Porphyrins play an extremely important role in both photodynamic (PDT) and sonodynamic therapy (SDT). These techniques, which have a lot in common, are largely based on the interaction between the sensitizer and light or ultrasounds (US), respectively, resulting in the formation of reactive oxygen species (ROS) that have the ability to destroy target cells. SDT requires the use of an appropriate frequency of US waves that are able to excite the chemical compound used. In this study, five porphyrin complexes were used: free-base meso-tetra(N-methyl-pyridinium-4-yl)porphyrin (TMPyP) and its transition metal complexes containing zinc(II), palladium(II), copper(II), and chloride-iron(II). The sonodynamic activity of these compounds was studied in vitro. The obtained results confirm the significant relationship between the chemical structure of the macrocycle and its stability and ability to generate ROS. The highest efficiency in ROS generation and high stability were demonstrated by non-metalated compound and its complex with zinc(II), while complex with copper(II), although less stable, were equally effective in terms of ROS production. Antibacterial activity tests showed the unique properties of the tested compounds, including a reduction in the number of both planktonic and biofilm antibiotic-resistant microorganisms above 5 log, which is rare among sonosensitizers.

HER2-negative breast cancers, particularly triple-negative (TNBC) and luminal B (LB) variants, require novel biomarkers for rapid diagnostic confirmation due to their aggressive nature and radiological challenges. This pilot study evaluated whether subset-specific CCR2 expression on peripheral monocytes could serve as a high-fidelity liquid biopsy biomarker. We analyzed monocyte subsets-classical (CD14++CD16-), intermediate (CD14++CD16+), and non-classical (CD14 + CD16++)-via flow cytometry in 60 HER2-negative breast cancer patients and 30 healthy controls. Results identified a significant systemic remodeling of the monocyte lineage. A dramatic, nearly four-fold increase in CCR2 expression was observed within the non-classical subset (18.32% vs. 4.29% in controls; p < 0.001). ROC analysis demonstrated that the percentage of CCR2+ non-classical monocytes distinguished cancer patients with 96% sensitivity and 96% specificity. Notably, this immunophenotypic shift was independent of tumor stage, grade, and systemic inflammatory markers. These findings suggest that 'inducible' non-classical monocytes could serve as a specific hallmark of early-stage HER2-negative breast cancer, potentially providing a minimally invasive tool for early diagnosis.

Senescence-associated secretory phenotype (SASP) signaling, along with key markers such as P16^INK4a/CDKN2A and LMNB1, has not been systematically studied in circulating lymphocyte subsets in head and neck squamous cell carcinoma (HNSCC). This study aimed to evaluate SASP-related genes and senescence markers in peripheral CD4⁺, CD8⁺, and CD19⁺ cells and assess their clinical relevance. Expression of IL-6, IL-1β, TNFα, CXCL1, P16^INK4a/CDKN2A, and LMNB1 was measured by RT-qPCR in sorted lymphocytes from 58 HNSCC patients at baseline, 31 post-treatment, and 13 controls. Statistical analyses included nonparametric tests, correlation analyses, and survival models (Kaplan–Meier, Cox regression). In the results, LMNB1 was significantly upregulated in all lymphocyte subsets of HNSCC patients. IL-6, CXCL1, and IL-1β were elevated in CD4⁺ T cells. A coordinated co-expression network involving IL-6, CXCL1, IL-1β, P16^INK4a/CDKN2A, and LMNB1 was observed. Clinically, IL-6 in CD8⁺ T cells was associated with higher nodal stage and worse survival, while CXCL1 in CD19⁺ B cells independently predicted survival. No differences were found between pre- and post-treatment samples. Circulating lymphocytes in HNSCC display coordinated expression of selected senescence-associated genes, with IL-6 and CXCL1 as candidate prognostic biomarkers linked to tumor progression that warrant further validation.

Despite the development of new drugs, chemoresistance constitutes a major obstacle in cancer treatment. To investigate mechanisms of resistance and potential therapeutic targets, we developed doxorubicin-resistant models of HER2− (D2F2/Dox) and HER2+ (D2F2E2/Dox) breast cancer cells. Compared with parental cells, the D2F2/Dox and D2F2E2/Dox differed in morphology, increased migratory potential, elevated levels of the transcription factor signal transducer and activator of transcription 3 (Stat3), and a lower proliferation rate in D2F2E2/Dox. Moreover, D2F2/Dox and D2F2E2/Dox differed in the expression profiles of genes related to cell stemness, apoptosis, and drug efflux. Stat3 gene silencing in both doxorubicin-resistant cell types reversed the expression profiles of some genes (different in each resistant cell line), and decreased migratory potential was observed only in D2F2 cells. These data indicate that the acquired doxorubicin resistance was associated with Stat3 status; however, HER2− and HER2+ breast cancer cells did not indicate the same mechanism of chemoresistance acquisition. Importantly, Stat3 silencing did not substantially restore doxorubicin sensitivity, suggesting that effective therapy may require simultaneous targeting of multiple pathways. Furthermore, we demonstrated that siStat3 therapeutics could be selectively delivered to HER2+ cancer cells using H2.1MS1:MS2KN silk spheres, indicating their potential for targeted drug delivery in vivo.