losartan-potassium and Squamous-Cell-Carcinoma-of-Head-and-Neck

Recurrent squamous cell carcinoma of the head and neck (SCCHN) carries a poor prognosis. Tumor hypoxia (TH) has been implicated as one of many factors contributing to SCCHN recurrence. TH leads to radiation resistance by reversing radiation-induced DNA damage. Effective strategies to overcome TH may improve outcomes in patients with SCCHN. We searched the English literature on PubMed and reviewed the reference sections of key articles related to TH (publications spanning from the early 1900s to the present). We summarized the underlying theory of TH in SCCHN, methods for quantifying it, and the numerous therapies developed to modulate it. We included articles that set the foundation of TH as a theory and the most relevant articles published within the last 15 years related to TH quantification and therapeutic targeting. Despite extensive research, targeting TH in SCCHN has not become a part of routine clinical practice in North America, and we analyze the pitfalls in hypoxia research that have led to this failure. We propose that future studies should test a combined approach of targeting the immune system in addition to cellular pathways rendered aberrant in TH and should include development of novel surrogate markers of TH and/or TH imaging.

Topics: Animals; Carcinoma, Squamous Cell; Erythropoietin; Head and Neck Neoplasms; Humans; Hyperthermia, Induced; Oxygen; Squamous Cell Carcinoma of Head and Neck; Tumor Hypoxia

This paper reports long-term results of RTOG 9903, to determine whether the addition of erythropoietin (EPO) would improve the outcomes of radiation therapy (RT) in mildly to moderately anemic patients with head and neck squamous cell carcinoma (HNSCCa).. The trial included HNSCCa patients treated with definitive RT. Patients with stage III or IV disease received concomitant chemoradiation therapy or accelerated fractionation. Pretreatment hemoglobin levels were required to be between 9.0 and 13.5 g/dL (12.5 g/dL for females). EPO, 40,000 U, was administered weekly starting 7 to 10 days before RT was initiated in the RT + EPO arm.. A total of 141 of 148 enrolled patients were evaluable. The baseline median hemoglobin level was 12.1 g/dL. In the RT + EPO arm, the mean hemoglobin level at 4 weeks increased by 1.66 g/dL, whereas it decreased by 0.24 g/dL in the RT arm. With a median follow-up of 7.95 years (range: 1.66-10.08 years) for surviving patients and 3.33 years for all patients (range: 0.03-10.08 years), the 5-year estimate of local-regional failure was 46.2% versus 39.4% (P=.42), local-regional progression-free survival was 31.5% versus 37.6% (P=.20), and overall survival was 36.9% versus 38.2% (P=.54) for the RT + EPO and RT arms, respectively. Late toxicity was not different between the 2 arms.. This long-term analysis confirmed that despite the ability of EPO to raise hemoglobin levels in anemic patients with HNSCCa, it did not improve outcomes when added to RT. The possibility of a detrimental effect of EPO could not be ruled out.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Carcinoma, Squamous Cell; Chemoradiotherapy; Combined Modality Therapy; Disease-Free Survival; Epoetin Alfa; Erythropoietin; Female; Head and Neck Neoplasms; Hematinics; Hemoglobin A; Humans; Male; Middle Aged; Recombinant Proteins; Squamous Cell Carcinoma of Head and Neck; Time Factors

Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors of the head and neck in the world. At present, the treatment methods include surgery, radiotherapy, and chemotherapy, but the 5-year survival rate is still not ideal and the quality of life of the patients is low. Due to the relative lack of immunotherapy methods, this study aims to build a risk prediction model of related immune genes, which can be used to effectively predict the prognosis of laryngeal cancer patients, and provide targets for subsequent immunotherapy.. We collected the 111 cases of laryngeal squamous cell carcinoma and 12 matched normal samples in the The Cancer Genome Atlas Database (TCGA) gene expression quantification database. The differentially expressed related immune genes were screened by R software version 3.5.2. The COX regression model of immune related genes was constructed, and the sensitivity and specificity of the model were evaluated. The risk value was calculated according to the model, and the risk curve was drawn to verify the correlation between related immune genes, risk score, and clinical traits.. We selected 8 immune-related genes that can predict the prognosis of LSCC in a COX regression model and plotted the Kaplan-Meier survival curve. The 5-year survival rate of the high-risk group was 16.5% (95% CI: 0.059-0.459), and that of the low-risk group was 72.9% (95% CI: 0.555-0.956). The area under the receiver operating characteristic (ROC) curve was used to confirm the accuracy of the model (AUG = 0.887). After univariate and multivariate regression analysis, the risk score can be used as an independent risk factor for predicting prognosis. The risk score (P = .021) was positively correlated with the clinical Stage classification.. We screened out 8 immune genes related to prognosis: RBP1, TLR2, AQP9, BTC, EPO, STC2, ZAP70, and PLCG1 to construct risk value models, which can be used to speculate the prognosis of the disease and provide new targets for future immunotherapy.

Topics: Aquaporins; Betacellulin; Biomarkers, Tumor; Databases, Genetic; Erythropoietin; Female; Gene Expression Regulation, Neoplastic; Glycoproteins; Humans; Immunoproteins; Intercellular Signaling Peptides and Proteins; Laryngeal Neoplasms; Male; Phospholipase C gamma; Prognosis; Proportional Hazards Models; Retinol-Binding Proteins, Cellular; Risk Assessment; Risk Factors; Sensitivity and Specificity; Squamous Cell Carcinoma of Head and Neck; Survival Rate; Toll-Like Receptor 2

Topics: Darbepoetin alfa; Denmark; Epoetin Alfa; Erythropoietin; Humans; Squamous Cell Carcinoma of Head and Neck