P53 nuclear stabilization is associated with <Emphasis Type="Italic">FHIT</Emphasis> loss and younger age of onset in squamous cell carcinoma of oral tongue

Background

Squamous cell carcinoma of tongue (SCCT) is expected to harbor unique clinico-pathological and molecular genetic features since a significant proportion of patients are young and exhibit no association with tobacco or alcohol.

Methods

We determined P53, epidermal growth factor receptor, microsatellite instability, human papilloma virus infection and loss of heterozygosity status at several tumor suppressor loci in one hundred and twenty one oral SCCT (SSCOT) samples and analyzed their association with clinico-pathological features and patient survival.

Results

Our results revealed a significantly higher incidence of p53 nuclear stabilization in early (as against late) onset SCCOT. FHIT loss was significantly associated with p53 nuclear stabilization and the association was stronger in patients with no history of tobacco use. Samples harboring mutation in p53 DNA binding domain or exhibiting p53 nuclear stabilization, were significantly associated with poor survival.

Conclusion

Our study has therefore identified distinct features in SCCOT tumorigenesis with respect to age and tobacco exposure and revealed possible prognostic utility of p53.

     

Design,synthesis and biological activity evaluation of novel pefloxacin derivatives as potential antibacterial agents

A facile and efficient method for the synthesis of novel derivatives of pefloxacin hydrazone via condensation of various aldehydes and pefloxacin acid hydrazide using conventional as well as solvent-free microwave irradiation methods was reported. The biological activity of these compounds was screened using array of techniques and found to exhibit promising broad spectrum of antibacterial activity against Gram-positive and Gram-negative bacteria, moderate antimycobacterial activity against Mycobacterium smegmatis and moderate antifungal activity opposed to Aspergillus clavatus and Candida albicans. Cytotoxic assay of the title compounds was evaluated against human Pc-3 cancer cell lines, and interestingly, very good anticancer properties were shown by the compounds. To explore the binding mode of the compounds and understand the key active site residues with Staphylococcus aureus DNA gyrase, a molecular docking study has been performed. The results of the docking studies of the reported derivatives were quite promising and manifested strong non-bonded interactions with DNA Gyrase.