A phase I/II study of ribociclib following radiation therapy in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG)

ConclusionsRibociclib administered following radiotherapy is feasible in DIPG and DMG. Increased tumor necrosis may represent a treatment effect. These data warrant further prospective volumetric analyses of tumors with necrosis. Feasibility and stabilization findings support further investigation of ribociclib in combination therapies.Trial registrationNCT02607124.
Source: Journal of Neuro-Oncology - Category: Cancer & Oncology Source Type: research

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Nutr Cancer. 2021 Aug 2:1-11. doi: 10.1080/01635581.2021.1957488. Online ahead of print.ABSTRACTGliomas are considered as one of the important brain tumors in adults due to their impact on life quality and cognitive functions. Current methods that are used for treating glioma are not satisfying enough. Understanding cellular and molecular events underlying its pathogenesis and progression may lead to the discovery of novel therapeutic approaches. Sterols are a subtype of steroids and are essential for the physiologic functions of eukaryotic cells. Sterols can be produced by protozoans and microheterotrophs. Moreover, they ...
Source: Nutrition and Cancer - Category: Cancer & Oncology Authors: Source Type: research
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Discussion Suppressor of cytokine signaling 1 is an essential molecule for maintaining immune homeostasis and subverting inflammation. Disorders arising from excess inflammation or SOCS1 deficiency can be potentially treated with SOCS1 mimetics (Ahmed et al., 2015). While SOCS1 has promising potential in many disorders, it should be noted that new targets and actions of SOCS1 are still being discovered and not all the effects of this protein are beneficial in autoimmune diseases and cancer. For instance, SOCS1 degrades IRS1 and IRS2, required for insulin signaling, via the SOCS Box domain, thus, limiting its potential in ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
AbstractBrain tumors emerge as the second commonest type of pediatric solid tumors following hematologic malignancies. Genomic profiling of low- and high-grade gliomas, ependymomas and medulloblastomas has revealed chromosomal abnormalities and specific gene mutations which have been associated with aberrant activation of crucial signal transduction pathways, including mitogen-activated protein kinase, mammalian target of rapamycin and retinoblastoma tumor suppressor signaling. Furthermore, pediatric high-grade gliomas are associated with chromatin remodeling defects and somatic histone gene mutations that affect prognosis...
Source: NeuroMolecular Medicine - Category: Neurology Source Type: research
Pediatric patients with brain tumors have limited treatment options and poor long-term survival. CDK4/6 bound with Cyclin D regulates cell proliferation by phosphorylating retinoblastoma protein (Rb) and releasing E2F, a positive regulator of the G1/S transition. Ribociclib, a CDK4/6 inhibitor is under clinical evaluation for treatment of pediatric malignancies. We evaluated its CNS penetration in two pediatric brain tumor models (diffuse intrinsic pontine glioma [DIPG] and Group 3 medulloblastoma [G3MB]) and in normal mouse brain using cerebral microdialysis. A plasma pharmacokinetic study of 100 mg/kg orally-ad...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: PEDIATRIC TUMORS - PRECLINICAL STUDIES (NON-IMMUNOLOGICAL) Source Type: research
The objective of this review then is to discuss the history and current state of containment around the San Jacinto waste pits and analyze spatial and temporal trends in the PCDD/PCDF deposition through the SJR system from the data available. We will discuss the current exposure and health risks represented by the Superfund site and the SJR system itself, as well as the discovery of liver, kidney, brain (glioma), and retinoblastoma cancer clusters in eastern Harris County across multiple census tracts that border the Superfund site. We will also cover the two primary management options, containment versus removal of the wa...
Source: Environmental Science and Pollution Research International - Category: Environmental Health Authors: Tags: Environ Sci Pollut Res Int Source Type: research
This article is protected by copyright. All rights reserved.
Source: International Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Short Report Source Type: research
Publication date: 2016 Source:Handbook of Clinical Neurology, Volume 134 Author(s): Hans-Georg Wirsching, Evanthia Galanis, Michael Weller Glioblastoma is the most common and aggressive primary brain tumor in adults. Defining histopathologic features are necrosis and endothelial proliferation, resulting in the assignment of grade IV, the highest grade in the World Health Organization (WHO) classification of brain tumors. The classic clinical term “secondary glioblastoma” refers to a minority of glioblastomas that evolve from previously diagnosed WHO grade II or grade III gliomas. Specific point mutations o...
Source: Handbook of Clinical Neurology - Category: Neurology Source Type: research
Conclusion Thus, the brain penetration of palbociclib is restricted by P-gp and BCRP, which may restrict the efficacy against GBM and DIPG. Moreover, preclinical studies with this agent should be conducted at a more clinically relevant dose level.
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research
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