87,734 research outputs found
Le informazioni sul Paese d'origine e la garanzia del contraddittorio
No full textNell’ambito della protezione internazionale dello straniero una delle problematiche più
rilevanti attiene alla dimostrazione dei presupposti necessari per ottenere il riconoscimento dello
status di rifugiato o di protezione sussidiaria, tra cui il fondato timore «di essere perseguitato» o di
correre «il rischio di subire un grave danno», ai sensi del d.leg. n. 251 del 2007, di attuazione della
Direttiva 2004/83/CE. Accertamenti che possono rivelarsi complessi in quanto è «la situazione
particolare dello straniero in casi di tale specie» che «esclude quasi sempre a priori che lo stesso
possa fornire tramite documenti o anche solo tramite testimoni la prova diretta di tali fatti costitutivi
del suo diritto». Cosicché, specie nella fase istruttoria del procedimento giurisdizionale, è il giudice
che incardina un ruolo rilevante nel relativo accertamento del diritto la cui prova sarà data
prevalentemente per presunzioni raffrontando il racconto della parte con le informazioni, aggiornate
e precise, sulla situazione del Paese di origine di quest’ultima. Il giudice, infatti, non è tenuto a
servirsi solo del materiale istruttorio offerto dalla parte e potrà assumere direttamente le cosiddette
COI (Country of origin information), risultando così titolare di un vero e proprio potere-dovere di
cooperare con il richiedente nell’accertamento del suo diritto
Herceptin-resistance in breast cancer cells: a proteomic study.
No full textHER-2 is a cell membrane protein that belongs to the ErbB family of receptor tyrosine kinases (HER-1, HER-2, HER-3, HER-4). The over-expression of HER-2, which results in the 25-30% of breast cancer patients, is considered a predictive and prognostic marker for breast cancer malignancy and invasiveness and makes HER-2 an excellent therapeutic target.
In the last years new therapeutic strategies have been improved in order to better deal tumor diseases an to minimize collateral effects due to classic chemotherapy in patients.
In this way, a new approach was the somministration of humanized antibodies directed against tumor-associated molecular targets. Among these ones Herceptin, an anti-neoplastic humanized monoclonal antibody (Herceptin®, Roche, CH), has been shown to be active against breast cancer cells over-expressing HER-2 receptor.
Unfortunately the initial response to Herceptin-based regimens is followed by drug-resistance occurring within 1 year in the majority of patients. Thus it becomes critical to understand the molecular mechanisms underlying primary or acquired Herceptin resistance in order to improve the survival of breast cancer patients whose tumors overexpress HER2.
On these bases, we focused our attention to investigate the effects caused by Herceptin treatment on SK-BR-3 breast cancer cells, which overexpress HER-2. To obtain drug-resistant cells, SK-BR-3 were treated with 10 μgr/ml of drug, until cells growth rate became synchronous compared to untreated parental cells. Parental and resistant cells were then properly collected and subjected to cell-lysis to obtain protein extracts, while respective conditioned media were harvested to perform analyses of cell-released gelatinolic activities, such as MMP-2 and MMP-9. These investigations are justified by previous observation of our group, showing a certain degree of correlation between gelatinase expression and HER-2 overexpression in vivo [1]. Protein extracts were subjected to IPG-2D electrophoresis, firstly to evaluate proteomic profiles of both resistant and parental cells, secondly to detect differentially expressed proteins in two above mentioned experimental conditions and thirdly to identify new Herceptin-resistance related proteins by means of MALDI-TOF mass spectrometry. The results so far obtained, have shown that prolonged Herceptin treatment induces dramatic changes in malignant resistant cells, such as rearrangement of cytoskeletal structures, evident effects on expression of proteins involved in cytoskeleyton remodelling, metabolic processes, stress responses and cell cycle and proliferation control. We suggest that present data may contribute significantly to the knowledge of the mechanisms underlying Herceptin drug resistance on breast cancer cells.
[1]La Rocca, G., Pucci-Minafra, I., Marrazzo, A., Taormina, P. & Minafra, S. 2004. British Journal of Cancer, 90: 1414-1421
Correlation between clinical and radiographic classification of osteoarthritis and SNPs linked to osteoarthritis susceptibility
No full textGene ontology-based annotation and comparative analysis of proteins extracted from proteomics of 100 breast cancer patients.
No full textBackground: Current clinical parameters for breast cancer diagnosis and therapy are: tumour size, axillary lymph node status, histological grading and presence or absence of metastases. Prognostic/predictive properties, such as oestrogen and progesterone receptor status, and human epidermal growth factor receptor (HER-2/neu) status are currently used for therapeutic decision. Conversely, it is now emerging that the number of genetic mutations and epigenetic deregulations in cancer is far more higher than previously thought. Therefore, proteomic screening for differential protein expression in subsets of tumor samples is an essential tool for generating data bases and biomarker discovery. The aim of present study was to extend to a significant number of proteins and patients our previous data, contributing to the knowledge of biological pathways involved in breast cancer and to the molecular-based classification of breast cancer patients.
Methods: Aliquots of breast cancer tissues and their adjacent non-tumoral tissues were obtained during surgical intervention from patients who did not receive any neoadiuvant therapy. Diagnosis of ductal infiltrating breast cancer (DIC) was confirmed by histopathology. Sample preparation for proteomics was performed as described (Pucci-Minafra et al. Proteomics Clinical Applications, 1, 118-129, 2007; Pucci-Minafra et al. Journal of Proteome Research 7, 1412-18, 2008). Quantitative determination of protein spots was normalized for actin.
Results: We have collected for the present study 100 proteomic maps from G2/G3-DIC patients, and 13 from non-tumoral mammary tissues. All detected proteins were identified, or confirmed, by mass spectrometry. Collectively we have annotated 209 protein spots, corresponding to 122 genes. Genes were analyzed by the instruments of DAVID Bioinformatics Resources (Dennis et al. 2003; Huang et al. 2009). The Gene Accession Conversion tool recognized 112 unambiguous Gene IDs, over the 122 ones present in our list. The gene list was correlated to 136 functional terms, but only 36 correlations were highly significant (Benjamini values from 1x10-8 to 5.6 x10-3). Nine terms over the 36 corresponded to the function of apoptotic processes and in particular 24 genes were related at the highest significant value (1x10-8) with the regulation of programmed cell death; 50% of the genes belonging to this category, codify for proteins with anti-apoptotic functions. The cluster of anti-apoptotic proteins, corresponding to 12 genes and 22 protein isoforms was compared among the 100 proteomics maps and the 13 reference non-tumoral tissue maps. The comparative proteomic profiling showed: 1) a highly significant overexpression of several members of the anti-apoptotic protein cluster in the cancer tissues vs non tumoral counterparts; 2) a relative variability of the expression levels of the normalized proteins within patients. Among proteins of this category reaching the high levels of expression, we observed the nucleophosmin (NPM), a crucial regulator of p53; the translationally-controlled tumor protein (TCTP1), a protein involved in calcium binding and microtubule stabilization; cofilin (COF1), an actin-binding protein responsible also for the signal translocation from cytoplasm to nucleus; annexin A1 (ANXA1) a calcium/phospholipid-binding protein which promotes membrane fusion and ruffling, and the glutathione s-transferase (GSTP1), which plays important roles in detoxification but having also a role in susceptibility to cancer.
Conclusions: The application of the powerful Bioinformatics Resources for gene/protein classification provided by DAVID knowledgebase, while confirming our previous protein classification, introduced new terms for further remodulation of protein clusters on the basis of the multiple functions for individual proteins. In particular we found a high number of proteins with specific biochemical functions, converging towards common pathways. Overall, a predominant pathway was the programmed cell-death, which resulted to be the most robust among patients, both as number of proteins involved and as level of significativity.We believe hat the present collection of human breast cancer proteomics represents a valid contribution for clinical applications to breast cancer
Share-wave elastography study of myotendinous junction of the medial gastrocnemius: normal patterns and dynamic evaluation in professional football players
No full textA Low Cost Correlator Employing a Personal Computer
No full textThe intention of this paper is to describe the design of a 16-bit correlation setup employing a personal computer (PC) used in intensity fluctuation spectroscopy. It is based on a hardware acquisition board which counts the photons detected in the selected sampling time. The calculation of the correlation coefficients is achieved with a PC by means of a suitable software program. This arrangement permits one to obtain various kinds of information from the recorded data, i.e., it is possible to evaluate other statistical estimators instead of the usual correlation function. Experimental tests of the apparatus have been obtained by measuring the light scattered by a liquid suspension of polystyrene latex spheres
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