Sample records for MUTACIONES SOMATICAS (somatic mutations)
from WorldWideScience.org

Sample records 1 - 19 shown.



1

Patogénesis del cáncer de páncreas/ Pathogenesis of pancreatic cancer

Lizarazo Rodríguez, Jorge Iván
2008-12-01

Resumen en español El adenocarcinoma pancreático es uno de los cánceres con mayor mortalidad, y la detección temprana y la sobrevida no han mejorado en la actualidad. Los estudios en las últimas dos décadas han demostrado que es una enfermedad fundamentalmente genética, causada por mutaciones hereditarias en línea germinal y/o mutaciones somáticas adquiridas en genes asociados con cáncer. Se han descrito lesiones precursoras de cáncer pancreático y alteraciones en varios genes im (mas) portantes en el inicio y la progresión de esta enfermedad. Es posible que el mejor entendimiento de estas alteraciones permita en un futuro mejorar métodos de diagnóstico y de tratamiento. Resumen en inglés Pancreatic Adenocarcinoma is a lethal disease for which early detection has not improved survival rates. Studies in the last two decades have shown that pancreatic cancer is fundamentally a genetic disease caused by inherited germ lines and acquired somatic mutations in genes associated with cancer. Multiple alterations of genes that are important in the progression of pancreatic cancer have been identified. It is possible that better understanding of these alterations will facilitate identification of new biomarkers for early detection and may lead to novel drug targets.

Scientific Electronic Library Online (Spanish)

2

La tiroides como modelo de mecanismos moleculares en enfermedades genéticas/ The thyroid as a model for molecular mechanisms in genetic diseases

Rivolta, Carina M.; Moya, Christian M.; Esperante, Sebastián A.; Gutnisky, Viviana J.; Varela, Viviana; Targovnik, Héctor M.
2005-06-01

Resumen en español Las enfermedades tiroideas constituyen una heterogénea colección de anormalidades asociadas a mutaciones en los genes responsables en el desarrollo de la tiroides: factor de transcripción tiroideo 1 (TTF-1), factor de transcripción tiroideo 2 (TTF-2) y PAX8, o en uno de los genes que codifican para las proteínas involucradas en la biosíntesis de hormonas tiroideas como tiroglobulina (TG), tiroperoxidasa (TPO), sistema de generación de peróxido de hidrógeno (DUOX2 (mas) ), cotransportdor de Na/I- (NIS), pendrina (PDS), TSH y receptor de TSH. El hipotiroidismo congénito ocurre con una prevalencia de 1 en 4.000 nacidos. Los pacientes con este síndrome pueden ser divididos en dos grupos: con hipotiroidismo congénito sin bocio (disembriogénesis) o con bocio (dishormonogénesis). El grupo de disembriogénesis, que corresponde al 85% de los casos, resulta de ectopía, agenesia o hipoplasia. En una minoría de estos pacientes, el hipotiroidismo congénito está asociado con mutaciones en los genes TTF-1, TTF-2, PAX-8, TSH o TSHr. La presencia de bocio congénito (15% de los casos) se ha asociado a mutaciones en los genes NIS, TG, TPO, DUOX2 o PDS. El hipotiroidismo congénito por dishormonogénesis es trasmitido en forma autonómica recesiva. Mutaciones somáticas en el TSHr han sido identificadas en adenomas tiroideos hiperfuncionantes. Otra enfermedad tiroidea bien establecida es la resistencia a hormonas tiroideas (RTH). Es un síndrome de reducida respuesta tisular a la acción hormonal causado por mutaciones localizadas en el gen del receptor b de hormonas tiroideas (TRb). Mutantes de TRb interfieren con la función del receptor normal por un mecanismo de dominancia negativa. En conclusión, la identificación de mutaciones en los genes de expresión tiroidea ha permitido un mayor entendimiento sobre la relación estructura-función de los mismos. La tiroides constituye un excelente modelo para el estudio molecular de las enfermedades genéticas. Resumen en inglés Thyroid diseases constitute a heterogeneous collection of abnormalities associated with mutations in genes responsible for the development of thyroid: thyroid transcription factor-1 (TTF-1), thyroid transcriptions factor-2 (TTF-2) and PAX8, or in one of the genes coding for the proteins involved in thyroid hormone biosynthesis such as thyroglobulin (TG), thyroperoxidase (TPO), hydrogen peroxide-generating system (DUOX2), sodium/iodide symporter (NIS), pendrin (PDS), TSH a (mas) nd TSH receptor (TSHr). Congenital hypothyroidism occurs with a prevalence of 1 in 4000 newborns. Patients with this syndrome can be divided into two groups: nongoitrous (dysem/bryogenesis) or goitrous (dyshormonogenesis) congenital hypothyroidism. The dysembryogenesis group, which accounts for 85% of the cases, results from ectopy, agenesis and hypoplasia. In a minority of these patients, the congenital hypothyroidism is associated with mutations in TTF-1, TTF-2, PAX-8, TSH or TSHr genes. The presence of congenital goiter (15% of the cases) has been linked to mutations in the NIS, TG, TPO, DUOX2 or PDS genes. The congenital hypothyroidism with dyshormonogenesis is transmitted as an autosomal recessive trait. Somatic mutations of the TSHr have been identified in hyperfunctioning thyroid adenomas. Another established thyroid disease is the resistance to thyroid hormone (RTH). It is a syndrome of reduced tissue responsiveness to hormonal action caused by mutations located in the thyroid hormone receptor b (TRb) gene. Mutant TRbs interfere with the function of the wild-type receptor by a dominant negative mechanism. In conclusion, the identification of mutations in the thyroid expression genes has provided important insights into structure-function relationships. The thyroid constitutes an excellent model for the molecular study of genetic diseases.

Scientific Electronic Library Online (Spanish)

3

Enfermedad granulomatosa crónica: Aspectos actuales/ Chronic granulomatous disease: Current aspects

Cos Padrón, Yanelkys; Marsán Suárez, Vianed; Sánchez Segura, Miriam; Macías Abraham, Consuelo
2004-12-01

Resumen en español La enfermedad granulomatosa crónica (EGC) es una inmunodeficiencia primaria causada por mutaciones en los genes que codifican para cualquiera de las 4 subunidades que conforman a la enzima adenina dinucleótido fosfato oxidasa (NADPH oxidasa), encargada de regular la producción de especies oxidantes microbicidas que constituyen la primera vía de defensa del organismo contra los microorganismos infecciosos. Esta es una deficiencia muy heterogénea clasificada en EGC lig (mas) ada al cromosoma X (subunidad gp91-phox) y autosómica recesiva, donde puede estar afectada cualquiera de las siguientes subunidades de la enzima: p22-phox, p47-phox y p67-phox. Dentro de los hallazgos clínicos más frecuentes se encuentran entre otros la linfadenopatía, hepatoesplenomegalia, neumonía. Para el tratamiento de la enfermedad se utilizan antibióticos de amplio espectro y el interferón gamma para el tratamiento de infecciones severas en la EGC ligada al cromosoma X. Actualmente se están realizando estudios para utilizar la terapia génica somática como posible cura de la enfermedad Resumen en inglés Chronic granulomatous disease is a primary immunodeficiency caused by mutations in genes encoding any of the 4 subunits that make up adenine dinucleotide phosphate oxidase (NADPH oxidase), the enzyme that regulates the production of microbial oxidizing species that are the first defensive pathway of the body against infectious microorganisms. This is a very heterogeneous deficiency classified as X chromosome-linked CGD (gp91-phox subunit) and as autosomal recessive chroni (mas) c granulomatous disease, where any of the subunits of the enzyme, that is, p22-phox, p47-phox and p67-phox, may be affected. The most frequent clinical findings include, among others, lymphadenopathy, splenohepatomegaly and pneumonia. Broad-spectrum antibiotics for the treatment of the disease and gamma interferon for the treatment of severe infections are used in X chromosome-linked chronic granulomatous disease. At present, studies are being carried out with a view to using somatic gene therapy as a likely disease cure

Scientific Electronic Library Online (Spanish)

4

The c-K-ras gene and human cancer

Kahn, S.; Yamamoto, F.; Almoguera, Concepción; Winter, E.; Forrester, K; Jordano, Juan; Perucho, M.
1987-01-01

Digital.CSIC (Spain)

5

The Drosophila spn-D gene encodes a RAD51C-like protein that is required exclusively during meiosis

Abdu, Uri; González-Reyes, Acaimo; Ghabrial, Amin; Schüpbach, Trudi
2003-09-01

Digital.CSIC (Spain)

6

Spectrum of genetic diversity and networks of clonal organisms

Rozenfeld, Alejandro F.; Arnaud-Haond, Sophie; Hernández-García, Emilio; Eguíluz, Víctor M.; Matías, Manuel A.; Serrão, Ester A.; Duarte, Carlos M.
2007-05-01

Digital.CSIC (Spain)

7

Rol patogénico del gen supresor de tumores PTEN en cáncer ovárico asociado a endometriosis/ Pathogenic role of PTEN tumor suppressor gene in ovarian cancer associated to endometriosis

Castiblanco G, Adriana; Pires N, Yumay; Wistuba O, Ignacio; Riquelme S, Erick; Andrade M, Leonardo; Corvalán R, Alejandro
2006-03-01

Resumen en inglés Background: Endometrioid carcinoma and clear cell carcinoma of the ovary are associated to endometriosis. Somatic mutations of PTEN (10q23.3) are present in endometrial endometrioid carcinoma. Therefore, these mutations could be also present in ovarian tumors. Molecular studies show that solitary endometriotic cysts are monoclonal, have aneuploid DNA, have a loss of 9p,11q and 22q heterozygosity (LOH) and a higher cellular proliferation index of the epithelial component. (mas) Aim: To determine the cellular proliferation index using Ki 67, the immunohistochemical expression of PTEN and LOH in patients with ovarian endometriosis without atypia (EN), ovarian endometriosis with atypia (EA) and endometriosis with adjacent ovarian carcinoma (ET). Material and methods: Paraffin embedded samples of 37 endometrioid and clear cell carcinomas of the ovary (CC/CE), 15 solitary ovarian EN and 15 ovarian EA, were studied. Expression of Ki 67 and PTEN was measured by immunohistochemistry. LOH of 10q23.3 locus was measured by polymerase chain reaction. Results: Ki 67 was 5.5 and 2.3% in EA and EN, respectively (p

Scientific Electronic Library Online (Spanish)

8

Overexpression of human DNA polymerase µ (Pol µ) in a Burkitt's lymphoma cell line affects the somatic hypermutation rate

Ruiz, José F.; Lucas, Daniel; García-Palomero, Esther; Saez, Ana I.; González, Manuel A.; Piris, Miguel A.; Bernad, Antonio; Blanco, Luis
2004-11-01

Digital.CSIC (Spain)

9

Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes

Almoguera, Concepción; Shibata, D.; Forrester, K.; Martin, J.; Amheim, N.; Perucho, M.
1988-01-01

Digital.CSIC (Spain)

10

La epigenética y los estudios en gemelos en el campo de la psiquiatría/ Epigenetics and twin studies in psychiatric domains

González Ramírez, Adriana Estrella; Díaz Martínez, Alejandro; Díaz-Anzaldúa, Adriana
2008-06-01

Resumen en español La secuencia de ADN genómico que caracteriza a nuestra especie constituye la piedra fundamental de la vida humana; parte de ella se refleja en la secuencia del ARN y a través de éste se dicta la información necesaria para que nuestras células produzcan proteínas. La genética contribuye de manera importante a los avances en el campo médico. Los descubrimientos genéticos han permitido desarrollar estrategias para modificar, prevenir y proponer nuevas terapias para (mas) diversas enfermedades. En el siglo XIX, Gregor Johann Mendel desarrolló un modelo teórico capaz de predecir la naturaleza y propiedades de los mecanismos de la herencia, que sigue siendo indispensable para explicar la base de la herencia humana. Otro suceso determinante en la historia de la Medicina se dio a conocer casi nueve décadas después cuando James Watson y Francis Crick describieron su modelo estructural para el ADN. Posteriormente se introdujeron la clonación posicional y la reacción en cadena de la polimerasa; más recientemente se publicó cerca del 99% de la secuencia del genoma humano. El período actual se conoce como la era post-genómica, ya que además de descifrar genomas completos, los investigadores pretenden, entre otras cosas, esclarecer los mecanismos que influyen en la activación e inactivación de los genes, lo cual en parte involucra un nivel epigenético. En las ciencias médicas los gemelos constituyen un grupo idóneo para abordar el estudio de las enfermedades hereditarias. En este tipo de padecimientos suelen observarse similitudes entre parientes, en especial si se trata de gemelos monocigóticos. Sin embargo, aun en este tipo de hermanos se detectan diferencias importantes. Parámetros como los grados de concordancia y porcentajes de heredabilidad han puesto de manifiesto que un gemelo monocigótico puede presentar trastornos hereditarios que su co-gemelo nunca tendrá. La epigenética es el estudio de los cambios en la función de los genes que no afectan la secuencia del ADN, por modificaciones que tienen lugar principalmente en las citosinas de éste y en las histonas de la cromatina. Se ha determinado que las modificaciones epigenéticas son mucho más frecuentes que aquellas que modifican la secuencia del ADN, por lo que constituyen uno de los fundamentos de la diversidad biológica, muestran la manera en que el ambiente puede modular la expresión genética y contribuyen así a nuestro fenotipo. Esta revisión reúne datos sobre la posible relevancia de la epigenética en el estudio de los trastornos mentales y como posible explicación parcial de las diferencias observadas entre gemelos >. Un conocimiento más profundo de los patrones epigenéticos podría contribuir a identificar factores de riesgo para estos trastornos. Resumen en inglés The sequence of the human genome integrates the keystone of our life. Part of it is transcribed to RNA, which in turn provides the information required by our cells to produce proteins. Discoveries in the genetics field have been essential to medicine and have been used to develop strategies to modify, prevent and propose new therapeutic approaches for human diseases. In the 19th Century, Gregor Johann Mendel developed a theoretical model which was able to predict in an a (mas) ccurate way hereditary mechanisms; indeed, his laws still explain the basis of human inheritance. Almost ninety years later, James Watson and Francis Crick announced their double-helix model of the DNA molecule. Then, positional cloning and the polymerase chain reaction (PCR) were introduced; more recently, almost 99% of the sequence of our genome was made public. The current period of time is known as the post-genomic era, due to the fact that researchers are not only obtaining the complete sequences of thousands of genomes, but are also searching for clues that may help understand the mechanisms that affect gene activation and deactivation, in which epigenetic factors are also involved. In medical domains, twins constitute a suitable group to study inherited disorders. Dizygotic or fraternal twins are produced by different egg and sperm cells, and even when these two fertilization events occur simultaneously, dizygotic twins share approximately the same percentage of genetic material than any pair of siblings, that is, around 50%. Some authors have suggested that the tendency for spontaneous dizygotic twinning could be attributed to a double ovulation which is genetically determined in an autosomal dominant manner. Monozygotic, as opposed to dizygotic twins, are produced by a single zygote whose cells are dissociated and originate two independent organisms; approximately a third of monozygotic twins are separated before the 5th day after fertilization, and the rest between the 5th and the 15th day. Most monozygotic twins are very similar; nevertheless, some few exceptions prove that in fact they actually do not have to be identical. Relatives of a person with a mental disorder tend to share traits associated with this disease, especially if the patient and the relative are monozygotic twins. However, important differences may be detected even between each pair of identical twins. Parameters such as concordance and heritability have shown that a monozygotic twin can develop an inherited disorder while his or her co-twin will always be disease-free. In addition to differences in susceptibility to inherited diseases, this kind of twins can display dissimilarities in somatic cell mutations (more overtly noticeable when ageing), their set of antibodies and T cell receptors, their number of mitochondrial DNA molecules, and chromosome X inactivation patterns in women, all of which are the main subject of many ongoing studies. A recent report shows that from 160 monozygotic twin pairs who were 3 to 74 years old, epigenetic patterns were identical early in life, but differences were more obvious at older ages, especially if twins were raised apart or if they had different medical history. Medical conditions, but also environmental factors such as pregnancy tobacco exposure, physical activity, and diet could contribute to differences in epigenetic patterns. It has been shown that epigenetic modifications (or epi-mutations) are more frequent than the ones that modify DNA sequence, so they are part of the fundamental causes of biological diversity, and they show how environment can modulate gene expression and contribute to our phenotype. Even when twin studies are sometimes considered purely genetic, they also give information about the influence of environmental factors. However, it is important to consider with caution the results from this type of studies. Heritability estimates are not unchangeable facts. They depend on the sample being analyzed, the genes involved in the specific sample, the characteristics of the environmental factors which members of this group were exposed to, and the precise moment the study was done. Epigenetics refers to changes that do not alter the DNA sequence but affect gene function due to chemical modifications which mainly occur in DNA cytosines and in chromatin-related histones. Epigenetic processes are covalent modifications which include the addition of functional groups (methyl, acetyl, phosphate, etc.) or proteins (ubiquitin, SUMO, etc.) to the DNA molecule or to associated proteins. These modifications contribute to the activation or inhibition of transcription, which leads to changes in messenger ARN expression that can ultimately influence the onset of disease. Pseudogenes are still being excluded while new genes are being confirmed in our genome sequence, but the current estimates indicate that each one of our nucleated cells contains almost 22000 genes (excluding mitochondrial DNA) which encode for polypeptides and more than 4,000 whose final product is RNA. Gene expression is partially controlled by DNA coiling around globular proteins called histones, which constitute a structure known as chromatin, a DNA-protein complex that represents the packaging of 3.25 billion base pairs of our genetic information. Physical and chemical chromatin modifications can also affect gene expression by changing DNA-protein interactions; in general terms, genes are inhibited when chromatin is packed and they are active when it is free. These dynamic states are controlled by epigenetic reversible modifications on DNA methylation or by changes in histones. It has been shown that subtle epigenetic differences between any two human beings are associated with dissimilar final chromatin remodeling, as well as expression/repression of genes.

Scientific Electronic Library Online (Spanish)

11

High incidence of c-K-ras oncogenes in human colon cancer detected by the RNAse A mismatch cleavage method

Forrester, K.; Almoguera, Concepción; Jordano, Juan; Grizzle, W.E.; Perucho, M.
1987-01-01

Digital.CSIC (Spain)

12

Hemoglobinuria paroxística nocturna: Actualización/ Paroxysmal nocturnal haemoglobinuria

Milanés Roldán, María Teresa; Fernández Delgado, Norma; Fundora Sarraff, Teresa; Jaime Facundo, Juan Carlos; Hernández Ramírez, Porfirio
2003-04-01

Resumen en español La hemoglobinuria paroxística nocturna (HPN) es una enfermedad clonal y adquirida causada por una mutación somática en el gen PIG-A que se encuentra en el cromosoma X y codifica una proteina involucrada en la síntesis del glicosilfosfatidilinositol (GPI), el cual le sirve como anclaje a muchas proteínas de la membrana celular. La mutación ocurre en el stem cell hematopoyético y da lugar a una deficiencia parcial o total de la proteína PIG-A con la consecuente alte (mas) ración en la síntesis del GPI de anclaje; como resultado, una parte de las células sanguíneas serán deficientes de todas las proteínas ligadas al GPI. La ausencia de estas proteinas en la HPN explica algunos de los síntomas clínicos de la enfermedad, como la hemólisis intravascular mediada por el complemento, la trombosis venosa, el déficit de la hematopoyesis, etc; pero no el mecanismo mediante el cual el clon HPN se expande en la médula ósea. Varios estudios han demostrado que la inactivación del gen PIG- A por sí sola, no confiere una ventaja proliferativa al stem cell mutado, uno o más factores ambientales externos son necesarios para la expansión de este clon mutado, los cuales ejercen una presión selectiva a favor del clon HPN. La causa por el cual el clon HPN se estimula a proliferar podría ser un daño selectivo a la hematopoyesis normal. En el tratamiento de esta enfermedad se han utilizado varios agentes terapéuticos, pero el único tratamiento curativo es el trasplante de progenitores hematopoyéticos Resumen en inglés The paroxysmal nocturnal haemoglobinuria (PNH) is a clonal acquired disease caused by a somatic mutation in the PIG-A gene that is located in the chromosome X and codifies a protein involved in the synthesis of glycosil phosphatidylinositol (GPI), which serves as an anchor for many proetins of the cellular membrane. The mutations occurs in the hematopoietic stem cell and gives rise to a partial or total deficiency of the protein PIG-A with the subsequent alteration in the (mas) synthesis of the anchored GPI. As a result, a part of the blood cells will be lacking all the proteins bound to the GPI. The absence of these proteins in the NPH explains some of the clinical symptoms of the disease, such as the intravascular hemolysis mediated by the complement, the venous thrombosis, the deficit of hematopoiesis, etc., but not the mechanism by which the NPH clone expands into the bone marrow. Some studies have proved that the inactivation of the GPI-A gene does not confer a proliferative advantage to the mutated stem cell. One or more external environmental factors are needed for the expansion of this mutated clone. These factors exert a selective pressure in favor of the NPH clone. The cause for which the NPH clone is estimulated to proliferate may be a selective damage to the normal hematopoiesis. Several therapeutic agents have been used in the treatment of this disease, but the only curative treatment is the transplantation of hematopoietic progenitors

Scientific Electronic Library Online (Spanish)

13

Genome-wide analysis of the "cut-and-paste" transposons of grapevine

Benjak, Andrej; Forneck, Astrid; Casacuberta, Josep M.
2008-09-03

Digital.CSIC (Spain)

14

Genome-Wide Analysis of the ‘‘Cut-and-Paste’’ Transposons of Grapevine

Benjak, Andrej; Forneck, Astrid; Casacuberta, Josep M.
2008-09-03

Digital.CSIC (Spain)

15

Envejecimiento cardiovascular/ Cardiovascular aging

Domenech, Raúl J; Macho, Pilar
2008-12-01

Resumen en inglés Aging produces its own cardiovascular changes, mainly remodelling of arteries, heart and the microcirculation. These progressive changes, detected since adolescence, represent a major rísk factor for the development of cardiovascular diseases. Remodelling of arteries produces a thickening of the intima-media with fracture of elastic fibers and their replacement by collagen. These alterations induce an increase of the pulse wave and aortic impedance, with greater resistan (mas) ce to ventrícular ejection, that in turns induces the remodelling of the left ventricle. Ventricular remodelling leads to systolic, diastolic and chronotropic dysfunctions that explain the reduced capacity of old people to increase cardiac output during exercise. These alterations together with oxidative endothelial dysfunction and somatic mitochondrial mutations in the skeletal muscle decrease aerobic capacity, especially in adults aged >70 years. On the other hand, the transmission of an increased pulse wave to microvessels, mainly of the brain and kidneys, damage these organs. There is a search for candidate genes associated to this phenotype, especially those associated with arterial structure. Atpresent no specific treatment is available for cardiovascular aging. Exercise preserves a better aerobic capacity but does not prevent its decline with age. Vasodilator drugs may decrease aortic impedance and perhaps delay remodelling. However there is no clinical evidence available to recommend these drugs in young healthy people. Finally new drugs that modify aortic molecular structure are been investigated

Scientific Electronic Library Online (Spanish)

16

El sistema inmune, herramienta estratégica en la batalla contra el cáncer/ The immune system-a strategic weapon in the battle against cancer

Salazar O, Flavio
2000-07-01

Resumen en español Las células tumorales ven alterada la regulación de su ciclo celular y comienzan a proliferar en forma descontrolada debido a mutaciones en su material genético. Además de las alteraciones en la proliferación, se producen modificaciones genéticas que dan origen a cambios en la expresión de proteínas en la célula maligna, lo que se manifiesta en la sobreexpresión de algunos genes o en su activación en tejidos normales, en los que comúnmente no son expresados. E (mas) stos genes originan proteínas que pueden ser reconocidas como aberrantes por el sistema inmune, generando una respuesta antitumoral. Recientemente, estudios realizados en animales de experimentación y en pacientes han demostrado que la principal actividad antitumoral está dada por la respuesta inmune celular. En esta situación, son los linfocitos T los que juegan un papel preponderante, reconociendo, a través de su receptor, antígenos que han sido procesados y presentados en asociación con las moléculas del complejo principal de histocompatibilidad (MHC). La gran mayoría de los antígenos asociados a tumor (AAT) y reconocidos por linfocitos T CD8+ citotóxicos (CTL) son péptidos derivados de proteínas que se expresan en las células tumorales y además se encuentran en el tejido normal que les dio origen. Así, en melanoma humano por ejemplo, existen antígenos inmunodominantes derivados de proteínas involucradas en la síntesis de melanina y expresados tanto en el tumor como en los melanocitos normales. Existen otros antígenos restringidos por MHC que son comunes a varios tipos de tumores. Estos derivan de proteínas embrionarias y normalmente no se expresan en tejidos somáticos. La identificación de varios AAT ha permitido desarrollo de modernas vacunas antitumorales, las que se encuentran en etapa de experimentación. Estas vacunas, basadas en los antígenos descritos, pueden ser de tipo peptídico o de ADN y vendrían a reemplazar las terapias inmunológicas menos especificas, como el tratamiento con citoquinas o las terapias adoptivas. Investigaciones clínicas y preclínicas llevadas a cabo durante los últimos dos años indican que la forma de inmunizar resulta esencial para inducir una respuesta inmune efectiva y evitar la anergia o tolerancia. Aquí juegan un papel determinante las células dendríticas en su función de células presentadoras de antígenos profesionales y algunas citoquinas pro-inflamatorias. La paradoja existente entre la presencia de células antitumorales en los pacientes con cáncer y la progresión sistemática de la enfermedad, sugieren la existencia de mecanismos mediados por el tumor para evadir la respuesta del sistema inmune. Estas estrategias van desde la secreción por parte del tumor de factores inmunoinhibidores hasta mutaciones de moléculas relacionadas con la presentación antigénica. La comprensión más acabada de los mecanismos inmunológicos involucrados en la respuesta antitumoral, permitirá el desarrollo de la inmunoterapia como tratamiento alternativo y/o complementario a los ya establecidos en la lucha contra el cáncer Resumen en inglés Tumor cells have an altered regulation of their cell cycle and commence to proliferate uncontrollably owing to mutations in their genetic material. Furthermore in addition to the altered proliferation there are genetic modifications which alter the expression of proteins in the malignant cell. This is manifested in the overexpression of some genes or activation which in normal tissue are not normally expressed. These genes encode for proteins which can be recognized as ab (mas) errant by the immune system thus generating an anti-tumor response. Recently in studies of animal models and in patients it has been shown that the principal anti-tumor effect is caused by the cellular immune response. In this situation it is the T lymphocyte which play a principal role, by way of their antigen receptors which have been processed and presented in association with the molecules of the major histocompatability complex (MHC). The majority of tumor associated antigens and recognized by CD8+ cytotoxic T lymphocytes are peptides derived from proteins expressed by the tumor cells and furthermore are encountered in the normal tissue of origin. For example in human melanoma exist antigens derived from proteins involved in the synthesis of melanin and expressed both in the tumor and normal melanocytes. There are other MHC restricted antigens which are common to various tumor types. These are embryologically derived proteins and normally are not expressed in the somatic tissues. The identification of various TAA has permitted the production of modern anti-tumor vaccines which are in the experimental stage. These vaccines based on descrete antigens which could be of peptide or DNA origen and would come to replace immunological therapies of less specificity, such as cytokines or adaptive therapy. Pre-clinical and clinical studies in the last two years indicate that the form of immunization essential in order to produce an effective immune response and avoid anergia or tolerance. Here play an important role the dendrite cells in their function as presenting cells of antigens and some preinflammatory citokines. The parody exists between the presence of anti-tumor cells in the patients with cancer and the systemic progression of the disease, this suggests the existence of mechanisms mediated by the tumor to evade the immune response. This strategies range from the secretion of factors immuno-inhibitory to mutations in the molecules related to the presenting antigen. An understanding of the immunological mechanisms involved in the anti-tumor response permits the development of immunotherapy as an alternative or complementary therapy to those already established in the fight against cancer

Scientific Electronic Library Online (Spanish)

17

Disparate roles of ATR and ATM in immunoglobulin class switch recombination and somatic hypermutation

Pan-Hammarström, Qiang; Lähdesmäki, Aleksi; Zhao, Yaofeng; Du, Likun; Zhao, Zhihui; Wen, Sicheng; Ruiz-Pérez, Victor L.; Dunn-Walters, Deborah K.; Goodship, Judith A.; Hammarström, Lennart
2006-01-23

Digital.CSIC (Spain)

18

Agenesias dentarias: en busca de las alteraciones genéticas responsables de la falta de desarrollo/ Tooth agenesis: in search of mutations behind failed dental development

Kolenc Fusé, Francisco Javier
2004-12-01

Resumen en español En conjunto, las agenesias dentarias son la malformación cráneofacial más frecuente. Su prevalencia alcanza el 20% en la dentición permanente, y su expresión puede variar desde la ausencia de una sola pieza, generalmente un tercer molar, hasta la de toda la dentición. En la pasada década, los estudios de ligamiento genético y biología molecular han permitido identificar algunas mutaciones responsables de distintos patrones de agenesias dentarias sindrómicas y no (mas) sindrómicas. Dichas mutaciones se encuentran en genes clave para el desarrollo de la dentición, como los que codifican a los factores de transcripción MSX1, PAX9 y PITX2, la proteína de señalización EDA y su receptor EDAR. Los estudios que están en curso podrían derivar en nuevas clasificaciones que relacionen los fenotipos observados con el defecto genético subyacente. De esta manera, se posibilitaría un diagnóstico previo a la aparición del defecto somático, que técnicas como la terapia génica o la ingeniería de tejidos y órganos, podrían llegar a solucionar. Resumen en inglés Tooth agenesis are the most common craniofacial malformations. Its prevalence in permanent dentition reaches 20% and its expressivity ranges from only one tooth, usually a third molar, to the whole dentition. Genetic linkage and molecular biology studies have allowed, in the last decade, the identification of mutations responsible for some patterns of syndromic and non-syndromic tooth agenesis. The mutated genes are key genes for the development of dentition, like the one (mas) s that encode the transcription factors MSX1, PAX9 and PITX2, the signalling protein EDA and its receptor EDAR. Current research would lead to the development of new classifications of tooth agenesis that took into account both the phenotypes and the genetic background. This would allow an early diagnosis of the condition, before the development of the somatic defect, that could eventually be repaired with gene therapy or tissue and organ engineering.

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