Search Results (971)

Background/Objectives: Combining chemotherapy with local magnetic hyperthermia (MHT) is promising because heating tumor tissue can increase cell damage, sensitize cells to cytostatic drugs, impair DNA repair, and change tumor microenvironment permeability. This creates conditions for enhancing the antitumor efficacy of chemotherapy while potentially reducing systemic toxicity. The aim of this study was to evaluate the efficacy of MHT with Zn_0.2Mn_0.8Fe₂O₄@OA nanoparticles alone and in combination with cisplatin in a Lewis lung carcinoma model. Methods: Four types of magnetic nanoparticles were synthesized and characterized: Fe₃O₄ and Zn_0.2Mn_0.8Fe₂O₄ coated with oleic acid (OA) or SiO₂-NH₂. Their physicochemical and magnetothermal properties, cytotoxicity, reactive oxygen species generation, and biodegradation in vivo were evaluated. Antitumor efficacy was studied in C57Bl/6 mice with LLC tumors after intratumoral administration of nanoparticles and two MHT sessions (100 kHz, 8 kA/m, 30 min). In combination therapy, ZnMn@OA and cisplatin at doses of 9 or 18 mg/kg were used. Results/Conclusions: Zn_0.2Mn_0.8Fe₂O₄@OA combined efficient heating, biodegradation, and the most pronounced effect among the MHT-alone groups, although MHT without chemotherapy did not provide sustained inhibition of tumor growth or a significant increase in survival. The combination of Zn_0.2Mn_0.8Fe₂O₄@OA-MHT with cisplatin 9 mg/kg produced the best therapeutic outcome: median survival increased significantly by two fold compared with the control group and by 1.8-fold compared with the chemotherapy-alone group at the comparable cisplatin dose. This regimen also stabilized body weight, reduced systemic toxicity, and restored RBC, HGB, and HCT parameters to the level of healthy animals by day 7 of the experiment. These data confirm the potential of MHT as a chemosensitizing approach that improves the efficacy and tolerability of cisplatin therapy. Full article

Background/Objectives: Glioblastoma (GBM) is the most lethal primary brain malignancy in adults, with a median overall survival of approximately 15 months. Temozolomide (TMZ) resistance develops in virtually all patients, and no second-line regimen has improved outcomes over the past two decades. The DNA methyltransferase inhibitor decitabine (DAC) has attracted interest as a chemosensitizer, but whether it directly reverses the TMZ-resistance transcriptome or operates through distinct, complementary mechanisms has not been tested at multi-omics resolution. Methods: We performed an integrative six-layer multi-omics analysis across five public GEO datasets (bulk RNA-seq, EPIC 850K methylation, and 21,676 single cells) re-purposed from studies conducted for unrelated aims, formally tested DAC-mediated reversal of the TMZ-resistance transcriptome across 11,707 genes, mapped pharmacogenomic targets with DGIdb v5, and built an exploratory, hypothesis-generating 11-gene prognostic model internally validated in TCGA-GBM (n = 166) and externally tested in the independent CPTAC-GBM cohort (n = 96). Results: DAC reprogrammed transcription across 1114–1882 differentially expressed genes per cohort and reactivated 146 direct epigenetic targets, identifying INPP5D/SHIP1 as the top-ranked direct epigenetic-reactivation target. Genome-wide reversal analysis across 11,707 co-detected genes showed a negligible effect (Spearman ρ = 0.073), but single-cell analysis revealed significant per-cell attenuation of MES-like and stem-like programs (Δ = −0.071 and −0.135, respectively; both p < 0.001). The 11-gene risk model achieved a Harrell’s C-index of 0.706 (apparent); after correcting for the two-stage gene selection with a full-pipeline bootstrap, the optimism-corrected C-index was 0.63, and external validation in an independent cohort (CPTAC-GBM, n = 96) showed only near-chance discrimination (C-index 0.55), indicating that the signature does not generalize and is exploratory. Pharmacogenomic mapping yielded 734 unique therapeutic agents (230 FDA-approved) across 69 druggable targets after excluding AR. Most of these agents are not GBM-directed, so this catalog-level mapping is hypothesis-generating rather than a set of therapeutic recommendations. Conclusions: DAC does not broadly reverse the TMZ-resistant transcriptome but acts through three complementary mechanisms: epigenetic reactivation of INPP5D/SHIP1, cancer-testis-antigen and type I interferon induction, and per-cell attenuation of mesenchymal–stem-like transcriptional intensity, supporting hypotheses for rationally designed DAC-based combination therapy in TMZ-resistant GBM. Full article

Therapeutic resistance remains a critical obstacle in rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma. Increasing evidence implicates redox adaptation in tumor survival and treatment failure. Here, we investigated the functional role and clinical relevance of catalase, a primary hydrogen peroxide-detoxifying enzyme, in modulating RMS therapeutic response. Integrated transcriptomic analyses revealed that while catalase is overall downregulated in RMS compared to healthy skeletal muscle, elevated expression strongly correlates with high-risk, metastatic disease and poor overall survival. In human RMS cell lines, catalase was detectable, and its pharmacological inhibition using 3-amino-1,2,4-triazole (3-ATA) promoted reactive oxygen species (ROS) accumulation, sensitizing cells to standard chemotherapeutics. Notably, robust catalase upregulation was observed in RMS cell models characterized by intrinsic and acquired radioresistance, with strong immunoreactivity validated on cell-block sections. Immunohistochemical validation across patient specimens revealed generally weak catalase expression in RMS tumors, whereas strong reactivity was observed in a secondary embryonal RMS (ERMS) arisen following chemoradiotherapy for nasopharyngeal carcinoma. Functionally, targeting catalase with 3-ATA restored both radio- and chemosensitivity in radioresistant RMS lines. Furthermore, co-targeting catalase and Akt using sub-toxic doses of 3-ATA and MK-2206 cooperatively enhanced oxidative stress-mediated cytotoxicity in resistant cells. Together, these findings identify catalase as a pivotal driver of adaptive radioresistance and establish dual catalase/Akt targeting as a promising pro-oxidant strategy to overcome radiotherapy resistance in RMS. Full article

Breast cancer (BC) is the most frequently diagnosed malignancy and generally the leading cause of cancer-related mortality among women worldwide. Molecular targeted therapies, including endocrine treatment for hormone-responsive tumors, anti-HER2 agents for HER2-positive tumors and PARP inhibitors (PARPis) for homologous recombination-deficient (HRD) tumors, have significantly improved patient outcomes, but several clinical challenges are still open. The development of acquired resistance strongly limits the long-term efficacy of current treatment strategies, underscoring the necessity to identify novel therapeutic approaches for breast cancer therapy. In this review, we summarize and discuss recently investigated natural compounds with anti-breast cancer activity, ranging from polyphenols, terpenoids, alkaloids, sulfur-containing compounds and the emerging plant-derived extracellular vesicles. We focus on their ability to induce DNA damage or oxidative stress, modulating the DNA damage response (DDR) and interfering with key oncogenic signaling pathways. We also discuss the potential of these compounds to enhance the efficacy of conventional therapies, thereby offering a promising role in overcoming clinical resistance. Despite clinical relevance remains under development and further studies are required; many of the natural compounds examined here appear to effectively target DDR signaling and oncogenic pathways, supporting their potential use in breast cancer therapy. Full article

Background and Objectives: Kaposi sarcoma (KS) is a rare angioproliferative malignancy driven by human herpesvirus-8 infection. Comparative real-world data on classic and AIDS-related KS from Mediterranean-endemic countries remain limited. Materials and Methods: We retrospectively analyzed 102 patients with histopathologically confirmed KS treated across five tertiary oncology centers in Turkey between January 2010 and December 2023. Demographic characteristics, clinical features, treatment patterns, and survival outcomes were compared between classic and AIDS-related KS subtypes. Results: Ninety-two patients (90.2%) had classic KS and ten (9.8%) had AIDS-related KS. The median age at diagnosis was significantly higher in the classic KS group (69 vs. 38.5 years; p < 0.001). Male sex predominated in both groups (classic KS: 76.1%; AIDS-related KS: 100%; p = 0.113). AIDS-related KS presented with more advanced disease at diagnosis, with 70% classified as poor-risk by ACTG-TIS criteria versus 9.8% Stage IV by Brambilla criteria in classic KS, and more frequent extracutaneous involvement (70% vs. 8.7%; p < 0.001). Paclitaxel was the most commonly used first-line agent in classic KS (42.9%), while pegylated liposomal doxorubicin predominated in AIDS-related KS (87.5%). Overall response rates were high and comparable between groups (90.7% vs. 88.9%). Median overall survival was significantly longer in classic KS (66.9 vs. 22.67 months; p = 0.012). Disease stage and lesion morphology were not significantly associated with survival in either group. Conclusions: Classic and AIDS-related KS differ substantially in clinical presentation and survival outcomes, yet demonstrate comparable chemosensitivity. Our findings in the AIDS-related Kaposi sarcoma group are preliminary and hypothesis-generating due to the small sample size, requiring confirmation in larger prospective cohorts. Full article

Colorectal cancer (CRC) remains a major cause of cancer-related mortality worldwide, largely due to the emergence of chemoresistance driven by metabolic adaptations. Among these alterations, lipid metabolic reprogramming has emerged as a critical determinant of tumor progression and therapeutic response. In particular, dysregulation of enzymes involved in phosphatidylcholine (PC) synthesis and remodeling, through the Kennedy pathway and the Lands cycle, has been associated with therapeutic resistance. Lysophosphatidylcholine acyltransferase 2 (LPCAT2), a key enzyme involved in PC remodeling, notably promotes lipid droplets (LD) accumulation in CRC cells and contributes to chemoresistance. In this context, natural compounds capable of modulating PC metabolism, such as the polyphenol resveratrol (RSV), may represent a relevant strategy to improve sensitivity to chemotherapies in chemoresistant colon tumor cells. In this study, RSV induced apoptosis and significantly reduced the proliferation of intrinsically resistant HT29 cells and SW620 cells engineered to overexpress LPCAT2. RSV also decreased the expression of key enzymes involved in the Kennedy pathway in chemoresistant CRC cell lines. These changes were accompanied by distinct time-dependent patterns of lipid droplet accumulation in the two cellular models. In addition, drug combination studies showed that RSV enhanced the response to 5-fluorouracil (5-FU), oxaliplatin (OXA) and the FOX regimen (5-FU + OXA, 1:1 ratio) with synergistic interactions for several dose combinations, together with favorable dose-reduction indices. Collectively, these in vitro findings indicate that RSV modulates PC-metabolism-related proteins and enhances chemotherapy sensitivity in resistant CRC models. Overall, our results identify RSV as a promising therapeutic strategy to target metabolic vulnerabilities associated with PC metabolism and overcome chemoresistance in CRC. Full article

Background/Objectives: PgRMC1 is a progesterone-binding protein often overexpressed in breast cancer, correlating with tumor progression and chemoresistance. Identifying predictive markers for neoadjuvant chemotherapy (NAC) response is crucial for guiding therapeutic decisions. This study examines PgRMC1 expression in breast cancer tissues and its correlation with clinicopathological characteristics and NAC response. Methods: PgRMC1 expression in normal and cancerous breast tissues was evaluated via immunohistochemistry (IHC). Expression of ER, PgR, HER2, AR, and PGRMC1 mRNA was determined by qPCR in 112 patients. A separate 44-patient neoadjuvant chemotherapy (NAC) cohort was assessed for intrinsic subtypes (pretreatment biopsies) alongside PgRMC1 IHC expression and pathological response (post-NAC surgical specimens). In vitro chemoresistance and qPCR analyses were performed in breast cancer cell lines following PgRMC1 overexpression or siRNA-mediated knockdown. Results: PgRMC1 expression was detected in breast cancer tissue, while no immunoreactivity was observed in normal breast tissue. PGRMC1 mRNA expression levels were significantly higher in luminal and HER2 subtypes. In the distinct cohort of patients treated with NAC, those with a poorer pathological response had significantly higher PgRMC1 expression than those with a good response. In vitro, forced overexpression of PgRMC1 in two breast cancer cell lines, MCF7 and MDA-MB-468, significantly reduced chemosensitivity. Overexpression of PgRMC1 modulated the expression of epithelial and differentiation markers, including CDH1, AR, KRT19, and GATA3. Conclusions: PgRMC1 may contribute to chemoresistance and serves as a candidate biomarker for assessing neoadjuvant chemotherapy sensitivity. Full article

Background: Diffuse large B-cell lymphoma (DLBCL) with TP53 abnormalities, corresponding to the LymphGen A53 molecular subtype, represents a biologically high-risk group associated with primary resistance to standard R-CHOP therapy. Epigenetic sensitization using hypomethylating agents may enhance chemosensitivity in this setting. We prospectively evaluated the clinical activity and safety of a molecularly adapted DAC-R-CHOP regimen in newly diagnosed A53-DLBCL. Methods: In this single-center prospective pilot cohort study, 70 consecutive patients with newly diagnosed DLBCL underwent targeted next-generation sequencing using a 60-gene panel with integrated copy number variation analysis. Six patients (8.5%) were classified as the A53 subtype. All patients received one cycle of standard R-CHOP. From cycle 2 onward, A53 patients received decitabine (10 mg/m² IV, days 1–5) prior to R-CHOP (DAC-R-CHOP), for a total of six cycles. The primary endpoint was complete metabolic response (CMR) according to Lugano 2014 criteria. Exact 95% confidence intervals (CI) were calculated. Results: The median age of the A53 cohort was 65 years. CMR was achieved in all six patients (100%; 95% CI, 54–100%). At a median follow-up of 6 months, all patients remained alive in confirmed CMR. Grade III–IV hematologic toxicity occurred in all cases. Febrile neutropenia developed in 100% of patients, requiring mandatory G-CSF support and anti-infective therapy; no treatment-related mortality or permanent dose reductions were observed. Two patients (33%) experienced gastrointestinal bleeding related to local tumor lysis, which was managed conservatively without protocol discontinuation. Conclusions: In this prospective molecularly stratified pilot cohort, integration of decitabine into front-line immunochemotherapy showed promising clinical activity in A53-DLBCL, albeit at the cost of substantial hematologic toxicity requiring intensive supportive care. Given the small sample size, short follow-up, and absence of a comparator arm, these findings should be considered hypothesis-generating and warrant validation in larger multicenter phase II studies with integrated translational biomarker analyses. Full article

Butyrophilin-like 9 (BTNL9), a member of the immunoglobulin superfamily containing a bZIP-like domain, has a poorly defined role in cancer. Here, we identify BTNL9 as a non-canonical transcriptional regulator and investigate its function in non-small cell lung cancer (NSCLC). Coiled-coil prediction, native PAGE, and co-immunoprecipitation demonstrated BTNL9 homodimerization via its bZIP-like region, while subcellular fractionation and immunofluorescence confirmed its presence in both the nucleus and cytoplasm. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis identified 9709 BTNL9-associated genomic regions, including sites proximal to transcription start sites, with enrichment of a cytosine-rich motif. Whether chromatin association reflects direct DNA binding or indirect co-regulatory interaction remains to be experimentally confirmed. Integrated transcriptomic and protein analyses revealed that BTNL9 overexpression represses genes involved in cell cycle progression and DNA replication while activating a subset of p53-associated pathways. Consistently, functional assays showed that increased BTNL9 expression induces cell cycle arrest, suppresses proliferation and clonogenicity, and inhibits tumor growth in xenograft models. In addition, cytotoxicity assays demonstrated enhanced sensitivity to bortezomib, with context-dependent effects on etoposide response. Analysis of public clinical datasets further showed that low BTNL9 expression is associated with advanced tumor stage, reduced remission rates, and poorer survival outcomes in NSCLC. These findings identify BTNL9 as a non-canonical tumor-suppressive transcriptional regulator with potential biomarker relevance in NSCLC. Full article

Background/Objectives: To date, the antineoplastic effect of cabozantinib in in vitro anaplastic thyroid cancer (ATC) cells has not yet been investigated. We aim to evaluate the antineoplastic and immunomodulatory effect of cabozantinib in both primary and continuous ATC cell cultures in vitro. Methods: The antineoplastic activity of cabozantinib was evaluated in ATC cell lines (8305C; CAL62) and in five different primary ATC cells obtained directly from patients. Results: Increasing concentrations of cabozantinib were tested showing a significant decrease in viability/proliferation and an increase in apoptosis in the treated cells vs. control. A scratch assay was also performed to evaluate the effect of cabozantinib on migration showing a significant inhibition of it vs. control. Moreover, we showed a decrease in the secretion of both CXCL10 and CCL2 (T-helper (Th)1 and (Th)2 chemokines) under the treatment with cabozantinib, thus suggesting an immunomodulatory effect of the drug. Conclusions: A personalized approach for each patient can be achieved by using primary human ATC cells obtained directly from the patient, since in vitro studies permit assessing the chemosensitivity of cells obtained from each subject. These results in our opinion are very promising for a future in vivo evaluation of cabozantinib in patients with ATC. Full article

Background: Triple-Negative Breast Cancer (TNBC) remains the most aggressive oncological challenge within the African continent, characterized by high molecular heterogeneity, early onset in African women, and the absence of hormonal receptors. Multi-drug resistance (MDR), driven by ATP-binding cassette (ABC) efflux pumps and supported by the persistence of cancer stem cells (CSCs) within the tumor microenvironment, significantly compromises clinical outcomes and traditional treatment efficacy. Objective: This systematic review evaluates the ethnobotanical relevance, phytochemical diversity, and toxicity of some medicinal plants from the African pharmacopoeia specifically utilized or investigated for their activity against the TNBC phenotype. Methods: Following PRISMA guidelines, a systematic search was executed across PubMed, ScienceDirect, Scopus, Web of Science, and AJOL. The study focuses on original research published between 2011 and 2026 utilizing TNBC-specific models (such as MDA-MB-231, BT-20, HCC1937, or 4T1) and analyses the growth habits, parts used, and traditional administration modes of the selected African plant species, distributed across Western, Central, Southern, and Eastern Africa. Following a rigorous multi-reviewer screening process, a final set of 52 primary articles representing 30 distinct genera and 22 botanical families was selected for qualitative and quantitative synthesis. Results: This review identifies plant species actively used or studied in Africa for their anti-TNBC potential, with the most representative botanical families being Asteraceae (13%), Fabaceae (7%), and Annonaceae (7%). These species are traditionally administered through various methods, including decoction, infusion, and mastication, utilizing diverse plant parts such as leaves, stem and root barks. Significant cytotoxic activities against TNBC cell lines (notably MDA-MB-231) were recorded, with IC₅₀ values as low as 5.10 ± 0.28 µg/mL for Catharanthus roseus and 13.56 µg/mL for Nauclea pobeguinii. Furthermore, species such as Vernonia amygdalina and Curcuma longa demonstrated a capacity to enhance the effectiveness of conventional chemotherapy like Doxorubicin, suggesting a strong potential for chemosensitization and therapeutic synergy in managing resistant breast cancer phenotypes. Conclusions: Standardized African phytomedicines represent a promising frontier in overcoming TNBC chemoresistance. However, the lack of clinical trials and end-to-end drug development infrastructure on the continent remains a significant barrier. Transitioning to nano-formulated delivery systems and establishing regional drug discovery hubs under the ethical framework of the Nagoya Protocol are essential steps toward developing precise and equitable oncology treatments from Africa’s rich biodiversity. Full article

Background/Objectives: Docetaxel is a frontline chemotherapeutic agent for breast cancer; however, therapeutic resistance remains a major clinical challenge. Emerging evidence suggests that chemotherapy-induced adaptive phosphorylation events can promote survival signaling and contribute to drug resistance. However, the phosphoproteomic mechanisms underlying docetaxel-induced adaptive responses remain poorly characterized. Methods: We performed integrated quantitative proteomic and phosphoproteomic profiling in breast cancer cells following docetaxel exposure. Candidate kinases associated with phosphorylation remodeling were identified and validated using TCGA-BRCA and CPTAC clinical datasets. The functional significance of PAK4 phosphorylation was validated using phosphomimetic and phospho-deficient mutants, pharmacological inhibition, and assessment of microtubule stabilization. Results: Integrated phosphoproteomic analysis revealed extensive phosphorylation remodeling following docetaxel treatment and identified PAK4 as a candidate kinase associated with the adaptive response. Analysis of the CPTAC phosphoproteomic dataset showed that phosphorylation of PAK4 at S474 was elevated in breast cancer tissues, increased with tumor stage, and was associated with poorer overall survival. In breast cancer cells, docetaxel induced phosphorylation of PAK4 at S474 without altering total PAK4 expression. Functionally, phosphomimetic PAK4 (S474D) reduced docetaxel sensitivity, whereas phospho-deficient PAK4 (S474A) enhanced drug sensitivity. Pharmacological inhibition of PAK4 using LCH-7749944 significantly enhanced the inhibitory effect of docetaxel on cell viability and increased apoptosis in breast cancer cells. Mechanistically, PAK4 inhibition enhanced docetaxel-induced microtubule stabilization, as evidenced by increased α-tubulin acetylation and accumulation of stabilized microtubule structures. Conclusions: Our study demonstrates that docetaxel induces global phosphorylation network reprogramming in breast cancer cells and identifies PAK4 S474 phosphorylation as a key determinant of docetaxel sensitivity. Inhibition of PAK4 enhances microtubule stabilization and improves the efficacy of docetaxel, providing a potential combinatorial strategy to overcome taxane resistance. Full article

Background/Objectives: Standard treatment for ovarian cancer includes surgery and chemotherapy, either as primary “debulking” surgery followed by adjuvant chemotherapy or neoadjuvant chemotherapy followed by interval debulking surgery. The degree of surgical resection correlates with overall survival, with “suboptimal debulking” (visible remaining cancer) being a poor prognostic variable. TGF-β pathway activation is associated with ovarian cancers that cannot be optimally debulked. To test the role of this pathway in ovarian cancer biology, modulation of the pathway was performed in in vitro and in vivo ovarian cancer model systems. Methods: A small molecule TGF-β receptor 1 (TGFBR1) kinase inhibitor, LY2157299, was used to test the in vitro cellular adhesion, proliferation, migration and invasive ability of ovarian cancer cells in culture. A TGF-β responsive reporter construct was used to determine the role of TGF-β pathway in those interactions. To test the effects of TGF-β inhibition in vivo, TGFBR1 and TGFBR2 CRISPR knockout cells were generated and examined for growth and sensitivity to chemotherapy. Results: For ovarian cancer cells responsive to exogenous TGF-β1 treatment, LY2157299-mediated the TGF-β pathway inhibition decreased cell migration and invasion, as well as mesothelial cell to cancer cell adhesion, proliferation, and migration. TGFBR1 and TGFBR2 CRISPR knockout cells showed decreased proliferation baseline or when treated with TGF-β and LY2157299. TGFBR2 CRISPR cells also showed increased sensitivity to cisplatin, with a significant decrease in tumor weight in vivo. Conclusions: TGF-β pathway inhibition successfully targeted many of the cancer cell behaviors that could contribute to suboptimally debulked patients and showed an additive anti-tumor effect in conjunction with cisplatin. LY2157299 treatment is clinically limited due to solubility, but other TGF-β inhibitors could be highly efficacious treatment options. Full article

Most studies on circular mineral-based materials report short-term mechanical properties without providing predictive frameworks that link chemical degradation to long-term mechanical performance. This study develops and validates a leaching-index-driven chemo-mechanical framework for predicting the degradation of a natural hydraulic lime (NHL)–pozzolan mortar exposed to sulfuric acid. A normalized ionic-release index was used to drive all parameters of a trilinear continuum damage mechanics (CDM) model, enabling the prediction of complete stress–strain responses from leachate chemistry alone. The framework was calibrated using an extensive experimental dataset comprising accelerated acidic exposure at pH 1.5, 2.0, and 3.0 for durations up to 6000 h. Iron release was identified as the most suitable degradation indicator based on its monotonic evolution and strong correlation with mechanical deterioration. Power-law relationships linking the normalized leaching index to elastic modulus, peak strength, transition strain, and post-peak energy were established and validated against independent exposure groups, yielding prediction errors generally below 20%. Validation was performed against three independent blind exposure groups withheld from calibration, yielding mean deviations of approximately 18% in the elastic modulus and 13% in the peak strength, so that the quantitative validation rests on this limited three-group set, whereas the extension to circular mineral binders is presented only on a prospective, non-validated basis. A kinetic sub-model was further introduced to relate exposure conditions to the leaching index, enabling a complete predictive chain from environmental exposure to mechanical response and service-life estimation. Sensitivity analysis showed that post-peak energy dissipation degrades approximately 1.3–1.5 times faster than stiffness and strength, indicating that ductility-related parameters govern long-term reliability. The methodological architecture is further discussed, on a prospective and non-validated basis, in relation to circular mineral binders relevant to Baltic industrial and municipal by-product streams, including municipal-waste bottom ash, slag, fly ash, and recycled glass. Although experimental validation is limited to the NHL–pozzolan system, the proposed framework provides a physically grounded and data-efficient pathway for durability assessment and future durability-oriented design of circular mineral binders in the Baltic region. Full article

Background/Objectives: The search for new drugs which could suppress drug resistance development in tumor cells is extremely important for clinical practice. Inhibitors of cell signaling pathways that control cell proliferation and death can be used in complex therapy of malignant tumors. Methods: Cell cycle assay using flow cytometry, In Vitro Cell Viability Assay Cell chemosensitivity was analyzed by direct cell counting after trypan blue staining using a microscope. Results: In the present work, we have shown that the combined action of doxorubicin and XMU-MP-1, the MST1/2 kinase inhibitor in the Hippo signaling pathway, prevents drug resistance development in Namalwa cells, significantly slows drug resistance development in K562 cells, and restores the sensitivity of resistant K562 cells to doxorubicin. We have shown that compared to monotherapy, the combination of doxorubicin and XMU-MP-1 causes a significant decrease in cell division rate and cell death in hematological tumor cells such as Burkitt’s lymphoma Namalwa and chronic myeloid leukemia (CML) K562 cells. Cell cycle analysis revealed that the combined action of XMU-MP-1 and doxorubicin caused a catastrophic cell cycle disruption and a significant increase in the number of cells undergoing apoptosis containing fragmented DNA. Conclusions: XMU-MP-1 can be potentially used in combination with anthracyclines for the treatment of hematological malignancies and, in particular, drug-resistant cancer types. Full article