Real-world use and outcomes of targeted therapy and immunotherapy for adjuvant treatment of BRAF -mutated melanoma patients in the United States.

Using a customized, harmonized US electronic health record database, real-world prescription patterns of first-line adjuvant immunotherapy and targeted therapy were retrospectively assessed for BRAF V600-mutated melanoma. Adults with BRAF V600 mutation-positive stage IIIA-D cutaneous melanoma who received first-line adjuvant immunotherapy (nivolumab or pembrolizumab) or targeted therapy (dabrafenib plus trametinib) between 1 January 2014 and 30 August 2020 in the NOBLE database were included. Patients were followed from first-line adjuvant therapy initiation for at least 6 months, until death, progression, follow-up loss, or data cutoff.

STING activation reprograms the microenvironment to sensitize NF1-related malignant peripheral nerve sheath tumors for immunotherapy.

Neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene that encodes neurofibromin, a RAS GTPase-activating protein. Inactivating NF1 mutations cause hyperactivation of RAS-mediated signaling, resulting in the development of multiple neoplasms, including malignant peripheral nerve sheath tumors (MPNSTs). MPNSTs are an aggressive tumor and the main cause of mortality in patients with NF1.

Gene Expression Analysis Links Autocrine Vasoactive Intestinal Peptide and ZEB1 in Gastrointestinal Cancers.

VIP (vasoactive intestinal peptide) is a 28-amino acid peptide hormone expressed by cancer and the healthy nervous system, digestive tract, cardiovascular, and immune cell tissues. Many cancers express VIP and its surface receptors VPAC1 and VPAC2, but the role of autocrine VIP signaling in cancer as a targetable prognostic and predictive biomarker remains poorly understood. Therefore, we conducted an in silico gene expression analysis to study the mechanisms of autocrine VIP signaling in cancer.

Passenger pathogens on physicians.

Background: Hospital acquired infections pose a significant risk for patients undergoing hematopoietic stem cell transplantation. Horizontal transfer of antimicrobial resistance genes contributes to prevalence of multidrug-resistant infections in this patient population.

Methods: At an academic bone marrow transplantation center, we performed whole genome DNA sequencing (WGS) on commonly used physician items, including badges, stethoscopes, soles of shoes, and smart phones from 6 physicians.

Step Length Estimation with Wearable Wrist Sensor using ANN.

Step Length is an important metric that can be used for the analysis and assessment of the gait. Proper dynamical models are not available in current literature associated with the wrist that can adequately determine the step length using recursive estimation techniques. This study presents a method to estimate the step length using angular velocity data from the wrist sensor.

Estimation of Step Length With Wearable Thigh Sensor Using an Unscented Kalman Filter.

The determination of step length, an important gait parameter, has been a challenging task. Although unobtrusive sensors (inertial measurement units) have been developed recently, they cannot facilitate the automatic estimation of step length. In this article, we use a model-based technique to determine the step length using the Unscented Kalman Filter with angular velocity from a gyroscope inside the thigh pocket.

Strategies to Overcome Failures in T-Cell Immunotherapies by Targeting PI3K-δ and -γ.

PI3K-δ and PI3K-γ are critical regulators of T-cell differentiation, senescence, and metabolism. PI3K-δ and PI3K-γ signaling can contribute to T-cell inhibition intrinsic mechanisms and regulation of suppressor cell populations, including regulatory T-cells and myeloid derived suppressor cells in the tumor. We examine an exciting new role for using selective inhibitors of the PI3K δ- and γ-isoforms as modulators of T-cell phenotype and function in immunotherapy.

Phosphoinositide 3-Kinase Signaling Can Modulate MHC Class I and II Expression.

Molecular events activating the PI3K pathway are frequently detected in human tumors and the activation of PI3K signaling alters numerous cellular processes including tumor cell proliferation, survival, and motility. More recent studies have highlighted the impact of PI3K signaling on the cellular response to interferons and other immunologic processes relevant to antitumor immunity. Given the ability of IFNγ to regulate antigen processing and presentation and the pivotal role of MHC class I (MHCI) and II (MHCII) expression in T-cell-mediated antitumor immunity, we sought to determine the impact of PI3K signaling on MHCI and MHCII induction by IFNγ.

Application of a telomerase-based circulating tumor cell (CTC) assay in bladder cancer patients receiving postoperative radiation therapy: a case study.

Background: Muscle invasive bladder carcinoma is an often lethal disease that requires aggressive treatment. Improved assays would contribute to better risk prediction and clinical management of this disease. A telomerase-based assay to detect circulating tumor cells (CTCs) may usefully fulfill this role.

Detection of brain tumor cells in the peripheral blood by a telomerase promoter-based assay.

Blood tests to detect circulating tumor cells (CTC) offer great potential to monitor disease status, gauge prognosis, and guide treatment decisions for patients with cancer. For patients with brain tumors, such as aggressive glioblastoma multiforme, CTC assays are needed that do not rely on expression of cancer cell surface biomarkers like epithelial cell adhesion molecules that brain tumors tend to lack. Here, we describe a strategy to detect CTC based on telomerase activity, which is elevated in nearly all tumor cells but not normal cells.

18F-fluorothymidine-pet imaging of glioblastoma multiforme: effects of radiation therapy on radiotracer uptake and molecular biomarker patterns.

Introduction. PET imaging is a useful clinical tool for studying tumor progression and treatment effects. Conventional (18)F-FDG-PET imaging is of limited usefulness for imaging Glioblastoma Multiforme (GBM) due to high levels of glucose uptake by normal brain and the resultant signal-to-noise intensity.

An integrated method for reproducible and accurate image-guided stereotactic cranial irradiation of brain tumors using the small animal radiation research platform.

Preclinical studies of cranial radiation therapy (RT) using animal brain tumor models have been hampered by technical limitations in the delivery of clinically relevant RT. We established a bioimageable mouse model of glioblastoma multiforme (GBM) and an image-guided radiation delivery system that facilitated precise tumor localization and treatment and which closely resembled clinical RT. Our novel radiation system makes use of magnetic resonance imaging (MRI) and bioluminescent imaging (BLI) to define tumor volumes, computed tomographic (CT) imaging for accurate treatment planning, a novel mouse immobilization system, and precise treatments delivered with the Small Animal Radiation Research Platform.

Oncogenic K-Ras signals through epidermal growth factor receptor and wild-type H-Ras to promote radiation survival in pancreatic and colorectal carcinoma cells.

Pancreatic and colorectal carcinomas frequently express oncogenic/mutant K-Ras that contributes to both tumorigenesis and clinically observed resistance to radiation treatment. We have previously shown that farnesyltransferase inhibitors (FTI) radiosensitize many pancreatic and colorectal cancer cell lines that express oncogenic K-ras at doses that inhibit the prenylation and activation of H-Ras but not K-Ras. In the present study, we have examined the mechanism of FTI-mediated radiosensitization in cell lines that express oncogenic K-Ras and found that wild-type H-Ras is a contributor to radiation survival in tumor cells that express oncogenic K-Ras.