Hyperpolyploidization of hepatocyte initiates preneoplastic lesion formation in the liver

Hepatocellular carcinoma (HCC) is the most predominant primary malignancy in the liver. Genotoxic and genetic models have revealed that HCC cells are derived from hepatocytes, but where the critical region for tumor foci emergence is and how this transformation occurs are still unclear. Here, hyperpolyploidization of hepatocytes around the centrilobular (CL) region is demonstrated to be closely linked with the development of HCC cells after diethylnitrosamine treatment. We identify the CL region as a dominant lobule for accumulation of hyperpolyploid hepatocytes and preneoplastic tumor foci formation. We also demonstrate that upregulation of Aurkb plays a critical role in promoting hyperpolyploidization. Increase of AURKB phosphorylation is detected on the midbody during cytokinesis, causing abscission failure and hyperpolyploidization. Pharmacological inhibition of AURKB dramatically reduces nucleus size and tumor foci number surrounding the CL region in diethylnitrosamine-treated liver. Our work reveals an intimate molecular link between pathological hyperpolyploidy of CL hepatocytes and transformation into HCC cells.

Effects of a Long-Term Administration of Aqueous Extract of Prunella vulgaris L. on Survival, Spontaneous Thyroid Carcinoma and Neoplastic C-cell Hyperplasia in Rats

Background: The continued global rise in thyroid carcinoma calls for alternative prevention and treatment strategies. Prunella vulgaris L. (PV) is a herbaceous plant with a medicinal property in the treatment of thyroid gland dysfunction, but its influence on thyroid carcinoma is unclear so far. This study was designed to investigate the effects of aqueous extract of PV on survival, spontaneous thyroid carcinoma and its preneoplastic lesion in rats.Methods: A total of 552 Wistar rats (half female and half male) were randomly assigned into 4 groups and given one of the following diets for 24 months: chow diet (control), 2.5 (low), 8.25 (middle) and 25 (high) g/kg bw PV diets. After intervention, serum metabolic parameters including indicators of liver and renal function, glucose and lipid profiles were measured. Histological examination was conducted to confirm the types of thyroid carcinoma and its preneoplastic lesion. Results: After intervention, serum aspartate transaminase of male rats in high PV group decreased significantly. No statistical differences among groups in terms of survival, body weight and other metabolic parameters were detected. In the control, low, middle and high PV groups, 14, 14, 15 and 8 rats developed thyroid carcinoma, respectively. Medullary thyroid carcinoma (MTC) emerged as the most common histological type in both sexes. Although PV failed to decrease risk of total thyroid carcinoma or each histological type, the incidence rates of neoplastic C-cell hyperplasia (CCH, a preneoplastic lesion of hereditary MTC) in PV groups were lower than that of control, and the lowest was observed in high PV group, manifesting as 5.25-time decrease in female rats and 5.5-time decrease in male rats.Conclusion: Our results suggested for the first time that, a long-term administration of aqueous extract of PV decreased the incidence of neoplastic CCH without impairing survival and metabolic parameters.

Hyperpolyploidization of hepatocyte initiates preneoplastic lesion formation in the liver

ABSTRACTHepatocellular carcinoma (HCC) is the most predominant primary malignancy in the liver. Genotoxic and genetic models have revealed that HCC cells are derived from hepatocytes, but where the critical region for tumor foci emergence is and how this transformation occurs are still unclear. Here, hyperpolyploidization of hepatocytes around the centrilobular (CL) region was demonstrated to be closely linked with the development of HCC cells after diethylnitrosamine treatment. We identified the CL region as a dominant lobule for accumulation of hyperpolyploid hepatocytes and preneoplastic tumor foci formation. We also demonstrated that upregulation of Aurkb plays a critical role in promoting hyperpolyploidization. Increase of AURKB phosphorylation was detected on the midbody during cytokinesis, causing abscission failure and hyperpolyploidization. Pharmacological inhibition of AURKB dramatically reduced nucleus size and tumor foci number surrounding the CL region in diethylnitrosamine-treated liver. Our work reveals an intimate molecular link between pathological hyperpolyploidy of CL hepatocytes and transformation into HCC cells.

Prostatic intraepithelial neoplasia- the story evolves

Prostatic intraepithelial neoplasia is preneoplastic lesion described from early of this 20th century. PIN includes a spectrum of features ranging from low grade to high grade neoplasia. The studies are focused on their influence to predict the occurence of prostatic carcinoma. This review analyses the various development in the identification and differentiation of PIN and their clinical implication.