Cancer therapy-related cardiovascular toxicity (CTR-CVT) is an umbrella term for myocardial, vascular, electrical, and inflammatory complications of cytotoxic, targeted, immune, and radiation-based therapies. Cancer therapy-related cardiac dysfunction (CTRCD) is used here more narrowly for treatment-related myocardial dysfunction, typically identified by changes in left ventricular ejection fraction, global longitudinal strain, and/or cardiac biomarkers. The pathophysiology of CTR-CVT is multifactorial, but the implicated pathways should not be interpreted as equally causal. The dominant initiating mechanism is therapy-specific - anthracycline injury is best supported by topoisomerase IIβ (TOP2B)-mediated DNA damage with secondary mitochondrial and redox injury; HER2-directed toxicity by disruption of NRG1-ERBB2/ERBB4 survival signalling; fluoropyrimidine toxicity by coronary vasomotor dysfunction; VEGF-pathway inhibition by endothelial dysfunction and hypertension; immune checkpoint inhibitor toxicity by loss of immune tolerance; and radiotherapy injury by endothelial and microvascular damage with progressive fibrosis. Mitochondrial dysfunction, oxidative stress, inflammation, calcium dysregulation, apoptosis, and ferroptosis frequently act as downstream or amplifying pathways, although the clinical relevance of several regulated cell-death mechanisms remains incompletely established. Genetic susceptibility may further modify risk, but the strength of evidence differs among reported loci. Replicated pharmacogenetic associations, rare variants in established cardiomyopathy genes, and preliminary candidate-gene findings should therefore be considered separately. Most available studies remain limited by small cohorts, heterogeneous phenotyping, ancestry imbalance, and incomplete external replication. This review critically evaluates the hierarchy and strength of mechanistic and genetic evidence and discusses the extent to which these findings can currently inform risk stratification, surveillance, prevention, and treatment in precision cardio-oncology.

Reliable biomarkers reflecting tumor biology and histopathological risk status in pheochromocytomas and paragangliomas (PPGL) remain limited. In this study, the expression of biomarkers associated with hypoxia, angiogenesis, and proliferation was evaluated, and their associations with histopathological differentiation in PPGL were investigated.

A total of 35 tumor foci from 31 patients with PPGL who were surgically treated were retrospectively examined. Expression levels of hypoxia-inducible factor-2 alpha (HIF-2α), vascular endothelial growth factor (VEGF), CD105 (endoglin), Ki-67, and succinate dehydrogenase subunit B (SDHB) were assessed using immunohistochemical methods. Associations between these markers and clinicopathological characteristics, Pheochromocytoma of the Adrenal Gland Scaled Score (PASS), and Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) scores were analyzed.

HIF-2α expression, CD105 microvessel density (MVD) score, and Ki-67 proliferation index were significantly higher in poorly differentiated tumors compared with moderately/well-differentiated tumors (p<0.05 for all). In contrast, VEGF expression did not differ significantly between the groups. The GAPP score showed positive correlations with HIF-2α (r=0.48; p<0.01), CD105 (r=0.54; p<0.001), and Ki-67 (r=0.77; p<0.001). In univariate analyses, bilateral disease, HIF-2α expression, CD105 MVD score, and loss of SDHB expression were associated with higher GAPP scores. However, in multivariable regression analysis, only CD105 was independently associated with the GAPP score (β=0.04; p=0.026).

Increased expression of CD105, HIF-2α, and Ki-67 was associated with poorer histopathological differentiation in PPGL. Among the biomarkers evaluated, only CD105 showed an independent association with the GAPP score, suggesting that tumor-associated neoangiogenesis may contribute to histopathological differentiation in PPGL. These findings support further investigation of CD105 as a potential biomarker for histopathological risk assessment. However, larger studies with long-term clinical outcome data are needed to establish its clinical prognostic value.

Cancer remains a major global health challenge, particularly as several tumors develop resistance to current therapies. Although doxorubicin is widely used to treat various cancers, its effectiveness is often limited by adverse effects, including cardiotoxicity and nephrotoxicity, which restrict its dosing. In search of safer and more effective options, a series of novel piperidine-embedded isoxazol-triazole conjugates (6a-6o) were designed, synthesized, and biologically evaluated against the MCF-7 cell line in this study. The synthesized compounds 6a-6o were characterized using FTIR, HRMS, and ¹H and ¹³C NMR spectroscopy analysis to confirm their structure and verify successful synthesis. The GI₅₀ (Growth Inhibition 50%) values of synthesized compounds 6a-6o were determined using the SRB assay. Among all synthesized compounds, 6m exhibited the most potent antiproliferative activity against MCF-7 cells, having GI50 <10 µg/mL (SI >5), comparable to adriamycin (doxorubicin, GI₅₀ <10 µg/mL). Overall, 6m is a novel anticancer agent with promising abilities against MCF-7 human breast cancer. The results support the compounds relevance as a biologically active agent with effective proliferation-suppressive properties.

Endometrial cancer (EC) is the most common gynecological malignancy in postmenopausal women. Patients with low estrogen receptor alpha (ERα) expression frequently develop aggressive pathological subtypes and have poor prognosis. The role of estradiol (E2) in ERα-low EC remains poorly understood. This study investigated the tumor-promoting effects of E2 using clinical data, in vitro functional assays, and a mouse xenograft model. We found that serum E2 levels were elevated in ERα-low patients, of whom 67.7% showed high tumor expression of G protein-coupled estrogen receptor (GPER). High GPER expression correlated with increased E2 levels, enhanced sphingosine kinase 1 (SphK1) activity, and higher Ki67 proliferation index. In vitro, E2 promoted proliferation, migration, and invasion of HEC-1A cells (low ERα, high GPER). These effects were suppressed by pharmacological inhibition or siRNA knockdown of GPER or SphK1. Mechanistically, E2 activated the ERK1/2 pathway via the GPER/SphK1 axis, leading to upregulation of Cyclin D1, Cyclin E1, and MMP-9. In vivo, E2 stimulated xenograft tumor growth, an effect mitigated by inhibitors of GPER, SphK1, and ERK. Our findings demonstrate that E2 drives progression of ERα-low endometrial cancer through the GPER/SphK1 signaling pathway, revealing potential therapeutic targets for this high-risk subgroup.

Ferroptosis, an iron-dependent form of regulated cell death, is frequently dysregulated in both tumor and immune cells, contributing to tumor progression and limiting the effectiveness of cancer immunotherapy. Defining the molecular mechanisms that govern ferroptosis and its effects within the tumor immune microenvironment is critical for understanding its dual role in cancer biology. While modulation of ferroptosis presents a promising therapeutic strategy, non-specific targeting may also impair normal tissues and tumor-infiltrating immune cells. In this context, nanoparticle-based delivery systems offer a potential approach to selectively regulate ferroptosis within tumors. Such strategies may enable precise remodeling of the tumor microenvironment and enhance antitumor immune responses, thereby improving immunotherapy outcomes. This review highlights the regulatory mechanisms linking ferroptosis and the tumor immune microenvironment, provides a critical discussion of recent developments in bionanomaterial-based therapeutic platforms, and outlines the challenges and prospects for clinical application of these platforms for immunotherapy.

Stroke is the second most common neurological complication in cancer patients after metastases. Cancer-associated coagulopathy (CAC) is an important mechanism of ischemic stroke in this population. We systematically reviewed the epidemiological, clinical, radiological, and pathophysiological features of CAC-related stroke, as well as associated biomarkers and treatment strategies.

A systematic search of PubMed/MEDLINE, Scopus, Cochrane Library, and Embase (2000-2025) was performed according to PRISMA 2020 guidelines. Search terms included "stroke", "cancer", "hypercoagulability", "coagulopathy", "disseminated intravascular coagulation", and "non-bacterial or marantic thrombotic endocarditis". Studies published in English or Spanish were included, whereas case reports and review articles were excluded. Data were synthesized qualitatively.

Eighty-two studies met inclusion criteria. CAC-related stroke occurs predominantly within six months of cancer diagnosis and is strongly associated with advanced or metastatic disease and a high risk of early recurrence. Adenocarcinoma, particularly lung and pancreatic cancer, is the most frequently associated histological subtype. Proposed mechanisms include mucin-mediated platelet aggregation, tissue factor-driven coagulation, extracellular vesicles, and neutrophil extracellular trap formation, leading to thromboinflammation and platelet-rich thrombi. D-dimer is the biomarker most consistently associated with recurrence and mortality, while C-reactive protein, fibrinogen, CA-125, and transcranial Doppler microembolic signals show limited specificity. Characteristic imaging findings include multiple infarcts involving more than two vascular territories, particularly the 'three territories sign'. Low-molecular-weight heparin and direct oral anticoagulants are the most commonly used secondary prevention strategies. Thirty-day mortality rates range from 25 to 50%.

CAC-related stroke is a distinct and underrecognized entity characterized by specific biological and radiological features and poor outcomes. Earlier recognition and optimized antithrombotic strategies may improve prognosis.

IQGAP2 gene defects can lead to aberrant cell proliferation and are associated with multiple diseases. Previous studies suggest that IQGAP2 knockdown can activate AKT/mTORC1 and thereby promote aberrant cell proliferation. However, the upstream molecular regulatory mechanisms remain unclear. In our study, we found that IQGAP2 knockdown enhances PI3K activity, leading to accumulation of PI(3,4,5)P₃, thereby activating downstream AKT and mTORC1 activity. Integrative multi-omics and co-immunoprecipitation analyses revealed that IQGAP2 downregulation promotes PI3K activation within the IQGAP1 complex, while simultaneously activating the Wnt/β-catenin and AREG/EREG-EGFR signaling axes, thereby directly or indirectly enhancing PI3K activity. Furthermore, we found that the IQGAP1/IQGAP2 expression ratio is significantly elevated in tumor tissues and this ratio is associated with poor patient survival prognosis by TCGA pan-cancer analysis. This study provides insights into the signaling mechanisms associated with IQGAP2 downregulation, suggesting that the IQGAP1/IQGAP2 expression ratio may have clinical potential as a pan-cancer prognostic biomarker, and providing a basis for further investigation of targeted interventions for IQGAP2-related diseases.

Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and reduce flux through the mevalonate pathway, which supplies both cholesterol and the non-sterol isoprenoids required for prenylation of small GTPases. Because this pathway is frequently activated in cancer, statins have become one of the most intensively studied candidates for oncological drug repurposing. Preclinical work indicates that statins can lower the threshold for apoptosis, modulate autophagy in either a pro-death or a cytoprotective direction, induce pyroptosis, and sensitize cells to ferroptosis, while also acting on CD8⁺ T cells, macrophages, dendritic cells, and cancer-associated fibroblasts within the tumor microenvironment. Clinical evidence, however, remains discordant with the strength of these mechanistic claims: favorable observational associations are susceptible to immortal-time bias, healthy-user bias, and confounding by indication, and randomized trials have been largely neutral for tumor-directed endpoints. This narrative review appraises the mechanistic, preclinical, and clinical literature using an explicit five-tier evidence hierarchy, and treats two constraints as analytical tools rather than closing caveats: the pharmacological heterogeneity of individual statins, and the one-to-two order-of-magnitude gap between concentrations used in cancer-cell experiments and free drug concentrations achievable in patients. We conclude that statins are biologically plausible but clinically unproven anticancer agents whose evaluation should proceed through biomarker-selected, pharmacodynamically validated combination trials rather than unselected add-on designs.

Allergic diseases are typically regarded as type 2 inflammatory disorders driven by interleukin-4, interleukin-5, and interleukin-13, which mediate immunoglobulin E class switching, eosinophilic inflammation, mucus hypersecretion, pruritus, tissue remodeling, and epithelial barrier dysfunction. However, type 2 cytokine activity alone does not fully account for variations in exacerbation risk, susceptibility to infections, comorbidities, or responses to biologic therapy. This narrative review proposes an asthma-centered type 2-interferon imbalance framework and discusses its cautious, disease-specific extension to atopic dermatitis, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, and food allergy. The model emphasizes that, particularly in asthma, allergic barrier inflammation arises and persists in injured tissues where excessive type 2 inflammation may coexist with impaired interferon-mediated host defense. Evidence is strongest in asthma, where deficiencies in type I and type III interferon responses are linked to rhinovirus susceptibility, delayed viral clearance, and recurrent exacerbations. In other allergic diseases, interferon dysfunction appears more variable, reflecting differences in tissue context, disease stage, and environmental exposure. In asthma, and potentially in selected allergic barrier diseases, persistent inflammation may result from a cycle of epithelial injury, alarmin release, cytokine amplification, impaired antiviral defense, ongoing exposure, and incomplete tissue repair. These mechanisms provide a rationale for tiered intervention, including blockade of upstream epithelial alarmins, inhibition of downstream type 2 effector pathways, and selected investigational approaches aimed at restoring mucosal host defense.

Lower respiratory tract infections (LRTIs) are among the leading causes of clinical deterioration and death in critically ill patients. In the intensive care unit (ICU), timely identification of the causative pathogen is essential for appropriate antimicrobial therapy; however, conventional culture methods take 3 to 5 days and have suboptimal positivity rates, particularly for fungi. Molecular approaches such as PCR shorten turnaround time but still depend on manual nucleic acid extraction and thermocycling, limiting their suitability for bedside use. This protocol describes a point-of-care workflow built around a fully integrated, disc-shaped microfluidic chip (CD chip) that couples magnetic bead-based nucleic acid purification with loop-mediated isothermal amplification (LAMP). After a simplified manual liquefaction and lysis step, the processed specimen is loaded onto the chip together with two prepackaged reagent vials. The instrument then autonomously performs extraction, amplification at 65 °C, and real-time fluorescence readout, returning qualitative results for 15 targets, namely 11 bacteria, 3 fungi, and 1 atypical pathogen, within 45 min of instrument run time (approximately 1 h for the complete sample-to-answer workflow, including the manual preprocessing step). We present detection data from 10 ICU specimens, including sputum, bronchial aspirates, and bronchoalveolar lavage fluid, encompassing both single-pathogen and polymicrobial co-infections involving up to 7 organisms on a single chip. The closed cartridge design minimizes the risk of aerosol contamination, and the single loading step requires no specialized training, positioning this system as a practical bedside diagnostic tool for ICU teams.