217 research outputs found
Human epidermal growth factor receptor 2 as amolecular biomarker formetastatic colorectal cancer
[No abstract available
The Amount of Evidence Needed to Support ERBB2 as a Biomarker for Resistance to EGFR Inhibitors in Metastatic Colorectal Cancer
Integrating liquid biopsies into the management of cancer
During cancer progression and treatment, multiple subclonal populations of tumour cells compete with one another, with selective pressures leading to the emergence of predominant subclones that replicate and spread most proficiently, and are least susceptible to treatment. At present, the molecular landscapes of solid tumours are established using surgical or biopsy tissue samples. Tissue-based tumour profiles are, however, subject to sampling bias, provide only a snapshot of tumour heterogeneity, and cannot be obtained repeatedly. Genomic profiles of circulating cell-free tumour DNA (ctDNA) have been shown to closely match those of the corresponding tumours, with important implications for both molecular pathology and clinical oncology. Analyses of circulating nucleic acids, commonly referred to as 'liquid biopsies', can be used to monitor response to treatment, assess the emergence of drug resistance, and quantify minimal residual disease. In addition to blood, several other body fluids, such as urine, saliva, pleural effusions, and cerebrospinal fluid, can contain tumour-derived genetic information. The molecular profiles gathered from ctDNA can be further complemented with those obtained through analysis of circulating tumour cells (CTCs), as well as RNA, proteins, and lipids contained within vesicles, such as exosomes. In this Review, we examine how different forms of liquid biopsies can be exploited to guide patient care and should ultimately be integrated into clinical practice, focusing on liquid biopsy of ctDNA-arguably the most clinically advanced approach
Proteomic analysis of somatic embryogenesis in Vitis vinifera
Two dimensional gel electrophoresis coupled to mass spectrometry has been used to study the somatic embryogenesis in Vitis vinifera, by comparing embryogenic and non embryogenic calluses of the Thompson seedless cv. More than 1,000 spots were reproducibly resolved in colloidal Coomassie brilliant blue stained gels over a pI nonlinear range of 3-10 in the first dimension and using homogeneous 12.5% polyacrylamide gels in the second dimension. The expression pattern of 35 spots differed significantly between the two samples. These spots were processed by mass spectrometry analysis and the protein identity was assigned by using both the non-redundant protein and EST databases. Several responsive proteins, some already known to be involved in the somatic embryogenesis process while others, for the first time put into relation with this process, have been described. Moreover, they have been subdivided in functional categories, and their putative role is discussed in terms of their relevance in the somatic embryogenesis process
La Comorbidità e lAgire Medico: Il caso degli ipotrattamenti nella cura del tumore della mammella
When a physician has to come to a decision while caring for a given patient, he is supposed to take into account several kind of information related to the disease, illness or patients' personal characteristics. Although it is well known that the framework in which such decision has to be taken is complex, most of the scientific knowledge is based on pieces of evidence that derive from studies where complexity is avoided by applying restriction rules. The goal of this approach is to enhance the internal validity while preserving the generalisability of the findings. But in some cases this approach raises more doubts than certainty. It is the case of the process to assemble practice guidelines to reduce the gap between the best care and what is observed into practice using the available knowledge (i.e., available literature or experts' recommendations). As a variety of relevant clinical and patients' personal characteristics are not available at all or little is known on their impact on patients global health status, variables that actually do drive the practice are not included in guidelines that are intended to change it. This paper introduces the conceptual model of such debate and assesses the impact of co-morbidity--a variable seldom taken into account in effectiveness, quality and appropriateness studies- on the kind of medical care given to a sample of 1019 patients with early stage breast cancer. Empirical results and future implications are eventually discussed
Central Nervous System as Possible Site of Relapse in ERBB2-PositiveMetastatic Colorectal Cancer:Long-term Results of TreatmentWith Trastuzumab and Lapatinib
Central Nervous System as Possible Site of Relapse in ERBB2 -Positive Metastatic Colorectal Cancer: Long-term Results of Treatment with Trastuzumab and Lapatinib
This secondary analysis of data from the HERACLES-A clinical trial examines long-term outcomes in 32 patients with colorectal cancer treated with trastuzumab and lapatinib
Seagrass light acclimation: 2-DE protein analysis in Posidonia leaves grown in chronic low light conditions
Posidonia oceanica meadows are among the most valuable coastal systems in the Mediterranean basin. They
provide nursery and forage areas for many commercially important species, including juvenile mollusc,
finfish, and crustaceans. In the Mediterranean Sea, P. oceanica beds have recently suffered from progressive
die-offs attributed to lower light availability from elevated water turbidity. In order to understand adaptive
low-light responses of this seagrass, we compared the protein expression in plants collected from turbid
waters (low-light) with plants collected from pristine-clear waters (high-light). More than 2600 proteins
were detected in leaves from both sites. Among them, 26 proteins were differentially expressed in low-light
conditions, 12 of which were identified through MASCOT analyses. The remaining 14 proteins, did not receive
significant identity scores due to a lack of genomic and proteomic information in available databases.
Nevertheless, we observed a 30% down-regulation of RuBisCo large subunit in low-light acclimated leaves.
Whereas, enzymes involved in carbohydrate cleavage (1-fructose-bisphosphate aldolase, nucleoside
diphosphate kinase, and beta-amylase) were upregulated in low-light conditions. Electron microscopy
studies also revealed substantial changes in the stroma lamellae/grana ratios in chloroplasts receiving lowlight,
possibly as a mechanism for re-establishing optimal PSI/PSII ratios. Furthermore, under low-light
conditions, four components of the ubiquitin/mediated proteolysis pathway (26 S proteasome regulatory,
proteasome beta type 1, proteasome 7 D beta type, and proteasome alpha 7), and the perchloric acid soluble
translation inhibitor protein, were upregulated. This suggests that, in P. oceanica leaves, enhanced protein
turnover mediates acclimation to low-light conditions. Also, enzymes involved in defending against cellular
stress (superoxide dismutase, pyridoxine, and 2-caffeic-acido-methyl transferase) were differentially
expressed in low-light regime. Subsequent aquaria studies involving P. oceanica transplants maintained in
low- and high-light conditions, also demonstrate RuBisCo down-regulation and proteasomes upregulation in
low-light acclimated plants
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