Search Results (542)

Background: Malnutrition and unintended weight loss are frequent in cancer patients and linked to poorer outcomes. However, data on long-term weight trajectories, particularly comparing different cancer entities, remain limited. Methods: In this retrospective, multicenter study, we analyzed 145 patients diagnosed with either head and neck cancer (HNC; n = 48) or high-grade B-cell lymphoma (HGBCL; n = 97). Body weight, C-reactive protein (CrP), albumin, and modified Glasgow Prognostic Score (mGPS) were assessed at diagnosis and at 3, 6, 9, and 12 months. Clinically relevant weight loss was defined as >5% from baseline. Survival analyses were performed for HGBCL patients. Results: Weight loss was common in both cohorts, affecting 32.2% at 3 months and persisting in 42.3% at 12 months. Nearly half of HNC patients had sustained >5% weight loss at one year, whereas HGBCL patients were more likely to regain weight, with significantly higher rates of weight gain at 6 and 12 months (p = 0.04 and p = 0.02). At baseline, HGBCL patients showed elevated CrP and lower albumin compared to HNC (both p < 0.001). Weight loss at 6 months was significantly associated with reduced overall survival in HGBCL (p < 0.01). Both Δweight at 6 months and mGPS emerged as useful prognostic indicators. Conclusions: This study reveals distinct patterns of weight change and systemic inflammation between HNC and HGBCL patients during the first year after diagnosis. These findings highlight the need for entity-specific nutritional monitoring and tailored supportive care strategies extending into survivorship. Prospective studies integrating body composition analyses are warranted to better guide long-term management. Full article

Background and objectives: Trismus is a frequent and debilitating complication in people with head and neck cancer (HNC) which leads to significant functional limitations and reduced quality of life. Rehabilitation interventions are commonly recommended to manage or prevent trismus. However, in many randomized controlled trials (RCTs), the theoretical justification for these interventions is poorly articulated, and the underlying biological or physiological mechanisms are not described in detail, limiting our understanding of why certain treatments may (or may not) work. This review aimed to identify and analyze how RCTs report the rationale for rehabilitation interventions and the explanations used to manage this population. Materials and Methods: A scoping review was conducted in accordance with the PRISMA-ScR guidelines. Five databases (PubMed, PEDro, Web of Science, Scopus, and EMBASE) were searched up to May 2025 for RCTs evaluating rehabilitation interventions for the management or prevention of treatment-induced trismus in patients with HNC. Data were extracted and synthesized narratively, focusing on the type of intervention, the rationale for its use, and the proposed mechanisms of action. Results: Of 2215 records identified, 24 RCTs met the inclusion criteria. Thirteen studies focused on preventive interventions—primarily exercise therapy—while the remainder addressed established trismus using exercise, manual therapy, electrotherapy, or combined treatment modalities. The rationales provided for intervention selection were heterogeneous and often lacked depth, with most studies justifying interventions based on their potential to improve mouth opening or reduce fibrosis but rarely grounding these claims in detailed pathophysiological models. Only half of the studies provided any mechanistic explanation for the intervention’s effects, and these were typically generic or speculative. Conclusions: RCTs investigating rehabilitation interventions for treatment-induced trismus in patients with HNC frequently lack comprehensive rationales and mechanistic explanations for their interventions. This gap limits the ability to refine and optimize treatment approaches, as the underlying processes driving clinical improvements remain poorly understood. Future research should be guided by theoretical models and include objective outcomes to better elucidate the mechanisms of action of interventions to inform clinical practice. Full article

Background/Objectives: Taste dysfunction is a highly prevalent yet underrecognized complication among patients with head and neck cancer (HNC), significantly impairing nutritional intake, treatment adherence, and quality of life (QoL). This comprehensive review synthesizes current knowledge on the pathophysiological mechanisms and clinical management of taste dysfunction associated with HNC and its treatments, particularly chemotherapy and radiotherapy. Methods: A structured literature search was performed across PubMed, Scopus, and Cochrane Library for articles published between January 2015 and February 2025. Studies were included if they investigated taste dysfunction related to HNC, focusing on pathophysiological mechanisms and therapeutic interventions. A total of 47 original studies were analyzed through a narrative synthesis due to heterogeneity in study designs and outcomes. Results: Taste dysfunction in HNC patients arises from tumor-related inflammation, cytotoxic injury from chemotherapy, and radiation-induced epithelial and neural damage. Chemotherapy and radiotherapy often exert synergistic negative effects on gustatory function. Management strategies identified include dietary counselling, nutritional supplementation (zinc, lactoferrin, monosodium glutamate, miraculin), pharmacological agents targeting salivary function, and non-pharmacological interventions such as acupuncture, photobiomodulation, and reconstructive surgery. However, the evidence is limited by small sample sizes, methodological variability, and the frequent exclusion of HNC patients from broader dysgeusia trials. Reported prevalence of taste dysfunction ranged from 39% to 97.4%, with higher rates observed among patients treated with radiotherapy and chemoradiotherapy. Conclusions: Taste dysfunction remains a critical yet unmet clinical challenge in HNC patients. High-quality, targeted research is urgently needed to develop standardized assessments and evidence-based management strategies to improve patient outcomes. Full article

Objective: To evaluate the effect of a probiotic combination on clinical and oral microbiological parameters in patients with head and neck cancer (HNC) undergoing radiotherapy. Materials and Methods: A randomised, double-blind, placebo-controlled clinical trial was conducted with 72 HNC patients who had received radiotherapy within the past year. Participants were randomly assigned to receive either daily probiotic sachets or placebo for 30 days. Salivary parameters—including unstimulated and stimulated flow rates and pH—were evaluated alongside oral microbiota profiles, including total bacterial load and selected periodontopathogens. Assessments were performed at baseline and post-intervention using sialometry, pH analysis, bacterial culture, and quantitative real-time PCR (qPCR). Results: Sixty-one patients completed the study (31 in the probiotic group, 30 in the placebo group). Stimulated salivary flow increased significantly in the probiotic group (p = 0.0016), while unstimulated flow improved in both groups (p < 0.05). Salivary pH decreased significantly in the probiotic group (p = 0.0209); however, no intergroup differences were observed at the end of the intervention (p = 0.9839). qPCR showed significant reductions in total bacterial load (p = 0.0209) and Fusobacterium nucleatum (p = 0.0080). Culture confirmed the reduction of F. nucleatum (p = 0.0026), with a trend towards significance for total cultivable bacterial count (p = 0.0502). Conclusions: Daily supplementation with a probiotic combination may serve as a practical and well-tolerated adjunctive measure in clinical settings to improve salivary function and reduce key oral pathogens, particularly Fusobacterium nucleatum, in patients undergoing or recovering from radiotherapy for head and neck cancer. These findings support its potential integration into routine supportive care protocols to mitigate xerostomia and oral dysbiosis in this population. Full article

Head and neck cancer (HNC) is a highly aggressive malignancy with limited treatment options and poor prognosis. Inflammation plays a critical role in HNC progression, with elevated levels of pro-inflammatory cytokines such as TNF, IL-6, IL-8, and IL-1β contributing to tumor development. In this study, a novel series of boronic chalcones was designed and synthesized as potential dual-action anticancer and anti-inflammatory agents. The most potent compounds were evaluated for their cytotoxicity against Squamous Cell Carcinoma (SCC-25), and their selectivity index (SI) was determined. Compound 5 emerged as the most promising, displaying cytotoxicity against cancer cells, with IC₅₀ values of 17.9 µM and a favorable SI (>3). Mechanistic studies revealed that its anticancer activity was independent of p53 status, and annexin V/PI staining indicated cell death via necrosis. Interestingly, compound 5 also significantly reduced pro-inflammatory cytokine levels, as TNF and IL-6. Furthermore, drug metabolism and pharmacokinetics (DMPK) studies demonstrated that compound 5 exhibited moderate solubility and high permeability. These findings underscore the crucial role of the boronic acid moiety in enhancing both anticancer and anti-inflammatory properties. Full article

Ferroptosis, a regulated form of iron-dependent lipid peroxidation-induced cell death, has emerged as a compelling therapeutic strategy to overcome treatment resistance in head and neck cancer (HNC). Glutathione peroxidase 4 (GPX4), a selenoenzyme responsible for detoxifying phospholipid hydroperoxides, plays a central role in blocking ferroptosis and is frequently upregulated in therapy-resistant HNC subtypes. In this review, we examine the multifaceted regulation of GPX4 expression and function, including transcriptional, post-transcriptional, epigenetic, and proteostatic mechanisms. We explore how GPX4 suppression through pharmacologic inhibitors (e.g., RSL3, withaferin A, statins), metabolic stress, or combined therapies (e.g., radiotherapy, EGFR inhibitors, immunotherapy) induces ferroptosis and resensitizes resistant tumors. We also summarize emerging biomarkers, including GPX4, ACSL4, SLC7A11, and NCOA4, that predict ferroptosis sensitivity and may guide patient selection for ferroptosis-targeted therapies. Single-cell and spatial transcriptomics reveal significant intratumoral heterogeneity in ferroptosis susceptibility, underscoring the need for precision approaches. Despite promising preclinical data, challenges such as drug delivery, toxicity, and resistance mechanisms remain. Nevertheless, the ferroptosis-GPX4 axis represents a unique vulnerability in HNC that can be therapeutically exploited. Integrating ferroptosis modulation into personalized oncology may transform outcomes for patients with refractory disease. Full article

Background/Objectives: Chimeric antigen receptor T-cell (CAR-T) therapy is a novel form of adoptive cellular immunotherapy that involves modifying autologous T cells to recognize and target tumor-associated antigens (TAAs) on malignant cells, independent of major histocompatibility complex (MHC) restriction. Although CAR-T therapy has shown remarkable success in treating hematologic malignancies, its efficacy in solid tumors remains limited, largely due to the lack of tumor-specific antigens and the complexity of the tumor microenvironment. This review aims to explore the rationale for continuing the development of adoptive cellular therapies in head and neck cancer (HNC), offering insights into the diagnostic and therapeutic challenges associated with this heterogeneous group of malignancies. Methods: We conducted a comprehensive literature review using the PubMed database to identify relevant studies on the application of CAR-T cell therapy in the management of HNC. Results: HNC presented numerous barriers to CAR-T cell infiltration, primarily due to the unique characteristics of its tumor microenvironment (TME). The TME in HNC is notably immunosuppressive, with a lymphocytic infiltrate predominantly composed of regulatory T cells (Tregs) and natural killer (NK) cells. These immune cells typically exhibit low expression of the CD16 receptor, which plays a crucial role in mediating antibody-dependent cellular cytotoxicity (ADCC), thereby limiting the effectiveness of CAR-T cell therapy. Conclusions: This comprehensive review suggests a potential clinical applicability of CAR-T therapy in HNC management. Full article

Background: Head and neck cancer (HNC) remains a global health challenge with a poor 5-year survival rate among patients with relapsed or advanced-stage disease. Immune checkpoint blockade therapies have emerged as a promising approach to improve outcomes; however, their effectiveness is limited, with response rates of only 15–20% because of immune evasion mechanisms. MicroRNA (miRNA) dysregulation plays a key role in facilitating such immune evasion. In this study, we aim to identify specific miRNAs whose altered expression contributes to immune escape in HNC. Methods: We employed an integrated bioinformatics approach, incorporating differential expression analysis, survival analysis, target prediction, KEGG immune pathway analysis, a protein–protein interaction network, and the identification of hub genes using in silico tools. Results: Our analysis revealed that a high expression of miR-18a and miR-2355 was associated with reduced survival, with the median survival decreasing from 42.9 to 27.8 months, respectively, in advanced-stage patients. Conversely, a low expression of let-7c and miR-6510 was linked to poor prognosis, with survival decreasing from 40.1 to 19.2 months and from 50.1 to 26.8 months, respectively, across disease progression. Further pathway analysis revealed that these miRNAs are significantly involved in the regulation of key immune evasion signaling pathways, including T cell receptor, PD-L1/PD-1 checkpoint, JAK-STAT, TGF-beta, NF-kappa B, and TNF signaling pathways. Hub gene analysis identified AKT1, STAT3, NFKB1, CD4, IL2RB, TLR4, and CTLA-4 as potential dysregulated miRNA targets, with enrichment in immune-related signaling pathways. Conclusions: Taken together, these findings suggest that targeting these miRNAs could modulate immune evasion mechanisms and potentially enhance the efficacy of ICB therapies in HNC. Full article

Background/Objectives: There is a varying need for nutritional support among head and neck cancer (HNC) patients. Unplanned hospitalization is frequent with definitive chemoradiation. However, the association of unplanned hospitalizations with cancer control outcomes and percutaneous endoscopic gastrostomy (PEG) tube placement is not well-understood. This study aims to evaluate the clinical outcomes stratified by unplanned hospitalizations and to identify the prognostic factors associated with unplanned hospitalizations. Methods: This retrospective cohort study included 657 HNC patients treated with definitive chemoradiation at a single institution between 2007 and 2023. Relevant clinical data were evaluated for unplanned hospitalizations, prophylactic vs. therapeutic PEG tube placement, and clinical outcomes. Multivariable, subgroup, and matched-pair analyses were performed to account for potential confounding variables. The main outcomes and measures used are overall survival (OS), progression-free survival (PFS), locoregional failure (LRF), distant failure (DF), and incidence of unplanned hospitalization. Results: Unplanned hospitalizations occurred in 190 (29%) patients, which were associated with worse OS (adjusted hazards ratio [aHR] of 2.07, 95% confidence interval [CI] of 1.53–2.81, p < 0.001) and progression-free survival (aHR 1.83, 95% CI 1.38–2.41, p < 0.001). However, hospitalizations were not associated with LRF or DF outcomes. Similar findings were noted on 180 matched pairs as well as subgroups stratified by p16 status. In addition, when compared to patients with a prophylactic PEG tube, therapeutic PEG tube placement was associated with a higher risk of hospitalization (adjusted odds ratio [aOR] of 1.96, 95% CI 1.10–3.54, p = 0.02), while those without PEG tubes were less likely to be hospitalized (aOR 0.48, 95% CI 0.27–0.86, p = 0.01). Conclusions: Unplanned hospitalization was an independent, adverse prognostic factor for poor survival, but not oncologic outcomes. Unplanned hospitalization incidence was largely driven by those who required a therapeutic PEG tube, while it was the lowest for those who never needed a PEG tube. Full article

Background/Objectives: Acetylsalicylic acid (ASA) medication has been suggested to have a beneficial effect on cancer risk and survival. Therefore, this retrospective case–control study investigated the correlation between ASA and HNC in over 11,000,000 patients to investigate the impact of ASA intake on the risk of developing HNC, five-year survival rates, and the likelihood of secondary malignant neoplasms and malignant lymph node involvement. Methods: Retrospective clinical data was retrieved from a federated EHR network. Patients prescribed ASA were assigned to Cohort I, while those who were not prescribed ASA were assigned to Cohort II. Moreover, patients diagnosed with HNC, and prescribed ASA were assigned to Cohort III, while those with HNC but no history of ASA use were assigned to Cohort IV. Results: After matching, Cohorts I and II included 5,716,056 patients each. HNC incidence was significantly lower (OR 0.88; 95% CI 0.86–0.90) in Cohort I (+ASA) compared to Cohort II (−ASA). Furthermore, five-year survival was higher for patients taking ASA medication (survival probability 67.93%) compared to patients who did not (65.54%). These findings coincide with a lower risk of death of 22.8% (+ASA) compared to 23.6% (−ASA), which was statistically significant (p = 0.006). Patients with ASA intake also showed a lower risk of malignant neoplasms of lymph nodes (17.4% vs. 18.5%). Conclusions: Our analyses revealed a lower risk of HNC, a higher five-year survival rate, and a lower risk of malignant neoplasms of lymph nodes in patients with ASA medication. However, the retrospective design and the lack of evaluation of confounders limit the significance of our data, and, therefore, further analyses should be considered. Full article

This study aimed to evaluate the effects of dietary nano-copper supplementation on growth performance, nutrient digestibility, antioxidant status, inflammatory response, and intestinal barrier function in weanling pigs under heat stress conditions. Forty 20-day-old weaned weanling pigs (Yorkshire × Landrace × Duroc) weighing 6.49 ± 0.08 kg were randomly divided into five treatments with eight replicates each. The pre-feeding period was 2 days, followed by a 22-day experimental period. All groups were exposed to high heat conditions at 35 ± 1 °C. The control group received a basal diet, while the low copper sulfate (LC) group received a diet with 50 mg/kg of copper sulfate, the high copper sulfate (HC) group received a diet with 150 mg/kg of copper sulfate, the low nano-copper (LNC) group received a diet with 50 mg/kg of nano-copper oxide, and the high nano-copper (HNC) group received a diet with 150 mg/kg of nano-copper oxide. Compared to the basal group, pigs supplemented with copper (either CuSO₄ or nano-CuO) exhibited significantly higher average daily gain (ADG, p < 0.048) and feed intake (ADFI, p = 0.005), with the 50 mg/kg nano-copper group showing improved nutrient digestibility (p < 0.05) and intestinal morphology. Nano-copper supplementation significantly enhanced mucosal SOD activity (p < 0.05), reduced MDA levels (p < 0.05), and downregulated pro-inflammatory cytokines such as IL-1β and IL-6 (p < 0.05). Notably, 50 mg/kg of nano-copper increased the apparent total tract digestibility (ATTD) of copper to 30.29%, significantly higher than the 16.55% observed in the 150 mg/kg CuSO₄ group (p < 0.05). Furthermore, fecal copper concentration was significantly reduced by 20.7% in the 50 mg/kg nano-copper group compared to copper sulfate (p < 0.001). In conclusion, nano-copper appears to be a promising alternative to copper sulfate for improving growth performance and reducing fecal copper concentrations in weanling pigs under heat stress conditions. Full article

Background: SARS-CoV-2 immunity is understudied in cancer patients. Here, we monitored natural/vaccine-induced SARS-CoV-2 immunity in patients with head and neck cancer (HNC) stratified as vaccinated (mRNA/adenovirus-based vaccines), convalescent, and hybrid immunity. Methods: Plasma/PBMC samples were collected from 49 patients with HNC and 14 non-oncologic controls recruited between August 2021 and March 2022. Longitudinal follow-up was performed on 25 HNC patients. Plasma antibodies (Abs) against Spike (S1/S2), receptor-binding domain (RBD), and nucleocapsid (NC) of IgG/IgA isotypes and 25 cytokines/chemokines were quantified using MILLIPLEX^® technology. The frequency, phenotype, and isotype of circulating SARS-CoV-2-specific B-cells were studied by flow cytometry using RBD tetramers (Tet⁺⁺). The proliferation of B-cells and CD4+ and CD8+ T-cells in response to Spike/NC peptides was monitored by a carboxyfluorescein succinimidyl ester (CFSE) assay. Results: Plasma SARS-CoV-2 S1/S2/RBD IgG/IgA Abs were detected in all HNC participants at enrollment median time since immunization (TSI) 117 days at levels similar to controls and were significantly higher in convalescent/hybrid versus vaccinated. NC IgG/IgA Abs were only detected after infection. The frequency of Tet++ B-cells, enriched in the CD27+ memory phenotype and IgG/IgA isotype, positively correlated with plasma levels of RBD IgG/IgA Abs and Spike-specific CD4+ T-cell proliferation, regardless of the immunization status and TSI. Spike/NC-specific B-cell proliferation reached the highest levels in convalescent HNC and was positively correlated with NC IgG Abs, but not with the frequency of Tet++ B-cells. Finally, Tet++ B-cell frequencies remained stable between the two subsequent visits (median TSI: 117 versus 341 days), indicating their ability to persist for a relatively long time. Conclusions: This study monitored SARS-CoV-2 humoral/cellular immunity in an HNC cohort relative to non-oncologic participants and demonstrates that SARS-CoV-2-specific B-cells persist beyond 11 months post-immunization. These findings have implications for the management of HNC in the context of SARS-CoV-2 infection and other viral infections. Full article

Cellular senescence is a complex physiological process in which cells permanently stop dividing and enter a stable state of cell-cycle arrest. This mechanism is typically triggered by various stressors, such as DNA damage, oxidative stress, telomere shortening, and oncogene activation. Senescent cells remain metabolically active and significantly influence their microenvironment through the senescence-associated secretory phenotype (SASP), which includes the secretion of inflammatory cytokines, growth factors, and proteases. While cellular senescence serves as a crucial tumor-suppressive mechanism by preventing the proliferation of damaged or potentially cancerous cells, it also plays a paradoxical role by promoting chronic inflammation, tissue dysfunction, and potentially oncogenesis. Therefore, understanding the regulation and impact of cellular senescence is vital for developing therapeutic interventions that leverage its benefits while minimizing adverse outcomes. In this review, we provide an overview of the current understanding of cellular senescence in cancer biology and discuss the emerging field of senescence-targeted therapies. We focus specifically on the role of senescence in head and neck cancers, examining the potential of induced senescence therapy to mitigate the progression of these tumors. This review aims to correlate the dual nature of senescence with innovative therapeutic strategies, highlighting its promise and challenges in improving treatment outcomes for HNC patients. Full article

Persistent organohalogen pollutants—including halogenated nitrophenols (HNCs), trichloroethylene (TCE), and per- and polyfluoroalkyl substances (PFAS)—pose serious environmental and health risks due to their stability, toxicity, and bioaccumulation potential. This review critically assesses current remediation technologies including advanced oxidation processes (AOPs), adsorption, membrane filtration, and thermal treatments. While these methods can be effective, they are often limited by high costs, energy demands, toxic byproduct formation, and sustainability concerns. Emerging biological approaches offer promising alternatives. Among these, fungal-based degradation methods (mycodegradation) remain significantly underrepresented in the literature, despite fungi demonstrating a high tolerance to contaminants and the ability to degrade structurally complex compounds. Key findings reveal that white-rot fungi such as Phanerochaete chrysosporium and Trametes versicolor possess enzymatic systems capable of breaking down persistent organohalogens under conditions that inhibit bacterial activity. This review also identifies critical research gaps, including the need for direct comparative studies between fungal and bacterial systems. The findings suggest that integrating mycodegradation into broader treatment frameworks could enhance the environmental performance and reduce the long-term remediation costs. Overall, this review highlights the importance of diversifying remediation strategies to include scalable, low-impact biological methods for addressing the global challenge of organohalogen contamination. Full article

Traditional oncological therapies have contributed to reducing the global cancer burden; however, they have not achieved complete eradication, nor have they effectively prevented relapses, minimized toxicity, or preserved immune function. Recent advances, particularly the introduction of immune checkpoint inhibitors (ICIs) and CAR-T cell therapies, have markedly improved clinical outcomes and overall survival in certain cancer subtypes. Nevertheless, response rates remain suboptimal, and adverse immunological events are frequent. This review starts by highlighting the FDA-approved ICIs currently utilized in cancer immunotherapy, emphasizing those that have demonstrated clinical efficacy in recent years. The true focus of our analysis is on the latest clinical applications of near-infrared photoimmunotherapy (NIR-PIT). This emerging modality is evaluated in patients with head and neck cancers (HNC), particularly in cases that are unresectable, locally advanced, or recurrent. Finally, the review explores the current landscape and prospects of NIR-PIT, considering its potential to enhance therapeutic efficacy and extend relapse-free survival. Photoimmunotherapy is a promising, molecularly targeted option for patients with limited prognosis, offering new hope where conventional therapies fail. By synthesizing recent clinical trial data, this work highlights how NIR-PIT could bridge the translational gap between preclinical research and clinical practice. The integration of advanced technologies and interdisciplinary collaboration among researchers, clinicians, and technologists will be critical in optimizing NIR-PIT, improving its accuracy, efficacy, and safety, and ultimately advancing standards of cancer care and patient survival. Full article