PCM-12morphine Improves Efficacy of Chemotherapy in an Intracranial Xenograft Model of Human Glioblastoma

Ros, Martina Da; Iorio, Anna Lisa; Lucchesi, M; Guidi, Milena; Fonte, Carla; Favre, Claudio; Genitori, Lorenzo; Sardi, Iacopo

doi:10.1093/neuonc/now080.12

Cited by 8 publications

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“…On the other hand, in vivo studies have suggested that stress associated with high doses morphine administration or withdrawal can influence the BBB function [ 17 , 33 , 34 ] and allow the accumulation and the efficacy of anticancer drugs [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…A total of 136 Foxn1 nude mice have been used in this study. The procedure of animals accommodation and care have been described in detail previously [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

“…Basing on literature data regarding the pharmacological modulation of BBB by morphine [ 17 ], the most commonly used opioid in oncological patients, we have recently demonstrated that this agent is able to increase delivery and efficacy of doxorubicin (Dox) in animal models, without increasing systemic toxicities [ 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

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Tumor response of temozolomide in combination with morphine in a xenograft model of human glioblastoma

et al. 2017

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Despite multimodal treatments comprising, radiation therapy (RT) and chemotherapy with temozolomide (TMZ), the prognosis of glioblastoma multiforme (GBM) remains dismal and consolidated therapy yields a median survival of 14.6 months.Blood Brain Barrier (BBB) mediated chemoresistance and high dose related toxicity make necessary the development of new therapeutic approach to sensitize GBM to TMZ.The aim of the present study was to investigate the potential of the treatment morphine plus TMZ metronmic doses (1,77 and 0,9 mg/kg) in GBM therapy.The effect of morphine, on tumor cell growth and P-glycoprothein (P-gp) activity, was investigate in in vitro models.The results demonstrated that GBM cells growth is not influenced by morphine treatment and, for the first time, we show that morphine is an inhibitor of the activity of P-gp efflux transporter who is markedly expressed on BBB.In vivo, response to the treatments TMZ plus morphine was investigated in an orthotopic nude mice model of GBM.Animals treated with TMZ metronomic doses showed a significant tumor growth inhibition compared to untreated mice and association with morphine appears to improve TMZ efficacy.Moreover, the combination of morphine with lower dose of TMZ result in a cytostatic effect on tumor growth over the period of the pharmacological treatments.In conclusion this novel approach could be a successful strategy to overcome chemoresistance and side effects TMZ mediated, reducing drug dosage and improving long term response, in GBM therapy.

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Section: Discussionmentioning

confidence: 99%

“…A total of 136 Foxn1 nude mice have been used in this study. The procedure of animals accommodation and care have been described in detail previously [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tumor response of temozolomide in combination with morphine in a xenograft model of human glioblastoma

et al. 2017

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“…Based on the results, the co-exposure to TMZ did not significantly improve the uptake of Aldox, itself able to accumulate in P-gp-overexpressed cells (upper panel, Figure 3B ) due to a negative regulation of the P-gp function. As shown in Figure 3B (lower panel), the mean fluorescence intensity of Aldox in MDCKII parental cells was superior to that of MDCKII P-gp cells; however, compared to untreated P-gp trasfected cells, the same samples exposed to Aldox contained a higher amount of the anthracycline, unlike the previously observed with Dox [ 23 ].…”

Section: Discussionmentioning

confidence: 74%

Aldoxorubicin and Temozolomide combination in a xenograft mice model of human glioblastoma

et al. 2018

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Glioblastoma Multiforme (GBM) is still an incurable disease. The front-line Temozolomide (TMZ)-based therapy suffers from poor efficacy, underlining the need of new therapies.Preclinically, Aldoxorubicin (Aldox), a novel prodrug of Doxorubicin (Dox), has been successfully tested against GBM, encouraging the study of its association with other agents.For the first time, we evaluated the effectiveness of Aldox combined to TMZ in preclinical models of GBM.Our in vitro results demonstrated that the anti–glioma effect of Aldox was more marked than TMZ and their combination increased the killing effect of the anthracycline in TMZ-resistant GBM cells. Moreover, unlike Dox, Aldox was able to accumulate in P-glycoprotein (P-gp)-overexpressed cells due to a negative regulation of the P-gp function.We also compared efficacy and safety of weekly administrations of Aldox (16 mg/kg), with or without TMZ (0.9 mg/kg, daily injections), in the U87 xenograft mouse model.Aldox therapy induced a moderate tumor volume inhibition (TVI) and an increased survival rate (+12.5% vs vehicle). On the other hand, when combined to TMZ, Aldox caused a significant TVI (P=0.0175 vs vehicle) and delayed the mortality during the experimental period, although TVI and endpoint survival percentage (+37.5% vs vehicle) were not significantly different from TMZ alone.Our preliminary data showed that Aldox exerts anti–glioma effects in vitro and in vivo. It also enhances its antitumor activity when combined with TMZ, resulting in a superior efficacy compared to the single agents, without adverse side effects.

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“…Among the various types of cancers, glioblastoma multiforme (GBM) is a common malignant brain tumor in adults and is considered to be incurable in most patients, with a very poor survival rate . The treatment options available for combating GBMs include neurosurgery, chemotherapy, radiation therapy (RT), or a combination of multiple modalities . Among them, RT is widely used in clinical treatments for GBMs.…”

Section: A Brief Literature Overview On the Various Boron‐containing mentioning

confidence: 99%

Engineering Novel Targeted Boron‐10‐Enriched Theranostic Nanomedicine to Combat against Murine Brain Tumors via MR Imaging‐Guided Boron Neutron Capture Therapy

et al. 2017

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Glioblastoma multiforme (GBM) is a very common type of "incurable" malignant brain tumor. Although many treatment options are currently available, most of them eventually fail due to its recurrence. Boron neutron capture therapy (BNCT) emerges as an alternative noninvasive therapeutic treatment modality. The major challenge in treating GBMs using BNCT is to achieve selective imaging, targeting, and sufficient accumulation of boron-containing drug at the tumor site so that effective destruction of tumor cells can be achieved without harming the normal brain cells. To tackle this challenge, this study demonstrates for the first time that an unprecedented B-enriched (96% B enrichment) boron nanoparticle nanomedicine ( BSGRF NPs) surface-modified with a Fluorescein isothiocyanate (FITC)-labeled RGD-K peptide can pass through the brain blood barrier, selectively target at GBM brain tumor sites, and deliver high therapeutic dosage (50.5 µg B g cells) of boron atoms to tumor cells with a good tumor-to-blood boron ratio of 2.8. The BSGRF NPs not only can enhance the contrast of magnetic resonance (MR) imaging to help diagnose the location/size/progress of brain tumor, but also effectively suppress murine brain tumors via MR imaging-guided BNCT, prolonging the half-life of mice from 22 d (untreated group) to 39 d.

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PCM-12morphine Improves Efficacy of Chemotherapy in an Intracranial Xenograft Model of Human Glioblastoma

Cited by 8 publications

References 0 publications

Tumor response of temozolomide in combination with morphine in a xenograft model of human glioblastoma

Tumor response of temozolomide in combination with morphine in a xenograft model of human glioblastoma

Aldoxorubicin and Temozolomide combination in a xenograft mice model of human glioblastoma

Engineering Novel Targeted Boron‐10‐Enriched Theranostic Nanomedicine to Combat against Murine Brain Tumors via MR Imaging‐Guided Boron Neutron Capture Therapy

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