Immune checkpoint inhibitors (ICIs) have revolutionized the management of gastric cancer; however, they can lead to rare immune-related adverse events (irAEs) affecting the urinary system. Herein, we report a case of non-bacterial cystitis complicated by acute kidney injury (AKI) in a 59-year-old male patient with Alpha-fetoprotein-producing gastric carcinoma (AFP-GC). Following treatment with toripalimab combined with SOX chemotherapy, the patient developed urinary tract irritation symptoms, gross hematuria, and stage II AKI. Cystoscopy revealed diffuse mucosal hemorrhage, and biopsy demonstrated extensive infiltration of CD3⁺, CD8⁺, CD4⁺, and CD20⁺ lymphocytes, along with high PD-L1 expression and TIA-1 positivity, confirming the diagnosis of non-bacterial cystitis. A full-dose methylprednisolone pulse of 200 mg/day effectively alleviated the symptoms and restored renal function. This case underscores the importance of vigilance for urinary system irAEs in patients receiving ICIs, emphasizing that early identification and systematic evaluation are critical. Full-dose corticosteroids should be used for moderate to severe irAEs. Moreover, this report provides valuable insights into immunotherapy practice and toxicity management in the rare AFP-GC subtype.

Cancer is a significant cause of mortality in kidney transplant recipients (KTr). Specifically, the relationship between cancer and kidney transplantation (KTx) is evident from the initial evaluation of CKD patients prior to their placement on the KTx waiting list. After KTx, a significant impact on the potential development of cancer is linked to immunosuppressive therapies, necessary to maintain renal function post-KTx, and to complications, especially infectious ones, typical of these patients. Ultimately, once cancer is diagnosed in a KTx, nephrologists and transplant specialists are forced to modulate suppressive therapies and, together with oncologists, manage specific cancer treatment therapies. In this highly complex scenario, unfortunately, there are few certainties, and they are limited to a few studies, often involving a small number of patients. This review integrates current data on risk, prevention, and treatment across the entire pathway: pre-transplant assessment, post-transplant surveillance, and management after a cancer diagnosis. A special focus will be reserved to the new evidences regarding the treatment with immune-checkpoint inhibitors (ICIs).

Glioblastoma (GBM), the deadliest primary brain malignancy, resists treatment because of the blood‒brain barrier (BBB) and intrinsic resistance mechanisms. Fluorescein (FL), a clinically approved fluorophore, shows promise as a sonosensitizer for sonodynamic therapy (SDT), but faces challenges in tumor delivery and incomplete mechanistic understanding beyond ROS-mediated damage. We developed a bioinspired platelet-based delivery platform exploiting the natural tumor-homing properties of platelets for targeted FL delivery. Platelets were loaded with fluorescein diacetate (FDA), a lipophilic prodrug that is converted intracellularly to active FL, combined with probenecid to inhibit MRP1-mediated efflux, generating the ultrasound-responsive FL@plt. In vitro, FL demonstrated sonocytotoxicity; upon low-intensity ultrasound, FL@plt rapidly released FL into GBM cells, producing significant cytotoxicity enhanced by probenecid-mediated retention. In subcutaneous and orthotopic mouse models, intravenous FL@plt with probenecid and sequential ultrasound achieved extensive tumor FL accumulation, massive necrosis, significant growth inhibition, and prolonged survival. Mechanistically, FL-SDT induces DNA damage while promoting HIF-1α degradation via the ubiquitin‒proteasome and autophagy‒lysosome pathways, thus suppressing downstream DNA repair enzymes (SMUG1 and LIG4). This dual mechanism combines direct genotoxicity with impaired DNA repair capacity, underlying the potent anti-GBM efficacy. Our platelet-based FL delivery represents a practical, safe, translational therapy for overcoming BBB limitations by disabling HIF-1α-regulated DNA repair.

Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 pathway have revolutionized cancer immunotherapy, yet their clinical benefit is constrained by variable response rates and immune-related adverse events.

This review systematically analyzes the molecular mechanisms by which key gut microbiota-derived metabolites-including short-chain fatty acids (SCFAs), tryptophan metabolites, and bile acids-modulate the PD-1/PD-L1 axis.

We synthesized and evaluated peer-reviewed preclinical and clinical studies published over the past decade, focusing on metabolite-immune interactions, biomarker validation, and combinatorial intervention strategies.

The summarized evidence demonstrates that these metabolites exert significant influences on the tumor microenvironment, enhance T-cell effector functions, and reshape immune tolerance, thereby affecting ICI responsiveness.

We critically assess the predictive value of microbiota metabolites as potential biomarkers and review current progress in probiotic supplementation, fecal microbiota transplantation, and metabolite-based combination therapies.

Despite promising translational prospects, several challenges-including inter-individual variability, lack of standardized protocols, and mechanistic gaps-remain to be addressed. Future directions should prioritize large-scale longitudinal studies and refined intervention designs to facilitate the clinical integration of microbiota-guided strategies, ultimately improving the precision and efficacy of cancer immunotherapy.

Nucleoporin 98 rearrangements (NUP98re) occur in a wide range of hematologic malignancies including acute leukemias with a variety of fusion partners. NUP98re is associated with adverse prognosis, especially in children. We aimed to better understand the genomics of acute leukemias with NUP98re including fusion partners and co-occurring genomic alterations (GA). Results from 5905 patients with acute leukemia undergoing standard-of-care next generation sequencing on FoundationOneHeme were included for analysis. A total of 78 (1.3%) patient samples harbored NUP98re with a median age of 19 years compared with 62 years for the cases with no NUP98 rearrangement (NUP98wt) (p < 0.001). Patients with NUP98re were more frequently of admixed American ancestry (p < 0.001). Among patients with acute myeloid leukemia, individual genomic alterations more frequently identified in NUP98re cases included WT1 (77% vs. 11%, p < 0.001) and FLT3 (49% vs. 26%, p < 0.001); Alterations more frequent in the NUP98wt cohort included NPM1, KMT2A, TET2, DNMT3A, ASXL1, SRSF2, STAG2, and BCOR (all p < 0.05). NUP98re are rare in patients with acute leukemia, more frequent in pediatrics and younger adults but distributed across all age groups. NUP98re is associated with a unique genomic landscape featuring increased frequencies of mutations with proliferative features (FLT3 and KRAS) and growth suppression (WT1). Alterations in WT1 had the highest co-occurrence rate in samples containing NUP98re. This work highlights the unique GA associated with NUP98 and emphasizes the need for clinical studies to reveal underlying biologic mechanisms and enhance optimal management in the presence of potentially targetable alterations such as NUP98re.

This study preliminarily examines the clinical value and molecular mechanisms of LINC00511 in breast cancer (BRCA) through bioinformatics analysis.

Expression data of LINC00511 and related information for BRCA samples were collected from the TCGA website. The levels of LINC00511 in cancerous and normal tissues were compared using the Wilcoxon rank-sum test. The relationship between LINC00511 levels and clinicopathological features was examined using the chi-square test. Additionally, Kaplan-Meier and Cox regression analyses were employed to evaluate the prognostic significance of LINC00511. Finally, to determine the biological functions and molecular mechanisms of LINC00511, functional enrichment and immune infiltration analyses were performed using the Xiantao Academic website.

LINC00511 was found to be upregulated in BRCA. LINC00511 expression was closely related to T stage, pathological stage, race, estrogen receptor (ER), and progesterone receptor (PR). For BRCA patients, independent prognostic factors included older age (≥65 years), advanced pathological stages (III and IV), and elevated LINC00511 levels. Enrichment analysis demonstrated the close association of LINC00511 with the IL-17 signaling pathway, estrogen signaling pathway, chemical carcinogenesis, and drug metabolism. Furthermore, LINC00511 expression was significantly related to the level of immune cell infiltration.

LINC00511 is significantly overexpressed in BRCA, and elevated levels of this factor are associated with a reduction in overall survival in BRCA patients. LINC00511 not only possesses a high degree of clinical value in the diagnosis and prognosis of BRCA but also has the potential to serve as a target for immunotherapy.

Breast cancer is the most common malignancy among women and a leading cause of cancer-related mortality worldwide. Current therapeutic strategies are associated with several limitations, including cytotoxic side effects and multidrug resistance. As a result, a shift toward drugs with fewer adverse effects and greater efficacy must occur. Recent studies have demonstrated the anticancer potential of both metformin and pitavastatin. This study aimed to investigate the synergistic effects of their combination on MDA-MB-468 triple-negative breast cancer cells.

The MTT assay was performed to assess the cytotoxicity of metformin and pitavastatin on MDA-MB-468 breast cancer cells. The anti-proliferative effects of the combined treatment were assessed using the trypan blue assay and the clonogenic assay. Additionally, a scratch assay was used to evaluate the migration ability of MDA-MB-468 cells after treatment with metformin and pitavastatin treatments.

Both metformin and pitavastatin significantly reduced the viability of MDA-MB-468 cells in a time- and dose-dependent manner. Metformin exhibited an IC₅₀ value of 0.92mM, while pitavastatin showed an IC₅₀ of 1.72µM. Notably, the combined treatment produced a stronger antiproliferative effect compared to either drug alone. Trypan blue data revealed a higher rate of cell death following combination therapy. Furthermore, colony formation was completely inhibited (100%) by the combined treatment compared with to the control group. The scratch assay demonstrated that the combination significantly suppressed cell migration, indicating a synergistic anti-migratory effect.

These findings indicate that the combination of metformin and pitavastatin exerts a synergistic anticancer effect against MDA-MB-468 breast cancer cells and may represent a promising therapeutic strategy for triple-negative breast cancer.

Three-dimensional (3D) cell culture systems provide superior simulation of the tumour microenvironment compared to traditional two-dimensional (2D) cultures. Chemoprevention agent curcumin analog-1.1 (CCA-1.1), a synthetic curcumin derivative, has demonstrated promising anticancer properties against triple-negative breast cancer (TNBC). This study aimed to develop and use a 3D agarose-based culture system for MDA-MB-231 cells to comprehensively evaluate the efficacy of CCA-1.1 as an anticancer agent.

MDA-MB-231 breast cancer cells were cultured in both a 2D monolayer and a 3D agarose-based spheroid system. Cytotoxicity was assessed using CCK-8 assays, and IC50 values were determined. Spheroid formation capacity was evaluated and compared with that of doxorubicin. Propidium iodide staining was performed to assess cell viability and structural integrity. Gene expression analysis of epithelial-mesenchymal transition (EMT) markers and metastasis-related proteins (E-cadherin, MMP2, and MMP9) was conducted using qRT-PCR.

CCA-1.1 demonstrated IC50 values of 1.48±0.28 µM in 2D cultures versus 6.12±0.27 µM in 3D cultures, while doxorubicin showed IC50 values of 0.79±0.22 µM (2D) and 2.65±0.3 µM (3D). CCA-1.1 reduced spheroid formation by 40% compared to controls, whereas doxorubicin achieved 96% inhibition. Propidium iodide staining showed that CCA-1.1 induced cell death while preserving the spheroid structure, unlike doxorubicin, which disrupted the architecture. Expression level analysis revealed that CCA-1.1 reduced MMP2 (0.15-fold, p=0.0001) and MMP9 (0.25-fold, p<0.0001) levels while increasing E-cadherin levels by 1.54-fold (p=0.379).

Our study using a 3D agarose-based spheroid culture confirms the cytotoxicity of CCA-1.1 against MDA-MB-231 and showed that the compound inhibited spheroid formation and epithelial-mesenchymal transition, and reduced the expression levels of matrix metalloproteinases. These data support the development of CCA-1.1 as a candidate chemotherapeutic agent for TNBC.

Breast cancer is a heterogeneous disease consisting of molecular subtypes with varying aggressiveness, growth rates, and therapeutic responses. MicroRNAs (miRNAs) hold potential as biomarkers owing to their role in gene expression regulation in cancer, as well as their specificity and stability in clinical samples. The mapping of miRNAs associated with disease recurrence and progression in each breast cancer subtype remains limited. This scoping review aimed to map the scientific literature on miRNAs related to recurrence and disease progression in TNBC, luminal, and HER2+ breast cancer subtypes.

Literature searches were conducted in the Scopus and PubMed electronic databases using predefined keywords. Retrieved records were screened, and duplicates were removed. Selection based on title, abstract, and full text was performed according to the established inclusion criteria. Data extracted from eligible studies included cancer subtype, stage, type and timing of sample collection, treatment, miRNA identification technique, miRNA expression patterns, target genes and molecular pathways, clinical outcomes, and biomarker types. This scoping review was developed using the PRISMA-ScR checklist.

A total of 28 studies were included and reviewed. miRNAs associated with the TNBC subtype were the most investigated in both profiling and non-profiling studies. The patterns of miRNA expression varied among the TNBC, luminal, and HER2+ subtypes. Of the 74 miRNAs identified across all breast cancer subtypes, only two miRNAs (miR-30c-5p and miR-195-5p) were found in different subtypes. The miRNAs in each breast cancer subtype were demonstrated to be prognostic, predictive, or both.

This scoping review provides an overview of the unique miRNA expression patterns associated with recurrence and disease progression in TNBC, luminal, and HER2+ breast cancer subtypes. The differences in miRNA expression between breast cancer subtypes emphasize the importance of investigating miRNA biomarkers specific to breast cancer subtypes.

Breast cancer stem cells (BCSCs) are responsible for chemotherapy resistance, metastasis, and tumor recurrence. Paclitaxel-primed mesenchymal stem cells (MSCs) can activate T cells, offering a novel immunotherapeutic approach. However, the molecular mechanisms underlying BCSC-immune interactions remain poorly understood.

To identify overlapping gene networks between BCSCs, paclitaxel-treated cells, activated T cells, and paclitaxel-primed MSCs, and to validate their functional relevance in targeting BCSCs.

Comparative transcriptomic analysis was performed using data from TCGA to identify genes co-expressed across BCSCs, paclitaxel-treated cells, activated T cells, and MSCs. Protein-protein interaction network analysis, Gene Ontology (GO) enrichment, and KEGG pathway mapping were conducted using STRING-DB, DAVID, and cBioPortal. Mutation analysis and survival correlations were assessed across 151 breast cancer samples. Experimental validation was performed using MTT viability assays and qRT-PCR in metastatic breast cancer cells treated with paclitaxel, activated T cell-conditioned medium, and MSC-derived factors.

We identified 158 genes co-expressed across all four conditions, forming a highly interconnected PPI network (136 nodes, 524 edges). Network centrality analysis revealed TP53, AKT1, and STAT3 as top hub genes. GO enrichment analysis demonstrated significant involvement in epithelial cell proliferation, stress responses, and transcriptional regulation. KEGG pathway analysis revealed enrichment in the PI3K-Akt signaling pathway, the PD-L1/PD-1 checkpoint pathway, and Th1/Th2 differentiation. TP53 was the most frequently mutated gene (77.5%), which correlated with a poor prognosis. Experimental validation demonstrated that combined paclitaxel and activated T cell treatment reduced BCSC viability by 75%, upregulated TP53 expression, and suppressed PIK3CA expression by 85%.

This study reveals critical molecular networks connecting BCSCs and immune activation, identifying TP53, AKT1, and STAT3 as central therapeutic targets. Paclitaxel-primed MSC-activated T cells synergize with chemotherapy to suppress BCSC viability by modulating the TP53 and PIK3CA pathways, providing a mechanistic rationale for combinatorial immunotherapy in breast cancer.