Polyphenols are a complex class of plant secondary metabolites that exert numerous beneficial effects on human health. The content of individual polyphenolic compounds varies considerably among plant species. Over the past few decades, polyphenols have attracted increasing interest because of their antioxidant and antimicrobial properties. They have also demonstrated beneficial effects in the prevention and treatment of various diseases, including cardiovascular and nervous system disorders, as well as different types of neoplasms. Because polyphenols have been shown to regulate plasma lipid levels and exhibit neuroprotective potential, they have gained attention as possible therapeutic and prophylactic agents for stroke, a neurological condition with a strong cardiovascular component. Quercetin is one of the most extensively studied plant-derived compounds in this context. A growing body of preclinical evidence suggests that it may contribute to stroke prevention and significantly support post-stroke recovery. This review compiles findings from in vitro studies, animal models, and clinical trials and presents the current state of knowledge regarding the biochemical and molecular mechanisms through which quercetin protects against cerebral ischemia.

Chronic myeloid leukemia (CML) is driven by constitutive BCR-ABL1 activity and remains clinically challenging due to disease persistence and resistance to tyrosine kinase inhibitors (TKIs). SIRT1, a NAD⁺-dependent deacetylase, has been implicated in leukemic cell survival and chemoresistance through negative regulation of p53. In this study, we evaluated the antileukemic effects of the Sechium hybrid H387 extract and its impact on the SIRT1-p53 signaling axis in K562 CML cells. Cell proliferation was assessed using a crystal violet assay, while gene and protein expression were analyzed by RT-qPCR, immunofluorescence, and flow cytometry. Apoptosis was determined by Annexin V/7-AAD staining. The extract significantly inhibited K562 cell proliferation and downregulated SIRT1 expression, reducing its nuclear localization. These effects were associated with increased p53 acetylation at lysine 382 (Ac-K382-p53) and enhanced apoptosis. Notably, a higher percentage of apoptotic cells was observed following extract treatment than with imatinib under the experimental conditions used, although the two agents have distinct mechanisms of action. These findings suggest that the antileukemic activity of Sechium hybrid H387 extract is associated with modulation of the SIRT1-p53 axis and induction of apoptosis in K562 cells.

The development of nanoparticle (NP)-based drug delivery systems that combine passive tumor targeting, physiological stability, and therapeutic efficacy remains a key challenge in cancer nanomedicine. Here, we report a pH-responsive peptide-functionalized poly(lactic-co-glycolic acid) (PLGA) NP system designed for cancer targeting. The PLGA core is coated with a short glutamic acid-lysine-histidine-phenylalanine x3 (EKHFFF) peptide shell, enabling tunable surface charge modulation around its isoelectric point and promoting environmental responsiveness. Physicochemical characterization confirms spherical NPs (~70-75 nm) with good colloidal stability, serum compatibility, and ion-dependent stability in physiological conditions. The peptide coating also provides pH-dependent modulation of the zeta potential. Evaluation of the NPs in ovarian cancer (OvCA) models, including immortalized and patient-derived cell lines (PDCLs), demonstrates efficient uptake across OvCA cell lines, with significantly enhanced internalization in PDCLs compared to immortalized cells. The EKHFFF nanoparticle (EKHFFF NP) induced minimal reactive oxygen species and nitric oxide production in macrophages, indicating low immunogenicity and favorable biocompatibility. Upon platinum loading (EKHFFF-Pt NP), the system exhibits potent cytotoxicity in both platinum-sensitive and platinum-resistant OvCA cell lines, outperforming carboplatin and showing comparable or improved efficacy relative to cisplatin in several cell lines. In vivo studies further demonstrate preferential tumor accumulation, sustained intratumoral retention, and measurable systemic circulation with a half-life of approximately 35 min.

Chlorogenic acid (CGA) exhibits anticancer activity in colorectal cancer (CRC), but its clinical application is limited by low lipophilicity. To improve its physicochemical properties, four CGA esters (methyl, ethyl, n-propyl, and n-butyl chlorogenates) were synthesized and evaluated. Physicochemical properties were characterized in silico, and their biological activity was assessed in SW480, HT-29, and non-tumoral NCM460 cell lines using viability assays and flow cytometry. Molecular docking studies were performed to investigate the interactions of CGA and its esters with proteins involved in cell-proliferation-related signaling pathways. In silico analysis showed a progressive increase in LogP values across ester derivatives. All esters complied with Lipinski's rule of five, whereas none met Veber's rule due to their predicted topological polar surface area (TPSA) values. The esters induced dose- and time-dependent reductions in cell viability, with n-butyl chlorogenate exhibiting the strongest cytotoxic activity and a significantly lower IC₅₀ value within the tested concentration range. This derivative showed preferential cytotoxic activity toward SW480 cells while exhibiting only limited effects in non-tumoral NCM460 cells. In addition, n-butyl chlorogenate induced changes in mitochondrial oxidative status and phosphatidylserine externalization, consistent with apoptosis-associated cellular changes. Overall, these findings demonstrate that esterification modifies the physicochemical profile of CGA ester derivatives and is associated with enhanced cytotoxic activity. Increased lipophilicity was associated with enhanced cytotoxic activity, supporting further optimization of these compounds for CRC research.

Pyridopyrimidine is an important heterocyclic scaffold widely explored in anticancer drug discovery. Its structural similarity to purine enables effective interaction with various biological targets, mainly kinases involved in cancer progression. This manuscript presents recent developments reported between 2021 and 2026, focusing on the biological evaluation, and structure-activity relationships of pyridopyrimidine derivatives. Many of these synthesized compounds act as inhibitors of key targets such as EGFR, CDK4/6, and the PI3K/mTOR pathway, which are closely associated with tumor growth, survival, and resistance mechanisms. Other targets such as ATR and PIM are also explored. Recent studies show that structural modifications, including substitution on the core ring and hybridization with pharmacologically active moieties like triazoles and thiazolidinediones, significantly improve anticancer activity. Several derivatives have demonstrated strong antiproliferative effects against different cancer cell lines and are capable of inducing apoptosis and cell cycle arrest. In addition, molecular docking and other computational studies support their binding efficiency and help explain their mechanisms of action. There is also increasing interest in the development of dual-target or multi-target inhibitors to overcome drug resistance and enhance therapeutic effectiveness. Overall, pyridopyrimidine- and pyridopyrimidinones-based compounds continue to show great promise as potential anticancer agents. Further research combining synthetic chemistry, biological studies, and computational approaches may lead to the development of more effective and safer drugs in the future.

To investigate the rate and predictors of recurrence at second-look ureterorenoscopy (URS) and to assess the adequate timeframe for second-look URS in upper tract urothelial carcinoma (UTUC).

This multicenter retrospective study included 179 patients who underwent endoscopic kidney-sparing surgery (KSS) and second-look URS for non-invasive UTUC between 2004 and 2017. We performed logistic and Cox proportional hazard regression analyses to investigate the association between clinical parameters and second-look recurrence, recurrence-free survival (RFS), and cancer-specific mortality. The optimal duration to second-look URS was extrapolated using restricted cubic splines.

Overall, 66 (36.9%) patients experienced recurrence at second-look URS. After second-look URS, further recurrence was observed in 87 (48.6%) patients during a median follow-up of 12 months. Female gender (OR [odds ratio] 2.3, 95% CI [confidence interval] 1.1-4.7, p = 0.026) and tumor size > 1 cm (OR 3.3, 95% CI 1.2-9.5, p = 0.027) were independently associated with recurrence at second look. Second-look recurrence was a strong prognostic factor for RFS (HR 5.0, 95% CI 3.1-8.0, p < 0.001). Second-look URS between 5 and 12 weeks after initial endoscopic laser ablation was an independent favorable factor for RFS (HR 0.5, 95% CI 0.3-0.9, p = 0.014).

Early recurrence at second-look URS appears to be one of the strongest predictive factors for RFS in patients undergoing endoscopic KSS. Our results suggest that second-look URS performed within 5 to 12 weeks is associated with a lower probability of further disease recurrence. Given that this interval was derived and tested in the same cohort, this finding should be regarded as hypothesis-generating and requires external validation before being adopted as a clinical standard.

Introduction: Cutaneous adnexal tumours are a heterogeneous group of tumours arising from the adnexal structures of the skin. These include follicular, eccrine, apocrine, and sebaceous lineages. These entities display a wide morphological spectrum with overlapping histopathological features, posing significant diagnostic challenges. This study aims to provide a detailed analysis of these neoplasms. Materials and Methods: We conducted a retrospective observational study including patients with primary cutaneous adnexal tumours diagnosed in excisional specimens at our centre between 2018 and 2025. Results: A total of 82 primary cutaneous adnexal tumours were analysed in patients aged 24-90 years. A female predominance was observed (62.19%), with a mean age of 56 years among female patients and 60 years among male patients. The head and neck region was the most frequently affected site (70.73%), followed by the upper limb, thorax, and lower limb. Sweat gland tumours markedly outnumbered follicular tumours (79.27% vs. 20.73%), with hidrocystomas and spiradenomas representing the most common benign lesions. Most tumours were benign (91.46%), while atypical spiradenoma (3.66%) and malignant tumours such as eccrine porocarcinoma, trichilemmal carcinoma, and basal cell carcinoma arising in association with trichoblastoma (4.88%) were rare but clinically significant findings. Surgical specimen volumes varied significantly by anatomical site, with scalp and limb lesions reaching the largest dimensions. Margin status differed according to biological behaviour, with malignant tumours showing greater proportion of close or infiltrated margins, while margins were non-assessable in all three atypical cases. Immunohistochemical evaluation supported diagnostic confirmation in atypical and malignant cases. Conclusions: Our findings highlight the broad clinical and morphological spectrum of cutaneous adnexal tumours and contribute data from an Eastern European cohort. This study adds regional data to the limited literature on the clinicopathological distribution of cutaneous adnexal tumours and emphasises rare, atypical, and malignant diagnostic scenarios.

Background/Objectives: Evidence regarding associations between local therapy before an indexed systemic regimen and subsequent outcomes in advanced soft tissue sarcoma (STS) remains limited. We evaluated outcomes within four regimen-defined cohorts and explored associations with prior local-therapy history. Methods: This retrospective cohort included 75 patients with recurrent or metastatic STS who contributed 155 treatment episodes: doxorubicin (n = 44), trabectedin (n = 31), pazopanib (n = 42), and eribulin (n = 38). Progression-free survival (PFS) and overall survival (OS) were measured from initiation of the indexed regimen. Surgery, local ablative therapy, and radiation therapy were assessed separately and in combined categories. Post hoc analyses were restricted to leiomyosarcoma. Results: Median PFS was 3.4, 3.1, 5.1, and 3.9 months, respectively. PFS was longer with any local therapy and surgery and/or ablation in the trabectedin cohort (p = 0.0342 and p = 0.0111) and with surgery and/or ablation in the eribulin cohort (p = 0.0352). Longer indexed-regimen OS was observed in surgery-containing categories in the doxorubicin and eribulin cohorts. In selected multivariable models, local therapy was associated with OS in doxorubicin- and eribulin-treated episodes and with PFS in eribulin-treated episodes. Leiomyosarcoma-restricted analyses did not consistently reproduce the full-cohort findings. Conclusions: Prior local-therapy history was associated with PFS or OS in selected within-cohort analyses. The associations may reflect local-treatment effects, differences among selected patients, or both; however, the study cannot distinguish these contributions. No between-regimen differences were formally tested. These findings support individualized multidisciplinary assessment and external validation.

MGN-3 (Biobran), a denatured hemicellulose compound derived from rice bran, possesses potent immunomodulatory and antitumor activity; however, its clinical application is constrained by non-specific tissue distribution, rapid systemic elimination, and poor cellular uptake. To overcome these pharmacological limitations, we engineered MGN-3-loaded lipid nanoparticles (MGN-3.LNPs) formulated with bioactive cinnamon and avocado oils to optimize targeted drug delivery against solid carcinoma. Mice bearing subcutaneous Ehrlich Ascites Carcinoma (EAC) solid tumors received free MGN-3, plain lipid nanoparticles (plain LNPs), or MGN-3.LNPs three times weekly from day 8 to day 26 post-inoculation. The administration of MGN-3.LNPs achieved superior tumor volume suppression (95.00%) compared to free MGN-3 (69.00%) and plain LNPs (63.00%) (p < 0.0001). Mechanistically, MGN-3.LNPs effectively inhibited cancer cell proliferation by suppressing Ki-67 expression while promoting expression shifts that strongly suggest the engagement of mitochondrial-mediated apoptotic signaling, including upregulation of tumor protein p53, Caspase-3, Caspase-9, poly(ADP-ribose) polymerase (PARP), and cytosolic cytochrome c (Cyt c), alongside an elevated Bax/Bcl-2 ratio and reduced 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. Flow cytometric analysis confirmed that MGN-3.LNPs induced marked G0/G1 cell cycle arrest and promoted sub-G1 apoptotic cell accumulation, which was corroborated by Annexin V/propidium iodide (Annexin V/PI) staining and semiquantitative histopathological evaluation. Furthermore, MGN-3.LNPs downregulated the gene expression of proinflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) while restoring redox homeostasis in tumor tissues. Overall, lipidic nanoencapsulation significantly enhances the therapeutic efficacy of MGN-3 against solid tumors through superior nanoscale tissue penetration, prolonged retention, and synergistic lipid-drug bioactivity.

Cancer cachexia is a multifactorial metabolic syndrome characterized by progressive skeletal muscle loss, affecting 30-60% of patients with advanced renal cell carcinoma (RCC). It significantly impacts treatment tolerance, quality of life, and prognosis, yet its diagnosis and management remain challenging due to fragmented RCC-specific evidence, particularly in the era of immune checkpoint inhibitor (ICI)-based therapy. The pathogenesis involves persistent systemic inflammation, metabolic reprogramming, and tumor-host interactions. The IL-6/STAT3 and TNF-α/NF-κB pathways are central to muscle catabolism, while tumor-derived mediators such as GDF15 and PTHrP, along with mitochondrial dysfunction, further drive cachexia progression. For prognostic assessment, CT-derived skeletal muscle mass evaluation combined with systemic inflammatory and nutritional biomarkers-including neutrophil-to-lymphocyte ratio (NLR), modified Glasgow Prognostic Score (mGPS), prognostic nutritional index (PNI), and cachexia index (CXI)-has improved risk stratification in advanced RCC. Preclinical and emerging clinical data suggest that targeted therapies may partially attenuate cachexia by modulating inflammatory signaling, while multimodal interventions integrating nutritional support and exercise rehabilitation remain the cornerstone of management. Novel strategies, such as inhibition of the GDF15/GFRAL axis, are under active investigation. Future research should prioritize identification of early biomarkers, standardization of cachexia assessment, and prospective evaluation of cachexia-directed interventions in the immunotherapy era. Integrating cachexia assessment into routine practice may ultimately enable personalized treatment and improve long-term outcomes for patients with advanced RCC.