Anti proliferative activity of ELACYT™ (CP-4055) in combination with cloretazine (VNP40101M), idarubicin, gemcitabine, irinotecan and topotecan in human leukemia and lymphoma cells

Adams, David J.; Sandvold, Marit Liland; Myhren, Finn; Jacobsen, Tove Flem; Giles, Frank; Rizzieri, David A.

doi:10.1080/10428190801935752

Cited by 29 publications

(12 citation statements)

References 31 publications

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“…A currently bourgeoning research area for cancer treatment is the drug combination method (Adams et al, 2008;Chou et al, 2006;Dicko et al, 2010;Feldman et al, 2007;Lee, 2012). Recent investigations documented the efficacy of combining cisplatin with other drugs, providing a rational basis for the design of new well-tolerated platinum-based treatment in cancer chemotherapies (Facy et al, 2011;Jiang et al, 2011;Rattan et al, 2011).…”

Section: Introductionmentioning

confidence: 97%

Liposomes loaded with a dirhenium compound and cisplatin: preparation, properties and improvedin vivoanticancer activity

Штеменко

Yegorova

et al. 2014

Journal of Liposome Research

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Liposomes loaded with the rhenium compound (bis-dimethylsulfoxido-cis-tetrachlorodi-μ-pivalatodirhenium(III) (cis-Re2((CH3)3CCOO)2Cl4.2DMSO, I) and cisplatin in the molar ratio of 4:1 as well as those loaded only with I were synthesized and characterized by scanning electron microscopy, transmission electron microscopy, dynamic light scattering and electronic absorption spectroscopy. The relative stability of liposomes loaded with I is reflected by a minimal change in the electronic absorption spectra over a period of 8 days whereas the stability of those loaded with both drugs is lower, which we ascribe to the formation of new Re-Pt species inside the liposomes. Furthermore, the investigations of the co-encapsulation effects on the anticancer activity of the Re-Pt system were undertaken. Importantly, the co-encapsulated liposomes exhibit synergistic or additive anticancer activities in vivo, e.g. introduction of these liposomes into tumor-bearing rats demonstrated their antianemic, nephro- and hepato-protecting effects. These liposomes, which are active in cancer treatment, protect the dirhenium compounds from hydrolysis and preserve the biological properties of the Re-Pt hybrid. This study reveals the importance of combined therapy in nanotechnology and medicine.

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Section: Introductionmentioning

confidence: 97%

Liposomes loaded with a dirhenium compound and cisplatin: preparation, properties and improvedin vivoanticancer activity

Штеменко

Yegorova

et al. 2014

Journal of Liposome Research

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“…Recent studies by our laboratory and others have shown that the therapeutic activity of drug combinations is often drug ratio dependent, where synergistic or antagonistic interactions occur when tumors are exposed to different drug/ drug ratios (12)(13)(14)(15). Thus, the full benefit of combination chemotherapy may not be realized in vivo unless the ratios of the drugs are carefully controlled and maintained to avoid exposure of tumor cells to antagonistic drug ratios.…”

Section: Introductionmentioning

confidence: 99%

Drug ratio–dependent antitumor activity of irinotecan and cisplatin combinations in vitro and in vivo

Tardi

Santos

Harasym

et al. 2009

Molecular Cancer Therapeutics

104

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Irinotecan and cisplatin are two established anticancer drugs, which together constitute an effective combination for treating small-cell lung cancer. We investigated whether the efficacy of this combination could be improved by controlling drug ratios following in vivo administration. Irinotecan and cisplatin combinations were evaluated systematically for drug ratio-dependent synergy in vitro using a panel of 20 tumor cell lines. In vitro screening informatics on drug ratio-dependent cytotoxicity identified a consistently antagonistic region between irinotecan/cisplatin molar ratios of 1:2 to 4:1, which was bordered by two synergistic regions. Liposomal co-formulations of these two agents were developed that exhibited plasma drug half-lives of 6 hours and maintained a fixed drug ratio for more than 24 hours. Drug ratio-dependent antitumor activity was shown in vivo for these liposome formulations, and irinotecan/cisplatin ratios between 5:1 and 10:1 were identified as therapeutically optimal. The relationship between irinotecan/cisplatin ratio and in vivo efficacy was consistent with in vitro drug ratio dependency results. Superior antitumor activity was observed for the liposome-encapsulated 7:1 molar ratio of irinotecan/cisplatin (designated CPX-571) compared with the free-drug cocktail in all models tested. Further efficacy studies in a range of human tumor xenografts, including an irinotecanresistant model, showed that both liposomal agents contributed to the overall efficacy in a manner consistent with in vivo synergy. These results show the ability of drug delivery technology to enhance the therapeutic activity of irinotecan/cisplatin combination treatment by maintaining synergistic ratios in vivo. CPX-571, a fixed-ratio formulation of irinotecan and cisplatin, is a promising candidate for clinical development.

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“…Drug interaction was assessed with ATP-based growth inhibition assays by combination index and combination effect endpoints using published methods of Chou [11] and Kanzawa [26], respectively, as reported previously [6, 37]. …”

Section: Methodsmentioning

confidence: 99%

BACPTDP: a water-soluble camptothecin pro-drug with enhanced activity in hypoxic/acidic tumors

Adams

Waud

Wani

et al. 2010

Cancer Chemother Pharmacol

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Hypoxia is a common feature of solid tumors. Up-regulation of hypoxia-inducing factor-1 (HIF-1) occurs in the majority of primary malignant tumors and in two-thirds of metastases, while most normal tissues are negative. HIF-1 induces the glycolytic phenotype, which creates an acidic extracellular microenvironment and associated pH gradient such that drugs that are weak acids are selectively taken up and retained in acidic tumors. 7-Butyl-10-amino-camptothecin (BACPT) is a prime example of an agent that can exploit the tumor pH gradient for enhanced selectivity. Purpose This study profiles the antitumor activity of BACPT in vitro and its water-soluble dipeptide ester, BACPTDP, in vivo. Methods Antitumor activity was evaluated by proliferation assays in cancer cell lines and in murine xenograft models for human neuroblastoma (IMR-32), colon (HT29), ovarian (SK-OV-3), pancreatic (Panc-1), glioma (SF-295) and non-small-cell lung (NCI-H460) cancers. Results BACPT had superior antiproliferative activity compared to established drugs in monolayer cultures of human neuroblastoma and pancreatic tumor cell lines and in 3-dimensional histocultures of colon and primary ovarian cancer. Antitumor activity of BACPTDP was comparable to irinotecan in IMR-32, HT29, SF-295 and NCI-H460 xenografts, significantly greater in SK-OV-3 and in Panc-1 where complete regressions were observed. Combination of BACPT with gemcitabine produced additive to synergistic interactions in Panc-1 cells that were independent of drug ratio and optimal when gemcitabine was administered 24 h prior to BACPT. Conclusions BACPTDP is a water-soluble camptothecin pro-drug that spontaneously generates the lipid-soluble active agent, BACPT. This topoisomerase inhibitor exploits solid tumor physiology for improved selectivity and activity against multiple tumor types with particular promise for use in treating pediatric neuroblastoma and pancreatic carcinoma.

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Anti proliferative activity of ELACYT™ (CP-4055) in combination with cloretazine (VNP40101M), idarubicin, gemcitabine, irinotecan and topotecan in human leukemia and lymphoma cells

Cited by 29 publications

References 31 publications

Liposomes loaded with a dirhenium compound and cisplatin: preparation, properties and improvedin vivoanticancer activity

Liposomes loaded with a dirhenium compound and cisplatin: preparation, properties and improvedin vivoanticancer activity

Drug ratio–dependent antitumor activity of irinotecan and cisplatin combinations in vitro and in vivo

BACPTDP: a water-soluble camptothecin pro-drug with enhanced activity in hypoxic/acidic tumors

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