Search Results (1,029)

Laryngeal squamous carcinoma is a major type of head and neck cancer. Despite a wide range of treatment options, it remains a challenge to identify which ones are the most effective for which groups of patients. One solution is to analyse selected biomarkers. In this paper, biomarkers are divided into distinctive groups according to the molecular pathways analysed or specific molecules within the cell or in tissue fluids. The paper provides a description of these groups, including genetic and apoptosis-associated factors, factors regulating angiogenesis, cell structure regulators, immune factors in the form of programmed cell death ligand (PD-L1), hormone receptors, molecules involved in growth factor pathways, and cell cycle regulators. Representative examples are discussed for each of these groups, indicating their potential usefulness in staging, assessing tumour aggressiveness, and making a prognosis. Full article

Canine mammary tumours often present as multiple synchronous nodules, necessitating decisions regarding staging intensity and surgical planning prior to histology. We developed two preoperative nodule-level prediction models using only the medical history and physical examination of client-owned bitches with mammary disease, which were staged using the WHO-modified TNM system with a M0 classification (no distant metastasis) at the time of presentation. This retrospective study analysed 286 surgically excised mammary nodules from 92 dogs managed under a standardised mammary oncology protocol; those with inflammatory mammary carcinoma or distant metastasis were excluded. The outcomes were (i) malignant versus benign/non-neoplastic histology (for all nodules) and (ii) intermediate/high histologic grade (II–III versus I) among carcinomas. Separate multivariable Firth penalised logistic regression models accounted for within-dog clustering with dog-level bootstrap internal validation. Multiple imputation was used in a sensitivity analysis for missingness in the detection-to-surgery interval. Malignancy was confirmed in 87/286 (30.4%) of the nodules (86 carcinomas), including 35/87 (40.2%) that measured less than 1 cm. Among complete cases (153 nodules), malignancy was associated with age at neutering, maximum tumour diameter, owner-reported rapid growth and a detection-to-surgery interval of more than 3.5 months (an exploratory ROC-derived threshold) with good discrimination (area under the curve (AUC) 0.805; optimism-corrected 0.799) and acceptable calibration. Among carcinomas (83 specimen), previous mammary tumours, bloody nipple discharge and fewer synchronous nodules were associated with intermediate/high malignancy grade (AUC 0.859). Sensitivity analyses yielded directionally consistent estimates. Routinely available clinical information may provide interpretable preoperative risk stratification to support staging and surgical planning, pending external validation. Full article

Objectives: To explore if MRI can monitor treatment and predict outcome in patients with human epidermal growth factor 2 (HER2)-negative breast cancer receiving neoadjuvant chemotherapy (NACT) with or without bevacizumab. Methods: Multiparametric MRI was performed at baseline and after 12 and 25 weeks of NACT. MRI assessment included tumour size, apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI), and signal intensity–time curves and vascular volume transfer constant (K^TRANS) from dynamic contrast-enhanced MRI (DCE). The reference standards were pathological complete response (pCR) at the time of surgery, and 10-year recurrence-free survival. Receiver operating characteristics analyses were performed to assess the predictive value of the MRI parameters. MRI findings and outcomes were compared between the treatment groups. Results: Seventy women were included from November 2008 to July 2012, with a median age of 49.5 years and median tumour diameter of 47 mm. Fourteen patients (20.0%) achieved pCR, while eleven (15.7%) had recurrence during the 10-year follow-up. The treatment significantly reduced tumour size, increased ADC, decreased K^TRANS, and shifted the signal intensity–time curves towards more benign shapes. The DCE parameters changed significantly more in the bevacizumab group. In the bevacizumab group, baseline K^TRANS predicted pCR (Area under curve (AUC) = 0.73), but the difference in pCR-rates between the treatment groups was not significant (p = 0.07). Only tumour size and shrinkage at 12 weeks predicted pCR (AUC = 0.71–0.85) regardless of size measuring method. No MRI parameters predicted survival. Conclusions: All MRI parameters reflected treatment response, but no parameter predicted survival or benefit from adding bevacizumab to chemotherapy. Full article

Cancer remains a significant challenge in the field of medicine, primarily due to its inherent plasticity and the development of resistance to conventional therapeutic interventions. Genomic mutations and the activation of oncogenes enable cancer cells to resist senescence and apoptosis, leading to uncontrolled growth with harmful consequences. Small peptides are molecules with interesting anti-tumour properties and represent a valid alternative to conventional treatments. Our group has previously identified a class of small peptides bound to the DNA that can be extracted from the chromatin of various tissues, including wheat germ and trout. These peptide pools have been shown to possess interesting antiproliferative and apoptotic properties, and they are associated with cell cycle regulation. However, given the complexity of the extraction process, it is necessary to identify a substrate that will enable a more efficient extraction of these peptides, while also ensuring a composition that is simple to investigate. The present study developed a method for the extraction of this group of peptides from yeast, and the extract was then tested on cancer cells in order to confirm its anti-tumoral properties. The peptides were obtained from chromatin extracted from Saccharomyces cerevisiae cells through alkalisation and purification by gel filtration chromatography. The extract was tested on HeLa cells to verify its effects on vitality and the cell cycle. The data demonstrate that the chromatographic profile of this peptide extract indicates a more basic composition than the pool extracted from other tissues and exhibits comparable antiproliferative properties. The ability to rapidly obtain a biologically active, analytically accessible, and adequately purified fraction from the widely available substrate Saccharomyces cerevisiae represents a significant advance in the study of these DNA-binding peptides. Full article

Objective: To evaluate the extent of intraoperative bacterial and tumour cell spillage during minimally invasive colorectal surgery and to assess the protective value of systematic specimen retrieval using a tear-proof extraction bag. Methods: This multicentre, prospective observational study included patients undergoing conventional or single-port laparoscopic colorectal surgery for adenocarcinoma, premalignant polyps, or chronic diverticulitis. Three intraoperative samples were obtained for microbiological and cytological analysis: after pneumoperitoneum induction (sample 1), after vascular ligation and bowel division (sample 2), and after specimen extraction using a retrieval bag (sample 3). Results: Eighty-eight patients were included. Bacterial contamination increased significantly throughout the procedure occurring in 11.4% of sample 1, 37.5% of sample 2, and 67% of sample 3 (p < 0.001). When sample 1 was positive, sample 2 was positive in 100% of cases; when sample 2 was positive, sample 3 was positive in 79% of cases. In 33 patients (37.5%), bacterial growth was detected exclusively in sample 3. Contamination in sample 2 was significantly associated with surgical approach (p = 0.013), anastomotic technique (p = 0.022), and malignant disease (p = 0.038). A longer hospital stay was significantly associated with contamination in samples 1 and 2 (p = 0.014 and p < 0.001, respectively). No tumour cells were detected in any sample, except for one case showing atypical cells without clinical relevance in sample 3. Conclusions: Intraoperative bacterial contamination progressively increases during minimally invasive colorectal surgery, peaking after specimen extraction. Most clinical and surgical variables did not significantly influence contamination rates. The use of a specimen retrieval bag demonstrated a potential protective effect by containing bacterial spillage. However, no protective effect regarding tumour cell dissemination could be demonstrated based on cytology analysis. Full article

Background: Osteosarcoma (OSA) is the most common type of bone cancer in canines. Novel therapies are required to prevent the growth, survival, and metastatic progression of this cancer, to increase life expectancy of patients. Immunohistochemical (IHC) studies and RNA sequencing help us gain a deeper understanding into the molecular mechanisms of the disease. Methods: We previously compared canine OSA tissues with patient matched non-tumour tissues, revealing 442 overexpressed genes within the samples. The present research used IHC staining for four of these genes in OSA tissues: G protein-coupled receptor 64 (GPR64), TOX High Mobility Group Box Family Member 3 (TOX3), Matrix Metallopeptidase 12 (MMP-12), and Forkhead Box F1 (FOXF1). H-scoring was performed to quantitatively assess protein expression and qualitatively contextualise staining locations. Additional analyses addressed whether gender or anatomical location of lesions (axial or appendicular tumours) affected protein expression. cBioPortal was employed to analyse expression and genetic alterations in patients. Results: GPR64, TOX3, MMP-12, and FOXF1 showed high mRNA expression and genetic alterations in people with OSA. GPR64, TOX3, MMP-12, and FOXF1 were all expressed in canine OSA with novel findings regarding cellular expression. Additionally, differential sex expression was revealed for GPR64 and TOX3. Potential biomarkers or therapeutic targets were identified. Conclusions: These studies, and subsequent analysis, have provided insights into the molecular mechanisms associated with OSA progression and revealed potential biomarkers for diagnostic and prognostic purposes. A deeper understanding of genetic and protein interactions will support and progress novel pathways towards diagnostic, prognostic, and treatment interventions for OSA in both veterinary and human medicine. Full article

Familial cancers are caused by inherited mutations in specific genes that regulate cell growth, division, and repair. Approximately 5–10% of all cancer cases have a hereditary component, where germline mutations in certain genes increase an individual’s susceptibility to developing cancer. Two major categories of genes are involved in cancer development: tumour suppressor genes and oncogenes. Both play critical roles in regulating normal cell behaviour, and when mutated, they can contribute to uncontrolled cell proliferation and tumour formation. In addition to genetic mutations, epigenetic alterations also play a significant role in familial cancer. Epigenetics refers to changes in gene expression due to DNA methylation, histone modifications, and the dysregulation of non-coding RNAs without alter the underlying DNA sequence. Familial cancer syndromes follow various inheritance patterns, including autosomal dominant, autosomal recessive, X-linked, and mitochondrial inheritance, each with distinct characteristics. Identifying genetic mutations associated with familial cancers is a cornerstone of genetic counselling, which helps individuals and families navigate the complex intersection of genetics, cancer risk, and prevention. Early identification of mutations enables personalized strategies for risk reduction, early detection, and, when applicable, targeted treatment options, ultimately improving patient outcomes. Full article

Background: Canine mammary carcinoma (CMC) is the most common malignant tumour in female dogs and, due to its similarities, is a valuable comparative model for human breast cancer. Kinase inhibitors have revolutionised the treatment of human breast cancer; their use in veterinary oncology remains marginal. Aim: This review summarises the current knowledge of kinase signalling pathways in CMC and assesses which kinase inhibitors approved for human use have potential in veterinary medicine. Methods: A systematic search of the PubMed database from 1985 to 2025 was performed, focusing on kinase-targeted therapies in both human and canine mammary carcinomas. Data were categorised according to molecular target, clinical approval status, and available preclinical or clinical veterinary evidence. Results: Key molecular pathways targeted by kinase inhibitors are conserved across species, supporting translational opportunities. In vitro studies demonstrate that palbociclib, alpelisib, everolimus, and lapatinib inhibit growth and signalling in CMC cell lines. Clinical trials have not been conducted. Conclusions: Approved kinase inhibitors for human use have untapped therapeutic potential in veterinary oncology. Translational research, including xenograft and organoid models, followed by clinical trials in dogs, is required. Gaining this knowledge could lead to targeted treatment for dogs while advancing comparative understanding of mammary cancer biology across species. Full article

The chorioallantoic membrane (CAM) is a well-vascularised extra-embryonic membrane that supports avian embryonic development and can be used as an implantation site for xenograft models of various cancers. CAM tumour research models are powerful and versatile, offering a rapid, cost-effective and ethical complement to mouse xenograft studies. Their capacity for real-time observation of tumour growth, angiogenesis and metastasis within an immunocompetent living organism is particularly compelling. While CAM models have been extensively utilised for investigating solid cancers, such as breast, lung and pancreatic, their potential for haematological malignancy research remains comparatively underexplored. This review examines the relevance, advantages and translational potential of avian CAM models in studying blood cancers. Their applications across three primary categories are discussed—leukaemias, lymphomas and myelomas—highlighting experimental approaches that replicate aspects of human disease progression and therapeutic responsiveness. Moreover, the review evaluates species-specific considerations relevant to model fidelity, including evolutionary distance and functional parallels between avian and human haematopoiesis. These comparisons underscore both the opportunities and limitations for utilising CAM models in haematologic malignancy research. For their potential to investigate mechanisms of cancer development and treatment in simple but immunocompetent in vivo settings, we propose that CAM tumour models offer high value as a bridge between in vitro and mammalian in vivo studies for haematology translational research. Full article

Matrix metallopeptidases (MMPs) are enzymes that, in balance with their inhibitors, play a vital role in extracellular matrix remodelling, particularly during orthodontic tooth movement (OTM). Despite growing interest, significant research is still required to fully comprehend the mechanisms and signalling pathways involved in periodontal ligament remodelling and OTM, particularly those mediated by MMPs. This review explores recent in vitro and in vivo evidence on how specific MMPs—namely, MMP-1, -2, -3, -8, -9, -12, -13, and -14—respond to compressive and tensile forces, regulate collagen degradation, and influence periodontal ligament fibroblast and osteoblast behaviour, ultimately shaping tissue resorption and formation. We also summarize the roles of periodontal ligament cells, hypoxia, the neurovascular and immune systems, and well-known molecules—including receptor activator of nuclear factor kappa β, receptor activator of nuclear factor kappa β ligand, osteoprotegerin, macrophage colony-stimulating factor, tumour necrosis factor α, transforming growth factor, and interleukins—in orchestrating these responses. Finally, we address the clinical relevance of these pathways, highlighting the potential for therapeutic strategies targeting MMPs activity. Overall, this review underscores the pivotal contribution of MMPs to extracellular matrix turnover and tissue adaptation during OTM and suggests that modulating the MMPs/tissue inhibitors of matrix metallopeptidase (TIMPs) balance may enhance orthodontic outcomes. Full article

Background: Suppressor of Cytokine Signalling 6 (SOCS6) is a cytokine signalling suppressor that regulates receptor tyrosine kinase pathways by promoting degradation of signalling proteins, thereby controlling cell growth and survival. One of these tyrosine kinase receptors, Erythropoietin Receptor (EPOR), plays a critical role in CRC progression by enhancing tumour metabolism, angiogenesis, proliferation, and growth. This study investigates the molecular mechanisms governing SOCS6’s role in CRC pathogenesis using in vitro cell models and examines its interaction with EPOR expression following gene knockdown. Methods: Bioinformatics interaction between SOCS6 and EPOR were investigated using molecular visualization. HT-29 and COLO 320DM colorectal cancer cells were transfected with SOCS6 siRNA followed by measurement of SOCS6 and EPOR expression levels by qRT-PCR. The selected knockdown concentration was used in functional assays assessing cell viability, colony formation, migration, apoptosis, and invasion. Results: Bioinformatic results showed interaction between SOCS6 and EPOR through polar bonds. Furthermore, SOCS6 silencing increased cell viability and colony formation in both cell lines and significantly enhanced migration in COLO 320DM cells. Active caspase-3 levels were elevated markedly in HT-29 cells post SOCS6 knockdown, consistent with caspase-3’s reported oncogenic role in CRC. Moreover, EPOR knockdown selectively altered SOCS6 expression in HT-29 cells, indicating a regulatory feedback loop. EPOR silencing elevated cell viability at 24 h in both cell lines but caused a significant decrease in COLO 320DM cells at 72 h. Conclusions: These findings identify the SOCS6–EPOR axis as a potential target for personalized CRC therapy, supporting SOCS6’s tumour-suppressive and diagnostic roles. Full article

Developing effective CAR-T cell therapy for solid tumours remains challenging because of biological barriers such as antigen escape and an immunosuppressive microenvironment. The aim of this study is to develop a mathematical model of the spatio-temporal dynamics of tumour processes in order to assess key factors that limit treatment efficacy. We propose a reaction–diffusion model described by a system of partial differential equations for the densities of tumour cells and CAR-T cells, the concentration of immune inhibitors, and the degree of antigen escape. The methods of investigation include stability analysis and numerical solution of the model using a finite-difference scheme. The simulations show that antigen escape produces a resistant tumour core and relapse after an initial regression; increasing the escape rate from $\gamma =0.001$ to $0.1$ increases the final tumour volume at $t=100$ days from approximately 35.3 a.u. to 36.2 a.u. Parameter mapping further indicates that for $\gamma \le 0.01$ tumour control can be achieved at moderate killing rates ($k_{CT}\approx 1{\mathrm{day}}^{-1}$), whereas for $\gamma \ge 0.05$ comparable control requires $k_{CT}\approx 2$–$5{\mathrm{day}}^{-1}$. Repeated CAR-T administration improves durability: the residual normalised tumour volume at $t=100$ days decreases from approximately 4.5 after a single infusion to approximately 0.9 (double) and approximately 0.5 (triple), with a saturating benefit for further intensification. We conclude that the proposed model is a valuable tool for analysing and optimising CAR-T therapy protocols, and that our results highlight the need for combined strategies aimed at overcoming antigen escape. Full article

Background: Neurofibromatosis 1 is an autosomal dominant disorder accompanied by extensive early-onset spinal manifestations, with or without dystrophic scoliotic features. While non-dystrophic subtypes can often be treated similarly to idiopathic scoliosis, dystrophic scoliosis typically requires more aggressive intervention, often involving instrumentation in severely compromised pedicles or vertebrae. Purpose: This review aims to present recent advances in the surgical treatment of Neurofibromatosis 1-associated scoliosis, including surgical techniques and emerging guidance methods. Methods: An electronic literature search was conducted in Web of Science and PubMed to identify surgical techniques for scoliosis in patients with Neurofibromatosis 1. Results: Forty-one studies on the operative treatment of dystrophic scoliosis or both subtypes were retrieved. Although aggressive treatment with combined anterior and posterior fusion are widely used, posterior-only methods, which avoid plexiform tumours, present encouraging results. Recent studies highlight the effectiveness of growing rod systems in early-onset cases, enabling delayed fusion while preserving T1-S1 growth. Promising results from sectional or segmented correction techniques demonstrate better sagittal balance and Cobb angle correction, respectively. Preoperative use of halo-gravity traction, which has been extensively studied, is associated with reduced neurological impairment and encourages better correction results, avoiding autofusion. Various studies have also reported more precise pedicle screw placement with guidance of O-arm and triggered electromyography (t-EMG). Conclusions: The correction of spinal scoliotic deformities presents a significant challenge. However, recent advances in surgical techniques and intraoperative guidance offer promising strategies for more effective management. Full article

Bone remodelling is a physiological process influenced by mechanical stimuli such as those generated during orthodontic treatment. Biochemical markers allow the phases of remodelling to be identified, its progression to be assessed, alterations to be detected and scaffold-based tissue regeneration to be evaluated. This study reviews the main markers involved in bone formation and resorption, highlighting their clinical relevance. A literature search was conducted in biomedical databases, selecting studies that analysed crevicular gingival fluid samples in areas of tension and compression. The markers were classified according to their function and location, and their baseline values, temporal variations and methods of analysis were compiled. Among the markers of bone formation, Osteoprotegerin (OPG), Transforming Growth factor β1 (TGF-β1) and Interleukin 27 (IL-27) stand out; while resorption markers include Receptor Activator of Nuclear Factor appa β Ligand (RANKL), Tumour Necrosis Factor (TNF-α) and Interleukin 1β (IL-1β). The results show different expression patterns depending on the type of force applied and the timing of the follow-up, allowing molecular profiles associated with each phase of remodelling to be established. This characterisation improves our understanding of tooth movement and provides a basis for the development of more precise scaffolds and functional biomaterials in orthodontics. Full article

Neuroblastoma is an embryonal tumour that arises from the malignant transformation of neural crest cells and remains one of the deadliest malignancies in children under five. Neural crest development is regulated by dynamic switches in transcriptional programmes, guided by a variety of growth factors. Due to its developmental origin, neuroblastoma is unique in that these tumours often retain overactivation of growth factor signalling, which can be targeted by receptor tyrosine kinase (RTK) inhibitors. However, mutations in kinases, except for ALK, are extremely rare in neuroblastoma. Furthermore, the high degree of intratumoural heterogeneity often renders RTK inhibition ineffective as a monotherapy. For high-risk tumours, which lack effective treatment options, there remains an unmet need for targeted therapies. This review summarises the roles of growth factor receptors in neural crest and neuroblastoma development in light of recent single-cell studies. We provide a systematic overview of RTK inhibitors that can target growth factor signalling in neuroblastoma and detail their current status in clinical development. We also explore the role of intratumoural heterogeneity in resistance to RTK inhibitors, focusing on the adrenergic-to-mesenchymal transition, which drives a switch in growth factor receptor expression. Finally, we discuss strategies to overcome RTK inhibitor resistance by targeting neuroblastoma cell plasticity, disrupting downstream signalling pathways, or inhibiting escape mechanisms from cell death. This review provides a theoretical basis for developing novel combination therapies incorporating RTK inhibitors. Full article