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18 pages, 644 KiB  
Article
Atrial Fibrillation Risk Scores as Potential Predictors of Significant Coronary Artery Disease in Chronic Coronary Syndrome: A Novel Diagnostic Approach
by Alexandru-Florinel Oancea, Paula Cristina Morariu, Maria Godun, Stefan Dorin Dobreanu, Miron Mihnea, Diana Gabriela Iosep, Ana Maria Buburuz, Ovidiu Mitu, Alexandru Burlacu, Diana-Elena Floria, Raluca Mitea, Andrei Vâță, Daniela Maria Tanase, Antoniu Octavian Petris, Irina-Iuliana Costache-Enache and Mariana Floria
Life 2025, 15(7), 1134; https://doi.org/10.3390/life15071134 - 18 Jul 2025
Viewed by 473
Abstract
Chronic coronary syndrome (CCS) and atrial fibrillation (AF) are prevalent cardiovascular conditions that share numerous risk factors and pathophysiological mechanisms. While clinical scores commonly used in AF—such as CHA2DS2VA (which includes congestive heart failure, hypertension, age ≥ 75, diabetes, [...] Read more.
Chronic coronary syndrome (CCS) and atrial fibrillation (AF) are prevalent cardiovascular conditions that share numerous risk factors and pathophysiological mechanisms. While clinical scores commonly used in AF—such as CHA2DS2VA (which includes congestive heart failure, hypertension, age ≥ 75, diabetes, stroke/TIA, vascular disease, and age 65–74), HAS-BLED (which incorporates hypertension, abnormal renal/liver function, stroke, bleeding history, labile INR, elderly age, and drug/alcohol use), and C2HEST (incorporating coronary artery disease, COPD, hypertension, elderly age ≥ 75, systolic heart failure, and thyroid disease)—are traditionally applied to rhythm or bleeding risk prediction, their value in estimating the angiographic severity of coronary artery disease (CAD) remains underexplored. We conducted a prospective, single-center study including 131 patients with suspected stable CAD referred for coronary angiography, stratified according to coronary angiographic findings into two groups: significant coronary stenosis (S-CCS) and non-significant coronary stenosis (N-CCS). At admission, AF-related scores (CHA2DS2, CHA2DS2VA, CHA2DS2VA-HSF, CHA2DS2VA-RAF, CHA2DS2VA-LAF, HAS-BLED, C2HEST, and HATCH) were calculated. CAD severity was subsequently assessed using the SYNTAX and Gensini scores. Statistical comparisons and Pearson correlation analyses were performed to evaluate the association between clinical risk scores and angiographic findings. Patients in the S-CCS group had significantly higher scores in CHA2DS2VA (4.09 ± 1.656 vs. 3.20 ± 1.338, p = 0.002), HAS-BLED (1.98 ± 0.760 vs. 1.36 ± 0.835, p < 0.001), CHA2DS2VA-HSF (6.00 ± 1.854 vs. 5.26 ± 1.712, p = 0.021), and C2HEST (3.49 ± 1.501 vs. 2.55 ± 1.279, p < 0.001). Multivariate logistic regression identified HAS-BLED and C2HEST as independent predictors of significant coronary lesions. A threshold value of HAS-BLED ≥ 1.5 and C2HEST ≥ 3.5 demonstrated moderate discriminative ability (AUC = 0.694 and 0.682, respectively), with acceptable sensitivity and specificity. These scores also demonstrated moderate to strong correlations with both Gensini and SYNTAX scores. AF-related clinical scores, especially HAS-BLED and C2HEST, may serve as practical and accessible tools for early CAD risk stratification in patients with suspected CCS. Their application in clinical practice may serve as supplementary triage tools to help prioritize patients for further diagnostic evaluation, but they are not intended to replace standard imaging or testing. Full article
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10 pages, 224 KiB  
Article
High-Frequency Basal Cell Carcinoma: Demographic, Clinical, and Histopathological Features in a Belgian Cohort
by Katharina Charlotte Wunderlich, Carmen Orte Cano, Mariano Suppa, Olivier Gaide, J. M. White, Hassane Njimi, Euromelanoma Working Group and Véronique Del Marmol
J. Clin. Med. 2025, 14(13), 4678; https://doi.org/10.3390/jcm14134678 - 2 Jul 2025
Viewed by 476
Abstract
Background: Basal cell carcinoma (BCC) is the most common skin cancer worldwide, with a multifactorial aetiology involving environmental and intrinsic factors. A small subset of patients develops high-frequency BCC (HF-BCC), defined as ≥9 BCCs within 3 years. Objective: To analyse demographic, [...] Read more.
Background: Basal cell carcinoma (BCC) is the most common skin cancer worldwide, with a multifactorial aetiology involving environmental and intrinsic factors. A small subset of patients develops high-frequency BCC (HF-BCC), defined as ≥9 BCCs within 3 years. Objective: To analyse demographic, clinical, and histopathological features of non-syndromic HF-BCC in a Belgian cohort, compared with low-burden BCC patients and healthy controls. Methods: A retrospective cohort study was conducted at Erasme Hospital (Brussels) using data from the EUSCAP platform. Clinical, behavioural, and histopathological data were collected and statistically analysed. Results: Of 783 patients, 16 with HF-BCC were identified. For comparison, 32 patients with 1–2 BCCs and 117 patients without BCC were selected. HF-BCC patients showed distinct characteristics, including a higher proportion of superficial BCCs (68.3% vs. 50%, p = 0.01) and fewer nodular subtypes (43.2% vs. 63.5%, p = 0.01). Their tumours were less frequently located on the nose and ears compared with patients having 1–2 BCCs. HF-BCC was associated with a personal history of squamous cell carcinoma (SCC) and actinic keratosis (AK). Conclusions: HF-BCC patients display distinct anatomical, histopathological and clinical characteristics, with a predominance of superficial BCC and an association with a personal history of SCC and AK. They show a lower frequency of tumours on the nose and ears, with a stronger tendency for localisation on the trunk and extremities. Identifying risk factors and genetic markers may contribute to improved early detection strategies, preventive measures, and the development of targeted therapies. Full article
(This article belongs to the Special Issue Skin Cancer: Prevention, Diagnosis and Treatment)
16 pages, 5224 KiB  
Article
Oral Microbial Dysbiosis Driven by Periodontitis Facilitates Oral Squamous Cell Carcinoma Progression
by Qing Yuan, Hao Wu, Hanyue Tan, Xinxing Wang, Yang Cao and Gang Chen
Cancers 2025, 17(13), 2181; https://doi.org/10.3390/cancers17132181 - 28 Jun 2025
Viewed by 641
Abstract
Background: Oral squamous cell carcinoma (OSCC), which accounts for over 90% of all oral malignancies, remains a major global health challenge due to its aggressive clinical course and poor prognosis. Periodontitis, a widespread chronic inflammatory condition affecting the supporting structures of the teeth, [...] Read more.
Background: Oral squamous cell carcinoma (OSCC), which accounts for over 90% of all oral malignancies, remains a major global health challenge due to its aggressive clinical course and poor prognosis. Periodontitis, a widespread chronic inflammatory condition affecting the supporting structures of the teeth, has increasingly been implicated as a potential risk factor for the development of various cancers. Emerging evidence suggests that microbial dysbiosis within the oral cavity may contribute to the creation of a pro-tumorigenic microenvironment, thereby promoting tumor initiation and progression. Nevertheless, the precise mechanisms linking periodontitis to OSCC, particularly through alterations in the oral microbiota, remain insufficiently understood. This article seeks to comprehensively analyze the association between periodontitis and OSCC and to elucidate the potential role of oral microbiota dysbiosis in mediating this relationship. Methods: In this study, a ligature-induced periodontitis model was established in C57BL/6J mice, and after two weeks, an OSCC model was introduced by the subcutaneous injection of SCC-7 cells to investigate the impact of periodontitis on OSCC progression. The effects of periodontitis on OSCC cell proliferation and invasion were assessed using scratch wound healing assays and CCK-8 proliferation assays. 16S rDNA high-throughput sequencing was conducted to profile the microbial communities present in the oral cavity and OSCC tissues, with particular emphasis on α-diversity indices (including Pielou’s evenness and Chao1 richness) and taxonomic composition at both the phylum and class levels. Furthermore, qPCR was utilized to assess the expression levels of cytokines in both periodontal and OSCC tissues, thereby elucidating the inflammatory milieu, potentially linking periodontitis to OSCC progression. Results: Our findings demonstrated that periodontitis significantly promoted OSCC growth and enhanced the invasive potential of OSCC cells. Microbial profiling revealed marked alterations in both the oral and OSCC microbiota, characterized by significant shifts in community composition and increased microbial diversity. Notably, these microbial changes exhibited consistent patterns between the oral cavity and the OSCC microenvironment, suggesting a potential mechanistic link between periodontitis-associated dysbiosis and OSCC progression. Consistently, qPCR analysis revealed elevated expression levels of IL-1β, IL-10, and IL-18 in both periodontal and OSCC tissues, providing evidence that the microbial alterations were accompanied by intensified inflammatory responses, which may contribute to OSCC progression. Conclusions: This study underscores the intricate interplay between periodontitis-induced microbial dysbiosis and the development of oral squamous cell carcinoma (OSCC). The findings suggest that periodontal inflammation, together with associated shifts in the oral microbiota, acts synergistically to drive OSCC progression. The elevated expression of cytokines further supports the role of a pro-inflammatory tumor microenvironment in mediating this interaction. These results offer important insights into the microbial and inflammatory mechanisms underlying the connection between periodontitis and OSCC, highlighting the critical role of maintaining periodontal health in the prevention and management of OSCC. Full article
(This article belongs to the Section Cancer Epidemiology and Prevention)
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14 pages, 1362 KiB  
Article
Serum Complement Factor H: A Marker for Progression and Outcome Prediction Towards Immunotherapy in Cutaneous Squamous Cell Carcinoma
by Glenn Geidel, Laura Adam, Sabrina Bänsch, Nathan Fekade, Benjamin Deitert, Alessandra Rünger, Julian Kött, Tim Zell, Isabel Heidrich, Daniel J. Smit, Klaus Pantel, Stefan W. Schneider and Christoffer Gebhardt
Cancers 2025, 17(13), 2162; https://doi.org/10.3390/cancers17132162 - 26 Jun 2025
Viewed by 450
Abstract
Background/Objectives: Tumor-immune system interactions shape the progression of cutaneous squamous cell carcinoma (cSCC). Serum biomarkers for risk stratification remain limited. Complement factor H (CFH) regulates the alternative complement pathway. It has been linked to immunosuppression and cSCC development in tissue-based studies. We investigated [...] Read more.
Background/Objectives: Tumor-immune system interactions shape the progression of cutaneous squamous cell carcinoma (cSCC). Serum biomarkers for risk stratification remain limited. Complement factor H (CFH) regulates the alternative complement pathway. It has been linked to immunosuppression and cSCC development in tissue-based studies. We investigated whether serum CFH is associated with tumor aggressiveness and may help predict immunotherapy outcomes in advanced cSCC. Methods: In this retrospective, single-center study, pre-treatment serum CFH levels were measured in 104 cSCC patients (62 high-risk and 42 advanced) using ELISA. Associations with clinical characteristics, disease stage, and response to cemiplimab were analyzed. Subgroup comparisons considered immune status and inflammatory comorbidities. Results: Advanced cSCC patients had significantly higher CFH levels than high-risk patients (OR 0.13, p = 0.026), independent of tumor diameter or invasion depth. Among advanced cSCC cases, lower baseline CFH was associated with more prolonged progression-free survival (median 19.8 vs. 3.07 months, p = 0.029; HR 0.29, p = 0.014), independent of covariates including immunosuppression. CFH levels during therapy did not predict treatment response. ROC analysis showed moderate discriminatory ability with CFH alone (AUC 0.625), which improved when combined with clinical variables in a multivariable risk model (AUC 0.767). Conclusions: Serum CFH is an independent predictor of cemiplimab response and reflects biological aggressiveness in cSCC beyond conventional high-risk features. These findings support the use of CFH in clinical risk models and warrant external validation in multicenter cohorts. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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24 pages, 3008 KiB  
Article
Quantitative Evaluation of Value for Money in Sponge City Construction Public–Private Partnership Projects Through a System Dynamics Model
by Heng Zhang, Jiang Chang and Tianci Lin
Systems 2025, 13(6), 471; https://doi.org/10.3390/systems13060471 - 14 Jun 2025
Viewed by 488
Abstract
The public–private partnerships (PPP) mode is very popular in public infrastructure projects. The PPP model for sponge city construction (SCC) provides an effective way to curb and manage the increasingly serious ecological water problems in China. The quantitative evaluation of value for money [...] Read more.
The public–private partnerships (PPP) mode is very popular in public infrastructure projects. The PPP model for sponge city construction (SCC) provides an effective way to curb and manage the increasingly serious ecological water problems in China. The quantitative evaluation of value for money (VFM) is an evaluation method that obtains quantitative values through a certain calculation process. However, the current studies lack a dynamic quantitative evaluation of VFM for the entire life cycle of SCC PPP projects, and cannot observe the impact of key factors on the VFM value. By constructing a system dynamics (SD) model for the VFM quantitative evaluation of SCC PPP projects from the perspective of the whole life cycle, this study can intuitively and transparently observe the impact of key factors (such as discount rate and profit margin) on the evaluation results and feasibility of adopting a PPP model in the project, offering policymakers a tool to mitigate the risks of “Pseudo-PPP” projects. After collecting cases in Anhui province from the China PPP Center, this study constructed a life cycle VFM quantitative evaluation system dynamics model suitable for SCC PPP projects that consist of the public sector comparison (PSC) value and PPP value. The results indicate that the system dynamics model can be effectively applied to the dynamic quantitative evaluation of SCC PPP projects and clarify the influence degree on and sensitivity of various factors to the VFM value. Specifically, when the discount rate increases, the decrease in the PPP value is greater than that in the PSC value, leading to an increase in the VFM value. Moreover, a reasonable profit margin is more sensitive to the VFM value and decreases as the reasonable profit margin increases. In addition, choosing different availability service fee calculation methods will result in varying the adjustment range to a reasonable profit margin that drives the adoption of VFM quantitative evaluation. These research findings have provided a viable dynamic research methodology for the quantitative VFM evaluation of SCC PPP projects. This methodology enables the dynamic visualization and easy determination of the acceptable ranges for relevant factors, offers rational policy recommendations for the quantitative evaluation of key factor values, and thereby effectively prevents PPP project violations, promoting fair and reasonable cooperation between governments and private enterprises. Full article
(This article belongs to the Section Systems Engineering)
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29 pages, 411 KiB  
Review
Selective Dry Cow Therapy in Modern Dairy Management: Balancing Udder Health and Antimicrobial Stewardship
by Ionela Delia Ut, Daniel Ionut Berean, Liviu Marian Bogdan, Simona Ciupe and Sidonia Gog Bogdan
Vet. Sci. 2025, 12(6), 580; https://doi.org/10.3390/vetsci12060580 - 12 Jun 2025
Viewed by 894
Abstract
In recent decades, Blanket Dry Cow Therapy (BDCT) has been regarded as a cornerstone strategy for the control of mastitis in dairy cows during the dry period. However, concerns regarding the rising incidence of antibiotic resistance and the associated zoonotic risks have prompted [...] Read more.
In recent decades, Blanket Dry Cow Therapy (BDCT) has been regarded as a cornerstone strategy for the control of mastitis in dairy cows during the dry period. However, concerns regarding the rising incidence of antibiotic resistance and the associated zoonotic risks have prompted a paradigm shift, leading to intensified research into alternative management approaches. In response, many countries have adopted a more targeted approach, known as Selective Dry Cow Therapy (SDCT), which focuses on the therapeutic use of antibiotics, administered only to cows or quarters that are either infected or at high risk of infection during the dry period. This review provides a comprehensive synthesis of the scientific literature regarding the main methods for selecting animals for SDCT, the impact of this strategy on udder health, milk production, farm economics, and antibiotic consumption, as well as the factors that may influence its effectiveness. Over time, a range of methods have been developed to identify infected animals, including bacteriological culture, somatic cell count (SCC), differential somatic cell count (DSCC), and the California Mastitis Test (CMT), which are often used alone or in combination with clinical mastitis history and/or parity. Among these methods, SCC has proven to be the most economically viable and best suited for practical use, while its combination with DSCC has been shown to significantly enhance diagnostic accuracy. According to the studies reviewed, SDCT is a safe and effective strategy for maintaining udder health and farm profitability, as long as infected cows are accurately identified, and internal teat sealants are used in quarters not treated with antibiotics during the dry period. However, since udder health is influenced by herd characteristics, management practices, and regional pathogens, the findings cannot be universally applied and must be adapted to each herd’s specific conditions. Full article
(This article belongs to the Section Veterinary Reproduction and Obstetrics)
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14 pages, 2280 KiB  
Article
Effects of Sodium Alginate Infusion on Intramammary Immunity Against Subclinical Mastitis in Dairy Cows
by Yu-I Pan, Yu-Chia Lin, Jai-Wei Lee, Perng-Chih Shen, Rolissa Ballantyne, Hsu-Hsun Lee and Kuo-Hua Lee
Int. J. Mol. Sci. 2025, 26(12), 5515; https://doi.org/10.3390/ijms26125515 - 9 Jun 2025
Viewed by 472
Abstract
Mastitis is a major issue in dairy cows, with subclinical mastitis (SCM) being hard to detect and potentially progressing to clinical mastitis. Antibiotic use raises concerns about resistance and milk contamination, highlighting the need for natural alternatives. Sodium alginate (SA), known for its [...] Read more.
Mastitis is a major issue in dairy cows, with subclinical mastitis (SCM) being hard to detect and potentially progressing to clinical mastitis. Antibiotic use raises concerns about resistance and milk contamination, highlighting the need for natural alternatives. Sodium alginate (SA), known for its antioxidant and immunomodulatory properties, may offer a solution, though its effects on mastitis are unclear. Intramammary infusion of 1% SA (30 mL) was tested in both healthy cows (n = 8; somatic cell count, SCC ≤ 100,000 cells/mL) and those with SCM (n = 12; SCC ≥ 200,000 cells/mL). The results showed that SA significantly increased SCC in both healthy and SCM cows, with peak levels at 48 h, returning to baseline levels thereafter. In cows with SCM, SA treatment led to a 58.3% cytological and 54.5% bacteriological cure rate after 14 days. Additionally, significant downregulation was observed in tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-4, IL-6, and interferon (IFN)-γ. Conversely, the levels of IL-8, IL-10, and IL-12 initially increased, then declined gradually. Importantly, there were no significant effects on milk composition. These findings suggest that SA may offer an alternative to antibiotics, aiding in immune response and bacterial clearance without the risk of antibiotic residues, thus preventing SCM progression to clinical mastitis. Full article
(This article belongs to the Special Issue Microbial Infections and Novel Biological Molecules for Treatment)
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27 pages, 1016 KiB  
Review
Current and Emerging Insights into the Causes, Immunopathogenesis, and Treatment of Cutaneous Squamous Cell Carcinoma
by Ronald Anderson, Nomzamo M. Mkhize, Mahlatse M. C. Kgokolo, Helen C. Steel, Theresa M. Rossouw, Lindsay Anderson and Bernardo L. Rapoport
Cancers 2025, 17(10), 1702; https://doi.org/10.3390/cancers17101702 - 19 May 2025
Cited by 1 | Viewed by 920
Abstract
The increasing incidence of cutaneous squamous cell carcinoma (cSCC), together with the ominous risks of metastasis and recurrence, underscores the importance of identifying novel therapies and validated biomarkers to augment patient management, particularly in the context of well-established and advanced disease. Following a [...] Read more.
The increasing incidence of cutaneous squamous cell carcinoma (cSCC), together with the ominous risks of metastasis and recurrence, underscores the importance of identifying novel therapies and validated biomarkers to augment patient management, particularly in the context of well-established and advanced disease. Following a brief overview of the well-recognized epidemiology, clinical features, and diagnosis of cSCC, the current review is focused on risk factors, most prominently excessive exposure to ultraviolet radiation (UVR) as a cause of persistent, pro-tumorigenic mutagenesis, and immune suppression. The next phase of the review encompasses an evaluation of the search for key driver mutations in the pathogenesis of cSCC, including the role of these and other mutations in the formation of immunologically reactive neoepitopes. With respect to additional mechanisms of tumorigenesis, immune evasion is prioritized, specifically the involvement of cell-free and infiltrating cellular mediators of immune suppression. Prominent amongst the former are the cytokine, transforming growth factor-β1 (TGF-β1), the prostanoid, prostaglandin E2, and the emerging immune suppressive nucleoside adenosine. In the case of the latter, tumor-infiltrating and circulating regulatory T cells have been implicated as being key players. The final sections of the review are focused on an update of the immunotherapy of established and advanced disease, as well as on the search for novel, reliable lesional and systemic biomarkers with the potential to guide patient management. Full article
(This article belongs to the Special Issue New Concepts and Recent Advances in the Management of Skin Cancer)
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32 pages, 1133 KiB  
Review
Laryngeal Cancer in the Modern Era: Evolving Trends in Diagnosis, Treatment, and Survival Outcomes
by Alexandru-Romulus Hut, Eugen Radu Boia, Diana Para, Gheorghe Iovanescu, Delia Horhat, Loredan Mikša, Maria Chiriac, Raphaël Galant, Alexandru Catalin Motofelea and Nicolae Constantin Balica
J. Clin. Med. 2025, 14(10), 3367; https://doi.org/10.3390/jcm14103367 - 12 May 2025
Viewed by 3670
Abstract
Background/Objectives: Laryngeal cancer (LC), predominantly squamous cell carcinoma (SCC), represents a considerable health burden worldwide. Tumour subsite heterogeneity (supraglottic, glottic, subglottic) influences clinical behavior and outcomes. This review synthesizes current knowledge on epidemiology, risk factors, diagnostics, histological variants, biomarkers, treatment modalities, and [...] Read more.
Background/Objectives: Laryngeal cancer (LC), predominantly squamous cell carcinoma (SCC), represents a considerable health burden worldwide. Tumour subsite heterogeneity (supraglottic, glottic, subglottic) influences clinical behavior and outcomes. This review synthesizes current knowledge on epidemiology, risk factors, diagnostics, histological variants, biomarkers, treatment modalities, and survival. Results: This narrative review synthesizes current literature on the epidemiology, risk factors, diagnosis, histological variants, biomarkers, and prognosis of LC. The review highlights the critical influence of tumour sites (supraglottic, glottic, subglottic) on metastatic patterns and survival. Key risk factors of LC include tobacco and alcohol use, human papillomavirus (HPV) infection, and occupational exposures. The diagnostic process encompasses clinical examination, endoscopy, biopsy, and imaging. Several biomarkers that aid in diagnosis, treatment plan determination, and prognosis prediction have been established. These biomarkers include long noncoding RNAs, cell cycle regulators, apoptosis regulators, oncogenes, tumour suppressor genes, growth factor pathway components, angiogenic factors, structural proteins, sex hormone receptors, and immunological markers. Current treatment modalities range from organ-preserving surgery and radiotherapy to combined chemoradiotherapy and total laryngectomy. Finally, survival data are presented and stratified by stage and subsite. Conclusions: The review underscores the need for a multidisciplinary approach to LC management, integrating clinical, pathological, and molecular information to optimize patient outcomes. Full article
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10 pages, 550 KiB  
Article
Predictors of Inguinal Lymph Node Metastasis in Penile Squamous Cell Carcinoma: Insights from a Single-Center Retrospective Study
by Francesco Passaro, Luigi Napolitano, Antonio Tufano, Roberto La Rocca, Claudio Marino, Biagio Barone, Luigi De Luca, Ugo Amicuzi, Michelangelo Olivetta, Francesco Mastrangelo, Pasquale Reccia, Felice Crocetto, Lorenzo Romano, Francesco Paolo Calace, Lorenzo Spirito, Celeste Manfredi, Davide Arcaniolo, Antonio De Palma, Carmine Turco, Carmine Sciorio, Vincenzo Maria Altieri, Gennaro Mattiello, Ernesto di Mauro, Giuseppe Celentano and Sisto Perdonàadd Show full author list remove Hide full author list
J. Clin. Med. 2025, 14(9), 2921; https://doi.org/10.3390/jcm14092921 - 23 Apr 2025
Viewed by 622
Abstract
Background: Squamous cell carcinoma (SCC) of the penis accounts for approximately 95% of penile cancers and is associated with substantial morbidity and mortality. SCC typically develops in uncircumcised men, most commonly affecting the foreskin or glans. While slow-growing, early detection is crucial to [...] Read more.
Background: Squamous cell carcinoma (SCC) of the penis accounts for approximately 95% of penile cancers and is associated with substantial morbidity and mortality. SCC typically develops in uncircumcised men, most commonly affecting the foreskin or glans. While slow-growing, early detection is crucial to improve survival outcomes. Risk factors include advanced age, lack of circumcision, poor hygiene, HPV infection (types 16 and 18), chronic inflammation, and smoking. Methods: We conducted a retrospective, single-center study at IRCCS Hospital “G. Pascale” of Naples, Italy, involving 59 patients treated between January 2015 and January 2023. The inclusion criteria were surgically treated primary tumors, confirmed SCC pathology, and pathologically verified inguinal lymph node metastasis (ILNM). We analyzed clinical variables including lymph node involvement, lymphovascular invasion (LVI), spongiosum corpus involvement (SCI), HPV infection, and tumor differentiation. Univariate and multivariate logistic regression analyses were performed to determine independent predictors of ILNM. Results: The mean age of patients was 66.67 ± 13.97 years. ILNM was confirmed in 24 patients (40.6%), while 35 (59.3%) had no lymph node involvement. Univariate analysis identified lymph node involvement at diagnosis (p = 0.005), LVI (p = 0.003), and SCI (p = 0.003) as significant predictors of ILNM. These factors were confirmed in the multivariate analysis, with lymph node involvement (p = 0.004), LVI (p = 0.025), and SCI (p = 0.028) as independent predictors. Conclusions: Lymph node status, LVI, and SCI are significant predictors of ILNM in penile SCC. Identifying these factors can aid in risk stratification, optimizing surgical decisions, and potentially reducing unnecessary morbidity. Further large-scale studies are recommended to validate these findings and refine prognostic models. Full article
(This article belongs to the Special Issue Genitourinary Cancers: Clinical Advances and Practice Updates)
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28 pages, 1908 KiB  
Review
The Current Roadmap of Lung Cancer Biology, Genomics and Racial Disparity
by Enas S. Alsatari, Kelly R. Smith, Sapthala P. Loku Galappaththi, Elba A. Turbat-Herrera and Santanu Dasgupta
Int. J. Mol. Sci. 2025, 26(8), 3818; https://doi.org/10.3390/ijms26083818 - 17 Apr 2025
Viewed by 1708
Abstract
Globally, lung cancer is the most prevalent cause of cancer-related death. There are two large histological groups of lung cancer: small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Based on histopathological and molecular features, adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are [...] Read more.
Globally, lung cancer is the most prevalent cause of cancer-related death. There are two large histological groups of lung cancer: small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). Based on histopathological and molecular features, adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are the two major histologic subtypes of NSCLC. Various epidemiological and environmental factors are linked with an increased risk of lung cancer. However, these risk factors show disparities in patients with divergent racial and ethnic backgrounds. Interestingly, different populations were found to harbor distinct molecular features as evidenced by variations in genetic mutation profiles. Moreover, diverse histological and molecular progression patterns are identified in lung cancer, which could be crucial in improving diagnosis, prognosis, and therapeutic planning. In concert with a plethora of nuclear genetic alterations, mitochondrial alteration, epigenetic reprogramming, microbial dysbiosis, and immune alteration signatures have been identified in various lung cancer types. This review article provides a comprehensive overview of screening tests and the treatment strategies for NSCLC and SCLC, including surgery, radiation therapy, chemotherapy, targeted therapies, and immunotherapies. Through the unification of these diverse aspects, this review article aspires to a complete understanding of lung cancer’s genomics, biology, microbial landscapes, and racial disparity and seeks to understand the essential role of racial and ethnic factors in lung cancer occurrence and treatment. Full article
(This article belongs to the Special Issue Advanced Molecular Research in Lung Diseases)
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13 pages, 608 KiB  
Review
The Role of HPV in the Development of Cutaneous Squamous Cell Carcinoma—Friend or Foe?
by Vasileios Dervenis
Cancers 2025, 17(7), 1195; https://doi.org/10.3390/cancers17071195 - 31 Mar 2025
Viewed by 1292
Abstract
The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing, with UV radiation being the main cause. Other risk factors are age, sex, skin type and immunosuppression. Human papillomaviruses (HPVs) are associated with benign and malignant skin tumours. In contrast to anogenital and [...] Read more.
The incidence of cutaneous squamous cell carcinoma (cSCC) is increasing, with UV radiation being the main cause. Other risk factors are age, sex, skin type and immunosuppression. Human papillomaviruses (HPVs) are associated with benign and malignant skin tumours. In contrast to anogenital and oropharyngeal carcinomas, which are caused by alpha papillomaviruses, the HPV types associated with cSCC belong to the beta-HPV genus. These viruses infect the skin epithelium and are widespread in skin samples from healthy people. It is assumed that HPV amplifies the DNA damage caused by UV radiation and disrupts the repair mechanisms of the cells, without remaining permanently detectable in the tumour tissue, the so-called hit-and-run theory. The HPV status of tumours appears to have a positive influence on prognosis and response to therapy due to increased immune infiltration, in particular by tissue-resident memory T cells and activation of immune effector cells. This favours responses to immunotherapies such as PD-1/PD-L1 inhibitors, whereas immunosuppression may promote a pro-carcinogenic effect. In conclusion, the role of beta HPV in the development of cSCC appears to be closely associated with the immune status of the host. Depending on the immune status, beta HPV can play either a protective or a tumour-promoting role, and in view of the increasing incidence of skin cancer worldwide, enhancing the immune response against virus-infected keratinocytes, e.g., through HPV vaccination, could represent a promising approach for the prevention and therapy of squamous cell carcinomas. Full article
(This article belongs to the Special Issue Views and Perspectives of Cutaneous Squamous Cell Carcinoma)
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15 pages, 1312 KiB  
Article
Studying the Impact of the DDB2 T338M Missense Mutation on the Development of Equine Squamous Cell Carcinoma and Sarcoid
by Hannah Quatember, Barbara Nell, Barbara Richter, Doris Rigler, Marlies Dolezal, Sabine Sykora and Barbara Wallner
Animals 2025, 15(7), 911; https://doi.org/10.3390/ani15070911 - 22 Mar 2025
Viewed by 671
Abstract
A missense mutation in damage-specific DNA binding protein 2 (DDB2 c.1013 C>T; p.Thr338Met) has been described as a risk factor for ocular squamous cell carcinoma (OSCC) in the Haflinger breed. Here, we examined the impact of DDB2 C>T allele status on the development [...] Read more.
A missense mutation in damage-specific DNA binding protein 2 (DDB2 c.1013 C>T; p.Thr338Met) has been described as a risk factor for ocular squamous cell carcinoma (OSCC) in the Haflinger breed. Here, we examined the impact of DDB2 C>T allele status on the development of OSCC, squamous cell carcinoma (SCC) at other localisations, or equine sarcoid (ES) in Haflingers and other breeds with a high incidence of these tumour types. We genotyped affected Haflinger, Noriker, Warmblood, and Icelandic horses. Results based on 56 Haflingers confirmed the significantly higher risk for OSCC in DDB2-TT Haflingers but also suggested an increased risk in heterozygous (DDB2-CT) Haflingers. We also found the DDB2-T allele in Norikers with OSCC but not in Warmbloods. Only one homozygous DDB2-T allele carrier was among the 23 Haflinger and 44 Noriker/Warmblood/Icelandic horses with an SCC at a localisation other than the eye or ES. Overall, our data underline the severity of the DDB2-T allele with regard to OSCC and provide no evidence for the impact of the DDB2 risk allele status on the development of ES and SCC at localisations other than the eye. Full article
(This article belongs to the Special Issue Advances in Equine Genetics and Breeding)
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15 pages, 1103 KiB  
Article
Immunosuppression and Outcomes in Patients with Cutaneous Squamous Cell Carcinoma of the Head and Neck
by Doriana Iancu, Ana Fulga, Doina Vesa, Iuliu Fulga, Dana Tutunaru, Andrei Zenovia, Alin Ionut Piraianu, Elena Stamate, Corina Sterian, Florentin Dimofte, Mihail Alexandru Badea and Alin Laurentiu Tatu
Clin. Pract. 2025, 15(1), 21; https://doi.org/10.3390/clinpract15010021 - 17 Jan 2025
Viewed by 1461
Abstract
Cutaneous squamous scell carcinoma (cSCC) is a frequent non-melanoma skin cancer that originates from keratinocytes with increased prevalence. cSCC can be either in situ, as in Bowen’s disease, or extended. Advanced age, accumulated sun exposure, light pigmentation, and prior skin cancer diagnosis are [...] Read more.
Cutaneous squamous scell carcinoma (cSCC) is a frequent non-melanoma skin cancer that originates from keratinocytes with increased prevalence. cSCC can be either in situ, as in Bowen’s disease, or extended. Advanced age, accumulated sun exposure, light pigmentation, and prior skin cancer diagnosis are all significant risk factors for cSCC. Although most cSCCs can be treated surgically, some recur and metastasize, resulting in death. The role of immune status is not yet determined in the prognosis of these patients. Objective. Immunosuppressed patients are more likely to develop cSCC, which is often characterized by more aggressive, multifocal lesions. This study aimed to determine the risks of mortality in patients with cSCC and immunosuppression versus non immunosuppression and to compare variations in overall survival based on different clinical features. Method. We evaluated clinical cases of patients at “Sfantul Apostol Andrei” Emergency Hospital of Galati, Romania, from 1 March 2018 to 1 April 2024. Subjects in the trial had to be at least 18 years old and have a pathologically confirmed diagnosis of cutaneous head and neck squamous cell carcinoma (cHNSCC). We divided the patients into two different categories based on whether they had immunosuppression. Results. In this cohort of 68 subjects with cSCC, patients with immunosuppression had significantly lower overall survival, as well as lower three- and five-year survival rates compared with those without immunosuppression, even after adjustment for age, sex, stage, and previous surgical treatment. The median survival time for immunosuppressed individuals ranged from 11 to 21 months, varying based on their particular characteristics, and most critically, on the presence of other malignancies, while that of immunocompetent patients ranged from 18 to 51 months. In addition, immune-deficient patients with early-stage disease had a 21-month median survival rate that changed to11 months for advanced-stage cases. In a similar manner, immunocompetent patients with early-stage cancer had a significantly better median survival than those withadvancedstages,43 versus 18months. Our results indicate that immunosuppression is a distinct risk factors associated with a less favorable outcome in patients with cHNSCC. Full article
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32 pages, 23527 KiB  
Review
Current Status and Future Directions of Artificial Intelligence in Post-Traumatic Stress Disorder: A Literature Measurement Analysis
by Ruoyu Wan, Ruohong Wan, Qing Xie, Anshu Hu, Wei Xie, Junjie Chen and Yuhan Liu
Behav. Sci. 2025, 15(1), 27; https://doi.org/10.3390/bs15010027 - 30 Dec 2024
Cited by 4 | Viewed by 6011
Abstract
This study aims to explore the current state of research and the applicability of artificial intelligence (AI) at various stages of post-traumatic stress disorder (PTSD), including prevention, diagnosis, treatment, patient self-management, and drug development. We conducted a bibliometric analysis using software tools such [...] Read more.
This study aims to explore the current state of research and the applicability of artificial intelligence (AI) at various stages of post-traumatic stress disorder (PTSD), including prevention, diagnosis, treatment, patient self-management, and drug development. We conducted a bibliometric analysis using software tools such as Bibliometrix (version 4.1), VOSviewer (version 1.6.19), and CiteSpace (version 6.3.R1) on the relevant literature from the Web of Science Core Collection (WoSCC). The analysis reveals a significant increase in publications since 2017. Kerry J. Ressler has emerged as the most influential author in the field to date. The United States leads in the number of publications, producing seven times more papers than Canada, the second-ranked country, and demonstrating substantial influence. Harvard University and the Veterans Health Administration are also key institutions in this field. The Journal of Affective Disorders has the highest number of publications and impact in this area. In recent years, keywords related to functional connectivity, risk factors, and algorithm development have gained prominence. The field holds immense research potential, with AI poised to revolutionize PTSD management through early symptom detection, personalized treatment plans, and continuous patient monitoring. However, there are numerous challenges, and fully realizing AI’s potential will require overcoming hurdles in algorithm design, data integration, and societal ethics. To promote more extensive and in-depth future research, it is crucial to prioritize the development of standardized protocols for AI implementation, foster interdisciplinary collaboration—especially between AI and neuroscience—and address public concerns about AI’s role in healthcare to enhance its acceptance and effectiveness. Full article
(This article belongs to the Special Issue Promoting Health Behaviors in the New Media Era)
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