Glutaminases as a Novel Target for SDHB-Associated Pheochromocytomas/Paragangliomas
CANCERS
Authors: Sarkadi, Balazs; Meszaros, Katalin; Krencz, Ildiko; Canu, Letizia; Krokker, Lilla; Zakarias, Sara; Barna, Gabor; Sebestyen, Anna; Papay, Judit; Hujber, Zoltan; Butz, Henriett; Darvasi, Otto; Igaz, Peter; Doczi, Judit; Luconi, Michaela; Chinopoulos, Christos; Patocs, Attila
Abstract
Pheochromocytoma/paragangliomas (Pheo/PGL) are rare endocrine cancers with strong genetic background. Mutations in the SDHB subunit of succinate dehydrogenase (SDH) predispose patients to malignant disease with limited therapeutic options and poor prognosis. Using a host of cellular and molecular biology techniques in 2D and 3D cell culture formats we show that SDH inhibition had cell line specific biological and biochemical consequences. Based on our studies performed on PC12 (rat chromaffin cell line), Hela (human cervix epithelial cell line), and H295R (human adrenocortical cell line) cells, we demonstrated that chromaffin cells were not affected negatively by the inhibition of SDH either by siRNA directed against SDHB or treatment with SDH inhibitors (itaconate and atpenin A5). Cell viability and intracellular metabolite measurements pointed to the cell line specific consequences of SDH impairment and to the importance of glutamate metabolism in chromaffin cells. A significant increase in glutaminase-1 (GLS-1) expression after SDH impairment was observed in PC12 cells. GLS-1 inhibitor BPTES was capable of significantly decreasing proliferation of SDH impaired PC12 cells. Glutaminase-1 and SDHB expressions were tested in 35 Pheo/PGL tumor tissues. Expression of GLS1 was higher in the SDHB low expressed group compared to SDHB high expressed tumors. Our data suggest that the SDH-associated malignant potential of Pheo/PGL is strongly dependent on GLS-1 expression and glutaminases may be novel targets for therapy.
Impact of dividend policy on corporate value: Experiment in Vietnam
INTERNATIONAL JOURNAL OF FINANCE & ECONOMICS
Authors: Hung Ngoc Dang; Van Thi Thuy Vu; Xuan Thanh Ngo; Ha Thi Viet Hoang
Abstract
The paper examines the impact of dividend policy on corporate value. Data collection is the result of listed companies on the Vietnamese stock market in the period of 2006-2017 with 2,278 observations. Using the general least square (GLS) approach, the authors have identified three factors that have a positive and significant impact on corporate value: dividend payout, profitability, and corporate sizes; and one factor that has a negative impact on corporate value is the degree of financial leverage. The study found that dividend policy has a significant impact on the corporate value of companies that implement a higher dividend payout policy. Conversely, firms that do not pay dividends or pay low dividends do not experience a significant impact of dividend policy on corporate value. The results of the study will be meaningful for businesses on dividend policy implementation.