Immune checkpoint inhibitors (ICIs) activate antitumor immunity by targeting immune checkpoint molecules such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed death receptor 1 (PD-1), and programmed death-ligand 1 (PD-L1). They have emerged as a key therapeutic modality for multiple malignancies. Nevertheless, excessive immune activation may trigger a spectrum of immune-related adverse events (irAEs). Though uncommon, uveitis is a sight-threatening irAEs that can result in permanent visual loss. The risk and prognostic outcomes of ICIs-associated uveitis remain poorly defined to date. Therefore, we performed this meta-analysis to systematically assess the correlation of ICIs therapy with uveitis risk and prognosis, with the goal of providing evidence-based recommendations for clinical identification and management of this ocular complication.

4-[4-(Bis(2-(nitrooxy)ethyl)amino)phenyl]butanoic acid (NPB), a phenylbutyrate-derived nitric oxide (NO) donor, has been developed as a potential anticancer agent for pancreatic cancer. In the present study, we investigated the cytotoxic effects of NPB under cellular stress conditions and examined its effects on autophagy-related pathways and hypoxia-inducible factor-1α (HIF-1α) signaling. NPB-induced cell death was enhanced under nutrient-deprived conditions in PANC-1 cells. In addition, NPB induced greater cell death under hypoxic conditions than under normoxic conditions in PANC-1 cells, whereas in BxPC-3 cells, NPB-induced cell death was slightly but significantly lower under hypoxic conditions than under normoxic conditions. Using GFP-LC3-RFP-LC3ΔG reporter cells, NPB suppressed starvation-induced autophagic flux. In pancreatic cancer cells, NPB decreased DAPGreen fluorescence, an indicator of autophagy-related vesicular activity, and increased propidium iodide-positive cells under hypoxic conditions. Western blot analysis showed that NPB induced the accumulation of p62 and LC3 under both normoxic and hypoxic conditions. Under hypoxic conditions, NPB also reduced HIF-1α expression. Under cobalt chloride (CoCl2)-induced HIF-1α-accumulating conditions, NPB and the NO donor NONOate suppressed HIF-1α expression, whereas OH-PB, a non-NO-releasing analog, showed little effect. Furthermore, the proteasome inhibitor MG132 restored HIF-1α accumulation in NPB-treated cells. Time-course analysis under CoCl2-treated conditions showed that NPB reduced HIF-1α expression concomitantly with p62 accumulation. These findings suggest that NPB induces pancreatic cancer cell death, particularly under nutrient-deprived and hypoxic conditions, accompanied by impairment of autophagy-related pathways and NO-dependent, proteasome-associated reduction of HIF-1α.

The optimal choice between sedating histamine H1 antagonists (sAHs) and non-sedating histamine H1 antagonists (nsAHs) for preventing infusion-related reactions (IRRs) during daratumumab subcutaneous (DARA-SC) therapy remains unclear. Here, we aimed to compare the efficacy and safety of nsAH and sAH as premedication for DARA-SC therapy. Patients with multiple myeloma or light-chain amyloidosis who received DARA-SC therapy at eight hospitals were enrolled in this prospective, multicenter, observational study. Patients were categorized into nsAH and sAH groups based on their premedication. IRRs and drowsiness were assessed using patient-reported questionnaires, including the Stanford Sleepiness Scale (SSS) and the Japanese Epworth Sleepiness Scale (JESS), at baseline, post-administration (Q2), and before bedtime (Q3). Overall, 104 patients (nsAH, n = 49; sAH, n = 55) were analyzed. No significant differences were observed in the IRR incidence between the nsAH and sAH groups at Q2 (8.2 vs. 9.1%) or Q3 (13 vs. 17%). Conversely, the incidence of new-onset drowsiness at Q2 was significantly lower in the nsAH group (13%) than in the sAH group (32%, p < 0.05). Additionally, the increase in SSS from baseline to Q2 was significantly lower in the nsAH group than in the sAH group (p < 0.05). No significant differences were observed in JESS scores. Thus, nsAH was associated with reduced early post-administration drowsiness and there were no statistically significant differences in IRR preventive effects compared to that for sAH, suggesting that nsAH may reduce sedation without a significant increase in the incidence of IRRs; however, these hypothesis-generating findings warrant verification through future prospective comparative trials.

Given the limited Japanese real-world evidence, this study aimed to evaluate the survival and safety of adjuvant nivolumab after neoadjuvant chemotherapy in patients with an incomplete pathological response to esophageal squamous cell carcinoma (ESCC).

Curcumin is a naturally occurring bioactive compound with well-characterized anti-inflammatory and antitumor properties; however, its clinical utility is limited by poor bioavailability and chemical instability. To overcome these limitations, various curcumin analogs have been developed. In this study, we investigated the antitumor and antimetastatic effects of 3,5-bis(2'-ethoxybenzylidene)-piperidine-4-one (E145), a monocarbonyl curcumin analog, with a particular focus on its ability to inhibit nuclear factor-kappaB (NF-κB) signaling in breast cancer cells. We first evaluated the effects of E145 on cell proliferation in murine 4T1 and human MDA-MB-231 breast cancer cell lines. E145 inhibited cell proliferation in a dose-dependent manner and suppressed phosphorylation of the NF-κB p65 subunit. Furthermore, E145 blocked tumor necrosis factor alpha-induced NF-κB activation by inhibiting both p65 phosphorylation and nuclear translocation. Consistently, E145 reduced the expression of NF-κB-regulated pro-tumorigenic factors, including vascular endothelial growth factor, matrix metalloproteinase-9, interleukin-1β (IL-1β), and IL-6. Functional assays demonstrated that E145 markedly suppressed the migration and invasion of breast cancer cells in vitro. In addition, experimental lung metastasis assays revealed that E145 treatment significantly reduced metastatic colonization of 4T1 cells in vivo. Collectively, these findings indicate that E145 exerts potent antimetastatic effects by inhibiting cell-intrinsic NF-κB activation and downstream inflammatory mediators. These results suggest that E145 is a promising therapeutic candidate for targeting NF-κB-driven breast cancer progression and metastasis.

Genetic profiling of a new HPV-negative cervical cancer model identified pathogenic variants in genes implicated in oncogenic signaling, cell cycle regulation, and DNA damage repair pathways, including homologous recombination, non-homologous end-joining, and mismatch repair. Deficiencies in BRCA2, RAD51 and MLH1 were among these actionable targets. The newly described cervical cancer model revealed sensitivity towards the PARP inhibitor olaparib, which was further augmented upon combination with platinum-based chemotherapeutics. In contrast, BRCA1/2-proficient cervical cancer cells exhibited greater resistance to these strategies. This study highlights the potential of in-depth genetic analysis to identify genetic susceptibilities to guide personalized medicine approaches.

Epithelioid angiomyolipoma (E-AML) is a rare renal tumor, which can exhibit malignant potential. Because angiomyolipomas frequently harbor TSC1/TSC2 alterations, mTOR inhibitors are commonly used. However, durable disease control remains inconsistent. The potential for long-lasting response with immune checkpoint inhibitors supports exploring their role in E-AML. We report a patient with highly symptomatic, locally advanced renal E-AML treated with first-line ipilimumab plus nivolumab. The patient experienced rapid symptomatic and radiographic improvement after treatment initiation. She subsequently developed immune-related sarcoidosis, which resolved after discontinuation of immunotherapy and with corticosteroids. Given sustained disease control, she underwent delayed nephrectomy demonstrating complete pathologic response in the primary tumor. Genomic analysis revealed a germline mutation in FLCN consistent with Birt-Hogg-Dubé syndrome. T-cell receptor sequencing identified a shared expanded T-cell clone in peripheral blood and within the tumor. With extended follow-up for over 5 years, she remains in durable remission after dual immune checkpoint blockade. To our knowledge, this is the first report of dual immune checkpoint blockade in renal E-AML. This case demonstrates that first-line ipilimumab plus nivolumab can induce deep, durable response-including complete pathologic response-in a rare malignancy with limited standard treatment options, supporting further evaluation of immunotherapy in this disease.

Bortezomib is a proteasome inhibitor used to treat cancers such as Multiple Myeloma and Mantle Cell Lymphoma. Due to its narrow therapeutic index, accurate quantification in biological matrices is essential for monitoring drug exposure, optimizing dosing, and assessing tissue distribution. The aim of this study was to develop and validate LC-MS/MS methods for the quantification of bortezomib in rat serum and rat sciatic nervous tissue. A rapid serum assay based on one-step protein precipitation and a nervous tissue assay were established using 2H8-Bortezomib as an isotope labeled internal standard. Calibration ranges were 0.920-100 ng/mL for serum and 4.00-100 ng/g for nervous tissue. Bortezomib and its internal standard were detected using high-resolution MRM in positive-mode electrospray ionization, with a total acquisition time of 4 min per run. The serum method was validated according to ICH M10 guideline, ensuring compliance with parameters including accuracy, precision, matrix effects, recovery, stability, selectivity, reinjection reproducibility, and carry-over. The nervous tissue method underwent partial validation, assessing key parameters to ensure reliable quantification. The application of these methods to authentic rat samples demonstrated their suitability. The developed assays provide rapid and sensitive quantification of bortezomib in serum and sciatic nervous tissue. The simple sample preparation procedures and short run times support their use in pharmacokinetic and tissue distribution studies.

This study explored the potential association between paclitaxel (PTX) and macular oedema (ME), a rare adverse event, through pharmacovigilance analysis using a large-scale spontaneous reporting database.

Chemotherapy/immune checkpoint inhibitor (ICI) therapy is increasingly standard of care for a range of cancers. Increasing numbers of emergency cancer presentations mean alternative pathways are required to ensure sustainable services and improve outcomes. Febrile neutropenia (FN) is common in patients treated with chemotherapy/ICI therapy. Risk stratifying patients with FN is essential to personalise acute management and optimise use of healthcare resources. Management of patients with low-risk FN in an outpatient setting is proven to be safe and effective. The MASCC score is well validated for risk stratification in FN, and patients with a score ≥ 21 are likely to be suitable for outpatient management. It has not been validated in patients treated with combined chemotherapy/ICI regimens. This MASCC position paper outlines an approach for acute ambulatory management of low-risk FN in this cohort and produces ten position points. A literature search was performed up to the 31st May 2025 for outpatient management of FN in patients treated with chemotherapy/ICI therapy. Only one paper met the criteria highlighting the need for prospective and real-world data. Patients treated with a MASCC score < 21 are high risk and require standard neutropenic sepsis management. Empirical usage of high-dose steroids in patients presenting with FN on chemo/ICI therapy with grade ≥ 3 diarrhoea and/or transaminitis is not recommended. Patients treated with chemotherapy/ICI therapy with low-risk FN should be treated on the same pathway as those treated with chemotherapy alone with inclusion criteria adapted to recognise their eligibility. ICI-mediated neutropenia should be considered in patients receiving combined chemotherapy/ICI therapy when the timing of presentation is unanticipated or there is a failure of neutrophil recovery with persistent grade 3/4 neutropenia 10 days following administration. Initial treatment of suspected ICI-mediated neutropenia is to commence high-dose steroids and consider short-acting G-CSF.

Triple-negative breast cancer (TNBC) primarily relies on traditional adjuvant chemotherapy and radiotherapy, which have significant side effects and are prone to drug resistance. Poly ADP-ribose polymerase inhibitor (PARPi) has been approved for TNBC patients with BRCA mutation, but some BRCA wild-type patients with homologous recombination deficiencies are also sensitive to PARPi. Therefore, it is important to identify potential molecules that influence PARPi sensitivity in BRCA wild-type TNBC and to explore their specific mechanisms. Through CRISPR-cas9 loss-of-function screening, the lncRNA MTUS2-AS1 was identified to be significantly correlated with PARPi sensitivity in BRCA wild-type TNBC cells. In vitro and in vivo experiments were performed to investigate its function and underlying mechanism. We found that MTUS2-AS1 knockdown suppressed DNA damage repair and enhanced the anticancer effects of PARPi in BRCA-wild TNBC cells. Mechanistically, MTUS2-AS1 upregulates DDX5 protein expression by maintaining its stability, thereby promoting R-loop resolution, and suppressing DNA damage. Knocking down MTUS2-AS1 accelerated DDX5 protein degradation, reduced DDX5 protein expression, inhibitd R-loop resolution, promoted DNA damage, and ultimately enhanced the PARPi sensitivity in TNBC cells. Our study provided new insights into exploring the key molecules and mechanisms influencing the sensitivity of PARPi treatment and had great significance for screening benefit population and expanding the indications of PARPi treatment.

Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, yet clinical responses remain highly variable, and microbiome-associated findings lack reproducibility across studies. Increasing evidence implicates the gut microbiome in modulating ICI efficacy; however, findings remain inconsistent at the taxonomic level, raising the possibility that functionally convergent immunological mechanisms may underlie this apparent variability. To address this, a critical synthesis was conducted, integrating bibliometric mapping of publications indexed in the Web of Science Core Collection (2013-2025; n = 2,195) with a secondary analysis of ClinicalTrials.gov to evaluate interventional activity. Bibliometric approaches assessed scientific production, thematic evolution, and co-citation structure, complemented by a cross-cohort functional integration of representative clinical and preclinical studies to evaluate whether microbiome-ICI interactions converge on shared immunological pathways despite divergent taxonomic signatures. Publication output increased steadily, with a marked translational surge following landmark clinical studies in 2018 and a peak in trial initiation in 2021. Thematic analyses revealed a shift from mechanistic and tumor-centered research toward clinically oriented and intervention-driven themes, including microbiome modulation, microbial metabolites, and the tumor microenvironment. Although individual response-associated taxa differed substantially across independent cohorts, qualitative functional integration supported a model of convergence in immunomodulatory pathways involving short-chain fatty acid production, dendritic cell activation, and CD8+ T-cell priming. Collectively, these findings suggest that apparent taxonomic inconsistencies across microbiome-ICI studies may reflect underlying functional convergence rather than biological contradiction, supporting a shift toward function-based frameworks for biomarker discovery and microbiome-directed immunomodulation.

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.

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.

The perioperative role of systemic therapy remains poorly defined in borderline resectable or unresectable non-head-and-neck locally advanced cutaneous squamous cell carcinoma (cSCC). We evaluated whether conversion-intent PD-1-based chemoimmunotherapy could restore surgical feasibility in this setting.

Ecteinascidins constitute a family of alkaloid compounds, originally isolated from marine tunicates, that exhibit strong antitumor activity. They act through binding to the DNA minor groove and forming covalent adducts with guanine residues. However, the limited availability of structural data restricts mechanistic insights into their mode of action and hampers the discovery of novel compounds. We report crystal structures of duplex DNA adducts with first-, second-, and third-generation ecteinascidins. The structures show that trabectedin, lurbinectedin, and PM54 bind through their shared A- and B-subunits, forming a covalent bond with the N2 atom of guanine and an extensive network of noncovalent interactions, leading to significant minor groove widening. In contrast, their C-subunit, which differs across the compounds, establishes distinct contacts with the modified strand that affect binding strength and sequence specificity. These structural findings, supported by Förster resonance energy transfer and biochemical assays, reveal the molecular determinants underlying differential sequence selectivity and reactivity. Our results provide a mechanistic framework for the anticancer activity of ecteinascidins and a structural basis to guide the design of next-generation analogues with improved therapeutic potential.

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.

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.

Cancer continues to pose a significant worldwide health concern, underscoring the need for the identification of innovative, safer, and more effective therapeutic agents. Phytochemicals obtained from medicinal plants are progressively acknowledged for their anticancer efficacy. This work investigates the antimitotic and antiproliferative properties of the ethanolic extract of Benincasa hispida seeds (EeBHS), known as winter melon, from the Cucurbitaceae family.

Gastric cancer is a major global health concern characterized by high incidence and mortality rates. One of the key challenges in treating gastric cancer is the development of resistance to chemotherapy drugs like cisplatin (DDP). This study aimed to investigate the efficacy of Zuo Jin Wan (ZJW), a traditional Chinese medicine, in overcoming DDP resistance in gastric cancer cells.