Cyclin C promotes development and progression of B-cell acute lymphoblastic leukemia by counteracting p53-mediated stress responses.

Despite major therapeutic advances in the treatment of acute lymphoblastic leukemia (ALL), resistances and long-term toxicities still pose significant challenges. Cyclins and their associated cyclin-dependent kinases are one focus of cancer research when looking for targeted therapies. We discovered cyclin C as a key factor for B-ALL development and maintenance.

Dysfunctional tumor-infiltrating Vδ1 + T lymphocytes in microsatellite-stable colorectal cancer.

Although γδ T cells are known to participate in immune dysregulation in solid tumors, their relevance to human microsatellite-stable (MSS) colorectal cancer (CRC) is still undefined. Here, using integrated gene expression analysis and T cell receptor sequencing, we characterized γδ T cells in MSS CRC, with a focus on Vδ1 + T cells. We identified Vδ1 T cells with shared motifs in the third complementarity-determining region of the δ-chain, reflective of antigen recognition.

A lineage-specific STAT5BN642H mouse model to study NK-cell leukemia.

Patients with T- and natural killer (NK)-cell neoplasms frequently have somatic STAT5B gain-of-function mutations. The most frequent STAT5B mutation is STAT5BN642H, which is known to drive murine T-cell leukemia, although its role in NK-cell malignancies is unclear. Introduction of the STAT5BN642H mutation into human NK-cell lines enhances their potential to induce leukemia in mice.

Triple-negative breast cancer cells rely on kinase-independent functions of CDK8 to evade NK-cell-mediated tumor surveillance.

Triple-negative breast cancer (TNBC) is an aggressive malignant disease that is responsible for approximately 15% of breast cancers. The standard of care relies on surgery and chemotherapy but the prognosis is poor and there is an urgent need for new therapeutic strategies. Recent in silico studies have revealed an inverse correlation between recurrence-free survival and the level of cyclin-dependent kinase 8 (CDK8) in breast cancer patients.

Functional gait measures correlate to fear of falling, and quality of life in patients with Hereditary Spastic Paraplegia: A cross-sectional study.

Objective: Gait impairment is the cardinal motor symptom in hereditary spastic paraplegias (HSPs) possibly linked to increased fear of falling and reduced quality of life (QoL). Disease specific symptoms in HSP are rated using the Spastic Paraplegia Rating Scale (SPRS). However, limited studies evaluated more objectively easy-to-apply gait measures by comparing these standardized assessments with patients' self-perceived impairment and clinically established scores.

Short-course radiotherapy promotes pro-inflammatory macrophages via extracellular vesicles in human rectal cancer.

Background: Tumor-associated macrophages (TAM) constitute the most abundant immune cells in the tumor stroma initiating pro-inflammatory (M1) or immunosuppressive (M2) responses depending on their polarization status. Advances in tumor immunotherapy call for a detailed understanding of potential immunogenic mechanisms of irradiation routinely applied in rectal cancer patients.

Methods: To test the effects of radiotherapy on TAM, we ex vivo irradiated tissue samples of human rectal cancer and assessed the phenotype by flow cytometry.

Loss of NKG2D in murine NK cells leads to increased perforin production upon long-term stimulation with IL-2.

NK cells are innate lymphocytes responsible for lysis of pathogen-infected and transformed cells. One of the major activating receptors required for target cell recognition is the NK group 2D (NKG2D) receptor. Numerous reports show the necessity of NKG2D for effective tumor immune surveillance.

Ascending Axonal Degeneration of the Corticospinal Tract in Pure Hereditary Spastic Paraplegia: A Cross-Sectional DTI Study.

Objective: To identify structural white matter alterations in patients with pure hereditary spastic paraplegia (HSP) using high angular resolution diffusion tensor imaging (DTI).

Methods: We examined 37 individuals with high resolution DTI, 20 patients with pure forms of hereditary spastic paraplegia and 17 age and gender matched healthy controls. DTI was performed using a 3 T clinical scanner with whole brain tract-based spatial statistical (TBSS) analysis of the obtained fractional anisotropy (FA) data as well as a region-of-interest (ROI)-based analysis of affected tracts including the cervical spinal cord.

Technical Validation of an Automated Mobile Gait Analysis System for Hereditary Spastic Paraplegia Patients.

Hereditary spastic paraplegias (HSP) represents a group of orphan neurodegenerative diseases with gait disturbance as the predominant clinical feature. Due to its rarity, research within this field is still limited. Aside from clinical analysis using established scales, gait analysis has been employed to enhance the understanding of the mechanisms behind the disease.

Segmentation of gait sequences using inertial sensor data in hereditary spastic paraplegia.

Gait analysis is an important tool for diagnosis, monitoring and treatment of neurological diseases. Among these are hereditary spastic paraplegias (HSPs) whose main characteristic is heterogeneous gait disturbance. So far HSP gait has been analysed in a limited number of studies, and within a laboratory set up only.