Structure and sedimentation environment of the Silurian and Devonian boundary deposits in the west of Zeravshan-Gissar mountain region (Obi-Safit section, Kitab State Geological Reserve, Uzbekistan)

Continuous sequence of the boundary carbonate sediments of the Silurian and Devonian in the Ludford - Lochkov interval (Kupruk and lower part of Madmon Formation) have been studied in the Zeravshan-Gissars mountainous region of southern Tian-Shan, Kitab State Geological Reserve, Uzbekistan. The data comes from the stratotype section and some additional small sections in the Obi-Safit Gorge.The Kupruk Formation (Ludford-Pridolian) is composed of limestone and irregularly spotted dolomitic limestone containing numerous dilapidated bioherms, intraformational breccias, dolomite interlayers, siliceous connections. The lower part of the Madmon Formation (Lochkov) is represented by massive micritic and micritic-clotted limestones with coral and amphiporous biorstroms and rare carbonate breccias. Despite the abundance of organic remains, in the section there are no finds of biostratigraphic frames established for the standard boundary of the Silurian and Devonian due to zonal species of graptolites and conodonts which absents here in the border interval. The Obi-Safit section was analyzed from sedimentary, cyclostratigraphic and event-paleogeographic positions. Structural-genetic types of rocks have been established, their typification has been carried out, and the features of the Kupruk and Madmon biota have been studied. The characteristic of paleogeographic environments of precipitation formation is given. According to the intensity of the hydrodynamic effect on bottom, sedimentation rate and salinity of the bottom waters, complexes corresponding to the energy zones of the M. Irwin profile are distinguished: Y (predominantly high-dynamic, shallow water) and Z (mostly low-dynamic shallow water). In the section of Obi-Safit there are 12 transgress-regressive cyclothems 10 to 50 m thick. For the Kupruk Formation, an ideal cyclotema consisting of seven structural-genetic types of layers was reconstructed and paleogeographic model of their distribution was made. For the first time determinations and images of foraminifera and algae from this section are given. The Kupruk strata were formed in a basin with increased magnesium content and a frequent change in the hydrodynamic regime. Sedimentation took place with pauses, which were accompanied by exposure and drying of the bottom or its partial dissolution. The Madmon sequences accumulated under more stable environment with a relatively higher sea level standing in conditions of shallow normal marine sedimentation environments located below the base of the wave destruction. The maximum of the transgression within one cycle is determined by the presence of organogenic buildings, and the regression maximum is due to the appearance of carbonate conglomerate-breccias, dolomites and dolomitic limestones. The currently used Silurian and Devonian boundary in the Obi-Safit section is lolocated near 335 meters from the base of the section, but it has no a biostratigraphic and facies evidence. Due to the lack of biostratigraphic standard for this boundary, it is proposed to use the paleogeographic event traced in the west of the Zeravshan Range, although its accuracy is not of high grade. It is caused by the disappearance of isolation of this territory, the subsequent penetration of waters of an open sea basin and fixed by the presence of the numerous crinoid fragments in the upper part of the IX cyclotema. The first appearance of abundant fragments of crinoid stems is located on the 295 meter of the section

Molecular and pathological signatures of epithelial–mesenchymal transitions at the cancer invasion front

Reduction of epithelial cell–cell adhesion via the transcriptional repression of cadherins in combination with the acquisition of mesenchymal properties are key determinants of epithelial–mesenchymal transition (EMT). EMT is associated with early stages of carcinogenesis, cancer invasion and recurrence. Furthermore, the tumor stroma dictates EMT through intensive bidirectional communication. The pathological analysis of EMT signatures is critically, especially to determine the presence of cancer cells at the resection margins of a tumor. When diffusion barriers disappear, EMT markers may be detected in sera from cancer patients. The detection of EMT signatures is not only important for diagnosis but can also be exploited to enhance classical chemotherapy treatments. In conclusion, further detailed understanding of the contextual cues and molecular mediators that control EMT will be required in order to develop diagnostic tools and small molecule inhibitors with potential clinical implications

Prospective noninterventional study on the use of panitumumab monotherapy in patients with recurrent or progressive colorectal cancer: the VECTIS study

Radek Lakomy,1,2 Wojciech Rogowski,3 Bela Piko,4 Zhasmina Mihaylova,5 Eva Pritzova,6 Lucia Kvocekova7 1Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Brno, Czech Republic; 2Faculty of Medicine, Masaryk University, Brno, Czech Republic; 3Department of Chemotherapy, Warmia and Masuria Oncology Center, Olsztyn, Poland; 4Pándy Kálmán County Hospital, Gyula, Hungary; 5Department of Medical Oncology, Military Medical Academy, Sofia, Bulgaria; 6F.D. Roosevelt Teaching Hospital with Policlinic, Banska Bystrica, Slovak Republic; 7AMGEN s.r.o., Prague, Czech Republic Purpose: Epidermal growth factor receptor-targeted monoclonal antibodies are active as monotherapy beyond second-line treatment. Skin toxicities (STs) are common during treatment, and a positive association between ST severity and patient outcome has been reported. This study collected information on panitumumab monotherapy use in patients with KRAS exon 2 wild-type metastatic colorectal cancer in clinical practice.Methods: This open-label, prospective, observational, noninterventional study included adult patients who had failed prior chemotherapy with 5-fluorouracil, oxaliplatin, and irinotecan. Patients received panitumumab monotherapy (6 mg/kg every 2 weeks) for ≤18 cycles. Effectiveness was assessed as disease control rate (DCR), tumor response, and freedom from progression. The incidence of ST and other adverse drug reactions (ADRs) was recorded, as were Eastern Cooperative Oncology Group performance status (ECOG PS) and quality of life. The KRAS analysis process was also evaluated.Findings: The full analysis set included 632 patients (64.6% male; mean age, 62.3 years), who completed a mean of 9.6 panitumumab cycles. ST, mainly grade 1/2, occurred in 84.3% of patients, 82.7% of whom required treatment. Nonskin ADRs occurred in 3.5% of patients. By the end of treatment, the DCR was 58.9% overall, and was 53.8% and 62.7%, respectively in patients with ST grade 0/1 and grade 2/3. Significant associations were observed between maximum ST grade and best response (P=0.0009), DCR (P=0.0046), tumor response (P=0.0002), and freedom from progression (P=0.0084). At the end of the study, 67.4% of the patients had an ECOG PS of 0/1. Quality of life was rated as “very good” or “good” in 70.3% of patients. Mean time to obtain KRAS results was 18.2 days; satisfaction with different aspects of KRAS testing was "very good" or “good” in 80%–97% of patients.Conclusion: Panitumumab monotherapy showed adequate effectiveness and safety in patients with heavily pretreated KRAS exon 2 wild-type metastatic colorectal cancer. The most common ADR was grade 1/2 ST. Keywords: observational study, panitumumab, metastatic colorectal cancer, skin toxicity, KRA

Abstracts Of The Proceedings And The Posters From The Third Scientific Session Of The Medical College Of Varna

October 2-3, 201

AMP-Activated Protein Kinase: A Metabolic Stress Sensor in the Heart

International audienceAMP-activated protein kinase (AMPK) is a central cellular signaling hub that senses and responds to different kinds of stress, mainly those triggered by impaired cellular energy homeostasis. Since this is of major importance for the heart, the kinase plays important roles for cardiovascular function in human health and disease. Here, we review recent progress on the molecular structure and role of AMPK and summarize regulation and biological actions of the AMPK pathway, in particular those relevant for the heart. Activation of the kinase is involved in the myocardial response to ischemia, pressure overload, and heart failure. Pharmacological activation of AMPK may prove to be a useful therapeutic strategy in the treatment of these pathologies. (PDF) AMP-Activated Protein Kinase: A Metabolic Stress Sensor in the Heart. Available from: https://www.researchgate.net/publication/283756966_AMP-Activated_Protein_Kinase_A_Metabolic_Stress_Sensor_in_the_Heart [accessed Dec 10 2018]