Functional precision medicine: the future of cancer care.

Functional precision medicine (FPM), combining ex vivo drug sensitivity testing with genomic profiling to identify treatment options for recurrent/refractory cancer, is feasible and poised to accelerate. This forum explores the history of FPM, recent clinical advancements, and barriers to expanding the clinical utility and accessibility for pediatric/adolescent and adult cancers.

Imaging neuroinflammation with TSPO: A new perspective on the cellular sources and subcellular localization.

Translocator Protein 18 kDa (TSPO), previously named Peripheral Benzodiazepine Receptor, is a well-validated and widely used biomarker of neuroinflammation to assess diverse central nervous system (CNS) pathologies in preclinical and clinical studies. Many studies have shown that in animal models of human neurological and neurodegenerative disease and in the human condition, TSPO levels increase in the brain neuropil, and this increase is driven by infiltration of peripheral inflammatory cells and activation of glial cells. Therefore, a clear understanding of the dynamics of the cellular sources of the TSPO response is critically important in the interpretation of Positron Emission Tomography (PET) studies and for understanding the pathophysiology of CNS diseases.

The Translocator Protein () Genetic Polymorphism A147T Is Associated with Worse Survival in Male Glioblastoma Patients.

Glioblastoma (GBM) is the most common primary brain tumor in adults, with few available therapies and a five-year survival rate of 7.2%. Hence, strategies for improving GBM prognosis are urgently needed.

Mapping chemotherapeutic drug distribution in cancer cell spheroids using 2D-TOF-SIMS and LESA-TIMS-MS.

Three-dimensional (3D) cancer cell cultures grown in the form of spheroids are effective models for the study of in vivo-like processes simulating cancer tumor pharmacological dynamics and morphology. In this study, we show the advantages of Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS) combined with in situ Liquid Extraction Surface Analysis coupled to trapped Ion Mobility Spectrometry Mass Spectrometry (LESA-TIMS-TOF MS) for high spatial resolution mapping and quantitation of ABT-737, a chemotherapeutic drug, at the level of single human colon carcinoma cell spheroids (HCT 116 MCS). 2D-TOF-SIMS studies of consecutive sections (∼16 μm thick slices) showed that ABT-737 is homogenously distributed in the outer layers of the HCT 116 MCS.

Tyrosyl-DNA Phosphodiesterase 1 and Topoisomerase I Activities as Predictive Indicators for Glioblastoma Susceptibility to Genotoxic Agents.

Glioblastoma (GBM) patients have an estimated survival of ~15 months with treatment, and the standard of care only modestly enhances patient survival. Identifying biomarkers representing vulnerabilities may allow for the selection of efficacious chemotherapy options to address personalized variations in GBM tumors. Irinotecan targets topoisomerase I (TOP1) by forming a ternary DNA-TOP1 cleavage complex (TOP1cc), inducing apoptosis.

The aberrant splicing of BAF45d links splicing regulation and transcription in glioblastoma.

Background: Glioblastoma, the most aggressive primary brain tumor, is genetically heterogeneous. Alternative splicing (AS) plays a key role in numerous pathologies, including cancer. The objectives of our study were to determine whether aberrant AS could play a role in the malignant phenotype of glioma and to understand the mechanism underlying its aberrant regulation.

Potentiation of morphine-induced antinociception and locomotion by citalopram is accompanied by anxiolytic-like effects.

Morphine and related opioids are the mainstay of analgesic treatment, especially in patients suffering chronic pain. Besides their antinociceptive effects they may also exhibit anxiolytic-like properties that could contribute to pain relief. The pharmacological manipulation of the serotonergic system may not only modulate pain transmission and processing but also other behavioral effects of opioids.

Analysis of SOX2-Regulated Transcriptome in Glioma Stem Cells.

Introduction: Glioblastoma is the most malignant brain tumor in adults and is associated with poor survival despite multimodal treatments. Glioma stem-like cells (GSCs) are cells functionally defined by their self-renewal potential and the ability to reconstitute the original tumor upon orthotopic implantation. They have been postulated to be the culprit of glioma chemo- and radio-resistance ultimately leading to relapse.

Correction: Characterization of the Antiglioma Effect of the Oncolytic Adenovirus VCN-01.

[This corrects the article DOI: 10.1371/journal.pone.

Characterization of the Antiglioma Effect of the Oncolytic Adenovirus VCN-01.

Despite the recent advances in the development of antitumor therapies, the prognosis for patients with malignant gliomas remains dismal. Therapy with tumor-selective viruses is emerging as a treatment option for this devastating disease. In this study we characterize the anti-glioma effect of VCN-01, an improved hyaluronidase-armed pRB-pathway-selective oncolytic adenovirus that has proven safe and effective in the treatment of several solid tumors.

The Oncolytic Adenovirus VCN-01 as Therapeutic Approach Against Pediatric Osteosarcoma.

Purpose: Osteosarcoma is the most common malignant bone tumor in children and adolescents. Despite aggressive chemotherapy, more than 30% of patients do not respond and develop bone or lung metastasis. Oncolytic adenoviruses engineered to specifically destroy cancer cells are a feasible option for osteosarcoma treatment.