scholarly journals Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA-altered head and neck cancer

2019 ◽  
Vol 216 (2) ◽  
pp. 419-427 ◽  
Author(s):  
Matthew L. Hedberg ◽  
Noah D. Peyser ◽  
Julie E. Bauman ◽  
William E. Gooding ◽  
Hua Li ◽  
...  
Keyword(s):  
Head And Neck ◽  
Patient Survival ◽  
Pik3ca Mutation ◽  
Nsaid Therapy ◽  
Hazard Ratio ◽  
Preclinical Models ◽  
Pik3ca Mutations ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
The Impact

PIK3CA is the most commonly altered oncogene in head and neck squamous cell carcinoma (HNSCC). We evaluated the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on survival in a PIK3CA-characterized cohort of 266 HNSCC patients and explored the mechanism in relevant preclinical models including patient-derived xenografts. Among subjects with PIK3CA mutations or amplification, regular NSAID use (≥6 mo) conferred markedly prolonged disease-specific survival (DSS; hazard ratio 0.23, P = 0.0032, 95% CI 0.09–0.62) and overall survival (OS; hazard ratio 0.31, P = 0.0043, 95% CI 0.14–0.69) compared with nonregular NSAID users. For PIK3CA-altered HNSCC, predicted 5-yr DSS was 72% for NSAID users and 25% for nonusers; predicted 5-yr OS was 78% for regular NSAID users and 45% for nonregular users. PIK3CA mutation predicted sensitivity to NSAIDs in preclinical models in association with increased systemic PGE2 production. These findings uncover a biologically plausible rationale to implement NSAID therapy in PIK3CA-altered HNSCC.

ASS und Kopf-Hals-Tumore

2019 ◽  
Vol 51 (03) ◽  
pp. 145-147
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Patient Survival ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

Hedberg ML, Peyser ND, Bauman JE et al. Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA-altered head and neck cancer. J Exp Med 2019; 216: 419–427. doi:10.1084/jem.20181936

Non-steroidal anti-inflammatory drugs inhibit telomerase activity in head and neck squamous carcinoma cell lines

Head & Neck ◽  
2001 ◽  
Vol 23 (12) ◽  
pp. 1049-1055 ◽  
Author(s):  
Dietmar Thurnher ◽  
Maia Bakroeva ◽  
Michael Formanek ◽  
Birgit Knerer ◽  
Johannes Kornfehl
Keyword(s):  
Head And Neck ◽  
Cell Lines ◽  
Carcinoma Cell ◽  
Squamous Carcinoma ◽  
Telomerase Activity ◽  
Carcinoma Cell Lines ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Squamous Carcinoma Cell

The Impact of Nonsteroidal Anti-inflammatory Drugs on Older Adult Trauma Patients With Hip Fractures

2020 ◽  
Vol 255 ◽  
pp. 583-593
Author(s):  
Krista L. Haines ◽  
Matthew Fuller ◽  
Justin G. Vaughan ◽  
Vijay Krishnamoorthy ◽  
Karthik Raghunathan ◽  
...  
Keyword(s):  
Older Adult ◽  
Hip Fractures ◽  
Trauma Patients ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
The Impact

scholarly journals Survival-Associated Metabolic Genes in Human Papillomavirus-Positive Head and Neck Cancers

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 253 ◽  
Author(s):  
Martin A. Prusinkiewicz ◽  
Steven F. Gameiro ◽  
Farhad Ghasemi ◽  
Mackenzie J. Dodge ◽  
Peter Y. F. Zeng ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Head And Neck ◽  
Patient Survival ◽  
Tricarboxylic Acid Cycle ◽  
Predictive Biomarkers ◽  
Head And Neck Cancers ◽  
The Cancer Genome Atlas ◽  
Metabolic Genes ◽  
Hpv Status ◽  
The Impact

Human papillomavirus (HPV) causes an increasing number of head and neck squamous cell carcinomas (HNSCCs). Altered metabolism contributes to patient prognosis, but the impact of HPV status on HNSCC metabolism remains relatively uncharacterized. We hypothesize that metabolism-related gene expression differences unique to HPV-positive HNSCC influences patient survival. The Cancer Genome Atlas RNA-seq data from primary HNSCC patient samples were categorized as 73 HPV-positive, 442 HPV-negative, and 43 normal-adjacent control tissues. We analyzed 229 metabolic genes and identified numerous differentially expressed genes between HPV-positive and negative HNSCC patients. HPV-positive carcinomas exhibited lower expression levels of genes involved in glycolysis and higher levels of genes involved in the tricarboxylic acid cycle, oxidative phosphorylation, and β-oxidation than the HPV-negative carcinomas. Importantly, reduced expression of the metabolism-related genes SDHC, COX7A1, COX16, COX17, ELOVL6, GOT2, and SLC16A2 were correlated with improved patient survival only in the HPV-positive group. This work suggests that specific transcriptional alterations in metabolic genes may serve as predictive biomarkers of patient outcome and identifies potential targets for novel therapeutic intervention in HPV-positive head and neck cancers.

scholarly journals Patient-Derived Xenograft and Organoid Models for Precision Medicine Targeting of the Tumour Microenvironment in Head and Neck Cancer

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3743
Author(s):  
Tet Woo Lee ◽  
Amy Lai ◽  
Julia K. Harms ◽  
Dean C. Singleton ◽  
Benjamin D. Dickson ◽  
...  
Keyword(s):  
Head And Neck ◽  
Precision Medicine ◽  
Patient Survival ◽  
Predictive Biomarkers ◽  
Tumour Microenvironment ◽  
Response To Therapy ◽  
Preclinical Models ◽  
Therapeutic Success ◽  
Patient Derived Xenograft ◽  
Individualise Therapy

Patient survival from head and neck squamous cell carcinoma (HNSCC), the seventh most common cause of cancer, has not markedly improved in recent years despite the approval of targeted therapies and immunotherapy agents. Precision medicine approaches that seek to individualise therapy through the use of predictive biomarkers and stratification strategies offer opportunities to improve therapeutic success in HNSCC. To enable precision medicine of HNSCC, an understanding of the microenvironment that influences tumour growth and response to therapy is required alongside research tools that recapitulate the features of human tumours. In this review, we highlight the importance of the tumour microenvironment in HNSCC, with a focus on tumour hypoxia, and discuss the fidelity of patient-derived xenograft and organoids for modelling human HNSCC and response to therapy. We describe the benefits of patient-derived models over alternative preclinical models and their limitations in clinical relevance and how these impact their utility in precision medicine in HNSCC for the discovery of new therapeutic agents, as well as predictive biomarkers to identify patients’ most likely to respond to therapy.

scholarly journals The impact of non-pharmacological treatments for diseases of the locomotor system on the prescribed drug use and lifestyles of the patients in the sanatoria in Busko-Zdroj

2015 ◽  
Vol 28 (4) ◽  
pp. 273-277
Author(s):  
Milena Korczak ◽  
Jacek Owczarek
Keyword(s):  
Quality Of Life ◽  
Rheumatoid Arthritis ◽  
Drug Use ◽  
Pharmacological Treatments ◽  
Locomotor System ◽  
The Third ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
The Impact

Abstract The article is the result of research on the impact of non-pharmacological therapies for diseases of the locomotor system on the prescribed drug use and lifestyles of the patients of the sanatoria in Busko-Zdroj. The reported research uses primary and secondary measures. The former includes the assessment of the impact of non-pharmacological sanatorium treatments for locomotor system diseases on the use of prescribed drug regimes, while the latter is aimed at assessing the patients’ quality of life. The research was conducted on adult patients of both genders in the sanatoria in Busko-Zdroj. The subjects were patients suffering from disorders of the musculoskeletal system such as rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, osteoporosis and discopathies. The research included two visits, the first at the start of the research and the second at the end of the research. The patients were examined for a period of three consecutive weeks. The study involved 170 patients, 50% of them were women and 50% men. A decline in the use of painkillers and anti-inflammatory drugs makes a very interesting finding. After the first week, as many as 38% of the examined patients limited the use of painkillers and/or anti-inflammatory drugs. After the second week, 62% of the patients reduced the use of the drugs, and after the third week of treatment, up to 90% of the patients did so. The improvement of patients’ lives is noticeable in the psychological, physical and motor fields.

Evaluation of PIK3CA Mutation As a Predictor of Benefit From Nonsteroidal Anti-Inflammatory Drug Therapy in Colorectal Cancer

2013 ◽  
Vol 31 (34) ◽  
pp. 4297-4305 ◽  
Author(s):  
Enric Domingo ◽  
David N. Church ◽  
Oliver Sieber ◽  
Rajarajan Ramamoorthy ◽  
Yoko Yanagisawa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Pik3ca Mutation ◽  
Predictive Biomarker ◽  
Disease Recurrence ◽  
Primary Treatment ◽  
Optimal Regime ◽  
Pik3ca Mutations ◽  
Regular Aspirin ◽  
Anti Inflammatory ◽  
Reduced Rate

Purpose Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) protect against colorectal cancer (CRC) and are associated with reduced disease recurrence and improved outcome after primary treatment. However, toxicities of NSAIDs have limited their use as antineoplastic therapy. Recent data have suggested that the benefit of aspirin after CRC diagnosis is limited to patients with PIK3CA-mutant cancers. We sought to determine the predictive utility of PIK3CA mutation for benefit from both cyclooxygenase-2 inhibition and aspirin. Methods We performed molecular analysis of tumors from 896 participants in the Vioxx in Colorectal Cancer Therapy: Definition of Optimal Regime (VICTOR) trial, a large randomized trial comparing rofecoxib with placebo after primary CRC resection. We compared relapse-free survival and overall survival between rofecoxib therapy and placebo and between the use and nonuse of low-dose aspirin, according to tumor PIK3CA mutation status. Results We found no evidence of a greater benefit from rofecoxib treatment compared with placebo in patients whose tumors had PIK3CA mutations (multivariate adjusted hazard ratio [HR], 1.2; 95% CI, 0.53 to 2.72; P = .66; PINTERACTION = .47) compared with patients with PIK3CA wild-type cancers (HR, 0.87; 95% CI, 0.64 to 1.16; P = .34). In contrast, regular aspirin use after CRC diagnosis was associated with a reduced rate of CRC recurrence in patients with PIK3CA-mutant cancers (HR, 0.11; 95% CI, 0.001 to 0.832; P = .027; PINTERACTION = .024) but not in patients lacking tumor PIK3CA mutation (HR, 0.92; 95% CI, 0.60 to 1.42; P = .71). Conclusion Although tumor PIK3CA mutation does not predict benefit from rofecoxib treatment, it merits further evaluation as a predictive biomarker for aspirin therapy. Our findings are concordant with recent data and support the prospective investigation of adjuvant aspirin in PIK3CA-mutant CRC.

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