Search Results (126,748)

Background: Carfilzomib (CFZ) is a proteasome inhibitor with known cardiotoxic effects used in multiple myeloma (MM) treatment. Cardio-oncology guidelines recommend cardiovascular risk assessment via echocardiography. Left atrial strain (LAS) is not yet included as a marker of cardiotoxicity, but it is emerging as a potential indicator of cardiac dysfunction. Objective: This study evaluates LAS as a predictor of CFZ-related hypertensive cardiovascular adverse events (CVAEs) in MM patients, with or without prior hypertension. Methods: A total of 125 MM patients treated with CFZ at the Hypertension Center, “Città della Salute e della Scienza” in Turin, were enrolled. Baseline assessments included transthoracic echocardiography for LAS analysis via Philips QLAB software. Results: During CFZ therapy, 52% of patients experienced hypertensive events. LAS conduit was significantly impaired in those who experienced CVAEs (−16.20 [−20.75; −12.65] vs. −20.80 [−26.30; −15.40], p = 0.006) and LAS conduit > −22 acted as a predictor of hypertensive adverse events in the normotensive population (OR 2.37 [1.02; 5.50]). Conclusion: These findings indicate that alterations in LAS conduit are linked to an increased risk of hypertensive adverse events during CFZ treatment. Incorporating LAS measurement into cardiovascular risk assessments may improve personalized risk stratification for MM patients, especially those without pre-existing hypertension. Full article

Background/Objectives: The role of tertiary lymphoid structures (TLSs) in cancer prognosis is well established, yet their significance in early-stage EGFR-mutant lung adenocarcinoma remains unclear. While outcomes for early-stage lung cancer are generally better than those of late-stage disease, recurrence remains a significant challenge. This study investigates the prognostic value of TLSs and their molecular characteristics in early-stage EGFR-mutant lung adenocarcinoma. Methods: TLSs were identified in tumor samples using multiplex immunohistochemistry (IHC), and their density was quantified. The PD-L1 tumor proportion score (TPS) and TLS density were analyzed for associations with disease-free survival (DFS). Gene expression profiling was performed to compare tumor microenvironment signatures between high- and low-TLS-density groups. Results: High TLS density correlated with significantly longer DFS (43 vs. 20.5 months, p = 0.0082). No relationship was found between TLS density and PD-L1 TPS or EGFR mutation subtype. Transcriptomic analysis revealed upregulated immune response genes in the high-TLS-density group, including those involved in T and B cell activation. Low-TLS-density tumors exhibited gene signatures promoting tumor growth, such as cell cycle and WNT pathway activation. Conclusions: In summary, TLS density is a potential prognostic biomarker for DFS in early-stage EGFR-mutant lung adenocarcinoma, independent of PD-L1 TPS or EGFR mutation subtype. Enhanced immune activation in high-TLS-density tumors highlights TLSs as a potential target for improving outcomes in these patients. Full article

Background: Exophiala spp. are dematiaceous fungi with opportunistic pathogenic potential and a widespread environmental presence. Clinical cases of Exophiala spp. fungemia are uncommon. Although rarely encountered in the general population, these organisms are increasingly reported in immunocompromised individuals or those with complex underlying health conditions. Objectives: This review seeks to examine all documented human cases of Exophiala spp. fungemia, with particular focus on aspects such as epidemiology, microbiological features, resistance patterns, therapeutic approaches and associated mortality rates. Methods: A narrative review was conducted using data sourced from the PubMed/MedLine and Scopus databases. Results: A total of 19 articles described infections in 32 patients involving Exophiala spp. fungemia. The mean patient age was 49.2 years, and 65.6% were male. Central venous catheters emerged as the leading predisposing factor (96.9%). Fever represented the most frequent clinical presentation (50%), followed by organ dysfunction (21.9%). The yeast generally demonstrated susceptibility to voriconazole and itraconazole. Voriconazole was also the most frequently administered antifungal (62.5%), followed by amphotericin (31.3%) and micafungin (28.1%). Overall mortality reached 34.4%, with 25% of deaths specifically caused by the infection. Conclusions: Given the potential of Exophiala spp. to cause severe fungemia, healthcare professionals, particularly clinicians and microbiologists, should consider this pathogen in the differential diagnosis when black yeast is detected in blood cultures, especially in patients with immunodeficiency or significant comorbidities, to ensure timely and accurate identification. Full article

Background/Objectives: The dual targeting of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) represents an effective approach for cancer treatment. The current study involved the design, synthesis, and biological evaluation of a new series of purine-containing hydrazones, 6–24 (a,b), as anticancer agents targeting EGFR and HER2 kinases. Methods: The proposed compounds were initially screened in silico using molecular docking to investigate their expected binding affinity to the active sites of EGFR and HER2 kinase domains. Subsequently, the compounds were synthesized and evaluated in vitro for their antiproliferative activity, using the MTT assay, against the various cancer cell lines A549, SKOV-3, A2780, and SKBR-3, with lapatinib as the reference drug. The most active derivatives were then examined to determine their inhibitory activity against EGFR and HER2 kinases. Results: Among the assessed compounds, significant antiproliferative activity was demonstrated by 19a, 16b, and 22b. 19a exhibited substantial anticancer efficacy against A549 and SKBR-3, with IC₅₀ values of 0.81 µM and 1.41 µM, respectively. This activity surpassed lapatinib, which has an IC₅₀ of 11.57 µM on A549 and 8.54 µM on SKBR-3 cells. Furthermore, 19a, 16b, and 22b exhibited superior EGFR inhibitory efficacy compared with lapatinib (IC₅₀ = 0.13 µM), with IC₅₀ values of 0.08, 0.06, and 0.07 µM, respectively. Regarding HER2, 22b demonstrated the greatest potency with an IC₅₀ of 0.03 µM, equipotent to lapatinib (IC₅₀ = 0.03 µM). Flow cytometry analysis of A549 cells treated with 19a and 22b indicated their ability to arrest the cell cycle during the G1 phase and to trigger cellular apoptosis. Conclusions: Compounds 19a, 16b, and 22b represent intriguing candidates for the development of an anticancer agent targeting EGFR and HER2 kinases. Full article

Tumor-associated macrophages (TAMs) are pivotal immune cells within the tumor stroma, whose dynamic alterations significantly impact tumor progression and therapeutic responses. Conventional methods for TAM detection, such as biopsy, are invasive and incapable of whole-body dynamic monitoring. In contrast, positron emission tomography (PET) and single-photon emission computed tomography (SPECT) offer a non-invasive imaging approach by targeting TAM-specific biomarkers like CD206, TSPO, and CCR2. This review comprehensively summarizes the advancements in TAM-targeted imaging probes, including cell surface markers, metabolic/functional markers, and multifunctional nanoprobe, while assessing their potential in tumor immune surveillance and tumor targeting therapeutic applications. While current probes, including ⁶⁸Ga-NOTA-anti-CD206 and ⁶⁴Cu-Macrin, have exhibited high specificity and theragnostic potential in preclinical and early clinical trials, challenges such as target heterogeneity, off-target effects, and clinical translation persist. Moving forward, the advancement of multi-target probes, optimization of pharmacokinetics, and incorporation of multimodal imaging technologies are anticipated to further enhance the impact of TAM-targeted imaging in precision medicine and tumor immunotherapy, fostering the refinement of personalized treatment strategies and improving patient outcomes. Full article

Background: Bone marrow mesenchymal stem cells (BM-MSCs) are significant in chemo- and radiotherapy resistance. Previous research has focused on BM-MSCs, demonstrating their functional involvement in cancer progression as mediators in the tumor microenvironment. They play multiple roles in tumorigenesis, angiogenesis, and metastasis. BM-MSC-derived exosomes (BM-MSCs-exo) are small vesicles, typically 50–300 nm in diameter, isolated from BM-MSCs. Some studies have demonstrated the tumor-suppressive effects of BM-MSCs-exo. Objective: This study aimed to investigate their role in modulating the impact of chemoradiotherapy (CRT) in different types of cervical cancer spheroid cells. Methods: The spheroids after treatment were subject to size measurement, cell viability, and caspase activity. Then, the molecular mechanism was elucidated by Western blot analysis. Results: We observed a reduction in spheroid size and an increase in cell death in HeLa spheroids, while no significant changes in size or cell viability were found in SiHa spheroids. At the molecular level, CRT treatment combined with BM-MSCs-exo in HeLa spheroids induced apoptosis through the activation of the NF-κB pathway, specifically via the NF-κB1 (P50) transcription factor, leading to the upregulation of apoptosis-related molecules. In contrast, CRT combined with BM-MSCs-exo in SiHa spheroids exhibited an opposing effect: although cellular viability decreased, caspase activity also decreased, which correlated with increased HSP27 expression and the subsequent downregulation of apoptotic molecules. Conclusion: Our study provides deeper insight into the potential of BM-MSCs-exo in cervical cancer treatment, supporting the development of more effective and safer therapeutic strategies for clinical application. Full article

Background and Objectives: Nausea and vomiting (NV) are common and distressing adverse effects among cancer patients undergoing treatment. Despite the widespread use of pharmacological antiemetics, these medications are often insufficient for controlling nausea and may cause medication interactions and side effects. Acupuncture has been proposed as a complementary therapy; however, the comprehensive analysis of its effects on NV across all emetogenic cancer treatments remains limited. This systematic review and meta-analysis aimed to evaluate the effectiveness and safety of acupuncture in managing NV in cancer patients undergoing chemotherapy, radiotherapy, or surgery. Materials and Methods: We conducted a comprehensive search across three electronic databases and two clinical registry platforms from inception to December 2024. Randomized controlled trials (RCTs) evaluating acupuncture for NV in cancer patients were included. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Safety outcomes were assessed based on the Common Terminology Criteria for Adverse Events (CTCAE). Results: Seventeen RCTs met the inclusion criteria, with twelve studies included in the meta-analysis. Acupuncture did not demonstrate significant effects on acute nausea (RR: 0.98; 95% CI: 0.84–1.15; p = 0.80) or acute vomiting (RR: 0.93; 95% CI: 0.65–1.32; p = 0.67). However, it significantly reduced delayed vomiting (RR: 0.76; 95% CI: 0.61–0.95; p = 0.02). Subgroup analysis demonstrated significant effects when acupuncture was administered for at least five days (RR: 0.56; 95% CI: 0.39–0.81; p = 0.002). The most frequently used acupoints were PC6, ST36, CV12, LI4, LR3, and ST25. No serious adverse events related to acupuncture treatments were reported, with only minor AEs such as localized bleeding and mild bruising observed. Conclusions: Acupuncture represents a safe and effective complementary therapy for managing delayed vomiting in cancer patients receiving emetogenic treatments. Clinicians can anticipate optimal benefits from at least five days of treatment, particularly using acupoints PC6, ST36, CV12, LI4, LR3, and ST25. Further high-quality studies are needed to establish standardized treatment regimens and explore its comprehensive effects on NV. Full article

Background: Male breast cancer (MBC) is extremely rare, representing less than 1% of breast cancer (BC). Owing to the rarity, there is a substantial knowledge gap regarding the survival trends of MBC compared with female breast cancer (FBC). Methods: We queried the National Cancer Database for BC patients diagnosed during 2004–2018 and utilized an inverse propensity weighted cox regression model assessed the association between sex and overall survival (OS) and survival trends over time by sex. Results: We identified 24,055 MBC and 2,532,470 FBC patients. Patients with MBC were older (mean age: 65.6 vs. 61.4 years), and more likely to have stage IV at diagnosis (7% vs. 4.7%), larger tumors (cT4: 6% vs. 3.7%), and node-positive disease (18.5% vs. 15.5%) (p < 0.001) compared with FBC. MBC were more likely to be estrogen (ER) (88.5% vs. 78.5%) and progesterone receptor (PR) (79.6% vs. 68%) positive and less likely to be HER2 receptor positive (7.9% vs. 9.3%) or triple negative (2.8% vs. 7.6%) compared with FBC (all p < 0.001). The OS rates were lower in MBC compared with FBC (5-year: 73% vs. 83%; 10-year: 54% vs. 70%, p < 0.001). In the propensity weighted cox-regression model, males had higher mortality than females with BC (HR 2.8, 95% CI 2.88–2.9, p < 0.001). The 5-year OS rates increased steadily for FBC from 2004–2015; however, the survival rates did not improve for MBC over the last decade. Conclusions: Our study shows that MBC patients continue to have poor OS compared with patients with FBC and no significant improvement in survival of MBC patients over the past decade. These results underscore the need to investigate personalized treatment interventions for patients with MBC to improve outcomes. Full article

Background: The aim was to explore the association between coping strategies (CSs) and health-related quality of life (HRQoL) in breast cancer (BC) survivors and to analyze the role of relevant sociodemographic and clinical variables. Methods: A cross-sectional study involving 305 women under follow-up for surgically treated BC in Spain. CSs were measured using the Brief Coping Orientation to Problems Experienced Scale and the HRQoL with the Short-Form Health Survey (SF-12). Results: The mean age at BC diagnosis for participants was 57.4 years, with 60.3% of diagnoses at the local stage. Most frequent complementary treatments were radiotherapy (53.4%) and chemotherapy (33.1%). Adaptative CS scores were positively associated both with higher physical HRQoL (adjusted regression coefficient: 2.19; 95% confidence interval: 0.11; 4.27, p-value: 0.039) and mental HRQoL scores (coef.: 2.65: 95%CI: 0.25; 5.04, p-value: 0.030). Maladaptive CS scores were inversely associated with mental HRQoL scores (coef.: −3.92; 95%CI: −6.62; −1.22, p-value: 0.005). The effects were stronger among women with a favorable BC prognosis. Conclusions: Adaptive CSs positively affected the physical and mental HRQoL, while maladaptive CSs negatively affected the mental HRQoL. Therefore, psychosocial interventions that promote adaptive CSs and avoid maladaptive ones could improve the well-being of women with a favorable BC prognosis. Full article

Background/Objectives: The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway is a critical mediator of immune regulation, inflammation, and cancer progression. Although implicated in colorectal cancer (CRC) pathogenesis, its molecular heterogeneity and clinical significance remain insufficiently characterized—particularly within early-onset CRC (EOCRC) and across diverse treatment and demographic contexts. We present AI-HOPE-JAK-STAT, a novel conversational artificial intelligence platform built to enable the real-time, natural language-driven exploration of JAK/STAT pathway alterations in CRC. The platform integrates clinical, genomic, and treatment data to support dynamic, hypothesis-generating analyses for precision oncology. Methods: AI-HOPE-JAK-STAT combines large language models (LLMs), a natural language-to-code engine, and harmonized public CRC datasets from cBioPortal. Users define analytical queries in plain English, which are translated into executable code for cohort selection, survival analysis, odds ratio testing, and mutation profiling. To validate the platform, we replicated known associations involving JAK1, JAK3, and STAT3 mutations. Additional exploratory analyses examined age, treatment exposure, tumor stage, and anatomical site. Results: The platform recapitulated established trends, including improved survival among EOCRC patients with JAK/STAT pathway alterations. In FOLFOX-treated CRC cohorts, JAK/STAT-altered tumors were associated with significantly enhanced overall survival (p < 0.0001). Stratification by age revealed survival advantages in younger (age < 50) patients with JAK/STAT mutations (p = 0.0379). STAT5B mutations were enriched in colon adenocarcinoma and correlated with significantly more favorable trends (p = 0.0000). Conversely, JAK1 mutations in microsatellite-stable tumors did not affect survival, emphasizing the value of molecular context. Finally, JAK3-mutated tumors diagnosed at Stage I–III showed superior survival compared to Stage IV cases (p = 0.00001), reinforcing stage as a dominant clinical determinant. Conclusions: AI-HOPE-JAK-STAT establishes a new standard for pathway-level interrogation in CRC by empowering users to generate and test clinically meaningful hypotheses without coding expertise. This system enhances access to precision oncology analyses and supports the scalable, real-time discovery of survival trends, mutational associations, and treatment-response patterns across stratified patient cohorts. Full article

Background: Epigenomic instability accelerates mutations in tumor suppressor genes and oncogenes, contributing to malignant transformation. Histone modifications, particularly methylation and acetylation, significantly influence tumor biology, with chromo-, bromo-, and Tudor domain-containing proteins mediating these changes. This study investigates how genes encoding these domain-containing proteins affect colorectal cancer (CRC) prognosis. Methods: Using CRC data from the GSE39582 and TCGA datasets, we identified domain-related genes via GeneCards and developed a prognostic signature using LASSO-COX regression. Patients were classified into high- and low-risk groups, and comparisons were made across survival, clinical features, immune cell infiltration, immunotherapy responses, and drug sensitivity predictions. Single-cell analysis assessed gene expression in different cell subsets. Results: Four domain-related genes (AKAP1, ORC1, CHAF1A, and UHRF2) were identified as a prognostic signature. Validation confirmed their prognostic value, with significant differences in survival, clinical features, immune patterns, and immunotherapy responses between the high- and low-risk groups. Drug sensitivity analysis revealed top candidates for CRC treatment. Single-cell analysis showed varied expression of these genes across cell subsets. Conclusions: This study presents a novel prognostic signature based on domain-related genes that can predict CRC severity and offer insights into immune dynamics, providing a promising tool for personalized risk assessment in CRC. Full article

The rapid and accurate detection of pathogenic bacteria and viruses is critical for infectious disease control and public health protection. While conventional methods (e.g., culture, microscopy, serology, and PCR) are widely used, they are often limited by lengthy processing times, high costs, and specialized equipment requirements. In recent years, metal nanocluster (MNC)-based biosensors have emerged as powerful diagnostic platforms due to their unique optical, catalytic, and electrochemical properties. This systematic review comprehensively surveys advancements in MNC-based biosensors for bacterial and viral pathogen detection, focusing on optical (colorimetric and fluorescence) and electrochemical platforms. Three key aspects are emphasized: (1) detection mechanisms, (2) nanocluster types and properties, and (3) applications in clinical diagnostics, environmental monitoring, and food safety. The literature demonstrates that MNC-based biosensors provide high sensitivity, specificity, portability, and cost-efficiency. Moreover, the integration of nanotechnology with biosensing platforms enables real-time and point-of-care diagnostics. This review also discusses the limitations and future directions of the technology, emphasizing the need for enhanced stability, multiplex detection capability, and clinical validation. The findings offer valuable insights for developing next-generation biosensors with improved functionality and broader applicability in microbial diagnostics. Full article

Air pollution caused by pesticide residues is an emerging concern in urban environments influenced by nearby agricultural activities. In this study, weekly air samples were collected between May 2018 and March 2020 in Strasbourg, France, to quantify 104 pesticides in both gas and particle phases using GC-MS/MS and LC-MS/MS. Herbicides and fungicides were the most frequently detected classes, appearing in 98% of both phases followed by insecticides. Key compounds such as metalaxyl-M, diphenylamine, and bifenthrin were present in over 90% of samples. Concentrations ranged from 2.5 to 63 ng m⁻³ weekly, with cumulative annual loads exceeding 1200 ng m⁻³. Gas–particle partitioning revealed that highly volatile compounds like azinphos-ethyl favored the gas phase, while less volatile ones like bifenthrin and tebuconazole partitioned >95% into particles. A third-degree polynomial regression (R² of 0.74) revealed a nonlinear relationship between Kₚ and particle-phase concentrations, highlighting a threshold above Kₚ of 0.025 beyond which compounds accumulate disproportionately in the particulate phase. Seasonal variability showed that 36% of the annual pesticide load occurred in autumn, with total airborne levels peaking near 400 ng m⁻³, while the lowest load occurred during summer. Principal component analysis identified rainfall and total suspended particles as major drivers of pesticide phase distribution. The inhalation health risk assessed yielded hazard index values < 1 × 10⁻⁷ for all population groups, suggesting negligible non-cancer risk. This study highlights the prevalence, seasonal dynamics, and partition behavior of airborne pesticides in urban air and underscores the need for regulatory attention to this overlooked exposure route. Full article

Bovine papillomatosis, caused by a growing group of bovine papillomaviruses (BPVs), is a disease with benign proliferative lesions (papillomas) that may progress to malignancies due to immunological, environmental, or viral factors. This study investigated BPV type diversity in cattle from the Province Santo Domingo de Tsáchilas in Ecuador. Warty lesions were collected from 30 cattle across eight farms. Nucleic acids were extracted using a silicon dioxide-based method, and the partial L1 gene was amplified with PCR. DNA sequences were analyzed using maximum likelihood phylogenetics. Fifty-seven warty lesions yielded ten well-known BPV types: BPV1, BPV2, BPV4, BPV6, BPV8, BPV9, BPV10, BPV13, BPV14, and BPV42. Recently described viral types, BPV-CR2 from Costa Rica and BPV/BR-UEL08 from Brazil, were also detected, alongside a putative novel viral type, BPVEC2024-6-22.1—likely belonging to the genus Xipapillomavirus. This genus had the highest overall count. In contrast, Deltapapillomaviruses were found across all sampled farms. This study underscores BPV diversity in this localized region of Ecuador, and includes genotypes linked to cancers such as enzootic hematuria. The findings provide important epidemiological insights, contributing to vaccine development or immune therapy and improved disease management. Full article