Search Results (3,903)

Background: The prognostic role of imaging with [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) in oropharynx cancer (OPC) has been demonstrated in the past. The aim of this study was to assess the prognostic impact of both baseline and post-treatment PET/CT in patients with OPC and treated with chemo- and/or radiotherapy. Methods: The PET/CT parameters of scans performed before and after therapy were collected and analyzed to find significant prognosticators for progression-free survival (PFS) and overall survival (OS). Human papillomavirus (HPV) infection’s influence on the prognosis was also taken into account. Results: A total of 66 patients were included in the study. The staging volumetric parameters of PET/CT were significant prognosticators for OS, while the same parameters were affordable predictors for PFS at the restaging evaluation. No significant correlations between HPV infection and PET/CT parameters were reported. Conclusion: The prognostic role of volumetric [18F]FDG PET/CT parameters in patients with OPC was reported. Full article

Objectives: Oral diseases are among the most prevalent diseases globally. Accumulating new evidence suggests considerable benefits of epigallocatechin-3-gallate (EGCG) for oral health. This review aims to explore the role and application of EGCG in main oral diseases. Methods: This narrative review thoroughly examines and summarizes the most recent literature available in scientific databases (PubMed, Web of Science, Scopus, and Google Scholar) reporting advances in the role and application of EGCG within the dental field. The major keywords used included “EGCG”, “green tea extract”, “oral health”, “caries”, “pulpitis”, “periapical disease”, “periodontal disease”, “oral mucosa”, “salivary gland”, and “oral cancer”. Conclusions: EGCG prevents and manages various oral diseases through its antibacterial, anti-inflammatory, antioxidant, and antitumor properties. Compared to traditional treatments, EGCG generally exhibits lower tissue irritation and positive synergistic effects when combined with other therapies. Novel delivery systems or chemical modifications can significantly enhance EGCG’s bioavailability, prolong its action, and reduce toxicity, which are current hotspots in developing new materials. Clinical significance: this review provides an exhaustive overview of the biological activities of EGCG to major oral diseases, alongside an exploration of applications and limitations, which serves as a reference for preventing and managing oral ailments. Full article

It is well established that microRNA-21 (miR-21) targets phosphatase and tensin homolog (PTEN), facilitating epithelial-to-mesenchymal transition (EMT) and drug resistance in cancer. Recent evidence indicates that PTEN activates its pseudogene-derived long non-coding RNA, PTENP1, which in turn inhibits miR-21. However, the dynamics of PTEN, miR-21, and PTENP1 in the DNA damage response (DDR) remain unclear. Thus, we propose a dynamic Boolean network model by integrating the published literature from various cancers. Our model shows good agreement with the experimental findings from breast cancer, hepatocellular carcinoma (HCC), and oral squamous cell carcinoma (OSCC), elucidating how DDR activation transitions from the intra-S phase to the G2 checkpoint, leading to a cascade of cellular responses such as cell cycle arrest, senescence, autophagy, apoptosis, drug resistance, and EMT. Model validation underscores the roles of PTENP1, miR-21, and PTEN in modulating EMT and drug resistance. Furthermore, our analysis reveals nine novel feedback loops, eight positive and one negative, mediated by PTEN and implicated in DDR cell fate determination, including pathways related to drug resistance and EMT. Our work presents a comprehensive framework for investigating cellular responses following DDR, underscoring the therapeutic potential of targeting PTEN, miR-21, and PTENP1 in cancer treatment. Full article

Head and neck cancer (HNC) entails a heterogenous neoplastic disease that arises from the mucosal epithelium of the upper respiratory system and the gastrointestinal tract. It is characterized by high morbidity and mortality, being the eighth most common cancer worldwide. It is believed that the mesenchymal/stem stromal cells (MSCs) present in the tumour milieu play a key role in the modulation of tumour initiation, development and patient outcomes; they also influence the resistance to cisplatin-based chemotherapy, the gold standard for advanced HNC. MSCs are multipotent, heterogeneous and mobile cells. Although no MSC-specific markers exist, they can be recognized based on several others, such as CD73, CD90 and CD105, while lacking the presence of CD45, CD34, CD14 or CD11b, CD79α, or CD19 and HLA-DR antigens; they share phenotypic similarity with stromal cells and their capacity to differentiate into other cell types. In the tumour niche, MSC populations are characterized by cell quiescence, self-renewal capacity, low reactive oxygen species production and the acquisition of epithelial-to-mesenchymal transition properties. They may play a key role in the process of acquiring drug resistance and thus in treatment failure. The present narrative review examines the links between MSCs and HNC, as well as the different mechanisms involved in the development of resistance to current chemo-radiotherapies in HNC. It also examines the possibilities of pharmacological targeting of stemness-related chemoresistance in HNSCC. It describes promising new strategies to optimize chemoradiotherapy, with the potential to personalize patient treatment approaches, and highlights future therapeutic perspectives in HNC. Full article

Background and Objectives: The objective of this study was to present a rare case of non-keratinizing squamous cell carcinoma (SCC) of the lacrimal sac (LS). Neoplasms of the lacrimal drainage system are extremely rare. These lesions are predominantly malignant and are associated with a high mortality rate. Case Presentation: A 51-year-old woman was referred to an ophthalmologist with a history of unilateral epiphora, presbyopia, and abnormal eye discharge. Antibiotic therapy was applied and modified later due to persisting symptoms. After five months, edema of the medial left eye angle occurred. A lacrimal sac incision was performed, and a subsequent magnetic resonance imaging (MRI) scan revealed a 2 cm, contrast-enhanced solid tumor. The patient was qualified for dacryocystectomy, which was conducted by the otolaryngology department. Postoperative histopathologic findings indicated the presence of non-keratinizing SCC. During a reoperation, margins were extended, and the surgery was found to be radical. Following the reoperation, no alarming symptoms were observed. However, a follow-up MRI and positron emission tomography (PET) scan six weeks later revealed metastases. Further treatment is being planned. Conclusions: LS tumors are life-threatening conditions that are challenging to diagnose at an early stage. Surgical excision is the preferred treatment option. Imaging studies play an important role in post-operative follow-up because of the possibility of recurrence and metastasis, even after radical surgery. Full article

Recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a challenging disease, requiring personalized management by a multidisciplinary team. The aim of this retrospective multicentric study was to characterize real-world healthcare resource use and patient care for R/M HNSCC in Portugal during the first year after diagnosis. A total of 377 patients ineligible for curative treatment were included, mostly male (92.8%), aged 50–69 years (74.5%), with heavy alcohol (72.7%) or smoking habits (89.3%). Oropharynx (33.2%) and oral cavity (28.7%) were primary tumor locations, with lung metastases being the most common (61.4%). Eligible patients for systemic treatment with palliative intent (80.6%) received up to four treatment lines, with varied regimens. Platinum-based combination chemotherapy dominated first-line treatment (>70%), while single-agent chemotherapy and anti-PD1 immunotherapy were prevalent in later lines. Treatment approaches were uniform across disease stages and primary tumor locations but varied geographically. Treated patients received more multidisciplinary support than those who were ineligible. This study provides the first Portuguese real-world description of R/M HNSCC patient characteristics, treatment patterns, and supportive care during the year after diagnosis, highlighting population heterogeneity and aiming to improve patient management. Full article

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) constituting 85% of cases. Among NSCLCs, squamous cell carcinoma (SqCC) is strongly associated with smoking. However, lung cancer in never smokers (LCINS) represents approximately 25% of lung cancer cases globally and shows increasing incidence, particularly in East Asia. LCINS-SqCC is less well-characterized, especially regarding its genomic alterations and their impact on clinical outcomes. We conducted a retrospective analysis over a 20-year period (July 2003–July 2023) at two major tertiary centers in the UK. The cohort included 59 patients with LCINS-SqCC who underwent radical surgical resection. Data collected included demographic information, comorbidities, histopathological details, and outcome metrics such as disease-free and overall survival. Molecular sequencing of tumor specimens was performed to identify genomic aberrations. The cohort had a median age of 71 years (IQR 62–77) and a median BMI of 25.4 (IQR 22.8–27.8), with a slight male predominance (53%). The majority of patients (93%) had a preoperative MRC of 1–2. Recurrent disease was observed in 23 patients (39%), and 32 patients (54%) had died at a median follow-up of 3 years. Median disease-free survival was 545 days (IQR 132–1496), and overall survival was 888 days (IQR 443–2071). Preoperative creatinine levels were higher in patients who experienced recurrence (p = 0.037). Molecular analysis identified biallelic SMARCB1 loss in two younger patients, associated with rapid disease progression despite R0 resection. These patients’ tumors were PDL1-negative, TTF-1-negative, and positive for cytokeratin, CD56, and p40. SMARCB1-deficient SqCC in never smokers represents a highly aggressive variant with poor disease-free survival, highlighting the importance of integrating advanced molecular diagnostics in clinical practice. This study underscores the necessity for personalized treatment strategies, including targeted therapies such as EZH2 inhibitors and immune checkpoint blockade, to address the unique molecular pathways in SMARCB1-deficient cancers. Further clinical trials are essential to optimize therapeutic approaches for this challenging subgroup of lung cancer. Full article

Ambiguity exists over treatment and surveillance strategies after endoscopic submucosal dissection (ESD) for esophageal squamous cell neoplasia (ESCN) with unfavorable histologic features. This study investigated the long-term outcomes of ESD in high-risk ESCN patients. We retrospectively included early ESCN patients treated with ESD at two medical centers in Taiwan between August 2010 and December 2023. Demographic, endoscopic and pathological data were collected. Among 146 patients (mean age 59.17 years) with 183 lesions, 73 (50%) had a history of head and neck cancer (HNC). En bloc and R0 resections were achieved in 100% and 95.6% of the lesions, respectively. The 5-year overall survival (OS), disease-specific survival (DSS) and local recurrence rates were 42.7%, 94.7% and 11%. R0 resections were significantly associated with recurrence in a univariate analysis (HR: 0.19, 95% CI: 0.06–0.66, p = 0.008). Alcohol abstinence was independently associated with lower recurrence (HR: 0.34, 95% CI: 0.16–0.73, p = 0.006). Patients with pT1a-MM (muscularis mucosa invasion) had comparable OS (p = 0.82), DSS (p = 0.617) and recurrence (p = 0.63) rates to those with pT1a-EP/LPM (epithelium/lamina propria invasion). The long-term outcomes of ESCN patients after ESD for expanded indications were satisfactory. ESD could be considered in selected ESCN patients involving the muscularis mucosa, notably among high-risk HNC patients. Full article

(1) Background: head and neck squamous cell carcinoma (HNSCC) is a common cancer whose prognosis is affected by its heterogeneous nature. We aim to predict 5-year overall survival in HNSCC radiotherapy (RT) patients by integrating radiomic and clinical information in machine-learning models; (2) Methods: HNSCC radiotherapy planning computed tomography (CT) images with RT structures were obtained from The Cancer Imaging Archive. Radiomic features and clinical data were independently analyzed by five machine-learning algorithms. The results were enhanced through a voted ensembled approach. Subsequently, a probability-weighted enhanced model (PWEM) was generated by incorporating both models; (3) Results: a total of 299 cases were included in the analysis. By receiver operating characteristic (ROC) curve analysis, PWEM achieved an area under the curve (AUC) of 0.86, which outperformed both radiomic and clinical factor models. Mean decrease accuracy, mean decrease Gini, and a chi-square test identified T stage, age, and disease site as the most important clinical factors in prognosis prediction; (4) Conclusions: our radiomic–clinical combined model revealed superior performance when compared to radiomic and clinical factor models alone. Further prospective research with a larger sample size is warranted to implement the model for clinical use. Full article

Platelet-rich fibrin (PRF), originally used to support soft tissue healing, is also considered a therapeutic option for treating oral lichen planus and leukoplakia. The progression from the two premalignant lesions to the aggressive malignant oral squamous cell carcinoma involves an inflammatory process linked to chemokine expression. Thus, there is a rationale for studying how PRF modulates the expression of chemokines in oral squamous carcinoma cells. To this aim, we expose the oral squamous carcinoma cell line HSC2 to IL1β and TNFα either alone or in the presence of lysates obtained from solid PRF membranes. We report here that in HSC2 cells, PRF lysates significantly reduce the forced transcription of chemokines, e.g., CXCL1, CXCL2, CXCL8, CXCL10, and CCL5. Moreover, PRF lysates attenuate the nuclear translocation of p65 in HSC2 oral epithelial cells when exposed to IL1β and TNFα. PRF lysates further reduce chemokine expression provoked by poly:IC HMW. Even though less pronounced, PRF lysates reduce IL1β- and TNFα-induced chemokine expression in TR146 cells. In primary oral epithelial cells, however, PRF lysates increase the basal expression of CXCL1, CXCL2 and CXCL8. Thus, PRF can exert a biphasic effect on chemokine expression in oral squamous cell carcinoma cell lines and primary oral epithelial cells. These findings suggest that PRF may reduce inflammation in a malignant environment while provoking an immunological response in healthy oral epithelium. Full article

Recently, microRNAs (miR) were identified to have potential links with oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) oncogenesis, specifically miR-21. Since HPV is a major risk factor for the development of these diseases, we aimed to search the literature regarding miR-21 expression in both HPV-positive and HPV-negative OSCC/OPSCC. The search was performed in the PubMed (MEDLINE), Scopus, Web of Science, and Cochrane electronic databases. The research question was as follows: Is there a difference in the tissue expression of miR-21 between patients with HPV-positive and those with HPV-negative OSCC/OPSCC? After conducting a meticulous search strategy, four studies were included, and they had a pooled sample size of 621 subjects with OSCC and/or OPSCC. Three studies did not find any significant difference in miR-21 expression between HPV-positive and HPV-negative OSCC/OPSCC. The findings of this systematic review showed that there are no differences in miR-21 expression between HPV-positive and HPV-negative OSCC/OPSCC. Nevertheless, it is worth noting that there are still insufficient studies regarding this important subject, because understanding how HPV influences miR-21 expression and its downstream effects can provide insights into the molecular mechanisms underlying OSCC/OPSCC development and progression. Full article

Patients with cutaneous malignancies and locoregional involvement represent a high-risk population for disease recurrence, even if they receive optimal surgery and adjuvant treatment. Here, we discuss how neoadjuvant therapy has the potential to offer significant advantages over adjuvant treatment, further improving outcomes in some patients with skin cancers, including melanoma, Merkel cell carcinoma, and cutaneous squamous-cell carcinoma. Both preclinical studies and in vivo trials have demonstrated that exposure to immunotherapy prior to surgical resection can trigger a broader and more robust immune response, resulting in increased tumor cell antigen presentation and improved targeting by immune cells, potentially resulting in superior outcomes. In addition, neoadjuvant approaches hold the possibility of providing a platform for evaluating pathological responses in the resected lesion, optimizing the prognosis and enabling personalized adaptive management, in addition to expedited drug development. However, more data are still needed to determine the ideal patient selection and the best treatment framework and to identify reliable biomarkers of treatment responses. Although there are ongoing questions regarding neoadjuvant treatment, current data support a paradigm shift toward considering neoadjuvant therapy as the standard approach for selecting patients with high-risk skin tumors. Full article

Esophageal cancer ranks the seventh in cancer incidence and the sixth in cancer death. Esophageal squamous cell carcinoma (ESCC) accounts for approximately 90% of the total cases of esophageal cancer. Chemotherapy is the most effective drug-based method for treatment of esophageal cancer. However, severe side effects of traditional chemotherapy limit its treatment efficacy. Targeted chemotherapy can deliver chemotherapeutic drugs to cancer cells and specifically kill these cells with reduced side effects. In the work, the bivalent aptamer-DNA carrier (BAD) was designed by using an ESCC cell-specific aptamer as the recognition molecule and a GC base-rich DNA sequence as the drug carrier. With doxorubicin (Dox) as chemotherapeutic drugs, the bivalent aptamer-DNA-Dox conjugate (BADD) was constructed for targeted killing of ESCC cells. Firstly, the truncated A2(35) aptamer with a retained binding ability was obtained through optimization of an intact A2(80) aptamer and was used to fuse with DNA carrier sequences for constructing the BAD through simple DNA hybridization. The results of gel electrophoresis and flow cytometry analysis showed that the BAD was successfully constructed and had a stronger binding affinity than monovalent A2(35). Then, the BAD was loaded with Dox drugs to construct the BADD through noncovalent intercalation. The results of fluorescence spectra and flow cytometry assays showed that the BADD was successfully constructed and can bind to target cells strongly. Confocal imaging further displayed that the BADD can be specifically internalized into target cells and release Dox. The results of CCK-8 assays, Calcein AM/PI staining, and wound healing assays demonstrated that the BADD can specifically kill target cells, but not control cells. Our results demonstrate that the developed BADD can specifically deliver doxorubicin to target ESCC cells and selectively kill these cells, offering a potentially effective strategy for targeted chemotherapy of ESCC. Full article

Background: Cutaneous squamous cell carcinoma is a common malignancy, which frequently develops in the areas exposed to the sun. Patients with locally advanced disease in the head and neck region are frequently disqualified from surgical resection and require systemic treatment. Methods: In this report, we present the clinicopathological features and treatment of two patients who received cemiplimab, a monoclonal antibody targeting programmed cell death receptor 1 (PD-1). Results: An 80-year-old female and 82-year-old male patient were admitted to the hospital for the treatment of large tumors diagnosed as squamous cell carcinomas. In both patients, surgical treatment was not recommended due to the large dimensions of the tumors. These patients qualified for systemic treatment with cemiplimab. In the first patient, immunotherapy was interrupted due to adverse events. Nevertheless, a continuous regression of the tumor was observed despite treatment cessation. The second patient experienced a pseudoprogression, which is an increase in the tumor size caused by infiltration of immune cells. The treatment significantly reduced tumor size in both patients, which highly improved their quality of life. Conclusions: Cemiplimab offers clinical benefits in patients with cutaneous squamous cell carcinoma who are ineligible for surgical treatment. Systemic treatment can significantly improve the quality of life and reduce tumor diameters. Full article

Background and Objectives: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous malignancy influenced by various genetic and environmental factors. Mast cells (MCs), typically associated with allergic responses, have recently emerged as key regulators of the HNSCC tumor microenvironment (TME). This systematic review explores the role of MCs in HNSCC pathogenesis and their potential as prognostic markers and therapeutic targets. Materials and Methods: A systematic search was conducted in the PubMed, Scopus and ClinicalTrials.gov databases until 31 December 2023, using “Mast cells” AND “Head and neck squamous cell carcinoma” as search terms. Studies in English which reported on MCs and HNSCC were included. Screening, data extraction and analysis followed PRISMA guidelines. No new experiments were conducted. Results: Out of 201 articles, 52 studies met the inclusion criteria, 43 of which were published between 2020 and 2023. A total of 28821 HNSCC and 9570 non-cancerous tissue samples had been examined. MC density and activation varied among normal tissues and HNSCC. Genetic alterations associated with MCs were identified, with specific gene expressions correlating with prognosis. Prognostic gene signatures associated with MC density were established. Conclusions: MCs have arisen as multifaceted TME modulators, impacting various aspects of HNSCC development and progression. Possible site-specific or HPV-related differences in MC density and activation should be further elucidated. Despite conflicting findings on their prognostic role, MCs represent promising targets for novel therapeutic strategies, necessitating further research and clinical validation for personalized HNSCC treatment. Full article