23^rd International Conference on
Cancer Research & Pharmacology

Biography:

Hiroshi Kobayashi received his Ph.D. in Biochemistry from University of Tokyo in 1974. After his postdoctoral training at Colorado University Medical Center, he started to study adaptation strategies of microorganisms to acidic environments at Chiba University in 1978. His research has been focused on mammalian cell functions under acidic conditions from 1996 at Graduate School of Pharmaceutical Sciences, Chiba University. His current challenge is to develop cancer chemotherapy specific to acidic nests. He retired in March 2012 and is now a professor emeritus at Chiba University. He works as an associate editor of International Immunopharmacology published by Elsevier B.V. from 2014.

Abstract:

Acidity in cancer nests has been investigated for over 80 years, but anti-cancer chemotherapy specific to acidic microenvironments has not been developed. Acidification of cancer nests is generally less than 2 pH units, and it has been argued that intracellular pH is not changed due to the cytosolic pH homeostasis. However, recent studies have revealed that cytosolic pH decreases with the acidification of extracellular environments, although the pH change in cytosolic space is less than that in the surroundings. For example, cytosolic pH values were reported to be 7.4 and 6.9 in media with a pH of 7.4 and 6.5, respectively. In another report, cytosolic pH values were 7.4 and 6.8 in media with a pH of 7.4 and 6.2, respectively. Many researchers had thought that such small pH changes do not affect cellular metabolisms, but the expression of many genes was found to increase under acidic conditions. These data suggest that some metabolic activities alter as the acidification of cancer nests, leading us to develop anti-cancer chemotherapy specific to acidic nests. Until now, four drugs have been found to have high efficacy to inhibit cancer progression under acidic conditions. These acidosis-dependent drugs have a great advantage to be less effective in normal tissues whose pH is slightly alkaline. On the basis of these findings, I would like to discuss the innovative chemotherapy specific to cancers progressing in acidified nests.

Biography:

Antonio Gómez-Muñoz received his Ph.D in Biochemistry from the University of the Basque Country, Bilbao (Spain) in 1988. He achieved postdoctoral training at the University of Alberta in Edmonton (Canada) from 1988 to 1994. He then accepted a Research position at the Spanish Research Council (CSIC) from 1995 to 1996. From 1997 to 1998, he worked as Research Associate at the University of British Columbia (Vancouver, Canada). Since then, he has been working at the University of the Basque Country in Bilbao (Spain), where he is currently Professor of Biochemistry and Molecular Biology. He belongs to the Editorial Advisory Board of various scientific journals. Since 2001, he is a member of the International Advisory Committee of the Charleston Ceramide Conference, and since 2005, he is permanent Co-chair of the European Sphingolipid Club. His research interest is on the regulation of lipid metabolism and signalling, and in recent years he focused on the targeting of sphingolipid metabolites and enzymes with the aim of developing new strategies for prevention of disease.

Abstract:

Pancreatic cancer is the fourth leading cause of cancer mortality with a 5-year survival rate of only 6%. This aggressive disease is characterized by invasiveness, rapid progression and profound resistance to treatment. Using an in vitro cell migration assay we have found that ceramide 1-phosphate (C1P) enhances human pancreatic cancer cell migration and invasion potently and that this effect is completely abolished by pertussis toxin (PTX), suggesting the participation of a Gi protein-coupled receptor in this process. Activation of the C1P receptor caused phosphorylation and activation of ERK1-2 and Akt, and inhibition of these kinases abolished C1P-stimulated cell migration/invasion. We have also observed that human pancreatic cancer PANC-1 and Mia PaCa-2 cells migrate spontaneously. Contrary to the effect of C1P, spontaneous cell migration was insensitive to treatment with PTX. Investigation into the mechanisms responsible for spontaneous migration of the pancreatic cancer cells revealed that ceramide kinase (CerK) is a key enzyme in the regulation of this process. In fact, inhibition of CerK activity with the selective inhibitor NVP-231, or treatment with specific CerK siRNA to silence the gene encoding this kinase, potently reduced migration of the pancreatic cancer cells. By contrast, overexpression of CerK stimulated cell migration, an action that was concomitant with prolonged phosphorylation of ERK1-2 and Akt, which are kinases involved in C1P-stimulated cell migration/invasion, in a PTX independent manner. It can be concluded that the axis CerK/C1P plays a critical role in pancreatic cancer cell migration/invasion, and that targeting CerK expression or activity may be a relevant factor for controlling pancreatic cancer cell dissemination.

Biography:

William T. Beck, PhD, is University Distinguished Professor and former Head of the Department of Biopharmaceutical Sciences in the College of Pharmacy at the University of Illinois at Chicago. His research efforts have focused on understanding the molecular and genetic mechanisms of anticancer drug action and tumor cell resistance to anticancer drugs. His current research focuses on splicing factor genes and their involvement in cancer initiation, progression, and resistance to therapy, as well as their potential as novel therapeutic targets in ovarian, breast, and brain cancers.

Abstract: