Corticosteroids impair epithelial regeneration in immune-mediated intestinal damage.

Corticosteroid treatment (CST) failure is associated with poor outcomes for patients with gastrointestinal (GI) graft-versus-host disease (GVHD). CST is intended to target the immune system, but the glucocorticoid receptor (GR) is widely expressed, including within the intestines, where its effects are poorly understood. Here, we report that corticosteroids (CS) directly targeted intestinal epithelium, potentially worsening immune-mediated GI damage.

A tissue-intrinsic IL-33/EGF circuit promotes epithelial regeneration after intestinal injury.

Intestinal stem cells (ISCs) maintain the epithelial lining of the intestines, but mechanisms regulating ISCs and their niche after damage remain poorly understood. Utilizing radiation injury to model intestinal pathology, we report here that the Interleukin-33 (IL-33)/ST2 axis, an immunomodulatory pathway monitored clinically as an intestinal injury biomarker, regulates intrinsic epithelial regeneration by inducing production of epidermal growth factor (EGF). Three-dimensional imaging and lineage-specific RiboTag induction within the stem cell compartment indicated that ISCs expressed IL-33 in response to radiation injury.

Assessing and improving the validity of COVID-19 autopsy studies - A multicentre approach to establish essential standards for immunohistochemical and ultrastructural analyses.

Background: Autopsy studies have provided valuable insights into the pathophysiology of COVID-19. Controversies remain about whether the clinical presentation is due to direct organ damage by SARS-CoV-2 or secondary effects, such as overshooting immune response. SARS-CoV-2 detection in tissues by RT-qPCR and immunohistochemistry (IHC) or electron microscopy (EM) can help answer these questions, but a comprehensive evaluation of these applications is missing.

Reactivating TP53 signaling by the novel MDM2 inhibitor DS-3032b as a therapeutic option for high-risk neuroblastoma.

Fewer than 50% of patients with high-risk neuroblastoma survive five years after diagnosis with current treatment protocols. Molecular targeted therapies are expected to improve survival. Although MDM2 has been validated as a promising target in preclinical models, no MDM2 inhibitors have yet entered clinical trials for neuroblastoma patients.

Targeting hedgehog signaling pathway in pediatric tumors: in vitro evaluation of SMO and GLI inhibitors.

Purpose: The successful use of SMO inhibitors in tumors with activating mutations in hedgehog signaling raised interests in their exploitation against other malignancies. The role of hedgehog signaling in pediatric malignancies remains unclear.

Methods: We investigated the hedgehog signaling and its inhibition in a panel of 18 tumor cell lines derived from six of the most common and highly aggressive pediatric tumor types.

Long-term survival of an infant with an atypical teratoid/rhabdoid tumor following subtotal resection and low-cumulative dose chemotherapy: a case report.

Introduction: Atypical teratoid/rhabdoid tumor (AT/RT) is an aggressive embryonal tumor of the central nervous system with a generally dismal prognosis, especially in patients younger than 12 months.

Discussion: We here describe the unusual case of an infant with AT/RT with long-term survival despite low-cumulative dose chemotherapy after subtotal resection. Due to a poor neurological situation and an unfavorable oncological prognosis, therapy was halted after two partial surgical resections and four of the nine chemotherapy courses recommended by the European Rhabdoid Registry, without the patient receiving either radiotherapy or high-dose chemotherapy.