Phase 1b/2 study of orally administered pexidartinib in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma.

Background: Glioblastoma (GBM) has a median survival of <2 years. Pexidartinib (PLX3397) is a small-molecule inhibitor of CSF1R, KIT, and oncogenic FTL3, which are implicated in GBM treatment resistance. Results from glioma models indicate that combining radiation therapy (RT) and pexidartinib reduces radiation resistance.

Effect of Pneumocystis jirovecii pneumonia prophylaxis on hematologic toxicity in patients receiving chemoradiation for primary brain tumors.

Purpose: Diffuse gliomas are managed with radiation and temozolomide; however, this therapy often results in hematologic toxicities. Patients undergoing chemoradiation also risk contracting Pneumocystis jirovecii pneumonia (PJP), and frequently receive prophylaxis against PJP during treatment. Independent of chemoradiation, some PJP prophylaxis drugs have the potential to cause myelosuppression, which could require cessation of chemotherapy.

An evaluation of biobanking and therapeutic clinical trial representation among adult glioma patients from rural and urban Utah.

Background: Social determinants of health (SDOHs)-specifically those related to rurality, health care accessibility, and income-may play as-yet-unidentified roles in prognosis for glioma patients, and their impact on access to clinical trials is important to understand. We examined SDOHs of patients enrolled in glioma clinical trials and evaluate disparities in trial participation and outcomes between rural and urban patients.

Methods: We retrospectively identified patients enrolled in glioma clinical trials at Huntsman Cancer Institute (HCI) from May 2012 to May 2022 to evaluate clinical trial participation.

Medical Management of Meningiomas.

Meningiomas represent the most common type of benign tumor of the extra-axial compartment. Although most meningiomas are benign World Health Organization (WHO) grade 1 lesions, the increasingly prevalent of WHO grade 2 lesion and occasional grade 3 lesions show worsened recurrence rates and morbidity. Multiple medical treatments have been evaluated but show limited efficacy.

Incidence and extent of disease progression on MRI between surgery and initiation of radiotherapy in glioblastoma patients.

Background: A post-operative MRI (MRI) performed within 72 h is routinely used for radiation treatment planning in glioblastoma (GBM) patients, with radiotherapy starting about 4-6 weeks after surgery. Some patients undergo an additional pre-radiotherapy MRI (MRI) about 2-6 weeks after surgery. We sought to analyze the incidence of rapid early progression (REP) between surgery and initiation of radiotherapy seen on MRI and the impact on radiation target volumes.

Consolidation regimens in primary central nervous system lymphoma: a single-center retrospective cohort evaluating survival outcomes and cost-benefit analysis.

Unlabelled: ABSTRACT: PURPOSE: Optimal treatment for primary central nervous system lymphoma (PCNSL) comprises polychemotherapy induction with high-dose methotrexate followed by consolidation therapy, but there is no standard treatment regimen because of a lack of comparative trials examining efficacy or relative value. We performed a retrospective outcome and relative cost analysis on consolidation regimens to gain perspective on how cost and benefit can be weighed in medical decisions for patients with PCNSL.

Methods: Patients with newly diagnosed PCNSL who completed consolidation at our institution from July 1, 2012, to March 1, 2019, were included.

Targeted Next-Generation Sequencing Reveals Divergent Clonal Evolution in Components of Composite Pleomorphic Xanthoastrocytoma-Ganglioglioma.

Composite pleomorphic xanthoastrocytoma-ganglioglioma (PXA-GG) is an extremely rare central nervous system neoplasm with 2 distinct but intermingled components. Whether this tumor represents a "collision tumor" of separate neoplasms or a monoclonal neoplasm with divergent evolution is poorly understood. Clinicopathologic studies and capture-based next generation sequencing were performed on extracted DNA from all available PXA-GG at 2 medical centers.

The use and efficacy of chemotherapy and radiotherapy in children and adults with pilocytic astrocytoma.

Purpose: The aim of this study was to understand the use of chemotherapy (CMT) and radiotherapy (RT) in pilocytic astrocytoma (PA) and their impact on overall survival (OS).

Methods: Data from the National Cancer Database (NCDB) for patients with non-metastatic WHO grade I PA from 2004 to 2014 were analyzed. Pearson's chi-squared test and multivariate logistic regression analyses were performed to assess the distribution of demographic, clinical, and treatment factors.

Treatment of Primary Central Nervous System Lymphoma: From Chemotherapy to Small Molecules.

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma that is typically confined to the brain, eyes, and cerebrospinal fluid (CSF) without evidence of systemic spread. PCNSL is an uncommon tumor, and only four randomized trials and one phase III trial have been completed so far, all in the first-line setting. The prognosis of patients with PCNSL has improved during the past few decades with the introduction of high-dose methotrexate (HD-MTX), which now serves as the backbone of all first-line treatment regimens.

Metastatic Complications of Cancer Involving the Central and Peripheral Nervous Systems.

Neurologic complications of cancer may involve both the central nervous system and peripheral nervous system manifesting as brain, leptomeningeal, intramedullary, intradural, epidural, plexus, and skull base metastases. Excluding brain involvement, neurologic complications affecting these other sites are relatively infrequent, but collectively they affect more than 25% of patients with metastatic cancer causing significant morbidity and mortality. Early diagnosis and intervention optimize quality of life and improve survival.

The elderly left behind-changes in survival trends of primary central nervous system lymphoma over the past 4 decades.

Background: There has been significant improvement in treatment outcomes of primary central nervous system lymphoma (PCNSL) at specialized centers over the past several decades; however, it is unclear if these changes have translated to benefits in the general population.

Methods: In this study, we utilized 2 national databases to examine survival trends over time for PCNSL: the Central Brain Tumor Registry of the United States (CBTRUS, 2000-2013) and 18 registries from the Surveillance, Epidemiology, and End Results program (SEER, 1973-2013).

Results: The annual incidence of PCNSL in 2013 was 0.

Association between treatment-related lymphopenia and overall survival in elderly patients with newly diagnosed glioblastoma.

Management of patients with glioblastoma (GBM) often includes radiation (RT) and temozolomide (TMZ). The association between severe treatment-related lymphopenia (TRL) after the standard chemoradiation and reduced survival has been reported in GBM patients with the median age of 57. Similar findings were described in patients with head and neck, non-small cell lung, and pancreatic cancers.

Adverse radiation effect after stereotactic radiosurgery for brain metastases: incidence, time course, and risk factors.

Object: The authors sought to determine the incidence, time course, and risk factors for overall adverse radiation effect (ARE) and symptomatic ARE after stereotactic radiosurgery (SRS) for brain metastases.

Methods: All cases of brain metastases treated from 1998 through 2009 with Gamma Knife SRS at UCSF were considered. Cases with less than 3 months of follow-up imaging, a gap of more than 8 months in imaging during the 1st year, or inadequate imaging availability were excluded.

Abundance and location of proteoglycans and hyaluronan within normal and myxomatous mitral valves.

Introduction: Extracellular matrix changes occur in many heart valve pathologies. For example, myxomatous mitral valves are reported to contain excess proteoglycans and hyaluronan. However, it is unknown which specific proteoglycans are altered in myxomatous valves.

Reversible secretion of glycosaminoglycans and proteoglycans by cyclically stretched valvular cells in 3D culture.

Mitral valve leaflets and chordae have been shown to contain different amounts and proportions of glycosaminoglycans (GAGs) and proteoglycans (PGs) corresponding to in vivo normal or diseased cyclic strain patterns. To understand the effect of cyclic strains on GAG/PG synthesis by valvular interstitial cells (VICs) isolated from valve leaflet and chordae separately, porcine VICs were seeded within collagen gels and alternately stretched or relaxed for 24 h periods for one week in a custom-designed tissue engineering bioreactor. We found cyclic-stretch-induced upregulation of total GAGs and of individual GAG classes secreted into the culture medium.

Influence of strain on proteoglycan synthesis by valvular interstitial cells in three-dimensional culture.

Differently loaded regions of the mitral valve contain distinct amounts and types of proteoglycans (PGs); these PG profiles are altered in abnormal loading and disease conditions. We developed an in vitro three-dimensional model to analyze PGs secreted by valvular interstitial cells (VICs) isolated from distinct regions of porcine mitral valves (leaflet or chordae) and subjected to either biaxial or uniaxial mechanical constraints. In addition, the PGs, DNA and collagen content of the collagen gels was monitored over time.

Functionalization density dependence of single-walled carbon nanotubes cytotoxicity in vitro.

The cytotoxic response of cells in culture is dependant on the degree of functionalization of the single-walled carbon nanotube (SWNT). After characterizing a set of water-dispersible SWNTs, we performed in vitro cytotoxicity screens on cultured human dermal fibroblasts (HDF). The SWNT samples used in this exposure include SWNT-phenyl-SO(3)H and SWNT-phenyl-SO(3)Na (six samples with carbon/-phenyl-SO(3)X ratios of 18, 41, and 80), SWNT-phenyl-(COOH)(2) (one sample with carbon/-phenyl-(COOH)(2) ratio of 23), and underivatized SWNT stabilized in 1% Pluronic F108.

Nano-C60 cytotoxicity is due to lipid peroxidation.

This study examines the biological effects of water-soluble fullerene aggregates in an effort to evaluate the fundamental mechanisms that contribute to the cytotoxicity of a classic engineered nanomaterial. For this work we used a water-soluble fullerene species, nano-C60, a fullerene aggregate that readily forms when pristine C60 is added to water. Nano-C60 was cytotoxic to human dermal fibroblasts, human liver carcinoma cells (HepG2), and neuronal human astrocytes at doses>or= 50 ppb (LC50=2-50 ppb, depending on cell type) after 48 h exposure.