Anthracyclines in haematology: preclinical studies, toxicity and delivery systems

Richardson, Deborah; Johnson, S. A. N.

doi:10.1016/s0268-960x(97)90020-5

Cited by 77 publications

(63 citation statements)

References 169 publications

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“…Dox induces apoptosis in the leukocytes by interfering with the DNA-replication machinery, or by inhibiting the synthesis of DNA and RNA. 28 This is also shown by the results of the present study, which showed extensive damage and a wide range of toxicity in the leukocytes of mice treated with free Dox. Dox can be well tolerated in liposomal form, as the mice from the groups treated with Lip-Dox showed significantly less toxicity.…”

Section: Discussionsupporting

confidence: 83%

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Combination of glycosphingosomes and liposomal doxorubicin shows increased activity against dimethyl-α-benzanthracene-induced fibrosarcoma in mice

Khan

Aljarbou

Aldebasi

et al. 2015

IJN

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The present study aimed to assess the antitumor effect of glycosphingolipid-incorporated liposomes (glycosphingosomes) in combination with liposomal doxorubicin (Lip-Dox) in a mouse model of fibrosarcoma. Glycosphingosomes were prepared by incorporating glycosphingolipids isolated from Sphingomonas paucimobilis into the liposomes of 1,2-dipalmitoyl- sn -glycero-3-phosphocholine, cholesterol, and cardiolipin. Tumors were induced by administering dimethyl-α-benzanthracene, and tumor-bearing mice were treated with various formulations of Dox, including free Dox, Lip-Dox, or glycosphingosomes + Lip-Dox. Mice were observed for 90 days to monitor their survival and tumor size. Free Dox, but not Lip-Dox or a combination of glycosphingosomes and Lip-Dox, caused the substantial depletion of leukocytes and significantly increased the levels of lactate dehydrogenase and creatinine kinase in mice. Tumor-bearing mice treated with a combination of glycosphingosomes and Lip-Dox showed restricted tumor growth and increased survival when compared to those treated with free Dox or Lip-Dox. The results of the present study suggest that a combination of glycosphingosomes and Lip-Dox may prove to be very effective in the treatment of tumors.

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Section: Discussionsupporting

confidence: 83%

“…18,28,29 The administration of Dox has been shown to cause toxicity and the depletion of leukocytes. 31,32 The results of the present study showed that free Dox induces both quantitative and qualitative changes in the leukocytes.…”

Section: Discussionmentioning

confidence: 99%

Combination of glycosphingosomes and liposomal doxorubicin shows increased activity against dimethyl-α-benzanthracene-induced fibrosarcoma in mice

Khan

Aljarbou

Aldebasi

et al. 2015

IJN

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“…Therefore, identifying the cause of drug resistance and developing biomarkers are critical. Anthracyclines have been shown to intercalate with DNA and indirectly inhibit the activity of the enzyme topoisomerase II, resulting in DNA strand breaks and induction of apoptosis (29). In the present study, it was hypothesized that miR-125b induced DNR resistance in leukemia cells through regulating apoptosis.…”

Section: Discussionmentioning

confidence: 82%

microRNA-125b promotes leukemia cell resistance to daunorubicin by inhibiting apoptosis

Zhou

Bai

Wang

et al. 2014

Molecular Medicine Reports

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Abstract. microRNA-125b (miR-125b) is overexpressed in several types of cancer and contributes to tumor resistance to chemotherapy. The present study investigated the effect of miR-125b on the resistance of leukemia cell lines to the chemotherapeutic agent daunorubicin (DNR). miR-125b expression was found to be upregulated in patients who had failed therapy compared with those who demonstrated event-free survival. The overexpression of miR-125b was observed to induce DNR resistance in K562, THP-1 and Jurkat cells by reducing apoptosis, whereas the suppression of miR-125b was found to enhance DNR cytotoxicity in REH cells. Furthermore, miR-125b was observed to mediate DNR resistance in leukemia cell lines through decreasing expression of G protein-coupled receptor kinase 2 and p53-upregulated modulator of apoptosis, which were shown to be direct targets of miR-125b using a dual-luciferase reporter. The present study provides a novel mechanism for understanding leukemia drug resistance and provides a novel method for calculating patient prognosis.

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“…1C and H). The biodistributions of DXR-encapsulated liposomes were evaluated in the liver, spleen, kidney, and heart, with the latter being an important indicator of doxorubicin-mediated cardiotoxicity (33). At all time points, the accumulation of DXR or liposomes in the heart was low (Fig.…”

Section: Resultsmentioning

confidence: 99%

Targeting Liposomal Chemotherapy via Both Tumor Cell–Specific and Tumor Vasculature–Specific Ligands Potentiates Therapeutic Efficacy

et al. 2006

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Neuroblastoma, the most common solid tumor of infancy derived from the sympathetic nervous system, continues to present a formidable clinical challenge. Sterically stabilized immunoliposomes (SIL) have been shown to enhance the selective localization of entrapped drugs to solid tumors, with improvements in therapeutic indices. We showed that SIL loaded with doxorubicin (DXR) and targeted to the disialoganglioside receptor GD 2 [aGD 2 -SIL(DXR)] led to a selective inhibition of the metastatic growth of experimental models of human neuroblastoma. By coupling NGR peptides that target the angiogenic endothelial cell marker aminopeptidase N to the surface of DXR-loaded liposomes [NGR-SL(DXR)], we obtained tumor regression, pronounced destruction of the tumor vasculature, and prolonged survival of orthotopic neuroblastoma xenografts. Here, we showed good liposome stability, long circulation times, and enhanced timedependent tumor accumulation of both the carrier and the drug. Antivascular effects against animal models of lung and ovarian cancer were shown for formulations of NGR-SL(DXR). In the chick embryo chorioallantoic assay, NGR-SL(DXR) substantially reduced the angiogenic potential of various neuroblastoma xenografts, with synergistic inhibition observed for the combination of NGR-SL(DXR) with aGD 2 -SIL(DXR). A significant improvement in antitumor effects was seen in neuroblastoma-bearing animal models when treated with the combined formulations compared with control mice or mice treated with either tumor-or vascular-targeted liposomal formulations, administered separately. The combined treatment resulted in a dramatic inhibition of tumor endothelial cell density. Long-term survivors were obtained only in animals treated with the combined tumor-and vascular-targeted formulations, confirming the pivotal role of combination therapies in treating aggressive metastatic neuroblastoma.

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Anthracyclines in haematology: preclinical studies, toxicity and delivery systems

Cited by 77 publications

References 169 publications

Combination of glycosphingosomes and liposomal doxorubicin shows increased activity against dimethyl-α-benzanthracene-induced fibrosarcoma in mice

Combination of glycosphingosomes and liposomal doxorubicin shows increased activity against dimethyl-α-benzanthracene-induced fibrosarcoma in mice

microRNA-125b promotes leukemia cell resistance to daunorubicin by inhibiting apoptosis

Targeting Liposomal Chemotherapy via Both Tumor Cell–Specific and Tumor Vasculature–Specific Ligands Potentiates Therapeutic Efficacy

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Anthracyclines in haematology: preclinical studies, toxicity and delivery systems

Cited by 77 publications

References 169 publications

Combination of glycosphingosomes and liposomal doxorubicin shows increased activity against dimethyl-&alpha;-benzanthracene-induced fibrosarcoma in mice

Combination of glycosphingosomes and liposomal doxorubicin shows increased activity against dimethyl-&alpha;-benzanthracene-induced fibrosarcoma in mice

microRNA-125b promotes leukemia cell resistance to daunorubicin by inhibiting apoptosis

Targeting Liposomal Chemotherapy via Both Tumor Cell–Specific and Tumor Vasculature–Specific Ligands Potentiates Therapeutic Efficacy

Contact Info

Product

Resources

About

Combination of glycosphingosomes and liposomal doxorubicin shows increased activity against dimethyl-α-benzanthracene-induced fibrosarcoma in mice

Combination of glycosphingosomes and liposomal doxorubicin shows increased activity against dimethyl-α-benzanthracene-induced fibrosarcoma in mice