Search Results (208)

Head and neck cancer (HNC) comprises a heterogeneous group of tumours, most often of squamous cell origin, characterized by both high morbidity and mortality rates. It is the seventh most common form of cancer diagnosed in humans, accounting for approximately 4.7% of all cancers. Among HNCs, neck squamous cell carcinoma (HNSCC) is predicted to become the most common form of human cancer. Some sources include oesophagus (ESCC) in this group due to their similar histology, being described as upper aerodigestive tract cancers (UADT). Unfortunately, 60–70% of cases are diagnosed late, i.e., at clinical stages III-IV. As a result, despite modern surgical techniques and oncological treatments, the survival rate remains below 40–60% due to frequent lymph node metastases and local tumour recurrence. There is a growing concern that diet and inflammatory dietary components may influence the initiation and development of HNSCC. The inflammatory potential of diets can be quantified by the Dietary Inflammatory Index (DII). The DII was derived from an analysis of 45 dietary constituents that either increase or decrease inflammation. Several recent clinical studies have noted a significant relationship between DII score and many inflammation-associated chronic diseases, such as obesity, cardiovascular and neurodegenerative disorders, and diabetes, and the incidence of various human cancers, i.e., prostate, ovarian, breast, colorectal cancer, and HNC. However, few studies have investigated the relationship between DII and HNSCC, with most being limited to observational, case-control, and cross-sectional studies. Therefore, the aim of this narrative review is to present the substantial oncological aspects of DII, discuss the use of DII and its modification, the Energy-Adjusted Dietary Inflammatory Index (E-DII), as indicators of HNSCC risk. It also introduces key diet-induced pro- and anti-inflammatory mechanisms and the cellular molecular signalling pathways determining the carcinogenesis of HNSCC. It provides a comprehensive overview of the current literature, including key opinion-forming systematic reviews, as well as molecular, observational, cross-sectional and case-control studies, all of which are accessible via scholarly databases such as PubMed/EMBASE/Web of Science. Thus, the work serves as a compendium of up-to-date knowledge on the relationship between DII/ED-II score and HNSCC etiopathogenesis and the influence of a diet-induced persistent inflammatory microenvironment. Full article

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine malignancy. Like cutaneous malignant melanomas, a subset of MCCs can clinically present without an identifiable primary tumour, termed Merkel cell carcinoma of unknown primary (UPMCC), with incompletely understood behaviour and prognosis. Our objectives are to evaluate the clinical presentation, management and survival outcomes in UPMCC and compare overall survival with metastatic MCC of known-primary origin. Methods: A retrospective review of 252 consecutive MCC patients (1992–2023) identified 20 cases of histologically confirmed nodal or metastatic UPMCC. Demographics, anatomical distribution, treatment and oncological outcomes were analysed. Overall survival was compared with patients presenting with metastatic MCC of known primary. Results: The cohort included 15 males and 5 females (mean age 76 years). Presentation most commonly involved inguinal (n = 7) and axillary (n = 6) nodes, followed by parotid and cervical basins (n = 4). Management was multimodal, including lymphadenectomy, radiotherapy and systemic therapy. Six patients remained disease-free at a mean follow-up of 63.3 months. The mean overall survival was 43.65 months for UPMCC versus 39.29 months for known-primary metastatic MCC. Conclusions: UPMCC most commonly presents as inguinal or axillary nodal disease. Survival outcomes suggest a trend toward improved prognosis compared to known-primary metastatic MCC. Full article

Cancer multidrug resistance (MDR), particularly mediated by ATP-binding cassette (ABC) transporters, can link ABC transporters’ ATP-dependent efflux to Nrf2-driven antioxidant defence. This connection reduces the oxidative threshold in MDR cancer cells. Natural or nature-inspired compounds can target this vulnerability and induce collateral sensitivity (CS) by simultaneously modulating the redox balance and ABC transporters’ activity in MDR cancer cells. Moreover, natural-origin compounds can act on multiple targets by combining efflux inhibition, redox modulation, and immune evasion into a unique therapeutic strategy. However, many challenges should be addressed in their characterisation and preclinical validation to ensure their usefulness for clinical application. These include poor bioavailability, pharmacokinetic interactions, safe toxicity windows, and tumour heterogeneity. In perspective, adaptive trial designs employing biomarker-guided patient stratification can translate natural-origin compounds from preclinical promise to precision partners in clinical oncology. Full article

Background: Neuroendocrine tumors—are relatively rare but increasingly diagnosed malignancies originating from diffuse neuroendocrine cells, most commonly affecting the gastroenteropancreatic system. Due to their long asymptomatic development and low incidence, pose a diagnostic and therapeutic challenge for physicians. Recently, the role of nuclear medicine has been growing not only in the diagnostic stage but also in treatment. Systemic radionuclide therapy using somatostatin analogs labelled with the radioisotope lutetium-177 is becoming increasingly common in patients with advanced-stage disease. Currently, most patients receive a standard activity of therapeutic radiopharmaceuticals. Recent clinical studies provide increasing evidence of a close relationship between the absorbed radiation dose in pathological lesions and the therapeutic effect of radioisotope therapy. Internal dosimetry is used to measure the doses of ionising radiation absorbed by the patient after administration of the radiopharmaceutical. The lack of individual internal dosimetry prior to therapy means that only a small fraction of patients receive optimal doses of radioactivity, which is markedly different from external beam radiotherapy planning. Methods: A narrative literature review was conducted using the PubMed/MEDLINE and Embase databases, focusing primarily on publications from the last years. The search strategy included combinations of keywords related to peptide receptor radionuclide therapy and dosimetry, such as “Lutetium-177”, “neuroendocrine tumors”, “dosimetry”, “PRRT”, “systemic radionuclide therapy” and “artificial intelligence”. Particular emphasis was placed on recent prospective clinical studies, multicenter investigations, systematic reviews and consensus documents published by major nuclear medicine societies, including the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). Seminal earlier publications considered essential for understanding the development of dosimetry concepts and clinical implementation were also included. Results: This study confirms the existence of a clinically significant dose-response relationship in ¹⁷⁷Lu-PRRT. Higher absorbed doses to tumour lesions are associated with longer progression-free survival. The lack of individualized internal dosimetry prior to therapy means that only a small proportion of patients receive optimal radiation doses. Simplified dosimetric approaches with a reduced number of imaging time points, together with emerging artificial intelligence–based tools, appear promising for reducing the complexity of the dosimetry process. Conclusions: The aim of this study was to analyse the current literature on the role of internal dosimetry in the treatment of neuroendocrine tumors using the radioisotope lutetium-177. Available data support the clinical relevance of individualized dosimetry and highlight its potential to optimize both therapeutic efficacy and treatment safety. Full article

Solitary fibrous tumour is an uncommon, predominantly benign tumour of mesenchymal origin, developing mainly in the thoracic cavity and on the pleural surface, although it has been reported in a wide variety of extrapleural sites. Its occurrence in the liver is particularly rare. We present the case of a 57-year-old woman in whom a large mass was identified in the left lobe of the liver, demonstrating inhomogeneous contrast enhancement without significant compression of the abdominal vessels. The lesion measured 170 mm in its greatest diameter and severely destroyed the surrounding liver parenchyma. SFT is characterised by haphazardly arranged ovoid and spindle-shaped cells with numerous mildly staghorn-like vessels lined by flattened endothelium. It typically shows NAB2–STAT6 gene rearrangement with CD34 and/or STAT6 positivity on immunohistochemistry. Since imaging methods are not specific regarding the nature of the lesion, pathological and immunohistochemical analyses are essential for establishing an accurate diagnosis and assessing differential diagnostic possibilities. Full article

Background: Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome, also known as Herlyn–Werner–Wunderlich syndrome (HWWS), is a rare Müllerian malformation. Gynaecologic malignancies reported in association with OHVIRA syndrome/HWWS are exceptional and scattered across isolated case reports and small case series, leading to significant challenges for screening, early diagnosis, and optimal management. The primary aim of this study was to comprehensively review and synthesize the clinicopathologic features, treatment approaches, and reported outcomes of patients with OHVIRA-associated gynaecologic neoplasms. Methods: A systematic review of published cases of gynecologic malignancies in OHVIRA/HWWS was conducted using PubMed/MEDLINE and Scopus from database inception through January 2026. To expand the current evidence, an illustrative novel institutional case is also presented and integrated into the analysis. Results: A total of 21 cases were identified and analysed; reported tumours predominantly involved the lower genital tract (vagina/cervix), with a recurrent representation of adenocarcinoma, particularly clear cell histology, and a frequent origin from the obstructed or non-visible compartment when side was described. Endometrial and ovarian involvement was uncommon. Conclusions: The anatomical complexity of OHVIRA syndrome creates a diagnostic blind spot that warrants heightened clinical suspicion, rigorous MRI-based anatomic delineation, and side-specific evaluation in symptomatic patients. By synthesizing the available literature, this review underscores the necessity for tailored, multidisciplinary management and proactive surveillance strategies in this rare population. Full article

Background/Objectives: Tenosynovial giant cell tumours (TGCT) are a group of mesenchymal tumours involving the synovium, bursae, and tendon sheaths, comprising two subtypes: nodular and diffuse. Although predominantly benign, diffuse forms can be locally aggressive, resulting in bone destruction. The pathogenesis of TGCTs is still poorly understood. The aim of this study was to systematically review the current literature on the factors, mechanisms, and markers involved in TGCT disease, focussing on their potential role in bone destruction. Methods: This systematic review was conducted using the PRISMA guidelines. A search was performed using PubMed, Scopus, and Cochrane Library, and all original scientific research into mechanisms/pathways/signalling involving TGCTs was included. Results: After the review process, 51 studies were included for data extraction. Extracted data included authorship, publication year, patient numbers and aetiology (nTGCT/dTGCT), demographics, investigative methods, and studied biological factors, mechanisms, and markers. Cross-tabulation of reported elements revealed 159 unique factors, with most appearing only once. Eight elements were reported five or more times: CSF1, CD68, Ki-67, MMP9, CD163, TRAP, TNF-α, and IL-1β. Although representing just 5% of all identified factors, these appeared in 69% of the included studies, highlighting their prominence in the literature. Conclusions: Apart from the well-known osteoclastogenesis factor CSF1, inflammatory cytokines (TNF-α and IL-1β) and monocyte–macrophage lineage makers (CD68, CD163) are signalling pathways key to TGCT disease progression and associated bone destruction. Full article

Canine prostatic adenocarcinoma is a rare but highly aggressive cancer that is typically diagnosed at an advanced stage, due to the lack of effective screening methods and poor recognition of early lesions. Cancer stem cells are known to drive tumour progression and treatment resistance in human prostate cancer, but their role in naturally occurring canine disease remains poorly defined. A deeper understanding of the biology of canine prostatic adenocarcinoma is therefore essential to improve prognosis and to develop relevant comparative models. We established and comprehensively characterised two novel canine prostatic adenocarcinoma cell lines, Kodiak and Bobby, with detailed comparison to their tumours of origin and, for Kodiak, xenografts generated in immunodeficient mice. Both lines displayed variable epithelial morphology influenced by culture conditions, and Kodiak xenografts recapitulated key histopathological patterns of the primary tumour. Expression of the luminal epithelial marker CK8/18 and the basal marker CK14 was largely retained across tumour, cell line, and xenograft, whereas the basal markers CK5 and p63, and the urothelial marker UPIII, were diminished or lost during in vitro culture. Evaluation of cancer stem cell-associated markers showed consistent expression of CD44, Nanog, Oct3/4, and Sox2 in the original tumours and cell lines, while CD133, Nestin, and Trop2 were present in the tumours but absent in vitro, indicating selective loss of specific stem-like populations. Media-dependent plasticity was evident in the Bobby line. These models retain key epithelial and stemness features and provide robust platforms for translational prostate cancer research in dogs and humans. Full article

Background: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer and is marked by pronounced intra-tumoural heterogeneity that complicates therapeutic response. Patient-derived organoids offer a physiologically relevant model to capture this diversity and evaluate treatment effects. When integrated with spatial transcriptomics, they might enable the mapping of spatially resolved transcriptional and isoform-level changes within the tumour microenvironment. Methods: We established a robust workflow for generating patient-derived ccRCC organoids, that are not passaged and retain original cellular components. These retain key features of the original tumours, including cancer cell, stromal, and immune components. Results: Spatial transcriptomic profiling revealed multiple transcriptionally distinct regions within and across organoids, reflecting the intrinsic heterogeneity of ccRCC. Isoform-level analysis identified spatially variable expression of glutaminase (GLS) isoforms, with heterogeneous distributions of both the GAC and KGA variants. Treatment with NUC-7738, a phosphoramidate derivative of 3′-deoxyadenosine, induced marked transcriptional remodelling of organoids, including alterations in ribosomal and mitochondrial gene expression. Conclusions: This study demonstrates that combining long-read spatial transcriptomics with patient-derived organoid models provides a powerful and scalable approach for dissecting gene and isoform-level heterogeneity in ccRCC and for elucidating spatially resolved transcriptional responses to novel therapeutics. Full article

Background: Ameloblastomas account for roughly 1% of all jaw tumours and cysts, typically manifesting as slow-growing, painless swellings that expand both buccal and lingual cortical plates and may infiltrate adjacent soft tissue, often leading to a delayed diagnosis. These benign tumours, characterized by local invasiveness, originate from epithelial tissues and may develop from dental lamina cell rests, the enamel apparatus, the epithelial lining of odontogenic cysts, or basal epithelial cells of the oral mucosa. Methods: This paper aims to describe the comprehensive and interdisciplinary management of an extensive ameloblastoma in a 16-year-old patient, emphasizing the diagnostic challenges, surgical resection, reconstructive procedures, and subsequent oral rehabilitation. Results: At the eleven-year follow-up, clinical and radiographic examinations showed no signs of tumour recurrence. The patient presented no symptoms, indicating neither pain nor functional impairment. The prosthetic rehabilitation utilizing implant-supported fixed restorations was successfully completed, resulting in satisfactory masticatory function and aesthetics. This case adds to the existing evidence on the management of extensive ameloblastomas by demonstrating successful long-term outcomes following interdisciplinary surgical reconstruction and rehabilitation. Conclusions: The presented case highlights the complexity of restoring the lost tissues and functions, as well as the long-term clinical, functional, and aesthetic outcomes over an eleven-years follow-up period. Full article

Background/Objectives: Preterm newborns (NBs) are at increased risk of motor developmental impairments. Evidence on inflammatory and neurotrophic biomarkers measured in the neonatal period as predictors of motor outcomes is scarce and heterogeneous. This systematic review synthesised data on inflammatory biomarkers and neurotrophic factors in Preterm NB as predictors of motor development (MD) up to 24 months of corrected age. Methods: MEDLINE, SciELO, Web of Science and Embase were searched for longitudinal observational studies of Preterm NB (World Health Organization definition) that measured one or more inflammatory biomarkers and/or neurotrophic factors in blood, urine or saliva and applied validated neurodevelopmental scales up to 24 months. Non-original reports, populations outside scope and studies with incomplete data were excluded. Methodological quality of primary studies was assessed with the Newcastle–Ottawa Scale (NOS). The protocol was registered in PROSPERO (CRD42022365839). Results: Of 1475 records, eight studies met the eligibility criteria. Higher neonatal concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) were generally associated with poorer motor performance, although null findings occurred in some cohorts. One study assessing neurotrophic factors reported elevated urinary brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) among infants with below-expected MD. Conclusions: Inflammatory biomarkers show promise as early indicators of adverse MD in Preterm NB, but heterogeneity in populations, biospecimens, sampling windows, assays and outcome scales limits comparability and precludes definition of risk thresholds. Larger, standardised cohorts are needed to clarify the prognostic value of inflammatory and neurotrophic biomarkers and to inform early risk stratification. Full article

Gliomas, particularly glioblastoma multiforme, remain among the most lethal brain tumours despite multimodal therapy. Increasing evidence indicates that systemic factors, including the gut microbiota, may influence glioma progression through immune, metabolic, and neurochemical pathways. We conducted a comprehensive systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines to synthesize recent evidence on the role of gut and intratumoral microbiota in glioma biology. Peer-reviewed studies published within the last five years were identified through structured searches of major biomedical databases, and original studies using human cohorts, animal models, or Mendelian randomization approaches were included. The 17 studies met the eligibility criteria. Glioma was consistently associated with gut dysbiosis characterized by a reduced Firmicutes:Bacteroidetes ratio and enrichment of Verrucomicrobia, particularly Akkermansia, alongside decreased short-chain fatty acids and altered neurotransmitter profiles, contributing to neuroinflammation, immune suppression, and blood–brain barrier dysfunction. Antigenic mimicry by Bacteroidetes-derived peptides may impair antitumour T-cell responses, while intratumoral Fusobacteriota and Proteobacteria appear to promote angiogenesis and pro-inflammatory chemokine expression. In contrast, SCFA-producing taxa such as Ruminococcaceae and probiotic genera including Lactobacillus and Bifidobacterium show protective associations. Evidence is limited by small cohorts and methodological heterogeneity. Standardized humanized models and integrated multi-omics approaches are required to clarify causal mechanisms and support microbiome-targeted therapies in glioma. Full article

Background/Objectives: Interactions between colorectal tumours and their immune microenvironment critically influence disease progression and response to immunotherapy. However, most organoid systems fail to preserve the complex architecture and immune composition of the original tissue. Here, we applied the air–liquid interface (ALI) organoid model to paired tumour and perilesional colon tissues from colorectal cancer patients to evaluate its ability to retain immune and genetic features and to reproduce responses to chemotherapy and immune checkpoint blockade. Methods: Fresh human tumour and matched healthy colon tissues were processed to generate ALI organoids. Their histological organization, immune cell composition (including CD45⁺ subsets), and genomic profiles were compared with those of the parental tissues and with conventional Matrigel organoids, either alone or co-cultured with peripheral blood mononuclear cells (PBMCs). Organoids were exposed to 5-FU and nivolumab (anti–PD-1) to assess local immune modulation. Results: ALI organoids faithfully preserved the three-dimensional architecture, native immune infiltrates, and somatic mutational landscape of the source tissues. Importantly, upon PD-1 blockade with nivolumab, ALI organoids consistently exhibited a local expansion of regulatory T cells (Tregs), a phenomenon that could contribute to adaptive immune resistance. This response was not reproduced in PBMC–Matrigel co-culture systems, highlighting the importance of preserving endogenous tumour–immune interactions. Conclusions: Patient-derived ALI organoids represent a physiologically relevant platform that conserves key structural, immunological, and genomic hallmarks of colorectal cancer. By capturing clinically relevant immune remodeling events, such as Treg expansion following PD-1 blockade, this model provides a powerful tool for dissecting tumour–immune interactions. 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

Prostate cancer is one of the most common cancers affecting men, and finding better ways to detect and monitor it remains a top priority in oncology. In recent years, scientists have focused their attention on different classes of extracellular bodies, among them the small ones called exosomes. Exosomes are nanoscale extracellular vesicles (30–200 nm) released into body fluids, where they transport molecular cargo reflective of their cell of origin. Instead of serving as liquid biopsies themselves, exosomes present in accessible fluids such as plasma and urine can be analyzed as part of minimally invasive liquid biopsy strategies without the need for surgery or tissue sampling. In prostate cancer, exosomes are not just passive carriers: they actively influence how cancer grows, spreads, and responds to treatment. Exosomes can be extracted from simple fluid samples, opening the door to faster, safer, and more personalised approaches to diagnosis and care. Exosome content is analysed for the molecular profiling of tumours, including genomics, transcriptomics, proteomics, and metabolomics. This has led to the discovery of new biomarkers that may help detect prostate cancer earlier, predict its aggressiveness, and monitor the effectiveness of treatment. This review synthesizes current multi-omics data on exosomal cargo in prostate cancer, highlighting diagnostic, prognostic, and therapeutic implications as well as existing challenges to clinical translation. Full article