2,442 research outputs found
Retrospective Proteomic Screening of 100 Breast Cancer Tissues
The present investigation has been conducted on one hundred tissue fragments of breast cancer, collected and immediately cryopreserved following the surgical resection. The specimens were selected from patients with invasive ductal carcinoma of the breast, the most frequent and potentially aggressive type of mammary cancer, with the objective to increase the knowledge of breast cancer molecular markers potentially useful for clinical applications. The proteomic screening; by 2D-IPG and mass spectrometry; allowed us to identify two main classes of protein clusters: proteins expressed ubiquitously at high levels in all patients; and proteins expressed sporadically among the same patients. Within the group of ubiquitous proteins, glycolytic enzymes and proteins with anti-apoptotic activity were predominant. Among the sporadic ones, proteins involved in cell motility, molecular chaperones and proteins involved in the detoxification appeared prevalent. The data of the present study indicates that the primary tumor growth is reasonably supported by concurrent events: the inhibition of apoptosis and stimulation of cellular proliferation, and the increased expression of glycolytic enzymes with multiple functions. The second phase of the evolution of the tumor can be prematurely scheduled by the occasional presence of proteins involved in cell motility and in the defenses of the oxidative stress. We suggest that this approach on large-scale 2D-IPG proteomics of breast cancer is currently a valid tool that offers the opportunity to evaluate on the same assay the presence and recurrence of individual proteins, their isoforms and short forms, to be proposed as prognostic indicators and susceptibility to metastasis in patients operated on for invasive ductal carcinoma of the breast
Proteomic profiling of 13 paired ductal infiltrating breast carcinomas and non-tumoral adjacent counterparts.
According to recent statistics, breast cancer remains one of the leading causes of death among women in Western countries. Breast cancer is a complex and heterogeneous disease, presently classified into several subtypes according to their cellular origin. Among breast cancer histotypes, infiltrating ductal carcinoma represents the most common and potentially aggressive form. Despite the current progress achieved in early cancer detection and treatment, including the new generation of molecular therapies, there is still need for identification of multiparametric biomarkers capable of discriminating between cancer subtypes and predicting cancer progression for personalized therapies. One established step in this direction is the proteomic strategy, expected to provide enough information on breast cancer profiling. To this aim, in the present study we analyzed 13 breast cancer tissues and their matched non-tumoral tissues by 2-DE. Collectively, we identified 51 protein spots, corresponding to 34 differentially expressed proteins, which may represent promising candidate biomarkers for molecular-based diagnosis of breast cancer and for pattern discovery. The relevance of these proteins as factors contributing to breast carcinogenesis is discussed
Differential occurrence of S100A7 in breast cancer tissues: A proteomic-based investigation
PURPOSE: The present study reports for the first time a large-scale proteomic screening of the occurrence, subcellular localization and relative quantification of the S100A7 protein among a group of 100 patients, clinically grouped for the diagnosis of infiltrating ductal carcinoma (IDC).
EXPERIMENTAL DESIGN: To this purpose, the methods of differential proteomics, Western blotting, and immunohistochemistry were used.
RESULTS: The identity of two isoforms of the protein was assessed by mass spectrometry and immunologically confirmed. Moreover, we proved by immunocytochemical applications the exclusive localization of the protein within the neoplastic cells. The correlation of S100A7 expression levels with the collective profile of cancer patients' proteomics predicted functional interactions, distinct for the two isoforms. The S100A7b isoform was significantly correlated with specific protein clusters (calcium binding, signaling and cell motion, heat shock and folding) and intercrossing pathways (antioxidant, metabolic and apoptotic pathways), while the more acidic isoform was correlated with a narrow number of proteins mainly unrelated to the b isoform.
CONCLUSIONS AND CLINICAL RELEVANCE: This study is the first proteomic-based report on S100A7 in a large series of IDC patients. The correlation with in silico data may significantly contribute the knowledge of possible pathways for S100A7, providing novel insights into the mechanism of action of this protein. We suggest that each S100A7 isoform is involved in critical phases of the breast cancer growth and progression, probably through interaction with different partner proteins
Proteomic Profiling of Colon Cancer Tissues: Discovery of New Candidate Biomarkers
Colon cancer is an aggressive tumor form with a poor prognosis. This study reports a comparative proteomic analysis performed by using two-dimensional differential in-gel electrophoresis (2D-DIGE) between 26 pooled colon cancer surgical tissues and adjacent non-tumoral tissues, to identify potential target proteins correlated with carcinogenesis. The DAVID functional classification tool revealed that most of the differentially regulated proteins, acting both intracellularly and extracellularly, concur across multiple cancer steps. The identified protein classes include proteins involved in cell proliferation, apoptosis, metabolic pathways, oxidative stress, cell motility, Ras signal transduction, and cytoskeleton. Interestingly, networks and pathways analysis showed that the identified proteins could be biologically inter-connected to the tumor-host microenvironment, including innate immune response, platelet and neutrophil degranulation, and hemostasis. Finally, transgelin (TAGL), here identified for the first time with four different protein species, collectively down-regulated in colon cancer tissues, emerged as a top-ranked biomarker for colorectal cancer (CRC). In conclusion, our findings revealed a different proteomic profiling in colon cancer tissues characterized by the deregulation of specific pathways involved in hallmarks of cancer. All of these proteins may represent promising novel colon cancer biomarkers and potential therapeutic targets, if validated in larger cohorts of patients
Timing performance of a double layer diamond detector
In order to improve the time precision of detectors based on diamonds sensors we have built a detector with two scCVD layers connected in parallel to the same amplifier. This work describes the design and the first measurements of such a prototype performed on a particle beam at CERN. With this different configuration we have obtained an improvement larger than a factor of 1.6-1.7 for the timing precision of the measurement when compared to a one layer scCVD diamond detector.Peer reviewe
LHC Optics Measurement with Proton Tracks Detected by the Roman Pots of the TOTEM Experiment
Precise knowledge of the beam optics at the LHC is crucial to fulfil the
physics goals of the TOTEM experiment, where the kinematics of the scattered
protons is reconstructed with the near-beam telescopes -- so-called Roman Pots
(RP). Before being detected, the protons' trajectories are influenced by the
magnetic fields of the accelerator lattice. Thus precise understanding of the
proton transport is of key importance for the experiment. A novel method of
optics evaluation is proposed which exploits kinematical distributions of
elastically scattered protons observed in the RPs. Theoretical predictions, as
well as Monte Carlo studies, show that the residual uncertainty of this optics
estimation method is smaller than 0.25 percent.Comment: 20 pages, 11 figures, 5 figures, to be submitted to New J. Phy
Double diffractive cross-section measurement in the forward region at LHC
The first double diffractive cross-section measurement in the very forward
region has been carried out by the TOTEM experiment at the LHC with
center-of-mass energy of sqrt(s)=7 TeV. By utilizing the very forward TOTEM
tracking detectors T1 and T2, which extend up to |eta|=6.5, a clean sample of
double diffractive pp events was extracted. From these events, we measured the
cross-section sigma_DD =(116 +- 25) mub for events where both diffractive
systems have 4.7 <|eta|_min < 6.5 .Comment: 5 pages, 1 figure, submitted for publicatio
Performance of the TOTEM Detectors at the LHC
The TOTEM Experiment is designed to measure the total proton-proton
cross-section with the luminosity-independent method and to study elastic and
diffractive pp scattering at the LHC. To achieve optimum forward coverage for
charged particles emitted by the pp collisions in the interaction point IP5,
two tracking telescopes, T1 and T2, are installed on each side of the IP in the
pseudorapidity region 3.1 < = |eta | < = 6.5, and special movable beam-pipe
insertions - called Roman Pots (RP) - are placed at distances of +- 147 m and
+- 220 m from IP5. This article describes in detail the working of the TOTEM
detector to produce physics results in the first three years of operation and
data taking at the LHC.Comment: 40 pages, 31 figures, submitted to Int. J. Mod. Phys.
Diamond Detectors for the TOTEM Timing Upgrade
This paper describes the design and the performance of the timing detector
developed by the TOTEM Collaboration for the Roman Pots (RPs) to measure the
Time-Of-Flight (TOF) of the protons produced in central diffractive
interactions at the LHC. The measurement of the TOF of the protons allows the
determination of the longitudinal position of the proton interaction vertex and
its association with one of the vertices reconstructed by the CMS detectors.
The TOF detector is based on single crystal Chemical Vapor Deposition (scCVD)
diamond plates and is designed to measure the protons TOF with about 50 ps time
precision. This upgrade to the TOTEM apparatus will be used in the LHC run 2
and will tag the central diffractive events up to an interaction pileup of
about 1. A dedicated fast and low noise electronics for the signal
amplification has been developed. The digitization of the diamond signal is
performed by sampling the waveform. After introducing the physics studies that
will most profit from the addition of these new detectors, we discuss in detail
the optimization and the performance of the first TOF detector installed in the
LHC in November 2015.Comment: 26 pages, 18 figures, 2 tables, submitted for publication to JINS
Production of monoclonal antibodies to Grapevine virus D and contribution to the study of its aetiological role in grapevine diseases
Six stable hybridoma cell lines secreting monoclonal antibodies (MAbs) to Grapevine virus D (GVD) were obtained by fusing spleen cells of immunized BALB/c mice with mouse myeloma cell line Sp 2/0-Ag 14, In ELISA all MAbs detected the virus in Nicotiana leaf extracts or cortical shavings from mature grapevine canes, The use of a polyclonal antiserum for coating plates and of monoclonal antibodies and antimouse-conjugated antibodies for antigen detection, gave highly efficient and reproducible results for identification of GVD in field-grown grapevines. The reliability of the ELISA kit was confirmed by GVD-transmission tests to herbaceous hosts, using in vitro explants as inoculum, 223 vines affected by one or more of the 4 syndroms of the rugose wood complex (Kober stem grooving, Corky bark, LN stem grooving and Rupestris stem pitting) were tested in ELISA for the detection of Grapevine virus A (GVA), Grapevine virus B (GVB) and GVD and by Western blot for the detection of Grapevine rupestris stem pitting associated virus (GRSPaV). The possible cause-effect relationship between GVA and KSG, GVB and Co, and GRSPaV and RSP was confirmed, but no consistent association was found between GVD and any of the 4 above syndromes, Intriguingly, a reduction in the expression of stem pitting symptoms in V. rupestris (from 90 % to 75 %) and of stem grooving symptoms in Kober 5BB (from 95 % to 70 %) was observed when vitiviruses and GRSPaV were contemporarily present in the same indicator. Preliminary data of a survey involving 676 grapevine samples showed a high incidence (31 %) of GVD, regardless of the geographical origin of samples.
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