Search Results (130,537)

(1) Background: Pharmacist interventions are key to optimizing medication therapy and improving patient outcomes. The CLEO multidimensional tool assesses the clinical, economic, and organizational impact of these interventions, though its use in Portuguese hospital settings is limited. This study explored the predicted impact of pharmacist interventions in the Oncology Department of a Portuguese hospital, using CLEO to quantify their potential contribution to patient care and healthcare system efficiency;(2) Methods: A retrospective observational study was conducted at the hospital’s Oncology Outpatient Pharmacy between April and December 2024. Data from 144 pharmacist interventions were analyzed, focusing on drug-related problems, corrective actions, and CLEO scores. Descriptive statistics were used for data analysis; (3) Results: The most frequent drug-related problems were incorrect administration frequency (57.6%), drug interactions (22.2%), and incorrect dosing (10.4%). Nearly half of the interventions (47.2%) resulted in prescription corrections. CLEO analysis demonstrated a predicted positive clinical impact (80% of interventions scored 1C–3C), potential economic benefits (40.3% scored 1E), and organizational improvements (79.9% scored 1O), especially in lung, breast, and colorectal cancer treatments; (4) Conclusions: Pharmacist interventions were predicted to be associated with improvements in clinical, economic, and organizational outcomes in oncology care. These findings suggest that systematic documentation and evaluation of interventions using CLEO may enhance patient safety and healthcare efficiency, although further multicenter and prospective studies are needed to confirm these observations. Full article

Background: Personalizing adjuvant chemotherapy (ACT) after curative resection in early-stage NSCLC remains unmet because prior ACT-biomarker findings rarely reproduce across studies. Key barriers are platform and preprocessing heterogeneity, dominant batch effects, and incomplete ACT annotations. As a result, many signatures that perform well in a single cohort fail during external validation. We created an open, harmonized meta-database linking gene expression with curated ACT exposure and survival to enable fair benchmarking and modeling. Methods: A PRISMA-guided search of 999 GEO studies (through January 2025) used LLM-assisted triage of titles, clinical tables, and free text to identify datasets with explicit ACT status and patient-level survival. Eight Affymetrix microarray cohorts (GPL570/GPL96) met eligibility. Raw CEL files underwent robust multi-array average; probes were re-annotated to Entrez IDs and collapsed by median. Covariate-preserving ComBat adjusted platform/study while retaining several clinical factors. Batch structure was quantified by principal-component analysis (PCA) variance, silhouette width, and UMAP. Two quality-control (QC) filters, median M-score deviation and PCA leverage, flagged and removed technical outliers. Results: The final meta-database comprises 1340 patients (223 (16.6%) ACT; 1117 (83.4%) observation), 13,039 intersecting genes, and 594 overall-survival events. Batch-associated variance (PC1 + PC2) decreased from 63.1% to 20.1%, and mean silhouette width shifted from 0.82 to −0.19 post-correction. Seven arrays (0.5%) were excluded by QC. Event depth supports high-dimensional survival and heterogeneity-of-treatment modeling, and the multi-cohort design enables internal–external validation. Conclusions: This first open, rigorously harmonized NSCLC transcriptomic database provides the sample size, demographic diversity, and technical consistency required to benchmark ACT-benefit markers. By making these data openly available, it will accelerate equitable precision-oncology research and enable data-driven treatment decisions in early-stage NSCLC. Full article

Ternary hybrid nanofluid have been revealed to possess a wide range of application disciplines reaching from biomedical engineering, detection of cancer, over or photovoltaic panels and cells, nuclear power plant engineering, to the automobile industry, smart cells and and eventually to heat exchange systems. Inspired by the recent developments in nanotechnology and in particular the high potential ability of use of such nanofluids in practical problems, this paper deals with the flow of a three phase nanofluid of MWCNT-Au/Ag nanoparticles dispersed in blood in the presence of a bidirectional stretching sheet. The model derived in this study yields a set of linked nonlinear PDEs, which are first transformed into dimensionless ODEs. From these ODEs we get a dataset with the help of MATHEMATICA environment, then solved using AI-based technique utilizing Levenberg Marquardt Feedforward Algorithm. In this work, flow characteristics under varying physical parameters have been studied and analyzed and the boundary layer phenomena has been investigated. In detail horizontal, vertical velocity profiles as well as temperature distribution are analyzed. The findings reveal that as the stretching ratio of the surface coincide with an increase the vertical velocity as the surface has thinned in this direction minimizing resistance to the fluid flow. Full article

Introduction: Gastrointestinal stromal tumors (GISTs) are primarily driven by mutations in KIT (KIT proto-oncogene receptor tyrosine kinase) or PDGFRA (platelet-derived growth factor receptor alpha), but resistance to tyrosine kinase inhibitors (TKIs) such as imatinib remains a major clinical challenge. Alterations in fibroblast growth factor receptor 2 (FGFR2), although rare, are emerging as important contributors to tumor progression and drug resistance. This review evaluates the molecular mechanisms, expression profiles, detection methods, and therapeutic implications of FGFR2 in GIST. Methods: We searched PubMed, Web of Science, Google Scholar, and ClinicalTrials.gov for studies published between January 2010 and June 2025, using combinations of keywords related to FGFR2, gastrointestinal stromal tumor, resistance mechanisms, gene fusion, amplification, polymorphisms, and targeted therapy. Eligible studies were critically assessed to distinguish GIST-specific data from evidence extrapolated from other cancers. Results:FGFR2 is expressed in multiple normal tissues and at variable levels in mesenchymal-derived tumors, including GIST. Its alterations occur in approximately 1–2% of GIST cases, most commonly as gene fusions (e.g., FGFR2::TACC2, <1%) or amplifications (1–2%); point mutations and clinically significant polymorphisms are extremely rare. These alterations activate the MAPK/ERK and PI3K/AKT pathways, contribute to bypass signaling, and enhance DNA damage repair, thereby promoting TKI resistance. Beyond mutations, mechanisms such as amplification, ligand overexpression, and microenvironmental interactions also play roles. FGFR2 alterations appear mutually exclusive with KIT/PDGFRA mutations but occasional co-occurrence has been reported. Current clinical evidence is largely limited to small cohorts, basket trials, or case reports. Conclusions:FGFR2 is an emerging oncogenic driver and biomarker of resistance in a rare subset of GISTs. Although direct evidence remains limited, particularly regarding DNA repair and polymorphisms, FGFR2-targeted therapies (e.g., erdafitinib, pemigatinib) show potential, especially in combination with TKIs or DNA-damaging agents. Future research should prioritize GIST-specific clinical trials, the development of FGFR2-driven models, and standardized molecular diagnostics to validate FGFR2 as a therapeutic target. Full article

Oxaliplatin is an anticancer drug used to treat colorectal and gastric cancers. In many cases, chemotherapy is discontinued due to adverse events caused by anticancer drugs. To address this challenge, we developed a sustained-release drug delivery system using polycaprolactone sheets embedded with oxaliplatin (oxaliplatin sheets) and evaluated their therapeutic potential in murine models of colon and gastric cancers. Antitumor efficacy was compared with conventional intraperitoneal administration by monitoring tumor volume, body weight, and systemic oxaliplatin concentrations over 21 days, along with histopathological assessment of tumors and hepatic tissue. Oxaliplatin sheets demonstrated superior tumor suppression, significantly reduced Ki-67 positivity, and mitotic indices. Additionally, antitumor effects and blood oxaliplatin levels were consistent regardless of implantation site. Notably, oxaliplatin sheets significantly decreased weight loss compared with intraperitoneal administration. In our analysis of liver pathology, we found that hepatic sinusoidal obstruction and hepatocellular degeneration were significantly increased after intraperitoneal administration compared with untreated mice and mice treated with oxaliplatin sheets. Furthermore, treatment with oxaliplatin sheets improved survival. Thus, our oxaliplatin sheets exhibited effective tumor control and reduced side effects, indicating their potential as a promising treatment for advanced gastric and colorectal cancers. Full article

Introduction: In minimally invasive, off-clamp partial nephrectomy (ocMIPN), the reconstructive strategy profoundly influences functional outcomes. Traditional nephrometry scores aid preoperative planning but do not directly inform the choice of closure technique. This dual-institutional study aimed primarily to identify preoperative CT-derived parameters predictive of renorrhaphy versus a sutureless approach, and secondarily to compare perioperative and functional outcomes between these techniques. Methods: We retrospectively analyzed 201 consecutive ocMIPN cases performed using a standardized off-clamp technique by two experienced surgical teams across robotic platforms and conventional laparoscopy. Preoperative CT scans were centrally reviewed to quantify morphometric features, including contact surface area (CSA), tumor radius, and Gerota’s fascia thickness. Univariable and multivariable logistic regression models—one restricted to radiologic variables and one expanded with RENAL score terms—were generated to identify independent predictors. Perioperative outcomes, renal functional metrics, and Trifecta rates were compared between cohorts. Results: Among the 201 patients, 101 (50.2%) underwent sutureless reconstruction and 100 (49.8%) renorrhaphy. Cohorts were comparable at baseline except for tumor size (3.1 vs. 3.6 cm; p = 0.04). In multivariable analysis, CSA > 15 cm² (OR 3.93; 95% CI 1.26–12.26; p = 0.02) and tumor radius (OR 1.14 per mm; 95% CI 1.01–1.29; p = 0.04) consistently predicted renorrhaphy, while Gerota’s fascia < 10 mm emerged as significant only in the expanded specification (OR 0.08; 95% CI 0.01–0.70; p = 0.02). Integration with RENAL improved predictive performance (ΔAUC 0.06; NRI 0.14; IDI 0.07), and the final model demonstrated strong discrimination (AUC 0.81) with satisfactory calibration. Perioperative outcomes, postoperative renal function, and Trifecta achievement were similar between groups (all p ≥ 0.21). Conclusions: A concise set of CT-derived morphologic markers—CSA, tumor radius, and perinephric fascia thickness—anticipated reconstructive strategy in ocMIPN and augmented the discriminatory power of RENAL nephrometry. When anatomy was favorable, sutureless repair was not associated with statistically significant differences in perioperative safety or renal function, although the study was not powered for formal equivalence testing. These findings support the integration of radiologic markers into preoperative planning frameworks for nephron-sparing surgery. Full article

Background/Objectives: In 2019, the European Society of Gynaecological Oncology (ESGO) published a set of quality indicators (QIs) for the surgical management of cervical cancer with the aim of improving clinical practice. The objective of this study is to evaluate the influence of ESGO QIs and clinicopathological factors on progression-free survival (PFS) in patients with early-stage cervical cancer in a retrospective cohort. Methods: A retrospective study was conducted in patients with early-stage cervical cancer who underwent radical surgery with pelvic lymph node assessment at La Paz University Hospital between 2005 and 2022. The cohort was divided into two groups according to the timing of surgery (before vs. after 2010), when MRI was implemented as a standardized diagnostic tool and the multidisciplinary tumor board was established. Univariate and multivariate Cox regression analyses were performed, including demographic and histopathological variables, as well as adherence to ESGO QIs, focusing on those related to the overall management. Hazard ratios and 95% confidence intervals were estimated. Kaplan–Meier survival curves were generated and compared between groups. Results: The implementation of systematic MRI and a multidisciplinary tumor board at our center was associated with a significant reduction in positive surgical margins (p = 0.003) and parametrial invasion (p < 0.001), as well as improved diagnostic accuracy, lowering the rate of upstaging from 31.6% before 2010 to 4.4% thereafter (p < 0.001). PFS in the post-2010 cohort was significantly improved (log-rank p = 0.0408), although no differences in overall survival (OS) were observed (log-rank p = 0.2602). Additionally, cervical conization prior to radical hysterectomy was associated with a markedly reduced risk of recurrence (HR 0.12, p < 0.001), representing the most significant prognostic factor for PFS in our cohort. Conclusions: The correct application of ESGO QIs, along with appropriate staging and pathological assessment, is essential to improve prognosis in cervical cancer. Systematic implementation of these standards is recommended to optimize clinical care. Full article

Mastic gum from Pistacia lentiscus L. has long been valued in Mediterranean medicine and food preservation, yet its bioactive potential remains underexplored in specific geographic contexts. In Morocco, the resin—locally known as Meska Horra—is abundant but insufficiently characterized. This study compared three extraction methods—cold maceration (CM), Soxhlet extraction (SE), and ultrasound-assisted extraction (UAE)—using sequential acetone and 70% ethanol to recover complementary phenolic compounds from defatted resin. Targeted UHPLC–ESI–MS/MS profiling identified and quantified 30 phenolics, mainly flavonoids and phenolic acids, providing the first systematic dataset for Moroccan mastic gum. UAE–EtOH extract displayed the strongest antioxidant activity (DPPH IC₅₀ = 0.029 mg/mL; ABTS•⁺ IC₅₀ = 0.026 mg/mL). SE–acetone and SE–EtOH extracts showed potent antifungal activity, particularly against Geotrichum candidum, Rhodotorula glutinis, and Aspergillus niger (MBC = 1.7%). The SE–acetone extract exhibited cytotoxicity toward MIA PaCa-2 pancreatic cancer cells (IC₅₀ = 19 µg/mL). These findings demonstrate that extraction method and solvent choice strongly influence phenolic recovery and associated bioactivities, supporting the valorization of Moroccan mastic gum as a promising source for nutraceutical and pharmaceutical applications. Full article

Background/Objectives: Advanced hepatocellular carcinoma (HCC) presents limited treatment options; however, immunotherapy demonstrates encouraging outcomes and acceptable adverse reactions in advanced HCC. This study evaluates the efficacy and safety of combining serplulimab, the bevacizumab biosimilar HLX04, and hepatic arterial infusion chemotherapy (HAIC) as a first-line therapy. Methods: This prospective, observational, single-center phase II trial enrolled untreated HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage C. All patients received serplulimab (4.5 mg/kg) and HLX04 (15.0 mg/kg) every 3 weeks, followed by the HAIC-FOLFOX regimen. The primary endpoint was the objective response rate (ORR). Secondary endpoints included the disease control rate (DCR), progression-free survival (PFS), and safety. Results: A total of 32 patients were enrolled. The best outcomes showed an ORR of 53.1%, including 17 partial responses (PR, 53.1%) and 12 stable diseases (SD, 37.5%), resulting in a DCR of 90.6%. Subgroup analysis showed a higher ORR in patients with a single lesion and those receiving ≥3 treatment cycles, with an ORR of 60.7% in the latter group. Additionally, five patients underwent successful hepatectomy after ≥3 treatment cycles, with postoperative pathology confirming extensive tumor necrosis. Kaplan–Meier analysis estimated PFS rates of 89.9% (95% CI: 79.5–100.0%) at 6 months and 70.8% (95% CI: 54.2–92.4%) at 12 months. No deaths related to adverse events (AEs) occurred; four (12.5%) patients experienced grade IV AEs and twelve (37.5%) patients experienced grade III AEs. Conclusions: Serplulimab, HLX04, and HAIC combined as a first-line treatment for advanced HCC have demonstrated promising efficacy, particularly in patients completing ≥3 cycles, with an acceptable safety profile. Further investigation in larger trials is required. Full article

Cancer-associated fibroblasts (CAFs) are a key constituent of the tumor microenvironment. CAFs may affect the development of tumor cells. The critical role of CAFs in the tumor microenvironment is linked to their epigenetic modifications, as a stable yet reversible regulation of cellular phenotypes. Current evidence indicates that their formation and function are closely linked to epigenetic mechanisms. Existing research indicates that the epigenetic alteration abnormalities are triggered by metabolic cues and stabilize the acquired phenotype of CAFs. This process is associated with transcriptional changes and patient outcomes in various tumors, providing a biological rationale and translational potential for reprogramming CAFs. Understanding of epigenetic modifications in CAFs remain insufficient, while DNA methylation in CAFs can alter CAF states through multiple pathways and thereby influence tumor progression. It is necessary to investigate the unique, identifiable epigenetic signatures of CAF. As an epigenetic reader couple histone acetylation to high-output oncogenic transcription; meanwhile, noncoding RNAs modulate CAF formation and therapeutic responses via bidirectional crosstalk between tumor cells and stroma. The interactions between different epigenetic modifications and their underlying regulatory logic may play a crucial role in developing new therapeutic strategies. This review focuses on the roles of DNA methylation, histone acetylation, and enhancer reprogramming in CAFs. Full article

Background/Objectives: Breast cancer (BC) is the most commonly diagnosed cancer in women and the leading cause of cancer-related deaths globally. Molecular subtyping is crucial for prognosis and treatment planning, with immunohistochemistry (IHC) being the most commonly used method. However, IHC has limitations, including observer variability, a lack of standardization, and a lack of reproducibility. Gene expression profiling is considered the ground truth for molecular subtyping; unfortunately, this is expensive and inaccessible to many institutions. This study investigates the potential of an artificial intelligence (AI) model to predict BC molecular subtypes directly from hematoxylin and eosin (H&E)-stained whole-slide images (WSIs). Methods: A pretrained deep learning framework based on multiple-instance learning (MIL) was validated on the Stavanger Breast Cancer (SBC) dataset, consisting of 538 BC cases. Three classification tasks were assessed, including two-class [triple negative BC (TNBC) vs. non-TNBC], three-class (luminal vs. HER2-positive vs. TNBC), and four-class (luminal A vs. luminal B vs. HER2-positive vs. TNBC) groups. Performance metrics were used for the evaluation of the AI model. Results: The AI model demonstrated strong performance in distinguishing TNBC from non-TNBC (AUC = 0.823, accuracy = 0.833, F1-score = 0.824). However, performance declined with an increasing number of classes. Conclusions: The study highlights the potential of AI in BC molecular subtyping from H&E WSIs, offering an easily applicable and standardized method to IHC. Future improvements should focus on optimizing multi-class classification and validating AI-based methods against gene expression analyses for enhanced clinical applicability. Full article

HPV-related head and neck cancers are increasing globally and although they constitute a major public health problem, there are currently no validated screening or early detection methods in widespread clinical use. This review discusses advances in clinical and molecular aspects of prevention, screening, and early detection of HPV-related head and neck cancers (HNCs), such as potential use of HPV blood or saliva seropositivity, RNA biomarkers, liquid biopsy, circulating tumor DNA, and proteomics. In addition to HPV vaccination, public education about vaccination, smoking, and safe sexual practices is warranted. Continued research is warranted to define optimal use and integration of approaches for prevention, screening, and early detection methods of HNCs. Full article

Avicennia marina, commonly known as the grey mangrove, is a salt-tolerant species widely distributed in coastal and estuarine ecosystems. Traditionally, it has been used in folk medicine to treat skin diseases, rheumatism, and ulcers due to its anti-inflammatory and antimicrobial properties. However, comprehensive studies on the chemical constituents and their pharmacological effects remain limited. The dried powder of the aerial parts of A. marina (3.6 kg) was successfully extracted three times with methanol (20 L × 3, each for 2 h) using a multifunctional ultrasonic cleaner operated at 25 °C with a 50% amplitude setting. In this study, the methanolic extract of the aerial parts of A. marina led to the isolation of eight compounds, including two previously unreported iridoid glycosides—avicenosides A and B (1 and 2)—and six known compounds: techtochrysin (3), 7,4′-di-O-methyl-apigenin (4), luteolin (5), kaempferol (6), trans-caffeic acid (7), and 3,4-dihydroxybenzoic acid (8). Their chemical structures were elucidated using nuclear magnetic resonance (NMR) spectroscopy and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and compared with previously published data. Moreover, the absolute configuration of the sugar moieties in the new compounds was also identified. All isolated compounds were evaluated for their cytotoxicity against HepG2 and A549 cancer cell lines. The results indicate potential cytotoxicity of the secondary metabolites from A. marina and provide evidence of their promising role as lead compounds for the development of novel anticancer agents. Full article

Cancer treatments are limited by poor tumor specificity and toxicity. We tested a radiosensitizing approach using PEG/RGD-functionalized gold nanoparticles (GNPs), a lipid-nanoparticle–encapsulated docetaxel prodrug (LNP_DTX–P), and external-beam radiotherapy (RT). In MIA PaCa-2 xenografts, intravenous GNPs (2 mg/kg) and LNP_DTX–P (6 mg/kg) were given before 5 Gy RT. Both LNP_DTX–P + RT and GNPs + LNP_DTX–P + RT reduced tumor volume by ~40% and significantly prolonged survival versus RT alone (p < 0.001). Adding GNPs did not enhance efficacy, indicating LNP_DTX–P was the main driver under this regimen. These results demonstrate nanocarrier-enabled radiosensitization in vivo and support further studies toward clinical translation. Full article