title: Therapeutic efficacy of combined PEGylated liposomal doxorubicin and radiofrequency ablation: Comparing single and combined therapy in young and old mice.
abstract: Antitumor therapy in the elderly is particularly challenging due to multiple, often chronic diseases, poly-therapy, and age-related physiological changes that affect drug efficacy and safety. Furthermore, tumors may become more aggressive and drug-resistant with advanced age, leading to poor patient prognosis. In this study, we evaluated in mice bearing medulloblastoma xenografts the effect of age on tumor progression and tumor therapy. We focused on therapeutic efficacy of two treatment modalities alone radiofrequency ablation therapy (RFA), PEGylated liposomal doxorubicin (PLD) equivalent to Doxil, and their combination. We demonstrated that tumor growth rate was higher and survival was lower in old versus young mice (p<0.05). Likewise, tumors in old mice were less susceptible to either PLD or RFA monotherapy. However, combined therapy of PLD and RFA succeeded to eliminate the age-related differences in anti-cancer treatment efficacy (p>0.05) by the two monotherapies. The results on PLD therapy are supported by preferable PEGylated nano-liposomes accumulation in tumors of young mice compared to old mice, as determined by near-infrared imaging with indocyanine green (ICG)-labeled PEGylated nano-liposomes. Taken together, our findings suggest that age effects on tumor progression and tumor monotherapy outcome may potentially be related to changes in tumor microenvironment, and that these changes can be overcome by RFA as this technique abolishes these differences and significantly improves success of PLD treatment.
authors.affiliation: Department of Biochemistry, Institute for Medical Research Israel-Canada, Hebrew University -Hadassah Medical School, P.O.B. 12272, Jerusalem 91120, Israel.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Andriyanov
authors.affiliation: Department of Biochemistry, Institute for Medical Research Israel-Canada, Hebrew University -Hadassah Medical School, P.O.B. 12272, Jerusalem 91120, Israel.
authors.forename: Emma
authors.initials: E
authors.lastname: Portnoy
authors.affiliation: Department of Biochemistry, Institute for Medical Research Israel-Canada, Hebrew University -Hadassah Medical School, P.O.B. 12272, Jerusalem 91120, Israel.
authors.forename: Erez
authors.initials: E
authors.lastname: Koren
authors.affiliation: Institute for Drug Research, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
authors.forename: Semenenko
authors.initials: S
authors.lastname: Inesa
authors.affiliation: Institute for Drug Research, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
authors.forename: Sara
authors.initials: S
authors.lastname: Eyal
authors.affiliation: Radiology Department, Hadassah Hebrew University Medical Center, Ein Karem, Jerusalem, Israel.
authors.forename: S Nahum
authors.initials: SN
authors.lastname: Goldberg
authors.affiliation: Department of Biochemistry, Institute for Medical Research Israel-Canada, Hebrew University -Hadassah Medical School, P.O.B. 12272, Jerusalem 91120, Israel. Electronic address: chezyb@ekmd.huji.ac.il.
authors.forename: Yechezkel
authors.initials: Y
authors.lastname: Barenholz
mesh_terms: D000375:Aging; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D017115:Catheter Ablation; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Cancer; Doxil; Indocyanine green; Liposomes; Radiofrequency ablation