PPARG and the PTEN-PI3K/AKT Signaling Axis May Cofunction in Promoting Chemosensitivity in Hypopharyngeal Squamous Cell Carcinoma.

It has been demonstrated that PPARG may interact with the PTEN-PI3K/AKT pathway, contributing to its involvement in the chemotherapy treatment of hypopharyngeal squamous cell carcinoma (HSCC). However, the underlying mechanism remains largely unknown. In this study, gene expression profiles of 17 HSCC patients, comprising 8 chemotherapy-sensitive patients (CSP) and 9 chemotherapy-nonsensitive patients (CNSP), were collected and analyzed to investigate expression patterns, correlations, influencing factors of the PPARG-PTEN-PI3K/AKT pathway, and its role in regulating chemosensitivity. The results revealed significantly increased expression (p < 0.04) of AKT1, AKT2, AKT3, PIK3CA, PPARG, and PTEN in the CSP group compared to the CNSP group. Specifically, AKT2 exhibited significant overexpression in tumor tissue (p = 0.01), while AKT2, AKT3, PPARG, and PTEN displayed significant increases in normal tissue (p ≤ 0.04). Positive correlations (R ∈ [0.43, 0.71], p < 0.014) were observed between PIK3CA, AKT1, AKT2, AKT3, and PTEN, with AKT2, AKT3, and PTEN also showing significant correlations with PPARG (R ∈ [0.35, 0.47], p < 0.04). Age, gender, and disease stage had no influence on PPARG, PIK3CA, and PTEN expression, but they may affect AKT expressions. Pathway analysis revealed that PPARG may interact with the PTEN-PI3K/AKT signaling pathway, playing a crucial role in regulating chemosensitivity in the normal tissue microenvironment. Our results suggest that AKT1 and PIK3CA may be associated with chemosensitivity in HSCC tumor cells, while PPARG and PTEN might exhibit a correlation with a specific segment of the PI3K/AKT pathway, potentially influencing chemosensitivity in the normal tissue microenvironment of HSCC patients.

Fabrication of hyaluronic acid-altered gold complex delivery for head and neck squamous cell carcinoma therapy with high antitumor efficacy and low in vivo toxicity.

The use of multifunctional nanomedicines in the treatment of tumors is gaining popularity. Here, we constructed a nanodrug delivery system (HA/Au-PDA@CZT) that targets tumors and responds to pH and near-infrared (NIR) dual stimuli. By precisely interacting with an overexpressed CD44 receptor in specific cancer cells, hyaluronic acid (HA) is coated on the Au-PDA NP surface for tumor-targeting abilities. When exposed to NIR radiation, polydopamine (PDA) and gold nanoshells exhibit exceptional photothermal performance that has the potential to both accelerate and kill HLAC 78 head and neck squamous cell carcinoma cells. Antitumor investigations conducted in vivo and in vitro demonstrated that nanomedicine had remarkable synergistic benefits with chemotherapy and photothermal treatment. Only 25.2% of the cells in the HA/Au-PDA@CZT with a NIR irradiation group were viable. Any group's lowest tumor volume was shown in the tumor mice subjected to HA/Au-PDA@CZT with NIR at 0.3 ± 0.1. Consequently, for synergistic chemo-photothermal therapy, our logically designed nanoplatform would be the potential for a head and neck squamous tumor-targeting drug delivery system.

Neoadjuvant PD-1/PD-L1 inhibitors combined with chemotherapy had a higher ORR than mono-immunotherapy in untreated HNSCC: Meta-analysis.

BACKGROUND: HNSCC is one of the most common types of cancer worldwide and immune checkpoint inhibitor has shown favorable therapeutic effect in R/M HNSC. However, the application of immunotherapy in untreated HNSCC still needs to be discovered since most R/M HNSCC patients have been treated before and their drug susceptibility and immune tumor microenvironment have changed. This meta-analysis tries to compare immunotherapy and immunochemotherapy in untreated HNSCC and give a reference for clinic application. METHODS: Electronic databases, including PubMed, Embase, and Web of Science, were systematically searched from inception through August 31, 2022. The primary outcomes were efficacy, evaluated by objective response rate, 1-year OS and 1-year PFS, and safety, evaluated by grade 3-4 adverse reaction rate. RESULTS: A total of 1092 patients from twenty-four studies were included, 282 (25.8%) of which had ORR reported. The average ORR was 37% (95%CI = 26%-49%). Immunochemotherapy could have higher ORR than immunotherapy patients (ORR: 61% vs 22%), and favorable 1-year overall survival from PD-L1 inhibitor (OS = 84%, 95%CI 76%-93%). Radiotherapy after neoadjuvant immunotherapy was equal with the other treatments like chemotherapy and surgery (84% vs 88%, subgroup df p = 0.7). There was no apparent difference between immunotherapy and immunochemotherapy (32% vs 42%, subgroup df p = 0.60). CONCLUSION: HNSCC patients could benefit more from neoadjuvant immunochemotherapy.

Induction chemotherapy-based organ-preservation protocol improve the function preservation compared with immediate total laryngectomy for locally advanced hypopharyngeal cancer-Results of a matched-pair analysis.

BACKGROUND: We performed a paired analysis to compare the therapeutic effect between the induction chemotherapy-based organ-preservation approach and immediate total laryngectomy in hypopharyngeal squamous cell carcinoma patients requiring total laryngectomy. METHODS: 351 patients who were treated with organ-preservation approach were compared with 110 patients who were treated with total laryngectomy. The main measures and outcomes were progression-free survival (PFS), overall survival (OS), and larynx function preservation survival (LFPS). RESULTS: No statistical difference was observed for 3-, 5-, and 10-year PFS and OS in two groups. In the organ-preservation group, the 3-, 5-, and 10-year LFPS was 30.7%, 23.3%, and 16.6%, respectively. The LFPS of Stage III > Stage IV, N0 > N1 > N2 > N3, T2 > T3 > T4, CR > PR > SD > PD patients (all p values <0.05). CONCLUSIONS: Survival outcomes did not significantly differ between the two groups. The organ-preservation approach allowed more than 70% of the survivors to retain their larynx function.

Review of biomarkers for response to immunotherapy in HNSCC microenvironment.

Head and neck squamous cell carcinoma are one of the most common types of cancer worldwide. Although a variety of treatment methods such as surgery, radiotherapy, chemotherapy, and targeted therapy are widely used in diagnosing and treating HNSCC, the survival prognosis of patients has not been significantly improved in the past decades. As an emerging treatment approach, immunotherapy has shown exciting therapeutic effects in R/M HNSCC. However, the current screening methods are still insufficient, and there is a significant need for reliable predictive biomarkers for personalized clinical management and new therapeutic strategies. This review summarized the application of immunotherapy in HNSCC, comprehensively analyzed the existing bioinformatic studies on immunotherapy in HNSCC, evaluated the current methods of tumor immune heterogeneity and immunotherapy, and aimed to screen molecular markers with potential predictive significance. Among them, PD-1 has obvious predictive relevance as the target of existing immune drugs. Clonal TMB is a potential biomarker for HNSCC immunotherapy. The other molecules, including IFN-γ, CXCL, CTLA-4, MTAP, SFR4/CPXM1/COL5A1, TILs, CAFs, exosomes, and peripheral blood indicators, may have suggestive significance for tumor immune microenvironment and prognosis of immunotherapy.

Development and Application Evaluation of a Nursing Simulation Teaching Information System Based on Hospital Information Systems.

Background: The extensive application of hospital information systems in the current information-driven era suggests that nursing education should focus on information education. Methods: The newly developed hospital information system was used and evaluated by 544 students to explore the feasibility and necessity of such applications for teaching. Results: Overall, 97.1% of the students expressed satisfaction, and 96.0% supported simulated information education for nursing. The usability was good, with the system receiving a usability score of 72.625 ± 13.0907. The junior students had a higher score than the sophomores regarding system availability, and the difference was statistically significant. Conclusions: Students generally had a high degree of satisfaction with the simulated information nursing education system and highly approved of the teaching method. However, the system needs to be upgraded.

Trading order for degree in creative telescoping.

We analyze the differential equations produced by the method of creative telescoping applied to a hyperexponential term in two variables. We show that equations of low order have high degree, and that higher order equations have lower degree. More precisely, we derive degree bounding formulas which allow to estimate the degree of the output equations from creative telescoping as a function of the order. As an application, we show how the knowledge of these formulas can be used to improve, at least in principle, the performance of creative telescoping implementations, and we deduce bounds on the asymptotic complexity of creative telescoping for hyperexponential terms.