mA-driven transcriptomic rewiring in tumor immune surveillance.

RNA molecules are subject to extensive post-transcriptional modifications that fine-tune their stability, localization, and function. Among the more than 100 known RNA modifications, N6-methyladenosine (mA) is the most abundant internal mark on eukaryotic messenger RNAs. This dynamic modification is installed by methyltransferases ("writers"), removed by demethylases ("erasers"), and interpreted by RNA-binding proteins ("readers") to modulate gene expression.

Testicular germ cell tumors and infertility: Exploring epigenetic dysregulation in the journey of the male germ cell towards new biomarkers and therapeutics.

The development of male germ cells comprises a series of differentiation events that culminate in the formation of spermatozoa. From the primordial germ cell (PGC) to the spermatid, an array of epigenetic events take place in different stages of life. Disruptions in these mechanisms due to external factors can ultimately lead to decreased fertility and to testicular germ cell tumors (TGCTs).

Adherence to Clinical Practice Guidelines for Management of Epithelial Precancerous Conditions and Lesions in the Stomach in Europe.

Background And Aims: The first international guideline for managing preneoplastic conditions of the stomach (MAPS I) was published in 2012, followed by an update (MAPS II) in 2019. As adherence to these guidelines remains uncertain, we evaluated adherence by comparing the management of preneoplastic gastric conditions before and after the introduction of MAPS I and II in selected European centers.

Methods: Patients data were retrieved from nine endoscopy units in seven European countries during three periods: pre-MAPS I (2010/2011), post-MAPS I (2017/2018), and post-MAPS II (2022/2023).

Studying therapy effects and disease outcomes in silico using artificial counterfactual tissue samples.

Understanding the interactions of different cell types inside the immune tumor microenvironment (iTME) is crucial for the development of immunotherapy treatments as well as for predicting their outcomes. Highly multiplexed tissue imaging (HMTI) technologies offer a tool which can capture cell properties of tissue samples by measuring expression of various proteins and storing them in separate image channels. HMTI technologies can be used to gain insights into the iTME and in particular how the iTME differs for different patient outcome groups of interest (e.

Lipid metabolism of clear cell renal cell carcinoma predicts survival and affects intratumoral CD8 T cells.

Background: Clear cell renal cell carcinoma (ccRCC), the most common RCC subtype, both accumulates and depletes selected lipid species. However, the prognostic role of lipid metabolic reprogramming in ccRCC has not been studied in detail so far. In addition, ccRCC can show a dense immune infiltration.

The absence of Peroxiredoxin-1 in human pancreatic ductal adenocarcinoma (PDAC) markedly reduces cell survival and tumor growth when coupled with the inhibition of Ref-1 redox signaling.

Pancreatic ductal adenocarcinoma (PDAC) remains highly resistant to therapy, surviving despite hypoxia, oxidative stress, and nutrient deprivation. Redox effector factor-1 (Ref-1) regulates several oncogenic transcription factors (TFs) and is controlled by peroxiredoxins (PRDX). We investigated how Ref-1 inhibition by APX2014, combined with PRDX expression, affects pancreatic cancer cells from multiple patient lines.

Randomized Phase II Trial of Pazopanib Versus Placebo in Patients With Advanced Extrapancreatic Neuroendocrine Tumors (Alliance A021202).

Purpose: Patients with advanced, well-differentiated extrapancreatic neuroendocrine tumors (epNETs) have limited systemic treatment options. Pazopanib, an oral multikinase inhibitor with activity against vascular endothelial growth factor receptor (VEGFR)-2 and -3, PDGFR-alpha and-beta, and c-Kit, was tested for efficacy in epNET.

Patients And Methods: We conducted a multicenter, randomized, double-blind, phase II study of pazopanib (800 mg once daily) versus placebo in low- to intermediate-grade epNET with radiologic progressive disease (PD) within 12 months of study entry.

TGFβ limits proximal CD8+ TCR signaling via PTPN22 following strong and moderate agonism.

Transforming growth factor beta (TGFβ) is an immunosuppressive cytokine that is overexpressed in tumor microenvironments. We have shown that CD8+ T cells with genetic ablation of the TGFβ type I receptor, Alk5 (CD8ΔALK5), were more sensitive to αCD3 stimulation resulting in enhanced proliferation and cytokine production. Based on these data, we hypothesized that TGFβ impaired T-cell receptor (TCR) signaling.

An allele-agnostic mutant-KRAS inhibitor suppresses tumor maintenance signals and reprograms tumor immunity in pancreatic cancer.

is among the most frequently mutated oncogenes in cancer, and for decades, efforts at pharmacological blockade of its function in solid cancers have been unsuccessful. A notable advance in this endeavor is the recent development of small-molecule KRAS inhibitors, which enable direct targeting of the mutant oncoprotein. Here, we comprehensively evaluated the preclinical efficacy of BI-2493, a first-in-class allele-agnostic mutant-KRAS inhibitor (panKRASi), in pancreatic ductal adenocarcinoma (PDAC).

The landscape of microbial associations in human cancer.

Oncomicrobes are estimated to cause 15% of cancers worldwide. When cancer whole-genome sequencing (WGS) data are collected, the microbes present are also sequenced, allowing the investigation of potential etiological and clinical associations. Interrogating the microbial community for 8908 patients encompassing 22 cancer types from the Genomics England WGS dataset revealed that only colorectal tumors exhibited unmistakably distinct microbial communities that can reliably be used to distinguish anatomical site [positive predictive value (PPV) = 0.

Combined inhibition of SHP2 overcomes adaptive resistance to type 1 BRAF inhibitors in BRAF V600E-driven high-grade glioma.

Background: -mutant gliomas can be targeted therapeutically using BRAF-selective inhibitors, yet responses are often transient due to adaptive resistance through reactivation of RAS-ERK signaling. Here, we evaluate the role of SHP2, a central regulator of RAS activity, and SHP2 inhibitors in overcoming resistance to BRAF inhibitors in glioma.

Methods: RNAseq and protein expression in human tissue samples and glioma cell lines were used to identify resistance mechanisms.

Potential Exposure to Environmental Toxic Emissions and Increased Cancer Risk in Puerto Rico.

Background: Toxic environmental pollutants are a risk factor for some cancers. We conducted an ecological study to assess the cancer risk in Puerto Rico after 15 years of exposure.

Methods: Cancer incidence data (2018-2022) were obtained from the Puerto Rico Central Cancer Registry.

Scrambler Therapy for the Treatment of Chronic Neuropathic Pain in Atypical Parkinsonian Disorders: A Case Series.

Background: Chronic pain is a common and distressing symptom associated with atypical parkinsonian disorders (APD); however, current pain treatment methods are often unsatisfactory. Scrambler therapy (ST), a noninvasive method of cutaneous electroanalgesia, can be an effective modality in treating chronic neuropathic pain in APD.

Case Report: We reviewed 7 consecutive patients with APD (2 with multiple system atrophy, 5 with corticobasal syndrome) who received ST to treat severe, refractory neuropathic pain.

Implementation of the precision oncology program in catalonia's public health system: results, lessons learned, and future prospects.

Purpose: The Precision Oncology Program (POP) in Catalonia aims to provide equitable access to molecular testing for individuals with cancer, integrating Next-Generation Sequencing (NGS) into clinical practice to inform diagnosis, prognosis, and treatment decisions for both adult and pediatric patients with solid and hematologic malignancies, including somatic and germline alterations. This study evaluates the program's outcomes and impact.

Methods: This evaluation covers the period from the program's implementation in July 2021 through December 2023, with a more detailed analysis focusing on 2022-2023.

ChatGPT's role in the rapidly evolving hematologic cancer landscape.

Many patients seek accurate, understandable information about their disease and treatment, turning to the internet or messaging providers. This study aims to validate chatbots' ability to deliver accurate information, contributing to the literature on AI's role in cancer care and helping to improve these tools for patients and caregivers. A set of questions about hematologic malignancies was created with input from oncologists and reputable websites and then submitted to ChatGPT 3.

Transition of Childhood Cancer Survivors into Adult Health Care: A Perspective from Adult Care.

The number of long-term childhood cancer survivors (CCSs) has been increasing, and the importance of transitioning from pediatric to adult care has been advocated. This study aimed to describe the health problems of adult CCSs from adult-care perspectives. We conducted a chart review of adult CCSs aged ≥18 years who visited a transition clinic in adult care between June 2019 and March 2024.

Real-world observations of GLP-1 receptor agonists and SGLT-2 inhibitors as potential treatments for Alzheimer's disease.

Introduction: Glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors have potential beneficial effects in Alzheimer's disease (AD).

Methods: We conducted pharmacoepidemiologic studies using two large-scale real-world databases. We fitted covariate-adjusted Cox models to compare the risks of AD among initiators of GLP-1 receptor agonists, SGLT-2 inhibitors, and DPP-4 inhibitors.

Comparative metabolomic analysis of human lung slices (hu-PCLS) exposed to either standard or FLASH protons: a pilot study.

Background: Recent advances in radiation biology and preclinical research have identified that high doses of radiation at ultra-high dose rate can lead to sparing of normal tissue, while maintaining tumor control. This has been termed the FLASH effect and has been extended from electrons to protons, heavy ions and photons. Lung cancer treatments, despite the advancements in radiotherapy with precise protons, are still associated with significant damage to the normal tissue.

Better health and less stress: an elicitation survey on quitting little cigars and cigarillos by young adults.

Introduction: Little cigars and cigarillos (LCCs) pose health risks similar to cigarettes yet remain popular among US young adults (YAs), particularly Black or African American YAs. While previous studies have explored beliefs surrounding LCC prevention and use, no research has yet focused on LCC cessation beliefs.

Aims And Methods: This study examined the beliefs of 134 YAs who currently or formerly used LCC aged 18-29, recruited via Qualtrics panels.

Influence of the number of images on threshold image contrast measurements with a phantom with gold disks in digital mammography.

Image quality, in addition to radiation dose, is the most important physical parameter in digital mammography. Image quality should be periodically monitored using the CDMAM phantom. The aim of this study is to investigate the effect of the number of analyzed images on the result of threshold image contrast measurements using the CDMAM phantom in different versions.

The current landscape of single-port robotic surgery in urology.

The advent of the purpose-built da Vinci single-port robotic platform marks a pivotal advancement in minimally invasive urological surgery. Designed to overcome the ergonomic and technical limitations of prior single-site approaches, the single-port system enables complex procedures through a single incision, with enhanced dexterity, optimized use of confined spaces and improved cosmetic and peri-operative outcomes. The single-port system has been increasingly used across a wide range of urological indications, including robot-assisted radical prostatectomy, partial nephrectomy, nephroureterectomy and reconstructive surgeries such as pyeloplasty and ureteral re-implantation.

Radical nephroureterectomy vs kidney sparing surgery for upper tract urothelial carcinoma in solitary kidney patients: a multi-institutional analysis of the ROBUUST 2.0 registry.

Purpose: Radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) in solitary kidney patients is a rare and underreported scenario. This study aims to compare the outcomes of UTUC solitary kidney patients becoming anephric after RNU to those of patients undergoing kidney-sparing surgery (KSS).

Methods: Data from patients with a solitary kidney were retrieved from the ROBUUST 2.

Exosomal ALPPL2 and THBS2 as biomarkers for early detection and disease monitoring of pancreatic ductal adenocarcinoma.

Background: Lack of reliable biomarkers for early detection and monitoring contributes to the poor prognosis of pancreatic ductal adenocarcinoma (PDAC), as the current clinical marker, CA19-9, lacks adequate specificity and sensitivity.

Methods: Serum concentrations of ALPPL2-positive and THBS2-positive exosomes were measured using an ExoView assay in two cohorts: a cohort of 219 subjects, including non-disease controls and patients with early- or late-stage PDAC, and a longitudinal cohort of 26 patients with advanced PDAC undergoing treatment.

Results: Exosomal ALPPL2 and THBS2 distinguished non-cancer cases from PDAC with high accuracy; area under the curve (AUC) values = 0.

Genome-wide CRISPR screen identifies Menin and SUZ12 as regulators of human developmental timing.

Embryonic development follows a conserved sequence of events across species, yet the pace of development is highly variable and particularly slow in humans. Species-specific developmental timing is largely recapitulated in stem cell models, suggesting a cell-intrinsic clock. Here we use directed differentiation of human embryonic stem cells into neuroectoderm to perform a whole-genome CRISPR-Cas9 knockout screen and show that the epigenetic factors Menin and SUZ12 modulate the speed of PAX6 expression during neural differentiation.

Pancancer outcome prediction via a unified weakly supervised deep learning model.

Accurate prognosis prediction is essential for guiding cancer treatment and improving patient outcomes. While recent studies have demonstrated the potential of histopathological images in survival analysis, existing models are typically developed in a cancer-specific manner, lack extensive external validation, and often rely on molecular data that are not routinely available in clinical practice. To address these limitations, we present PROGPATH, a unified model capable of integrating histopathological image features with routinely collected clinical variables to achieve pancancer prognosis prediction.