NOTCH and PTP4A3 alterations emerge as novel predictive biomarkers and potential therapeutic targets in pleural mesothelioma.

Background: Previous studies showed opposite effects of NOTCH1 and NOTCH2 on mesothelioma cell survival under hypoxia. Mechanisms underlying these effects are not still clear and this pathway plays a key role in angiogenesis and cancer stem cells (CSCs) self-renewal processes.

Purpose: In this study we evaluated whether NOTCH1, NOTCH2 copy number alterations (CNAs) might predict prognosis of patients with pleural mesothelioma (PM) and if the modulation of this pathway might target CSCs, potentiating pemetrexed activity, also in hypoxic conditions.

Preclinical evaluation of the CD38-targeting engineered toxin body MT-0169 against multiple myeloma.

Despite significant progress in the treatment of multiple myeloma (MM), relapsed/refractory patients urgently require more effective therapies. We here describe the discovery, mechanism of action, and preclinical anti-MM activity of engineered toxin body MT-0169, a next-generation immunotoxin comprising a CD38-specific antibody fragment linked to a de-immunized Shiga-like toxin A subunit (SLTA) payload. We show that specific binding of MT-0169 to CD38 on MM cell lines triggers rapid internalization of SLTA, causing cell death via irreversible ribosome inhibition, protein synthesis blockade, and caspase 3/7 activation.

QSPRpred: a Flexible Open-Source Quantitative Structure-Property Relationship Modelling Tool.

Building reliable and robust quantitative structure-property relationship (QSPR) models is a challenging task. First, the experimental data needs to be obtained, analyzed and curated. Second, the number of available methods is continuously growing and evaluating different algorithms and methodologies can be arduous.

Adjuvant immunotherapy in patients with resected gastric and oesophagogastric junction cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): European Organisation of Research and Treatment of Cancer (EORTC) 1707 VESTIGE study.

Background: Patients with gastro-oesophageal adenocarcinoma with tumour-positive lymph nodes (ypN+) or positive surgical margins (R1) following neoadjuvant chemotherapy and resection are at high risk of recurrence. Adjuvant nivolumab is effective in oesophageal/oesophagogastric junction cancer and residual pathological disease following chemoradiation and surgery. Immune checkpoint inhibition has shown efficacy in advanced gastro-oesophageal cancer.

Karyotype evolution in response to chemoradiotherapy and upon recurrence of esophageal adenocarcinomas.

The genome of esophageal adenocarcinoma (EAC) is highly unstable and might evolve over time. Here, we track karyotype evolution in EACs in response to treatment and upon recurrence through multi-region and longitudinal analysis. To this end, we introduce L-PAC (low-purity inference of absolute copy-number alterations [CNAs]), a bio-informatics technique that allows inference of absolute CNAs of low-purity samples by leveraging the information of high-purity samples from the same cancer.

Causes of death among patients diagnosed with chronic lymphocytic leukemia: A population-based study in the Netherlands, 1996-2020.

Chronic lymphocytic leukemia (CLL) manifests heterogeneously with varying outcomes. This population-based study examined causes of death (CODs), as registered by the physician who established the death, among 20,588 CLL patients diagnosed in the Netherlands between 1996 and 2020. Utilizing cause-specific flexible parametric survival models, we estimated cause-specific hazard ratios (HRs) and cumulative incidences of death due to CLL, solid malignancies, other hematological malignancies, infections, and other causes.

Remote Patient Monitoring Using Mobile Health Technology in Cancer Care and Research: Patients' Views and Preferences.

Purpose: There is an increasing interest in studying the potential of mobile health (mHealth) technologies, such as smartphone apps and wearables, as monitoring tools for patients with cancer during or after their treatment. However, little research is dedicated to exploring the opinions and concerns of patients regarding the adoption of these technologies. This study aimed to gain insight into patients' perspectives and preferences for participating in mHealth-based monitoring in cancer care.

Gastric Cancer Risk among Immigrants and Socioeconomic Groups in the Netherlands.

Background: Identification of groups at a high risk of gastric cancer could facilitate targeted screening in countries with a low gastric cancer incidence. Our aim was to identify such high-risk groups based on individual-level population data on migration history and socioeconomic status (SES) in the Netherlands.

Methods: In this retrospective cohort study, patient data from the Netherlands Cancer Registry were linked to demographic data of Statistics Netherlands in the period 2010 to 2022.

Chromosomal copy number based stratification of gastric cancer has added prognostic value to Lauren's histological classification.

Background: The Cancer Genome Atlas (TCGA) recognizes four molecular subgroups of gastric cancer: Epstein-Barr virus (EBV) positive, microsatellite instable (MSI), genomically stable (GS), and chromosomal instable (CIN). Since a GS/CIN classifier is lacking, alternative markers such as Lauren's histopathology or CDH1/p53 immunohistochemistry are commonly applied. Here we compared survival of gastric cancer subgroups determined by four methods.

Comparison of surgical effectiveness: kidney sparing surgery for upper tract urothelial carcinoma.

Purpose Of Review: This review provides an overview of the recent publications on kidney-sparing-surgery (KSS) for upper tract urothelial carcinoma (UTUC), an alternative to radical nephroureterectomy (RNU) for an increasing number of indications.

Recent Findings: Recent studies highlight comparable survival outcomes between KSS [ureterorenoscopy with tumour ablation (URS) or segmental ureteral resection (SUR)] and RNU, even in high-risk UTUC patients. KSS has shown to preserve renal function without significantly compromising oncologic control in appropriately selected patients.

Development of a Versatile Cancer Vaccine Format Targeting Antigen-Presenting Cells Using Proximity-Based Sortase A-Mediated Ligation of T-Cell Epitopes.

Cancer vaccines are a promising strategy to increase tumor-specific immune responses in patients who do not adequately respond to checkpoint inhibitors. Cancer vaccines that contain patient-specific tumor antigens are most effective but also necessitate the production of patient-specific vaccines. This study aims to develop a versatile cancer vaccine format in which patient-specific tumor antigens can be site-specifically conjugated by a proximity-based Sortase A (SrtA)-mediated ligation (PBSL) approach to antibodies that specifically bind to antigen-presenting cells to stimulate immune responses.

Hypoxia and TNF-alpha modulate extracellular vesicle release from human induced pluripotent stem cell-derived cardiomyocytes.

Extracellular vesicles (EVs) have emerged as important mediators of intercellular communication in the heart under homeostatic and pathological conditions, such as myocardial infarction (MI). However, the basic mechanisms driving cardiomyocyte-derived EV (CM-EV) production following stress are poorly understood. In this study, we generated human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) that express NanoLuc-tetraspanin reporters.

The UPFRONT project: tailored implementation and evaluation of a patient decision aid to support shared decision-making about management of symptomatic uterine fibroids.

Objective: To evaluate implementation of a patient decision aid for symptomatic uterine fibroid management to improve shared decision-making at five clinical settings across the United States.

Methods: We used a type 3 hybrid effectiveness-implementation stepped-wedge design and the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) planning and evaluation framework. We conducted clinician training, monthly reach tracking with feedback to site clinical leads, patient and clinician surveys, and visit audio-recordings.

Online video versus face-to-face patient-surgeon consultation: a systematic review.

Background: Online video consultation (OVC) is increasingly used in patient-surgeon pre-surgical and follow-up consultation but a comprehensive review assessing its benefits and downsides as compared to face-to-face (F2F) consultation is currently lacking. This systematic review evaluated the effectiveness of OVC as compared to F2F consultation.

Methods: A literature search (Ovid/Medline, Embase, and Clarivate Analytics/Web of Science Core Collection) was conducted including studies comparing efficacy, patient and surgeon satisfaction, and information recall between OVC and F2F patient-surgeon consultation (inception-December 4, 2023).

Impact of patient age on outcome of minimally invasive versus open pancreatoduodenectomy: a propensity score matched study.

Background: Pancreatoduodenectomy in elderly patients may be associated with increased postoperative mortality, but studies in minimally invasive pancreatoduodenectomy (MIPD) are scarce.

Methods: International multicenter retrospective study including patients aged >60 years undergoing MIPD (robot-assisted and laparoscopic) and open pancreatoduodenectomy (OPD), were categorized by age: 60-69, 70-79, and 80+ years. In each category, propensity score matching (PSM) was performed (1:1 ratio) between MIPD and OPD.

Vδ2 T-cell engagers bivalent for Vδ2-TCR binding provide anti-tumor immunity and support robust Vγ9Vδ2 T-cell expansion.

Background: Vγ9Vδ2 T-cells are antitumor immune effector cells that can detect metabolic dysregulation in cancer cells through phosphoantigen-induced conformational changes in the butyrophilin (BTN) 2A1/3A1 complex. In order to clinically exploit the anticancer properties of Vγ9Vδ2 T-cells, various approaches have been studied including phosphoantigen stimulation, agonistic BTN3A-specific antibodies, adoptive transfer of expanded Vγ9Vδ2 T-cells, and more recently bispecific antibodies. While Vγ9Vδ2 T-cells constitute a sizeable population, typically making up ~1-10% of the total T cell population, lower numbers have been observed with increasing age and in the context of disease.

Generation and characterization of two isogenic induced pluripotent stem cell lines from a young female with microcephaly carrying a compound heterozygous mutation in BUB1 gene.

Mutations in the Budding uninhibited by benzimidazoles (BUB1) gene were recently associated with neurodevelopmental disorders (Carvalhal et al., 2022). Here, we describe the generation and characterization of two induced pluripotent stem cells (iPSC) clones from a young female with microcephaly.

Shared decision making in primary malignant bone tumour surgery around the knee in children and young adults: protocol for a prospective study.

Background: Children and young adults needing surgery for a primary malignant bone tumour around the knee face a difficult, life-changing decision. A previous study showed that this population wants to be involved more in the decision-making process and that more involvement leads to less decisional stress and regret. Therefore, a well-designed and standardized decision-making process based on the principles of shared decision-making needs to be designed, implemented, and evaluated.