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In recent years, whey proteins (WP) have attracted increasing attention in health and disease for their bioactive functions. The aim of this study was to evaluate the benefit of WP isolate (WPI) supplementation in addition to nutritional counseling in malnourished advanced cancer patients undergoing chemotherapy (CT). In a single‐center, randomized, pragmatic, and parallel‐group controlled trial (ClinicalTrials.gov: NCT02065726), 166 malnourished advanced cancer patients with mixed tumor entities candidate to or undergoing CT were randomly assigned to receive nutritional counseling with (N = 82) or without (N = 84) WPI supplementation (20 g/d) for 3 months. The primary endpoint was the change in phase angle (PhA). Secondary endpoints included changes in standardized PhA (SPA), fat‐free mass index (FFMI), body weight, muscle strength, and CT toxicity (CTCAE 4.0 events). In patients with the primary endpoint assessed (modified intention‐to‐treat population), counseling plus WPI (N = 66) resulted in improved PhA compared to nutritional counseling alone (N = 69): mean difference, 0.48° (95% CI, 0.05 to 0.90) (P = .027). WPI supplementation also resulted in improved SPA (P = .021), FFMI (P = .041), body weight (P = .023), muscle strength (P < .001), and in a reduced risk of CT toxicity (risk difference, −9.8% [95% CI, −16.9 to −2.6]; P = .009), particularly of severe (grade ≥ 3) events (risk difference, −30.4% [95% CI, −44.4 to −16.5]; P = .001). In malnourished advanced cancer patients undergoing CT, receiving nutritional counseling, a 3‐month supplementation with WPI resulted in improved body composition, muscle strength, body weight, and reduced CT toxicity. Further trials, aimed at verifying the efficacy of this nutritional intervention on mid‐ and long‐term primary clinical endpoints in newly diagnosed specific cancer types, are warranted. Whey proteins (WP) have attracted increasing attention in health and disease for their bioactive functions. In malnourished advanced cancer patients undergoing chemotherapy (CT) and receiving nutritional counseling, a 3‐month supplementation with WP resulted in improved body composition, muscle strength, and reduced CT toxicity.

Natural killer (NK) cells are emerging as unique players in the immune response against cancer; however, only limited data are available on tumor infiltrating NK cells in head and neck squamous cell carcinoma (HNSCC), one of the most common cancer. Occurrence of HNSCC is closely related to the immune microenvironment, and immunotherapy is increasingly being applied to this setting. However, the limited success of this type of treatment in this tumor calls for further investigation in the field. Surgical HNSSC specimens of 32 consecutive patients were mechanically and enzymatically dissociated. Tumor cells were separated from infiltrating cells by short centrifugation and infiltrating NK cells were phenotypically and functionally characterized by multiple antibody staining and flow cytometry. Tumor infiltrating NK cells in HNSCC showed a peculiar phenotype predominantly characterized by increased NKG2A and reduced Siglec-7, NKG2D, NKp30 and CD16 expression. This phenotype was associated with a decreased ability to perform antibody-dependent cellular cytotoxicity (ADCC). However, NK, CD4 and CD8 shared an increment of glucocorticoid-induced tumor necrosis factor-related (GITR) costimulatory receptor which could be exploited for immunotherapy with agonistic anti-GITR antibodies combined with checkpoint inhibitors.

Recurrent respiratory papillomatosis (RRP) is a condition caused by human papilloma virus (HPV) infection. Curative treatments aren't identifiable, and conservative surgery is often the best option to preserve respiratory functions. To date monoclonal antibodies are considered to be a treatment choice with both good efficacy and safety profile. A web-based search of MEDLINE/PubMed library from 2000 to 2024 of English-language papers was performed to identify articles by using \"respiratory or laryngeal papillomatosis\" and \"HPV respiratory infection, papillomatosis treatment, papillomatosis vaccine immunization, papillomatosis systemic treatment\". Furthermore, a manual screening of references from original articles was done to identify additional studies. We selected 34 articles. Since 2009, the systemic administration of Bevacizumab has been used to treat RRP not responding to surgical treatment. The efficacy of an anti-VEGF monoclonal antibody in RRP lesions can be related to their vascular nature. The major concern is the rebound papilloma growth within the cessation of treatment. An interesting solution could be the concomitant use of immunotherapy to both reduce the burden of residual disease and activate the immune system against the HPV-infected cells. Bevacizumab has a safe profile with a short-term local eradication of HPV. Further prospective research with long-term follow-up is needed to better define its safety and results against the disease recurrence. Considering the role of the anti-HPV vaccine, both, in the prophylaxis of the infection and in the adjuvant setting, the actual data underline the need for evaluation of its therapeutic efficacy for the management of RRP.

Mesenchymal stem cells (MSCs) have gained recognition as a highly versatile and promising cell source for repopulating bioengineered scaffolds due to their inherent capacity to differentiate into multiple cell types. However, MSC implantation techniques have often yielded inconsistent clinical results, underscoring the need for advanced approaches to enhance their therapeutic efficacy. Recent developments in three-dimensional (3D) bioengineered scaffolds have provided a significant breakthrough by closely mimicking the in vivo environment, addressing the limitations of traditional two-dimensional (2D) cell cultures. Among these, nanofibrous scaffolds have proven particularly effective, offering an optimal 3D framework, growth-permissive substrates, and the delivery of trophic factors crucial for MSC survival and regeneration. Furthermore, the selection of appropriate biomaterials can amplify the paracrine effects of MSCs, promoting both proliferation and targeted differentiation. The synergistic combination of MSCs with nanofibrous scaffolds has demonstrated remarkable potential in achieving repair, regeneration, and tissue-specific differentiation with enhanced safety and efficacy, paving the way for routine clinical applications. In this review, we examine the most recent studies (2013–2023) that explore the combined use of MSCs and nanofibrous scaffolds for differentiation into cardiogenic, epithelial, myogenic, tendon, and vascular cell lineages. Using PubMed, we identified and analyzed 275 relevant articles based on the search terms “Nanofibers”, “Electrospinning”, “Mesenchymal stem cells”, and “Differentiation”. This review highlights the critical advancements in the use of nanofibrous scaffolds as a platform for MSC differentiation and tissue regeneration. By summarizing key findings from the last decade, it provides valuable insights for researchers and clinicians aiming to optimize scaffold design, MSC integration, and translational applications. These insights could significantly influence future research directions and the development of more effective regenerative therapies.

Olfactory and taste disorders (OTD) are commonly found as presenting symptoms of SARS-CoV-2 infection in patients with clinically mild COVID-19. Virus-specific T cells are thought to play an important role in the clearance of SARS-CoV-2; therefore the study of T cell specific immune responses in patients with mild symptoms may help to understand their possible role in protection from severe disease. We evaluated SARS-CoV-2-specific T cell responses to four different peptide megapools covering all SARS-CoV-2 proteins during the acute phase of the disease in 33 individuals with mild or no other symptom beside OTD and in 22 age-matched patients with severe infection. A control group of 15 outpatients with OTD and consistently negative nasopharyngeal SARS-CoV-2 RNA swabs and virus-specific IgG serology was included in the study. Increased frequencies of virus-specific CD4 + and CD8 + T cells were found in SARS-CoV-2 positive patients with OTD compared with those with severe COVID-19 and with SARS-CoV-2 negative OTD individuals. Moreover, enhanced CD4 + and CD8 + T-cell activation induced by SARS-CoV-2 peptides was associated with higher interferon (IFN)γ production. Increased frequencies of Spike (S1/S2)-specific CD4 + T cells showing enhanced IFNγ secretion and granzyme B content were associated with serum spike-specific IgG in the OTD group. In conclusion, patients with SARS-CoV-2 induced OTD develop highly functional virus-specific CD4 + and CD8 + T cells during the symptomatic phase of the disease, suggesting that robust and coordinated T-cell responses provide protection against extension of COVID-19 to the lower respiratory tract.

Head and neck squamous cell carcinoma (HNSCC) presents significant challenges in oncology due to its complex biology and poor prognosis. Traditional two-dimensional (2D) cell culture models cannot replicate the intricate tumor microenvironment, limiting their usefulness in studying disease mechanisms and testing therapies. In contrast, three-dimensional (3D) in vitro models provide more realistic platforms that better mimic the architecture, mechanical features, and cellular interactions of HNSCC. This review explores the mechanical properties of 3D in vitro models developed for HNSCC research. It highlights key 3D culture techniques, such as spheroids, organoids, and bioprinted tissues, emphasizing their ability to simulate critical tumor characteristics like hypoxia, drug resistance, and metastasis. Particular attention is given to stiffness, elasticity, and dynamic behavior, highlighting how these models emulate native tumor tissues. By enhancing the physiological relevance of in vitro studies, 3D models offer significant potential to revolutionize HNSCC research and facilitate the development of effective, personalized therapeutic strategies. This review bridges the gap between preclinical and clinical applications by summarizing the mechanical properties of 3D models and providing guidance for developing systems that replicate both biological and mechanical characteristics of tumor tissues, advancing innovation in cancer research and therapy.

Refractory or metastatic nasopharyngeal carcinoma (NPC) patients have a poor prognosis due to the lack of effective salvage treatments and prolonged survival by means of combination chemotherapy being described only for a minority of younger patients with oligometastatic disease. Targeting the Epstein - Barr virus (EBV) proteins expressed in NPC cells has been shown to be a feasible strategy that could help control systemic disease. Between 2011 and 2014, 16 patients with recurrent/metastatic EBV-NPC received first-line chemotherapy (CT) followed by 2 doses of autologous cytotoxic EBV specific T-lymphocytes (15-25 x 10 total cells/dose, 2 weeks apart), based on our previous studies showing the feasibility and efficacy of this infusion regimen. Cumulative overall survival (OS) and median OS were analysed in the whole population and according to specific clinical and biological parameters. All patients received the planned T-cell therapy schedule, 9 after reaching partial (n=5) or complete (n=4) disease remission with CT, and 7 after failing to obtain benefit from chemotherapy. No severe adverse events were recorded. Patients who received cytotoxic T-lymphocytes (CTLs) had a cumulative 10-year OS of 44%, with a median OS of 60 months (95% CI 42-62). Patients responding to CT, with oligometastatic disease (<3 disease sites), and plasma EBV-DNA <1000 copies/mL had a better outcome. Autologous EBV-specific CTLs transplanted following conventional first-line CT demonstrated promising efficacy with several patients obtaining long-lasting disease control. The rationale provided by this study, with the crucial role likely played by the timing of CTL administration when trying to induce synergy with conventional treatment needs to be confirmed in a prospective controlled trial.

PurposeThe aim of this study is to evaluate the prognostic value of pre-treatment advanced lung cancer inflammation index (ALI) in patients with HPV-negative HNSCC undergoing up-front surgical treatment.MethodsThe present multi-centre, retrospective study was performed in a consecutive cohort of patients who underwent upfront surgery with or without adjuvant (chemo)-radiotherapy for head and neck squamous cell carcinoma (HNSCC). Patients were stratified by ALI, and survival outcomes were compared between groups. In addition, the prognostic value of ALI was compared with two other indices, the prognostic nutritional index (PNI) and systemic inflammatory index (SIM).ResultsTwo hundred twenty-three patients met the inclusion criteria (151 male and 72 female). Overall and progression-free survival were significantly predicted by ALI < 20.4 (HR 3.23, CI 1.51–6.90 for PFS and HR 3.41, CI 1.47–7.91 for OS). Similarly, PNI < 40.5 (HR = 2.43, 95% CI: 1.31–4.51 for PFS and HR = 2.40, 95% CI: 1.19–4.82 for OS) and SIM > 2.5 (HR = 2.51, 95% CI: 1.23–5.10 for PFS and HR = 2.60, 95% CI: 1.19–5.67 for OS) were found to be significant predictors. Among the three indices, ALI < 20.4 identified the patients with the worst 5-year outcomes. Moreover, patients with a combination of low PNI and low ALI resulted to be a better predictor of progression (HR = 5.26, 95% CI: 2.01–13.73) and death (HR = 5.68, 95% CI: 1.92–16.79) than low ALI and low PNI considered alone.ConclusionsOur results support the use of pre-treatment ALI, an easily measurable inflammatory/nutritional index, in daily clinical practice to improve prognostic stratification in surgically treated HPV-negative HNSCC.

Background: To make the regenerative process more effective and efficient, tissue engineering (TE) strategies have been implemented. Three-dimensional scaffolds (electrospun or 3D-printed), due to their suitable designed architecture, offer the proper location of the position of cells, as well as cell adhesion and the deposition of the extracellular matrix. Moreover, the possibility to guarantee a concomitant release of drugs can promote tissue regeneration. Methods: A PLA/PCL copolymer was used for the manufacturing of electrospun and hybrid scaffolds (composed of a 3D-printed support coated with electrospun fibers). Dexamethasone was loaded as an anti-inflammatory drug into the electrospun fibers, and the drug release kinetics and scaffold biological behavior were evaluated. Results: The encapsulation efficiency (EE%) was higher than 80%. DXM embedding into the electrospun fibers resulted in a slowed drug release rate, and a slower release was seen in the hybrid scaffolds. The fibers maintained their nanometric dimensions (less than 800 nm) even after deposition on the 3D-printed supports. Cell adhesion and proliferation was favored in the DXM-loading hybrid scaffolds. Conclusions: The hybrid scaffolds that were developed in this study can be optimized as a versatile platform for soft tissue regeneration.