Aim: To evaluate the anticancer, apoptotic, and antioxidant effects of Alo on A549 cells, both alone and in combination with CP, and to elucidate the molecular mechanisms underlying the death of cancer cells.

Aim: To evaluate the anti-tumor potential of SAXA on A549 cells and assess its combinatory effects with CP on cell viability and apoptosis markers.

Pharmacological reversal of abnormal promoter DNA hypermethylation at tumor suppressor genes (TSGs) is a key therapeutic paradigm for cancer management. However, the clinical efficacy of currently approved nucleoside analog hypomethylating agents (HMAs) is limited by dose-dependent toxicity and high resistance rates. Nonnucleoside, DNA methyltransferase 1 (DNMT1)-selective inhibitors offer a promising alternative. To date, only limited chemotypes, exemplified by the dicyanopyridine derivative GSK3685032 (GSK5032), have demonstrated translatable DNMT1 inhibition, with resistance emerging upon prolonged exposure. To address these limitations, we employ structure-guided scaffold hopping and chemical optimization to develop a series of DNMT1 inhibitors (DNMT1i) featuring a bicyclic 7-azaindole scaffold. We identify DMI46, a potent enzymatic DNMT1i capable of reversing cancer-specific DNA methylation abnormalities and TSG silencing, leading to robust antileukemic effects and favorable tolerability. Cryoelectron microscopy (cryo-EM) studies reveal that the 7-azaindole inhibitor exhibits enhanced intercalation into hemi-methylated CpG dyads and increased minor-groove contacts within the DNMT1/hemimethylated DNA complex compared to GSK5032. These structural features enable sustained DNMT1 targeting and significant antiproliferative activity of DMI46 in GSK5032-resistant acute myeloid leukemia (AML) cells. We also demonstrate DMI46's capacity to overcome AML resistance to nucleoside-based HMAs both in vitro and in vivo. These findings introduce a distinct DNMT1i chemotype with enhanced on-target engagement and broad applicability against HMA-resistant AML.

Copyright: © 2026 Aleid et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Acquired resistance to tyrosine kinase inhibitors (TKIs) remains the primary obstacle to long-term disease control in targeted cancer therapy, yet whether resistance emerges gradually through clonal selection or abruptly via mutation acquisition remains unclear. We develop a four-dimensional ordinary differential equation model coupling drug-sensitive and drug-resistant tumor populations with dynamic vascular support and explicit TKI pharmacokinetics. Mathematical analysis establishes solution positivity and uniform boundedness, characterizes all equilibrium states, and determines local stability conditions via Jacobian eigenvalue analysis, revealing threshold relationships between drug efficacy and evolutionary outcomes. We perform systematic parameter estimation using differential evolution on longitudinal tumor mass data from a gastrointestinal stromal tumor patient treated with imatinib. Models assuming continuous effective drug pressure fail systematically, with best fit achieving only coefficient of determination R-squared equals 0.721, unable to reproduce the observed 24-fold tumor mass increase during relapse. In striking contrast, incorporating a sigmoid resistance modulation function-where cytotoxicity progressively vanishes due to mutant clonal expansion near day 683-yields near-perfect agreement with R-squared equals 0.999, accurately capturing all three clinical phases. The estimated transition rate implies a rapid 10â€"90 percent clonal takeover within approximately 2.5 days, providing quantitative evidence that explosive relapse reflects abrupt mutation acquisition rather than gradual selection.

Immune checkpoint inhibitors (ICIs) deliver durable benefit to only a subset of patients and can be limited by immune-related adverse events (irAEs). The gut microbiome has emerged as an actionable, host-level modulator of ICI drug sensitivity and toxicity. This mini-review links microbial ecology to antigen presentation, T-cell priming and fitness, metabolite signaling, and barrier inflammation, and summarizes interventional evidence across three modalities. Responder-derived fecal microbiota transplantation (FMT) provides the strongest proof-of-concept for re-sensitization in anti-PD-1-refractory melanoma. Microbiome repair can also improve refractory ICI-associated colitis. Early trials of live biotherapeutics and defined consortia support scalability but highlight context dependence and design pitfalls, including antibiotic preconditioning. We discuss practical determinants of reproducibility, including co-medications, diet, engraftment and functional readouts, and conclude with safety, regulatory, and reporting priorities for clinically deployable microbiome engineering.

To evaluate the efficacy and safety of anlotinib combined with programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in the treatment of malignant solid tumors.

Locally advanced or metastatic urothelial carcinoma (la/mUC) is associated with poor prognosis and limited treatment options. Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic approach. While previous meta-analyses have shown the efficacy and safety of ADCs in UC, the rapid development of new ADC agents and combination therapies necessitates an updated and comprehensive evidence synthesis.

Overcoming resistance to immune checkpoint inhibitors (ICIs) remains a critical challenge in the treatment for hepatocellular carcinoma (HCC).

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the flow cytometric plots shown in Fig. 3 on p. 372, the C/U2OS and 48 h/U2OS, C/143B and 48 h/143B, and C/MG63 and 72 h/143B data panels, respectively, were strikingly similar, suggesting that this figure has been assembled incorrectly, and that these data were derived from a smaller number of original sources. The authors have been contacted by the Editorial Office to offer an explanation for the apparent duplication of these data panels within this figure, and we are waiting their response. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [Oncology Reports 31: 370‑375, 2014; DOI: 10.3892/or.2013.2862].

Ulcerative colitis (UC), a major form of inflammatory bowel disease, has a global incidence of ~10.6 per 100,000 individuals. The long‑term side effects and dependency issues associated with conventional UC therapies have become increasingly evident, highlighting the need for more effective and safer treatment options. In previous years, clinical research on small‑molecule targeted drugs against UC has achieved notable progress; however, the underlying pathogenesis and therapeutic mechanisms of UC still require deeper investigation. The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor that binds both pathogen‑associated molecular patterns and damage‑associated molecular patterns, thereby mediating inflammatory and cellular stress responses. Concurrently, vascular endothelial growth factor (VEGF), a key regulator of angiogenesis, is markedly upregulated in patients with UC and associates with disease severity. The RAGE/VEGF signaling axis has thus emerged as a notable target for antiangiogenic therapy in UC. Interventions aimed at disrupting the interaction between RAGE and its ligands, inhibiting RAGE pathway activation or suppressing VEGF upregulation have demonstrated promising potential to alleviate symptoms and slow disease progression. The present review summarizes previous advances in UC‑targeted therapeutics and elucidates the role of the RAGE/VEGF axis in UC pathophysiology, highlighting the potential mechanisms and clinical prospects of antiangiogenic strategies targeting this pathway.

Ovarian clear cell carcinoma (OCCC) is an endometriosis-associated ovarian cancer subtype. Somatic mutations in OCCC are reported in ARID1A, PIK3CA, and the TERT promoter (TERTp), as well as less commonly in KRAS and TP53 among other genes. OCCC is typically resistant to standard-of-care chemotherapy, especially after relapse. While recent studies have seen favourable responses to immunotherapy, patients with OCCC face limited therapeutic options.

Antiangiogenic combination therapy-antiangiogenic agents combined with immune checkpoint inhibitors and/or chemotherapy-has become an important treatment strategy for advanced driver-negative non-small cell lung cancer (NSCLC). We conducted a network meta-analysis to compare efficacy and safety and identify optimal antiangiogenic combinations.

Chemotherapy is associated with multiple side effects (e.g., fatigue, functional decline, emotional distress), but research suggests that the side effects can be mitigated or prevented through regular engagement in physical activity. Yet, there is a known decline in physical activity during chemotherapy. Understanding what a woman affected by breast cancer experiences during chemotherapy may provide insight into ways to increase physical activity engagement. This study explores the experience of women with breast cancer receiving chemotherapy and how they navigate physical activity participation during chemotherapy.

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.

In this article, we discuss the clinical and histopathologic findings of cutaneous adverse reactions to newer medications, including those recently approved to treat inflammatory skin diseases, such as dupilumab for atopic dermatitis and IL-12/-23 and IL-23 specific inhibitors for psoriasis, as well as those with oncologic indications, including immune checkpoint inhibitors, mogamulizumab, and enfortumab vedotin.

Marine organisms are a valuable source of lead compounds for drug development, and basic research. This field has been active for nearly half a century. However, because of their unique structures and poor chemical stability, it is difficult to achieve a sustainable, large-scale supply of marine natural products and thus, their use in drug development is rare. Renieramycin was first reported in 1982 by Fricke and Faulkner as a trace secondary metabolite from the blue sponge Reniera sp. Dimeric 1,2,3,4-tetrahydroisoquinoline derivatives, such as renieramycins, have attracted attention as novel anticancer agents. Therefore, challenges related to chemical stability and transformations, as well as development of total syntheses were overcome. Several excellent reviews on renieramycin marine natural products have been published. Research in the renieramycin family has been developed based on the results of various previous studies on saframycin, an antibiotic discovered from the Actinomycete Streptomyces lavendulae No. 314. In this review, we will introduce from a new perspective the results of ongoing efforts in the medicinal chemistry. We will explore the discovery, chemical transformation, total synthesis, and structure-activity relationships of renieramycin marine natural products, highlighting unexpected findings that emerged during the research process.1.

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.

Chemotherapy-induced hypersensitivity reactions (CIHSRs) are common in outpatient infusion settings, requiring infusion nurses to recognize and respond quickly for optimal outcomes. This article supports novice nurses by outl.