Patient Perspectives on the Value of Stereotactic Body Radiotherapy in the Management of Breast Cancer: The PERSPECTIVE Study.

Aims: Oligometastatic disease describes limited metastases amenable to therapy such as stereotactic body radiotherapy (SBRT). This study aims to understand which outcomes are most important to patients when considering SBRT as a treatment option. The insights gained will help inform future patient-directed trial endpoints and provide valuable guidance to clinicians supporting patients through their decision-making process.

Segmentation aware probabilistic phenotyping of single-cell spatial protein expression data.

Spatial protein expression technologies can map cellular content and organization by simultaneously quantifying the expression of >40 proteins at subcellular resolution within intact tissue sections and cell lines. However, necessary image segmentation to single cells is challenging and error prone, easily confounding the interpretation of cellular phenotypes and cell clusters. To address these limitations, we present STARLING, a probabilistic machine learning model designed to quantify cell populations from spatial protein expression data while accounting for segmentation errors.

N6-methyladenosine modification of 3'tRF-AlaAGC impairs PD-1 blockade efficacy by promoting lactic acid accumulation in the tumor microenvironment of gastric carcinoma.

The balance between CD8 T cells and regulatory T (Treg) cells in the tumor microenvironment (TME) plays a crucial role in the immune checkpoint inhibition (ICI) therapy in gastric carcinoma (GC). However, related factors leading to the disturbance of TME and resistance to ICI therapy remain unknown. In this study, we applied N6-methyladenosine (m6A) small RNA Epitranscriptomic Microarray and screened out 3'tRF-AlaAGC based on its highest differential expression level and lowest inter-group variance.

The Landmark Series: Neoadjuvant Radiotherapy in Extremity Soft Tissue Sarcoma-The Way to Hypofractionation.

For patients with nonmetastatic soft tissue sarcoma (STS) who are at high risk of local recurrence, the standard of care for limb-conserving local management is combined radiotherapy and surgery. Radiotherapy for STS entails 5 weeks of conventionally fractionated radiotherapy (25 × 2 Gy) preoperatively or 6 or more weeks postoperatively. There is growing interest in the use of preoperative hypofractionated regimes, viz.

The correlation between LAG-3 expression and the efficacy of chemoimmunotherapy in advanced biliary tract cancer.

In our previous phase II T1219 trial for advanced biliary tract cancer (ABTC), the combination of nivolumab with modified gemcitabine and S-1 exhibited promising efficacy, while the programmed-death-ligand-1 (PD-L1) expression did not predict chemoimmunotherapy efficacy. Lymphocyte-activation-gene-3 (LAG-3), a negative immune checkpoint, is frequently co-expressed with PD-L1. This study assessed the predictive value of LAG-3 expression in ABTC patients who received chemoimmunotherapy.

[Tumor-associated macrophages promote pre-metastatic niche formation in ovarian cancer].

Patients with ovarian cancer (OC) are often diagnosed at an advanced stage and have a poor prognosis because of extensive tumour metastasis. Tumour metastasis usually occurs in stages, which means that before the invasion of tumour cells, a pre-metastatic niche (PMN) has been formed to support the subsequent colonisation and growth of tumour cells. Tumour-associated macrophages (TAMs) are highly heterogeneous in terms of origin, phenotype and function.

Pan-cancer drivers of metastasis.

Metastasis remains a leading cause of cancer-related mortality, irrespective of the primary tumour origin. However, the core gene regulatory program governing distinct stages of metastasis across cancers remains poorly understood. We investigate this through single-cell transcriptome analysis encompassing over two hundred patients with metastatic and non-metastatic tumours across six cancer types.

Downregulation of PAX1 in OSCC Enhances Stemness and Immunosuppression via IFIT1 and PD-L1 Pathways.

Objective: Our study investigated how arecoline-induced extracellular vesicle (EV) secretion suppresses PAX1 protein production through DNA hypermethylation and examined whether PAX1 downregulation enhances cancer stemness and immunosuppression in the tumor microenvironment.

Materials And Methods: EVs were isolated from SAS/TW2.6 cancer cell lines using ultracentrifugation and identified using transmission electron microscopy.

A novel deep synthesis-based insider intrusion detection (DS-IID) model for malicious insiders and AI-generated threats.

Insider threats pose a significant challenge to IT security, particularly with the rise of generative AI technologies, which can create convincing fake user profiles and mimic legitimate behaviors. Traditional intrusion detection systems struggle to differentiate between real and AI-generated activities, creating vulnerabilities in detecting malicious insiders. To address this challenge, this paper introduces a novel Deep Synthesis Insider Intrusion Detection (DS-IID) model.

Structural insights into distinct mechanisms of RNA polymerase II and III recruitment to snRNA promoters.

RNA polymerase III (Pol III) transcribes short, essential RNAs, including the U6 small nuclear RNA (snRNA). At U6 snRNA genes, Pol III is recruited by the snRNA Activating Protein Complex (SNAPc) and a Brf2-containing TFIIIB complex, forming a pre-initiation complex (PIC). Uniquely, SNAPc also recruits Pol II at the remaining splicesosomal snRNA genes (U1, 2, 4 and 5).

Oncogenic RARγ isoforms promote head and neck cancer proliferation through vinexin-β-mediated cell cycle acceleration and autocrine activation of EGFR signal.

Results of retinoid-based therapies in head and neck cancer (HNC) are generally disappointing, indicating a lack of understanding of retinoic acid signaling. The role of retinoic acid receptor gamma (RARγ) and its isoforms in HNC is yet to be established. In this study, we found that RARγ1, 2, 4 are the predominant RARγ isoforms expressed in various types of human cancers, including HNC.

Ku70 targets BRD3-MYC/Cyclin D1 axis to drive hepatocellular carcinoma progression.

Hepatocellular carcinoma (HCC) is a common cancer characterized by robustly proliferative and metastatic capabilities. Bromodomain-containing proteins are critical to the development of diverse diseases via regulating cell proliferation, differentiation, and death. However, the role of Bromodomain-containing protein 3 (BRD3) in HCC is elusive.

The Effects of Anlotinib Combined with Chemotherapy following Progression on Cyclin-Dependent Kinase 4/6 Inhibitor in Hormone Receptor-Positive Metastatic Breast Cancer.

Purpose: Endocrine therapy combined with cyclin-dependent kinase (CDK) 4/6 inhibitors (CDK4/6i) is the preferred treatment for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). However, there are currently no recommendations for therapeutic strategies after progression on CDK4/6i-based treatment. This study aimed to examine the efficacy and safety of anlotinib plus chemotherapy in HR+/HER2- MBC after progression on CDK4/6 inhibitors.

Reprogramming Dysfunctional Dendritic Cells by a Versatile Catalytic Dual Oxide Antigen-Captured Nanosponge for Remotely Enhancing Lung Metastasis Immunotherapy.

Dendritic cells (DCs) play a crucial role in initiating antitumor immune responses. However, in the tumor environment, dendritic cells often exhibit impaired antigen presentation and adopt an immunosuppressive phenotype, which hinders their function and reduces their ability to efficiently present antigens. Here, a dual catalytic oxide nanosponge (DON) doubling as a remotely boosted catalyst and an inducer of programming DCs to program immune therapy is reported.

N-methyladenosine in 28S rRNA promotes oncogenic mRNA translation and tyrosine catabolism.

Aberrant N-methyladenosine (mA) modification on mRNA results in dysregulated mRNA translation and cancer progression; however, the role of mA modification on rRNA remains unclear in cancers. Here, we show that ZCCHC4 and its mediated mA modification on 28S rRNA are upregulated in various cancers and correlated with poor survival. Functionally, ZCCHC4 promotes intrahepatic cholangiocarcinoma (ICC) progression via its catalytic activity.

Unraveling the protein kinase C/NDRG1 signaling network in breast cancer.

N-myc downstream-regulated gene 1 (NDRG1) is a member of the NDRG family of intracellular proteins and plays a central role in a wide range of biological processes including stress response, differentiation, and metabolism. The overexpression of NDRG1 is an indicator of poor prognosis in various types of cancer. Here, we found that NDRG1 is an independent prognostic marker of poor outcome in breast cancer (BC).

Intraperitoneal Steroid Therapy for Recurrent Malignant Ascites in Advanced Cancer Patients: A Case Series.

Intraperitoneal administration of depot corticosteroids following an initial paracentesis reduces ascitic fluid formation and extends the interval between subsequent paracentesis sessions. This approach may effectively manage recurrent malignant ascites and enhance patients' quality of life.

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Standard: Human gastric cancer organoids.

Gastric cancer is one of the most common malignancies with poor prognosis. The use of organoids to simulate gastric cancer has rapidly developed over the past several years. Patient-derived gastric cancer organoids serve as in vitro models that closely mimics donor characteristics, offering new opportunities for both basic and applied research.

Application value of personalized 3D printing vaginal model for the Image-guided adaptive brachytherapy of cervical cancer.

Objective: To explore the application value of using 3-dimensional (3D) printing (3DP) technology to create individualized vaginal molds for brachytherapy (BT) in high-dose-rate 3D cervical cancer through reverse engineering of needle placement.

Methods: Prospectively, 11 patients with cervical cancer were treated with 3DP-intracavitary/interstitial (IC/IS) BT using 3DP to create individualized vaginal molds. All patients were performed BT after completion of external beam radiotherapy (EBRT).

Impact of vancomycin therapeutic drug monitoring on mortality in sepsis patients across different age groups: a propensity score-matched retrospective cohort study.

Background: Due to its potent antibacterial activity, vancomycin is widely used in the treatment of sepsis. Therapeutic drug monitoring (TDM) can optimize personalized vancomycin dosing regimens, enhancing therapeutic efficacy and minimizing nephrotoxic risk, thereby potentially improving patient outcomes. However, it remains uncertain whether TDM affects the mortality rate among sepsis patients or whether age plays a role in this outcome.