This study investigated the contribution of peritoneal macrophages to tumor control using a DBA/2-SL2 murine model of concomitant tumor immunity.

Female DBA/2 mice were subjected to a concomitant tumor model in which SL2 lymphoma cells were injected subcutaneously (SC) to establish a primary tumor, followed by intraperitoneal (IP) SL2 challenge to induce secondary tumors. Peritoneal immune cells were analyzed by flow cytometry 4 days after IP challenge. Absolute cell numbers were calculated from total viable cell recovery. To assess functional antitumor activity, CD11b⁺F4/80⁺ peritoneal macrophages were isolated by magnetic separation and adoptively transferred into naïve mice together with SL2 cells. In additional experiments, mice received repeated IP injections of SL2 cells. Non-parametric statistical tests were used for data analysis.

Prolonged survival in mice with secondary IP SL2 tumors was associated with pronounced alterations in peritoneal immune composition. Flow cytometric analysis revealed a marked accumulation of small peritoneal macrophages (SPMs) and dendritic cells (DCs) in mice with secondary IP tumors. Absolute counts of SPMs (CD11b^intF4/80^int) and DCs (CD11c⁺) were significantly increased in the secondary IP tumor group, with a positive, not statistically significant, correlation between these population. In contrast, mice with primary IP tumors showed expansion of CD11c^-CD11b^- F4/80^- cells, which may include SL2 tumor cells, reduced numbers of B lymphocytes (CD19⁺) and large peritoneal macrophages (LPMs) (CD11b^hiF4/80^hi) and an increased number of CD11b^lowF4/80^int cells. Adoptive transfer of peritoneal macrophages from mice with secondary IP tumors did not prolong survival. Repeated IP administration of SL2 cells was associated with improved survival in mice bearing SC tumors in 3 of 5 mice, compared with 1 of 5 mice in the SC tumor-only group, although this difference did not reach statistical significance.

Prolonged survival of DBA/2 mice with secondary IP SL2 tumors is associated with a distinct peritoneal immune landscape characterized by accumulation of SPMs and DCs. While macrophages alone were insufficient to control tumor growth, repeated IP tumor challenge suggested a trend toward systemic antitumor activity. Collectively, these findings highlight SPMs and DCs as prominent cells associated with survival benefit in this model.

The extensive expression of STING in patients with non-small cell lung cancer (NSCLC) is closely associated with overall survival and other factors. Activation of the STING pathway can suppress NSCLC. However, the clinical translation of STING agonists remains hindered by challenges such as off-target effects, metabolic instability, and suboptimal pharmacokinetics.

In this study, we engineered two oncolytic adenoviruses (OAds), OAd-HcGAS and OAd-McGAS, expressing human or murine cGAS, respectively, using an Ad5/3 chimeric adenovirus platform under regulation by the hTERT promoter to evaluate whether OVs carrying the cGAS gene are capable of specifically activating the STING pathway within tumors and enhancing the anti-tumor efficacy of OVs both in vitro and in vivo.

In vitro, OAd-HcGAS exhibited robust replication and potent cytolytic activity in tumor cells. It activated the STING-TBK1-IRF3 signaling axis, triggering a strong type I interferon (IFN-I) and pro-inflammatory cytokine response without compromising viral replication. In a murine Lewis lung carcinoma allograft model, intratumoral (i.t.) administration of OAd-McGAS led to substantial cGAS expression and consequential activation of the STING pathway. Moreover, the combination with anti-PD-L1 therapy resulted in tumor regression in over half of the cases. Notably, this armed oncolytic virus strategy enhanced the activation and infiltration of multiple immune cell populations.

Collectively, these findings establish cGAS-expressing oncolytic adenoviruses as a novel and effective therapeutic strategy for lung cancer treatment.

Virilization in girls younger than 2 years should prompt careful evaluation for pathological androgen excess and should be interpreted as a practical clinical reminder rather than as a stand-alone diagnostic tool. Pediatric adrenocortical tumors (ACTs) are rare but are usually hormonally active, and their interpretation requires pediatric-specific clinicopathological criteria rather than direct application of adult adrenal carcinoma criteria.

A 19-month-old girl presented with a 6-month history of progressive voice deepening, pubic hair growth, and clitoromegaly. Beard-like facial hair, acne, axillary hair, adult-type body odor, and vaginal bleeding were not reported. Basal gonadotropins were suppressed, gonadotropin-releasing hormone analogue stimulation showed a non-pubertal luteinizing hormone response, bone age was advanced, and dehydroepiandrosterone sulfate was markedly elevated (>1,000 μg/dL; above the assay upper reportable limit). Imaging identified an approximately 5-cm right adrenal mass. The patient underwent open surgical resection. Histopathology showed an ACT of uncertain malignant potential with a formally reported Wieneke score of 3, based on increased or borderline-high mitotic activity as interpreted in the pathology report, atypical mitotic figures, and capsular invasion. Immunohistochemistry showed steroidogenic marker expression, a missense-mutant p53 pattern, focal reticulin rarefaction, and a Ki-67 hotspot index of approximately 30%. Postoperative androgen levels declined markedly, and biochemical remission was maintained at 4 and 8 months.

Androgen-dominant virilization preceded and outweighed mild breast development, serving as a practical reminder to prioritize adrenal-focused assessment in very young girls with rapidly progressive virilization. Preoperative ultrasonography, contrast-enhanced computed tomography, and magnetic resonance imaging were performed; dedicated postoperative contrast-enhanced abdominal CT or MRI had not yet been obtained during the available follow-up period. Genetic testing was incomplete because the family declined germline testing after counseling; testing of the proband should be re-offered during follow-up, with cascade testing for first-degree relatives if a pathogenic germline variant is identified.

Long-term surveillance should include endocrine assessment, pubertal monitoring, genetics re-counseling, and protocolized cross-sectional imaging, because early biochemical remission does not exclude recurrence or later secondary central precocious puberty.

Acupuncture therapy shows promise for polycystic ovary syndrome (PCOS), but its molecular mechanisms remain unclear. This study investigates whether acupuncture alleviates PCOS by regulating granulosa cell (GC) ferroptosis via extracellular vesicles (EVs).

Bioinformatic analysis of KGN cell transcriptome data identified heme oxygenase-1 (HMOX1) as a key candidate. Its role was validated in a PCOS rat model and GCs using RT-qPCR, western blot, and immunohistochemistry. Ferroptosis was assessed via malondialdehyde (MDA), glutathione (GSH), and ferroptosis-related proteins (GPX4, FTH1, SLC7A11, NCOA4). HMOX1 gain/loss-of-function, rescue experiments (ferrostatin-1), and transmission electron microscopy defined its function. PCOS rats received acupuncture for 4 weeks; ovarian function and ferroptosis markers were analyzed. EVs from follicular fluid were characterized, and miRNA candidates targeting HMOX1 were screened. The EV-miRNA mechanism was tested via co-culture and inhibition assays.

HMOX1 was upregulated in PCOS. Its overexpression induced ferroptosis and impaired GC proliferation, reversible by ferrostatin-1. Acupuncture improved ovarian histology and oocyte maturation, concurrently normalizing HMOX1 and ferroptosis markers. It specifically enriched miR-873-5p in EVs. These EVs delivered miR-873-5p to GCs, downregulating HMOX1 and alleviating ferroptosis, an effect blocked by miR-873-5p inhibition.

Acupuncture mitigates PCOS by promoting EV-mediated transfer of miR-873-5p, which targets HMOX1 to inhibit GC ferroptosis and restore ovarian function. This identifies a novel acupuncture-EV-miRNA-HMOX1-ferroptosis axis as a therapeutic mechanism for PCOS.

Immunotherapy combined with anti-angiogenic agents and chemotherapy has emerged as a novel therapeutic option for non-squamous non-small cell lung cancer (non-sqNSCLC) after resistance to tyrosine kinase inhibitors (TKIs). This study evaluated the efficacy, safety, and cost-effectiveness of these regimens in patients with TKI-resistant non-sqNSCLC in China.

A network meta-analysis was performed to compare the efficacy and safety of ivonescimab plus chemotherapy (Ivon-Chem), sintilimab plus bevacizumab and chemotherapy (Sint-Beva-Chem), and atezolizumab plus bevacizumab and chemotherapy (Atez-Beva-Chem). A Markov model was constructed to assess the cost-effectiveness of Ivon-Chem, Sint-Beva-Chem, Atez-Beva-Chem, and chemotherapy until the survival probability fell below 1% in any regimen. The incremental cost-effectiveness ratio (ICER) and net monetary benefit (NMB) were estimated using a willingness-to-pay (WTP) threshold of $41,859. Sensitivity analyses and scenario simulations were also performed.

Ivon-Chem, Sint-Beva-Chem, and Atez-Beva-Chem improved efficacy but were associated with poorer safety profiles than chemotherapy. Compared with chemotherapy, Ivon-Chem, Sint-Beva-Chem, and Atez-Beva-Chem were not cost-effective, with ICERs of $61,882.3/QALY, $68,657.0/QALY, and $188,820.5/QALY, respectively. Moreover, the NMBs of Ivon-Chem, Sint-Beva-Chem and Atez-Beva-Chem were all negative, indicating that none of these regimens was economically acceptable. Scenario analyses indicated that, compared with chemotherapy, Ivon-Chem would become cost-effective if the price of ivonescimab were reduced by at least 47.2%. Similarly, Sint-Beva-Chem and Atez-Beva-Chem would achieve cost-effectiveness following price reductions of 59.3% for both sintilimab and bevacizumab, and 84.4% for both atezolizumab and bevacizumab, respectively.

These immunotherapy-based regimens provided significant survival benefits in patients with TKI-resistant non-sqNSCLC. However, from the perspective of the Chinese healthcare system, Ivon-Chem, Sint-Beva-Chem, and Atez-Beva-Chem were not cost-effective. Substantial price reductions would be required to improve their economic viability.

This study aimed to characterize cancer patients presenting to the emergency department (ED) and to identify factors associated with ED length of stay (LOS) and 72-hour revisits.

This retrospective study analyzed the medical records of adult cancer patients who visited the ED of a tertiary hospital in Seoul between June and November 2023. Among 21,495 ED visits, 2,225 met the inclusion criteria. Variables included general characteristics, cancer-related characteristics, and ED visit-related characteristics. Outcomes were ED LOS and 72-hour revisits. Data were analyzed using the t-test, analysis of variance, chi-square test, multiple linear regression, and logistic regression.

The mean age was 64.75 ± 14.85 years, and 51.0% of patients were men. Gastrointestinal cancers were the most common cancer type (49.6%), and abdominal pain was the most frequent chief complaint (17.4%). The mean ED LOS was 245.93 ± 189.79 minutes, and the 72-hour revisit rate was 5.4%. Factors associated with longer ED LOS included older age, previous ED visits, off-hours arrival, higher acuity, ambulance transport, abnormal respiratory rate, and administration of nonsteroidal anti-inflammatory drugs, acetaminophen, or opioids. Factors influencing 72-hour revisits included the absence of a do-not-resuscitate (DNR) order, abnormal systolic blood pressure, and admission.

For older cancer patients with high acuity who visit the ED by ambulance during off-hours, early assessment of dyspnea and prior ED utilization, along with prompt symptom-based pharmacologic interventions, is recommended. At discharge, providing education tailored to the patient's clinical condition, including DNR status, admission status, and vital signs, and ensuring early outpatient or telephone follow-up may strengthen continuity of care and reduce short-term ED revisits.

The tumor microenvironment (TME) is a complex ecosystem with harsh conditions, such as hypoxia, nutrient deprivation, metabolic acidosis and oxidative stress, that promote tumor progression and shape immune responses. In this environment, endoplasmic reticulum stress and the unfolded protein response are activated, with the transcription factor X‑box binding protein 1 (XBP1) serving a key role. XBP1 not only maintains cell protein homeostasis, but also modulates the generation, metabolic adaptation and immunosuppressive function of myeloid‑derived suppressor cells (MDSCs). The TME and tumor‑derived factors, such as exosomes, remotely activate XBP1 in MDSCs, enhancing their survival and immunosuppressive capability by reprogramming lipid and glucose metabolism and upregulating the expression of arginase‑1, inducible nitric oxide synthase, reactive oxygen species and immunosuppressive cytokines. The present review aimed to describe the TME stress‑XBP1‑MDSC‑immunosuppression axis, its molecular mechanisms and the role of XBP1 in MDSC heterogeneity and plasticity. Targeting XBP1 may enhance the efficacy of existing therapies, particularly immune checkpoint blockade, by alleviating MDSC‑mediated immunosuppression, offering a novel paradigm for understanding and reversing tumor immune escape.

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is a classification system first released in 2018. It provides a standardized categorization for salivary gland lesions. Cell blocks can be prepared from fine-needle aspirations (FNAs) and can be utilized for the diagnostics of salivary gland lesions. This study aims to evaluate the distribution of the MSRSGC categories and the associated risks of malignancy (ROM) in salivary gland FNAs incorporating cell block preparations.

A PubMed literature search was conducted between March 3 and May 20, 2025, to identify studies with both cell block and MSRSGC applications in salivary gland FNAs. Data on sample size and the ROM for individual MSRSGC categories were extracted into Microsoft Excel and subsequently analyzed using OpenMetaAnalyst.

Five studies were identified with a total of 1132 FNA samples processed to cell blocks. The pooled distributions of samples in the present meta-analysis were 21.9% in non-diagnostic (ND), 6.4% in non-neoplastic (NN), 8.2% in atypia of undetermined significance (AUS), 30.0% in benign neoplasm (BN), 8.0% in salivary gland neoplasm of uncertain malignant potential (SUMP), 1.9% in suspicious for malignancy (SM), and 19.4% in malignant (MN). The pooled ROMs from this meta-analysis was 25.3% in ND, 16.5% in NN, 26.3% in AUS, 2.0% in BN, 28.7% in SUMP, 84.8% in SM, and 97.7% in MN.

The ROMs of the AUS and SUMP categories were lower than the compared meta-analyses. The cell block application utilizes architecture and ancillary studies, leading to better performance in indeterminate categories.

Phase II and III trials have demonstrated progression-free survival (PFS) benefits of pyrotinib plus capecitabine over lapatinib plus capecitabine in HER2-positive metastatic breast cancer (MBC). However, long-term overall survival (OS) data from a single-center cohort remain limited. This pooled analysis compared OS between the two regimens and explored outcomes across prespecified subgroups.

We included patients with HER2-positive MBC from our center enrolled in a Phase Ic study, a Phase II study, or the Phase III PHOEBE trial. The primary endpoint was OS. OS was analyzed using Kaplan-Meier estimates, log-rank tests, and a multivariable Cox model adjusted for ECOG performance status, pathological grade, prior anti-HER2 therapy, trastuzumab exposure duration, trastuzumab resistance, and prior chemotherapy lines. The proportional hazards assumption was assessed using Schoenfeld residuals. Exploratory subgroup analyses used prespecified categories.

At data cutoff, 82 patients were included; 53 received pyrotinib plus capecitabine and 29 received lapatinib plus capecitabine. Baseline characteristics were comparable between groups. Median OS was 74.61 months (95% CI 41.10-not reached) with pyrotinib plus capecitabine and 30.98 months (26.12-50.76) with lapatinib plus capecitabine (log-rank p = 0.0053). Cox models suggested a reduced risk of death with pyrotinib plus capecitabine. Subgroup analyses were exploratory and should be interpreted cautiously because several subgroup estimates were imprecise.

In this single-center pooled analysis, pyrotinib plus capecitabine was associated with significantly longer OS than lapatinib plus capecitabine in patients with HER2-positive MBC. These exploratory results are consistent with prior Phase II/III trials and provide evidence supporting the OS benefit of pyrotinib.

Colorectal cancer (CRC) is a leading cause of cancer-related death and is associated with high recurrence rates. Solute carrier family 7 member 5 (SLC7A5), a core transporter that facilitates the transmembrane movement of tryptophan, plays a role in various cancers. However, whether and how SLC7A5 promotes colorectal liver metastasis (CRLM) through tryptophan metabolism reprogramming and immune remodelling remain unexplored.

We integrated public datasets and clinical specimens to analyse SLC7A5 expression and prognosis, and validated its role in proliferation and metastasis using in vitro assays and in vivo models. Targeted metabolomics and isotope tracing identified kynurenine (Kyn) and xanthurenic acid (XANA) as downstream metabolites of SLC7A5. Single-cell RNA sequencing (scRNA-seq) and conditioned medium experiments were used to assess the impact of SLC7A5 on the tumour immune microenvironment (TIME).

SLC7A5 expression increases sequentially in normal tissue, primary tumours and liver metastases, and higher SLC7A5 levels are associated with worse prognosis. SLC7A5 facilitates CRC cell growth, metastasis and epithelial‒mesenchymal transition (EMT) by promoting the production of Kyn and XANA and subsequent activation of the aryl hydrocarbon receptor (AhR). scRNA-seq analysis and conditioned medium experiments demonstrated that SLC7A5 knockdown reprograms the TIME by driving macrophages towards an antigen-presenting phenotype, alleviating CD8⁺ T-cell exhaustion, polarising CD4⁺ T cells towards Th1/Th17 subsets and triggering antigen-driven immunoglobulin G (IgG)-secreting B-cell clonal expansion, effects that were reversed by exogenous Kyn/XANA supplementation. Moreover, combination therapy with the SLC7A5 inhibitor JPH203 and anti-programmed cell death protein 1 (PD-1) antibody produced synergistic tumour growth inhibition and heightened antitumour immune responses.

Collectively, our findings reveal that SLC7A5 drives CRLM through tryptophan/Kyn/XANA-AhR signalling and concomitant remodelling of the TIME, positioning SLC7A5 as a promising target for combination therapy with anti-PD-1 in CRLM.