Search Results (50,638)

Oxidative stress in the tumor microenvironment, which is its own intrinsic property, is frequently utilized to deal with the drug-targeting issue in the nanoparticle drug delivery system. For this purpose, reactive oxygen species (ROS)-sensitive nanoparticles encapsulating doxorubicin (DOX) and chlorin e6 (Ce6) were synthesized for treatment of MDA-MB-231 breast cancer cells. Hyaluronic acid (HA) with a reductive end was conjugated with methoxy poly(ethylene glycol) (PEG) using thioketal diamine (ThdNH₂) linkage (HA-b-PEG copolymer). Then, Ce6 were conjugated to the carboxylic acid group of HA via ThdNH₂ (HA(Ce6)-b-PEG copolymer). DOX was physically incorporated to make DOX-incorporated HA(Ce6)-b-PEG copolymer nanoparticles (DOX-NP). HA(Ce6)-b-PEG copolymer nanoparticles (empty NP) and DOX-NP have a tiny particle size, less than 200 nm, with spherical morphology. They were responsively disintegrated according to the hydrogen peroxide (H₂O₂) concentration, then the release rate of Ce6 or DOX was accelerated, indicating that empty NP and DOX-NP have ROS sensitivity. DOX-resistant MDA-MB-231 cells were prepared by continuous treatment of DOX for three months. DOX-NP were efficiently internalized into the cells while intra-cellular delivery of DOX itself was inhibited. DOX-NP has higher anticancer activity against DOX-resistant MDA-MB-231 cells than that of DOX itself since cells were resistant to DOX itself. Under light irradiation, DOX-NP significantly decreased the viability of DOX-resistant MDA-MB-231 cells while DOX itself did not properly affect cell viability. Empty NP also efficiently inhibited cell viability rather than that of Ce6 itself while both of them did not affect the cell viability in the absence of light irradiation. Furthermore, empty NP showed higher ROS generation than that of Ce6 itself. DOX-NP more efficiently induced apoptosis/necrosis than DOX itself. In DOX-resistant MDA-MB-231 cell-bearing mice, DOX-NP was efficiently delivered to tumor tissue. DOX-NP greatly inhibited the growth of tumors under light irradiation, more than that of DOX itself or empty NP. In conclusion, DOX-NP showed promising antitumor activity against DOX-resistant MDA-MB-231 cells. Full article

Background/Objectives: Moderately hypofractionated radiotherapy (MHRT) may shorten treatment duration for cervical cancer but raises concerns regarding toxicity due to substantial interfractional pelvic organ motion. This prospective study evaluated the feasibility, workflow efficiency, dosimetric benefits, and acute toxicities of daily online adaptive radiotherapy (oART)-guided MHRT. Methods: Thirty patients with FIGO 2018 stage IB1–IIB or IIIC1 cervical squamous cell carcinoma receiving definitive chemoradiotherapy were prospectively included between September 2023 and April 2024 (NCT05994300). All patients underwent daily oART, receiving 43.35 Gy in 17 fractions to the pelvic target volume, with a simultaneous integrated boost to 54.40 Gy in 17 fractions for involved lymph nodes. The adaptive workflow consisted of iterative cone-beam computed tomography acquisition, artificial intelligence-assisted contouring, physician review, plan adaptation, and treatment verification. Workflow efficiency, plan selection, target coverage, organ-at-risk (OAR) sparing, treatment completion, early tumor response and acute toxicity were prospectively assessed. Results: A total of 510 adaptive fractions were delivered. The first-attempt adaptation success rate was 99.0%, and adapted plans were selected in 99.4% of fractions. The mean adaptive workflow and total treatment times were 17.3 and 23.3 min per fraction, respectively. Compared with scheduled plans, adapted plans significantly improved target coverage, with V_100% increasing by 7.26% for the planning target volume of the uterus and 8.79% for planning target volume of the cervix (both p < 0.001), while significantly reducing doses to the bladder, rectum, small bowel, bone marrow, and femoral heads. All patients achieved complete clinical response at 3 months. Acute toxicity was generally manageable; Grade ≥ 3 gastrointestinal, genitourinary, and hematologic toxicities occurred in 10%, 0%, and 40% of patients, respectively, including one Grade 4 neutropenia event, and no treatment interruptions. Conclusions: Daily oART-guided MHRT was feasible and efficient, providing improved target coverage and reduced OAR doses compared with scheduled plans. Acute toxicity was acceptable. These findings provide early prospective evidence supporting the feasibility of this treatment strategy and warrant further validation in larger prospective studies with longer follow-up. Full article

Background/Objectives: This exploratory post hoc analysis evaluated clinical and biomarker-defined treatment effects and accumulated nanvuranlat exposure in advanced biliary tract cancer (BTC). Methods: BICR-assessed progression-free survival (PFS) and overall survival (OS) were analyzed in the randomized Phase 2 full analysis set of 104 patients (nanvuranlat, n = 69; placebo, n = 35). Formal treatment-by-subgroup interaction tests assessed prior primary tumor resection status, LAT1 expression, and anatomical BTC subtype, evaluated both as a four-category variable and as pooled IHC/EHC/GBC versus AVC. Accumulated-exposure analyses pooled Phase 1 and Phase 2 data and were descriptive. Results: Median PFS was 46 versus 43 days (HR, 0.557; 95% CI, 0.344–0.903), and median OS was 155 versus 144 days (HR, 0.875; 95% CI, 0.551–1.390). Interaction tests were nominally significant for resection status with OS (p = 0.028) and for the four-category BTC-subtype variable with PFS (global p = 0.035), but not for LAT1 expression (PFS, p = 0.157; OS, p = 0.586) or pooled IHC/EHC/GBC versus AVC (PFS, p = 0.511; OS, p = 0.208). The binary and four-category subtype analyses addressed different hypotheses and were not considered contradictory. Higher accumulated-exposure quartiles showed numerically longer survival, but these analyses were susceptible to immortal-time bias, reverse causation, and time-dependent confounding. Conclusions: Nanvuranlat was associated with a lower hazard of progression or death than placebo, whereas the OS estimate was less conclusive. The subgroup and exposure findings remain exploratory but support prospective evaluation of resection status, anatomical subtype, and LAT1 expression. Full article

Gastric cancer (GC) remains a major global health challenge, ranking among the most lethal malignancies due to late diagnosis, high tumor heterogeneity, and limited treatment efficacy. The search for safer, nutritionally based adjuncts to conventional therapies is therefore a research priority. Donkey milk (DM), traditionally used as a hypoallergenic substitute for infants, is emerging as a functional food with remarkable bioactivity. Its composition closely resembles human milk, with high levels of bioactive proteins, a favorable polyunsaturated lipid profile, antioxidant vitamins, and immune-supportive minerals. Despite its growing nutraceutical appeal, the anticancer potential of DM in GC has not yet been explored. This study represents the first investigation of DM in human gastric adenocarcinoma (AGS) cells. Using increasing concentrations of whole DM (25–100%), a dose-dependent inhibition of cell viability and migration was observed. Mechanistic insights reveal that DM induces mitochondrial oxidative stress, disrupts cell cycle progression (S/G2 accumulation at 75%, G2 arrest at 100%), and unexpectedly triggers a pro-inflammatory gene signature suggesting stress-driven immunostimulation rather than canonical apoptosis. These findings highlight a non-classical, context-dependent cytotoxic mechanism that distinguishes DM from conventional pro-apoptotic agents. DM may represent a promising nutraceutical candidate for GC management, bridging traditional food resources with modern oncology. By inhibiting hallmark cancer traits while engaging unique immunological pathways, DM offers a sustainable, low-toxicity approach with translational potential. Future studies will focus on the characterization of active components, validation in organoid and animal models, and exploring clinical applications of DM-derived bioactive components in cancer prevention and therapy. Full article

Cardiovascular complications increasingly challenge survivors of urological cancers, given the cardiotoxicity of therapies such as androgen deprivation, vascular endothelial growth factor receptor inhibitors, tyrosine kinase inhibitors, immune checkpoint inhibitors, and chemotherapy. This narrative review addresses the complex crosstalk between urological cancer treatment and cardiovascular disease. It summarizes cardiovascular toxicities linked to major antineoplastic agents, explores underlying mechanisms including metabolic and immune-mediated effects, and proposes strategies for surveillance, diagnosis, and management. Highlighting the need for multidisciplinary collaboration, it outlines future directions for research to optimize cardiovascular outcomes in this high-risk population. The increasing complexity of cardiovascular care in patients with urological malignancies highlights the need for closer collaboration between cardiologists, urologists, and oncologists, with uro-cardio-oncology emerging as an important multidisciplinary field. Full article

Background: Metronomic chemotherapy (MCT), understood as continuous, low-dose cytotoxic administration without prolonged drug-free intervals, has become an established strategy in several solid tumors, acting primarily through antiangiogenic, immunomodulatory, and direct cytostatic mechanisms rather than replication-dependent cytotoxicity. Despite an expanding evidence base, including positive randomized trials, validated predictive biomarkers of response remain unavailable. Methods: We searched PubMed/MEDLINE, Embase, and ClinicalTrials.gov (January 2000 to July 2026) for phase II/III randomized trials, prospective cohorts, and selected retrospective analyses of MCT in breast cancer, head and neck squamous cell carcinoma, NSCLC, and mCRC, and extracted biomarker data from embedded translational substudies of eligible trials. Results: In breast cancer, phase III SYSUCC-001 (adjuvant metronomic capecitabine, improved DFS in TNBC) and MECCA (metronomic capecitabine plus aromatase inhibitor in HR+/HER2− disease) provide the strongest evidence, supported by randomized phase II data for the VEX regimen (METEORA-II) and MCT-anti-PD-1 combinations. TEMPO LUNG established metronomic vinorelbine as effective in platinum-unfit NSCLC, while CAIRO3 confirmed metronomic capecitabine–bevacizumab as an effective mCRC maintenance therapy. Most recently, the phase III TMC-I trial extended positive randomized evidence to head and neck cancer. Candidate biomarkers span angiogenic, immune, tumor proliferative, molecular, pharmacodynamic cytokine, on-treatment clinical (adverse-event-based), and gut–microbiome domains, with FOXC1, circulating endothelial cell kinetics, VEGF pathway markers, and regulatory T-cell dynamics among the most promising; however, none has been prospectively validated in a dedicated confirmatory trial. Conclusions: MCT has moved from empirical use to an evidence-based strategy across multiple tumor types, but the lack of validated predictive biomarkers limits informed patient selection. Future trials should incorporate biomarker-driven designs, particularly FOXC1, endothelial cell kinetics, and immune profiling as co-primary objectives. Defining an MCT-sensitive biological phenotype remains the key translational challenge for the field. Full article

Acute kidney injury (AKI) is a frequent and serious complication in patients with cancer, associated not only with increased morbidity and mortality, but also with the interruption or modification of anticancer therapy. In critically ill patients with cancer, AKI arises from a complex interplay of cancer-related, treatment-related, and patient-related factors, with many patients requiring renal replacement therapy (RRT) and admission to the intensive care unit (ICU). This narrative review summarizes the etiology of AKI in patients with cancer and discusses the role of extracorporeal organ support (ECOS) therapies, with particular emphasis on continuous renal replacement therapy (CRRT). Understanding the underlying etiology of AKI in this patient population is essential for guiding treatment decisions, particularly when therapeutic plasma exchange, hemadsorption, or other extracorporeal modalities are considered which may directly target the pathophysiology driving organ dysfunction. Although observational data suggest that ECOS use may improve both short- and long-term outcomes, robust evidence demonstrating consistent benefit remains lacking. Furthermore, limited pharmacokinetic data for anticancer drugs in patients undergoing dialysis or RRT creates significant uncertainty regarding optimal dosing strategies. By providing a structured overview of extracorporeal organ support strategies in cancer-associated AKI, this review aims to support multidisciplinary decision-making and facilitate more individualized critical care for this high-risk population. Full article

Breast cancer is among the most common cancers globally. While several advancements have been made to improve breast cancer management, there is still a need to find innovative ways to deliver drug therapy to improve efficacy and side effects associated with treatment. Among these methods, local and targeted drug delivery is particularly promising. The current review highlights localized polymer-based methods to effectively deliver breast cancer therapy, with a specific focus on the strengths and limitations of these systems. Injectable and surgically implanted scaffolds, microneedles, topical patches, liquid and semisolid topical drug carriers are amongst some of the delivery systems discussed. Highlighted in the discussion is how physiological changes that occur during breast cancer should be considered and utilized when developing drug formulations, by specifically exploiting the tumor microenvironment. Remaining gaps and future areas for drug delivery research are highlighted including personalized medicine and insights into novel drug delivery systems like nanomedicines and three-dimensional drug printing. Full article

Modeling the dynamics of three tumor cell populations, i.e., sensitive, persister, and resistant tumor cells, during molecularly targeted therapy with tyrosine kinase inhibitors (TKIs) would be valuable for adjusting treatment plans for patients with epidermal growth factor receptor-mutated non-small cell lung cancer (EGFR-mt NSCLC). We hypothesized the time-variant tumor growth trajectories (TGTs) of patients with stage IV EGFR-mt NSCLC for the three tumor cell populations could be expressed using differential models after several follow-up computed tomography examinations. We aimed to propose differential models for TGTs in three cell populations from patients with EGFR-mt NSCLC treated with an EGFR-TKI (osimertinib). We selected two differential equations—Bertalanffy–Pütter (BP) and Gompertz—to develop TGT models. The parameters of the models were optimized based on a dual annealing method within parameter ranges determined using synthetic patient data. Using CT examinations that were not employed for model fitting, the mean absolute percentage errors (MAPEs) for BP-based and Gompertz-based models were 36.1 ± 40.2% and 43.9 ± 60.1%, respectively, for three follow-up computed tomography (FCT) examinations, which indicated no statistically significant difference (p = 0.61). This study suggests that the proposed BP-based and Gompertz-based differential models could have the potential to express TGTs in patients with stage IV EGFR-mt NSCLC treated with EGFR-TKIs after three follow-up CT examinations, although MAPEs should be mitigated in future works. Full article

Background/Objectives: Vitamin D deficiency is commonly observed in patients with breast cancer and may affect disease course and treatment outcomes. The determinants of vitamin D status in this population remain incompletely understood, particularly with respect to lifestyle, psychosocial, and tumour-related factors. The aim of this study was to identify environmental and clinical factors associated with serum 25-hydroxyvitamin D [25(OH)D] concentrations in women with breast cancer, with particular emphasis on dietary patterns, psychological distress, sleep quality, and tumour molecular subtype. Methods: A cross-sectional observational study was conducted among 101 women with histopathologically confirmed invasive breast cancer, recruited at the St. John of Dukla Oncology Centre of the Lublin Region (COZL) in Lublin, Poland, between 2018 and 2019. Serum 25(OH)D concentrations were measured by electrochemiluminescence immunoassay (ECLIA; Roche Diagnostics) within 2–8 weeks after surgical treatment. Clinical and lifestyle data were collected using standardised questionnaires and medical records. Dietary patterns were assessed with the KomPAN questionnaire (pro-healthy diet index pHDI-10 and non-healthy diet index nHDI-14). Psychological distress was measured with the Distress Thermometer. Multiple linear regression with backward stepwise elimination was applied to identify factors independently associated with of 25(OH)D concentration. Results: Insufficient vitamin D status (25(OH)D < 30 ng/mL) was found in 56.4% of participants. The multivariable regression model was statistically significant (F(6,92) = 15.298; p < 0.001), explaining 49.9% of the variance in 25(OH)D concentrations. Factors independently associated with lower 25(OH)D included higher BMI (b = −0.715; p = 0.005), sleep disturbances (b = −6.257; p = 0.020), higher psychological distress score (b = −2.263; p < 0.001), and luminal B versus luminal A subtype (b = −5.909; p = 0.025). A higher pro healthy diet index (pHDI-10) was independently associated with higher 25(OH)D (b = 0.245; p = 0.040). Conclusions: Vitamin D status in patients with breast cancer is shaped by complex interactions among modifiable lifestyle factors and tumour characteristics. Targeted interventions addressing diet quality, psychological well-being, sleep health, and weight management may improve vitamin D status in this population. The association between molecular subtype and 25(OH)D concentrations warrants further prospective investigation. These findings should be interpreted with caution, as vitamin D supplementation and direct measures of sun exposure—both established determinants of 25(OH)D—could not be included as covariates and may account, at least in part, for the associations reported. Full article

Background/Objectives: Cutaneous adverse events (cAEs) are among the most common toxicities associated with modern anticancer therapies and can significantly affect quality of life, treatment adherence, and therapeutic outcomes. This narrative review aims to provide an updated overview of the mechanisms, clinical manifestations, prognostic implications, and management strategies of cancer therapy-related cutaneous toxicities, with a particular focus on precision oncodermatology. Methods: A narrative review of the recent literature was performed, integrating evidence from clinical studies, meta-analyses, pharmacovigilance investigations, consensus guidelines, and translational research. The review examines cutaneous toxicities associated with immune checkpoint inhibitors, targeted therapies, antibody–drug conjugates, and other emerging anticancer treatments. Results: Four major axes were identified: immune disinhibition, epithelial signaling inhibition, cytotoxic epithelial injury, and cytokine-driven immune activation. Cutaneous immune-related adverse events (cirAEs) emerged as potential biomarkers of treatment efficacy, particularly vitiligo, lichenoid, and psoriasiform eruptions. Increasing evidence supports the use of steroid-sparing biologic therapies, including dupilumab, omalizumab, anti-IL-17 agents, and Janus kinase inhibitors, although prospective validation remains limited. Recent advances in immunologic endotyping have identified distinct inflammatory pathways that may enable personalized therapeutic approaches. Antibody–drug conjugates represent an expanding source of unique dermatologic toxicities requiring dedicated management strategies. Emerging biomarkers, including cytokine signatures and microRNAs, may further refine risk stratification and treatment selection. Conclusions: The management of cancer therapy-related cutaneous toxicities is evolving toward a precision medicine model integrating clinical phenotype, immunologic endotype, and biomarker profiling. Early multidisciplinary intervention and mechanism-based therapeutic strategies may improve patient outcomes while preserving anticancer efficacy. Prospective studies are needed to validate biomarker-guided and steroid-sparing approaches in oncodermatology. Full article

Background: Immune checkpoint inhibitors and adoptive T-cell therapies have substantially improved cancer treatment outcomes, but their use is often limited by immune-related toxicities, including cytokine release syndrome. The role of interleukin (IL)-17A in tumor immunity remains controversial, hindering its therapeutic applications in cancer. A concern is that application of IL-17 blocking agents to release cytokine storms caused by tumor immunotherapy reverses anti-tumor immunity. Methods: In this study, we evaluated the effect of IL-17A blockade alone and in combination with anti–PD (programmed cell death)-1 therapy or tumor-specific CD8⁺ T cells in melanoma, colon, and lung tumors, and in UVB-induced skin carcinogenesis. Results: Our results showed that blocking IL-17A inhibited tumor development, and did not impair the efficacy of tumor immunotherapies with checkpoint inhibitors or tumor-specific T cells. Combined treatment with anti-IL-17A and anti-PD-1 antibodies significantly enhanced tumor suppression compared to single-agent therapies in all tested tumor models. Moreover, IL-17A blockade improved the efficacy of adoptive CD8⁺ T-cell therapy. Mechanistic analyses revealed that the combination therapy increased infiltration of activated antigen-specific CD8⁺ T cells in tumors. In none of the tested tumor models did IL-17A blockade negatively affect the efficacy of tumor immunotherapy with checkpoint inhibitors or T-cell therapy. Conclusions: These findings suggest that the combined application of anti-IL-17A blocking agents with current tumor immunotherapy at the same time is a promising strategy to enhance the efficacy and potentially diminish immune-related adverse effects. Full article

Background: Breast cancer-related lymphedema (BCRL) is a potentially debilitating outcome following breast cancer treatment. Much attention has been given to preventive and curative strategies for BCRL. Patients with inflammatory breast cancer (IBC) are at particularly increased risk, with approximately half of patients with IBC developing BCRL. We present preliminary outcome data for inflammatory breast cancer patients who undergo a multipronged preventative strategy with immediate lymphatic reconstruction at the time of axillary lymph node dissection, compressive arm sleeve wearing, and occupational therapy. We also present a literature review on IBC and BCRL. Methods: A retrospective review of patients with IBC undergoing immediate lymphatic reconstruction with lymphovenous bypass at the time of axillary lymph node dissection was performed. All patients were referred to occupational therapy for establishment of care and arm sleeve fitting and had at least 12 months of follow-up. The primary outcome of interest was the development of lymphedema. Additionally, a narrative review of the literature was performed. All English language studies pertaining to BCRL in patients with IBC were considered. Results: Eighteen patients with IBC underwent immediate lymphatic reconstruction with lymphovenous bypass between April 2022 and September 2023 by three reconstructive microsurgeons. Average follow-up time was 24.4 months (range 12.5–33.9 months). All patients underwent successful lymphovenous bypass of at least 1 channel. Of the 18 patients, 3 (16.6%) developed symptoms of lymphedema, such as heaviness of the posterior arm (2/3, 67%) or edema of the forearm (1/3, 33%). No patients developed >10% change in extremity volume. Conclusions: BCRL is a debilitating and common outcome following breast surgery in patients with IBC. Immediate reconstruction with lymphovenous bypass coupled with occupational therapy and compression sleeve management may reduce the risk for BCRL in this population. Full article

Oxidative stress and inflammation are the causes of many colonic diseases. Therefore, the aim of this study was to maximize the biological activity of hawthorn seed preparations aimed at modulating oxidative stress and the inflammatory response in the colon through selective fractionation and enrichment in compounds with antioxidant, anti-inflammatory, and cytotoxic potential. Fractionation of hawthorn seed extract (CE) was performed using C18 resin, and detailed phytochemical analysis was performed using ultra-performance liquid chromatography (UPLC-MS/MS). This work resulted in four fractions (F1-F4), with differential distribution of 28 identified polyphenolic compounds. Phenolic acids dominated in F1, flavan-3-ols in F2, and flavonols in F3 and F4. In terms of quantitative composition, the obtained fractions can be ranked in the order F1 > F2 > F3 > F4. In biological activity studies, the highest antioxidant activity in a chemical model was demonstrated for F2, which was also confirmed in a cellular model–colonocyte cells (CCD841CoN line) stimulated with H₂O₂. F2 also demonstrated the highest inhibition of ROS production by colonocytes and NO production by macrophages. High F2 activity was also demonstrated in studies of the proliferation, migration, and invasion of colon cancer cells. These findings underscore the validity of fractionation of hawthorn seed extract and its potential use in the prevention and treatment of colon diseases. Future studies should include in vivo models and estimation of the activity of the fraction truly bioavailable after digestion. Full article