Genetic polymorphisms of matrix metalloproteinases and their inhibitors in potentially malignant and malignant lesions of the head and neck

Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases that are capable of cleaving all extra cellular matrix (ECM) substrates. Degradation of matrix is a key event in progression, invasion and metastasis of potentially malignant and malignant lesions of the head and neck. It might have an important polymorphic association at the promoter regions of several MMPs such as MMP-1 (-1607 1G/2G), MMP-2 (-1306 C/T), MMP-3 (-1171 5A/6A), MMP-9 (-1562 C/T) and TIMP-2 (-418 G/C or C/C). Tissue inhibitors of metalloproteinases (TIMPs) are naturally occurring inhibitors of MMPs, which inhibit the activity of MMPs and control the breakdown of ECM. Currently, many MMP inhibitors (MMPIs) are under development for treating different malignancies. Useful markers associated with molecular aggressiveness might have a role in prognostication of malignancies and to better recognize patient groups that need more antagonistic treatment options. Furthermore, the introduction of novel prognostic markers may also promote exclusively new treatment possibilities, and there is an obvious need to identify markers that could be used as selection criteria for novel therapies. The objective of this review is to discuss the molecular functions and polymorphic association of MMPs and TIMPs and the possible therapeutic aspects of these proteinases in potentially malignant and malignant head and neck lesions. So far, no promising drug target therapy has been developed for MMPs in the lesions of this region. In conclusion, further research is required for the development of their potential diagnostic and therapeutic possibilities

Identification of BKCa channel openers by molecular field alignment and patent data-driven analysis

In this work, we present the first comprehensive molecular field analysis of patent structures on how the chemical structure of drugs impacts the biological binding. This task was formulated as searching for drug structures to reveal shared effects of substitutions across a common scaffold and the chemical features that may be responsible. We used the SureChEMBL patent database, which provides search of the patent literature using keyword-based functionality, as a query engine. The extraction of data of the BKCa channel openers and aligning them for molecular field similarity with newly designed structures did provide a probable validation method with accurate values. Therefore, in an attempt to increase the true positives, we report a procedure that functions on a multiple analyses modeled on molecular field similarity and common sub-structural search with consensus scoring and high confidence values to obtain greater accuracy during conventional virtual screening

Association of betel nut with carcinogenesis: revisit with a clinical perspective.

Betel nut (BN), betel quid (BQ) and products derived from them are widely used as a socially endorsed masticatory product. The addictive nature of BN/BQ has resulted in its widespread usage making it the fourth most abused substance by humans. Progressively, several additives, including chewing tobacco, got added to simple BN preparations. This addictive practice has been shown to have strong etiological correlation with human susceptibility to cancer, particularly oral and oropharyngeal cancers.The PUBMED database was searched to retrieve all relevant published studies in English on BN and BQ, and its association with oral and oropharyngeal cancers. Only complete studies directly dealing with BN/BQ induced carcinogenesis using statistically valid and acceptable sample size were analyzed. Additional relevant information available from other sources was also considered.This systematic review attempts to put in perspective the consequences of this widespread habit of BN/BQ mastication, practiced by approximately 10% of the world population, on oral cancer with a clinical perspective. BN/BQ mastication seems to be significantly associated with susceptibility to oral and oropharyngeal cancers. Addition of tobacco to BN has been found to only marginally increase the cancer risk. Despite the widespread usage of BN/BQ and its strong association with human susceptibility to cancer, no serious strategy seems to exist to control this habit. The review, therefore, also looks at various preventive efforts being made by governments and highlights the multifaceted intervention strategies required to mitigate and/or control the habit of BN/BQ mastication

Simplified flow chart of main events of BN induced carcinogenesis.

<p>The simplified flow chart is intended to highlight the complexity of BN and its constituents, and how they affect different metabolic components and systems of a cell to eventually lead to carcinogenic transformation. For more details see reviews in references 2–5.</p

Potentially malignant and malignant conditions associated with BN mastication.

<p>Prolonged mastication of BN/BQ eventually manifest itself in development of cancerous condition in the oral cavity of the masticator. Potentially malignant lesions in the oral cavity include lichenoid lesion(s) in the cheek (arrow) close of the site of mastication (A) or even tongue (not shown). At a late stage, lichenoid lesions lead to formation of Oral lichen planus (OLP), which is a type-IV contact hypersensitive type of potentially malignant lesion seen in the oral cavity of BN chewers (arrow) (B). A patient with history of prolonged use of BN alone (without tobacco) eventually shows development of a cancerous condition clinically known as Oral squamous cell carcinoma OSCC (arrow) in his right cheek (C), which was the primary site of BN mastication.</p

p53 associated alterations in betel nut (BN) and/or betel quid (BQ) associated human precancerous lesions/cancers.

<p>p53 associated alterations in betel nut (BN) and/or betel quid (BQ) associated human precancerous lesions/cancers.</p

Flow chart of included studies.

<p>The flow chart depicts the number of citations and resource materials that have been screened, excluded and/or included in the systematic review.</p