Despite advances in traditional therapies, the global burden of malignant tumors remains substantial. Although immunotherapy has achieved remarkable breakthroughs by activating the host immune system, its clinical benefits are limited to a subset of patientsowing to low response rates and drug resistance. Emerging evidence highlights the pivotal role of the gut microbiota in determining immunotherapy outcomes. Within this ecosystem, the genus Enterococcus acts as a "double-edged sword": whereas certain strains can enhance antitumor immunity, other species notably Enterococcus faecalis, drive tumor progression by inducing DNA damage and inflammatory cascades. Therefore, elucidating the intricate interactions between Enterococcus and the host immune system is imperative for optimizing immunotherapeutic strategies and developing novel microbiome-based therapies.

The global incidence of bladder cancer continues to rise. Treatments for this disease, particularly radical cystectomy and urinary diversion, can profoundly disrupt sexual function and intimate relationships, leading to physiological, psychological, relational, and existential changes. However, qualitative evidence syntheses that integrate these experiences remain limited. This review aimed to synthesize qualitative research on bladder cancer patients' sexual life and intimate relationship experiences in order to inform the development of couple-centered interventions and continuous sexual rehabilitation services.

This study was conducted as a systematic review and qualitative meta-synthesis and was reported in accordance with ENTREQ. PubMed, Web of Science, Embase, Cochrane Library, CINAHL, CNKI, WanFang, and VIP were searched from database inception to January 2026 for qualitative studies on the sexual life and intimate relationship experiences of bladder cancer patients. Studies were selected according to predefined PICoS-based eligibility criteria. Methodological quality was independently appraised by two reviewers using the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research, and the findings were synthesized using Thomas and Harden's three-stage thematic synthesis approach.

A total of 10 studies involving 183 participants were included in the synthesis. Fifty-four qualitative findings were aggregated into nine categories and then synthesized into three overarching findings: (1) multiple changes and challenges in sexual life after treatment; (2) changes and adjustments in intimate relationships; and (3) needs and expectations for sexual rehabilitation.

Bladder cancer patients face complex physiological, psychological, relational, and existential challenges in their sexual lives and intimate relationships. Healthcare professionals should address these issues through holistic, couple-centered, and culturally sensitive care that supports both sexual recovery and long-term quality of life.

https://www.crd.york.ac.uk/PROSPERO/view, identifier CRD420251027779.

Pancreatic cancer (PC) is a highly aggressive malignancy with an unclear pathogenesis, limited therapeutic options, and poor prognosis. Vezatin (VEZT), an adherens junction transmembrane protein, has been implicated in the development and progression of several malignancies, including gastric cancer. However, its biological role and underlying mechanisms in pancreatic cancer remain largely unexplored. This study aimed to investigate the role of VEZT in pancreatic cancer progression and elucidate the molecular mechanism by which VEZT regulates mitochondrial homeostasis through Solute Carrier Family 25 Member 24 (SLC25A24), thereby suppressing apoptosis and promoting malignant progression.

The expression patterns and clinical significance of VEZT and SLC25A24 were analyzed using public datasets from TCGA and GTEx. Their biological functions were systematically evaluated through a series of in vitro experiments, including cell proliferation, migration, invasion, apoptosis, protein interaction, and mitochondrial function assays.

VEZT and SLC25A24 were both significantly upregulated in pancreatic cancer tissues, and their elevated expression was closely associated with unfavorable patient prognosis. Both molecules also exhibited good diagnostic performance. Immune infiltration analysis showed that the expression levels of VEZT and SLC25A24 were significantly associated with multiple tumor-infiltrating immune cell populations. Functional assays demonstrated that VEZT knockdown markedly inhibited pancreatic cancer cell proliferation, colony formation, migration, and invasion, while promoting apoptosis; restoration of SLC25A24 expression partially reversed these effects. Further investigations revealed a protein interaction between VEZT and SLC25A24. VEZT knockdown reduced the stability and expression level of SLC25A24 protein and was accompanied by impaired mitochondrial function.

This study reveals the oncogenic role of VEZT in pancreatic cancer and identifies SLC25A24 as an important downstream effector. The VEZT/SLC25A24 axis may promote pancreatic cancer progression by modulating mitochondrial function and apoptosis, highlighting its potential value for prognostic assessment and therapeutic targeting.

To investigate the molecular mechanisms by which calcium signaling pathways regulate the paclitaxel resistance and the survival of oral squamous cell carcinoma (OSCC) cells.

A paclitaxel-resistant OSCC cell model was established through continuous low-dose paclitaxel induction with dose escalation. The stability of the paclitaxel-resistant model was assessed using the Cell Counting Kit-8 (CCK-8) and imaging flow cytometry. RNA sequencing (RNA-seq) was performed to analyze differentially expressed genes and functional enrichment. Quantitative real-time PCR (qPCR) was conducted to analyze the differential expression of the CAMK2a gene. Protein expression levels were assessed by Western blot (WB). CAMK2a expression was inhibited using KN93 and CAMK2a small interfering RNA (siRNA).

A paclitaxel-resistant OSCC cell model was successfully established. Gene Ontology (GO) enrichment analysis of the sequencing data revealed differences in the calcium signaling pathways in resistant cells. The expression of multiple genes of the CAMK2 family was upregulated, and CAMK2a expression increased by 12% (P < 0.05). After inhibiting CAMK2a by treatment with KN93, an inhibitor, and CAMK2a siRNA-mediated gene knockdown, the proliferative capacity of paclitaxel-resistant cells decreased by 35% (P < 0.0001). Furthermore, the expression levels of phosphorylated Erk1/2 (p-Erk1/2) and its downstream signaling molecules also decreased following CAMK2a inhibition.

CAMK2a regulates drug resistance and the proliferative capacity of paclitaxel-resistant cells by activating the MAPK-Erk1/2 pathway and represents a potential new therapeutic target for clinical treatment of drug-resistant patients.

To investigate the effects of microRNA-429 (miR-429) on the invasion, migration, and ferroptosis of lung adenocarcinoma (LUAD) cells, and to provide new insights into the clinical inhibition of LUAD invasion and migration and the promotion of ferroptosis.

The expression profile of miR-429 in LUAD tissues was analyzed using the starBase database. Quantitative real-time PCR (qRT-PCR) was performed to assess miR-429 expression levels in normal human bronchial epithelial cells (the BEAS-2B cell line) and LUAD cells (the A549 and H1975 cell lines), and to evaluate the plasmid transfection efficiency. The effects of miR-429 on A549 cell proliferation, migration, and invasion were assessed using 5-ethynyl-2^'-deoxyuridine (EdU) incorporation assay, scratch wound healing assay, and Transwell invasion assay, respectively. Potential ferroptosis-related proteins targeted by miR-429 were predicted using bioinformatics databases, and the targeting relationship between miR-429 and heme oxygenase 1 (HMOX1) was validated by a dual-luciferase reporter assay. Further functional experiments were performed to examine the effect of miR-429 targeting HMOX1 on the malignant phenotypes of A549 cells. The levels of reactive oxygen species (ROS) and lipid ROS (L-ROS) were measured to analyze the regulatory effects of miR-429 and HMOX1 on oxidative stress in LUAD cells. The contents of malondialdehyde (MDA), glutathione (GSH), and ferrous ion (Fe²⁺) were measured to evaluate evaluate the effects of miR-429 and HMOX1 on key ferroptosis-associated indicators in LUAD cells.

miR-429 expression was significantly higher in LUAD cell lines (A549 and H1975) compared with that in normal cells (BEAS-2B), with the highest expression level observed in A549 cells. Functional experiments demonstrated that miR-429 promoted A549 cell proliferation, migration, and invasion. The dual-luciferase assay confirmed that miR-429 directly targeted HMOX1, and their expression levels were negatively correlated in LUAD cells. HMOX1 overexpression inhibited the proliferation, invasion, and migration of A549 cells, while miR-429 overexpression reversed these inhibitory effects. Mechanistically, miR-429 targeted and inhibited HMOX1, which led to reduced intracellular levels of ROS, L-ROS, MDA, and Fe²⁺ and increased GSH levels in A549 cells, thereby decreasing cellular sensitivity to ferroptosis.

miR-429 promotes the invasion and migration of LUAD cells and inhibits ferroptosis by targeting and inhibiting HMOX1.

Neoadjuvant drug therapy has become an important component of multidisciplinary cancer treatment, but newer targeted, immunotherapy-based, and multi-agent regimens are often associated with higher costs and uncertainty regarding long-term economic value. This systematic review evaluates the economic evidence for neoadjuvant drug regimens in cancer and summarizes key cost-effectiveness findings across tumor types and healthcare settings.

We systematically searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from database inception to June 1, 2026. Eligible studies were full economic evaluations comparing neoadjuvant drug regimens or assessing the addition of a specific drug component to a baseline neoadjuvant regimen in patients with cancer. Studies comparing neoadjuvant drug regimens with non-drug-based or non-neoadjuvant strategies were excluded. Study selection and data extraction were performed independently by two reviewers. Reporting completeness was assessed using the CHEERS 2022 checklist, potential sources of bias were assessed using the ECOBIAS checklist, and findings were narratively synthesized.

A total of 2,572 records were identified, and 7 studies met the inclusion criteria. The included studies were published between 2015 and 2024 and involved breast cancer, muscle-invasive bladder cancer, and borderline resectable or locally advanced pancreatic cancer. Five studies focused on breast cancer, mainly HER2-positive disease. Most studies used model-based approaches and quality-adjusted life-years as the primary outcome. Pertuzumab-based neoadjuvant regimens for HER2-positive breast cancer and FOLFIRINOX for pancreatic cancer were generally reported to be cost-effective in their respective healthcare settings. In contrast, neoadjuvant pembrolizumab for muscle-invasive bladder cancer and AC-TH compared with TCH for breast cancer were not cost-effective under base-case assumptions. Key drivers included pathological complete response, recurrence or progression risk, drug costs, utility values, adverse event costs, time horizon, and assumptions linking short-term efficacy to long-term outcomes.

Current economic evidence remains limited and concentrated mainly in HER2-positive breast cancer. Cost-effectiveness conclusions depend strongly on drug prices, downstream treatment costs, and model-based extrapolation of early efficacy endpoints. Future studies should incorporate long-term follow-up and real-world evidence.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420261462564, Identifier CRD420261462564.

Locally advanced non-small-cell lung cancer (LA-NSCLC) is a subtype of lung cancer with substantial heterogeneity in clinical prognosis. Immune injury induced by radiotherapy exposure is a critical factor affecting treatment response and long-term outcomes. This study enrolled patients with LA-NSCLC to investigate the prognostic value of complete blood count (CBC) parameters combined with the estimated dose of radiation to immune cells (EDRIC), aiming to facilitate precision prognostic stratification and tailored treatment strategies in clinical practice.

This study included 329 patients with LA-NSCLC who received radiotherapy (RT) at our institution. Serial CBC measurements were obtained pre-RT, weekly during RT, and 1-month post-RT. EDRIC was calculated based on the model developed by Jin et al. and improved by Ladbury et al. We subsequently evaluated the associations of EDRIC and CBC parameters with overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS).

Univariate and multivariate analyses demonstrated that EDRIC, together with week 3 platelet-to-lymphocyte ratio (PLR), was significantly associated with OS, LRFS, DMFS, and PFS (P < 0.05). In multivariate models, neither MHD, MLD, nor MBD was significantly associated with survival outcomes, regardless of the inclusion of EDRIC; however, EDRIC demonstrated a significant correlation. For OS discrimination, Harrell's C-index reached 0.622 for the EDRIC-alone model, 0.734 for the model integrating clinical covariates and CBC markers, and 0.740 for the combined model incorporating clinical features, serial CBC indices and EDRIC.

EDRIC is an independent prognostic biomarker for OS, LRFS, PFS and DMFS in LA-NSCLC patients undergoing definitive thoracic (chemo)radiotherapy. Week 3 PLR also independently predicts all four survival endpoints. Compared with the EDRIC-only model, the integrated model incorporating pretreatment EDRIC, clinical variables, and on-treatment inflammatory markers (NLR and PLR) yields more accurate and comprehensive prognostic stratification for patients with LA-NSCLC.

pAc/Emm55 (IFx-Hu2.0) is a plasmid DNA therapy encoding a Streptococcus pyogenes-derived bacterial gene. It shows anti-tumor activity in preclinical models, but the mechanisms of anti-melanoma immunity and additive effects with immune checkpoint blockade remain unclear.

B16 melanoma tumor-bearing mice were treated intratumorally with pAc/Emm55 alone and/or intraperitoneally with PD-1, CTLA-4, or LAG-3 blockade and monitored for tumor growth. Antibodies against Emm55 and melanoma cells (B16 or YUMM) were quantified by flow cytometry. Bone marrow-derived dendritic cells (BMDCs) from WT, MyD88 KO, TLR2 KO, or TLR7 KO mice were assessed for antigen uptake, OVA cross-presentation, and OT-I priming after pulsing with cell lysates from Emm55- or empty-transfected melanoma cells. Tumor immune infiltration by CD8 and CD11c cells were evaluated by immunohistochemistry.

IFx-Hu2.0 significantly reduced tumor growth, correlating with increased intratumoral CD8⁺ T cell infiltration and enhanced systemic antibody responses against melanoma cells. TLR deficiency did not alter OVA uptake or basal BMDC cross-presentation. However, Emm55-enhanced OT-I priming and IFN-γ production required TLR2 and MyD88, but not TLR7, supporting a TLR2-MyD88-dependent mechanism. Emm55 monotherapy and anti-PD-1 each reduced tumor burden. The combination further improved inhibition. Adding anti-CTLA-4 or anti-LAG-3 to anti-PD-1 did not provide additional meaningful benefit.

Emm55 facilitates the TLR2-MyD88 pathway in DCs and subsequent IFN-γ production by OT-I CD8 T cells. Combining intratumoral IFx-Hu2.0 with PD-1 blockade improves tumor control, supporting clinical evaluation of this strategy as also suggested by the first-in-human clinical trial of IFx-Hu2.0.

Simvastatin (SIM), a member of the statin family, is commonly used to lower blood cholesterol levels, particularly low-density lipoprotein. Statins inhibit the action of hydroxy-methyl-glutaryl-coenzyme A reductase, an important enzyme in the synthesis of cholesterol and isoprenoids; they also have anti-inflammatory effects and can regulate membrane synthesis in cancer cells. Preliminary evidence suggests an association between SIM use and reduced cancer incidence. SIM's anti-cancer efficacy in vivo has been shown in studies on several solid tumors, but little is known about its effects on hematological cancers, such as Multiple Myeloma (MM).

Initially, we searched for such as an association in a large community database and observed a significantly lower MM incidence among SIM users. We proceeded to test the effect of SIM on both murine and human MM cell lines and the tested the effect of long-term SIM treatment on development of MM in an animal model.

SIM exposure led to apoptosis in both murine and human MM cell lines. We show that long-term intake of SIM reduced tumor load and positively impacted bone marrow CD8+ T levels as well as cell-mediated anti-myeloma cytotoxicity. SIM treatment also elevated the total IgA and IgG serum concentrations in healthy mice.

These results suggest that SIM, which many adults use to control cholesterol levels, may play a dual role in the management of MM, by influencing membrane synthesis in myeloma cells leading to apoptotic cell death and enhancing the T-cell mediated anti-tumor cell response in MM.

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are established components of endocrine therapy for hormone receptor-positive (HR+), HER2-negative breast cancer. Beyond RB-dependent G1 arrest, these drugs alter antigen presentation, interferon signaling, checkpoint-ligand expression, suppressive immune-cell populations, and CD8+ T-cell fate. The direction and durability of these effects vary across tumors and treatment settings. Early combinations with immune checkpoint inhibitors (ICIs) have produced activity signals, but hepatotoxicity and pneumonitis have limited several regimens. Radiotherapy and antibody-drug conjugates (ADCs) offer different routes to antigen release and innate immune activation. Therapeutic vaccination and dendritic-cell support provide a further route to exploit treatment-induced antigen display, although this rationale remains preclinical. We examine CDK4/6 inhibitors as conditional immune-priming agents whose value depends on baseline immune contexture, tumor-cell-cycle dependence, endocrine therapy, drug and dose, exposure duration, partner treatment, and organ reserve. Here, immune priming is an operational term for a treatment-induced immune state that a subsequent therapy may use; it does not imply proven de novo activation of naïve T cells. Evidence is separated into clinical outcomes, human translational findings, preclinical mechanisms, and testable hypotheses. This synthesis supports a therapeutic-window strategy in which a defined exposure is assessed for a measurable immune change before treatment is escalated. The immediate translational challenge is to identify that window, determine when it can be exploited, and recognize when continued exposure is more likely to reinforce resistance or toxicity.

https://clinicaltrials.gov/study/,identifier NCT05766410.