Purpose: We explored the association between metastatic cancer, chemotherapy, and the risk for suicide attempts (suicide injuries) in adult trauma patients.Methods: We conducted a retrospective analysis of the Trauma Quality Program Participant Use File (2017-2019), comprising 27,474 patients from 700 U.S. Trauma Centers. Self-harm/suicide injury (compared to controls) was the dependent variable; presence of metastatic cancer and current chemotherapy were the key independent variables. We adjusted for age, sex, race/ethnicity, method of payment, facility levels, and discharge year (Model 1), and Model 1 plus trauma type, injury location, stay length, comorbidities, Injury Severity Score, and Glasgow Coma Scale (Model 2). We employed chi-square analysis, Fisher's exact test, and unadjusted and adjusted logistic regression using Stata v18, setting statistical significance at P≤0.05.Results: Of 27,474 patients, 249 (0.91%) reported suicide injuries. Significantly higher attempts were noted among patients with metastatic cancer (201 out of 249; 80.72%) and those not receiving chemotherapy (184 out of 249; 73.90%), P<0.001. Metastatic cancer was associated with higher odds of suicide injuries (unadjusted OR:2.252, 95%CI: 1.642-3.089; adjusted OR in Model 1:1.925, 95%CI:1.302-2.848). Chemotherapy was associated with lower odds of suicide injuries (unadjusted OR:0.408, 95%CI:0.307-0.541; adjusted OR in Model 1:0.444, 95%CI:0.311-0.636). However, neither metastatic cancer nor chemotherapy was significantly associated with suicide injuries in adjusted Model 2, suggesting the crucial role of other factors in influencing this risk.Conclusion: Patients with metastatic cancer exhibited notable prevalence of suicide injuries. Findings suggested metastatic cancer was associated with higher odds, and chemotherapy with lower odds, of suicide injuries. Multifaceted factors were associated with suicide risk beyond the presence of metastatic cancer or chemotherapy status, underscoring the importance of mental health assessments and interventions in oncology care, particularly for those with advanced cancer.

Immune checkpoint inhibitors (ICIs) can essentially treat cancer but only in a small subset of patients. Treatment strategies capable of effectively and robustly sensitizing refractory patients to ICIs represent a highly coveted yet unmet clinical need. In this study, we identified DJ-1 as a negative T cell regulator. DJ-1 knockout boosts antitumor immunity and significantly potentiates PD-1 and TIM-3 blockades in murine cancer models. Single-cell sequencing of tumor-infiltrating CD45+ cells revealed that DJ-1 deficiency indirectly activates T cells by reprogramming macrophages. Mechanistically, loss of DJ-1 increases reactive oxygen species (ROS) in macrophages, activating NF-κB/STAT3 signaling to promote differentiation into Cxcl9+ immune-stimulatory phenotypes while reducing immune-suppressive Spp1+ macrophages. Notably, this reprogramming may be stable across tumor microenvironments because the transplanted DJ-1-deficient macrophages maintain T cell-activating capacity. Pharmacological inhibition of DJ-1 by disulfiram markedly potentiated antitumor efficacy of PD-1 blockade. This designates DJ-1 as a promising target for overcoming immune checkpoint resistance and optimize combination therapies.

Oral mucositis is a frequent adverse effect of chemotherapy that significantly affects patients' quality of life and treatment continuity. Despite its clinical relevance, effective preventive strategies remain limited. This study aims to compare the efficacy and safety of betamethasone mouthwash with those of sodium gualenate hydrate mouthwash for preventing chemotherapy-induced oral mucositis.

Telomerase is active in the majority of high-risk neuroblastomas, a pediatric tumor associated with poor patient outcomes. In other cancer types, resistance to immune checkpoint blockade was overcome by induction of telomere dysfunction using the telomerase substrate precursor 6-thio-2'-deoxyguanosine (6-thio-dG). Here, we explored whether induction of telomere dysfunction improves the anti-tumor efficacy of immune checkpoint inhibition in neuroblastoma. 6-thio-dG treatment induced the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway and programmed cell death ligand-1 (PD-L1) expression in murine neuroblastoma cells in vitro. In a MYCN;ALKF1174L-driven transgenic neuroblastoma mouse model, 6-thio-dG treatment delayed tumor growth and prolonged survival. Treatment with anti-PD-L1 also led to growth delay and improved survival, which occurred; however, only after an initial lag phase. Combination with anti-PD-L1 improved the anti-tumor effects of 6-thio-dG and overcame the initial lag phase of anti-PD-L1 treatment. Mechanistically, 6-thio-dG combined with anti-PD-L1 treatment induced cGAS and PD-L1 expression and promoted immune cell infiltration in the tumors. Our findings suggest that 6-thio-dG treatment activates the cGAS-STING pathway in neuroblastoma and that induction of telomere dysfunction in combination with immune checkpoint blockade boosts intratumoral immune cell infiltration and improves survival in a high-risk neuroblastoma mouse model.

Hyperthermia has been used as an adjuvant therapy alongside radiotherapy and chemotherapy for cancer treatment in some countries. However, since the 2000s, growing evidence has indicated that hyperthermia exerts regulatory effects not only on cancer cells but also on stromal immune cells and the research interest in this topic has grown notably in the current "era of immunotherapy". Of particular interest to oncoimmunologists and hyperthermia researchers, recent studies have shown that hyperthermia modulates the expression of a wide range of immune checkpoint and co-stimulatory molecules. In addition to the PD-1/PD-L1 and CTLA-4/CD80/CD86 checkpoints previously reported and intensively discussed in existing reviews, recent studies indicate that hyperthermia exerts a broader regulatory effect on many other checkpoint and co-stimulatory molecules, include TIGIT/CD155, Tim-3/Gal-9, OX40/OX40L, and 4-1BB/4-1BBL on T cells, CD47/SIRPα on macrophages, and CD40/CD40L on dendritic cells. The present review aims to provide a complementary update, focusing specifically on recent advances in understanding how hyperthermia regulates the expression of these newer targets, as well as preclinical evidence for combining hyperthermia with novel therapeutic agents targeting these molecules. The insights gained from these preclinical studies could serve as a valuable foundation for future experimental investigations and clinical translation.

Urological Cancers pose a serious threat to human health and represent a major challenge to healthcare systems worldwide. Among these, bladder cancer (BC), prostate cancer (PCa), and renal cancer (RC) are the most prevalent. Primary clinical management involves local or radical resection. However, for patients with advanced or inoperable disease, as well as those at high risk of post-surgical recurrence, chemotherapy remains an essential alternative or adjuvant treatment. Nevertheless, the lack of tumor targetability leads to low bioavailability and significant side effects of drugs, limiting the clinical application of chemotherapeutic agents. In recent years, plant lectins have gained significant attention in cancer therapy research owing to their unique tumor-recognition capabilities. Unlike traditional chemotherapeutic agents, they inherently bind specifically to abnormal glycans on urological tumor cells, endowing them with unparalleled targeted therapy advantages and great potential to address traditional chemotherapy's core limitations and improve clinical outcomes. This paper presents a systematic, comprehensive and structured review with integrated critical analysis of the progress in this field. It first describes the clinical treatment methods for common urinary system tumors, including an analysis of the importance and limitations of chemotherapy. It then elaborates on the biological activities and antitumor mechanisms of plant lectins, highlighting on recent advances in the use of native lectins and lectin-modified drug delivery systems (DDS) for treating these malignancies. Finally, based on full collation and overall understanding of the existing literature, the application limitations of plant lectins are summarized, and their prospects are discussed.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis in arteries, veins or small blood vessels, and/or obstetric APS (OAPS), as well as persistent positive antiphospholipid antibodies. In recent years, some authors have proposed that the pathogenesis of APS is closely related to activation of vascular endothelial cells, immune cells, and complement activation. However, further exploration is still needed. Previous studies have shown that the mammalian target of rapamycin (mTOR) is associated with pro-inflammatory and pro-coagulant processes. This indicates that the activation of the mTOR signaling pathway may function as an intermediate mediator, causing immune disorders, thereby leading to thrombosis and OAPS. Therefore, we should correctly understand the potential pathogenic role of the mTOR signaling pathway in APS, which will be more conducive to clinicians' understanding of the pathogenesis of this disease and the search for new therapeutic targets. We hope this can open up a new window for the management of APS.

Terminalia macroptera (Combretaceae) is an important medicinal plant in the traditional pharmacopeia in most tropical areas, where its different parts are used in treating illnesses including cancer.

Pharmacovigilance has revealed an alarming correlation between certain medications and a higher risk of cancer. In this narrative review, included research from 2020 to 2025, along with a few seminal older studies, so that it provides a clear picture of which drugs actually set off cancer and mechanisms involved at the molecular level. An extensive literature review of the subject was designed on PubMed, Embase, Scopus, and Web of Science using systematic search. Search words and phrases included: "Carcinogenic drugs," "drug-induced cancer," "medication-induced carcinogenesis," "immunosuppressant cancer risk," "hormone therapy and cancer," "chemotherapy-induced secondary malignancies," and names of relevant drugs.

Skin rash is the most common adverse effect in patients with cancer receiving epidermal growth factor receptor inhibitors (EGFRIs), which can impair quality of life and lead to treatment discontinuation. Numerous primary studies have explored factors that may predict the development of skin rash. However, the wide range of variables and substantial heterogeneity among these studies limit the availability of high-quality, synthesised evidence. A comprehensive scoping review is therefore warranted to systematically map and synthesise the risk factors for EGFRI-induced skin rash in patients with cancer.

Despite advancements in multimodal therapies, oral squamous cell carcinoma (OSCC) continues to exhibit poor clinical outcomes, particularly in advanced and recurrent cases. Recent studies have identified the calcium-binding protein S100A2 as a critical mediator of OSCC progression and resistance to therapy. Our prior work demonstrated that cytoplasmic overexpression of S100A2 in oral cancer patients is associated with tumor recurrence and reduced survival. Given its reported role in promoting epithelial-to-mesenchymal transition (EMT), cellular proliferation, and invasiveness, we investigated the in vitro functional impact of S100A2 inhibition in OSCC.

Breast cancer (BC) is a complex illness that affects millions of women globally. As its incidence rises, new treatment strategies are needed. Veratrum viride, a traditional medicinal herb, is known for its therapeutic potential, yet its molecular mechanism of action against BC remains unclear. The purpose of this preliminary investigation is to assess V. viride's anti-breast cancer potential by identifying its active compounds and using bioinformatics techniques to clarify their multi-target mechanisms.

Both CDK2 (cyclin-dependent kinase 2) and EGFR (epidermal growth factor receptor) play significant roles in the development and progression of colorectal cancer. In vitro studies of several hydroxyxanthone derivatives for the treatment of WiDr cancer cell lines have revealed potential anticancer activity against colorectal cancer. The present study aims to identify hydroxyxanthone derivatives as potential drug candidates for colorectal cancer treatment through an in silico approach.

Cervical cancer is the second leading cause of mortality in women globally, with its incidence increasing due to multidrug resistance (MDR) and adverse side effects associated with chemotherapeutic agents. Hence, this study was carried out to investigate the selective cytotoxicity and apoptotic induction potential of Buddleja polystachya leaf diethyl ether (BPL-DE) extract on cervical cancer HeLa cell lines.

The aim of the study was to determine how the chemotherapeutic alkylating agent dacarbazine, together with the application of the miR-204-5p mimic in vivo, affects the presence of disseminated melanoma cells in distant organs - the lungs and liver.

Monastrol, a DHPM-based Eg5 inhibitor with well-known antiproliferative activity but limited therapeutic potential due to poor solubility and low bioavailability, was selected as the lead compound for the design of styryl-modified 3,4-dihydropyrimidin-2(1H)-ones with an improved pharmaceutical profile. Twelve derivatives (10-21) were synthesized via the Biginelli reaction and evaluated for cytotoxicity in HeLa and MCF-7 cells. Styryl derivatives 16 and 17 emerged as the most active. In HeLa cells, derivatives 17 (IC50 = 1.3 µM) and 16 (IC50 = 3.7 µM) were approximately 85-fold and 30-fold more potent than monastrol (IC50 = 111 µM), respectively. In MCF-7 cells, derivatives 16 and 17 displayed 18- to 20-fold higher potency than monastrol, respectively. Biological results also indicate that styryl derivatives 16 and 17 induce apoptosis in both HeLa and MCF-7 cells. In HeLa cells, activation of caspase-8, -9, and -3 suggests the involvement of both intrinsic and extrinsic pathways. In contrast, in MCF-7 cells, the increased expression of p53 and p21, together with PARP cleavage, suggests a p53-dependent apoptotic response. Derivatives 16 and 17 emerged as promising Eg5 inhibitors from docking studies, but their poor aqueous solubility (0.2-0.7 µM), despite high biological stability, highlights the need for formulation strategies to improve drug-like properties.

Malignant pleural effusion (MPE) portends poor prognosis in advanced cancer. Strategies that integrate potent tumor killing with immunosuppressive microenvironment reprogramming are crucial for the treatment of MPE. Studies show that irradiated tumor cell-derived microparticles (RT-MPs) possess natural tumor-targeting cytotoxicity and innate immune activation properties. To further boost the tumoricidal effects of RT-MPs, we developed innovative chemoradiotherapy-integrated tumor cell-derived microparticles (CR-MPs) by loading RT-MPs with chemotherapeutic agents, including methotrexate (MTX), monomethyl auristatin E (MMAE), or doxorubicin (DOX). CR-MPs exhibited superior tumoricidal activity over both RT-MPs and free drugs against a range of tumors. Specifically, MTX-loaded CR-MPs (CR-MPs@MTX) triggered mitochondrial oxidative stress and immunogenic ferroptosis in tumor cells, while directly reprogramming macrophages toward the M1 phenotype and stimulating dendritic cells via cGAS-STING/NF-κB pathway activation. In murine MPE models, CR-MPs effectively suppressed tumor progression, extended survival, and demonstrated favorable biosafety. When combined with immunotherapy, this approach achieved a cure rate of up to 70%, induced durable immunological memory, and retained efficacy against chemotherapy-resistant tumors. This study establishes CR-MPs as a novel platform with robust therapeutic efficacy against MPE, highlighting their translational potential as a precision concurrent chemoradiotherapy strategy for MPE management in clinical settings.

Although cisplatin (CDDP) is widely employed in combination immunotherapy, no CDDP-based regimen has shown a survival benefit when treating the ovarian cancers. This is mainly because the impact of CDDP on immunotherapy is not fully understood. A critical gap concerns how CDDP reshape the tumour microenvironment, especially through extracellular vesicles (EVs)-mediated communication. In this work, using human and murine ovarian cancer cells as a model, we demonstrate that CDDP boosts the secretion of EVs from cancer cells, while exerting no such effect on non-cancerous cells. These CDDP-induced tumour-derived EVs, in turn, drive the differentiation of CD4+ T cells towards immunosuppressive regulatory T cells (Treg cells), which are known to limit the efficacy of immunotherapy. Based on next-generation sequencing, a significant enrichment of miR-181a-5p was identified in CDDP-induced tumour-derived EVs, and further functional studies confirmed that this microRNA promoted Treg cell differentiation via suppressing sirtuin 1 (SIRT1), a key regulator of the transcription factor forkhead box protein P3 (FOXP3). Importantly, inhibition of miR-181a-5p abrogated the Treg-promoting effect of CDDP-induced tumour-derived EVs, a finding further validated in vivo, where blockade of miR-181a-5p not only impaired Treg differentiation but also restored T-cell-mediated antitumour immunity and restrained tumour growth. Together, these findings uncover a previously unrecognised mechanism by which CDDP exacerbates immunosuppression via miR-181a-5p-enriched EVs and suggest that targeting this pathway could improve the therapeutic efficacy of combination immunotherapy in ovarian cancer.

This network meta-analysis evaluated the efficacy of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, with or without Dexamethasone (D), for preventing chemotherapy-induced nausea and vomiting (CINV) in patients undergoing highly emetogenic chemotherapy (HEC) who were limited to these regimens.

Cancer stem cells (CSCs) contribute to an immunosuppressive microenvironment through complex mechanisms and tumor-immune interactions. However, the key determinants of CSC characteristics in driving tumor progression, immune suppression, and response to ICIs remain unclear and require systematic investigation. This study developed a quantitative systems pharmacology (QSP) model covering various CSC properties, thereby capturing the temporal dynamics and CSC-immune interactions in triple-negative breast cancer (TNBC). Using the unified longitudinal dataset of tumor growth, CSC frequency, and immune cell dynamics that we obtained from BALB/c mice bearing wild-type or Cd274-knockout 4T1 cells under various inoculation conditions, which provides multi-dimensional insights into CSC-related biology, the QSP model was calibrated and validated. Simulations and sensitivity analysis indicated that TNBC tumors with strong stemness exhibited significantly accelerated tumor growth and reduced infiltration of cytotoxic immune cells such as cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. These were associated with CSCs' enhanced self-renewal capacity, stemness maintenance, secretion of transforming growth factor beta (TGF-β) and vascular endothelial growth factor (VEGF), and PD-1/PD-L1-mediated immunosuppression. ICIs showed minimal efficacy in tumors with enhanced stemness, which was also linked to the aforementioned characteristics. Both the administration sequence and initiation timing of ICIs differentially influenced the therapeutic outcomes. These findings elucidate the roles of CSCs in TNBC progression, tumor immunity, and ICI efficacy while identifying the key underlying CSC characteristics, suggesting the potential value of assessing CSC biomarkers or abundance before ICI treatment and support the development of ICIs and anti-CSC combination therapies.