Strategies for Targeting Tumors and Tumor Vasculature for Cancer Therapy

Sreeramoju, Prashanth; Libutti, Steven K.

doi:10.1016/s0065-2660(10)69015-3

Cited by 15 publications

(11 citation statements)

References 50 publications

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“…Advances in the treatment of cancer improved cancer-free survival and unfortunately highlighted the occurrence of previously unrecognized complications such as secondary neoplasms and off-target organ toxicity [1]–[4]. The potent anti-cancer effects of anthracyclines are limited by their cardiac toxicity [5].…”

Section: Introductionmentioning

confidence: 99%

Comparative Cardiac Toxicity of Anthracyclines In Vitro and In Vivo in the Mouse

et al. 2013

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PurposeThe antineoplastic efficacy of anthracyclines is limited by their cardiac toxicity. In this study, we evaluated the toxicity of doxorubicin, non-pegylated liposomal-delivered doxorubicin, and epirubicin in HL-1 adult cardiomyocytes in culture as well as in the mouse in vivo.MethodsThe cardiomyocytes were incubated with the three anthracyclines (1 µM) to assess reactive oxygen generation, DNA damage and apoptotic cell death. CF-1 mice (10/group) received doxorubicin, epirubicin or non-pegylated liposomal-doxorubicin (10 mg/kg) and cardiac function was monitored by Doppler echocardiography to measure left ventricular ejection fraction (LVEF), heart rate (HR) and cardiac output (CO) both prior to and 10 days after drug treatment.ResultsIn HL-1 cells, non-pegylated liposomal-doxorubicin generated significantly less reactive oxygen species (ROS), as well as less DNA damage and apoptosis activation when compared with doxorubicin and epirubicin. Cultured breast tumor cells showed similar sensitivity to the three anthracyclines. In the healthy mouse, non-pegylated liposomal doxorubicin showed a minimal and non-significant decrease in LVEF with no change in HR or CO, compared to doxorubicin and epirubicin.ConclusionThis study provides evidence for reduced cardiac toxicity of non-pegylated-liposomal doxorubicin characterized by attenuation of ROS generation, DNA damage and apoptosis in comparison to epirubicin and doxorubicin.

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Section: Introductionmentioning

confidence: 99%

Comparative Cardiac Toxicity of Anthracyclines In Vitro and In Vivo in the Mouse

et al. 2013

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“…Furthermore, some quinones are also known to have narrow therapeutic indices with substantial toxicities to normal tissues 21. These limitations of the anticancer chemotherapies have been overcome by the use of various drug delivery approaches that provide selective, and sufficiently high, localization of ‘‘active’’ drug at the tumor site,22 thereby improving the tumoricidal efficacy and reducing the systemic toxicity of the entrapped drug. Among the various particulate drug carriers, liposomes have gained most attention.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Pharmacokinetic, Biodistribution, Pharmacodynamic, and Toxicity Profile of Free Juglone and Its Sterically Stabilized Liposomes

Aithal

Kumar

Rao

et al. 2011

Journal of Pharmaceutical Sciences

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“…To date, current approaches to gene therapy have had disappointing results, because of the inability to achieve expression of the transgene in different tumor-cell populations and in all tumor-site locations. 1 In view of the constant requirement for vascular supply in solid tumors, and considering that tumor-associated neovascularization involves the recruitment of endothelial progenitor cells (EPCs) as well as endothelial cells to the tumor vasculature, 2 use of EPCs as carriers of therapeutic agents to tumor sites and inhibition of tumor-induced neovascularization have been an effective anticancer approach.…”

Section: Introductionmentioning

confidence: 99%

Interferon-β efficiently inhibited endothelial progenitor cell-induced tumor angiogenesis

et al. 2011

Gene Ther

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Neovascularization has a critical role in the growth and metastatic spread of tumors, and involves recruitment of circulating endothelial progenitor cells (EPCs) from bone marrow. In this study, we examined whether EPCs could promote tumor angiogenesis, and found that the tumor growth was enhanced by the administration of EPCs. To test the hypothesis that genetically modified bone marrow-derived EPCs can be effective carriers of therapeutic agents to tumor sites, we conducted human interferon-beta (HuIFN-b) gene transfection of EPCs with a virus vector in vitro. When HuIFN-b was applied in the ex vivo culture of EPCs, HuIFN-b-transduced EPCs achieved efficient killing of the total population of SPC-A1 cells, indicating a bystander effect was elicited by HuIFN-b-transduced EPCs in vitro. When SCP-A1 cancer cells were coimplanted along with ex vivo cultivated EPCs subcutaneous injection in nude mice, the tumor growth was increased. However, the anti-tumor effect of interferon-beta (IFN-b) offset the tumor-progressive character of EPCs and the tumor growth, and the vascular density of tumor tissues increased by coimplanted EPCs were decreased upon IFN-b treatment. In addition, overall expression levels of vascular endothelial growth factor in tumor tissues were decreased upon IFN-b treatment. Therefore, our results suggest that gene-transfected EPCs could be useful as a tumor-specific drug delivery system.

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Strategies for Targeting Tumors and Tumor Vasculature for Cancer Therapy

Cited by 15 publications

References 50 publications

Comparative Cardiac Toxicity of Anthracyclines In Vitro and In Vivo in the Mouse

Comparative Cardiac Toxicity of Anthracyclines In Vitro and In Vivo in the Mouse

Evaluation of Pharmacokinetic, Biodistribution, Pharmacodynamic, and Toxicity Profile of Free Juglone and Its Sterically Stabilized Liposomes

Interferon-β efficiently inhibited endothelial progenitor cell-induced tumor angiogenesis

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