Roles of the WHHL Rabbit in Translational Research on Hypercholesterolemia and Cardiovascular Diseases

Conquering cardiovascular diseases is one of the most important problems in human health. To overcome cardiovascular diseases, animal models have played important roles. Although the prevalence of genetically modified animals, particularly mice and rats, has contributed greatly to biomedical research, not all human diseases can be investigated in this way. In the study of cardiovascular diseases, mice and rats are inappropriate because of marked differences in lipoprotein metabolism, pathophysiological findings of atherosclerosis, and cardiac function. On the other hand, since lipoprotein metabolism and atherosclerotic lesions in rabbits closely resemble those in humans, several useful animal models for these diseases have been developed in rabbits. One of the most famous of these is the Watanabe heritable hyperlipidemic (WHHL) rabbit, which develops hypercholesterolemia and atherosclerosis spontaneously due to genetic and functional deficiencies of the low-density lipoprotein (LDL) receptor. The WHHL rabbit has been improved to develop myocardial infarction, and the new strain was designated the myocardial infarction-prone WHHL (WHHLMI) rabbit. This review summarizes the importance of selecting animal species for translational research in biomedical science, the development of WHHL and WHHLMI rabbits, their application to the development of hypocholesterolemic and/or antiatherosclerotic drugs, and future prospects regarding WHHL and WHHLMI rabbits

Phospho-TCTP as a therapeutic target of Dihydroartemisinin for aggressive breast cancer cells

Upregulation of Translationally Controlled Tumor Protein (TCTP) is associated with poorly differentiated aggressive tumors, including breast cancer, but the underlying mechanism(s) are still debated. Here, we show that in breast cancer cell lines TCTP is primarily localized in the nucleus, mostly in the phosphorylated form.The effects of Dihydroartemisinin (DHA), an anti-malaria agent that binds TCTP, were tested on breast cancer cells. DHA decreases cell proliferation and induces apoptotic cell death by targeting the phosphorylated form of TCTP. Remarkably, DHA enhances the anti-tumor effects of Doxorubicin in triple negative breast cancer cells resulting in an increased level of apoptosis. DHA also synergizes with Trastuzumab, used to treat HER2/neu positive breast cancers, to induce apoptosis of tumor cells.Finally, we present new clinical data that nuclear phospho-TCTP overexpression in primary breast cancer tissue is associated with high histological grade, increase expression of Ki-67 and with ER-negative breast cancer subtypes. Notably, phospho-TCTP expression levels increase in trastuzumab-resistant breast tumors, suggesting a possible role of phospho-TCTP as a new prognostic marker.In conclusion, the anti-tumor effect of DHA in vitro with conventional chemotherapeutics suggests a novel therapeutic strategy and identifies phospho-TCTP as a new promising target for advanced breast cancer

Vita del venerabile servo di Dio P. Sebastiano Valfré della Congregazione dell'Oratorio di Torino raccolta da'processi fatti per la sua beatificazione . Marino, Francesco <1692-1780>

Vita del venerabile servo di Dio P. Sebastiano Valfré della Congregazione dell'Oratorio di Torino raccolta da'processi fatti per la sua beatificazione .. In Torino : nella stamperia d'Alessandro Vimercati stampatore del S. Officio, 1748 XI, [1!, 416, 16 p., [1! c. di tav. : ritr. ; 4º Di Francesco Marino, cfr. Melzi, G. Anonime e pseudonime, v. 3, p. 237 Precede il front.: ritr. calcogr. di Sebastiano Valfré dis. e inciso da Carlo Gregori Segnatura: (croce)⁶ A-3F⁴ (ast)⁴ B⁴ Frontespizio stampato in rosso e nero Marca (due colombe appoggiate su una corona con due rami d'ulivo incrociati) sul frontespizio Iniz. e fregi xil Irregolarita nelle ultime segnature Var. B: etichetta a stampa a correggere il tit.: Vita del beato p.Sebastiano Valfrè ..