Network targeting combination therapy of synthetic lethal vulnerabilities in deficient glioblastoma: A case report.

Background: Patients with relapsed or progressive glioblastoma only rarely respond to salvage therapies. Nevertheless, comprehensive genomic profiling can provide insight that can identify promising approaches. Signaling pathway analyses have revealed synthetic lethal partnerships, which create the possibility of targeting vulnerabilities arising from the loss of tumor suppressor genes.

Contrast-enhanced ultrasound for abdominal image-guided procedures.

Introduction: Since FDA approval for contrast-enhanced ultrasound (CEUS), clinical applications have increased to include diagnostic imaging of hepatic, renal, and other abdominal lesions. The modality has also demonstrated utility in certain image-guided procedures. Intravascular ultrasound contrast agents use microbubbles to improve visibility of solid tumors.

Population Pharmacokinetic Analysis from First-in-Human Data for HDAC Inhibitor, REC-2282 (AR-42), in Patients with Solid Tumors and Hematologic Malignancies: A Case Study for Evaluating Flat vs. Body Size Normalized Dosing.

Background And Objectives: REC-2282 is a novel histone deacetylase inhibitor that has shown antitumor activity in in vitro and in vivo models of malignancy.  The aims of this study were to characterize the population pharmacokinetics of REC-2282 (AR-42) from the first-in-human (NCT01129193) and phase I acute myeloid leukemia trials (NCT01798901) and to evaluate potential sources of variability. Additionally, we sought to understand alternate body size descriptors as sources of inter-individual variability (IIV), which was significant for dose-normalized maximum observed concentration and area under the concentration-time curve (AUC).

Tumor heterogeneity and acquired drug resistance in FGFR2-fusion-positive cholangiocarcinoma through rapid research autopsy.

Cholangiocarcinoma is a highly aggressive and lethal malignancy, with limited treatment options available. Recently, FGFR inhibitors have been developed and utilized in FGFR-mutant cholangiocarcinoma; however, resistance often develops and the genomic determinants of resistance are not fully characterized. We completed whole-exome sequencing (WES) of 11 unique tumor samples obtained from a rapid research autopsy on a patient with FGFR-fusion-positive cholangiocarcinoma who initially responded to the pan-FGFR inhibitor, INCB054828.

Analytic validation and real-time clinical application of an amplicon-based targeted gene panel for advanced cancer.

Multiplex somatic testing has emerged as a strategy to test patients with advanced cancer. We demonstrate our analytic validation approach for a gene hotspot panel and real-time prospective clinical application for any cancer type. The TruSight Tumor 26 assay amplifies 85 somatic hotspot regions across 26 genes.

Interval Magnetic Resonance Imaging: an Alternative to Guidelines for Indeterminate Nodules Discovered in the Cirrhotic Liver.

Background: Current guidelines for the management of indeterminate nodules discovered on surveillance imaging recommend alternate imaging modality or biopsy. This study evaluates the use of short interval MRI rather than immediate CT or biopsy.

Method: This retrospective cohort study examines outcomes of 111 patients with indeterminate nodules reviewed by a single institution's Liver Tumor Board 2011-2016.

Pretransplant Locoregional Therapy for Hepatocellular Carcinoma: Evaluation of Explant Pathology and Overall Survival.

Background And Objectives: Liver transplant is an important treatment option for patients with hepatocellular carcinoma (HCC) within Milan criteria. We sought to determine the rate of complete tumor necrosis after bridging therapy.

Methods: The medical records of all 178 patients undergoing liver transplantation between January 1, 2008 and July 31, 2015 were reviewed.

Increased expression of CYP24A1 correlates with advanced stages of prostate cancer and can cause resistance to vitamin D3-based therapies.

A major limitation of exogenous vitamin D3 administration for the treatment of prostate cancer is the marginal, if any, clinical efficacy. We dissected the basis for the resistance to the vitamin D3 antitumor properties and specifically examined the effect of its major catabolic enzyme, CYP24A1, in prostate cancer. Local CYP24A1 expression levels and the effect of selective modulation were analyzed using tissue microarrays from needle core biopsy specimens and xenograft-bearing mouse models.

Pulsed high-intensity focused ultrasound enhances systemic administration of naked DNA in squamous cell carcinoma model: initial experience.

Purpose: To determine whether exposures to pulsed high-intensity focused ultrasound can enhance local delivery and expression of a reporter gene, administered with systemic injection of naked DNA, in tumors in mice.

Materials And Methods: The study was performed according to an approved animal protocol and in compliance with guidelines of the institutional animal care and use committee. Squamous cell carcinoma (SCC7) tumors were induced subcutaneously in both flanks of female C3H mice (n = 3) and allowed to grow to average size of 0.

Transient spleen enlargement in peripheral blood progenitor cell donors given G-CSF.

The administration of granulocyte colony-stimulating factor (G-CSF) to peripheral blood progenitor cell (PBPC) donors causes spleen length to increase, but the duration of enlargement is not known. Eighteen healthy subjects were given 10 microg/kg of G-CSF for 5 days and a PBSC concentrate was collected by apheresis. Ultrasound scans were used to assess craniocaudal spleen length before and after G-CSF administration.