Molecular docking analysis of cetuximab with NOTCH signalling pathway targets for oral cancer.

Notch signaling is an evolutionarily ancient mechanism which intricated in cell-cell communication and it plays a crucial role in various developments in malignancies. Inactivating mutations of NOTCH targets are present in about 10 % of cases of squamous cell carcinoma of the skin, oral cavity, and esophagus that rendering it one of the most frequently mutated genes in oral squamous cell carcinoma. Therefore, it is of interest to document the molecular docking analysis of cetuximab with the NOTCH signaling targets such as NOTCH1, NICD, and HES1. These results suggest that targeting the NOTCH signaling with cetuximab might leads to the better outcome for suppression of invasion and metastasis in oral carcinoma.

Molecular docking analysis of proflavin with the Wnt pathway targets for OSCC.

Wnt signaling pathway plays a critical role in tumor progression and metastasis of various cancer types. Therefore, it is of interest to document the molecular docking analysis of proflavin with the Wnt pathway targets (GSK3ß, ß-catenin, and VIM) for oral squamous cell carcinoma (OSCC). These results suggest that targeting the wnt signaling downstream targets with proflavine might leads to the better outcome for therapeutic outcome for the inhibition of invasion and metastasis in oral squamous cell carcinoma.

Molecular docking analysis of imiquimod with the TGF-ß targets for oral carcinoma.

TGF-ßsignalling pathway is the main signalling pathways that regulate various biological functions such as cell proliferation, apoptosis, metabolic dysregulation, and metastasis in many cancer cells. Previous studies have elaborated the role of TGF-ßsignalling targets have a significant regulatory function in various cancers. Moreover targeting the epithelial to mesenchymal transition markers in oral squamous cell carcinoma not yet elucidated. Therefore, it is of interest to document the molecular docking analysis of TGF-ßsignalling pathway targets such as Smad2, GATA2 and MAFG with imiquimod. These results suggest that targeting the TGF-ßsignaling pathway downstream targets with imiquimod might leads to an improved outcome as potential therapeutic options in oral carcinoma.

Transcription factors: a potential therapeutic target in head and neck squamous cell carcinoma.

Squamous cell carcinoma is the most common histopathological type of head and neck cancer; it often spreads to and involves the cervical lymph nodes. The tumorigenesis of head and neck squamous cell carcinoma (HNSCC) is a multistep process mediated by various transcription factors involved in progression and metastasis. Alterations in transcription factors such as FOSL1, YY1, FOXD1 and NF-κB have been associated with increased cell proliferation, cell migration and poor survival rates in patients with HNSCC. Stimulation of the NF-κB pathway results in transcriptional activation of other target genes associated with cell survival and proliferation. Understanding these molecular mechanisms will helps us develop new treatment strategies that target these transcription factors and may eventually decrease the morbidity and mortality associated with HNSCC.

Significance of tumour budding and invasive characteristics in grading of oral squamous cell carcinoma.

Background: Tumour budding has been recognized as a morphologic marker of tumour invasion. Invasive characteristics such as depth of invasion, mode of invasion and worst pattern of invasion are potentially powerful parameters predicting the regional metastasis. Aim: This study was done to understand the significance of tumour budding and various characteristics of invasion and their impact on grading of oral squamous cell carcinoma. Materials and Methods: An immunohistochemical study was performed on tissue sections obtained from 34 paraffin-embedded blocks of clinically and histologically diagnosed cases of oral squamous cell carcinoma. The sections were stained with pan cytokeratin and observed under high power magnification. Results: Tumour budding and the invasive patterns were found to be significant in OSCC. A proposed grading system based on tumour budding and cell nest was found to have a significant correlation with the WHO grading system. Conclusion: This study demonstrated the importance of using tumour buds as an additional parameter in the grading system and also assessed the importance of invasive patterns, cellular atypia and stromal contents in OSCC.

Evaluation of salivary MMP-9 in oral squamous cell carcinoma and oral leukoplakia using ELISA.

Background: Cancer of the lip and the oral cavity is collectively the sixth most common malignancy worldwide, out of which 90% are oral squamous cell carcinomas (OSCCs). Oral cancer survival rates depend mainly upon the stage in which it is diagnosed. Successful early detection would eventually increase the survival rate. OSCCs may be preceded by potentially malignant disorders (PMDs) that are characterised by visible clinical changes in the oral mucosa. Correct diagnosis and timely treatment of PMDs may help prevent malignant transformation in oral lesions. Oral leukoplakia (OL) is the best known potentially malignant disorder of the oral mucosa with a malignant transformation rate of about 3% to 33%. Tumour markers in saliva have emerged as a new diagnostic tool in the early detection of oral cancer. Matrix metalloproteinase 9 (MMP-9) is a gelatinase which plays an important role in tumourogenisis. The present study was done to evaluate the salivary levels of MMP-9 in OSCC and oral leukoplakia patients using enzyme-linked immunosorbent assay (ELISA). Materials and Methods: The study was conducted among 102 subjects, which included 34 OSCC patients (group I), 34 OL patients (group II), and 34 healthy subjects (group III). Unstimulated saliva was collected by the passive drooling method from all the study subjects during the study period, centrifuged, and stored at -80°C. The salivary MMP-9 was estimated in mg/ml using the sandwich ELISA technique. The data were analysed using a statistical software package, EZR. One-way analysis of variance was used for the comparison of salivary MMP-9 levels in OSCC, OL, and normal oral mucosa. Scheffe's multiple comparison was carried out to compare salivary MMP-9 levels among the different histological grades of OSCC and oral epithelial dysplasia. For all statistical interpretations, P ≤ 0.0 was considered the threshold for statistical significance. Results and Conclusion: The mean salivary MMP-9 level in OSCC, OL, and normal oral mucosa was 50.9 ± 5.7 ng/ml, 31.6 ± 6 ng/ml, and 16.2 ± 4.8 ng/ml, respectively. Patients with OSCC had significantly higher levels of salivary MMP-9 when compared to OL and normal mucosa. Higher levels of salivary MMP-9 were observed in poorly differentiated OSCC when compared to well and moderately differentiated OSCCs. The salivary MMP-9 was higher in severe oral epithelial dysplasia when compared to mild and moderate oral epithelial dysplasias. As malignant transformation rates are higher in patients with severe oral epithelial dysplasia when compared to mild and moderate oral epithelial dysplasia, salivary MMP-9 could be considered as a surrogate marker of malignant transformation.