Partitioning of mesophyll conductance for CO2 into intercellular and cellular components using carbon isotope composition of cuticles from opposite leaf sides.

We suggest a new technique for estimating the relative drawdown of CO2 concentration (c) in the intercellular air space (IAS) across hypostomatous leaves (expressed as the ratio cd/cb, where the indexes d and b denote the adaxial and abaxial edges, respectively, of IAS), based on the carbon isotope composition (δ13C) of leaf cuticular membranes (CMs), cuticular waxes (WXs) or epicuticular waxes (EWXs) isolated from opposite leaf sides. The relative drawdown in the intracellular liquid phase (i.e., the ratio cc/cbd, where cc and cbd stand for mean CO2 concentrations in chloroplasts and in the IAS), the fraction of intercellular resistance in the total mesophyll resistance (rIAS/rm), leaf thickness, and leaf mass per area (LMA) were also assessed. We show in a conceptual model that the upper (adaxial) side of a hypostomatous leaf should be enriched in 13C compared to the lower (abaxial) side. CM, WX, and/or EWX isolated from 40 hypostomatous C3 species were 13C depleted relative to bulk leaf tissue by 2.01-2.85‰. The difference in δ13C between the abaxial and adaxial leaf sides (δ13CAB - 13CAD, Δb-d), ranged from - 2.22 to + 0.71‰ (- 0.09 ± 0.54‰, mean ± SD) in CM and from - 7.95 to 0.89‰ (- 1.17 ± 1.40‰) in WX. In contrast, two tested amphistomatous species showed no significant Δb-d difference in WX. Δb-d correlated negatively with LMA and leaf thickness of hypostomatous leaves, which indicates that the mesophyll air space imposes a non-negligible resistance to CO2 diffusion. δ13C of EWX and 30-C aldehyde in WX reveal a stronger CO2 drawdown than bulk WX or CM. Mean values of cd/cb and cc/cbd were 0.90 ± 0.12 and 0.66 ± 0.11, respectively, across 14 investigated species in which wax was isolated and analyzed. The diffusion resistance of IAS contributed 20 ± 14% to total mesophyll resistance and reflects species-specific and environmentally-induced differences in leaf functional anatomy.

[Coffee in Cancer Chemoprevention]. / Káva v chemoprevenci nádoru.

Coffee consumption is associated with a reduced risk of several diseases including cancer. Its chemopreventive effect has been studied in vitro, in animal models, and more recently in humans. Several modes of action have been proposed, namely, inhibition of oxidative stress and damage, activation of metabolizing liver enzymes involved in carcinogen detoxification processes, and anti-inflammatory effects. The antioxidant activity of coffee relies partly on its chlorogenic acid content and is increased during the roasting process. Maximum antioxidant activity is observed for medium-roasted coffee. The roasting process leads to the formation of several components, e.g., melanoidins, which have antioxidant and anti-inflammatory properties. Coffee also contains two specific diterpenes, cafestol and kahweol, which have anticarcinogenic properties. Roasted coffee is a complex mixture of various chemicals. Previous studies have reported that the chemopreventive components present in coffee induce apoptosis, inhibit growth and metastasis of tumor cells, and elicit antiangiogenic effects. A meta-analysis of epidemiological studies showed that coffee consumption is associated with a lower risk of developing various malignant tumors. This review summarizes the molecular mechanisms and the experimental and epidemiological evidence supporting the chemopreventive effect of coffee.Key words: coffee - chemoprevention - antioxidative enzyme - detoxification enzyme - anti-inflammatory effect The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 11. 9. 2016Accepted: 24. 11. 2016.

[Anticancer Effect of Fish Oil - a Fable or the Truth?]. / Protinádorový efekt rybího oleje -  mýtus, nebo realita?

Omega-3 fatty acids from fish oil have several health benefits for cancer patients. Recent findings indicate that, besides their well-known anti-cachectic effect, they can act synergistically with chemotherapeutic agents and may enhance tumor radio-sensitivity. The mechanisms underlying their anti-tumor effects are complex. The following effects have been reported after administration of omega-3 fatty acids: increased lipid peroxidation during therapy; disturbed tumor receptor signal pathways; lower levels level of pro-inflammatory cytokines that induce tumor cell proliferation; promotion of apoptosis in tumor tissues; immune modulation; and changes in hormonal metabolism. Epidemiological and experimental evidence support the conjecture that fish oil has an anticancer benefit for both animals and humans. However, Western countries have a diet rich in omega-6 fatty acids, which interfere with the health benefits of omega-3 fatty acids because they compete for the same rate-limiting enzymes. For this reason, the consumption of omega-6 fatty acids in Western diet needs to be lowered to observe the anti-tumor effect of omega-3 fatty acids. Some epidemiological studies report conflicting results, which may be explained by inconsistencies in the methodologies employed.

Epidermal growth factor receptor (EGFR) expression and mutations in the EGFR signaling pathway in correlation with anti-EGFR therapy in head and neck squamous cell carcinomas.

UNLABELLED: Epidermal growth factor receptor (EGFR) is an important therapeutic target and a poor prognosis factor in head and neck squamous cell carcinoma (HNSCC). The aim of the study was to analyze EGFR expression and KRAS and EGFR mutational status and to correlate it with treatment response to anti-EGFR therapy combined with radiotherapy in 29 patients with advanced head and neck squamous cell carcinomas (HNSCC).EGFR gene expression normalized to GAPDH and EGFR variant type III (EGFRvIII) was detected in tumor tissue using real time reverse transcription -PCR. The mutational status of the EGFR and KRAS genes was investigated by real time PCR with sequence specific primers.Gene expression median values were 3.1x10(8) GAPDH gene copies per µg of RNA, and 8x10(6) EGFR gene copies per µg of RNA. The median EGFR/GADPH ratio reached 0.14. Patients, who achieved complete response after Cetuximab combined with radiotherapy, had significantly higher expression of the EGFR gene in tumors than patients with partial remission or patient without treatment response. An EGFRvIII mutation was found in 20.7 % of patients and no association was found between this mutation and treatment response. 27 patients (93.1 %) had an EGFR gene wild type tumor, and deletion in exon 19 was found in two patients with a poor clinical outcome. Most of the patients (82.8%) had a KRAS wild type tumor; a p.Gly12Cys was found in three patients and a p.Gly12Val mutation in one. Presence of a p.Gly12Val mutation in the KRAS gene was associated with an absence of response to treatment. CONCLUSION: Our data suggest that KRAS mutation (p.Gly12Val) and somatic EGFR mutation located in exon 19 may contribute to the limited clinical response to therapy with cetuximab + radiotherapy. Higher EGFR gene expression serves as an independent indicator of good clinical response to EGFR-targeted therapy + radiotherapy.

[A growing problem--human papillomavirus and head and neck cancers]. / Rostoucí problém--lidský papilomavirus a nádory hlavy/krku.

High-risk human papillomavirus (HPV) are implicated in the development of a subset of head and neck cancers, especially those arising from the lingual or palatine tonsils. HPV-associated cancer of the head and neck represent a different disease entity from those associated with the traditional risk factors of tobacco and alcohol use. There has been as increase in the annual incidence of HPV-related cancers in Europe and USA in the past years. It has now become clear that a subset of the head and neck tumors is a sexually transmitted disease with distinct pathogenesis and clinical and pathological features. Research efforts are now focusing on deintensification of treatment to reduce treatment associated morbidity. The potential application of HPV targeted terapies in HPV associated cancers is an area of active research.

Mutations in EGFR signal pathway in correlation with response to treatment of head and neck cancers.

UNLABELLED: The prognostic and predictive value of the epidermal growth factor receptor (EGFR) expression and some genetic alterations in an EGFR signal pathway, such as the EGFR amplification, the EGFR activating tyrosine kinase domain mutations or the k-ras gene mutation were investigated in our study. The aim of the research was to evaluate the occurrence of the above-mentioned biomarkers in correlation with a therapeutic response and survival in patients with locoregionally advanced spinocellular head and neck cancers. KEYWORDS: Head and neck cancer, EGFR, predictive marker, k-ras, EGFR amplification, EGFR tyrosine kinase domain mutation.