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Archive - Feb 17, 2020

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Novel Formulation Permits Use of Toxin from Rattlesnake Venom to Treat Chronic Pain

Crotoxin, extracted from the venom of the South American rattlesnake Crotalus durissus terrificus, has been studied for almost a century for its analgesic, anti-inflammatory, and antitumor activities and as an even more powerful muscle paralyzer than botulinum toxin. However, the toxicity of crotoxin limits its medicinal use. A new study, published online on November 20, 2019, by Brazilian researchers in the journal Toxins, shows that crotoxin's therapeutic effects can be enhanced and its toxicity reduced when it is encapsulated in nanostructured SBA-15 silica, a material originally developed for use in vaccine formulations. The open-access Toxins article is titled “Crotoxin Conjugated to SBA-15 Nanostructured Mesoporous Silica Induces Long-Last Analgesic Effect in the Neuropathic Pain Model in Mice. The study was conducted under the aegis of Brazil's National Science and Technology Institute (INCT) on Toxins, one of the INCTs supported by FAPESP (São Paulo Research Foundation) in São Paulo State in partnership with the National Council for Scientific and Technological Development (CNPq), an agency of the Brazilian government. The INCT's principal investigator is Osvaldo Augusto Sant'Anna, PhD. The study was part of the doctoral research of Morena Brazil Sant'Anna, whose thesis advisor is Gisele Picolo, PhD. Dr. Picolo herself was the principal investigator for a project on the same topic. Researchers Flavia Souza Ribeiro Lopes and Louise Faggionato Kimura participated in the study, which was performed at Butantan Institute in São Paulo. Dr.

HIF-2α Is Pivotal for Progression of Clear Cell Renal Cell Carcinomas (ccRCC) and Can Be Disabled by New Experimental Drug, PT2385

An experimental drug already shown to be safe and to help some patients with clear cell renal cell carcinoma (ccRCC), a deadly form of kidney cancer, effectively disables its molecular target. The finding from a team of researchers at the UT Southwestern Medical Center’s Kidney Cancer Program, was published in the February 14, 2020 issue of Clinical Cancer Research, reveals a weakness in this cancer that could be further exploited with other targeted treatments in the future. The article is titled “HIF-2 Complex Dissociation, Target Inhibition, and Acquired Resistance with PT2385, a First-in-Class HIF-2 Inhibitor, in Patients with Clear Cell Renal Cell Carcinoma.” Approximately 70,000 new cases of ccRCC are diagnosed every year in the U.S. The five-year life expectancy after diagnosis is low compared with other cancers, at about 10-12 percent. Unlike many other forms of cancer, ccRCC doesn’t respond to chemotherapy or conventional radiation. When study lead author James Brugarolas, MD, PhD, Professor of Internal Medicine (Hematology/Oncology) and Director of the Kidney Cancer Program at UT Southwestern, began his career two decades ago, only one medication was approved to treat this cancer. There are now over a dozen approved drugs for ccRCC; however, says Dr. Brugarolas, each offers only a modest effect on survival and comes with a host of side effects. Searching for better pharmaceuticals to fight this cancer, researchers at the Kidney Cancer Program focused on a protein known as hypoxia-inducible factor 2α (HIF-2α), which investigators at UTSW first discovered and described in the late 1990s. HIF-2α is a target of a tumor suppressor protein called von Hippel-Lindau (VHL) protein that’s characteristically inactivated in most cases of ccRCC.