«Salivaomics» of Different Molecular Biological Subtypes of Breast Cancer

The aim of the study was to determine the metabolic characteristics of saliva depending on the molecular biological subtype of breast cancer, as well as depending on the expression levels of HER2, estrogen receptors (ER), and progesterone receptors (PR). The study included 487 patients with morphologically verified breast cancer and 298 volunteers without breast pathologies. Saliva samples were obtained from all patients strictly before the start of treatment and the values of 42 biochemical indicators were determined. It has been established that the saliva of healthy volunteers and patients with various molecular biological subtypes of breast cancer differs in 12 biochemical indicators: concentrations of protein, urea, nitric oxide, malondialdehyde, total amino acid content, and activity of lactate dehydrogenase, alkaline phosphatase, gamma-glutamyltransferase, catalase, amylase, superoxide dismutase, and peroxidases. The saliva composition of patients with basal-like breast cancer differs from other subtypes in terms of the maximum number of indicators. Changes in biochemical indicators indicated an increase in the processes of lipid peroxidation and endogenous intoxication and a weakening of antioxidant protection, which correlates with the severity of the disease and the least favorable prognosis for this subtype of breast cancer. An analysis was made of the individual contribution of the expression level of HER2, estrogen, and progesterone receptors to changes in the biochemical composition of saliva. The HER2 (−)/HER2 (+) group, which should be considered as a single group, as well as ER-positive breast cancer, differ statistically significantly from the control group. For ER/PR-positive breast cancer, a more favorable ratio of saliva biochemical indicators was also noted compared to ER/PR-negative breast cancer.     

Doses of Ukrainian female clean-up workers with diagnosed breast cancer

The Chernobyl reactor accident in 1986 has caused significant exposure to ionizing radiation of the Ukrainian population, in particular clean-up workers and evacuees from the exclusion zones. A study aiming at the discovery of radiation markers of the breast cancer was conducted from 2008 to 2015 within a collaborative project by HZM, LMU, and NRCRM. In this study, post-Chernobyl breast cancer cases both in radiation-exposed female patients diagnosed at age less than 60 from 1992 to 2014 and in non-exposed controls matched for residency, tumor type, age at diagnosis, TNM classification as well as tumor grading were investigated for molecular changes with special emphasis to copy number alterations and miRNA profiles. Cancer registry and clinical archive data were used to identify 435 breast cancer patients among female clean-up workers and 14 among evacuees from highly contaminated territories as candidates for the study. Of these, 129 breast cancer patients fit study inclusion criteria and were traced for individual reconstruction of the target organ (breast) doses. The doses were estimated for 71 exposed cases (clean-up workers and evacuees from which biomaterial was available for molecular studies and who agreed to participate in a dosimetric interview) by the use of the well-established RADRUE method, which was adjusted specifically for the assessment of breast doses. The results of 58 female clean-up workers showed a large inter-individual variability of doses in a range of about five orders of magnitude: from 0.03 to 929 mGy, with median of 5.8 mGy. The study provides the first quantitative estimate of exposures received by female clean-up workers, which represent a limited but very important group of population affected by the Chernobyl accident. The doses of 13 women evacuated after the accident who did not take part in the clean-up activities (from 4 to 45 mGy with median of 19 mGy) are in line with the previous estimates for the evacuees from Pripyat and the 30-km zone.     

Joint Russian—Finnish study of radioactive contamination in the NW part of Lake Ladoga

In August 1992 a joint Russian-Finnish expedition was arranged to the NW part of Lake Ladoga to study radioactive contamination in the region. Special attention was paid to the area surrounding the Heinämaa Islands, where the wreck of the former mine carrier ship Kit had been lying about 30 years before it was moved to Novaya Zemlya in 1991. During this period the wreck had been used as a store for radioactive waste containing principally ⁹⁰Sr, ¹³⁷Cs and ^239,24OPu. Lake water, bottom sediment and some biological samples were collected for strontium, plutonium and gammaspectrometric analyses. In all the samples the radioactivity concentrations were very low, indicating radioactive contamination of about the same level as caused by global fallout in the 1960's and the Chernobyl fallout in the area. Only in two water samples taken close to the former site of the wreck slightly elevated ^239,240Pu concentrations were detected. The great water volume of Lake Ladoga and effective water exchange at the wreck site may explain the very low levels of radioactive wastes detected in the aquatic environment.     

Olive cultivation in the heart of the Persian Achaemenid Empire: new insights into agricultural practices and environmental changes reflected in a late Holocene pollen record from Lake Parishan,SW Iran

Ancient Persia witnessed one of its most prosperous cultural and socio-economic periods between 550 bc and ad 651, with the successive domination of the Achaemenid, Seleucid, Parthian and Sassanian Empires. During this period agricultural activities increased on the Iranian plateau, as demonstrated by a remarkable arboricultural expansion. However, available data are not very informative about the spatial organization of agricultural practices. The possible links between climate conditions and agricultural activities during this millennium of continuous imperial domination are also unclear, due to the lack of parallel human-independent palaeoclimatic proxies. This study presents a new late Holocene pollen-based vegetation record from Lake Parishan, SW Iran. This record provides invaluable information regarding anthropogenic activities before, during and after the empires and sheds light on (i) spatial patterning in agricultural activities and (ii) possible climate impacts on agro-sylvo-pastoral practices during this period. Results of this study indicate that arboriculture was the most prominent form of agricultural activity in SW Iran especially during the Achaemenid, Seleucid and Parthian periods. Contrary to the information provided by some Greco-Roman written sources, the record from Lake Parishan shows that olive cultivation was practiced during Achaemenid and Seleucid times, when olive cultivation was significant, at least in this basin located close to the capital area of the Achaemenid Empire. In addition, pollen from aquatic vegetation suggests that the period of the latter centuries of the first millennium bc was characterized by a higher lake level, which might have favoured cultural and socio-economic prosperity.     

Simple oxygraphic analysis for the presence of adenylate kinase 1 and 2 in normal and tumor cells

The adenylate kinase (AK) isoforms network plays an important role in the intracellular energy transfer processes, the maintenance of energy homeostasis, and it is a major player in AMP metabolic signaling circuits in some highly-differentiated cells. For this purpose, a rapid and sensitive method was developed that enables to estimate directly and semi-quantitatively the distribution between cytosolic AK1 and mitochondrial AK2 localized in the intermembrane space, both in isolated cells and tissue samples (biopsy material). Experiments were performed on isolated rat mitochondria or permeabilized material, including undifferentiated and differentiated neuroblastoma Neuro-2a cells, HL-1 cells, isolated rat heart cardiomyocytes as well as on human breast cancer postoperative samples. In these samples, the presence of AK1 and AK2 could be detected by high-resolution respirometry due to the functional coupling of these enzymes with ATP synthesis. By eliminating extra-mitochondrial ADP with an excess of pyruvate kinase and its substrate phosphoenolpyruvate, the coupling of the AK reaction with mitochondrial ATP synthesis could be quantified for total AK and mitochondrial AK2 as a specific AK index. In contrast to the creatine kinase pathway, the AK phosphotransfer pathway is up-regulated in murine neuroblastoma and HL-1 sarcoma cells and in these malignant cells expression of AK2 is higher than AK1. Differentiated Neuro-2a neuroblastoma cells exhibited considerably higher OXPHOS capacity than undifferentiated cells, and this was associated with a remarkable decrease in their AK activity. The respirometric method also revealed a considerable difference in mitochondrial affinity for AMP between non-transformed cells and tumor cells.