Kanker-actueel Injecties met 3-bromopyruvate (3-BrPA) in tumorweefsel zou effectiever werken dan operatie en chemo bij borstkanker..Deze antiglycolitic therapie beinvloed metabolisch proces in kankercel en leidt tot natuurlijke celdood

De combinatie van twee innovatieve strategieën - metabole therapie via ultra sound begeleiding - is effectiever dan de huidige behandelingen van chirurgische resectie of verwijdering van de tumor in de behandeling van borstkanker. Dit stellen onderzoekers aan de universiteit van de Johns Hopkins University School of Medicine in Baltimore, Maryland. In laboratoriumproeven en dierproeven en nu bij enkele patienten zijn onder ultra sound begeleiding injecties gegeven met een zogeheten ALK agent. Dr Geschwind en collega's gebruikten een minimaal invasieve ultrasound-geleide intratumorale behandelings strategie om de antiglycolytic-agent 3-bromopyruvate (3-BrPA) direct in te spuiten bij borsttumoren bij muizen. Het resultaat was een statistisch significant verschil in tumorvolume tussen behandelde muizen en muizen in de controlegroep. In de groep behandeld met 5 mmol / L 3-BrPA, de resultaten werden gemeten op dag 6 van de behandeling (256 vs 1809 mm3 in de controlegroep, P <0.05), in de groep behandeld met 1,75 mmol / L 3-BrPA, werden de resultaten gemeten op dag 12 (1160 vs 4188 mm3, P <0.05).

Wat deze injecties met 3-bromopyruvate (3-BrPA) doen, zover ik dit goed begrijp uit het medische engels, is dat door beinvloeding van de glucose opname van de kankercel, (kankercellen nemen veel en veel meer glucose op dan gewone gezonde cellen) de kankercel als het ware wordt gedwongen tot een natuurlijke dood. Er zijn verschilende studies gedaan bij verschillende vormen van kanker en alle dierstudies geven opmerkelijk positieve resultaten zonder noemenswaardige bijwerkingen. Hier het abstract van de studie gedaan met borstkanker en enkele citaten uit een artikel van Medscape over deze studie.

The combination of 2 innovative strategies — metabolic therapy and imaging guidance — is more effective than the current treatments of surgical resection or tumor removal in the treatment of breast cancer.

Bron: Medscape

Dr. Geschwind and colleagues used a minimally invasive ultrasound-guided intratumoral treatment strategy to deliver the antiglycolytic agent 3-bromopyruvate (3-BrPA) directly to breast tumors in mice. The strategy maximized 3-BrPA delivery to the tumor and minimized the exposure of healthy tissue to the 3-BrPA. The result was a statistically significant difference in tumor volume between treated and control mice. In the group treated with 5 mmol/L 3-BrPA, results were seen on day 6 of treatment (256 vs 1809 mm³ in the control group; P < .05); in the group treated with 1.75 mmol/L 3-BrPA, results were seen on day 12 (1160 vs 4188 mm³; P < .05).

Dr. Geschwind also presented data describing the research team's work to determine the half maximal inhibitory concentration of the breast cancer cell line used in the study (200 µmol/L). They characterized an in vitro dose-dependent decrease in adenosine triphosphate levels, starting at a concentration of 50 µmol/L of 3-BrPA. When tested using a wound-migration assay, the penetration of breast cancer cells treated with 100 µmol/L of 3-BrPA decreased by 70%, compared with untreated control cells.

One in 8 women is diagnosed with breast cancer during her life, and breast cancer is the second leading cause of cancer death in women in the United States. Increased cancer awareness and the implementation of screening programs have resulted in an increased proportion of early-stage carcinomas at the time of diagnosis. Unfortunately, a significant number of patients experience treatment failure after an initial response to chemotherapy or radiation.

Most cancer cells exhibit upregulation of the energy-producing glycolytic pathway. Dr. Geschwind explained to Medscape Medical News that "cancer cells have a unique way of finding enough glucose to satisfy their needs. There is a big dichotomy between normal cells and cancer cells and their needs for glucose. This is something that can be targeted."

The goal of therapy is to treat the process of cancer growth and to freeze the process of cancer metastases with 2 to 4 injections. It appears to do this by decreasing the expression and activity of matrix metalloproteinases (MMP)-2 and MMP-9, which are required for the migration and invasion of tumor cells.

Bron: Current Pharmaceutical Biotechnology

-Bromopyruvate: A New Targeted Antiglycolytic Agent and a Promise for Cancer Therapy
	pp.510-517 (8) Authors: S. Ganapathy-Kanniappan, M. Vali, R. Kunjithapatham, M. Buijs, L.H. Syed, P.P. Rao, S. Ota, B.K. Kwak, R. Loffroy, J.F. Geschwind

Abstract

The pyruvate analog, 3-bromopyruvate, is an alkylating agent and a potent inhibitor of glycolysis. This antiglycolytic property of 3-bromopyruvate has recently been exploited to target cancer cells, as most tumors depend on glycolysis for their energy requirements. The anticancer effect of 3-bromopyruvate is achieved by depleting intracellular energy (ATP) resulting in tumor cell death. In this review, we will discuss the principal mechanism of action and primary targets of 3-bromopyruvate, and report the impressive antitumor effects of 3-bromopyruvate in multiple animal tumor models. We describe that the primary mechanism of 3-bromopyruvate is via preferential alkylation of GAPDH and that 3- bromopyruvate mediated cell death is linked to generation of free radicals. Research in our laboratory also revealed that 3- bromopyruvate induces endoplasmic reticulum stress, inhibits global protein synthesis further contributing to cancer cell death. Therefore, these and other studies reveal the tremendous potential of 3-bromopyruvate as an anticancer agent.

Affiliation: Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock Building, Room 545, Baltimore, MD 21287, USA


	pp.510-517 (8) Authors: S. Ganapathy-Kanniappan, M. Vali, R. Kunjithapatham, M. Buijs, L.H. Syed, P.P. Rao, S. Ota, B.K. Kwak, R. Loffroy, J.F. Geschwind