TET2 guards against unchecked BATF3-induced CAR T cell expansion.

Further advances in cell engineering are needed to increase the efficacy of chimeric antigen receptor (CAR) and other T cell-based therapies. As T cell differentiation and functional states are associated with distinct epigenetic profiles, we hypothesized that epigenetic programming may provide a means to improve CAR T cell performance. Targeting the gene that encodes the epigenetic regulator ten-eleven translocation 2 (TET2) presents an interesting opportunity as its loss may enhance T cell memory, albeit not cause malignancy.

Representativeness of initial skin biopsies showing pure desmoplastic melanoma: implications for management.

Desmoplastic melanoma (DM) is an uncommon subtype of melanoma with distinct clinicopathological features. It is classified into pure desmoplastic melanoma (PDM) when the proportion of desmoplastic melanoma is ≥90% of the dermally-invasive component, and mixed desmoplastic melanoma (MDM) when the proportion of desmoplastic melanoma is <90%. Studies have reported a lower sentinel lymph node biopsy (SLNB)-positivity rate in PDM compared to MDM and non-DM.

Innovative nanotheranostics: Smart nanoparticles based approach to overcome breast cancer stem cells mediated chemo- and radioresistances.

The alarming increase in the number of breast cancer patients worldwide and the increasing death rate indicate that the traditional and current medicines are insufficient to fight against it. The onset of chemo- and radioresistances and cancer stem cell-based recurrence make this problem harder, and this hour needs a novel treatment approach. Competent nanoparticle-based accurate drug delivery and cancer nanotheranostics like photothermal therapy, photodynamic therapy, chemodynamic therapy, and sonodynamic therapy can be the key to solving this problem due to their unique characteristics.

Patterned cPCDH expression regulates the fine organization of the neocortex.

The neocortex consists of a vast number of diverse neurons that form distinct layers and intricate circuits at the single-cell resolution to support complex brain functions. Diverse cell-surface molecules are thought to be key for defining neuronal identity, and they mediate interneuronal interactions for structural and functional organization. However, the precise mechanisms that control the fine neuronal organization of the neocortex remain largely unclear.

Health-Related Quality of Life Following Simultaneous Resection for Synchronous Colorectal Cancer Liver Metastases.

Introduction: Up to 25% of colorectal cancer patients present with synchronous liver metastases that can be treated with two operations or a single 'simultaneous' operation. Morbidity and mortality appear similar between approaches, however changes in health-related quality-of-life following simultaneous resection are not well reported.

Methods: A prospective, feasibility trial for simultaneous resection of synchronous colorectal liver metastases was conducted.

Paediatric Strategy Forum for medicinal product development in mitogen-activated protein kinase pathway inhibitors: ACCELERATE in collaboration with the European Medicines Agency with participation of the Food and Drug Administration.

As the mitogen-activated protein kinase (MAPK) signalling pathway is activated in many paediatric cancers, it is an important therapeutic target. Currently, a range of targeted MAPK pathway inhibitors are being developed in adults. However, MAPK signals through many cascades and feedback loops and perturbing the MAPK pathway may have substantial influence on other pathways as well as normal development.

Clonal somatic copy number altered driver events inform drug sensitivity in high-grade serous ovarian cancer.

Chromosomal instability is a major challenge to patient stratification and targeted drug development for high-grade serous ovarian carcinoma (HGSOC). Here we show that somatic copy number alterations (SCNAs) in frequently amplified HGSOC cancer genes significantly correlate with gene expression and methylation status. We identify five prevalent clonal driver SCNAs (chromosomal amplifications encompassing MYC, PIK3CA, CCNE1, KRAS and TERT) from multi-regional HGSOC data and reason that their strong selection should prioritise them as key biomarkers for targeted therapies.

The Association between Peptic Ulcer Disease and Gastric Cancer: Results from the Stomach Cancer Pooling (StoP) Project Consortium.

Background: Gastric cancer (GC) is the fifth most common type of cancer and the fourth most common cause of cancer-related mortality. Although the risk of GC and peptic ulcer disease (PUD) is known to be increased by infection, evidence regarding the direct relationship between PUD and GC across ethnicities is inconclusive. Therefore, we investigated the association between PUD and GC in the Stomach cancer Pooling (StoP) consortium.

Standardised lesion segmentation for imaging biomarker quantitation: a consensus recommendation from ESR and EORTC.

Background: Lesion/tissue segmentation on digital medical images enables biomarker extraction, image-guided therapy delivery, treatment response measurement, and training/validation for developing artificial intelligence algorithms and workflows. To ensure data reproducibility, criteria for standardised segmentation are critical but currently unavailable.

Methods: A modified Delphi process initiated by the European Imaging Biomarker Alliance (EIBALL) of the European Society of Radiology (ESR) and the European Organisation for Research and Treatment of Cancer (EORTC) Imaging Group was undertaken.

Mortality of early treatment for radiation-induced brain necrosis in head and neck cancer survivors: A multicentre, retrospective, registry-based cohort study.

Background: The evidence of early treatment for radiation-induced brain necrosis (RN) in head and neck cancer survivors remains insufficient. This study aimed to determine whether early anti-RN treatment was associated with lower mortality.

Methods: In this cohort study, we utilized data from the Study in Radiotherapy-related Nervous System Complications (NCT03908502) and Hong Kong Cancer Registry.

Preferential Antibody and Drug Conjugate Targeting of the ADAM10 Metalloprotease in Tumours.

ADAM10 is a transmembrane metalloprotease that sheds a variety of cell surface proteins, including receptors and ligands that regulate a range of developmental processes which re-emerge during tumour development. While ADAM10 is ubiquitously expressed, its activity is normally tightly regulated, but becomes deregulated in tumours. We previously reported the generation of a monoclonal antibody, 8C7, which preferentially recognises an active form of ADAM10 in human and mouse tumours.

The mediating role of combined lifestyle factors on the relationship between education and gastric cancer in the Stomach cancer Pooling (StoP) Project.

Background: The causal pathway between high education and reduced risk of gastric cancer (GC) has not been explained. The study aimed at evaluating the mediating role of lifestyle factors on the relationship between education and GC METHODS: Ten studies with complete data on education and five lifestyle factors (smoking, alcohol drinking, fruit and vegetable intake, processed meat intake and salt consumption) were selected from a consortium of studies on GC including 4349 GC cases and 8441 controls. We created an a priori score based on the five lifestyle factors, and we carried out a counterfactual-based mediation analysis to decompose the total effect of education on GC into natural direct effect and natural indirect effect mediated by the combined lifestyle factors.

Tea consumption and gastric cancer: a pooled analysis from the Stomach cancer Pooling (StoP) Project consortium.

Background: Evidence from epidemiological studies on the role of tea drinking in gastric cancer risk remains inconsistent. We aimed to investigate and quantify the relationship between tea consumption and gastric cancer in the Stomach cancer Pooling (StoP) Project consortium.

Methods: A total of 9438 cases and 20,451 controls from 22 studies worldwide were included.

HDR prostate brachytherapy plan robustness and its effect on in-vivo source tracking error thresholds: A multi-institutional study.

Purpose: The purpose of this study was to examine the effect of departmental planning techniques on appropriate in-vivo source tracking error thresholds for high dose rate (HDR) prostate brachytherapy (BT) treatments, and to determine if a single in-vivo source tracking error threshold would be appropriate for the same patient anatomy.

Methods: The prostate, rectum, and urethra were contoured on a single patient transrectal ultrasound (TRUS) dataset. Anonymized DICOM files were disseminated to 16 departments who created an HDR prostate BT treatment plan on the dataset with a prescription dose of 15 Gy in a single fraction.

Salt intake and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project.

Purpose: Previous studies show that consuming foods preserved by salting increases the risk of gastric cancer, while results on the association between total salt or added salt and gastric cancer are less consistent and vary with the exposure considered. This study aimed to quantify the association between dietary salt exposure and gastric cancer, using an individual participant data meta-analysis of studies participating in the Stomach cancer Pooling (StoP) Project.

Methods: Data from 25 studies (10,283 cases and 24,643 controls) from the StoP Project with information on salt taste preference (tasteless, normal, salty), use of table salt (never, sometimes, always), total sodium intake (tertiles of grams/day), and high-salt and salt-preserved foods intake (tertiles of grams/day) were used.

Crimean-Congo haemorrhagic fever during the COVID-19 pandemic in Africa: Efforts, recommendations and challenges at hand.

Since the beginning of the COVID-19 pandemic, millions have suffered globally and as a result, attention and resources for other diseases, such as Crimean-Congo Haemorrhagic Fever (CCHF), has declined. Despite a significantly lower incidence rate compared to COVID-19, CCHF has a considerably higher mortality rate at approximately 30%. Both diseases share symptoms such as headache, fever, nausea and vomiting, fatigue, sore throat, however they have different modes of transmission, mortality rates, and incubation periods.

Systematic review and meta-analysis of survival outcomes in T2a and T2b gallbladder cancers.

Background: The 8th edition of AJCC TNM staging of Gallbladder cancer subdivided T2 stage into T2a and T2b based on tumour location. This meta-analysis aimed to investigate the long-term outcomes in T2a and T2b gallbladder cancers.

Methods: Literature search of Medline, Web of science, Embase and Cochrane databases was performed.

Quantification of microRNAs in Cells and Tissues Using Stem-Loop RT PCR and qPCR.

MicroRNA s are small RNA molecules that regulate gene expression by binding to the 3' untranslated region of the mRNA of their target genes. MicroRNA expression is altered in medulloblastoma as compared to the normal brain and this alteration is often associated with the pathogenesis of this tumor. The quantification of microRNA expression is carried out using quantitative/real-time polymerase chain reaction (PCR).

Validation of microRNA Target Genes Using Luciferase Reporter assay and Western Blot Analysis.

MicroRNA s regulate gene expression by binding to the 3'untranslated region (UTR) of the mRNA of their target genes. Identification of microRNA target genes enables the determination of their functional role in the cells. A single microRNA can target multiple genes, all of which have a microRNA binding site in their 3' UTR.

Simultaneous resection for synchronous colorectal cancer liver metastases: A feasibility clinical trial.

Background And Objectives: We tested the feasibility of a simultaneous resection clinical trial in patients with synchronous colorectal cancer liver metastases to obtain the necessary information to plan a randomized trial.

Methods: Multicenter feasibility single-arm trial enrolling patients with synchronous colorectal cancer liver metastases eligible for simultaneous resection. Prespecified criteria for feasibility were: proportion of eligible patients enrolled ≥66%, and the proportion of enrolled patients who completed simultaneous resection ≥75%.

A systematic review and meta-analysis of effects of psychosocial interventions on spiritual well-being in adults with cancer.

Objective: Spiritual well-being (SpWb) is an important dimension of health-related quality of life for many cancer patients. Accordingly, an increasing number of psychosocial intervention studies have included SpWb as a study endpoint, and may improve SpWb even if not designed explicitly to do so. This meta-analysis of randomized controlled trials (RCTs) evaluated effects of psychosocial interventions on SpWb in adults with cancer and tested potential moderators of intervention effects.