Early diagnosis of liver cancer: an appraisal of international recommendations and future perspectives

AbstractAll Societies, AASLD, EASL, APASL and JSH, identify patients with cirrhosis as a target population for surveillance, with minor differences for additional categories of patients, such as chronic hepatitis B and hepatitis C patients with advanced fibrosis. According to AASLD, liver disease related to metabolic diseases including diabetes and obesity is a recognized target of screening, since those conditions have been causally related to HCC. All societies endorse radiological non‐invasive techniques as the mainstay for early diagnosis of HCC, but discrepancies exist between Societies on the utilization of contrast‐enhanced ultrasound and utilization of serum markers for surveillance and diagnosis of HCC. The diagnostic algorithm of the international societies differ substantially in the anatomic paradigm of EASL and APASL which identify 1 cm size as the starting point for radiological diagnosis of HCC compared to APASL algorithm based on the dynamic pattern of contrast imaging, independently on tumour size. While strengthening prediction in individual patients is expected to improve cost‐effectiveness ratios of screening, the benefits of pre‐treatment patient stratification by clinical, histological and genetic scores remain uncertain and exclusion of patients with severe co‐morbidities and advanced age is still debated

Gigantomastia During Pregnancy Due to Burkitt Lymphoma

Gigantomastia is a rare complication of pregnancy usually associated with benign conditions and rarely with malignancies. This paper reports a non-Hodgkin lymphoma case associated with gigantomastia during pregnancy. The patient was a 30-year-old gravida one woman, with a history of rapidly enlarging right breast at 2 weeks prior to presentation. After the first diagnosis of benign gigantomastia, the continuous growth of the breast, despite the delivery and bromocriptine therapy, required further investigation of the case. The histological analysis revealed the presence of Burkitt lymphoma. Malignant causes of unilateral gigantomastia in pregnancy should be considered in the differential diagnosis of this condition

BC-SIM-TR-032 HRIC ICO4 REPORT

The present document has been issued to describe the Instrument Check Out Phase (ICO#4) Tests of HRIC, channel of the Spectrometers and Imagers for MPO BepiColombo Integrated Observatory SYStem (SIMBIO-SYS)

ATM inhibition blocks glucose metabolism and amplifies the sensitivity of resistant lung cancer cell lines to oncogene driver inhibitors

Background: ATM is a multifunctional serine/threonine kinase that in addition to its well-established role in DNA repair mechanisms is involved in a number of signaling pathways including regulation of oxidative stress response and metabolic diversion of glucose through the pentose phosphate pathway. Oncogene-driven tumorigenesis often implies the metabolic switch from oxidative phosphorylation to glycolysis which provides metabolic intermediates to sustain cell proliferation. The aim of our study is to elucidate the role of ATM in the regulation of glucose metabolism in oncogene-driven cancer cells and to test whether ATM may be a suitable target for anticancer therapy. Methods: Two oncogene-driven NSCLC cell lines, namely H1975 and H1993 cells, were treated with ATM inhibitor, KU55933, alone or in combination with oncogene driver inhibitors, WZ4002 or crizotinib. Key glycolytic enzymes, mitochondrial complex subunits (OXPHOS), cyclin D1, and apoptotic markers were analyzed by Western blotting. Drug-induced toxicity was assessed by MTS assay using stand-alone or combined treatment with KU55933 and driver inhibitors. Glucose consumption, pyruvate, citrate, and succinate levels were also analyzed in response to KU55933 treatment. Both cell lines were transfected with ATM-targeted siRNA or non-targeting siRNA and then exposed to treatment with driver inhibitors. Results: ATM inhibition deregulates and inhibits glucose metabolism by reducing HKII, p-PKM2Tyr105, p-PKM2Ser37, E1α subunit of pyruvate dehydrogenase complex, and all subunits of mitochondrial complexes except ATP synthase. Accordingly, glucose uptake and pyruvate concentrations were reduced in response to ATM inhibition, whereas citrate and succinate levels were increased in both cell lines indicating the supply of alternative metabolic substrates. Silencing of ATM resulted in similar changes in glycolytic cascade and OXPHOS levels. Furthermore, the driver inhibitors amplified the effects of ATM downregulation on glucose metabolism, and the combined treatment with ATM inhibitors enhanced the cytotoxic effect of driver inhibitors alone by increasing the apoptotic response. Conclusions: Inhibition of ATM reduced both glycolytic enzymes and OXPHOS levels in oncogene-driven cancer cells and enhanced apoptosis induced by driver inhibitors thus highlighting the possibility to use ATM and the driver inhibitors in combined regimens of anticancer therapy in vivo

BC-SIM-TR-025 HRIC ICO3 REPORT

The present document has been issued to describe the Instrument Check Out Phase (ICO#3) Tests of HRIC, channel of the Spectrometers and Imagers for MPO BepiColombo Integrated Observatory SYStem (SIMBIO-SYS)

BC-SIM-TR-028 SIMBIO-SYS ICO#03 Interchannel Test Report

This document contains the results and the discussion on the interchannel test performed during the Instrument Check Out Phase (ICO#3) of the Spectrometers and Imagers for MPO BepiColombo Integrated Observatory SYStem (SIMBIO-SYS)

A Mercury surface radiometric model for SIMBIO-SYS instrument suite on board of BepiColombo mission

The BepiColombo mission represents the cornerstone n.5 of the European Space Agency (ESA) and it is composed of two satellites: the Mercury Planetary Orbiter (MPO) realized by ESA and the Mercury Magnetospheric Orbiter (MMO) provided by the Japan Aerospace Exploration Agency (JAXA). The payload of the MPO is composed by 11 instruments. About half of the entire MPO data volume will be provided by the Spectrometer and Imagers for MPO BepiColombo Integrated Observatory System" (SIMBIO-SYS) instrument suite. The SIMBIO-SYS suite includes three imaging systems, two with stereo and high spatial resolution capabilities, which are the Stereoscopic Imaging Channel (STC) and High Resolution Imaging Channel (HRIC), and a hyper-spectral imager in the Vis-NIR range, named Visible and near Infrared Hyper-spectral Imager (VIHI). In order to test and predict the instrument performances, a radiometric model is needed. It consists in a tool that permits to know what fraction of the incoming light is measured by the detector. The obtained signal depends on the detector properties (such as quantum efficiency and dark current) and the instrument transmission characteristics (transmission of lenses and filter strips, mirrors reflectivity). The radiometric model allows to correlate the radiance of the source and the signal measured by each instrument. We used the Hapke model to obtain the Mercury reflectance, and we included it in the radiometric model applied to the STC, HRIC and VIHI channels. The radiometric model here presented is a useful tool to predict the instruments performance: it permits to calculate the expected optical response of the instrument (the position in latitude and longitude of the filter footprints, the on-ground px dimensions, the on-ground speed, the smearing and the illumination angles of the observed points), and the detector behavior (the expected signal and the integration time to reach a specific SNR). In this work we derive the input flux and the integration times for the three channels of SIMBIO-SYS, using the radiometric model to obtain the source radiance for each Mercury surface area observed

BC-SIM-PL-006 SIMBIO-SYS Checkout#04 Test Summary

In this document we describe all the tests to be performed during the Instrument CheckOut (ICO) # 04 for the Spectrometers and Imagers for MPO BepiColombo Integrated Observatory SYStem (SIMBIO-SYS)

BC-SIM-TN-013 STC Inflight Dark Calibration

In this document, we reported the history of the tests performed on the STC detector in the first two years of the BepiColombo’s cruise phase. The scope of these tests was to monitor the dark current behavior of the STC channel’s detector. A detailed description is provided for each test phase: data acquired, the deducted results and conclusions. The STC Channel is part of SIMBIO-SYS, a scientific payload of the BepiColombo ESA-JAXA mission to Mercury. During the NECP (Near-Earth Commissioning Phase ), all the initial commissioning activities were completed and the three channels of SIMBIO-SYS have operated properly demonstrating that all the channels and subsystems worked nominally. Since then, every six months different instrument checkouts have been carried-out to check the performance of the three SIMBIO-SYS channels and improve their calibration. This document reports the conclusion on the Dark calibration of STC Channel due to the analysis of the ICOs tests

SIMBIO-Sim: a performance simulator for the SIMBIO-SYS suite on board the BepiColombo mission

The SIMBIO-SYS simulator is a useful tool to test the instrument performance and to predict the instrument behaviour during the whole scientific mission. It has been developed with Interactive Data Language (IDL), and it give three groups of output data: i) the geometrical quantities related to the spacecraft and the channels, which include both the general information about the spacecraft and the information for each filter; ii) the radiometric outputs, which include the planet reflectance, the radiance and the expected signal measured by the detector; iii) the quantities related to the channel performance, which are for example the integration time (IT), which has to be defined to avoid the detector saturation, the expected dark current of the detector