Search Results (1,300)

Recent advancements in deep learning have significantly enhanced brain tumor segmentation from MRI data, providing valuable support for clinical diagnosis and treatment planning. However, challenges persist in effectively integrating prior medical knowledge, capturing global multimodal features, and accurately delineating tumor boundaries. To address these challenges, the Hybrid Network for Multimodal Brain Tumor Segmentation (HN-MBTS) is proposed, which incorporates prior medical knowledge to refine feature extraction and boundary precision. Key innovations include the Two-Branch, Two-Model Attention (TB-TMA) module for efficient multimodal feature fusion, the Linear Attention Mamba (LAM) module for robust multi-scale feature modeling, and the Residual Attention (RA) module for enhanced boundary refinement. Experimental results demonstrate that this method significantly outperforms existing approaches. On the BraT2020 and BraT2023 datasets, the method achieved average Dice scores of 87.66% and 88.07%, respectively. These results confirm the superior segmentation accuracy and efficiency of the approach, highlighting its potential to provide valuable assistance in clinical settings. Full article

Objective: To evaluate the outcomes of a modified infratemporal fossa approach (ITFA) that preserves the posterior external auditory canal (EAC) in patients with tumors in the infratemporal fossa and skull base, focusing on postoperative hearing and facial nerve function. Methods: This retrospective study included nine patients who underwent ITFA with posterior EAC preservation for tumor removal while minimizing facial nerve rerouting. All surgeries were performed by a single surgeon. Preoperative and postoperative hearing levels, facial nerve function, tumor characteristics, and surgical outcomes were analyzed. Air-bone gaps (ABG) were assessed using pure tone audiometry, and facial nerve function was assessed using the House–Brackmann grading system. Results: The cohort consisted of eight female patients and one male patient, with a mean tumor size of 3.0 cm. Surgical outcomes were promising, with no statistically significant increase in postoperative ABG and well-preserved facial nerve function. Only one patient developed postoperative grade II facial palsy. A residual tumor was identified in one case with extensive meningioma, which has remained stable, and no recurrence or regrowth was noted during the follow-up period (mean: 3.7 years). The modified approach minimized complications related to conductive hearing loss and facial nerve dysfunction. Conclusions: The modified ITFA with posterior EAC preservation provides a promising alternative to conventional ITFA for managing deep-seated tumors. It preserves both hearing and facial nerve function while ensuring adequate tumor resection. Full article

In familial Alzheimer’s disease (FAD), presenilin 1 (PSEN1) E280A cholinergic-like neurons (ChLNs) induce aberrant secretion of extracellular amyloid beta (eAβ). How PSEN1 E280A ChLNs-eAβ affects microglial activity is still unknown. We obtained induced microglia-like cells (iMG) from human peripheral blood cells (hPBCs) in a 15-day differentiation process to investigate the effect of bolus addition of Aβ42, PSEN1 E280A cholinergic-like neuron (ChLN)-derived culture supernatants, and PSEN1 E280A ChLNs on wild type (WT) iMG, PSEN1 E280A iMG, and sporadic Alzheimer’s disease (SAD) iMG. We found that WT iMG cells, when challenged with non-cellular (e.g., lipopolysaccharide, LPS) or cellular (e.g., Aβ42, PSEN1 E280A ChLN-derived culture supernatants) microenvironments, closely resemble primary human microglia in terms of morphology (resembling an “amoeboid-like phenotype”), expression of surface markers (Ionized calcium-binding adapter molecule 1, IBA-1; transmembrane protein 119, TMEM119), phagocytic ability (high pHrodo™ Red E. coli BioParticles™ phagocytic activity), immune metabolism (i.e., high generation of reactive oxygen species, ROS), increase in mitochondrial membrane potential (ΔΨm), response to ATP-induced transient intracellular Ca²⁺ influx, cell polarization (cluster of differentiation 68 (CD68)/CD206 ratio: M1 phenotype), cell migration activity according to the scratch wound assay, and especially in their inflammatory response (secretion of cytokine interleukin-6, IL-6; Tumor necrosis factor alpha, TNF-α). We also found that PSEN1 E280A and SAD iMG are physiologically unresponsive to ATP-induced Ca²⁺ influx, have reduced phagocytic activity, and diminished expression of Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) protein, but when co-cultured with PSEN1 E280A ChLNs, iMG shows an increase in pro-inflammatory phenotype (M1) and secretes high levels of cytokines IL-6 and TNF-α. As a result, PSEN1 E280A and SAD iMG induce apoptosis in PSEN1 E280A ChLNs as evidenced by abnormal phosphorylation of protein TAU at residue T205 and cleaved caspase 3 (CC3). Taken together, these results suggest that PSEN1 E280A ChLNs initiate a vicious cycle between damaged neurons and M1 phenotype microglia, resulting in excessive ChLN death. Our findings provide a suitable platform for the exploration of novel therapeutic approaches for the fight against FAD. Full article

Pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC), ranks among the most lethal malignancies, with a 5-year survival rate of under 10%. The most prevalent KRAS mutations occur in three hotspot residues: glycine-12 (G12), glycine-13 (G13), and glutamine-61 (Q61), leading to the constant activation of the Ras pathway, making them the primary focus in oncologic drug development. Selective KRAS G12C inhibitors (e.g., sotorasib, adagrasib) have demonstrated moderate efficacy in clinical trials; however, this mutation is infrequent in PDAC. Emerging therapies targeting KRAS G12D and G12V mutations, such as MRTX1133, PROTACs, and active-state inhibitors, show promise in preclinical studies. Pan-RAS inhibitors like ADT-007, RMC-9805, and RMC-6236 compounds provide broader coverage of mutations. Their efficacy and safety are currently being investigated in several clinical trials. A major challenge is the development of resistance mechanisms, including secondary mutations and pathway reactivation. Combination therapies targeting the RAS/MAPK axis, SHP2, mTOR, or SOS1 are under clinical investigation. Immunotherapy alone has demonstrated limited effectiveness, attributed to an immunosuppressive tumor microenvironment, although synergistic effects are noted when paired with KRAS-targeted agents. Furthermore, KRAS mutations reprogram cancer metabolism, enhancing glycolysis, macropinocytosis, and autophagy, which are being explored therapeutically. RNA interference technologies have also shown potential in silencing mutant KRAS and reducing tumorigenicity. Future strategies should emphasize the combination of targeted therapies with metabolic or immunomodulatory agents to overcome resistance and enhance survival in KRAS-mutated PDAC. Full article

When non-functioning pituitary adenomas (NFPAs) behave aggressively or recur after first-line surgical treatment, it can be challenging to decide whether and how to escalate therapy. Up to 47% of patients with residual tumor after transsphenoidal surgery will show disease recurrence or progression and may require an intervention. Repeat surgical resection can be attempted in select cases if the tumor is accessible; for the remainder of patients, non-surgical treatment options may need to be considered. Radiotherapy can control tumor growth in 75% of NFPAs, but confers increased risk of hypopituitarism and other disorders. Currently, there are no medical therapies approved for patients with recurrent or aggressive NFPA. However, several have been investigated, including temozolomide, somatostatin receptor ligands, dopamine agonists, immune checkpoint inhibitors, vascular endothelial growth factor inhibitors, and peptide receptor radionuclide therapy. We present a review of the available evidence to provide guidance for pituitary endocrinologists and neuro-oncologists when treating patients with recurrent or aggressive NFPA. Full article

Background and Objectives: The Hippo pathway, via Yes-associated protein 1 (YAP1), regulates cell proliferation, apoptosis, and tissue regeneration. Aberrant YAP1 activation is linked to tumor progression and immune evasion in various cancers, including breast carcinoma, despite conflicting evidence on its prognostic value. Preclinical studies have explored drugs targeting YAP1–TEAD interactions, but therapeutic application is limited. Materials and Methods: This study included 50 patients with locally advanced breast cancer, who were assessed by a multidisciplinary tumor board and underwent neoadjuvant treatment per tumor subtype and clinical guidelines. Eligibility required both pre-treatment core biopsy and post-treatment surgical resection samples. Due to the absence of residual tumor in some patients achieving complete pathological response, post-treatment tissue was available and analyzable in 30 patients. YAP1 expression was evaluated immunohistochemically for nuclear and cytoplasmic staining patterns. ROC analysis identified a cutoff for YAP1 expression, defining tumors with ≥70% nuclear and ≥80% cytoplasmic staining. Results: YAP1 expression had a significant relationship with tumor subtype (p = 0.001), being most frequent in HER-2-positive tumors (55.6%) and least frequent in luminal tumors (11.1%). YAP1 positivity significantly predicted axillary pathological complete response (pCR) (p = 0.01). In YAP1-positive patients, 77.8% achieved axillary pCR compared to 31.7% in YAP1-negative patients, though the YAP1 status and breast pCR association were insignificant (p = 0.07). The Mann–Whitney U test indicated that higher Ki-67 values were significantly associated with positive YAP1 expression (p = 0.028). In contrast, there was no association between ER, PR status, age, and tumor size. Following treatment, there was a statistically significant change in YAP1 expression, with nuclear staining decreasing (p = 0.004) while cytoplasmic staining increased (p = 0.002). YAP1 was significantly linked to axillary pCR, HER-2 status, and Ki-67. Conclusions: Post treatment, nuclear YAP1 decreased, whereas cytoplasmic expression increased, showing a localization shift. These results suggest that YAP1 may predict treatment response and become a future therapeutic target. Full article

Background and Clinical Significance: Neurofibromatosis type 1 (NF1) predisposes individuals to various peripheral nerve sheath tumors (PNSTs), including benign neurofibromas, malignant peripheral nerve sheath tumors (MPNSTs), and intermediate lesions known as atypical neurofibromatous neoplasms of uncertain biologic potential (ANNUBP), previously often termed atypical neurofibroma. These atypical lesions are considered premalignant precursors to MPNST. Case Presentation: We present the case of a 33-year-old male with NF1 who developed a rapidly growing, painful mass in his right calf. Clinical examination revealed signs consistent with NF1. Magnetic resonance imaging showed a large, heterogeneous mass in the lateral compartment. Biopsy revealed a neurofibroma with hypercellularity, moderate atypia, scarce S100 positivity, focal CD34 positivity, and an elevated Ki-67 proliferation index of 10–12%, consistent with ANNUBP. The patient underwent wide surgical resection, including the fibula and peroneal muscles. At the 30-month follow-up, there was no local recurrence, though the patient had a mild residual limp. Discussion: This case highlights the clinical presentation, diagnostic features, and management considerations for ANNUBP in NF1, emphasizing the importance of recognizing warning signs and the role of pathology in guiding treatment for these high-risk precursor lesions. Full article

Background/Objectives: Thirty to fifty percent of ductal carcinoma in situ (DCIS) cases are high-grade and at risk of progressing to invasive carcinoma. The most important treatment-related risk factor for recurrence is the presence of residual DCIS. The aim of our study was to evaluate the relationship between size and imaging features on preoperative mammography and magnetic resonance imaging (MRI) and histopathological size and nuclear grade in patients with pure DCIS. Methods: Between 2015 and 2023, 90 patients who underwent surgery for DCIS, had no microinvasive/invasive component, and underwent a preoperative mammography and MRI were included in this study. Results: DCIS was detected in 91.1% of patients using mammography and 95.5% using MRI. Microcalcifications (MCs) were most common in mammography (85.4%). Thin pleomorphic and thin linear branching MCs were detected in 42% of high-grade DCIS, while amorphous (42%) MCs were most common in low-grade DCIS. In low-grade DCIS cases, a grouped distribution of MCs was observed most commonly (69%). There was a statistically significant difference between DCIS groups in terms of MC morphology and distribution (p = 0.043, p = 0.005, respectively). Diffusion restriction on MRI was associated with high-grade DCIS (p = 0.043). The tumor size was greater than the pathological size and correlated poorly with mammography and moderately with MRI. Conclusions: Compared to mammography, MRI is more effective in detecting and estimating the size of DCIS. Both methods overestimate tumor size compared to histopathological size. The nuclear grade is associated with a poor prognosis and local recurrence in DCIS. Full article

Background/Objectives: PEGylated liposomes are widely recognized for their biocompatibility and capacity to extend systemic circulation via “stealth” properties. However, the PEG corona often limits tumor penetration and cellular internalization. Targeting matrix metalloproteinase-2 (MMP-2), frequently upregulated in breast cancer stroma, presents an opportunity to enhance tissue-specific drug delivery. In this study, we engineered MMP-2-responsive GPLGVRG peptide-modified cleavable PEGylated liposomes for targeted paclitaxel (PTX) delivery. Methods: Molecular docking simulations employed the MMP-2 crystal structure (PDB ID: 7XJO) to assess GPLGVRG peptide binding affinity. A cleavable, enzyme-sensitive peptide-PEG conjugate (Chol-PEG_2K-GPLGVRG-PEG_5K) was synthesized via small-molecule liquid-phase synthesis and characterized by ¹H NMR and MALDI-TOF MS. Liposomes incorporating this conjugate (S-Peps-PEG_5K) were formulated to evaluate whether MMP-2-mediated peptide degradation triggers detachment of long-chain PEG moieties, thereby enhancing internalization by 4T1 breast cancer cells. Additionally, the effects of tumor microenvironmental pH (~6.5) and MMP-2 concentration on drug release dynamics were investigated. Results: Molecular docking revealed robust GPLGVRG-MMP-2 interactions, yielding a binding energy of −7.1 kcal/mol. The peptide formed hydrogen bonds with MMP-2 residues Tyr A:23 and Arg A:53 (bond lengths: 2.4–2.5 Å) and engaged in hydrophobic contacts, confirming MMP-2 as the primary recognition site. Formulations containing 5 mol% Chol-PEG_2K-GPLGVRG-PEG_5K combined with 0.15 µg/mL MMP-2 (S-Peps-PEG_5K +MMP) exhibited superior internalization efficiency and significantly reduced clonogenic survival compared to controls. Notably, acidic pH (~6.5) induced MMP-2-mediated cleavage of the GPLGVRG peptide, accelerating S-Peps-PEG_5K dissociation and facilitating drug release. Conclusions: MMP-2-responsive, cleavable PEGylated liposomes markedly improve PTX accumulation and controlled release at tumor sites by dynamically modulating their stealth properties, offering a promising strategy to enhance chemotherapy efficacy in breast cancer. Full article

Colorectal carcinoma remains one of the primary contributors to cancer deaths; however, it is also considered a preventable type of cancer, because the prognosis of the disease is directly dependent on its timely detection. Developing accurate risk prediction models for colorectal cancer is crucial for identifying individuals at both low and high risk, as risk stratification determines the need for additional interventions, which carry their own risks. The development of new non-invasive diagnostic methods based on biomaterial analysis, alongside standard diagnostic techniques such as colonoscopy with biopsy, computed tomography scanning, and magnetic resonance imaging, can address multiple objectives: improving screening accuracy, providing a comprehensive assessment of minimal residual disease, identifying patients at a high risk of colorectal cancer, and evaluating the effectiveness of ongoing treatments. The lack of sensitive diagnostic methods drives contemporary research toward the discovery of new tools for detecting tumor cells, particularly through the examination of biological materials, including blood, exhaled air, and tumor tissue itself. In this article, we analyze current studies regarding biomarkers in colorectal cancer and prognostic significance. Full article

Background: Many patients harbor minimal residual disease (MRD)—small clusters of residual tumor cells that survive therapy and evade conventional detection but drive recurrence. Although advances in molecular and computational methods have improved circulating tumor DNA (ctDNA)-based MRD detection, these approaches face challenges: ctDNA shedding fluctuates widely across tumor types, disease stages, and histological features. Additionally, low levels of driver mutations originating from healthy tissues can create background noise, complicating the accurate identification of bona fide tumor-specific signals. These limitations underscore the need for refined technologies to further enhance MRD detection beyond DNA sequences in solid malignancies. Methods: Profiling circulating cell-free mRNA (cfmRNA), which is hyperactive in tumor and non-tumor microenvironments, could address these limitations to inform postoperative surveillance and treatment strategies. This study reported the development of OncoMRD BREAST, a customized, gene signature-informed cfmRNA assay for residual disease monitoring in breast cancer. OncoMRD BREAST introduces several advanced technologies that distinguish it from the existing ctDNA-MRD tests. It builds on the patient-derived gene signature for capturing tumor activities while introducing significant upgrades to its liquid biopsy transcriptomic profiling, digital scoring systems, and tracking capabilities. Results: The OncoMRD BREAST test processes inputs from multiple cutting-edge biomarkers—tumor and non-tumor microenvironment—to provide enhanced awareness of tumor activities in real time. By fusing data from these diverse intra- and inter-cellular networks, OncoMRD BREAST significantly improves the sensitivity and reliability of MRD detection and prognosis analysis, even under challenging and complex conditions. In a proof-of-concept real-world pilot trial, OncoMRD BREAST’s rapid quantification of potential tumor activity helped reduce the risk of incorrect treatment strategies, while advanced predictive analytics contributed to the overall benefits and improved outcomes of patients. Conclusions: By tailoring the assay to individual tumor profiles, we aimed to enhance early identification of residual disease and optimize therapeutic decision-making. OncoMRD BREAST is the world’s first and only gene signature-powered test for monitoring residual disease in solid tumors. Full article

Purpose: Neoadjuvant endocrine therapy (NET) represents a valuable treatment option for hormone receptor-positive (HR+)/HER2-negative breast cancer, particularly in postmenopausal women. This study aimed to evaluate the clinical and histopathological efficacy of NET and to explore early and late changes in Ki-67 and progesterone receptor (PgR) expression as indicators of endocrine response. Methods: A prospective cohort of 127 postmenopausal patients with stage cT1–4N0–3M0 HR+/HER2− breast cancer was enrolled between 2019 and 2021. Patients received NET (mostly letrozole) for a mean of 7.7 months. In 80 cases, a second core biopsy was performed after four weeks. Tumor size, histological grade, and biomarkers (Ki-67, PgR) were assessed pre- and post-treatment. Results: NET led to a significant reduction in tumor size, with median shrinkage of 47.0% (from 32.0 mm to 17.0 mm, p < 0.0001). Breast-conserving surgery (BCS) was performed in 52.2% of patients and lymph node negativity (pN0) was observed in 50.4%. Median Ki-67 decreased from 20.0% at baseline to 5.0% after four weeks (p < 0.0001) and remained low in surgical specimens (median 5.0%, p < 0.0001). In 33.3% of patients, Ki-67 dropped below 2.7%, and 67.0% showed a concordant decrease in both Ki-67 and PgR. PgR expression declined significantly during treatment (p < 0.0001). HER2 status conversion was noted in 6.4% of patients during treatment. Pathological complete response (pCR) occurred in 3.5%, while minimal or moderate residual disease (RCB I–II) was identified in 71.3% of cases. Conclusions: NET effectively reduced tumor burden and histological aggressiveness, enabling higher rates of BCS. Early reduction in Ki-67 and PgR may serve as surrogate markers of endocrine responsiveness, supporting their use for treatment stratification and monitoring during NET in HR+/HER2− breast cancer. Full article

The deep learning-based analysis of liver CT images is expected to provide assistance for clinicians in the diagnostic decision-making process. However, the accuracy of existing methods still falls short of clinical requirements and needs to be further improved. Therefore, in this work, we propose a novel multi-level hierarchical framework for liver tumor segmentation. In the first level, we integrate inter-slice spatial information by a 2.5D network to resolve the accuracy–efficiency trade-off inherent in conventional 2D/3D segmentation strategies for liver tumor segmentation. Then, the second level extracts the inner-slice global and local features for enhancing feature representation. We propose the Res-Inception-SE Block, which combines residual connections, multi-scale Inception modules, and squeeze-excitation attention to capture comprehensive global and local features. Furthermore, we design a hybrid loss function combining Binary Cross Entropy (BCE) and Dice loss to solve the category imbalance problem and accelerate convergence. Extensive experiments on the LiTS17 dataset demonstrate the effectiveness of our method on accuracy, efficiency, and visual results for liver tumor segmentation. Full article

Head and neck squamous cell carcinomas (HNSCCs) that develop from the mucosal epithelium in the oral cavity, pharynx, and larynx are a heterogeneous group of malignant tumors. A lack of appropriate screening and diagnostic methods leads to late diagnoses, with the majority of patients having locally advanced disease, which is associated with a high risk of local recurrence and a poor prognosis and is usually treated with combination therapies. Biomarkers for predicting the therapy response and risk of recurrence in HNSCC patients are urgently needed. Liquid biopsy, e.g., the profiling of circulating biomarkers in bodily fluids, is a promising approach with increasing utility in the early detection and diagnosis of cancer, monitoring cancer progression, patient stratification and treatment selection, detecting minimal residual disease (MRD), and predicting recurrence across different cancer types, including HNSCC. Among liquid biomarkers, circulating tumor DNA (ctDNA), which is based on detecting tumor-specific mutations, insertions/deletions, copy number alterations, and methylation, is the most promising transformative tool in cancer management and personalized cancer treatment. In this review, we provide an update of recent data on the role of non-viral ctDNA in the management of HNSCC patients. Accumulating data suggests the enormous potential of ctDNA profiling by serial sampling during and after definitive therapy in detecting MRD and predicting recurrence in HNSSC patients treated with a single treatment modality (surgery or radiotherapy) or with combination therapies, including immune-checkpoint-inhibitor-based immunotherapy. By incorporating the latest immunotherapy trials and organizing the data by the treatment modality, this review offers a novel perspective not found in previous surveys. Full article

Background/Objectives: Tumor-infiltrating lymphocytes (TILs) and inflammation status are emerging prognostic markers in various cancers, but their significance in high-grade serous ovarian carcinoma (HGSC) remains unclear. Our objective was to evaluate different TIL subtypes and inflammation status in relation to progression-free survival (PFS) in primary HGSC. Methods: CD3⁺/CD4⁺/CD8⁺/PD-1+ stromal TILs (sTILs) and intraepithelial TILs (iTILs) were evaluated by manual assessment and digital image analysis (DIA), following TIL Working Group recommendations. Inflammation status was evaluated through the following scores: systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), CA125, and lactate dehydrogenase (LDH). Results: CD8⁺ TILs were the most prevalent subtype in both iTILs and sTILs. However, sTILs were significantly more abundant than iTILs (p < 0.001) among all subsets, except for PD-1+ cells. DIA results of TIL assessments were in agreement with manual assessments. High stromal CD3⁺ and CD8⁺ TILs, PIV, CA125, and LDH, were associated with improved PFS. Potential independent prognostic factors for PFS in manual assessment were PIV (HR = 0.32, CI 95% = 0.12–0.82) and CD8⁺ sTILs (HR = 0.30, CI 95% = 0.12–0.79), whereas in DIA assessment they were CD3⁺ sTILs (HR = 0.31, CI 95% = 0.15–0.67), PIV (HR = 0.35, 95% CI 0.13–0.96), and residual disease (HR = 0.21 95% CI 0.08–0.53). Conclusions: CD3⁺/CD8⁺ sTILs and PIV are promising prognostic indicators in HGSC; however, further research is needed to confirm their clinical utility. Full article