Salivary microRNAs identified by small RNA sequencing as potential predictors of response to intensity-modulated radiotherapy in head and neck cancer patients.

PURPOSE: Progress in radiation therapy of head and neck squamous cell carcinomas (HNSCCs) is logically linked to the development of molecular predictors that would help to enhance individually tailored treatment. MicroRNA (miRNA) expression profiles in tumors have repeatedly been tested to optimize the molecular diagnostics of HNSCC. In addition to tumor tissues, miRNAs are stably present in body fluids, including saliva, and can thus be collected non-invasively. The aim of our current study was to evaluate whether salivary miRNAs have potential as response predictors in HNSCC patients treated with intensity modulated radiation therapy (IMRT). METHODS: In total 48 HNSCC patients treated by definitive IMRT were enrolled in our prospective study. To identify predictive salivary miRNAs, we used small RNA sequencing in 14 saliva samples of HNSCC patients and qRT-PCR validation of selected miRNA candidates in an independent set of 34 patients. RESULTS: We found that salivary miR-15a-5p and miR-15b-5p exhibited differential levels between patients with and without complete remission (p = 0.025 and p = 0.028, respectively). Subsequent Kaplan-Meier analysis confirmed that patients with higher levels of miR-15a-5p reached a significantly longer locoregional progression-free survival (LPFS) than those with low levels (p = 0.024). Finally, multivariate Cox regression analysis revealed that miR-15a-5p may serve as an independent predictive biomarker of LPFS in HNSCC patients treated with IMRT (HR 0.104; 95% CI 0.004-0.911; p = 0.04). CONCLUSIONS: We conclude that salivary miR-15a-5p may represent a potential biomarker for individualized treatment decision-making in HNSCC patients.

Immunostimulatory and anticancer effect of Reishi and Coriol extracts at the level of clinical studies and their implementation in practice.

BACKGROUND: Mushrooms Reishi and Coriolus have been used for centuries in Asian countries to treat various diseases, mainly respiratory tract infections or pulmonary diseases, and more recently also cancers. Polysaccharides and triterpenes, which are found in these mushrooms, are their main bio-active components. Preclinical and clinical studies in humans presented their beneficial effects as immunomodulators; besides this, they possess a direct anticancer effect. In Asia, they are used after cancer treatment as single agents or in combination with chemotherapy or radiotherapy. Extracts from Coriolus have been approved for more than 30 years as an effective adjuvant addition to standard cancer treatment in Japan and China without obvious toxicity. PURPOSE: In this review, clinical studies with Reishi and Coriolus in cancer patients and their meta-analyses are briefly summarized. CONCLUSION: Both extracts from Reishi and Coriolus, if used in combination with standard therapy or as an adjuvant single agent, have shown benefits at immune function measures, tumor-related symptoms and performance status of cancer patients. Moreover, they have prolonged their disease-free interval and overall survival. They are well tolerated even in advanced cancer diseases and could be safely used continuously for long periods of time. Because of clinically approved efficacy and safety, they are applied mainly in some countries as a complementary therapy for various types of cancers.

Prognostic Significance of Serum Free Amino Acids in Head and Neck Cancers.

Despite distinctive advances in the field of head and neck squamous cell cancer (HNSCC) biomarker discovery, the spectrum of clinically useful prognostic serum biomarkers is limited. As metabolic activities in highly proliferative transformed cells are fundamentally different from those in non-transformed cells, specific shifts in concentration of different metabolites may serve as diagnostic or prognostic markers. Blood amino acids have been identified as promising biomarkers in different cancers before, but little is known about this field in HNSCC. Blood amino acid profiles of 140 HNSCC patients were examined using high-performance liquid chromatography. Cox proportional hazards regression model was used to assess the prognostic value of amino acid concentrations in serum. Colony forming assay was used to identify the effect of amino acids that were significant in Cox proportional hazards regression models on colony forming ability of FaDu and Detroit 562 cell lines. In the multivariable Cox regression model for overall survival (OS), palliative treatment was associated with an unfavourable prognosis while high serum levels of methionine have had a positive prognostic impact. In the relapse-free survival (RFS) multivariable model, methionine was similarly identified as a positive prognostic factor, along with tumor localization in the oropharynx. Oral cavity localization and primary radio(chemo)therapy treatment strategy have been linked to poorer RFS. 1mM serine was shown to support the forming of colonies in both tested HNSCC cell lines. Effect of methionine was exactly the opposite.

MicroRNA-15b-5p Predicts Locoregional Relapse in Head and Neck Carcinoma Patients Treated With Intensity-modulated Radiotherapy.

BACKGROUND/AIM: Head and neck cancers are a heterogenous group of epithelial tumors represented mainly by squamous cell carcinomas (HNSCC), which are the sixth most common type of cancer worldwide. Surgery together with radiotherapy (RT) is among the basic treatment modalities for most HNSCC patients. Various biomarkers aiming to predict patients' response to RT are currently investigated. The reason behind this effort is, on one hand, to distinguish radioresistant patients that show weak benefit from RT and, on the other hand, reduce the ionizing radiation dose in less aggressive radiosensitive HNSCC with possibly less acute or late toxicity. MATERIALS AND METHODS: A total of 94 HNSCC patients treated by definitive intensity-modulated radiotherapy were included in our retrospective study. We used a global expression analysis of microRNAs (miRNAs) in 43 tumor samples and validated a series of selected miRNAs in an independent set of 51 tumors. RESULTS: We identified miR-15b-5p to be differentially expressed between patients with short and long time of locoregional control (LRC). Kaplan-Meier analysis confirmed that HNSCC patients with higher expression of miR-15b-5p reach a significantly longer locoregional relapse-free survival compared to patients expressing low levels. Finally, multivariable Cox regression analysis revealed that miR-15b-5p is an independent predictive biomarker of LRC in HNSCC patients (HR=0.25; 95% CI=0.05-0.78; p<0.016). CONCLUSION: miR-15b-5p represents a potentially helpful biomarker for individualized treatment decisions concerning the management of HNSCC patients.

Expression of CD44, EGFR, p16, and their mutual combinations in patients with head and neck cancer: Impact on outcomes of intensity-modulated radiation therapy.

BACKGROUND: Progress in radiation treatment of head and neck squamous cell carcinoma (HNSCC) deserves the studies focused on molecular predictors that would help to enhance individually tailored treatment. METHODS: p16/epidermal growth factor receptor (EGFR)/cluster of differentiation-44 (CD44) was immunohistochemically analyzed in 165 HNSCC patients. RESULTS: In the entire group and the p16 negative cohort, better 3-year overall survival and locoregional control correlated with p16 positivity, CD44, and EGFR negativity were observed. Combined analysis revealed the worst results in the CD44+/p16-, EGFR+/p16-, and EGFR+/CD44+ groups and in the EGFR+/CD44+ within p16 negative cohort. Multivariate analysis found tumor stage, Karnofsky index, p16, and CD44 as prognostic factors of overall survival and clinical stage, and p16 as a prognostic factor for locoregional control. Clinical stage and Karnofsky index affected overall survival and tumor stage. EGFR affected locoregional control in the p16 negative subgroup. CONCLUSION: Our study confirmed the negative effect of CD44 and EGFR and the positive effect of p16 on radiotherapy results.

Prognostic impact of combined immunoprofiles in oropharyngeal squamous cell carcinoma patients with respect to AJCC 8th edition.

OBJECTIVES: To examine combined immunoprofiles of epidermal growth factor receptor (EGFR), CD44, and p16 in oropharyngeal squamous cell carcinoma (OPSCC) and to correlate them with radiotherapy treatment outcomes and clinicopathological parameters. Prognostic impact of the American Joint Committee on Cancer (AJCC) 8th edition staging system in comparison with 7th edition was analyzed. METHODS: The study included 77 OPSCC patients treated by definitive intensity-modulated radiotherapy (IMRT). Clinical staging was assessed according to the AJCC, both 7th and 8th edition. Immunohistochemical (IHC) analysis of CD44 and EGFR was performed on primary biopsy tumor tissues. To evaluate the HPV status, IHC detection of p16 was employed. RESULTS: The AJCC 8th edition staging system revealed correlations between overall survival (OS), progression-free survival (PFS), locoregional control (LRC), and clinical stage. EGFR and CD44 positivity (+) and p16 negativity (-) were associated with clinical stage IV of the disease. CD44+ and EGFR+ OPSCC displayed worse OS and LRC, and these cases also showed the worst 3-year OS and LRC. Combined analysis of protein expressions identified an association between p16- and EGFR+, p16- and CD44+, EGFR+, and CD44+. Combined immunoprofiles CD44+/p16-, EGFR+/p16-, and EGFR+/CD44+ were associated with worst OS and LRC. CONCLUSIONS: Combined immunoprofiles of p16, EGFR, and CD44 might provide valuable prognostic and predictive information for the individual OPSCC patients, especially in terms of response to IMRT and prediction of treatment outcomes. Application of the AJCC 8th edition staging for HPV+ OPSCC proved to improve hazard discrimination and prognostication of OPSCC.

[Sore throat treatment]. / Lécba bolesti v hrdle.

The article deals with sore throat, gives definition of acute and chronic pain and describes their causes. Further describes possibilities of diagnosis with regard to differential diagnosis. Special attention is focused on differentiation between viral and streptococcal infection. Accented is the necessity of causal treatment and possibilities of supportive local treatment.Key words: sore throat, sore throat causes, sore throat diagnosis, causal treatment, local supportive treatment.

MicroRNAs Involvement in Radioresistance of Head and Neck Cancer.

Resistance to the ionizing radiation is a current problem in the treatment and clinical management of various cancers including head and neck cancer. There are several biological and molecular mechanisms described to be responsible for resistance of the tumors to radiotherapy. Among them, the main mechanisms include alterations in intracellular pathways involved in DNA damage and repair, apoptosis, proliferation, and angiogenesis. It has been found that regulation of these complex processes is often controlled by microRNAs. MicroRNAs are short endogenous RNA molecules that posttranscriptionally modulate gene expression and their deregulated expression has been observed in many tumors including head and neck cancer. Specific expression patterns of microRNAs have also been shown to predict prognosis and therapeutic response in head and neck cancer. Therefore, microRNAs present promising biomarkers and therapeutic targets that might overcome resistance to radiation and improve prognosis of head and neck cancer patients. In this review, we summarize the current knowledge of the functional role of microRNAs in radioresistance of cancer with special focus on head and neck cancer.

[Can fish oil improve wound healing in surgery?]. / Dokáze rybí olej zlepsit hojení ran v chirurgii?

UNLABELLED: A surgical insult induces both local and systemic inflammatory responses which, if inappropriate, could impair wound healing. According to many studies ω-3 polyunsaturated fatty acids from fish oil improve the process of wound healing by their immunomodulatory effect. In contrast to current anti-inflammatory drugs, which could alter immune defence and impair the resolution of inflammation, ω-3 fatty acids have a simultaneous anti-inflammatory pro-resolution effect which is not immunosuppressive. Besides that they improve cicatrix quality. With regard to this effect they prevent excessive or prolonged inflammation and wound complications. KEY WORDS: anti-inflammatory agent - cicatrix - fish oil - macrophage - ω-3 fatty acid - resolution of inflammation - Toll-like receptor - wound healing.

[Importance of taste in maintaining homeostasis and pathological impact of orosensory reflexes distraction in relation to sweet taste after non-caloric sweeteners consumption]. / Význam chuti v udrzení homeostázy organizmu a patologický dopad vyrusení orocefalických reflexu ve vazbe na sladkou chut v následku konzumace nekalorických sladidel.

Taste signals and their reflexes have important signalling function in nature. They protect organism against toxic substances in food with help of taste aversion, they help to cope nutrition deficiencies through taste preferences, on the other hand, they act in many postprandial reflexes to maintain energy homeostasis. It is well-known that sweet taste is important oro-sensory stimulus for mammals. It acts as predictor of caloric food intake even before its entry into stomach and circulation. Taste and other oro-sensory signals from oral cavity affect not only the intake regulation, but also influence hormonal, neural and metabolic pathways to maintain homeostasis. The aim is to utilize effectively food energy and prevent energy instability of organism. Oro-sensory reflexes mediated by taste cells develop naturally from the first contact with sweet breast milk in infancy. It has been proven that the attenuation of reflexes due to the use of artificial sweeteners that don´t bring any caloric value to human body leads to hormonal and energetic dysregulation of organism and may contribute to metabolic syndrome.