Electrochemical Effects after Transarterial Chemoembolization in Combination with Percutaneous Irreversible Electroporation: Observations in an Acute Porcine Liver Model.

PURPOSE: To evaluate the effects of combined use of transarterial chemoembolization and irreversible electroporation (IRE) for focal tissue ablation in an acute porcine liver model. MATERIALS AND METHODS: Two established interventional techniques were combined: IRE with zones of irreversible and reversible electroporation and chemoembolization with microspheres, iodized oil, and doxorubicin. IRE was performed before chemoembolization in two pigs (pigs 1 and 2; IRE/chemoembolization group), chemoembolization was performed before IRE in two pigs (pigs 3 and 4; chemoembolization/IRE group), and only IRE was performed in two pigs (pigs 5 and 6). Five study groups were defined: IRE/chemoembolization (pigs 1 and 2), chemoembolization/IRE (pigs 3 and 4), IRE only (pigs 5 and 6), chemoembolization only (tissue outside the IRE zones in pigs 1-4), and control (untreated liver tissue outside the IRE zones in pigs 5 and 6). Animals were euthanized 2 hours after intervention. Size and shape of IRE zones on contrast-enhanced computed tomography, cell death on light microscopy, and doxorubicin tissue concentrations on chromatography and fluorescence microscopy were analyzed. RESULTS: Size and shape of IRE zones were not significantly different (eg, P = .067 for volume). A histologic marker for irreversible cell death was positive in IRE/chemoembolization, chemoembolization/IRE, and IRE groups only in the macroscopically visible IRE zones. Doxorubicin tissue concentrations were not significantly different (P = .873). However, in the reversible electroporation (RE) zones, broad areas with intense intranuclear doxorubicin accumulation were observed in IRE/chemoembolization but not in chemoembolization/IRE and chemoembolization groups. CONCLUSIONS: IRE before chemoembolization enhances the intranuclear accumulation of doxorubicin in the RE zone.

Specific killing of multiple myeloma cells by (-)-epigallocatechin-3-gallate extracted from green tea: biologic activity and therapeutic implications.

Epigallocatechin-3-gallate (EGCG), a polyphenol extracted from green tea, is an antioxidant with chemopreventive and chemotherapeutic actions. Based on its ability to modulate growth factor-mediated cell proliferation, we evaluated its efficacy in multiple myeloma (MM). EGCG induced both dose- and time-dependent growth arrest and subsequent apoptotic cell death in MM cell lines including IL-6-dependent cells and primary patient cells, without significant effect on the growth of peripheral blood mononuclear cells (PBMCs) and normal fibroblasts. Treatment with EGCG also led to significant apoptosis in human myeloma cells grown as tumors in SCID mice. EGCG interacts with the 67-kDa laminin receptor 1 (LR1), which is significantly elevated in myeloma cell lines and patient samples relative to normal PBMCs. RNAi-mediated inhibition of LR1 resulted in abrogation of EGCG-induced apoptosis in myeloma cells, indicating that LR1 plays an important role in mediating EGCG activity in MM while sparing PBMCs. Evaluation of changes in gene expression profile indicates that EGCG treatment activates distinct pathways of growth arrest and apoptosis in MM cells by inducing the expression of death-associated protein kinase 2, the initiators and mediators of death receptor-dependent apoptosis (Fas ligand, Fas, and caspase 4), p53-like proteins (p73, p63), positive regulators of apoptosis and NF-kappaB activation (CARD10, CARD14), and cyclin-dependent kinase inhibitors (p16 and p18). Expression of related genes at the protein level were also confirmed by Western blot analysis. These data demonstrate potent and specific antimyeloma activity of EGCG and provide the rationale for its clinical evaluation.