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Chimeric antigen receptor (CAR) T cell treatment has provided notable results in hematological tumors. Unfortunately, this evidence has not been translated into improved outcomes in solid malignancies so far, where several reports have suggested that T cells encounter substantial difficulties in penetrating and surviving in the tumor microenvironment (TME). Thus, researchers have recently investigated other immune cell types as CAR platforms, in order to overcome the limitations of CAR T cells. Among them, CAR-macrophages (M) technology has emerged as a novel perspective for cancer patients, on the basis of preclinical studies observing that CAR expression in human macrophages could play a crucial role in enhancing phagocytosis, polarizing M2 to M1 phenotype, and stimulating T cell anti-tumor activity. Herein, we provide an overview of current scenario of CAR-Ms in several solid tumors, also focusing on the biological rationale behind this promising therapeutic approach and future research directions in this setting.TP53 is the most commonly mutated gene in human cancer with over 100,000 literature citations in PubMed. This is a heavily studied pathway in cancer biology and oncology with a history that dates back to 1979 when p53 was discovered. The p53 pathway is a complex cellular stress response network with multiple diverse inputs and downstream outputs relevant to its role as a tumor suppressor pathway. While inroads have been made in understanding the biology and signaling in the p53 pathway, the p53 family, transcriptional readouts, and effects of an array of mutants, the pathway remains challenging in the realm of clinical translation. While the role of mutant p53 as a prognostic factor is recognized, the therapeutic modulation of its wild-type or mutant activities remain a work-in-progress. This review covers current knowledge about the biology, signaling mechanisms in the p53 pathway and summarizes advances in therapeutic development.Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) with episodes of inflammatory demyelination and remyelination. While remyelination has been linked with functional recovery in MS patients, there is evidence of ongoing tissue damage despite complete myelin repair. In this study, we investigated the long-term consequences of an acute demyelinating white matter CNS lesion. Caspase Inhibitor VI mw For this purpose, acute demyelination was induced by 5-week-cuprizone intoxication in male C57BL/6 J mice, and the tissues were examined after a 7-month recovery period. While myelination and oligodendrocyte densities appeared normal, ongoing axonal degeneration and glia cell activation were found in the remyelinated corpus callosum. Neuropathologies were paralleled by subtle gait abnormalities evaluated using DigiGait™ high speed ventral plane videography. Gene array analyses revealed increased expression levels of various inflammation related genes, among protein kinase c delta (PRKCD). Immunofluorescence stains revealed predominant microglia/macrophages PRKCD expression in both, cuprizone tissues and post-mortem MS lesions. These results support the hypothesis that chronic microglia/macrophages driven tissue injury represents a key aspect of progressive neurodegeneration and functional decline in MS.The E4 allele of apolipoprotein E (apoE4) is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). However, apoE4 may cause innate brain abnormalities before the appearance of AD-related neuropathology. Understanding these primary dysfunctions is vital for the early detection of AD and the development of therapeutic strategies. Recently we reported impaired extra-hippocampal memory in young apoE4 mice, a deficit that was correlated with attenuated structural pre-synaptic plasticity in cortical and subcortical regions. Here we tested the hypothesis that these early structural deficits impact learning via changes in basal and stimuli evoked neuronal activity. We recorded extracellular neuronal activity from the gustatory cortex (GC) of three-month-old humanized apoE4 (hApoE4) and wildtype rats expressing rat apoE (rAE), before and after conditioned taste aversion (CTA) training. Despite normal sucrose drinking behavior before CTA, young hApoE4 rats showed impaired CTA learning, consistent with our previous results in target-replacement apoE4 mice. This behavioral deficit was correlated with decreased basal and taste-evoked firing rates in both putative excitatory and inhibitory GC neurons. Further taste coding analyses at the single neuron and ensemble levels revealed that GC neurons of the hApoE4 group correctly classified tastes, but were unable to undergo plasticity to support learning. These results suggest that apoE4 impacts brain excitability and plasticity early in life that may act as an initiator for later AD pathologies.Deep brain stimulation (DBS) surgery offers a unique opportunity to record local field potentials (LFPs), the electrophysiological population activity of neurons surrounding the depth electrode in the target area. With direct access to the subcortical activity, LFP research has provided valuable insight into disease mechanisms and cognitive processes and inspired the advent of adaptive DBS for Parkinson's disease (PD). A frequency-based framework is usually employed to interpret the implications of LFP signatures in LFP studies on PD. This approach standardizes the methodology, simplifies the interpretation of LFP patterns, and makes the results comparable across studies. Importantly, previous works have found that activity patterns do not represent disease-specific activity but rather symptom-specific or task-specific neuronal signatures that relate to the current motor, cognitive or emotional state of the patient and the underlying disease. In the present review, we aim to highlight distinguishing features of frequency-specific activities, mainly within the motor domain, recorded from DBS electrodes in patients with PD. Associations of the commonly reported frequency bands (delta, theta, alpha, beta, gamma, and high-frequency oscillations) to motor signs are discussed with respect to band-related phenomena such as individual tremor and high/low beta frequency activity, as well as dynamic transients of beta bursts. We provide an overview on how electrophysiology research in DBS patients has revealed and will continuously reveal new information about pathophysiology, symptoms, and behavior, e.g., when combining deep LFP and surface electrocorticography recordings.