ABSTRACT
Ameloblastoma is a non-cancerous but aggressive oral tumor emerging from odontogenic epithelial tissue involved during odontogenesis. Since there is lack in unravelling the complete molecular pathogenesis of ameloblastoma, chemotherapy is less attempted and a lot of disagreement over the optimal treatment option. Hence, till date, wide surgical resection is considered to be the reliable treatment for ameloblastoma. The Neurotrophin Signaling pathway plays an important role in neuron signaling and it is closely related with the MAPK pathway, which on the other hand regulated cell differentiation, apoptosis, proliferation, plasticity and survival. Protein- Protein Interaction analysis was analysed with STRING tool using WNL value, identified that CTNNB1, HRAS, NGFR, NGFR, and SORT1 having high interacting with BDNF, NT4, p75NTR, NGF, and NT3. The results of ontology analysis revealed that Neurotrophin signaling pathway is associated with Cell surface receptor signaling pathway, regulation of cell differentiation, regulation of development process, EGFR tyrosine kinase inhibitor resistance, MAPK signaling pathway, PI3K-Akt signaling pathway and Ras signaling pathway leading to pathogenesis involving genes. Further, clustering coefficient values of proteins BDNF, NT4, p75NTR, NGF & NT3 were identified as 0.627, 0.708, 0.367, 0.644 & 0.415. The results of molecular docking studies revealed among the selected ligands Methyl-É£-oresellinate, N-(4-Hydroxy-phenyl)-2-phenyl-N-phenylacetyl-acetamide, Atranorin and Oresellinate exhibited high binding affinity with selected protein. The key genes involved in Neurotrophin signaling pathway leading to ameloblastoma pathogenesis is revealed, which are closely associated with cell differentiation, cell proliferation, pro-apoptosis, and pro-survival regulations. Further it can be concluded that Neurotrophin signaling pathway could be one of the promising pathway to tailor the targeted drug therapy for Ameloblastoma treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00223-2.
ABSTRACT
BACKGROUND: Tobacco is one of the main reasons behind the occurrence of oral cancer. Oral cancer, even though being the tenth most common cancer in the world, gets diagnosed at an advanced stage and ends up with poor prognosis. So early diagnosis is the need of the hour. Our study aimed to evaluate the genotoxic changes in patients with different tobacco habits using buccal exfoliated cells. METHODS: Buccal smears were taken from smokers (30), smokeless tobacco users (30), combined tobacco users (30) and controls (30) with clinically normal oral mucosa. All the smears were stained with Papanicolaou stain and Feulgen stain and viewed under light microscope for the evaluation of mean number of micronuclei, mean micronuclei per cell, frequency of cells showing micronuclei, nuclear area, cytoplasmic area, nuclear-cytoplasmic ratio. RESULTS: Mean number of micronuclei, mean micronuclei per cell, frequency of cells showing micronuclei, and nuclear area were significantly increased in tobacco users than controls, especially in combined tobacco users. Nuclear-cytoplasmic ratio was increased and cytoplasmic area was decreased in tobacco users than controls. CONCLUSION: Tobacco in any consumable form is genotoxic. Smoking and smokeless tobacco, when consumed together, synergistically causes higher genetic damage. Different tobacco habits have different deleterious effects on oral mucosa, and these effects are more pronounced when the patients have combined habits. So, detecting the genotoxic changes through exfoliative cytology can be used as a simple yet reliable marker for early detection of carcinogenesis.
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Subject(s)
Micronuclei, Chromosome-Defective , Micronucleus Tests , Mouth Mucosa/cytology , Mutagenicity Tests , Tobacco Use Disorder/pathology , Adult , Case-Control Studies , Female , Humans , Male , Mouth Neoplasms/genetics , Mouth Neoplasms/pathologyABSTRACT
INTRODUCTION: Ameloblastoma holds a unique position among benign tumours by its locally destructive and invasive nature. Recently improvised molecular techniques helped researchers to unravel the myth behind such biologic behaviour. Though interesting findings have been delivered, the rhythmic correlation regarding the exact mechanism still remains lacking. Neurotrophins and their receptor mediated pathways play a crucial role in survival, death and differentiation of many neuroectoderm derived cells. With this background, the study has been aimed to investigate the expression of p75-NTR (Neurotrophin Receptor) in follicular and plexiform ameloblastoma. AIM: To analyze the immunohistochemical expression pattern of p75-NTR in ameloblastoma and to compare the immunohistochemical expression pattern of p75-NTR among the histological types of ameloblastoma, follicular and plexiform patterns. MATERIALS AND METHODS: Total 22 ameloblastomas (12 follicular, 10 plexiform) were immuno-stained with anti-human p75-NTR mouse IgG monoclonal antibody and the pattern of staining is statistically analyzed. RESULTS: Only 11 (10 follicular, 1 plexiform) out of 22 ameloblastomas showed immuno-reactivity to p75-NTR. In ameloblastoma, only the peripheral pre-ameloblast like tall columnar cells showed reactivity whereas the stellate reticulum-like cells were immuno-negative. The staining pattern was membranous in the immuno-reactive cells. The results were studied with the downstream pathways from the literature and a possible mechanism has been proposed. CONCLUSION: The expression pattern of p75-NTR was found to be more in follicular ameloblastoma than plexiform.
