Search Results (13,159)

Background/Objectives: HER2, a critical diagnostic marker and therapeutic target in breast cancer, is a membrane receptor that forms diverse signaling complexes, the constituents of which have not been fully characterized in actual breast cancer tissues. Methods: In this study, we applied the Rapid Immunoprecipitation Mass Spectrometry of Endogenous Proteins (RIME) method, originally developed to explore transcription factor complexes, to identify the complexes formed by HER2 in HER2-positive breast cancer specimens. Results: Through our approach, we successfully identified multiple complex components, including MARCKS, a novel HER2-interacting partner, which we verified using both proximal ligation assay in cultured cells and immunohistochemistry in tissue sections. TCGA analysis further revealed that high MARCKS expression significantly correlates with ER negativity, as confirmed by multivariate analysis, suggesting its potential role as a prognostic indicator in aggressive breast cancer subtypes. Conclusions: These results demonstrate the capability of RIME to elucidate interactomes of membrane proteins such as HER2 in clinical tissue specimens. Furthermore, this study highlights its broader applicability beyond nuclear proteins, underscoring its potential for discovering novel prognostic and diagnostic clinical markers in diverse cancer types. Full article

In online communities, polarization refers to the phenomenon in which individuals become more divided and extreme in their opinions due to their exposure to specific content. In this paper, we present a network-based framework for evaluating polarization levels in Online Social Networks (OSNs). Starting from a dataset of comments, our framework creates a network of user interactions and leverages the Louvain algorithm, the Rao’s Quadratic Entropy, and ego networks to assess the polarization level of communities and the most influential users. To test our framework, we leveraged a dataset of tweets about climate change. After performing Extraction, Transformation and Loading activities on the dataset, we evaluated its labels, identified communities, and analyzed their polarization level and that of the most influential users. We also analyzed the ego networks of believers and deniers and the aggressiveness of the corresponding tweets. Our analysis revealed the existence of polarized communities and homophily among the most influential users. It also showed that the type of communication used to disseminate information influences the polarization level of both communities and individual users. These results demonstrate our framework’s ability to support the polarization analysis in OSNs. Full article

Neuroblastoma (NB) is an aggressive pediatric cancer, with high-risk patients facing a five-year survival rate of ~50%. Standard therapies, including surgery, chemotherapy, radiation, and immunotherapy, are associated with significant long-term toxicities and frequent relapse. Histone deacetylase (HDAC) inhibitors have emerged as promising agents for cancer therapy, given their role in modulating gene expression and tumor phenotypes. This study evaluated M344 [4-(dimethylamino)-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide], an HDAC inhibitor, for its efficacy and mechanisms of action against NB. Analysis of clinical NB Gene Expression Omnibus data revealed advanced-stage tumors exhibit higher HDAC expression relative to early-stage samples. M344 treatment effectively increased histone acetylation, induced G0/G1 cell cycle arrest, and activated caspase-mediated cell death. Relative to vorinostat, an HDAC inhibitor in clinical use for lymphoma and clinical trials for NB, M344 displayed superior cytostatic, cytotoxic, and migration-inhibitory effects. In vivo, metronomic M344 dosing suppressed tumor growth and extended survival. Combination therapy with M344 and topotecan improved topotecan tolerability, while M344 co-administration with cyclophosphamide reduced tumor rebound post-therapy. In total, M344 demonstrated strong therapeutic potential for NB, offering improved tumor suppression, reduced off-target toxicities, and enhanced control of tumor growth post-therapy. These findings support further investigation of HDAC inhibitors, such as M344, for clinical application in NB treatment. Full article

Glioblastoma multiforme (GBM), the most aggressive primary brain tumor in adults, has a poor prognosis due to rapid recurrence and treatment resistance. This review examines the evolution of radiotherapy (RT) for GBM management, from whole-brain RT to modern techniques like intensity-modulated RT (IMRT) and volumetric modulated arc therapy (VMAT), guided by 2023 European Society for Radiotherapy and Oncology (ESTRO)-European Association of Neuro-Oncology (EANO) and 2025 American Society for Radiation Oncology (ASTRO) recommendations. The standard Stupp protocol (60 Gy/30 fractions with temozolomide [TMZ]) improves overall survival (OS) to 14.6 months, with greater benefits in O6-methylguanine-DNA methyltransferase (MGMT)-methylated tumors (21.7 months). Tumor Treating Fields (TTFields) extend median overall survival (mOS) to 31.6 months in MGMT-methylated patients and 20.9 months overall in supratentorial GBM (EF-14 trial). However, 80–90% of recurrences occur within 2 cm of the irradiated field due to tumor infiltration and radioresistance driven by epidermal growth factor receptor (EGFR) amplification, phosphatase and tensin homolog (PTEN) mutations, cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions, tumor hypoxia, and tumor stem cells. Pseudoprogression, distinguished using Response Assessment in Neuro-Oncology (RANO) criteria and positron emission tomography (PET), complicates response evaluation. Targeted therapies (e.g., bevacizumab; PARP inhibitors) and immunotherapies (e.g., pembrolizumab; oncolytic viruses), alongside advanced imaging (multiparametric magnetic resonance imaging [MRI], amino acid PET), support personalized RT. Ongoing trials evaluating reirradiation, hypofractionation, stereotactic radiosurgery, neoadjuvant therapies, proton therapy (PT), boron neutron capture therapy (BNCT), and AI-driven planning aim to enhance efficacy for GBM IDH-wildtype, but phase III trials are needed to improve survival and quality of life. Full article

Monilinia fructigena, a causal agent of brown rot in apple and other fruit crops, poses a significant threat to fruit production and postharvest quality in temperate regions. This study reports on the molecular and morphological identification of M. fructigena isolates obtained from symptomatic apple fruits in the Almaty region of Kazakhstan. Nine isolates were characterized through a combination of morphological assessment, real-time PCR, target locus (ITS and TEF1-α gene) sequencing, and whole genome sequencing using nanopore sequencings. Morphological analysis revealed typical features of M. fructigena, including blastoconidia and microconidia. Pathogenicity tests on ‘Idared’ and ‘Golden Delicious’ apples confirmed the high aggressiveness of the isolates, with lesion development observed within 24–48 h post-inoculation. Molecular identification via real-time PCR and target sequencing confirmed all isolates as M. fructigena with high mapping quality and sequence identity. The whole genome sequencing of a representative isolate further validated the species identity based on comparative alignment with Monilinia reference genomes. Thus, the combination of the used traditional and molecular methods allowed us to unambiguously identify the isolated fungus as M. fructigena. This integrative approach enhances the understanding of Monilinia species in Central Asia and supports the implementation of modern molecular tools for phytopathogen surveillance and agricultural biosecurity. Full article

Background/Objectives: Gingival recession poses significant challenges in periodontal therapy, particularly in procedures aimed at achieving predictable root coverage and long-term stability of grafts. Conditioning of the root surface plays a crucial role in improving biomaterial adhesion and facilitating periodontal regeneration. This in vitro study aimed to evaluate the morphological and microroughness alterations of root cementum following different mechanical and chemical conditioning protocols commonly used in mucogingival surgery. Methods: Forty extracted human single-rooted teeth were randomly allocated into eight groups: untreated control, mechanical scaling alone, and scaling combined with ethylenediaminetetraacetic acid (EDTA), citric acid, phosphoric acid, tetracycline, doxycycline, or saline. Surface roughness was measured using contact profilometry, while structural modifications were analyzed via scanning electron microscopy. Results: Statistically significant intergroup differences (p < 0.05) were observed. Baneocin treatment produced the most conservative changes, with limited surface roughness and minimal structural alteration, whereas phosphoric acid, tetracycline, and EDTA caused pronounced demineralization and surface porosity. Citric acid and doxycycline induced moderate alterations, with partial preservation of cementum integrity. The null hypothesis assuming no surface or morphological changes was rejected. Conclusions: These findings indicate that low-aggressiveness agents may achieve an optimal balance between surface decontamination and cementum preservation, which is critical for enhancing graft integration and improving clinical outcomes in root coverage surgery. Full article

Background: Gastrointestinal neuroectodermal tumour (GNET), also known as clear cell sarcoma (CCS) of the gastrointestinal tract, is a rare neural crest-derived malignancy characterized by EWSR1-ATF1 or EWSR1-CREB1 fusions. Due to its rarity, there is limited evidence and no established guidelines for standard management. GNET is aggressive, with high rates of local recurrence, metastasis, and mortality. Case Presentation: We report the case of a 46-year-old woman with a family history of gastrointestinal cancers who was diagnosed in 2020 with an intestinal GNET. She underwent a segmental enterectomy as the first step of multimodal therapy. After three years of follow-up, she developed hepatic and peritoneal metastases. In November 2023, she began combined therapy with the anti-VEGF tyrosine kinase inhibitor cabozantinib and the immune checkpoint inhibitor nivolumab. The patient has maintained stable disease for 18 months with good tolerance and no adverse events. Molecular analysis of the tumour, which showed an EWSR1-CREB1 fusion, supported the selection of targeted therapy and immunotherapy as the preferred treatment approach. Conclusions: Immunotherapy and targeted therapy show promise for GNET/CCS treatment, but clinical standards are lacking, and evidence comes primarily from case reports. Additional data are needed to determine the best sequence and combination of therapies for this very rare disease. Full article

Background and Clinical Significance: Rhabdomyosarcoma (RMS) is a rare and aggressive malignant soft-tissue sarcoma (STS) arising from skeletal connective tissues and is most commonly seen in the pediatric population. The pleomorphic subtype is mostly seen in adults in the sixth and seventh decades of life, representing 1% of all histological types of RMS and having a very poor prognosis. Case Presentation: This report presents the case of a 63-year-old male with a medical history of papillary thyroid cancer, who presented with an ulcer-hemorrhagic malignant tumor, namely, a poorly differentiated desmin-positive pleomorphic rhabdomyosarcoma (PRMS), with impressive dimensions located on the posterior thoracic wall. This tumor was surgically removed via a wide resection, followed by palliative chemotherapy and radiotherapy. However, the patient relapsed locally, with pulmonary, bone, and lymph node metastases. The peculiarity of this case is represented by the rapid growth, aggressive nature, and high metastatic potential of the adult RMS, as well as its poor response to treatment. Conclusions: The presented case underscores the need for early diagnosis, multidisciplinary management, and exploration of molecular profiling for therapeutic planning. Full article

Objective: Sinonasal squamous cell carcinoma (SNSCC) is a rare and aggressive malignancy, with limited treatment strategies in the recurrent or metastatic cases. Although immune checkpoint inhibitors (ICIs) have shown efficacy in head and neck cancers (HNCs), clinical data specific to SNSCC are scarce. This study aimed to evaluate the therapeutic efficacy and prognosis of ICIs in patients with SNSCC. Methods: We conducted a retrospective review of 18 patients with pathologically confirmed SNSCC treated with nivolumab or pembrolizumab at Gifu University Hospital between May 2017 and December 2024. Treatment response was assessed using RECIST v1.1 criteria. Overall response rate (ORR) and disease control rate (DCR) were evaluated as treatment effects, and overall survival (OS) and progression-free survival (PFS) were evaluated as prognoses. Subgroup analyses were performed according to treatment regimen. Results: The ORR and DCR for all patients were 43.8% and 56.3%, respectively. Pembrolizumab-treated patients showed higher response rates (ORR: 66.7%; DCR: 83.3%) compared to those treated with nivolumab (ORR: 30%; DCR: 40%). Median OS and PFS were 21.5 and 7.9 months, respectively. Long-term durable responses exceeding two years were observed in several cases. Although pembrolizumab tended to result in better outcomes, no statistically significant difference was found between groups. Immune-related adverse events were infrequent and manageable. Conclusions: This study suggests that a subset of patients with SNSCC may benefit from ICI therapy, particularly in combination with chemotherapy. Despite the rarity of SNSCC, accumulating clinical evidence—including prospective studies—is essential to establish standardized treatment strategies for this disease. Full article

WWOX and HIF1α proteins are involved in cancer progression; their functions are closely related. WWOX binds HIF1α through its WW domains, sequestering it in the cytoplasm and inhibiting its transcriptional activity. This study evaluates the prognostic significance of the WWOX/HIF1A interaction across cancers, breast cancer subtypes, glioblastoma (GBM), low-grade glioma (LGG), and hepatocellular carcinoma (HCC) through gene expression and pathway analysis focused on metabolism, ECM, and epithelial–mesenchymal transition. In breast cancer, metabolic pathways correlated with good prognosis in basal subtypes. HER2 subtypes showed enrichment in DNA replication pathways. Luminal A subtypes showed favourable prognosis via TNF and PI3K/AKT signalling, while luminal B subtypes had poor prognosis tied to metabolic activity; genes associated with good prognosis mirrored those tied to poor prognosis in luminal A. In HCC, enhanced metabolic activity was associated with good prognosis. In contrast, poor prognosis involved TNF signalling and cytoskeleton-related pathways, indicating more aggressive tumour behaviour. In LGG, good prognosis was linked to metabolic and cAMP pathways, while poor outcomes involved TNF, cell cycle, apoptosis, and focal adhesion pathways. GBM showed similar patterns: metabolic and cAMP pathways indicated better outcomes, while NFKB, TNF, JAK-STAT, and PI3K/AKT pathways marked poor prognosis. These findings suggest the WWOX/HIF1A ratio is a robust prognostic marker and a possible guide for developing targeted treatments. Full article

Background/Objectives: To assess the impact of the 2023 FIGO staging revision on stage distribution, survival outcomes, and prognostic performance in endometrial cancer compared to the 2009 system. Methods: This retrospective cohort study analyzed 2969 patients with FIGO 2009 stage I–III endometrial cancer diagnosed at Samsung Medical Center (1994–2023). Patients were reclassified per the 2023 FIGO system. Stage migration, progression-free survival (PFS), and overall survival (OS) were evaluated. Prognostic performance was compared using the Akaike information criterion (AIC), Bayesian information criterion (BIC), concordance index (C-index), and area under the receiver operating characteristic curve (AUC). Results: Stage migration occurred in 20.2% of patients, with 98.3% involving upstaging from FIGO 2009 stage I, largely due to the inclusion of aggressive histology, p53 abnormality, and substantial lymphovascular space invasion (LVSI). The proportion of stage I tumors decreased from 81.5% to 65.2%, while stage II increased to 21.9%, including 14.8% newly classified as stage IIC. Patients remaining in stage I showed favorable outcomes (5-year PFS: 95.3%, OS: 98.5%), whereas those upstaged—especially to stage IIC—had significantly worse outcomes (5-year PFS: 76.5%, OS: 83.1%). Tumors with p53 abnormalities had poorer survival (PFS: 70.8%, OS: 76.6%). The 2023 FIGO system outperformed the 2009 system in prognostic discrimination across all metrics. Conclusions: The FIGO 2023 staging revision improves prognostic accuracy in endometrial cancer by integrating histopathologic and molecular risk factors. These refinements enhance risk stratification and may support more individualized treatment strategies. Full article

Youth-onset type 2 diabetes (T2D) is a growing public health challenge. This narrative review aims to provide a comprehensive overview of epidemiology, pathophysiology, diagnosis, complications, and therapeutic strategies in children and adolescents with T2D, highlighting the most recent evidence and the distinctive features that differentiate youth-onset from adult-onset disease. Over recent decades, its incidence has increased worldwide, closely linked to rising rates of childhood obesity, sedentary behavior, and socioeconomic disparities. The disease typically emerges around puberty, a period marked by physiological insulin resistance, and is influenced by a complex interplay of genetic, environmental, and developmental factors. Diagnosis can be delayed or missed due to overlapping features with type 1 diabetes and limitations in current screening tools. The clinical course is often aggressive, with early onset of microvascular and macrovascular complications. Management is particularly challenging due to the limited number of pharmacologic agents approved for pediatric use and the psychological and behavioral complexities of adolescence. While metformin remains the first-line treatment, newer therapies such as GLP-1 receptor agonists and SGLT2 inhibitors show promise in improving metabolic outcomes. In conclusion, early diagnosis, multidisciplinary management, and equitable access to effective therapies are essential to improve long-term outcomes in this vulnerable population. Full article

Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with very poor survival. Prior research suggests rural–urban disparities on a regional scale. We aimed to elucidate these disparities in treatment and disease-specific survival (DSS) for ICC patients on a national scale using the SEER database. Methods: The SEER database was queried to identify biopsy-confirmed cases of ICC from 2000 to 2021. Differences in clinicopathologic features and treatment between rural and urban patients were assessed using Chi-square and Fischer’s exact tests. Disease-specific survival was compared using Kaplan–Meier and log-rank tests as well as multivariable Cox regressions. Results: A total of 14,940 ICC patients were identified. Rural patients were less likely than urban patients to receive chemotherapy (789 of 1588 [49.7%] vs. 7112 of 13,352 [53.3%], p = 0.006) and surgical treatment (305 of 1588 [19.2%] vs. 2922 of 13,352 [21.9%], p = 0.013). Rural patients experienced reduced 5- and 10-year DSS rates (7.0% and 4.0%) compared to urban patients (9.0% and 6.0%, p < 0.001). In multivariable analysis, rural residence independently demonstrated a 17% increased risk of disease-specific mortality compared to their urban counterparts (aHR 1.17, 95% CI 1.03–1.32). Conclusions: This study demonstrates significant rural–urban disparities in ICC treatment and survival throughout the US, independent of other prognostic factors. Further investigation into factors driving these disparities is warranted to improve outcomes for rural ICC patients. Full article

Background/Objectives: Glioblastomas are a part of adult-type diffuse gliomas, the most common and most aggressive primary brain tumors in adults (glioblastoma, IDH-wildtype). The identification of the genetic factors associated with glioblastoma could be an important contribution to the diagnosis and early prevention of this disease. We compiled data from the global literature and analyzed clinically relevant variants implicated in glioblastoma risk. Methods: PubMed, Web of Science, and Scopus were used as databases. Associations between the SNPs and glioblastoma risk were calculated as a measure of pooled odds ratios (ORs) and 95% confidence intervals. Pearson’s analysis was used for epidemiological correlation (only p-values less than 0.05 were statistically significant), and data were obtained from the World Health Organization platform and the 1000 Genomes Project. Statistical analysis was performed using Review Manager (RevMan) 5.4 and BioEstat 5.0. Results: CCDC26 rs891835 G/T, G/G, and G/T-G/G genotypes were analyzed and determined to increase glioblastoma risk (G/T OR = 1.96, 95% CI: 1.38–2.77, p = 0.0002, I² = 0%; G/G OR = 1.33, 95% CI: 0.46–3.85, p = 0.60, I² = 0%; G/T − G/G OR = 1.96, 95% CI: 1.39–2.76, p = 0.0001, I² = 0%). Epidemiological correlation also demonstrated that the higher the frequency of the CCDC26 rs891835 variant, the higher the incidence of that variant in the European population. Conclusions: CCDC26 rs891835 may serve as a predictive biomarker for glioblastoma, IDH-wildtype risk and may influence higher glioblastoma incidence rates in the European population. Full article

Systemic inflammation plays a key role in cancer progression, and markers such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have gained attention as potential prognostic tools in colorectal cancer. However, their comparative utility in colon cancer remains unclear. Objective: This study was aimed to assess and compare the prognostic value of preoperative NLR and PLR in evaluating tumor aggressiveness in colon cancer patients undergoing elective surgery. Methods: We conducted a retrospective observational study on 64 patients with histologically confirmed colon cancer treated between 2019 and 2022. Only elective cases were included; rectal and emergency surgeries were excluded. Demographic, clinical, pathological, and laboratory data were collected. Tumor aggressiveness was assessed based on tumor size, histologic grade, lymphovascular and perineural invasion, and lymph node involvement. Statistical analysis included Pearson correlation, ANCOVA, logistic regression, and principal component analysis (PCA). Results: PLR showed a significant positive correlation with tumor size (r = 0.428, p < 0.001) and tumor stage (r = 0.314, p = 0.012), whereas NLR did not. Logistic regression and PCA indicated that PLR better reflected tumor burden, while NLR was more associated with systemic inflammation. Neither marker significantly predicted postoperative complications or in-hospital mortality. Conclusions: PLR may serve as a useful, non-invasive biomarker for assessing tumor aggressiveness in colon cancer, supporting its integration into preoperative risk stratification. The results from this single-center, retrospective cohort showed moderate associations between PLR and tumor size and stage, whereas NLR did not. These findings are hypothesis-generating and insufficient for clinical implementation; prospective, adequately powered studies with survival endpoints are required. Full article