Treatment Of Pediatric Low-grade Gliomas Research Articles

Preclinical Evaluation of Dipotassium Bisperoxo (Picolinato) Oxovanadate V for the Treatment of Pediatric Low-Grade Gliomas

The treatment of pediatric low-grade gliomas with current treatment modalities still remains ineffective among a subset of patients; hence, justifying the need to further investigate more effective therapies. Dipotassium bisperoxo (picolinato) oxovanadate V (Bpv[pic]), is a derivative of the trace metal vanadium and a potent inhibitor of protein tyrosine phosphatases, which are important mediators of oncogenic and tumor suppressive activities in cancers. In this study, we undertook a preclinical evaluation of the antineoplastic functions of Bpv(pic) in the treatment of pediatric low-grade gliomas. We utilized pediatric low-grade glioma cell lines (Res186, Res259 and R286) in a wide variety of cancer assays to determine whether Bpv(pic) can abrogate the neoplastic properties of these cells. Our preclinical evaluation of the antineoplastic properties of Bpv(pic) in pediatric low-grade gliomas reveals a significant dose-dependent decrease in cell viability as a consequence of decreased proliferation and sustained induction of growth arrest and apoptosis. Bpv(pic) significantly decreases cell migration/invasion and anchorage-independent growth in soft agarose. Within cells, Bpv(pic) functions by attenuating CDC25A activity, and by decreasing the expression of multiple protein tyrosine phosphatases, DNA repair genes, microtubule-associated genes, such as PLK1, AURKA and HDAC6, and conversely augmenting the expression of proapoptotic mediators such as BAK, AIFM and CTSL1. Collectively, our data strongly suggest novel evidence of Bpv(pic) being a potent antineoplastic drug and a suitable alternative for the treatment of pediatric low-grade gliomas.

Objective response of multiply recurrent low‐grade gliomas to bevacizumab and irinotecan

Chemotherapy has taken on a prominent role in the treatment of pediatric low-grade gliomas not amenable to gross total resections; however, there are few proven effective options for children with multiply recurrent tumors. Bevacizumab, a humanized immunoglobulin, monoclonal antibody that inhibits the activity of vascular endothelial growth factor and irinotecan have been used with some success in adults with malignant gliomas. Ten children with multiply recurrent low-grade gliomas were treated with the combination of bevacizumab and irinotecan. Patients received treatment at a median of 5.2 years of age, range 1.5-11.1 years. The majority had diencephalic tumors, three had neurofibromatosis type 1, and two had disseminated disease at the time of treatment. Nine of 10 patients had progressed after three or greater chemotherapy regimens and one also had received radiation therapy. Seven patients had an objective neuroradiographic response, which was a complete response in one, partial response in three, and minor response in three. Clinical improvements were noted in seven, including improved visual acuity (2), improved motor function (2), weight gain in four with a diencephalic syndrome, and reversal of psychomotor retardation (3). Dose-limiting toxicities included transient leukoencephalopathy (1) and grade 3 protienuria (1). Response was durable in the majority of patients and six remain on treatment, for up to 22 months. Multiply recurrent low-grade gliomas in children are responsive to the combination of bevacizumab and irinotecan. The drug combination has been relatively well tolerated, including in patients with neurofibromatosis type 1, and warrants further study.