Single-Cell Heterogeneity of EGFR Pathway Is Linked to Unique Signatures of Drug Response and Malignancy in Patient Derived Glioblastoma Stem Cells.

Purpose: In glioblastoma, the therapeutically intractable and resistant phenotypes can be derived from glioma stem cells, which often have different underlying mechanisms from non-stem glioma cells. Aberrant signaling across the EGFR-PTEN-AKT-mTOR pathways have been shown as common drivers of glioblastoma. Revealing the inter and intra-cellular heterogeneity within glioma stem cell populations in relations to signaling patterns through these pathways may be key to precision diagnostic and therapeutic targeting of these cells.

Analysis of tumor template from multiple compartments in a blood sample provides complementary access to peripheral tumor biomarkers.

Targeted cancer therapeutics are promised to have a major impact on cancer treatment and survival. Successful application of these novel treatments requires a molecular definition of a patient's disease typically achieved through the use of tissue biopsies. Alternatively, allowing longitudinal monitoring, biomarkers derived from blood, isolated either from circulating tumor cell derived DNA (ctcDNA) or circulating cell-free tumor DNA (ccfDNA) may be evaluated.

Automated reagent-dispensing system for microfluidic cell biology assays.

Microscale systems that enable measurements of oncological phenomena at the single-cell level have a great capacity to improve therapeutic strategies and diagnostics. Such measurements can reveal unprecedented insights into cellular heterogeneity and its implications into the progression and treatment of complicated cellular disease processes such as those found in cancer. We describe a novel fluid-delivery platform to interface with low-cost microfluidic chips containing arrays of microchambers.

A molecular screening approach to identify and characterize inhibitors of glioblastoma stem cells.

Glioblastoma (GBM) is among the most lethal of all cancers. GBM consist of a heterogeneous population of tumor cells among which a tumor-initiating and treatment-resistant subpopulation, here termed GBM stem cells, have been identified as primary therapeutic targets. Here, we describe a high-throughput small molecule screening approach that enables the identification and characterization of chemical compounds that are effective against GBM stem cells.

Microfluidics for positron emission tomography probe development.

Owing to increased needs for positron emission tomography (PET), high demands for a wide variety of radiolabeled compounds will have to be met by exploiting novel radiochemistry and engineering technologies to improve the production and development of PET probes. The application of microfluidic reactors to perform radiosyntheses is currently attracting a great deal of interest because of their potential to deliver many advantages over conventional labeling systems. Microfluidics-based radiochemistry can lead to the use of smaller quantities of precursors, accelerated reaction rates, and easier purification processes with greater yield and higher specific activity of desired probes.

A microfluidic platform for systems pathology: multiparameter single-cell signaling measurements of clinical brain tumor specimens.

The clinical practice of oncology is being transformed by molecular diagnostics that will enable predictive and personalized medicine. Current technologies for quantitation of the cancer proteome are either qualitative (e.g.

Clinical outcome in pediatric glial and embryonal brain tumors correlates with in vitro multi-passageable neurosphere formation.

Background: Cultured brain tumors can form neurospheres harboring tumorigenic cells with self renewal and differentiation capacities. Renewable neurosphere formation has clinical predictive value in adult malignant gliomas, yet its prognostic role for pediatric brain tumors is unknown.

Methods: Established neurosphere conditions were used for culturing samples from glial, embryonal and mixed glioneuronal tumors from 56 pediatric patients.

Outcomes of laser thermal therapy for recurrent head and neck cancer.

Objective: To review the outcomes of a phase II study using laser-induced thermal therapy (LITT) as a palliative treatment for 106 patients with recurrent head and neck tumors.

Study Design: Retrospective study.

Setting: Tertiary hospital in the United States.

Neurosphere formation is an independent predictor of clinical outcome in malignant glioma.

Renewable neurosphere formation in culture is a defining characteristic of certain brain tumor initiating cells. This retrospective study was designed to assess the relationship among neurosphere formation in cultured human glioma, tumorigenic capacity, and patient clinical outcome. Tumor samples were cultured in neurosphere conditions from 32 patients with glioma, including a subpopulation of 15 patients with primary glioblastoma.

Maternal embryonic leucine zipper kinase is a key regulator of the proliferation of malignant brain tumors, including brain tumor stem cells.

Emerging evidence suggests that neural stem cells and brain tumors regulate their proliferation via similar pathways. In a previous study, we demonstrated that maternal embryonic leucine zipper kinase (Melk) is highly expressed in murine neural stem cells and regulates their proliferation. Here we describe how MELK expression is correlated with pathologic grade of brain tumors, and its expression levels are significantly correlated with shorter survival, particularly in younger glioblastoma patients.

Ultrasound-guided laser-induced thermal therapy of malignant cervical adenopathy.

Objectives: Laser-induced thermal therapy (LITT) for cancer is a technique whereby a source of energy (laser, radiofrequency, ultrasonic, cryoenergy, and so on) is directly applied into a tumor at various depths. Recent studies have demonstrated the efficiency of ultrasound (UTZ) and magnetic resonance imaging (MRI) for real- or "near" real-time tumor and vessel identification as well as monitoring and quantifying energy-induced tissue damage. The objective of this study is to report UCLA's experience using UTZ monitoring of Nd:YAG laser thermal ablation of malignant cervical adenopathy in a phase II study.

Cancerous stem cells can arise from pediatric brain tumors.

Pediatric brain tumors are significant causes of morbidity and mortality. It has been hypothesized that they derive from self-renewing multipotent neural stem cells. Here, we tested whether different pediatric brain tumors, including medulloblastomas and gliomas, contain cells with properties similar to neural stem cells.

Distal slit valve and clinically relevant CSF overdrainage in children with hydrocephalus.

Introduction: Distal slit valve (DSV) is a system designed for the treatment of hydrocephalus. It has been assumed that, by dispensing with an anti-siphon (AS) mechanism, the DSV induces a set of clinical symptoms associated with fluid overdrainage in patients. Nonetheless, there is no published evidence to support this assumption.