MicroRNA Expression in High-Grade B-Cell Lymphoma With 11q Aberration.

Mature aggressive B-cell lymphomas, such as Burkitt lymphoma (BL) and Diffuse large B-cell lymphoma (DLBCL), show variations in microRNA (miRNA) expression. The entity of High-grade B-cell lymphoma with 11q aberration (HGBCL-11q) shares several biological features with both BL and DLBCL but data on its miRNA expression profile are yet scarce. Hence, this study aims to analyze the potential differences in miRNA expression of HGBCL-11q compared to BL and DLBCL.

Perioperative Chemotherapy or Preoperative Chemoradiotherapy in Esophageal Cancer.

Background: The best multimodal approach for resectable locally advanced esophageal adenocarcinoma is unclear. An important question is whether perioperative chemotherapy is preferable to preoperative chemoradiotherapy.

Methods: In this phase 3, multicenter, randomized trial, we assigned in a 1:1 ratio patients with resectable esophageal adenocarcinoma to receive perioperative chemotherapy with FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) plus surgery or preoperative chemoradiotherapy (radiotherapy at a dose of 41.

The importance of preclinical models for cholangiocarcinoma drug discovery.

Introduction: Biliary tract cancer (BTC) comprises a clinically diverse and genetically heterogeneous group of tumors along the intra- and extrahepatic biliary system (intrahepatic and extrahepatic cholangiocarcinoma) and gallbladder cancer with the common feature of a poor prognosis, despite increasing molecular knowledge of associated genetic aberrations and possible targeted therapies. Therefore, the search for even more precise and individualized therapies is ongoing and preclinical tumor models are central to the development of such new approaches.

Areas Covered: The models described in the current review include simple and advanced in vitro and in vivo models, including cell lines, 2D monolayer, spheroid and organoid cultures, 3D bioprinting, patient-derived xenografts, and more recently, machine-perfusion platform-based models of resected liver specimens.

Real-world experience with TTFields in glioma patients with emphasis on therapy usage.

Tumor Treating Fields (TTFields) has emerged as a significant adjunctive component in the treatment of high-grade gliomas following the EF-14 trial in 2017. The incorporation of TTFields, alongside cyclic temozolomide therapy, has demonstrated improved patient outcomes when the usage exceeds 18 h per day (75% usage). analysis of the EF-14 trial has demonstrated that therapy usage exceeding 90% is associated with an additional benefit, while rates above 50% have also proven effective in literature.

Multinational retrospective analysis of bridging therapy prior to chimeric antigen receptor t cells for relapsed/refractory acute lymphoblastic leukemia in children and young adults.

Anti-CD19 chimeric antigen receptor T cells (CAR) are a well-established treatment option for children and young adults suffering from relapsed/refractory B-lineage acute lymphoblastic leukemia. Bridging therapy is used to control disease prior to start of lymphodepletion before CAR infusion and thereby improve efficacy of CAR therapy. However, the effect of different bridging strategies on outcome, side effects and response to CAR therapy is still poorly understood.

Flow Cytometric Assessment of FcγRIIIa-V158F Polymorphisms and NK Cell Mediated ADCC Revealed Reduced NK Cell Functionality in Colorectal Cancer Patients.

Antibody-dependent cell-mediated cytotoxicity (ADCC) by NK cells is a key mechanism in anti-cancer therapies with monoclonal antibodies, including cetuximab (EGFR-targeting) and avelumab (PDL1-targeting). Fc gamma receptor IIIa (FcγRIIIa) polymorphisms impact ADCC, yet their clinical relevance in NK cell functionality remains debated. We developed two complementary flow cytometry assays: one to predict the FcγRIIIa-V158F polymorphism using a machine learning model, and a 15-color flow cytometry panel to assess antibody-induced NK cell functionality and cancer-immune cell interactions.

Tracking Nongenetic Evolution from Primary to Metastatic ccRCC: TRACERx Renal.

Using joint genomic-transcriptomic analysis of 243 samples, we reveal recurrent patterns of nongenetic evolution in ccRCC not exclusively governed by genetic factors, including T-cell depletion, tumor T-cell receptor coevolution, potential cGAS-STING repression, and increased cell proliferation. These patterns can aid clinical management and guide novel treatment approaches.

A novel prognostic risk model for patients with refractory/relapsed acute myeloid leukemia receiving venetoclax plus hypomethylating agents.

Off-label hypomethylating agents and venetoclax (HMA/VEN) are often used for relapsed and refractory (R/R) AML patients. However, predictors of outcome are elusive. The objective of the current retrospective observational multicenter study of 240 adult patients (median age 68.

Generation of effective and specific human TCRs against tumor/testis antigen NY-ESO-1 in mice with humanized T cell recognition system.

Generation of high avidity T cell receptors (TCRs) reactive to tumor-associated antigens (TAA) is impaired by tolerance mechanisms, which is an obstacle to effective T cell therapies for cancer treatment. NY-ESO-1, a human cancer-testis antigen, represents an attractive target for such therapies due to its broad expression in different cancer types and the restricted expression in normal tissues. Utilizing transgenic mice with a diverse human TCR repertoire, we isolated effective TCRs against NY-ESO-1 restricted to HLA-A*02:01.

Acute Myeloid Leukemia Skews Therapeutic WT1-specific CD8 TCR-T Cells Towards an NK-like Phenotype that Compromises Function and Persistence.

Acute myeloid leukemia (AML) that is relapsed and/or refractory post-allogeneic hematopoietic cell transplantation (HCT) is usually fatal. In a prior study, we demonstrated that AML relapse in high-risk patients was prevented by post-HCT immunotherapy with Epstein-Barr virus (EBV)-specific donor CD8 T cells engineered to express a high-affinity Wilms Tumor Antigen 1 (WT1)-specific T-cell receptor (T). However, in the present study, infusion of EBV- or Cytomegalovirus (CMV)-specific T did not clearly improve outcomes in fifteen patients with active disease post-HCT.

Systematic literature review and meta-analysis informing the EULAR points to consider on the initiation of targeted therapies in patients with inflammatory arthritis and a history of cancer.

Background: Targeted therapies have been associated with potential risk of malignancy, which is a common concern in daily rheumatology practice in patients with inflammatory arthritis (IA) and a history of cancer.

Objectives: To perform a systematic literature review to inform a Task Force formulating EULAR points to consider on the initiation of targeted therapies in patients with IA and a history of cancer.

Methods: Specific research questions were defined within the Task Force before formulating the exact research queries with a librarian.

Impact of inhibitory KIR ligand mismatch and other variables on outcomes following myeloablative posttransplant cyclophosphamide-based T-cell-replete haploidentical bone marrow transplantation.

Introduction: Posttransplant cyclophosphamide (PTCy) has revolutionized the landscape of human leukocyte antigen (HLA)-haploidentical hematopoietic cell transplantation (haplo-HCT), providing a pivotal therapeutic option for patients with hematological malignancies who lack an HLA-matched donor.

Methods: In this retrospective analysis involving 54 adult patients undergoing PTCy-based haplo-HCT, we evaluated the impact of inhibitory killer immunoglobulin-like receptor (KIR)/HLA mismatch, alongside patient, donor, and transplant factors, on clinical outcomes within a homogeneous cohort characterized by a myeloablative conditioning regimen and bone marrow graft.

Results: With a median follow-up of 73.

Frequency, characteristics, and immunological accompaniments of ataxia in anti-NMDAR antibody-associated encephalitis.

Introduction: Very rarely, adult NMDAR antibody-associated encephalitis (NMDAR-E) leads to persistent cerebellar atrophy and ataxia. Transient cerebellar ataxia is common in pediatric NMDAR-E. Immune-mediated cerebellar ataxia may be associated with myelin oligodendrocyte glycoprotein (MOG), aquaporin-4 (AQP-4), kelch-like family member 11 (KLHL11), and glutamate kainate receptor subunit 2 (GluK2) antibodies, all of which may co-occur in NMDAR-E.

- a large-scale dataset of 3D medical shapes for computer vision.

Objectives: The shape is commonly used to describe the objects. State-of-the-art algorithms in medical imaging are predominantly diverging from computer vision, where voxel grids, meshes, point clouds, and implicit surface models are used. This is seen from the growing popularity of ShapeNet (51,300 models) and Princeton ModelNet (127,915 models).

Cancer Organoids as reliable disease models to drive clinical development of novel therapies.

On September 23-24 (2024) the 6th Workshop IRE on Translational Oncology, titled "Cancer Organoids as Reliable Disease Models to Drive Clinical Development of Novel Therapies," took place at the IRCCS Regina Elena Cancer Institute in Rome. This prominent international conference focused on tumor organoids, bringing together leading experts from around the world.A central challenge in precision oncology is modeling the dynamic tumor ecosystem, which encompasses numerous elements that evolve spatially and temporally.

Radiographic and visual response to the type II RAF inhibitor tovorafenib in children with relapsed/refractory optic pathway glioma in the FIREFLY-1 trial.

Background: Due to their anatomical locations, optic pathway gliomas (OPGs) can rarely be cured by resection. Given the importance of preserving visual function, we analyzed radiological and visual acuity (VA) outcomes for the type II RAF inhibitor tovorafenib in the OPG subgroup of the phase 2 FIREFLY-1 trial.

Methods: FIREFLY-1 investigated the efficacy (arm 1, n=77), safety, and tolerability (arms 1/2) of tovorafenib (420 mg/m2 once weekly; 600 mg maximum) in patients with BRAF-altered relapsed/refractory pediatric low-grade glioma (pLGG).

Maintenance therapy with trofosfamide, idarubicin and etoposide in patients with rhabdomyosarcoma and other high-risk soft tissue sarcomas (CWS-2007-HR): a multicentre, open-label, randomised controlled phase 3 trial.

Background: Rhabdomyosarcoma and other soft tissue sarcomas (STS) with high-risk features are still associated with an unsatisfactory outcome. We evaluated the efficacy of oral maintenance therapy added at the end of standard therapy in patients with high-risk rhabdomyosarcoma and STS.

Methods: CWS-2007-HR was a multicentre, open-label, randomised controlled, phase 3 trial done at 87 centers in 5 countries.

Mortality in adult patients with chronic spontaneous urticaria: A real-world cohort study.

Background: Chronic spontaneous urticaria (CSU), a common and debilitating disease, is widely held not to be life limiting, but the mortality of CSU has not been investigated.

Objective: We sought to assess all-cause mortality in patients with CSU, risk for comorbidities that are leading causes of death, and impact of guideline-recommended urticaria treatments on mortality rates.

Methods: This was a retrospective population-based cohort study of electronic health records of 272,190 adult patients with CSU and 12,728,913 controls without urticaria from the US collaborative network TriNetX.

From evidence to care delivery: Opportunities and risks in health and science policy. A position paper of the Association of the Scientific Medical Societies in Germany (AWMF).

Objective: After over 25 years of developing clinical practice guidelines, the Association of the Scientific Medical Societies in Germany (AWMF) held a symposium to discuss the following topics in order to improve the way evidence is implemented in the delivery of care: expansion of the data pool for guideline development, the regulatory policy framework for this expansion, the transfer of clinical practice guideline statements to medical practice, the associated opportunities and risks resulting from the European legislation.

Methods: The AWMF held its Berlin Forum on 27 April 2022 where experts from scientific medical societies and national institutions in the healthcare sector reported their experiences and perceptions on the topics mentioned. Three writing groups compiled the key statements from these contributions to and discussions made at the Berlin Forum into a position paper.

π-HuB: the proteomic navigator of the human body.

The human body contains trillions of cells, classified into specific cell types, with diverse morphologies and functions. In addition, cells of the same type can assume different states within an individual's body during their lifetime. Understanding the complexities of the proteome in the context of a human organism and its many potential states is a necessary requirement to understanding human biology, but these complexities can neither be predicted from the genome, nor have they been systematically measurable with available technologies.