Tag Archives: wistar

Polymorphism, bacteria inside us help dictate inflammation, antitumor activity

The research reveals a more explicit role about the symbiotic relationship humans have with the various bacteria that inhabit our body and their role during tumor progression. “Our research indicates that interactions between the helpful bacteria in our bodies and immune cells at places situated away from tumors influence systemic responses in the host that alter how these tumors are able to progress,” said Jos� Conejo-Garcia, M.D., Ph.D., Associate Professor and Program Leader in the Tumor Microenvironment and Metastasis Program at The Wistar Institute and lead author of the study…

‘Rewired’ mice show signs of longer lives with fewer age-related illnesses

In healthy cells, TRAP-1 is an important regulator of metabolism and has been shown to regulate energy production in mitochondria, organelles that generate chemically useful energy for the cell. In the mitochondria of cancer cells, TRAP-1 is universally overproduced. The Wistar team’s report, which appears in the journal Cell Reports, shows how “knockout” mice bred to lack the TRAP-1 protein compensate for this loss by switching to alternative cellular mechanisms for making energy…

Cutting off all points of escape for melanoma cells

They found that resistant melanomas acquired a mutation in the MEK2 gene and multiple copies of the mutant BRAF oncogene, simultaneously decreasing the sensitivity to both drug targets. Their findings also uncovered a new potential target for melanoma therapy, a protein called S6K. Additionally, early studies in a laboratory model for melanoma show that a triple combination of drug inhibitors halted the growth of resistant tumors. "Melanoma tumors are particularly adept at rewiring themselves so that anticancer drugs lose their effectiveness, and we must continue to outthink the disease in order to block off all points at which it can evade therapy," said Jessie Villanueva, Ph.D., assistant professor in Wistar’s NCI-designated Cancer Center and member of The Wistar Institute Melanoma Research Center. …

Protein ‘motif’ crucial to telomerase activity

Their findings are published in the October 8 issue of the journal Structure, available online now. "Telomerase is a unique protein-RNA complex where the protein subunit uses its RNA component as a template to add identical fragments of DNA to the end of chromosomes," said Emmanuel Skordalakes, Ph.D., associate professor in the Gene Expression and Regulation program of Wistar’s NCI-designated Cancer Center. …

Diabetes drug points the way to overcoming drug resistance in melanoma

Their studies, conducted in cell and animal models of melanoma, demonstrate that the combined therapy could destroy a subset of drug-resistant cells within a tumor. "We have found that the individual cells within melanoma tumors are not all identical, and tumors contain a sub-population of cells that are inherently drug resistant, which accounts for the fact that advanced melanoma tumors return no matter how much the tumor is depleted," said Meenhard Herlyn, D.V.M., D.Sc., professor and director of Wistar’s Melanoma Research Center. "We found that these slow-growing, drug-resistant cells are marked by a high rate of metabolism, which makes them susceptible to diabetes therapeutics." "Our findings suggest a simple strategy to kill metastatic melanoma — regardless of cell type within the tumor — by combining anticancer drugs with diabetes drug," Herlyn said. "The diabetes drug puts the brakes on the cells that would otherwise repopulate the tumor, thus allowing the anticancer drug to be more effective." In the Cancer Cell article, the researchers describe how various anticancer drugs, including cisplatin and the targeted therapy vemurafenib, which targets melanomas with the BRAF mutation, become more effective when co-delivered with phenformin. …