Colorectal cancer (CRC) with microsatellite-stable (MSS)/pMMR status resists immune checkpoint blockade due to its immunologically "cold" tumor microenvironment. We developed Lipo-LPS-Rg3, a dual-functional nanoliposome co-delivering lipopolysaccharide (LPS) and ginsenoside Rg3, to simultaneously ignite pyroptosis and attenuate PD-L1-associated immune suppression. LPS triggered GSDMD-mediated pyroptosis, releasing DAMPs and recruiting CD8⁺ T cells, while Rg3 reduced PD-L1 expression in vitro, at least partly by inhibiting NFATc1 nuclear translocation. In vivo, Lipo-LPS-Rg3 decreased PD-L1 protein expression in tumor tissues and promoted both CD8⁺ T-cell infiltration and IFN-γ-producing effector function. The nanoplatform achieved tumor-targeted delivery, induced near-complete regression in colorectal cancer, and exhibited minimal systemic toxicity. By converting "cold" tumors into "hot" and supporting antitumor T-cell activity, Lipo-LPS-Rg3 offers a promising strategy for MSS/pMMR CRC immunotherapy.

Prostate cancer (PCa) is a prevalent malignancy in males with high morbidity and mortality. Although treatment modalities have evolved considerably, tumor resistance, recurrence, and metastasis persist, urgently requiring the exploration of alternative therapies for PCa. There is ongoing research on finding and identifying the use of traditional plant medicine (TPM). Cellular homeostasis comprises a sophisticated network of metabolic processes that functions cooperatively to preserve a stable intracellular environment. Programmed cell death (PCD) plays an important role in PCa mechanism. Thus, they represent an effective strategy for targeting PCa. TPM has been proven to induce PCD through multiple pathways and target in the treatment of PCa. Recent reviews have only focused on the one of the PCD, and autophagy, apoptosis, pyroptosis, ferroptosis, and necroptosis are not simultaneously reviewed.

The search strategy: articles with the title containing "prostate cancer", "therapeutic", "traditional medicine", "apoptosis", "pyroptosis", autophagy", "in vivo/in vitro", "active ingredients", "Herbal", "real modules", "dose", "pathway", "effects/mechanisms", "extract", "pure compound", "drug type", "anticancer activity", "Chinese herbal compounds", "necroptosis" and "ferroptosis" had been initially selected in the past five years databases of PubMed, Web of Science, and ScienceDirect. The references were screened according to the strategy.

Forty-two drugs in the TPM have been chosen in this review. The plant extract, Chinese herbal compound, and pure compound of TPM exhibit significant anticancer activity against PCa by regulating multiple kinds of PCD. More importantly, PI3K/AKT/mTOR, AMPK/mTOR pathways, AKT1/Bcl2/NF-κB, GPBAR1/NF-κB, Keap1/Nrf2/ARE, PINK1/Parkin signaling pathways serve as critical molecular targets mediating the anticancer activities of TPMs in PCD. Autophagy, apoptosis, and ferroptosis are research hotspots, while pyroptosis and necroptosis are less explored. Apoptosis is co-detected with autophagy, or necroptosis. Ferroptosis is co-detected with necroptosis, or pyroptosis. Notably, the interrelationships between these cell death modes are rarely investigated in depth in the treatment of TPM in PCa. TPM has been induced apoptosis, ferroptosis, necroptosis in PCa. But the effect of TPM on the autophagy and pyroptosis need further evidence to clarify the mechanism.

Hence, it is imperative to focus on elucidating the role of PCD modulators to refine therapeutic strategies of TPM in PCa.

Multiple myeloma remains largely incurable despite advances in proteasome inhibitors and monoclonal antibodies. Chimeric antigen receptor (CAR)-T-cell therapy targeting B-cell maturation antigen (BCMA) has achieved deep responses in relapsed/refractory multiple myeloma; however, its clinical utility is constrained by cytokine release syndrome (CRS). CRS is a multicellular hyperinflammatory process driven by CAR-T-derived cytokines, monocyte/macrophage activation, and amplification of the IL-1β-IL-6 axis, leading to endothelial dysfunction and metabolic reprogramming. While IL-6 blockade is the standard of care, severe CRS often persists due to redundant upstream inflammatory signalling. This mini-review evaluates the emerging roles of IL-37 and IL-38, anti-inflammatory members of the IL-1 superfamily, as endogenous regulators of CAR-T-associated hyperinflammation. IL-37 functions primarily as a systemic mediator that suppresses NF-κB/MAPK signalling, inflammasome activity, and endothelial injury. In contrast, IL-38 acts as a tissue-resident regulator that restrains early innate immune priming and modulates macrophage-dendritic cell interactions within the bone marrow microenvironment. We propose a phase-dependent regulatory axis wherein IL-38 limits inflammatory initiation while IL-37 suppresses systemic amplification during peak CRS. These pathways represent promising immunoregulatory checkpoints with translational potential as biomarkers and therapeutic targets. Leveraging these cytokines through recombinant proteins or "armoured" CAR-T-cells equipped with inducible regulatory circuits may improve the safety and efficacy of cellular immunotherapies in multiple myeloma.

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.