Breast cancer survivors are increasing in number and living longer but often experience reduced quality of life (QOL) from treatment sequelae. Physical activity (PA) interventions can improve QOL, but many rely on costly specialists or are difficult to scale. We adapted an evidence-based peer-mentoring program (moving forward together) for web delivery (webMFT). The platform centralizes peer-coach matching, delivery, and coordination to reduce administrative burden and improve scalability.

We evaluated webMFT's cost-effectiveness.

In a 12-week randomized trial (N = 61), survivors were assigned to webMFT (n = 30; weekly phone calls plus activity self-monitoring) or MVPA Tracking (n = 31; activity self-monitoring only). From a payer's perspective, we estimated incremental cost-effectiveness ratios (ICERs) for quality-adjusted life years (QALYs) and device-measured moderate-to-vigorous physical activity (MVPA). Intervention costs were collected from time logs for research staff and peer coaches. We conducted sensitivity analyses by bootstrapping and constructing cost-effectiveness planes and cost-effectiveness acceptability curves (CEACs).

In the base-case analysis the ICER for webMFT was $38 430 per QALY gained versus MVPA Tracking. At the high end of probabilistic implementation-cost sensitivity analyses that considered wider ranges of wages, platform costs, and implementation times, the mean ICER was $43 418 per QALY and the probability of cost-effectiveness was 87% at the commonly used $150 000 per QALY threshold. WebMFT increased QALYs but did not produce greater increases in device-measured PA compared with MVPA Tracking.

At a $150 000 per QALY threshold, webMFT appears cost-effective for improving QALYs among breast cancer survivors. Larger studies are needed to confirm these findings.

This underlying clinical trial was registered at clinicaltrials.gov (NCT05409664).

Patients with newly diagnosed gynecologic cancers often seek information online, but the quality of available resources may be inconsistent. Although GPT-4 may offer an alternative to traditional internet search engines, its performance remains largely under-studied in gynecologic oncology.

This study aimed to compare the completeness, accuracy, and reference quality of responses generated by GPT-4 with those generated by Google in clinical scenarios involving a new diagnosis of a gynecologic cancer.

Clinical scenarios representing early- and advanced-stage endometrial, ovarian, and cervical cancers were developed by gynecologic oncologists using publicly available patient education materials. Each scenario included 4 standardized questions addressing etiology, prognosis, treatment, and treatment efficacy. GPT-4 and Google were queried for each question, with new sessions for GPT-4 and private browsing for Google to minimize bias. Responses were independently evaluated by 4 gynecologic oncology experts who were blinded to each other's ratings. Accuracy was scored on a 6-point Likert scale; completeness and reference quality were scored on 3-point scales. Reference quality was categorized as low (commercial), medium (institutional or government), or high (peer reviewed). Optional free-text reviewer comments were collected and summarized descriptively to provide context for the quantitative findings. Descriptive statistics and Wilcoxon signed-rank tests were used for analysis.

Across 6 clinical scenarios and 21 standardized questions (N=84 total responses), GPT-4 outperformed Google across all evaluated domains. The median accuracy score was 6.00 (IQR 5.00-6.00) for GPT-4 and 5.00 (IQR 4.00-6.00) for Google (P=.04). The median completeness score was 3.00 (IQR 3.00-3.00) for GPT-4 and 2.00 (IQR 1.00-3.00) for Google (P=.009). Reference quality was also higher for GPT-4, with a median score of 3.00 (IQR 3.00-3.00) compared to 2.00 (IQR 2.00-2.00) for Google (P=.009). Reviewer comments noted that GPT-4 provided more accurate, comprehensive, and personalized responses, while Google returned less detailed content from general consumer health websites rather than peer-reviewed sources.

GPT-4 may serve as a reliable and high-quality resource for information in gynecologic oncology. Compared to Google, it delivered more accurate and complete content, with higher-quality references. Further research is needed to assess the readability and accessibility of GPT-4-generated content across diverse patient populations.

Cushing's disease (CD) is an endocrine condition characterized by an excessive production of adrenocorticotropic hormone (ACTH) by the anterior pituitary, which determines an increase in the production of cortisol in the adrenal glands and secondary clinical manifestations. The differential diagnosis includes a corticotropic pituitary tumor or ACTH-producing ectopic neuroendocrine syndrome (EAS). In addition, non tumoral hypercortisolism (NtH) should be taken into account, which may be clinically indistinguishable from CD. Pituitary magnetic resonance imaging (MRI) with gadolinium is the imaging modality of choice; however, conventional MRI can identify only 50-60% of the cases. This has led to the use of bilateral inferior petrosal sinus sampling and the development of dynamic tests, which may allow etiologic certainty and, thus, avoid unnecessary procedures. This review outlines the evidence underpinning the different diagnostic strategies for this disease.

Recent studies have described an ability of cancer cells to survive engagement of apoptotic pathways following chemical and therapeutic insults, challenging the prevailing model that caspase activation inevitably leads to cellular demise. Gasdermin E (GSDME), whose expression is frequently down-regulated or silenced in many tumors and tumor-derived cell lines, is a putative tumor suppressor capable of facilitating the induction of antitumor immunity. We found that GSDME expression precluded high caspase activity before cellular membrane rupture downstream of chemical and immune-mediated insults, and its absence allowed for enhanced activities downstream of caspase activation, including the DNA-damaging effects of caspase-activated deoxyribonuclease. Loss of GSDME allowed cells that had sustained DNA damage to survive, resulting in development and propagation of mutated clones. We conclude that GSDME functions as a key rheostat for determining cell death outcomes by tuning the tolerance to the activities of caspases and their substrates during apoptosis. In analyzing solid tumors in The Cancer Genome Atlas, we found that tumor mutational burden was higher in tumors with low GSDME expression and high immune signatures, supporting the possibility that the effects we describe affect tumor mutation in response to immune assault.

Hepatocellular carcinoma (HCC) remains a major challenge threatening global health. It has a high incidence with poor prognosis, and its response to current conventional therapies is not satisfactory, so we need to explore new effective therapies to address this problem. Targeted therapy represents a promising approach, but the therapeutic efficacy of targeting ion transporters and nuclear transport proteins, such as Na+/K+/2Cl- cotransporter 1 (NKCC1) and Karyopherin β1 (KPNβ1), remains poorly investigated. This study aims to assess the therapeutic efficacy of targeting NKCC1 and KPNβ1 individually and in combination. We also explored the roles of these transporters in tumor cell proliferation and HCC progression. To achieve this aim, an HCC rat model was used, induced by diethylnitrosamine and phenobarbital. The evaluation included histopathological examination and assessment of liver function biomarkers (alanine aminotransferase and aspartate aminotransferase), cell cycle regulators (Cyclin D1, p21, E2F1), proliferation (Ki-67), apoptosis (Caspase-3), and expression of NKCC1 and KPNβ1. This study revealed that NKCC1 and KPNβ1 were upregulated in the HCC group. This increase was associated with increased proliferation and suppressed apoptosis. Targeting these proteins, particularly in combination, significantly improved liver function. It also induced cell cycle arrest, reduced proliferative markers, and enhanced apoptosis. These findings indicate that NKCC1 and KPNβ1 could serve as possible therapeutic targets in HCC treatment.

Due to the late stage at which most gastric cancer patients are diagnosed, the prognosis is often poor. Current treatments have limited efficacy for advanced cases. This study delves into the involvement of circARID1A and the mechanisms behind its role in gastric cancer progression. GES-1 cell line and GC cell lines HGC-27, AGS, MKN45, and SNU-16 were cultured and subjected to various assays. RNA interference and overexpression techniques were used to modulate circARID1A and miR-147a levels in vitro, while xenograft tumor models in BALB/c nude mice were used to assess tumor growth in vivo. Cellular growth, migration, and invasion were assessed using CCK8, colony formation, and Transwell assays. Dual-luciferase reporter assays, qPCR and Western blot were utilized to investigate the interactions between circARID1A, miR-147a, and SNAI2. CircARID1A promotes GC cell proliferation, migration, and invasion by regulating the miR-147a/SNAI2 axis. In vivo, knockdown of circARID1A inhibits tumor growth in subcutaneous xenograft models.

Oral squamous cell carcinoma (OSCC) is represented as a major global health concern with few treatment options. Codon usage bias (CUB) is a non-random selection of synonymous codons. It offers information on gene expression patterns and molecular evolution.

This study examined CUB patterns in 1328 differentially expressed genes (651 up-regulated, 677 down-regulated) from oral cancer tissues. Nucleotide composition analysis, effective number of codons (ENC), Relative Synonymous Codon Usage (RSCU) analysis, neutrality plot analysis, and gene expression analysis were performed to assess codon usage patterns and their relationship to gene expression levels and pathway classification.

Nucleotide composition analysis indicated a clear GC-rich tendency with base frequencies arranged as C > G > A > T for up-regulated genes and C > A > G > T for down-regulated genes. The average ENC values were 47.21 (up-regulated) and 49.08 (down-regulated), suggesting a low codon usage bias. RSCU analysis revealed 25 more frequently used (mean RSCU >1.0) and 34 less frequently used (mean RSCU <1.0) codons in up-regulated genes, while down-regulated genes had 30 more frequently used and 29 less frequently used codons. Neutrality plot analysis showed that both gene groups were predominantly shaped by selective constraints rather than mutational pressure (slopes of 0.202 and 0.228 for up- and down-regulated genes, respectively), though these slopes provide only indirect, qualitative evidence and should not be interpreted as exact quantitative contributions. Gene expression analysis revealed 1328 differentially expressed genes with functional enrichment in metabolic pathways and cellular components.

These discoveries offer molecular insights into the genetic pathways that support oral cancer development. It implies that codon optimization could affect the translation efficiency of cancer-promoting genes.

Protein inhibitor of activated STAT 2 (PIAS2) is highly expressed in various solid tumors. Its precise function as a ferroptosis regulator in hepatocellular carcinoma (HCC) is still unknown. The purpose of this work was to determine whether PIAS2 overexpression attenuates erastin-induced ferroptotic changes and, in turn, is associated with the development of HCC in a manner that correlates with changes in Glutathione Peroxidase 4 (GPX4) protein levels and small ubiquitin-like modifier 3 (SUMO3) modification signals.

Erastin (Era) was used to induce ferroptosis in HepG-2 and H22 cells, while Ferrostatin-1 (Fer-1) was employed for validation. Western blotting, qPCR, and co-immunoprecipitation (Co-IP) were used to examine the expression and interaction of PIAS2 and GPX4. Ferroptosis markers (lipid-reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), Fe²⁺), cell viability, migration, and invasion were all analyzed. Functional rescue experiments were performed using PIAS2 overexpression (oe-PIAS2) and GPX4 knockdown (sh-GPX4). In addition, a murine model of H22 cells in the right groin/lateral abdomen was established for in vivo validation. Tumor weight and volume were measured in these animals. Additionally, tumor tissues were collected and subjected to immunohistochemical staining for Ki-67 expression, as well as biochemical analysis of ferroptosis-related markers (GSH, MDA, Fe²⁺).

In HCC cells, Era-induced ferroptosis resulted in a significant downregulation of PIAS2 and GPX4 expression, as well as elevated levels of lipid ROS, MDA, and Fe²⁺, decreased GSH content, and decreased cell viability, migration, and invasion. Under Era-treated conditions, overexpression of PIAS2 effectively reversed these changes, suppressing ferroptosis and partially restoring malignant phenotypes within the context of Era challenge. Co-treatment with Fer-1 significantly reversed Era-induced ferroptotic changes and rescued cell viability, migration, and invasion, without affecting PIAS2 expression, while also restoring GPX4 levels. Mechanistic studies revealed that PIAS2 and GPX4 co-immunoprecipitate in HCC cells, and PIAS2 overexpression was associated with increased SUMO3 modification signals and higher remaining GPX4 protein levels at the examined 12- and 24-h CHX time points. GPX4 knockdown attenuated the phenotypes observed under PIAS2 overexpression, suggesting possible involvement of GPX4 in the effects of PIAS2. In Era-treated tumor-bearing mice, PIAS2 overexpression was associated with increased tumor growth, elevated Ki-67 and GPX4 levels, and reduced ferroptosis indicators.

PIAS2 overexpression was associated with increased GPX4 SUMO3 modification signals and higher GPX4 protein levels at the examined CHX time points, together with reduced ferroptotic changes under Era-treated conditions.

Accumulating evidence suggests that neddylation contributes to tumor initiation and progression. Nonetheless, its biological functions and regulatory mechanisms in lung adenocarcinoma (LUAD) remain poorly understood.

Bioinformatics analyses integrated single-cell RNA sequencing (scRNA-seq) datasets from the Gene Expression Omnibus (GEO) with bulk RNA-seq data from The Cancer Genome Atlas (TCGA). The Seurat package was used for scRNA-seq processing, including cell clustering, annotation, cell-cell interaction analysis, and pseudotime trajectory inference. The survival and pROC packages were used for Kaplan-Meier (KM) survival and receiver operating characteristic (ROC) analyses, respectively. Tissue microarray (TMA) and immunohistochemistry (IHC) analyses were performed to validate biomarker expression. Functional assays, including Cell Counting Kit-8 (CCK-8), colony formation, wound healing, and Transwell assays, were conducted in A549 and NCI-H1975 cells with DNAJB1 knockdown.

Eight major cell populations were identified at the single-cell level, among which T/NK cells, particularly CD8+ effector memory T cells (CD8+ Tem), exhibited strong associations with neddylation. T/NK cells displayed extensive ligand-receptor-mediated interactions with other cell types. A transcription factor (TF)-target regulatory network was constructed, revealing that Surfactant Protein C (SFTPC), Lipopolysaccharide-Induced TNF Factor (LITAF), Serine/Threonine Kinase 17B (STK17B), Enah/Vasp-Like Protein (EVL), FYN Proto-Oncogene, Src Family Tyrosine Kinase (FYN), and Lymphocyte-Specific Protein 1 (LSP1) were associated with favorable prognosis, whereas DNAJB1 correlated with poor survival in LUAD patients. Pseudotime trajectories further delineated dynamic differentiation pathways of T/NK subsets and differential TF target expression across states. IHC analysis showed elevated DNAJB1 expression in tumors compared with adjacent normal tissues. Moreover, silencing DNAJB1 significantly inhibited proliferation, migration, and invasion in A549 and NCI-H1975 cells.

This study identifies neddylation-associated cellular phenotypes and clinically relevant biomarkers in LUAD, providing new mechanistic insights and highlighting potential therapeutic targets for LUAD treatment.

Renal cell carcinoma (RCC) is a common urological malignancy, yet the cytokine landscape of the tumor microenvironment, especially in early-stage tumors, remains poorly defined. Using antibody arrays, 174 tumor-related cytokines were measured in 20 sets of normal, para-cancerous, and tumor tissues from early-stage RCC patients. Selected cytokines were validated by ELISA. Functional enrichment was analyzed via DAVID, while transcriptional expression, survival outcomes, and immune infiltration were assessed using GEPIA, Kaplan-Meier Plotter, and TIMER databases. Thirty-four differentially expressed cytokines were identified in tumors versus controls, enriched in cytokine signaling, TNF, PI3K-Akt, Ras, HIF-1, and Toll-like receptor pathways. ELISA confirmed reduced IL-2, IL-15, IGFBP-2, HGF, ErbB3, and FLT3LG, and increased CCL4, CXCL9, and Angiopoietin-2 in tumors. Serum levels of HGF, ErbB3, and CCL4 were decreased in RCC patients, while urinary ErbB3 was also reduced. IL-2, IL-15, and CCL4 were upregulated in T1-T2 metastatic tumors. Several cytokines correlated with poor survival, except ErbB3, which associated with improved outcomes. Several cytokine-related genes, including CXCL9 and CCL4, correlated with inferred immune cell infiltration patterns. These findings suggest that early-stage RCC may be associated with a cytokine expression profile characterized by reduced immune-stimulating factors and elevated pro-angiogenic and inflammatory signals. Urinary ErbB3 emerged as a candidate non-invasive biomarker requiring further validation.