The family of human matrix metalloproteinases (MMPs) comprises several tightly regulated classes of proteases. These enzymes and their specific inhibitors play important roles in tumor progression and the metastatic process by facilitating extracellular matrix (ECM) degradation. As scientific understanding of the MMPs has advanced, therapeutic strategies focusing on blocking these enzymes by MMP inhibitors (MMPIs) have rapidly developed. This paper reviews MMPs in detail. Their perspectives in therapeutic intervention in cancer are also mentioned.
Matrix metalloproteinases (MMPs) are a family of zinc dependent extracellular matrix (ECM) remodelling endopeptidases having the ability to degrade almost all components of extracellular matrix and implicated in various physiological as well as pathological processes. Carcinogenesis is a multistage process in which alteration of the microenvironment is required for conversion of normal tissue to a tumour. Extracellular matrix remodelling proteinases such as MMPs are principal mediators of alterations observed in the microenvironment during carcinogenesis and according to recent concepts not only have roles in invasion or late stages of cancer but also in regulating initial steps of carcinogenesis in a favourable or unfavourable manner. Establishment of relationships between MMP overproduction and cancer progression has stimulated the development of inhibitors that block proteolytic activity of these enzymes. In this review we discuss the MMP general structure, classification, regulation roles in relation to hallmarks of cancer and as targets for therapeutic intervention.
Oral dysplasia is a potentially precancerous lesion diagnosed histologically. While the risk of progression is associated with histological grade, it is currently impossible to predict accurately which lesions will progress. Although most oral pathologists recognize and accept the criteria for grading epithelial dysplasia based on architectural and cytological changes, there can be considerable interexaminer and intraexaminer variation in the assessment of the presence or absence and the grade of oral epithelial dysplasia. This article reviews the alterations, criteria, different grading systems and the markers used for assessing the malignant transformation of epithelial dysplasia.
The oral cavity constitutes a site of low prevalence for metastasis of malignant tumors. However, oral metastasis of a renal origin is relatively more common and represents 2% of all cancer deaths. Renal cancer may metastasize to any part of the body, with a 15% risk of metastasis to the head and neck regions, and pose one of the greatest diagnostic challenges in medical sciences. Approximately 25% of patients have a metastatic disease at initial assessment, which is often responsible for initiating the diagnosis in the first place. Here we present a review of literature of renal cell carcinoma along with a case of gingival metastasis.
Context: The bcl-2 proto-oncogene was discovered at the chromosomal breakpoint of t (14;18) found in follicular lymphoma. Histological changes in dysplasia are considered the earliest signs preceding the progression into squamous cell carcinoma. Serving as critical regulators of apoptotic pathways, bcl-2 prohibits programmed cell death and subsequently assists in uncontrolled neoplastic growth. Settings and Design: This study included 48 cases, eight each of epithelial dysplasia and squamous cell carcinoma. Immunohistochemical staining using bcl-2 antibody was performed and different histological parameters were correlated with bcl-2 positive cells in all the cases. Materials and Methods: All 3 μm thick sections were stained with bcl-2 antibody. After identifying four representative fields at 40x, their images were obtained for assessment of bcl-2 labelled cells and their intensity along with different histological parameters in all the cases. Statistical Analysis: The differences between different histological parameters were analysed using the Anova test, post hoc test and Bonferroni test. Pearson's Chi-square test was carried out to determine the level of correlation between the bcl-2 positive cells in both epithelial dysplasia and oral squamous cell carcinoma cases. Conclusion: Sequential increase in the bcl-2 expression was observed in increasing grades of epithelial dysplasia, whereas bcl-2 expression was significantly decreased in ascending stages of squamous cell carcinoma thus, suggesting a possible role of bcl-2 in disease progression from premalignancy to malignancy.
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