The effect of DDW on pancreatic tumors was evaluated in in vitro tests ad a retrospective clinical study. In the in vitro tests, the effect of DDW was studied alone and in combination with the cytostatic Cisplatin on a Gemzar-resistant MIA PaCa-2 pancreas tumor cell line by means of the xCELLigence RTCA system (Roche Applied Sciences). This method is of advance because the cells are being monitored under physiological conditions, and cell division can be followed in real time without radioactive labelling and manipulating the cells. In the tests, changes of electric resistance are measured by means of a meshwork of microelectrodes on the bottom of the culture dish. The measured impedance increases in parallel with the growth and adhesion of the cells. This is described with the normalized cell index (CI). DDW (with 135, 125, 115, 105, 85, 65 and 40 ppm deuterium) inhibited the growth of MIA PaCa-2 pancreas tumor cells in vitro in a dose-dependent manner, with significant (p<0.02) CI decrease vs. control (150 ppm D). The cytotoxicity of Cisplatin was tested at the concentrations 20, 40 and 60 μM, combined with DDW (50 ppm D), on the MIA PaCa-2 cells. Combined application dose-dependently decreased CI, and synergism was observed. This raised the possibility that the same efficiency could be achieved with lower concentrations of the cytostatic, that is, with lower toxicity. Cisplatin showed maximum efficiency at 40 μM in presence of 50 ppm D, or already at 20 μM if 25 ppm deuterium was in the medium. This is another proof of synergism between Cisplatin and DDW in Gemzar-resistant MIA PaCa-2 cells.
The results clearly show that combination of DDW and chemotherapy allows lowering the dose of cytostatics, with preserved efficiency but substantially reduced harmful side effects. In the retrospective clinical study, the survival of pancreas tumor patients was increased 6.5 times – from 6 to 39 months – by supplemental application of deuterium depletion, if DDW treatment was started within 60 days after diagnosis (n=18). In those patients (n=14) who were involved in the study more than 60 days after diagnosis, MST was 16 months.
DDW inhibited the growth of MIA PaCa-2 pancreas tumor cells in vitro. Applied together with conventional therapy, DDW prolonged MST of patients with progressive, inoperable pancreatic cancer 4-6 times.
Boros L.G., Meuillet E.J., Somlyai I., Jancsó G., Jákli G., Krempels K., Puskás L.G., Nagy L., Molnár M., Laderoute K.R., Thompson P.A., Somlyai G. (2014) Fumarate hydratase and deuterium depletion control oncogenesis via NADPH-dependent reductive synthesis. AACR 2014 - Annual Meeting, April 5-9, San Diego, CA, USA, DOI: 10.12918/HYD2014AACRPOST