Oncogene-induced senescence (OIS) explains the phenomenon of cellular senescence triggered by the action of oncogenes. It is a mechanism adopted by a cell to inhibit progression of benign tumors into malignancy, occurs in premalignant lesions, and is almost never present in malignant lesions. BRAF mutations occur in about 40-45% of all papillary thyroid carcinomas (PTCs) and of which 99.7% is the BRAFV600E mutation. A unique phenotype of the BRAFV600E mutation is the upregulation of the thyroid-stimulating hormone receptor (TSHR) on thyrocyte membranes. Despite the overexpression of the receptor, BRAFV600E cells undergo cell cycle arrest leading to OIS via a negative feedback signaling mechanism. A simultaneous increase in serum thyroid-stimulating hormone (TSH) in response to hypothyroidism (common in autoimmune diseases such as Hashimoto's thyroiditis) would cause senescent tumor cells to overcome OIS and proceed towards malignancy, hence showing the importance of TSH/TSHR signaling in the development of PTCs. Increase in TSH/TSHR signaling triggers an increase in levels of downstream enzymes such as manganese superoxide dismutase (MnSOD) and dual-specific phosphatase 6 (DUSP6) which eventually results in the production of oncogenic proteins such as c-Myc. Therefore, the detection of these genetic alterations as effective biomarkers for premalignant lesions of PTC is important in clinical settings and techniques such as polymerase chain reaction-mediated restriction fragment length polymorphism (PCR-RFLP) and real-time PCR can be used to detect the BRAFV600E point mutation and overexpression of TSHR, MnSOD, and DUSP6, respectively.
This paper reports the histopathological responses of the gill, liver and tail muscle tissues in tadpoles of the Asian Common Toad Duttaphrynus melanostictus (Schneider, 1799) exposed to chlorpyrifos a common organophosphorus pesticide. Tadpoles of Gosner stages 24-26 were continuously exposed to low, mid and high (500, 1000 and 1500 µgl -1 ) concentrations of chlorpyrifos for two weeks. Histological alterations in the tissues of the surviving larvae were microscopically examined both at the end of the exposure period and after a week following the final exposure. Several histological alterations were noted in the gills, liver and tail muscles of the larvae exposed to 1500 µgl -1 of chlorpyrifos. The gills of exposed larvae showed architectural distortion resulting from reduced primary and secondary gill lamellae and blood vessels, and alterations in the gill epithelium. In the liver sinusoidal congestion and dilation, cytoplasmic vacuolation and changes in hepatocytes such as hyperchromatic nuclei and nuclear fragmentation were observed. The tail muscle tissue suffered from severe atrophy and myotomal disintegration. Although histological alterations in the gill and liver tissues were noted only at the high concentration, changes in the muscle tissue i.e. muscle degeneration and atrophy, were apparent at both low and mid concentrations. The degree of damage in surviving larvae in a week following the final exposure was lower than that observed during the exposure, probably indicating recovery or resistance. The findings of the present study emphasize the need to investigate possible sublethal damage induced by pesticides in amphibians inhabiting agricultural habitats.
Objectives: To determine the validity of Fine needle aspiration cytology (FNAC) in diagnosing thyroid neoplasms and to identify the causes of false positive and negative results.
Method:Thyroid FNACs of 100 patients with subsequent histology were analysed. The diagnostic categories used included Thy 1 to Thy 5. Thy 3 was subdivided into Thy 3a and Thy 3b depending on the presence or absence of features suggestive of a follicular neoplasm. Histology results were categorized as neoplastic or non neoplastic. Results of FNACs were correlated with histology.Results: FNAC predicted the presence of neoplasms with a sensitivity of 77.7.8%, specificity of 83% and had a diagnostic accuracy of 90%. The false negative rate was 8% and the cause was non diagnosis of impalpable papillary micro carcinomas.Conclusion: Sensitivity could be increased by ultrasound scan guided aspiration in non palpable lesions. Sub categorization of Thy 3 into a and b increases the specificity of FNAC in detecting thyroid malignancy.
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