Search Results (4,762)

Introduction: Radon is a radioactive noble gas formed from uranium decay in the Earth’s crust. The most significant isotope, 222Rn, emits alpha particles capable of damaging lung tissue and inducing cancer. Radon exposure is affected by geophysical and building characteristics and is recognized as a Group 1 carcinogen by the IARC. Despite regulatory thresholds (e.g., EURATOM standards), health risks remain. Various mitigation methods aim to reduce indoor radon exposure and its impact. Materials and Methods: This systematic review followed PRISMA guidelines. PubMed, Scopus, and Web of Science were searched up to 28 February 2025, using a defined string. Studies with original data on radon exposure and lung cancer risk or mitigation efficacy were included. Independent screening and quality assessment (Newcastle–Ottawa Scale) were conducted by multiple reviewers. Results: Of the 457 studies identified, 14 met the inclusion criteria. Eleven of these investigated the link between indoor radon and lung cancer risk, and three evaluated mitigation strategies. Radon levels were commonly measured using passive alpha track detectors. Levels varied depending on geographical location, season, building design and ventilation, these were higher in rural homes and during the colder months. Case–control studies consistently found an increased lung cancer risk with elevated radon exposure, especially among smokers. Effective mitigation methods included sub-slab depressurisation and balanced ventilation systems, which significantly reduced indoor radon concentrations. Adenocarcinoma was the most common lung cancer subtype in non-smokers, whereas squamous and small cell carcinomas were more prevalent in smokers exposed to radon. Discussion and Conclusions: This review confirms the robust association between indoor radon exposure and lung cancer. Risks persist even below regulatory limits and are amplified by smoking. While mitigation techniques are effective, their application remains uneven across regions. Stronger public education, building codes, and targeted interventions are needed, particularly in high-risk areas. To inform future prevention and policy, further research should seek to clarify radon’s molecular role in lung carcinogenesis, especially among non-smokers. Full article

Introduction: The 9th edition of the TNM classification for lung cancer implemented significant revisions, notably the subdivision of the N2 and M1c categories, to enhance anatomical precision and prognostic accuracy. Nonetheless, the actual effects of these modifications on stage distribution, histology-specific patterns, and clinical interpretation remain to be fully evaluated. Objectives: To compare lung cancer staging distributions between the 8th and 9th TNM editions, analyze patterns of stage migration, and evaluate histology-specific reclassification trends. Although TNM 9 applies the same descriptors across all histological subtypes, the magnitude of stage migration varies. In our cohort and in international datasets, adenocarcinoma demonstrated a higher likelihood of reclassification into advanced stages compared to other subtypes. Methods: A retrospective analysis was performed on a cohort of lung cancer patients staged according to the 8th and 9th editions of the TNM classification. Stage distribution alterations were analyzed by chi-squared tests, whereas McNemar’s test examined the directional shifts in upstaging and downstaging. Further investigations evaluated the correlation between histological subtype and stage reclassification. Results: A statistically significant redistribution of stages was noted (χ² = 1013.03, df = 64, p < 0.0001), with a notable prevalence of upstaging (p = 0.0019). The most significant proportional increase was observed in stage IIIA, mostly attributable to the N2 subdivision (N2a vs. N2b). Adenocarcinoma was the predominant histological subtype at all stages and showed a greater tendency for reclassification into advanced stages, specifically IIIA and IIIB. Squamous cell carcinoma was predominantly observed in stages IIB and IIIA, whereas small cell and large cell carcinomas were concentrated in advanced stages. These histology-specific patterns correspond with international findings, including research confirming the prognostic relevance of N2 subdivision. Conclusions: The 9th edition of the TNM classification results in significant stage migration, particularly in adenocarcinoma cases, indicating the improved sensitivity of the updated criteria in identifying advanced nodal disease. These modifications significantly impact prognostic evaluation and global comparability of clinical cohorts, supporting the implementation of TNM 9 as a more anatomically and biologically relevant staging system. Full article

Background: Esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC) follow divergent incidence trajectories in the United States. Rising use of electronic nicotine delivery systems (ENDS) and evolving demographic risk profiles may be reshaping these trends. We aimed to characterize national incidence patterns of EAC and ESCC from 2000 through 2022—stratified by age, sex, and race/ethnicity—and to place these in the context of changing behavioral exposures. Methods: We performed a retrospective cohort study using Surveillance, Epidemiology, and End Results SEER 21 registry data (covering 48% of the U.S. population). We included first-primary, histologically confirmed EAC (ICD-O-3 codes 8140–8576) and ESCC (8050–8084) in individuals aged ≥ 15 years diagnosed between 2000 and 2022. Age-adjusted incidence rates (per 100,000 person-years; 2000 U.S. standard) and annual percent changes (APCs) were estimated via Joinpoint regression models. Results: A total of 90,290 EAC and 47,916 ESCC cases were identified. EAC incidence increased from 2.3 to 2.8 per 100,000 (APC +0.90%; 95% CI, 0.45–1.35), with the largest relative rises in ages 15–39 years (APC +1.50%) and among women (APC +2.65%). Non-Hispanic Black and American Indian/Alaska Native populations experienced the most pronounced EAC increases. Overall ESCC incidence declined (APC −0.78%; 95% CI, −1.10 to −0.46), though Asian/Pacific Islander (+3.59%) and American Indian/Alaska Native (+1.58%) groups saw rising rates. Conclusions: EAC incidence continues to climb—especially in younger adults, women, and select racial/ethnic minorities—while ESCC declines are uneven. These histology-specific patterns highlight the urgency of tailored prevention, targeted early-detection efforts, and mechanistic studies on emerging exposures such as vaping. Full article

Background/Objectives: Persistent human papillomavirus (HPV) infection is the leading cause of cervical intraepithelial neoplasia (CIN), a known precursor to cervical squamous carcinoma. While progesterone receptor membrane component 1 (PGRMC1) has been implicated in various cancers, its specific role in cervical carcinogenesis has remained uncertain. This study aimed to elucidate the function of PGRMC1 in the progression of CIN. Methods: Bioinformatics techniques were employed to assess the expression levels of PGRMC1 in cervical cancer tissues and to investigate its correlation with patient prognosis. To explore the functional role of PGRMC1, we manipulated its expression in the cervical cancer cell line HeLa using siRNA. Subsequently, we evaluated cell migration via the scratch assay, and invasion through the Transwell assay. We employed mass spectrometry to identify proteins interacting with PGRMC1 and confirmed these interactions using co-immunoprecipitation (co-IP). Further co-IP experiments were conducted to pinpoint the specific binding sites of these protein interactions, and immunofluorescence staining was utilized to observe the spatial distribution of interacting proteins within the cells. The phosphorylation status of VIM was further confirmed by WB. At the clinical level, we collected cervical biopsy specimens from HPV-positive patients and verified the expression patterns of PGRMC1 and VIM using immunohistochemical staining in cervical squamous cell carcinoma (CSCC) tissues. Results: We discovered a correlation between progressively increasing PGRMC1 expression and the severity of CIN as well as a poor prognosis. Knockdown of PGRMC1 resulted in the inhibition of migration and invasion capabilities in cervical cancer cells. Furthermore, PGRMC1 was found to physically interact and colocalize with Vimentin (VIM). Notably, PGRMC1 knockdown specifically increased phosphorylation at the Ser-39 residue of VIM. Conclusions: Our findings suggest that PGRMC1 facilitates CIN progression by binding to VIM and suppressing Ser-39 phosphorylation, thereby promoting the migration and invasion of cervical carcinoma cells. This study enhances our understanding of PGRMC1’s role in CIN progression and lays an experimental foundation for targeted therapeutic approaches to cervical squamous carcinoma. Full article

Mucins are a family of heavily glycosylated proteins that form the main organic component of the oral mucosal barrier complex. Transmembrane mucin 1 (tMUC1) is anchored at the superficial epithelial surface to provide a protective function. The interaction of tMUC1 with oral microbes provides nutrients and physicochemical protection, promotes adhesion, and increases the microbe residence time in the oral cavity. Mucin-degrading microorganisms in the consortia also offer some advantages to oral microbes. The high molecular weight of mucin glycoproteins is hard to study because of their size, complexity, and heterogeneity. This review discusses how mucin facilitates oral microbiome colonization and how mucin–microbial interactions influence the development of oral cancer, mainly oral squamous cell carcinoma. Full article

Cervical cancer (CC) is the fourth most common cancer among women globally, with venous thromboembolism (VTE) representing a life-threatening complication. Cancer-associated thrombosis (CAT) arises from tumor-driven activation of hemostasis, worsening prognosis. Recently, circulating microRNAs (miRNAs) have emerged as potential biomarkers for both CAT and cervical tumorigenesis. Thus, this study aimed to assess the implications of five miRNAs—miR-20a-5p, -23a-3p, -125b-5p, -145-5p, and -616-3p—in CC-related VTE context. These miRNAs were quantified by RT-qPCR in plasma from 69 CC patients before treatment. Briefly, VTE occurred in nine patients, decreasing overall survival (OS) [log-rank test, p = 0.005; hazard ratio (HR) = 4.78; 95% confidence interval (CI), 1.42–16.05]. Lower miR-20a-5p levels predicted VTE (ꭓ² test, p = 0.027) and, in subgroup analyses, they were linked to cervical squamous cell carcinoma (CSCC) and older age (ꭓ² test, p = 0.003 and p = 0.043, respectively). In VTE patients, miR-145-5p downregulation was associated with improved OS (log-rank test, p = 0.018), an effect also observed in the adenocarcinoma (ADC) subgroup (log-rank test, p = 0.039). The remaining miRNAs showed subtype-specific links to clinicopathological features and survival. These findings highlight the potential value of circulating miRNAs in thrombotic risk and prognosis assessment in CC. Full article

Background/Objectives: Accurate identification of vulvar high-grade squamous intraepithelial lesions (HSIL) is essential for preventing progression to invasive squamous cell carcinoma. This study addresses the gap in artificial intelligence (AI) applications for vulvar lesion diagnosis by developing and validating the first convolutional neural network (CNN) model to automatically detect and classify HPV-related vulvar lesions—specifically HSIL and low-grade squamous intraepithelial lesions (LSIL)—based on vulvoscopy images. Methods: This bicentric study included data from 28 vulvoscopies, comprising a total of 9857 annotated frames, categorized using histopathological reports (HSIL or LSIL). The dataset was divided into training, validation, and testing sets for development and assessment of a YOLOv11-based object detection model. Results: The CNN demonstrated a recall (sensitivity) of 99.7% and a precision (positive predictive value) of 99.1% for lesion detection and classification. Conclusions: This is the first AI model developed for detecting and classifying HPV-related vulvar lesions. The integration of such models into vulvoscopy could significantly improve diagnostic accuracy and positively impact women’s health by reducing the need for potentially invasive and anatomy-altering procedures. Full article

Background: Head and neck squamous cell carcinoma (HNSCC) is a prevalent malignancy with poor clinical outcomes. microRNA-7-5p (miR-7-5p) has been described as both a tumour suppressor and an oncomiR depending on the tissue context, but its role in HNSCC remains unclear. This study aimed to clarify the clinical significance and biological function of miR-7-5p in HNSCC by integrating data from multiple sources. Methods: A systematic review of the literature was conducted to identify studies analysing miRNA expression in human head and neck tissues. A meta-analysis of individual patient data from Gene Expression Omnibus (GEO), ArrayExpress, and The Cancer Genome Atlas (TCGA) was performed to assess miR-7-5p expression in tumours and normal tissues, and its associations with clinical parameters and prognostic outcomes. Bioinformatics analyses were used to predict miR-7-5p target genes, classify hub genes, and perform gene ontology enrichment analysis. MicroRNA in situ hybridisation (miRNA ISH) and real-time quantitative PCR (RT-qPCR) were conducted on tissue samples, HNSCC cell lines, and an in vitro model of oral oncogenesis to validate miR-7-5p expression patterns. Results: miR-7-5p was significantly upregulated in tumours compared to normal tissues and associated with larger tumour size, HPV-negative status, poor disease-specific survival, and shorter progression-free intervals. Bioinformatics analysis highlighted miR-7-5p target genes enriched in pathways related to cell growth, survival, and tumourigenesis. Despite evidence supporting the anti-cancer role of exogenous miR-7-5p in preclinical models, the observed endogenous upregulation in tumours suggests that miR-7-5p expression may represent a compensatory or stress-responsive mechanism during tumourigenesis, rather than acting as a primary oncogenic driver. Conclusions: This study provides new insights into the complex role of miR-7-5p in HNSCC, supporting its potential as both a biomarker and a therapeutic target. Understanding the context-specific functions of miR-7-5p is essential for its development as an RNA-based therapeutic in HNSCC. Full article

Introduction: The analysis of exhaustion marker expression, like immune checkpoint molecules (ICMs) on tumor-infiltrating lymphocytes as well as peripheral immune cells of patients with head and neck squamous cell carcinoma (HNSCC), is of high interest since it reveals information about the patient’s immune status and the effectiveness of immune modulation. However, data regarding age-dependent expression are lacking. Here, we demonstrate an increase in most ICMs associated with age and disease, suggesting immune checkpoint modulation as an evidence-based option for the treatment of aged HNSCC patients. Material and Methods: Peripheral blood mononuclear cells (PBMCs) (healthy: n = 30 with an age range from 21 to 84 years/HNSCC: n = 37 with an age range from 37 to 94 years) were analyzed via flow cytometry following (density gradient separation) standard protocol. Flow cytometry was performed using CD4 and CD8 as backbone markers as well as co-stimulatory molecules like CD137, OX40, GITR, and CD27 or ICM like PD-1, CTLA4, BTLA, LAG3, or TIM3 using a Gallios flow cytometer (Beckman Coulter, Brea, CA, USA). Results: We found a statistically significant decreased ICM expression on the PBMCs of healthy donors with increasing age. However, the expression of ICMs in HNSCC was significantly increased (PD1 on CD4⁺ T cells: p = 0.001), while we found a decreased co-stimulatory molecule expression (e.g., CD27 on CD4⁺ T cells and CD39⁺ T cells: p = 0.003 and p = 0.009, respectively). Immune cells of HPV^neg HNSCC have a significant age-dependent decrease in CD27 expression on CD8⁺, CD4⁺, and CD39⁺ T cells (p = 0.0426, p = 0.0078, and p = 0.0078, respectively). Conclusions: This study sheds light on the changing co-stimulatory molecule/ICM expression regarding the patient’s age and reveals an increase in most immune checkpoint molecules for HNSCC patients according to their age. This new evidence is valuable in ensuring individualized therapeutic approaches in the increasingly relevant field of checkpoint inhibition, even in old age. Full article

Immunogenic cell death (ICD) is a specialized form of cell death that triggers antitumor immune responses. In tumors, ICD promotes the release of tumor-associated and tumor-specific antigens, thereby reshaping the immune microenvironment, restoring antitumor immunity, and facilitating tumor eradication. However, the regulatory mechanisms of ICD and its immunological effects vary across tumor types, and a comprehensive understanding remains limited. We systematically analyzed the expression of 34 ICD-related regulatory genes across 33 tumor types. Differential expression at the RNA, copy number variation (CNV), and DNA methylation levels was assessed in relation to clinical features. Associations between patient survival and RNA expression, CNVs, single-nucleotide variations (SNVs), and methylation were evaluated. Patients were stratified into immunological subtypes and further divided into high- and low-risk groups based on optimal prognostic models built using a machine learning framework. We explored the relationships between ICD-related genes and immune cell infiltration, stemness, heterogeneity, immune scores, immune checkpoint and regulatory genes, and subtype-specific expression patterns. Moreover, we examined the influence of immunotherapy and anticancer immune responses, applied three machine learning algorithms to identify prognostic biomarkers, and performed drug prediction and molecular docking analyses to nominate therapeutic targets. ICD-related genes were predominantly overexpressed in ESCA, GBM, KIRC, LGG, PAAD, and STAD. RNA expression of most ICD-related genes was associated with poor prognosis, while DNA methylation of these genes showed significant survival correlations in LGG and UVM. Prognostic models were successfully established for 18 cancer types, revealing intrinsic immune regulatory mechanisms of ICD-related genes. Machine learning identified several key prognostic biomarkers across cancers, among which NT5E emerged as a predictive biomarker in head and neck squamous cell carcinoma (HNSC), mediating tumor–immune interactions through multiple ligand–receptor pairs. This study provides a comprehensive view of ICD-related genes across cancers, identifies NT5E as a potential biomarker in HNSC, and highlights novel targets for predicting immunotherapy response and improving clinical outcomes in cancer patients. Full article

Epidermolysis bullosa (EB) is a group of debilitating, genetic skin disorders characterized by excessive skin fragility, blistering, and ulcerations that cause a cyclical wound healing process. EB presents itself in various subtypes, such as EB simplex (EBS), junctional EB (JEB), dystrophic (DEB), and Kindler Syndrome (KS), which all differ in their genetic cause, severity, and harbor different causes of mortality. Of these variants, JEB and DEB are the most severe, with EBS being the mildest form of the disease and KS presenting in extremely rare cases. The JEB variant tends to cause mortality early on in children less than two years of age due to failure to thrive, sepsis from wound infections, and airway obstruction. In the recessive form of DEB (RDEB), cutaneous squamous cell carcinoma (cSCC) is the major cause of death in patients, with one study reporting a mere 4-year survival after the first EB-cSCC diagnosis. Cutaneous SCCs in the setting of RDEB are particularly concerning because they are often more aggressive and show greater metastatic potential, as compared to ultraviolet-induced SCCs. This review aims to explore the pathophysiology of these EB variants as well as their implications for developing cSCCs. It will also discuss elements of the clinical presentation of such lesions in EB patients and the challenges associated with making a definitive diagnosis. Additionally, we will illuminate various diagnostic techniques, current and future management and treatment strategies for both cSCC and EB, and the importance of early screening and education for patients with EB to maximize patient lifespan and quality of life. Full article

Background/Objectives: Head and neck cancer (HNC) is the sixth most common cancer worldwide, with a high mortality, particularly from head and neck squamous cell carcinoma (HNSCC). Although some therapeutic strategies are available, they might cause severe side effects. For example, surgery may result in disfigurement and functional loss, severely impacting the patient’s quality of life. Thus, minimally invasive and more effective alternatives are needed. Gold nanoparticle (AuNP)-mediated photothermal therapy (PTT) is a promising approach for HNC, which relies on AuNP photothermal efficiency and tumor localization. This study aimed to synthesize and characterize AuNPs, evaluate their safety without laser activation, and assess their efficacy with laser activation. Methods and Results: Their physicochemical and photostability over three months and sterility were confirmed. In vitro safety was tested using human non-cancerous and HNC cell lines, while in vivo biocompatibility was evaluated in the hen’s egg chorioallantoic membrane (CAM) model, with no adverse effects observed. Upon laser activation, AuNPs reduced HNC cell viability by 50–70%, including HNSCC lines. In vivo biodistribution studies showed that AuNPs remained at the injection site for up to one month without toxicity. Conclusions: Overall, the developed AuNP formulation demonstrates stability, biocompatibility, and prolonged local retention, key attributes for effective and targeted PTT. These findings support the potential of AuNP-mediated photothermal therapy as a promising treatment modality for HNC, although further preclinical and clinical studies are needed to optimize treatment parameters. Full article

Introduction: Prostate cancer is one of the most common neoplasia in men, and its clinical evolution is highly influenced by psycho-emotional factors, especially in elderly patients. Comorbidities, the perception of one’s identity and its impact on life quality become relevant variables in the therapeutic decision. Sexual dysfunction after treatment along with decreased libido, erectile dysfunction and ejaculatory dysfunction are significant problems in patients with prostate cancer. Case presentation: The present study presents the oncological evolution of an elderly patient with a dual diagnosis, prostate adenocarcinoma and lung squamous cell carcinoma, who faced a significant amount of medical and psychological challenges. Reluctance to hormone therapy was closely linked to the fear of sexual dysfunction, a very common reaction in elderly men concerned with maintaining autonomy and intimacy. The peculiarity of the case consists in the interaction between the evolution of the disease, the therapeutic decisions and the psychological impact on the patient. Discussion: Androgen deprivation therapy negatively influences multiple aspects of sexual function, significantly impairing the life quality of patients diagnosed with prostate cancer. In this context, therapy through acceptance and commitment is the appropriate one, its main purpose being to change the patient’s relationship with suffering—from struggle and rejection to active acceptance and value of the present. The intervention of the psychologist or the psychotherapist is essential in decision-making counseling, using coping techniques, the clarification of personal values and the involvement of the family in the decision-making process. Oncological psychology helps the patient redefine their life goals and priorities, not just to choose a treatment. Conclusions: Sexuality and psychological health are deeply affected by prostate cancer. Psychological flexibility and emotional support can mitigate this negative impact. The integration of therapy through acceptance and commitment in the rehabilitation after treatment increases effectiveness and patient satisfaction. Full article

Erythema ab igne (EAI), also known as “hot water bottle rash” or “toasted skin syndrome”, is a benign cutaneous condition caused by chronic exposure to low-level infrared heat. It typically begins as transient erythema and evolves into a reticulated brown pigmentation with telangiectasias. A skin biopsy, ideally taken from the central area of the hyperpigmented lesion, is recommended to exclude differential diagnoses. Although usually benign, EAI has been associated with rare malignant transformations, supported only by low-level evidence. Elimination of the heat source is essential, and topical treatments such as hydroquinone or retinoids may be considered, while agents like 5-fluorouracil or imiquimod are reserved for dysplastic lesions. Women with endometriosis frequently use heating devices to alleviate dysmenorrhea and chronic pelvic pain. However, prolonged or inappropriate heat application can lead to chronic thermal injury, including EAI, and may delay medical consultation. While controlled trials confirm short-term analgesic efficacy of heat therapy, extrapolating these findings to unrestricted home use without standardized safety recommendations can be misleading. EAI illustrates the broader impact of chronic pain in endometriosis, linking cutaneous manifestations with neuroplastic alterations and psychiatric comorbidities. A nuanced approach combining patient education on safe use of heat, close dermatologic monitoring, and multidisciplinary pain management is warranted. Full article