TY  - JOUR
AB  - Cancer cells convert glucose preferentially to lactate even in the presence of oxygen (aerobic glycolysis-Warburg effect). New concepts in cancer treatment aim at inhibition of aerobic glycolysis. Pyruvate dehydrogenase converts pyruvate to acetylCoA thus preventing lactate formation. Therefore, the aim of this study was to evaluate compounds that could activate pyruvate dehydrogenase in cancer cells. We investigated the effects of (R)-(+)-alpha-lipoic acid (LPA) and dichloroacetate (DCA), possible activators of pyruvate dehydrogenase, on suppression of aerobic glycolysis and induction of cell death. The neuroblastoma cell lines Kelly, SK-N-SH, Neuro-2a and the breast cancer cell line SkBr3 were incubated with different concentrations (0.1-0 mM) of LPA and DCA. The effects of both compounds on cell viability/proliferation (WST-1 assay), [18F]-FDG uptake, lactate production and induction of apoptosis (flow cytometric detection of caspase-3) were evaluated. Furthermore, NMRI nu/nu mice that had been inoculated s.c. with SkBr3 cells were treated daily for four weeks with LPA (i.p, 18.5 mg/kg) starting at day 7 p.i.. Tumour development was measured with a sliding calliper and monitored via [18F]-FDG-PET. Residual tumours after therapy were examined histopathologically. These data suggests that LPA can reduce (i) cell viability/proliferation, (ii) uptake of [18F]-FDG and (iii) lactate production and increase apoptosis in all investigated cell lines. In contrast, DCA was almost ineffective. In the mouse xenograft model with s.c. SkBr3 cells, daily treatment with LPA retarded tumor progression. Therefore, LPA seems to be a promising compound for cancer treatment.
AU  - Feuerecker, B.*
AU  - Pirsig, S.*
AU  - Seidl, C.*
AU  - Aichler, M.
AU  - Feuchtinger, A.
AU  - Bruchelt, G.*
AU  - Senekowitsch-Schmidtke, R.*
C1  - 11204
C2  - 30580
SP  - 1425-1435
TI  - Lipoic acid inhibits cell proliferation of tumor cells in vitro and in vivo.
JO  - Cancer Biol. Ther.
VL  - 13
IS  - 14
PB  - Landes Bioscience
PY  - 2012
SN  - 1538-4047
ER  - 

TY  - JOUR
AB  - Anti-angiogenic therapy by blocking VEGF signalling combined with standard chemotherapy is a novel strategy for clinical cancer treatment. The mechanisms for enhanced antitumoral effects are still a matter of controversial debate. Tumor vessel "normalization" upon anti-angiogenic therapy leading to improved drug delivery has been proposed as possible mechanism. Therefore, aim of the study was to investigate tumor microvascular function upon anti-VEGFR treatment in highly vascularized melanomas. A detailed intravital-microscopic analysis of tumor microcirculation including the distribution pattern of vessel diameters and blood flow velocities was performed in melanomas grown in dorsal skinfold chambers of hamsters. Animals with highly vascularized established tumors were treated by a VEGFR tyrosin kinase inhibitor (SU5416) on 3 repetitive days. Tumor tissue oxygenation was measured by phosphorescence quenching technique. Overall tumor microcirculation of subcutaneous tumors was investigated by contrast enhanced MRI (CE-MRI). Vessel density was significantly decreased in treated animals. A significant shift in the distribution patterns towards increased vessel diameters and faster red blood cell velocities in remaining tumor vessels was observed upon anti-VEGF treatment, compensating reduced vascular density. Moreover, a trend towards elevated pO(2) levels in treated tumors was observed. Compared to controls, inflow kinetics of tumors quantified by CE-MRI as well as overall uptake of contrast agent in tumor tissue were significantly increased following short-term SU5416 treatment. In conclusion the results confirm temporarily improved tumor microvascular function in highly vascularized melanomas upon short term anti-VEGFR treatment leading to enhanced tumor blood supply and oxygenation potentially improving the efficacy of simultaneous chemo- or radiotherapy.
AU  - Eichhorn, M.E.*
AU  - Strieth, S.*
AU  - Luedemann, S.*
AU  - Kleespies, A.*
AU  - Nöth, U.
AU  - Passon, A.*
AU  - Brix, G.*
AU  - Jauch, K.W.*
AU  - Bruns, C.J.*
AU  - Dellian, M.*
C1  - 3474
C2  - 25460
SP  - 1006-1013
TI  - Contrast enhanced MRI and intravital fluorescence microscopy indicate improved tumor microcirculation in highly vascularized melanomas upon short-term anti-VEGFR treatment.
JO  - Cancer Biol. Ther.
VL  - 7
IS  - 7
PB  - Landes Bioscience
PY  - 2008
SN  - 1538-4047
ER  - 

TY  - JOUR
AU  - Eichhorn, M.E.*
AU  - Becker, S.*
AU  - Strieth, S.*
AU  - Werner, A.*
AU  - Sauer, B.*
AU  - Teifel, M.*
AU  - Ruhstorfer, H.
AU  - Michaelis, U.*
AU  - Griebel, J.*
AU  - Brix, G.*
AU  - Jauch, K.-W.*
C1  - 3288
C2  - 23580
SP  - 89-96
TI  - Paclitaxel encapsulated in cationic lipid complexes (MBT-0206) impairs functional tumor vascular properties as detected by dynamic contrast enhanced magnetic resonance imaging.
JO  - Cancer Biol. Ther.
VL  - 5
PY  - 2006
SN  - 1538-4047
ER  -