HIGH EXPRESSION OF CANCER TESTIS ANTIGENS MAGE-A, MAGE-C1/CT7, MAGE-C2/CT10, NY-ESO-1, AND GAGE IN ADVANCED SQUAMOUS CELL CARCINOMA OF THE LARYNX

Background. Despite diagnostic and therapeutic advances in head and neck cancer, the 5-year survival of patients with laryngeal cancer has not improved in the last 30 years. Several recent studies indicate that specific targets for immunotherapeutic approaches can be useful in the control of cancer. There is considerable interest in the expression of cancer testis antigens in human cancers since they may serve as the basis for an immunologic approach to therapy. Methods. We evaluated by immunohistochemical analysis the expression of cancer testis antigens MAGE-A4 (57B), MAGE-C1 (CT7-33), MAGE-A1 (MA454), MAGE-A3 (M3H67), MAGE-C2 (CT10.5), NY-ESO-1 (E978), and GAGE (GAGE) in squamous cell carcinoma (SCC) of the larynx. Results. A total of 63 cases (57 men and 6 women) of laryngeal SCC were available for this study. The findings were correlated with the clinical course and laboratory data. Expression of at least 1 cancer testis antigen was detected in 42 of 63 of the laryngeal SCCs (67%). In 34 of 42 of the positive cases (81%) there was simultaneous expression of >= 2 cancer testis antigens. There was significant correlation between antigen expression and advanced tumor stage (stage III/IV) in cases with reactivity to only 1 antibody (p = .01) as well as in the cases with reactivity to >= 2 primary antibodies (>= 2 mAbs, p = .04). There was no association between survival and expression of any of the analyzed antigens. Conclusions. We find a high incidence of cancer testis antigen expression in SCCs of the larynx, which was correlated with advanced clinical stage. Our data indicate that cancer testis antigens could be valuable vaccine targets in laryngeal tumors, especially in those with a worse prognosis. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 702-707, 2011

Les Actituds del professorat de l'ESO vers les pràctiques inclusives: un estudi longitudinal

En aquest treball s’exposa l’estudi realitzat en un centre educatiu ordinari d’Educació Secundària Obligatòria. En aquest centre, el curs acadèmic 2002-2003 s’hi implanten dues unitats d’educació especial amb la finalitat d’aconseguir una escolarització amb un caràcter més normalitzat per als alumnes que les integren. Fruit d’aquesta implantació se’ns ofereix l’oportunitat de realitzar un estudi al voltant del funcionament d’aquest procés. Degut a la importància que tenen en els processos d’aquesta índole, entre d’altres motius, decidim decantar-nos per l’estudi de les actituds del professorat vers les pràctiques inclusives. Així doncs en aquest treball s’hi recullen quines són les actituds dels professorat d’aquest IES, en dos moments diferents al llarg del temps, al voltant de diferents aspectes relacionats amb les pràctiques inclusives, l’instrument dissenyat per a recollir aquestes actituds, així com també les pràctiques amb caràcter inclusiu que s’han dut a terme en aquest IES.

Una Aproximació a la construcció significativa del coneixement matemàtic a l'ESO

This study displays and analyzes the contents of the Mathematics subject in ESO’s second cycle from a constructivist perspective. This analysis has been carried out by contrasting two groups of participants (control group and experimental group). These groups were formed by a sample of 240 students between the ages of 14 and 16 from four different educational centres of the Osona area. Research – Action methodology has been employed, combining quantitative techniques (statistical study with the SPSS package) with qualitative analysis (transcriptions of interviews and discussion group). This study has been carried out after years of classroom observation, reflection and action. The theoretical framework employed is a cognitive one, based on Ausubel’s Significative Learning Theory. Quantitative analysis shows how the researcher’s design improves, on the one hand, the students’ academic motivation and, on the other hand, their comprehensive memory, enabling them to achieve a more significant learning of the subjects’ contents. Furthermore, our analysis shows that the proposed method is more comprehensive than those employed by teachers collaborating with control groups. The main aim of the qualitative analysis is that of identifying the elements which configure the programme and contribute to an improvement of the aspects mentioned above. The key elements here are: co-operation as the basis of group dynamics; the employment, in some cases, of easily handled materials; the type of interaction between teacher and students, where, through open discussion, students are lead by teaching staff towards the course objectives; induction, that is, deducing formulae by initially using examples which are close to the students’ knowledge and experience or taken from everyday life (what we could call “down-top” mathematics). We should add here that the qualitative analysis does not only corroborate the results obtained by quantitative techniques, but also displays an increase of motivation in teaching staff. Teachers did show a positive attitude and welcomed the use and development of these materials in the next academic year. Finally, we discuss possible directions for further research.

La reflexió gramatical a les àrees de l'ESO

El projecte pretén de fer un diagnòstic del tractament de la reflexió gramatical a les àrees de llengua catalana, castellana, anglesa i francesa de 2n d'ESO a partir de les anàlisis dels llibres de text, de la visió que en té el professorat que els usa i de les representacions dels escolars sobre l'ensenyament de la gramàtica. Els referents bàsics per al desenvolupament de la recerca són: a) les propostes per a una renovació de l'ensenyament de la gramàtica que a partir de referents de la psicologia de l'educació, la lingüística i la psicolingüística atenen la promoció de l'activitat reflexiva com a inductora de la construcció de coneixement, i l'establiment de continuïtats entre la gramàtica de la frase i la del text; b) els estudis que, des de la perspectiva de la planificació de l'ensenyament, les característiques del coneixement lingüístic dels multilingües i l'anàlisi contrastiva, advoquen per un tractament integrat de les àrees de llengua a l'educació obligatòria. L'objectiu general que es pretén assolir és ajudar a renovar les concepcions sobre el rol de la gramàtica en la formació lingüística dels escolars i millorar la planificació del seu ensenyament a partir del seu tractament coordinat des de les diferents llengües del currículum.(...)

Correlation of tumor-associated antigens MAGE, NY-ESO-1 and P53 expression with clinical and pathological relationships of patients with oral squamous cell carcinoma

Despite advances in the diagnosisand treatment of head and neck cancer,survival rates have not improvedover recent years. New therapeuticstrategies, including immunotherapy,are the subject of extensive research.In several types of tumors, the presenceof tumor infiltrating lymphocytes(TILs), notably CD8+ T cellsand dendritic cells, has been correlatedwith improved prognosis. Moreover,some T cells among TILs havebeen shown to kill tumor cells in vitroupon recognition of tumor-associatedantigens. Tumor associated antigensare expressed in a significant proportionof squamous cell carcinoma ofthe head and neck and apparently mayplay a role in the regulation of cancercell growth notably by inhibition ofp53 protein function in some cancers.The MAGE family CT antigens couldtherefore potentially be used as definedtargets for immunotherapy andtheir study bring new insight in tumorgrowth regulation mechanisms. Between1995 - 2005 54 patients weretreated surgically in our institution forsquamous cell carcinoma of the oralcavity. Patient and clinical data wasobtained from patient files and collectedinto a computerized database.For each patient, paraffin embeddedtumor specimens were retrieved andexpression of MAGE CT antigens,p53, NY-OESO-1 were analyzed byimmunohistochemistry. Results werethen correlated with histopathologicalparameter such as tumor depth,front invasion according to Bryne andboth, local control and disease freesurvival. MAGE-A was expressed in52% of patients. NY-ESO-1 and p53expression was found in 7% and 52%cases respectively. A higher tumordepth was significantly correlatedwith expression of MAGE-Aproteins(p = 0.03). No significant correlationcould be made between the expressionof both p53 andNY-OESO-1 andhistopathological parameters. Expressionof tumor-associated antigendid not seem to impact significantlyon patient prognosis. As does thedemonstration of p53 function inhibitionby CT antigens of MAGE family,our results suggest, that tumor associatedantigens may be implicated in tumorprogression mechanisms. Thishypothesis need further investigationto clarify the relationship betweenhost immune response and local tumorbiology.

Estudi epidemiològic de l'obesitat de 1r d'ESO de l'IES Pedraforca

Treball de recerca realitzat per una alumna d'ensenyament secundari i guardonat amb un Premi CIRIT per fomentar l'esperit científic del Jovent l'any 2009. L'obesitat és una malaltia crònica que es caracteritza per un augment de la massa grassa i en conseqüència per un augment de pes. En el segle XXI aquesta malaltia, considerada epidèmia, està arribant a la població infantil i adolescent, i ha cridat l'atenció de totes les institucions de salut pública que estan lluitant per evitar aquesta alta prevalença d'obesitat i sobrepès. Aquest estudi confirma que existeix un alt percentatge d'obesitat i sobrepès en l'edat infantil i que està relacionat amb factors de risc (alguns modificables) que poden ser clau per a evitar aquesta malaltia. El mètode emprat és la realització d’un estudi epidemiològic transversal sobre una mostra de nens compresa en 39 individus de 12 a 14 anys d'edat. Es van determinar el pes, la talla, el plec bicipital i tricipital, l'ample del canell i del colze, a més de la realització d'una enquesta sobre hàbits alimentaris en l’esmorzar i dades socioculturals. L'obesitat i el sobrepès es van definir com resultats de IMC iguals als percentils 85 i 97 de les taules Orbegozo, respectivament. Els resultats van mostrar una prevalença de sobrepès i obesitat en la nostra mostra de població que va ser de 28,2%, la de només sobrepes del 15,4% i la de només obesitat del 12,8%. La prevalença d'obesitat és major en nens amb un 13,6% que en nenes 12,5% igual que el sobrepès. L'obesitat i sobrepès és major quan els estudis materns són inferiors als universitaris, també quan existeixen famílies amb 3 o més fills i quan es veu la TV més de 3 hores al dia.

CD8+ T-cell response to NY-ESO-1: relative antigenicity and in vitro immunogenicity of natural and analogue sequences.

We have shown previously that HLA-A*0201 melanoma patients can frequently develop a CTL response to the cancer testis antigen NY-ESO-1. In the present study, we have analyzed in detail the relative antigenicity and in vitro immunogenicity of natural and modified NY-ESO-1 peptide sequences. The results of this analysis revealed that, although suboptimal for binding to the HLA-A*0201 molecule, peptide NY-ESO-1 157-165 is, among natural sequences, very efficiently recognized by specific CTL clones derived from three melanoma patients. In contrast, peptides NY-ESO-1 157-167 and NY-ESO-1 155-163, which bind very strongly to HLA-A*0201, are recognized less efficiently. In agreement with previous data, substitution of peptide NY-ESO-1 157-165 COOH-terminal C with various other amino acids resulted in a significantly increased binding to HLA-A*0201 molecules as well as in an increased CTL recognition, although variable at the clonal level. Among natural peptides, NY-ESO-1 157-165 and NY-ESO-1 157-167 exhibited good in vitro immunogenicity, whereas peptide NY-ESO-1 155-163 was poorly immunogenic. The fine specificity of interaction between peptide NY-ESO-1 C165A, HLA-A*0201, and T-cell receptor was analyzed at the molecular level using a series of variant peptides containing single alanine substitutions. The findings reported here have significant implications for the formulation of NY-ESO-1-based vaccines as well as for the monitoring of either natural or vaccine-induced NY-ESO-1-specific CTL responses in cancer patients.

Desarrollo de contenidos educativos aplicados a las matemáticas de primer ciclo de ESO

Aquest projecte pretén oferir orientació als docents que es proposin desenvolupar continguts educatius en l'àrea de Matemàtiques de primer cicle d'ESO. Per aconseguir aquest objectiu no es necessita cap coneixement extra de complicats programes per assolir resultats atractius i útils. Es proporcionarà als docents la recopilació i estructuració de materials digitals que estan distribuïts a la xarxa, així com el desenvolupament de diferents activitats didàctiques basades en el nou disseny curricular.

A long, naturally presented immunodominant epitope from NY-ESO-1 tumor antigen: implications for cancer vaccine design.

The tumor antigen NY-ESO-1 is a promising cancer vaccine target. We describe here a novel HLA-B7-restricted NY-ESO-1 epitope, encompassing amino acids 60-72 (APRGPHGGAASGL), which is naturally presented by melanoma cells. The tumor epitope bound to HLA-B7 by bulging outward from the peptide-binding cleft. This bulged epitope was not an impediment to T-cell recognition, however, because four of six HLA-B7(+) melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX vaccine generated a potent T-cell response to this determinant. Moreover, the response to this epitope was immunodominant in three of these patients and, unlike the T-cell responses to bulged HLA class I viral epitopes, the responding T cells possessed a remarkably broad TCR repertoire. Interestingly, HLA-B7(+) melanoma patients who did not receive the NY-ESO-1 ISCOMATRIX vaccine rarely generated a spontaneous T-cell response to this cryptic epitope, suggesting a lack of priming of such T cells in the natural anti-NY-ESO-1 response, which may be corrected by vaccination. Together, our results reveal several surprising aspects of antitumor immunity and have implications for cancer vaccine design.

L'ús del català i del castellà a l'aula, una realitat més enllà de qualsevol model : Anàlisi de les pràctiques lingüístiques en una aula de 4t d'ESO de l'Institut Lluís de Peguera de Manresa

Anàlisi de l'ús del català i del castellà en una aula de 4t d'ESO de l'Institut Lluís de Peguera de Manresa.

PD-1 is a regulator of NY-ESO-1-specific CD8+ T cell expansion in melanoma patients.

The programmed death 1 (PD-1) receptor is a negative regulator of activated T cells and is up-regulated on exhausted virus-specific CD8(+) T cells in chronically infected mice and humans. Programmed death ligand 1 (PD-L1) is expressed by multiple tumors, and its interaction with PD-1 resulted in tumor escape in experimental models. To investigate the role of PD-1 in impairing spontaneous tumor Ag-specific CD8(+) T cells in melanoma patients, we have examined the effect of PD-1 expression on ex vivo detectable CD8(+) T cells specific to the tumor Ag NY-ESO-1. In contrast to EBV, influenza, or Melan-A/MART-1-specific CD8(+) T cells, NY-ESO-1-specific CD8(+) T cells up-regulated PD-1 expression. PD-1 up-regulation on spontaneous NY-ESO-1-specific CD8(+) T cells occurs along with T cell activation and is not directly associated with an inability to produce cytokines. Importantly, blockade of the PD-1/PD-L1 pathway in combination with prolonged Ag stimulation with PD-L1(+) APCs or melanoma cells augmented the number of cytokine-producing, proliferating, and total NY-ESO-1-specific CD8(+) T cells. Collectively, our findings support the role of PD-1 as a regulator of NY-ESO-1-specific CD8(+) T cell expansion in the context of chronic Ag stimulation. They further support the use of PD-1/PD-L1 pathway blockade in cancer patients to partially restore NY-ESO-1-specific CD8(+) T cell numbers and functions, increasing the likelihood of tumor regression.

MHC class II/ESO tetramer-based generation of in vitro primed anti-tumor T-helper lines for adoptive cell therapy of cancer.

Generation of tumor-antigen specific CD4(+) T-helper (T(H)) lines through in vitro priming is of interest for adoptive cell therapy of cancer, but the development of this approach has been limited by the lack of appropriate tools to identify and isolate low frequency tumor antigen-specific CD4(+) T cells. Here, we have used recently developed MHC class II/peptide tetramers incorporating an immunodominant peptide from NY-ESO-1 (ESO), a tumor antigen frequently expressed in different human solid and hematologic cancers, to implement an in vitro priming platform allowing the generation of ESO-specific T(H) lines. We isolated phenotypically defined CD4(+) T-cell subpopulations from circulating lymphocytes of DR52b(+) healthy donors by flow cytometry cell sorting and stimulated them in vitro with peptide ESO(119-143), autologous APC and IL-2. We assessed the frequency of ESO-specific cells in the cultures by staining with DR52b/ESO(119-143) tetramers (ESO-tetramers) and TCR repertoire of ESO-tetramer(+) cells by co-staining with TCR variable β chain (BV) specific antibodies. We isolated ESO-tetramer(+) cells by flow cytometry cell sorting and expanded them with PHA, APC and IL-2 to generate ESO-specific T(H) lines. We characterized the lines for antigen recognition, by stimulation with ESO peptide or recombinant protein, cytokine production, by intracellular staining using specific antibodies, and alloreactivity, by stimulation with allo-APC. Using this approach, we could consistently generate ESO-tetramer(+) T(H) lines from conventional CD4(+)CD25(-) naïve and central memory populations, but not from effector memory populations or CD4(+)CD25(+) Treg. In vitro primed T(H) lines recognized ESO with affinities comparable to ESO-tetramer(+) cells from patients immunized with an ESO vaccine and used a similar TCR repertoire. In this study, using MHC class II/ESO tetramers, we have implemented an in vitro priming platform allowing the generation of ESO-monospecific polyclonal T(H) lines from non-immune individuals. This is an approach that is of potential interest for adoptive cell therapy of patients bearing ESO-expressing cancers.

Estudi dels fenòmens de contacte de llengües en el lèxic d'escolars de primera llengua castellana i la seva l'evolució lingüística (de 6è de primària a 1r d'ESO)

Aquest treball estudia els fenòmens de contacte de llengües que apareixen a la llengua oral catalana d'una mostra d'adolescents de primera llengua castellana de Manlleu en dos punts temporals (6è de primària i 1r d'ESO) i compara els resultats obtinguts amb dos estudis precedents (Vila, 1996; Galindo, 2006)

Striking immunodominance hierarchy of naturally occurring CD8+ and CD4+ T cell responses to tumor antigen NY-ESO-1.

Immunodominance has been well-demonstrated in many antiviral and antibacterial systems, but much less so in the setting of immune responses against cancer. Tumor Ag-specific CD8+ T cells keep cancer cells in check via immunosurveillance and shape tumor development through immunoediting. Because most tumor Ags are self Ags, the breadth and depth of antitumor immune responses have not been well-appreciated. To design and develop antitumor vaccines, it is important to understand the immunodominance hierarchy and its underlying mechanisms, and to identify the most immunodominant tumor Ag-specific T cells. We have comprehensively analyzed spontaneous cellular immune responses of one individual and show that multiple tumor Ags are targeted by the patient's immune system, especially the "cancer-testis" tumor Ag NY-ESO-1. The pattern of anti-NY-ESO-1 T cell responses in this patient closely resembles the classical broad yet hierarchical antiviral immunity and was confirmed in a second subject.