Search Results (317)

Background: Long non-coding RNAs (lncRNAs) are increasingly recognized as pivotal regulators in both inflammatory and neoplastic skin disorders. Their implications in numerous biological processes, including gene expression, immune responses, and epidermal homeostasis, suggest potential applications as diagnostic and prognostic markers, as well as therapeutic targets. Methods: We conducted a literature search on lncRNAs involved in both psoriasis and cutaneous squamous cell carcinoma (cSCC), highlighting overlapping pathogenic mechanisms. Results: Several lncRNAs, such as HOTAIR, MALAT-1, H19, and uc.291, display dysregulated expression in both psoriasis and cSCC, influencing keratinocyte proliferation and apoptosis, immune modulation, cytokine signaling, and the synthesis of epidermal proteins. Conclusions: The intersection of lncRNA function in chronic inflammation and skin carcinogenesis underscores their role in mediating the transition from psoriatic inflammation to tumorigenesis, offering new insights into disease susceptibility; further investigation through functional studies and clinical validation are required. The study of lncRNA-mediated molecular pathways is particularly relevant given the increased risk of non-melanoma skin cancers and lymphoproliferative disorders among patients with chronic and severe forms of psoriasis. Full article

Intravascular lymphoma (IVL) is a rare, aggressive subtype of non-Hodgkin lymphoma (NHL) characterized by the selective proliferation of neoplastic lymphoid cells within small and medium-sized blood vessels, most frequently of B-cell origin (IVLBCL). Its protean clinical presentation, lack of pathognomonic findings, and absence of tumor masses or lymphadenopathies often lead to diagnostic delays and poor outcomes. IVLBCL can manifest in classic, hemophagocytic syndrome-associated (HPS), or cutaneous variants, with extremely variable organ involvement including the central nervous system (CNS), skin, lungs, and endocrine system. Diagnosis requires histopathologic identification of neoplastic intravascular lymphoid cells via targeted or random tissue biopsies. Tumor cells are highly atypical and display a non-GCB B-cell phenotype, often expressing CD20, MUM1, BCL2, and MYC; molecularly, they frequently harbor mutations in MYD88 and CD79B, defining a molecular profile shared with ABC-type DLBCL of immune-privileged sites. Therapeutic approaches are based on rituximab-containing chemotherapy regimens (R-CHOP), often supplemented with CNS-directed therapy due to the disease’s marked neurotropism. Emerging strategies include autologous stem cell transplantation (ASCT) and novel immunotherapeutic approaches, potentially exploiting the frequent expression of PD-L1 by tumor cells. A distinct but related entity, intravascular NK/T-cell lymphoma (IVNKTCL), is an exceedingly rare EBV-associated lymphoma, showing unique own histologic, immunophenotypic, and molecular features and an even poorer outcome. This review provides a comprehensive overview of the current understandings about clinicopathological, molecular, and therapeutic landscape of IVL, emphasizing the need for increased clinical awareness, standardized diagnostic protocols, and individualized treatment strategies for this aggressive yet intriguing malignancy. Full article

Plants produce an extensive repertoire of secondary metabolites, developed over evolutionary time to support survival. Among these, D-limonene, a monoterpene exuded by citrus fruits, has demonstrated a broad range of pharmacological activities. This review elucidates limonene’s biological versatility, spanning antioxidant, anti-inflammatory, antitumor, antidiabetic, neuroprotective, and gastroprotective domains. Synthesizing data from both preclinical and early-phase clinical research, we explore its molecular mechanisms, ranging from reactive oxygen species mitigation and apoptosis induction to metabolic remodeling and neurotransmitter modulation. Special attention is given to limonene’s emerging role in oncological therapeutics, notably in breast and liver cancers, and its capacity to ameliorate pathophysiological hallmarks of diabetes and neurodegeneration. Its low toxicity and high bioavailability support its potential as a safe adjunct or alternative in phytotherapy. This review advocates for continued investigation into limonene’s translational potential across a spectrum of neoplastic and non-neoplastic diseases. Full article

Gastroesophageal reflux disease (GERD) is associated with inflammatory and neoplastic changes in the esophageal epithelium. Despite widespread PPI use, esophageal adenocarcinoma (EAC) incidence continues to rise, implicating non-acidic reflux components such as pepsin in disease progression. We performed transcriptomic profiling to assess pepsin-induced changes and the protective effect of amprenavir in vitro. Het-1A (normal) and BAR-T (Barrett’s) cells (n = 3) were treated at pH 7.0 with pepsin and/or 10 μM amprenavir for 1 h. RNA-seq identified DEGs (FDR ≤ 0.05, |log₂FC| ≥ 0.375), and Ingenuity Pathway Analysis revealed enriched pathways. Pepsin exposure altered mitochondrial function, oxidative phosphorylation, epithelial integrity, signaling, and inflammatory pathways in both cell lines. Amprenavir attenuated these transcriptomic perturbations, preserving mitochondrial and stress-response pathways. Notably, BAR-T cells exhibited heightened activation of wound-healing and epithelial repair pathways, whereas Het-1A cells showed greater mitochondrial and systemic stress pathway alterations. Pepsin drives transcriptomic dysregulation in esophageal epithelial cells under non-acidic conditions, and amprenavir shows potential to counteract peptic injury. Further studies are needed to validate these findings and explore amprenavir’s therapeutic utility in GERD management and EAC prevention. Full article

Systemic cancer progression culminating in metastatic disease is implicitly dependent on tumour cell interactions with the vascular system. Indeed, different facets of the micro- and macro-vasculature can be regarded as rate-limiting ‘vascular checkpoints’ in the process of cancer dissemination. The underlying complex communication networks drive tumour neovascularization, angiogenesis, immunoregulation, activation of the coagulation system, angiocrine interactions, and non-angiogenic vascular responses across multiple cancer types. Yet, each cancer may represent a unique vascular interaction scenario raising a prospect of targeted modulation of blood and lymphatic vessels for therapeutic purposes, beyond the traditional notion of tumour anti-angiogenesis. While the emphasis of studies aiming to understand this circuitry has traditionally been on soluble, or ‘mono-molecular’ mediators, the rise of the particulate secretome encompassing heterogeneous subpopulations of extracellular vesicles (EVs; including exosomes) and particles (EPs) brings another dimension into the tumour–vascular communication web during the process of metastasis. EVs and EPs are nanosized cellular fragments, the unique nature of which lies in their ability to encapsulate, protect and deliver to target cells a range of bioactive molecular entities (proteins, RNA, DNA) assembled in ways that enable them to exert a wide spectrum of biological activities. EVs and EPs penetrate through biological barriers and are capable of intracellular uptake. Their emerging vascular functions in metastatic or infiltrative cancers are exemplified by their roles in pre-metastatic niche formation, thrombosis, vasectasia or angiocrine regulation of cancer stem cells. Here, we survey some of the related evidence supporting the biological, diagnostic and interventional significance of EVs/EPs (EVPs) in disseminated neoplastic disease. Full article

Artificial intelligence (AI) is rapidly transforming diagnostic approaches in different fields of medical sciences, demonstrating an emerging potential to revolutionize dermatopathology due to its capacity to process large amounts of data in the shortest possible time, both for diagnosis and research purposes. Different AI models have been applied to neoplastic skin diseases, especially melanoma. However, to date, very few studies have investigated the role of AI in dermatoses. Herein, we provide an overview of the key aspects of AI and its functioning, focusing on medical applications. Then, we summarize all the existing English-language literature about AI applications in the field of non-neoplastic skin diseases: superficial perivascular dermatitis, psoriasis, fungal infections, onychomycosis, immunohistochemical characterization of inflammatory dermatoses, and differential diagnosis between the latter and mycosis fungoides (MF). Finally, we discuss the main challenges related to AI implementation in pathology. Full article

Progranulin (PGRN) is a pluripotent growth factor that has shown promise as a diagnostic and prognostic biomarker for various neoplastic conditions in humans. This study aims to explore the PGRN as a novel biomarker for diagnosing and predicting the prognosis in canine tumors. Dogs (n = 104) with tumors as the chief complaint were selected and classified based on clinical categorization, malignancy, and metastasis. The control group (n = 30) consisted of healthy dogs with no evidence of neoplastic diseases. Serum PGRN levels were quantified using enzyme-linked immunosorbent assay (ELISA). Dogs with tumors exhibited significantly elevated PGRN levels compared to control dogs (p < 0.0001), with a high sensitivity of 90.91%. Malignant tumors demonstrated markedly higher PGRN levels relative to the control group (p = 0.0012), while no significant difference was found between benign tumors and the control group. Additionally, serum PGRN was identified as a significant marker for differentiating metastatic tumors from non-metastatic ones (p = 0.0264). PGRN exhibited high sensitivity for tumor detection, suggesting that it may serve as a screening biomarker. Prognostically, increased PGRN correlated with unfavorable outcomes, notably linked to malignancy and metastasis. This study underscores the potential of PGRN as a novel biomarker with early diagnostic and prognostic value in canine oncology. Full article

Background/objectives: Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized by chromosome instability and predisposition to develop myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML). Clonal chromosome aberrations (CCAs) in chromosomes 1, 3, and 7 frequently appear in the bone marrow (BM) of patients with FA and are associated with MDS/AML progression. Given the underlying DNA repair defect that characterizes FA, non-clonal chromosomal abnormalities (NCCAs) are expected to be common events in the FA BM; in this study, we investigated the presence and significance of NCCA and CCA in the bone marrow (BM) of patients with FA. Methods: Here, we transversally examined the BM karyotypes of 43 non-transplanted patients with FA, 41 with non-clinically detectable hematologic neoplasia and two with diagnosed MDS. We searched for the presence of NCCAs, complex karyotypes (CKs), and CCAs as well as their association with the natural history of the disease, including age, degree of BM failure, and neoplastic transformation. Results: NCCAs were observed in the metaphase spreads of 41/43 FA patients; CKs were observed in 25/43 patients; CCAs were found in 15/43 patients; CCAs involving chromosomes 1, 3 and/or 7 were found in four patients; and other autosomes were found in the remaining 11 patients. Overall, we observed a baseline large karyotypic heterogeneity in the BM of FA patients, demonstrated by the ubiquitous presence of NCCA; such karyotypic heterogeneity precedes the eventual emergence of CKs and selection of cells carrying fitness-improving CCAs. Finally, CCAs involving chromosomes 1, 3 and 7, well-known drivers of hematological malignancy in FA, become established. Overall, we observed that the frequency of NCCAs and CCAs increased with age, even though a significant correlation was not found. Conclusions: These observations fit the model of evolution towards cancer that comprises a first phase of macroevolution represented by NCCAs and karyotypic heterogeneity, followed by the establishment of clones with CCAs, leading to microevolution and cancer. NCCAs are the most frequent chromosomal alterations in the bone marrow of patients with AF and constitute a genome with extensive karyotypic heterogeneity that evolves into clones with more complex genomes and can eventually progress to cancer. Full article

Heterogeneous nuclear ribonucleoprotein H1 (hnRNPH1) is a multifunctional RNA-binding protein (RBP) that plays a central role in post-transcriptional regulation. Through its quasi-RNA recognition motifs and low-complexity domains, hnRNPH1 specifically binds guanine-rich RNA sequences, including G-quadruplex structures, to precisely modulate multiple aspects of RNA metabolism, such as alternative splicing, mRNA stability, translation, and subcellular localization. Accumulating evidence has implicated hnRNPH1 dysfunction in the pathogenesis of several human diseases. In cancer, hnRNPH1 often acts as a pro-tumorigenic factor, albeit in a context-dependent manner, influencing the alternative splicing of crucial oncogenes, mRNA stability, and tumor cell sensitivity to therapeutic agents. In the nervous system, hnRNPH1 is involved in neurodevelopment, neurodegenerative diseases, and drug addiction and plays an essential role in maintaining neuronal function and homeostasis. Furthermore, it exerts regulatory functions in reproductive system development and fertility and in non-neoplastic pathologies, including cardiovascular diseases, autoimmune disorders, and viral hepatitis. Given its pathophysiological significance, hnRNPH1 has emerged as a promising biomarker and therapeutic target. This review provides an overview of the structural basis and core molecular function of hnRNPH1. Its mechanisms of action and pathological significance in various diseases have also been detailed. Additionally, this review summarizes the current therapeutic strategies targeting hnRNPH1, discusses the associated challenges, outlines optimization approaches, and considers future research directions. Overall, this review aims to deepen our understanding of hnRNPH1 biology and inspire the development of novel diagnostic and therapeutic interventions. Full article

Splanchnic vein thrombosis (SVT) is a heterogeneous group of disorders affecting the portal, mesenteric, splenic, and hepatic veins. While frequently associated with liver cirrhosis and malignancy, SVT also occurs in non-cirrhotic, non-neoplastic patients. This narrative review evaluates the epidemiology and risk factors for SVT in this population. The prevalence and incidence of SVT in non-cirrhotic, non-neoplastic patients remain incompletely characterized, with estimates varying widely across studies. The clinical significance of SVT relates to potential complications, including intestinal ischemia, portal hypertension, and a possible underlying systemic disorder. Risk factors for SVT can be categorized into local abdominal conditions, thrombophilias, and systemic disorders. Local factors include inflammatory bowel disease, pancreatitis, abdominal surgery, and trauma. Thrombophilias, both inherited and acquired, are significant contributors to SVT risk. Systemic conditions associated with SVT include autoimmune disorders, pregnancy, hematological diseases, and infections. The complex interplay of these risk factors highlights the need for a comprehensive evaluation of SVT patients. Early recognition and management of these conditions can prevent potentially life-threatening complications and guide decisions regarding anticoagulation and long-term follow-up. Full article

Domestic cats are currently recognized to be infected by 10 different Felis catus papillomavirus (FcaPV) types that are classified into three genera. Examination of a skin sample from a cat with presumptive allergic dermatitis revealed clusters of large amphophilic intracytoplasmic bodies within epidermal cells. A 312 bp section of DNA from a novel PV type was amplified from the sample, while the entire 7569 bp genome was amplified and sequenced from a skin swab. The novel PV, which was designated FcaPV11, was predicted to contain coding regions for five early proteins and two late ones. Phylogenetic analysis of the L1 gene sequence showed FcaPV11 clusters with members of the Treisetapapillomavirus genus and shares less than 64% similarity with any of the previously fully sequenced FcaPV types. FcaPV11 DNA was not detected in a series of neoplastic and non-neoplastic skin samples from an additional 30 cats. These results show, for the first time, that cats can be infected by members of the Treisetapapillomavirus genus and suggest PVs in this genus may have co-evolved with a common Carnivora ancestor. While FcaPV11 was considered unlikely to have caused skin lesions in this cat, the prominent PV-induced cell changes indicate the PV can influence cell regulation. This suggests FcaPV11 may have the potential to cause skin disease in cats. Full article

(1) Background: Extrapulmonary tuberculosis (EPTB) of the head and neck is a rare but difficult diagnosis due to mostly absent pulmonary involvement and high clinical resemblance to neoplastic or chronic inflammatory conditions. This diagnosis still poses a challenge for otorhinolaryngologists, due to non-specific symptoms and the low index of suspicion in non-endemic regions. (2) Methods: This study presents a retrospective review of nine cases of head and neck EPTB diagnosed at two regional hospitals in southern Romania. Patients presented with pharyngeal, laryngeal, or cervical lymph node involvement. All cases underwent surgical biopsies for histopathological and microbiological confirmation, followed by standard anti-tubercular therapy. (3) Results: In all nine cases, surgical biopsies were essential for the accurate diagnosis and excluded malignancy or other granulomatous diseases. Diagnostic delays were observed due to atypical clinical presentations. Integration of biopsy findings with anti-tubercular treatment resulted in favorable disease control and clinical recovery. (4) Conclusions: Head and neck EPTB requires a high index of suspicion and clinical discernment. Surgical biopsy remains a critical diagnostic tool in practice and should be considered early in the diagnostic process when encountering atypical lesions. A timely use improves diagnostic accuracy, may eliminate delays, ensures patient safety, and improves therapeutic outcomes. Full article

Cardiac tumors, though rare, present significant diagnostic and therapeutic challenges due to their heterogeneous nature and anatomical complexity. This narrative review synthesizes current evidence on prevalence, diagnostic modalities, and management strategies for primary and metastatic cardiac tumors. Echocardiography, cardiac MRI, and CT remain cornerstone imaging tools for differentiating tumors from non-neoplastic masses, while advances in PET/CT and tissue characterization techniques refine staging and treatment planning. Surgical resection with clear margins (R0) is critical for resectable tumors, particularly benign myxomas, though malignant tumors like sarcomas require multimodal approaches combining surgery, radiotherapy, and systemic therapies. Emerging strategies such as heart autotransplantation and staged resections offer promise for complex cases, while oligometastatic disease management highlights the role of stereotactic radiotherapy and immunotherapy. Key challenges include standardizing resection margins, optimizing neoadjuvant therapies, and addressing high recurrence rates in malignancies. Future directions emphasize integrating AI-driven imaging analysis, molecular biomarkers, and genomic profiling to personalize therapies, alongside global registries to enhance data on rare tumors. Equitable access to advanced diagnostics and multidisciplinary collaboration are essential to improve outcomes. This review underscores the need for standardized guidelines, technological innovation, and patient-centered research to address gaps in cardiac oncology. Full article

Background/Objectives: Oral cancer is a significant global public health concern. Understanding the prevalence and associated risk factors of oral lesions is essential for developing effective preventive strategies. This study aimed to assess the prevalence and risk factors of oral lesions submitted for biopsy in a Portuguese subpopulation. A retrospective cross-sectional analysis was conducted using data from patients who sought dental care at the Egas Moniz Dental Clinic (EMDC) in the Lisbon metropolitan area. Methods: Data analysis was performed on a sample of 264 patients who attended the EMDC between October 2016 and December 2019 to ascertain the presence of oral lesions, their different types, and their correlation with potential risk factors. The analysis included all patients who underwent biopsy, and their pathology reports were reviewed. Results: The prevalence of oral lesions was 10.3%, affecting 58.7% females and 41.3% males, with a mean age of 55 years. The most frequently biopsied site was the buccal mucosa (23.5%). Non-neoplastic lesions accounted for 75.0% of cases, while mesenchymal lesions were the most common neoplastic category (58.5%). The most prevalent diagnosis was fibroepithelial hyperplasia (36.7%). A statistically significant association was observed between neoplastic lesions and statin use, as well as between both neoplastic and non-neoplastic lesions and the use of antidiabetic medications. Conclusions: Oral lesions are prevalent, with non-neoplastic lesions being the most frequent. Understanding their nature, prevalence, and associated risk factors is crucial for early and accurate diagnosis, aiding in disease prevention and management. Full article

The peritoneum is a thin membrane that lines the abdominal cavity and covers the abdominal organs. It serves as a conduit for the spread of various pathological processes, including gas and fluid collections, inflammation, infections, and neoplastic conditions. Peritoneal carcinomatosis is the most common and well-known pathology involving the peritoneum, typically resulting from the dissemination of gastrointestinal and pelvic malignancies. However, numerous benign and malignant peritoneal diseases can mimic the imaging appearance of peritoneal carcinomatosis. The aim of this review is to revisit the anatomy of peritoneal compartments and elucidate the patterns of peritoneal disease spread. Emphasis is placed on identifying the distinctive imaging features of both neoplastic and non-neoplastic peritoneal diseases that differ from peritoneal carcinomatosis. Full article