic recontouring and is under regular follow-up postoperatively.

Podoplanin--a novel marker in oral carcinogenesis.

Podoplanin, a transmembrane sialoglycoprotein, is a specific marker for lymphatic endothelial cells which in recent years has gained prominent notoriety for its role in tumor progression and metastasis. It is an extensively studied biomarker for predictive assessment of malignant transformation as well as biologic behavior in both human precancer and cancer, respectively. This review summarizes the association of podoplanin overexpression in oral potentially malignant disorders and oral cancer with special emphasis on its putative role in carcinogenesis as well as its prospective use in targeted therapy.

Adenomatoid odontogenic tumor with clear cell changes.

Adenomatoid odontogenic tumor (AOT) has a limited biological profile and been an attention-grabbing tumor for a century for its origin. Though described earlier, it was widely accepted after Harbitz from Norway reported about this uncommon benign tumor in 1915. There has been a long debate as whether this tumor is a hamartoma or a neoplasm. Here, we present a case of AOT in a 20-year-old female with details of clinical, radiological and histological features along with clear cell changes, signifying AOT to be more aggressive in nature than assessed from earlier literature. Thus, we did an extensive search of PubMed literature on AOT with all its histopathological features associated until date to find the report of clear cell changes yet.

The evolving concepts of cancer stem cells in head and neck squamous cell carcinoma.

There is increasing evidence that the growth and spread of cancers is driven by a small subpopulation of cancer stem cells (CSCs)--the only cells that are capable of long-term self-renewal and generation of the phenotypically diverse tumor cell population. CSCs have been identified and isolated in a variety of human cancers including head and neck squamous cell carcinoma (HNSCC). The concept of cancer stem cells may have profound implications for our understanding of tumor biology and for the design of novel treatments targeted toward these cells. The present review is an attempt to conceptualize the role of CSCs in HNSCC--its implication in tumorigenesis and the possible additional approach in current treatment strategies.

Clear cell odontogenic carcinoma of maxilla: A case report and mini review.

Clear cell odontogenic carcinoma is a rare odontogenic tumor occurring predominantly in posterior mandible during 5(th)-7(th) decades with a female predilection. It is a potentially aggressive tumor, capable of frequent recurrences and loco-regional and distant metastases. Till date, only 73 cases have been reported in the literature. Current case is of a 55-year-old woman with tumor mass extending from canine to molar region on the left maxillary arch. Being locally aggressive tumor with the capacity to metastasize, it demands to be distinguished from other primary and metastatic clear cell tumors of the oral and maxillofacial region. A brief compilation of the reported cases is being attempted in the current article to better understand the behavior of the tumor.

Emphasizing on heat shock protein 90's utility in head and neck squamous cell carcinoma treatment.

Heat shock protein 90 (Hsp90) a member of the heat shock proteins (HSPs) family, is an adenosine triphosphate dependent molecular chaperone protein, which integrates multiple oncogenic pathways. Clinically, encouraging results have been demonstrated in melanoma, acute myeloid leukemia, castrate refractory prostate cancer, non-small cell lung carcinoma and multiple myeloma using the first generation Hsp90 inhibitors. Hsp90 as the target of anticancer activity of geldanamycin sparked much interest in the inhibition of Hsp90 as a strategy for the treatment of cancer. Hsp90 inhibitors demonstrate rapid clearance from normal tissues and the blood compartment with prolonged retention in tumors making it a sought after modality for treating cancer. Our review emphasizes its role as anti-cancer therapy for head and neck squamous cell carcinoma.