Plasma kinetics of a cholesterol-rich microemulsion (LDE) in patients with Hodgkin’s and non-Hodgkin’s lymphoma and a preliminary study on the toxicity of etoposide associated with LDE

Pinheiro, Ketlin V.; Hungria, Vania T.M.; Ficker, Elisabeth Salvatori; Valduga, Claudéte J.; Mesquita, C.H.; Maranhão, Raul C.

doi:10.1007/s00280-005-0090-8

Cited by 61 publications

(51 citation statements)

References 32 publications

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“…In the etoposide, 300 mg/m 2 dose/3 weeks, administered over 6 cycles. 17 This dose scheme corresponds to those routinely used in the clinical oncology practice. During the treatment, no clinical and laboratorial toxicities, including anemia or other myelotoxicities, were observed in both patients.…”

Section: Discussionmentioning

confidence: 99%

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Reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions

Tavares¹,

Freitas²,

Diament³

et al. 2011

IJN

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Objectives Cholesterol-rich nanoemulsions (LDE) bind to low-density lipoprotein (LDL) receptors and after injection into the bloodstream concentrate in aortas of atherosclerotic rabbits. Association of paclitaxel with LDE markedly reduces the lesions. In previous studies, treatment of refractory cancer patients with etoposide associated with LDE had been shown devoid of toxicity. In this study, the ability of etoposide to reduce lesions and inflammatory factors in atherosclerotic rabbits was investigated. Methods Eighteen New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30, nine animals were treated with four weekly intravenous injections of etoposide oleate (6 mg/kg) associated with LDE, and nine control animals were treated with saline solution injections. Results LDE-etoposide reduced the lesion areas of cholesterol-fed animals by 85% and intima width by 50% and impaired macrophage and smooth muscle cell invasion of the intima. Treatment also markedly reduced the protein expression of lipoprotein receptors (LDL receptor, LDL-related protein-1, cluster of differentiation 36, and scavenger receptor class B member 1), inflammatory cytokines (interleukin-1β and tumor necrosis factor-α), matrix metallopeptidase-9, and cell proliferation markers (topoisomerase IIα and tubulin). Conclusion The ability of LDE-etoposide to strongly reduce the lesion area and the inflammatory process warrants the great therapeutic potential of this novel preparation to target the inflammatory-proliferative basic mechanisms of the disease.

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Section: Discussionmentioning

confidence: 99%

“…15 Reduction of toxicity of chemotherapeutic agents by associating them to LDE was confirmed at clinical level. In trials enrolling patients with advanced cancers treated with LDE-carmustine, 10 LDE-paclitaxel, 16 and LDE-etoposide, 17 the toxicity of high-dose treatments was minimal or absent.…”

mentioning

confidence: 99%

Reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions

Tavares¹,

Freitas²,

Diament³

et al. 2011

IJN

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“…In those leukemias and also in Hodgkin and non-Hodgkin lymphomas, LDL cholesterol levels may decrease, resulting from the increased removal of LDL from the circulation by the neoplastic tissues. [3][4][5][6] correspondence: raul c Maranhão laboratório de Metabolismo de lípides, instituto do coração (incOr) do hospital das clínicas FMUsP, 44 avenida Doutor enéas de carvalho aguiarBloco 2, 1ss, são Paulo 05403-900, Brazil Tel +55 11 2661 5951 Fax +55 11 2661 5574 email ramarans@usp.br…”

Section: Introductionmentioning

confidence: 99%

“…Because it is prepared only with lipids present in the organism, LDE has no immunogenic potential and no safety issues related to materials in the nanoemulsion composition. 5,14,22,23 Due to the aggressiveness of the malignant neoplastic processes, adjuvant strategies with the potential to increase the effectiveness of anticancer therapies should always be considered for testing. In this respect, statins, the most important cholesterol-lowering class of drugs, have been reported as inducers of apoptosis and antitumor activity of antineoplastic drugs, such as carmustine, cisplatin, 5-fluorouracil, doxorubicin, and PTX, and investigated as adjuvants in cancer treatment and prevention.…”

Section: Introductionmentioning

confidence: 99%

“…17,19,21,84 In pilot clinical trials performed in patients with advanced cancers, LDE-carmustine, LDE-etoposide, and LDE-PTX showed no observable clinical or laboratorial toxicities in doses corresponding to those used in routine cancer treatment. 5,14,23 Therefore, the LDE system and eventually others that explore the LDL-receptor endocytic pathways as drug-delivery gateway are creditable candidates for introduction in clinical oncology practice. In this setting, the use of statins can further enhance the anticancer activity of drugs carried in this type of drug-delivery system.…”

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confidence: 99%

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Simvastatin increases the antineoplastic actions of paclitaxel carried in lipid nanoemulsions in melanoma-bearing mice

Kretzer¹,

Maria²,

Guido³

et al. 2016

IJN

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Purpose Lipid nanoemulsions (LDEs) that bind to low-density lipoprotein (LDL) receptors used as carriers of paclitaxel (PTX) can decrease toxicity and increase PTX antitumoral action. The administration of simvastatin (Simva), which lowers LDL-cholesterol, was tested as an adjuvant to commercial PTX and to PTX associated with LDE (LDE-PTX). Materials and methods B16F10 melanoma-bearing mice were treated with saline solution or LDE (controls), Simva, PTX, PTX and Simva, LDE-PTX, and LDE-PTX and Simva: PTX dose 17.5 μmol/kg (three intraperitoneal injections, 3 alternate days): Simva 50 mg/kg/day by gavage, 9 consecutive days. Results Compared with saline controls, 95% tumor-growth inhibition was achieved by LDE-PTX and Simva, 61% by LDE-PTX, 44% by PTX and Simva, and 43% by PTX. Simva alone had no effect. Metastasis developed in only 37% of the LDE-PTX and Simva, 60% in LDE-PTX, and 90% in PTX and Simva groups. Survival rates were higher in LDE-PTX and Simva and in LDE-PTX groups. The LDE-PTX and Simva group presented tumors with reduced cellular density and increased collagen fibers I and III. Tumors from all groups showed reduction in immunohistochemical expression of ICAM, MCP-1, and MMP-9; LDE-PTX and Simva presented the lowest MMP-9 expression. Expression of p21 was increased in the Simva, LDE-PTX, and LDE-PTX and Simva groups. In the Simva and LDE-PTX and Simva groups, expression of cyclin D1, a proliferation and survival promoter of tumor cells, was decreased. Therapy with LDE-PTX and Simva showed negligible toxicity compared with PTX and Simva, which resulted in weight loss and myelosuppression. Conclusion Simva increased the antitumor activity of PTX carried in LDE but not of PTX commercial presentation, possibly because statins increase the expression of LDL receptors that internalize LDE-PTX.

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Current Awareness in Hematological Oncology

2006

Hematological Oncology

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of hematological oncology. Each bibliography is divided into 14 sections: 1 Books, Reviews & Symposia; 2 General; Leukemias: 3 Lymphoblastic; 4 Myeloid & Myelodysplastic Syndromes; 5 Chronic; 6 Others; Lymphomas: 7 Hodgkin's; 8 Non‐Hodgkin's; 9 Plasmacytomas/Multiple Myelomas; 10 Others; 11 Bone Marrow Transplantation; 12 Cytokines; 13 Diagnosis; 14 Cytogenetics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted.

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Plasma kinetics of a cholesterol-rich microemulsion (LDE) in patients with Hodgkin’s and non-Hodgkin’s lymphoma and a preliminary study on the toxicity of etoposide associated with LDE

Abstract: Our results suggest that lymphomas overexpress LDL receptors that make room for using LDE as drug-targeting vehicle and that the LDE-etoposide preparation is suitable for patient use.

Cited by 61 publications

References 32 publications

Reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions

Reduction of atherosclerotic lesions in rabbits treated with etoposide associated with cholesterol-rich nanoemulsions

Simvastatin increases the antineoplastic actions of paclitaxel carried in lipid nanoemulsions in melanoma-bearing mice

Current Awareness in Hematological Oncology

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