Exosomes are nanoscale vesicles that are attractive for liquid biopsy, but most methods deliver ensemble averages and obscure how surface biomarkers vary across individual vesicles. We develop a single-particle impact electrochemistry (SPIE) assay to profile epithelial cell adhesion molecule (EpCAM) on single exosomes. EpCAM-positive vesicles are labeled with silver nanoparticle-aptamer conjugates. Each labeled exosome yields an silver oxidation spike upon collision with a polarized ultramicroelectrode. Impact frequency reports the abundance of EpCAM-positive exosomes, while the integrated spike charge provides a semiquantitative proxy for per-vesicle EpCAM. Using MCF-7 (EpCAM-high) and HeLa (EpCAM-low) exosomes, we confirm EpCAM-dependent signals and resolve intrapopulation heterogeneity. For serum samples from healthy donors and breast cancer patients at different clinical stages, SPIE reveals stage-dependent increases in both EpCAM-positive exosome counts and per-vesicle EpCAM load, consistent with nanoflow cytometry. This nonoptical platform enables semiquantitative single-exosome protein phenotyping in complex matrices, offering potential for disease-state-associated exosome analysis, clinical research, and future multiplexed profiling.

Blood levels of high-density lipoprotein (HDL) are significantly inversely correlated with the risk of numerous malignancies and overall mortality in most tumor types. This review focuses on the antitumor role of HDL and its main protein component, apolipoprotein A-I (apoA-I). The association of HDL/apoA-I with various cancer types and the probable mechanisms of their antitumor action, including cholesterol removal from tumor cells, modulation of the tumor microenvironment, and involvement in the regulation of oncogenic signaling pathways, are discussed. The identified high expression of the SR-B1 receptor in tumor cells supports the use of HDL and its synthetic analogs (apoA-I mimetics) as a platform for the targeted delivery of antitumor agents. Using various tumor models, it has been demonstrated that the use of these plasma components for targeted drug delivery enhanced their antitumor effect and reduced side effects.

Stabilised hyaluronic acid (sHA) gel can be used as a breast cancer tumour bed marker. This study aimed to assess the gel on post-treatment surveillance mammography (MMG) and breast ultrasound (USS).

Patients who underwent breast-conserving surgery and adjuvant radiotherapy, with sHA gel markers (0.3-0.5 mL drops) in breast tissue had their routine 1- and 2-year post-treatment MMG and USS undergo central review by one experienced radiologist. The central review questionnaire included whether the gel was visible, description if visible, and whether it impacted diagnostic assessment of the images using a 5-point Likert scale. The images were also standardly reported by radiologists who were blinded to the gel history.

Of the 33 patients eligible for evaluation, sHA gel was visible on the 1-year post-treatment MMG in 3% of patients, described as well circumscribed nodules adjacent to the surgical scar. sHA gel was visible on the 1-year post-treatment USS in 38% of patients, described as simple round cystic lesions near the surgical bed. sHA gel was still visible on the same patient's 2-year post-treatment MMG (3%) and was visible on the 2-year post-treatment USS in 19% of patients. In all cases, the gel was rated 'unlikely' or 'very unlikely' to impair diagnostic assessment of the images and did not lead to any additional investigations. The blinded radiologists reported the gel as non-suspicious appearing cysts without clinical concern.

sHA gel used as breast tumour bed marker was not visible in most patients' post-treatment MMG and USS and did not affect diagnostic assessment.

Loss of the Y chromosome (LOY) is a frequent event in male tumors and has been linked to cancer progression. However, the degree of mosaic LOY (mLOY) within normal tissues from men with or without cancer remains uncharacterized.

Here we used a FISH-based assay targeting X- and Y-chromosome centromeres to perform a pan-organ analysis of mLOY in 1,000 male tissue samples from 405 individuals representing 11 organs. Automated image processing generated a quantitative FISH-based mLOY score (YchrFISH) that we validated against a transcriptomic surrogate of Y-chromosome dosage from RNA-seq data.

mLOY burden varied by tumor type, with highest degree in colorectal carcinoma. Across tissue groups, YchrFISH scores declined progressively from normal tissues of cancer-free men to histologically normal tissues adjacent to cancer and carcinoma (P < 0.0001). Paired analyses confirmed consistently greater mLOY in malignant compared with tumor-adjacent histologically normal tissue in different organs. Spatially resolved RNA-seq maps of bladders removed for cancer demonstrated a transcriptional gradient of Y-chromosome loss from normal urothelium through intraepithelial neoplasia to invasive carcinoma.

mLOY gradients exist across histologically normal and malignant tissues, consistent with the concept of field cancerization. Our findings support epithelial mLOY as a biomarker of early malignant transformation and, to our knowledge, a previously unrecognized hallmark of male oncogenesis.

NIH grants R35CA294022, P01CA163227, and P50CA97186 (the Pacific Northwest Prostate Cancer SPORE) and the Institute for Prostate Cancer Research.

CRD42022343066.

Cancer frequently arises from the impaired functioning of the Mitogen-activated protein kinase (MAPK) signaling system, driven by mutation or overexpression of key signaling components. RAF, MEK, ERK, and KRAS inhibitors have significantly improved clinical outcomes, but efficacy is still restricted due to pathway reactivation, adaptive resistance, and signaling cross-talk. These limitations have led to the search for novel therapeutic approaches and molecular targets in the MAPK network. Melanoma, thyroid carcinoma, and pancreatic adenocarcinoma were selected because MAPK pathway alterations contribute to their pathogenesis and influence treatment response. This review examines the biological importance of MAPK signaling in these cancers and discusses MAPK-targeted therapies, mechanisms of resistance, and combination treatment options. It also addresses the expanding evidence on natural compounds that modulate MAPK- related signaling networks and reviews recent transcriptomic findings that have enhanced the identification of clinically relevant molecular targets. Additionally, MAP4K4 has been linked to tumor progression and metastasis, and poor clinical outcomes, indicating its potential as a therapeutic target for future clinical studies. The findings presented in this review suggest that combining transcriptomic evidence with molecular and pharmacological analyses could aid target prioritization and accelerate the development of targeted strategies for MAPK-driven malignancies.

A 93-year-old woman presented herself with subacute exertional dyspnea in our primary care setting. Imaging revealed a large pericardial cyst without echocardiographic evidence of hemodynamic compromise. Instead, findings were consistent with heart failure with preserved ejection fraction (HFpEF) in the context of hypertensive and valvular heart disease. Optimization of heart failure therapy, including initiation of an SGLT-2 inhibitor, led to clinical improvement. This case highlights the importance of integrating imaging findings into the overall clinical context in primary care.

Melanoma remains a highly lethal malignancy, often associated with limited therapeutic efficacy and substantial systemic toxicity caused by conventional chemotherapy. Triptolide (TP) exhibits potent antitumor activity, but its clinical application is limited by poor aqueous solubility and a narrow therapeutic window. In this study, folate-decorated Pluronic nanomicelles (TP-FPNPs) were developed to enhance TP delivery. The resulting spherical micelles, with an average diameter of 152 nm, exhibited an encapsulation efficiency of 79% and sustained drug release for up to 48 h. By targeting folate receptors (FRs), TP-FPNPs increased cellular uptake in B16F10 and reduced the IC₅₀ to 18.94 nm (2.08-fold decrease). Conversely, the IC₅₀ in HUVECs increased from 19.51 to 37.89 nm (1.94-fold), indicating reduced toxicity toward normal endothelial cells. Mechanistically, TP-FPNPs downregulated glutathione peroxidases (GPx), increased intracellular Reactive Oxygen Species (ROS) levels, and promoted apoptosis. In vivo, TP-FPNPs achieved a tumor inhibition rate of 89.6% with negligible toxicity, significantly outperforming free TP. These results suggest that TP-FPNPs are a promising targeted delivery system that improves the therapeutic index of TP for melanoma therapy.

Homeopathic medicines, including Arsenicum iodatum, have attracted increasing interest as potential adjunctive approaches in cancer research. However, the cellular mechanisms underlying their reported biological effects remain poorly understood. This study investigated the effects of homeopathic Arsenicum iodatum on apoptosis, cell cycle progression, and caspase activation in A549 human lung adenocarcinoma cells.

A549 cells were treated with Arsenicum iodatum potencies (6C, 12C, 30C, and 200C). Apoptosis and cell cycle distribution were assessed by flow cytometry, while Caspase-7 and Caspase-9 activities were determined using indirect ELISA to evaluate the involvement of the intrinsic apoptotic pathway.

All tested potencies increased apoptotic cell populations compared with the control groups. The most pronounced biological effects were observed at the 30C and 200C potencies. These higher potencies were also associated with increased Caspase-7 and Caspase-9 activities, suggesting activation of the intrinsic apoptotic pathway. Vehicle-treated cells exhibited only minimal changes, indicating that the observed effects were not attributable to the solvent alone.

Homeopathic Arsenicum iodatum induced measurable apoptosis-associated and cell cycle-related changes in A549 cells, accompanied by increased caspase activity. The strongest responses were observed at the 30C and 200C potencies. These findings suggest the involvement of intrinsic apoptotic signaling and warrant further mechanistic investigation. As this study represents an exploratory in vitro analysis, validation in additional experimental models and independent biological systems is required before broader conclusions can be drawn.

Breast spindle cell lesions (BrSCL) are rare pathologies encompassing a wide range of conditions, from benign reactive processes to aggressive malignancies. Their diverse and overlapping clinical, radiological and histological features pose significant diagnostic challenges. This study examines the clinical, radiological and histological characteristics of BrSCL to improve diagnostic accuracy and inform management strategies.

This retrospective, single-centre cohort study included all cases of BrSCL identified on core biopsy from 2008 to 2020, excluding fibroepithelial lesions and metaplastic cancers. It examined clinical presentations, imaging findings, formal excisional pathology and clinical outcomes.

Thirty cases were analysed, with 70% (n = 21) presenting due to breast symptoms and 30% (n = 9) detected through breast screening or incidentally. Eligible cases were histologically subdivided into atypical (ASCL) (n = 10) and bland (BSCL) (n = 20) spindle cell lesion groups. Following formal excision, 80% of ASCLs were malignant (sarcoma: n = 1; malignant phyllodes tumour: n = 3; metaplastic cancer: n = 4), whilst 20% (n = 2) were benign. Eleven BSCLs underwent excisional biopsy, with no malignancy found (benign: n = 10; no lesion: n = 1). Nine patients underwent radiological and clinical surveillance.

BrSCLs are rare and diagnostically complex entities. Lesions detected on core biopsy with features of ASCL carry a high risk of malignancy and should undergo surgical excision. In contrast, BSCL from core biopsy are frequently benign and those demonstrating low-risk imaging features and benign core biopsy findings may be considered for surveillance. A multidisciplinary approach is essential for optimising outcomes in this challenging and uncommon subset of breast pathology.