Search Results (3,709)

Fluorene poses ecological and health hazards that originate from biomass combustion and petroleum. However, some microorganisms can counter fluorene through complex enzymatic degradation pathways. This research aimed to explore the catalytic efficiency of enzymes on metabolites and their toxicity levels throughout the fluorene biodegradation pathway. Several web servers and software were used to characterize them and analyse molecular dockings between ligands and proteins. Fluorene and its metabolites have mild toxicities to the brain, lung, neurons, and kidneys, and consequent endpoints cause mutations, cancer, and ecotoxicity at different levels. The catalytic enzymes are well-folded, single-chained, medium-sized proteins that are acidic, thermostable, and with few exceptions, hydrophilic, cytoplasmic, non-allergenic, and nonvirulent, possessing multiple active sites. The ERRAT, PROCHECK, and VERIFY 3D tools successfully validated the SWISS-modelled 3D structures of proteins. Molecular docking results showed moderate binding affinities between proteins and ligands, ranging from −9.4 to −6.1 kcal/mol, indicating potential activities of the enzymes. This computational study supports the conventional fluorene degradation pathway and may provide a new avenue for further research. Full article

Brain metastases remain a major problem for cancer patients, impacting their treatment and survival. The pathogenesis of brain metastases is largely unknown. Recent reports indicate that the adhesion molecule protocadherin γ C3 (PCDHGC3) is differentially expressed in various cancer cells and endothelial cells of the blood–brain barrier (BBB), suggesting its involvement in the development of brain metastases. Therefore, we generated a PCDHGC3 knockout (KO) in the triple-negative breast cancer cell line HCC1806 and the malignant melanoma cell line A2058. Control and KO cells were compared using cell proliferation, adhesion and invasion assays, gene expression analyses and matrix metalloproteinase (MMP) activity assays. While the PCDHGC3 KO mutation led to increased proliferation in HCC1806 cells, with no difference observed in A2058, it significantly increased adhesion to in vitro BBB models as well as invasion in both HCC1806 and A2058 KO cell lines. Although changes in mRNA expression of genes involved in metastasis, angiogenesis and cell adhesion were found in PCDHGC3 KO breast cancer and melanoma cells, the number of genes with significantly increased mRNA expression was higher in A2058 KO cells than in HCC1806 KO cells. While the mRNA expression of MMP1 and 2 was increased in A2058 KO cells, no significant changes were found in HCC1806 KO cells. However, increased MMP activity in the cell culture medium was detected in HCC1806 KO cells, while A2058 KO cells showed lower MMP-activity compared to control. These findings provide insights into the role of PCDHGC3 in cancer cell extravasation during metastatic process and identify potential therapeutic targets for further investigation. Full article

Non-small-cell lung cancer (NSCLC) constitutes approximately all lung cancers (LCs), and metastasis remains a major challenge in its treatment, thus necessitating the detection of novel molecular players involved in this process. In this study, we performed a comprehensive analysis of microarray and RNA-seq cohorts extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) and associated them with metastasis-related genes involved in brain metastasis (BM) in NSCLC. We thus identified differentially expressed metastatic genes (DEMGs) and constructed a protein–protein interaction network (PPIN) using these DEMGs. These DEMGs were further analyzed for associations with patient age, gender, and tumor stage, and the significant impact of specific genes on overall survival (OS) was assessed to determine the prognostic significance of the identified targets. We finally constructed a three-node microRNA (miRNA) feed-forward loop (FFL) involving miR-23b-3p, CD44, and five transcription factors (TFs) [EOMES, FOS, FOSL1, GLIS3, TP63] specific to NSCLC metastasis. Further mutational analysis of these FFL elements revealed that all were altered in the patient samples analyzed. Thus, our study identified potential genomic drivers that may play crucial roles in NSCLC BM. Overall, it provides valuable insights for the discovery of novel therapeutic targets in the management of NSCLC metastasis. However, further in vitro and in vivo experimentations are needed to justify the prognostic role of NSCLC biomarkers in BM pathogenesis. Full article

Background: Evaluation of chromosome aneuploidy and gene-level copy number alterations for diagnosis, prognosis, and therapeutic decision-making in solid tumors is the standard of care. Chromosomal microarray (CMA), next-generation sequencing (NGS), immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH) are the gold standard for detecting these variants in tumor tissue. In contrast to most solid tumors, cancers of the central nervous system (CNS) pose a unique challenge for effective detection via plasma due to the blood–brain barrier (BBB), with the additional challenges of brain biopsy or surgery being highly invasive and posing a significant risk to the patient. The Belay Ascent™ liquid biopsy test uses low-pass whole-genome sequencing (LP-WGS) to report on chromosome arm-level aneuploidy and gene-level copy number variants (CNVs) in cerebrospinal fluid (CSF) to inform diagnosis, prognosis, and therapeutic decision-making in CNS tumors. Methods: This study presents the equivalence of Ascent™ in detecting chromosome arm-level aneuploidy and gene-level CNVs using 48 tissue specimens followed by a clinical validation using a cohort of 32 CSF specimens with matched tissue-based tumor profiling information. Results: Equivalence of Ascent™ in detecting chromosome arm-level aneuploidy and gene-level CNVs using 48 tissue specimens was shown to have 100% and 97% positive percent agreement (PPA), respectively, compared to the gold standard of CMA/NGS. The validation cohort of 32 CSF specimens demonstrated 78% and 90% PPA for aneuploidy and gene-level CNVs, respectively. Clinical impact of Ascent™ was demonstrated, with 243 production cases able to inform the diagnosis and management of CNS tumors with high accuracy. Conclusions: Given the paucity of cells in CSF, limiting the use of karyotyping, CMA, IHC, and FISH, the Belay Ascent™ test provides a highly sensitive novel minimally invasive method for the evaluation of chromosome aneuploidy and gene-level CNVs in CSF. Full article

The demand for advanced detection methods and accurate staging remains a global challenge in cancer diagnosis. Even though traditional deep learning models in medical imaging achieve high precision, they suffer from limited explainability and multimodal reasoning due to their black-box nature, thereby limiting their clinical applicability. To address this gap, recent research has increasingly explored multimodal approaches that integrate visual and textual clinical data to enhance diagnostic accuracy and interpretability. This study presents a bibliometric analysis of 408 publications from 2021 to 2025, collected from Web of Science and Scopus, using VOSviewer and R-Bibliometrix to map citation networks, co-authorship, and keyword co-occurrences. The results reveal a rapid growth from 1 publication in 2021 to 269 in 2025, with significant contributions from leading countries and institutions. Thematic analysis indicates a shift from conventional convolutional approaches toward transformer-based and self-supervised methods, alongside increasing attention to multimodal learning in cancer imaging tasks such as breast, lung, and brain cancer analysis. Overall, this study provides a structured overview of the evolving research landscape, highlighting key trends, emerging themes, and research gaps to inform future developments in multimodal artificial intelligence for cancer diagnosis. Full article

Background/Objectives: Several trials have highlighted the importance of PARP inhibitors (PARPi) in the treatment of BRCA-associated breast cancers (BC), initiating changes in practice. However, data on the real-life outcomes of PARPi therapy is limited. In this study, we characterized the clinical characteristics and outcomes of patients with advanced BC and germline BRCA pathogenic variants (PVs) who received PARPi therapy. Methods: We conducted a retrospective single-institution cohort study of patients with advanced BC and germline BRCA1/2 PVs treated with PARPi. Outcomes included objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Survival was estimated using Kaplan–Meier methods, and prognostic factors were evaluated using Cox regression analysis. Results: Of the 107 patients treated with PARPi, 48 (44.9%) and 59 (55.1%) had BRCA1 and BRCA2 PVs, respectively. Ninety-seven patients (90.7%) had invasive ductal carcinoma and 42 (39.3%) had triple-negative BC. Nineteen (17.8%) patients had de novo metastatic BC. Sixty-two (57.9%) patients received at least one line of systemic therapy before PARPi; 24 (22.4%) patients received prior platinum. ORR was 62.6%, and the median duration of response (DoR) was 7 months (range, 2.1–96.2). The median PFS was 9 months (95% CI, 6.9–10.5) and median OS was 25.8 months (95% CI, 18.7–31.5). In multivariable models for PFS, bone metastases (HR = 2.25; 95% CI, 1.40–3.61; p = 0.0008) and lung metastases (HR = 2.40; 95% CI, 1.45–3.98; p = 0.0007) were independently associated with increased risk of progression or death. In multivariable models for OS, brain metastases (HR = 3.54; 95% CI, 1.59–7.90; p = 0.0020), bone metastases (HR = 2.22; 95% CI, 1.27–3.88; p = 0.0050), and lung metastases (HR = 2.38; 95% CI, 1.38–4.11; p = 0.0018), were independently associated with increased risk of death. Conclusions: The clinical outcomes of our real-world patients are similar to those reported in previous clinical trials. In addition, metastatic site distribution was independently prognostic for survival outcomes and may support baseline risk stratification at the time of PARPi initiation. Further studies of predictive markers of response and resistance, as well as sequencing with platinums and combinations with other targeted agents, are needed to optimize the benefits of PARPi in this patient population. Full article

Background: The care and management of a pregnant woman suffering from end-stage brain cancer is surrounded by medical, legal, and ethical controversies. When this brain pathology leads to brain death (BD), continuation of life-sustaining treatments has been considered futile and unethical. An exception could be the case of pregnancy, in order to deliver a healthy neonate. Aim: The presentation of a pregnant woman with a terminal stage brain astrocytoma, admitted in the intensive care unit (ICU) to support the pregnancy, until optimal fetal viability, after she had neurological deterioration and confirmed BD, and a brief literature review of previously relevant published cases. Case Presentation: A 36-year-old woman with a medical history of brain astrocytoma in the last 2 years was admitted in ICU for the first time due to status epilepticus, six months after she stopped anticonvulsant therapy. Her epilepsy was controlled, and a pregnancy of 14 weeks was confirmed. Two weeks later, she deteriorated. After a multidisciplinary approach, it was decided to mechanically ventilate the patient and support the pregnancy. Brain death was determined after a couple of days. Results: A cesarean section was performed 11 weeks after BD diagnosis (at 27 weeks of gestational age) resulting in the delivery of a live, premature infant, weighing 549 gr. Conclusions: Maternal corporeal support can maximize the chances for survival in the neonate by prolonging the pregnancy of a brain-dead woman. Full article

Surgical precision is critical in oncology, where complete tumor resection while preserving healthy tissue directly influences patient outcomes. Traditional intraoperative diagnostic tools, such as frozen-section analysis, are limited by time constraints, tissue sampling, and interpretative variability. Intraoperative mass spectrometry (MS) has recently emerged as a transformative approach, enabling rapid, label-free molecular profiling of surgical specimens in real time. Several technologies—including Rapid Evaporative Ionization Mass Spectrometry (REIMS, “iKnife”), Desorption Electrospray Ionization (DESI-MS), Matrix-Assisted Laser Desorption/Ionization (MALDI-MS) Imaging, Picosecond InfraRed Laser mass spectrometry (PIRL-MS), and novel devices such as the MasSpec Pen—offer unique strategies for intraoperative tumor characterization. Applications have been demonstrated across multiple cancer types, including brain, breast, gastrointestinal, and urogenital malignancies, where MS can improve margin assessment, tumor classification, and surgical guidance. Beyond its clinical promise, intraoperative MS faces technical and translational challenges, including high infrastructure costs, a lack of standardization, and the need for robust multicenter validation. Integration with artificial intelligence, imaging modalities, and multi-omics approaches may further enhance its clinical utility. This review summarizes current technologies, clinical applications, limitations, and future perspectives of intraoperative MS in oncology, highlighting its potential to reshape surgical oncology practice. Full article

While the Blood–Brain Barrier (BBB) is essential for the protection and function of the Central Nervous System (CNS), it also represents a challenge for drug delivery in the treatment of CNS disorders due to its limited permeability and high expression of efflux transporters. Crossing the BBB becomes even more difficult when dealing with biomolecular therapeutics (e.g., monoclonal antibodies and Antisense Oligonucleotides) due to their hydrophilic nature and high molecular weight. Over the years, different strategies have been developed in order to maximize the ability of biopharmaceuticals to cross the BBB and be delivered to the CNS. Both non-invasive techniques, mainly consisting of developing innovative vectors or using non-conventional routes of administration (e.g., intranasal delivery), and invasive methods, such as intracerebroventricular/intrathecal administration, have been tested individually and in combination. Given the improvements achieved nowadays with both approaches, here, we plan to compare the advances in invasive techniques, such as those based on the use of device-assisted strategies, and the employment of the intranasal route of administration. We are also interested in reporting the applicability of both strategies in the treatment of aggressive forms of cancer, such as glioblastoma, as well as neurodegenerative diseases, in order to determine which technique can be considered a better choice in each specific case. Full article

Background: Minimal residual disease (MRD) assessment is an emerging tool for refining the risk of relapse following definitive therapy in non-small-cell lung cancer (NSCLC). However, data regarding its clinical impact on the decision-making process remain limited. We evaluated MRD feasibility and its impact in the real-world setting. Methods: A pooled retrospective analysis of longitudinal MRD data in NSCLC patients (n = 34: Signatera™ (Exome), n = 25, Guardant Reveal™, n = 9) was implemented. Co-primary endpoints: MRD feasibility and clinical impact on management (changes in surveillance intensity or therapy escalation/de-escalation). Secondary endpoints: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy for recurrence detection, and MRD lead time. Results: MRD was feasible in 32/34 patients (94.1%); longitudinal testing included two samples in 15 patients (44.1%) and three samples in 2 patients (5.9%). Signatera™ (Exome) failed in 2/25 (8.0%) due to insufficient tissue. MRD influenced management in 20/34 (58.8%) patients, most commonly supporting therapy de-escalation (15/34, 44.1%), followed by imaging surveillance modification (3/34, 8.8%) and therapy escalation (2/34, 5.9%). In univariable analysis, tumor grade and STAS were associated with MRD-driven management impact, but neither remained significant in multivariable analysis. With a median follow-up of 18.9 months (IQR 8.5–30.7), MRD was positive in 6/32 (18.8%), while recurrence/progression occurred in 10/32 (31.3%) patients. MRD yielded 21 true negatives, five true positives, five false negatives (including two isolated brain recurrences), and one false positive, corresponding to a sensitivity of 50.0%, specificity of 95.5%, PPV of 83.3%, NPV of 80.8%, and an accuracy of 81.3%. The median MRD lead time (n = 5) was 1.31 months (range, 0.46–5.52). Conclusions: In this real-world cohort, MRD testing was feasible and frequently guided clinical decisions, mainly supporting treatment de-escalation. MRD was highly specific but less sensitive. Prospective studies are needed to define optimal testing intervals and validate MRD-guided strategies. Full article

Background: Many studies evaluating central nervous system (CNS) metastases in breast cancer (BC) combine germline BRCA1 and BRCA2 pathogenic variant carriers, limiting gene-specific interpretation. We evaluated gene-specific overall survival (OS) after CNS metastasis and time to CNS involvement. Methods: We retrospectively identified BC patients with confirmed CNS metastases (1995–2022) from the Medical University of Vienna and the kConFab consortium. Germline status was classified as gBRCA1 PV, gBRCA2 PV, or non-carrier. Primary endpoint was OS from CNS metastasis diagnosis; secondary endpoint was CNS metastasis-free interval from primary BC diagnosis. Kaplan–Meier/log-rank tests were used for group comparisons. Multivariable Cox models assessed OS in complete cases, stratified by molecular subtype and adjusted for prognostic factors. Sensitivity analyses included subtype-adjusted and time-period models. Results: Among 115 patients (gBRCA1 n = 32, gBRCA2 n = 18, and non-carriers n = 65), median OS differed by germline status (p = 0.019): 20.0 months (95% CI 6.7–60.0) for gBRCA2 versus 7.1 months (95% CI 3.7–10.0) for gBRCA1 and 7.6 months (95% CI 3.4–12.0) for non-carriers. In subtype-stratified analyses, gBRCA1 showed similar mortality to non-carriers (HR 0.90, 95% CI 0.49–1.64, p = 0.730), while gBRCA2 showed a lower but non-significant hazard (HR 0.48, 95% CI 0.18–1.25, p = 0.131). Median CNS metastasis-free interval was longer for gBRCA2 (8.4 years) versus gBRCA1 (3.0 years) and non-carriers (3.1 years; p = 0.020). Sensitivity analyses were consistent. Conclusions: gBRCA2 carriers demonstrated longer unadjusted OS after CNS metastasis and a longer CNS metastasis-free interval compared with gBRCA1 carriers and non-carriers. However, these associations were attenuated and not statistically significant after adjustment, and should therefore be interpreted as hypothesis-generating. These findings supports further investigation of gene-specific CNS disease trajectories in larger cohorts. Full article

Glioblastoma (GBM) is the most aggressive and prevalent primary brain tumor in adults, characterized by rapid growth, diffuse infiltration, and a dismal prognosis. Despite advances in conventional therapies, the median survival remains approximately one year, emphasizing the urgent need for novel therapeutic strategies. GD2, a disialoganglioside overexpressed in several malignancies, has been implicated in tumorigenesis and metastasis and has been identified as a cancer stem cell marker. While previous reports have identified high levels of GD2 expression in gliomas compared to normal brain tissue, its role in GBM stemness remains controversial. In this study, we revisited prior findings refuting GD2′s involvement in GBM stemness by replicating key tumorigenesis experiments and further explored its impact on stemness properties such as migration and metabolic plasticity. Additionally, a phytochemical screen was used to identify natural compounds as potential inhibitors targeting GD2-mediated tumorigenesis. Our findings aim to clarify GD2′s role in GBM and provide insights into novel therapeutic interventions. Full article

Despite Morocco’s emergence as the world’s fourth-largest berry exporter, no comprehensive review has evaluated the polyphenol composition, antioxidant properties, and health benefits of raspberries (Rubus idaeus), blackberries (Rubus fruticosus), and blueberries (Vaccinium corymbosum) specifically within the Moroccan cultivation context. This narrative review synthesized evidence from phytochemical analyses, in vitro and in vivo studies, randomized controlled trials (RCTs), meta-analyses, and epidemiological data sourced from PubMed, Scopus, and Web of Science. Blackberries exhibited the highest total polyphenol content (149 μmol GAE/L) and antioxidant capacity, driven primarily by anthocyanin concentration and diversity. Antioxidant mechanisms included free radical scavenging, transition metal chelation, and upregulation of endogenous antioxidant enzymes. Pooled RCT data demonstrated that regular consumption (150–300 g/day) significantly reduced systolic blood pressure (−2.72 mmHg), LDL cholesterol (−0.21 mmol/L), and fasting glucose (−2.70 mg/dL). Additional benefits included neuroprotection via blood-brain barrier crossing and brain-derived neurotrophic factor (BDNF) elevation, prebiotic modulation of Bifidobacterium, Lactobacillus, and Akkermansia populations, and anti-cancer activity via nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) inhibition. Processing significantly affected bioactive retention: freezing preserved phenolic compounds effectively, while conventional drying reduced anthocyanin content by up to 49%. These findings support the integration of Moroccan-cultivated berries—particularly from the Gharb, Loukkos, and Souss-Massa regions—into evidence-based dietary and functional food strategies. Priority research gaps include bioavailability assessment, dose-response characterization, and cultivar-specific phytochemical profiling under Moroccan agro-climatic conditions. Full article

Background: Breast cancer brain metastases (BCBMs) are clinically challenging, and treatment decisions are influenced by tumor biology. Because receptor profiles may differ between primary breast tumors and brain metastases and brain biopsy may be impractical, non-invasive imaging biomarkers may provide useful biologic correlates. We evaluated whether diffusion-weighted imaging (DWI)-derived apparent diffusion coefficient (ADC) histogram metrics from BCBM were associated with primary tumor estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status; the Ki-67 proliferation index; and luminal status. Methods: This retrospective exploratory single-center study included 72 adults with BCBM who underwent standardized 1.5T brain magnetic resonance imaging. The largest lesion in each patient was segmented on ADC maps in FireVoxel. ADC histogram features, including percentiles, were extracted. Using primary tumor biomarker status as the reference, candidate metrics were screened by univariable logistic regression. Parsimonious multivariable models included age, log-transformed lesion volume, and a single selected ADC percentile scaled by ×10. Discriminatory performance was assessed using area under the receiver operating characteristic curve (AUC); thresholds were derived with the Youden index. No external validation was performed. Results: Low-percentile ADC metrics were associated with ER positivity, PR positivity, and luminal disease, whereas no meaningful ADC histogram discrimination was observed for HER2. In multivariable models, ADC10×10 predicted ER positivity (odds ratio [OR] 0.441; AUC 0.847) and PR positivity (OR 0.478; AUC 0.819). Ki-67 positivity was best predicted by ADC75×10 (OR 3.095; AUC 0.905), although this finding should be interpreted cautiously. Luminal status (non-luminal vs. luminal) was predicted by ADC10×10 (OR 2.251; AUC 0.832). Conclusions: ADC histogram analysis from DWI in BCBM showed exploratory associations with primary tumor hormone receptor status and luminal subtype, but not HER2. These findings support ADC histogram features as candidate imaging biomarkers, but the Ki-67 result and all model performance estimates require cautious interpretation and independent external validation in multicenter cohorts. Full article

Glioblastomas (GBMs) are the most aggressive form of brain cancer recalcitrant to both current standard-of-care and immune checkpoint therapies that benefit other cancer patients. Adoptive cell therapies (ACT) using patients’ own immune cells have long been explored as a treatment strategy, including the historically studied lymphokine-activated killer (LAK) cells, the evolving chimeric antigen receptor (CAR) directed immune cells, the newly emerging tumor-infiltrating T lymphocyte (TIL) therapies, and others. Preclinical and clinical studies have shown promise but also highlighted significant challenges. In this review, we summarize these findings, highlight recent developments, discuss current limitations, and emphasize how ACT may benefit from contemporary and future insights into the co-evolution of TILs with other cells within the GBM tumor microenvironment (TME). Full article