Introduction Excess release of catecholamines and prostaglandins has been shown to mediate pro-metastatic processes of stress and surgery, specifically during the critical perioperative period. Material and methods Here, in two randomised placebo controlled clinical trials in colorectal (CRC, n=34) and in breast cancer patients (BC, n=38), we tested the combined 20 day perioperative use of the b-blocker, propranolol, and the COX2-inhibitor, etodolac, initiated 5 days before surgery. Tumour samples were collected during surgery, and were subjected to histological analyses, whole genome mRNA profiling, and transcriptional control pathways analyses. In BC patients, four blood samples were also collected perioperatively. Results and discussions Drugs were well tolerated, with adverse effects equivalent to placebo. In blood samples, treatment reduced serum IL-6 and CRP levels even before surgery, improved markers of NK cytotoxicity, and enhanced induced production of IFNg and IL-12, without affecting anti-inflammatory soluble factors (cortisol and IL-10). In both studies, whole genome mRNA profiling of excised tumours showed decreased epithelial-to-mesenchymal transition (EMT); downregulation of the transcriptional activity of CREB, NFkB, GATA family, and STAT3; reduced presence of tumor-associated monocytes; and increased presence of NK cells in CRC and B cells in BC tissue. The tumour proliferation marker Ki67 was tested in BC patients, and was significantly reduced by drug treatment. In CRC patients, three-year follow-up showed large but statistically insignificant improvement in disease free survival (DFS) in the treatment group (1/15 vs 5/ 19), further suggesting the safety of the paradigm. Conclusion These findings suggest a critical impact to the short pre-operative period, clearly indicate the efficacy of this combined drug regimen, and suggest its metastatic-reducing impact, which should be tested in larger clinical trials. Such a stress-inflammatory-reducing approach can be exploited during the critical perioperative period, potentially improving longterm survival rates. Introduction Active areas of research in head and neck squamous cell carcinoma (HNSCC) include the identification of novel targets, exploration of resistance mechanisms to current therapies, and identification of combination strategies. Recent progress in molecular biology and translational research has initiated an era of personalised medicine in head and neck clinical oncology. The genetic information defined by biomarker analysis in tumours and individuals is indispensable for the administration of molecular targeting agents. PO-025Carcinogenesis is determined by various epigenetic events, such as histone deacetylation. Inhibition of histone deacetylase enzymes (HDACs) has been well documented as an attractive target for the development of chemotherapeutic drugs. The purpose of this study was to investigate the effects of Entinostat, an HDAC inhibitor, on cell viability and cell cycle in oral squamous cell carcinoma (OSCC) cell lines. Th...
This study was undertaken to compare the speech loudness discomfort levels (LDL's) with two instructional sets which have been proposed for saturation sound pressure level selection of hearing aids. The phraseology recommended by McCandless and by Berger was presented to normalhearins and hearing-impaired listeners. The normal-hearing subjects obtained mean LDL's of 94.6 and 11 1.9 dB SPL for these respective instructions, which was statistically significant. The hearing-impaired listeners also showed LDL's with Berger's instructions (1 14.7 dB SPL) to be significantly higher than with McCandless' instructional set (109.3 dB SPL). Consequently, this investigation suggests that these two instructional sets may lead to substantially different saturation sound pressure levels. Further studies are needed to determine the most appropriate phraseology for LDL measurement, including the assessment of speech intelligibility at various saturation sound pressure levels. Another instructional set was constructed which (1 )includes an explanation to patients of the purpose and importance of the test, (2) requests listeners to indicate the upper level they are "willing" to listen as opposed to the level they are "able" to listen, (3) instructs patients to search thoroughly around their LDL before making a final judgment, and (4) contains a statement that the LDL should be made with the undgrstanding that the speech could be listened to for a period of time. Whatever instructions are used, clinicians are advised to interpret their LDL's very cautiously until validational studies are available.
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