La inestabilidad microsatélite y la hipermetilación del promotor mlh1 se asocian con la aparición tardía del cáncer de endometrio

[ES] El silenciamiento del gen reparador de mutaciones MLH1 por hipermetilación de su promotor es la principal causa de inestabilidad microsatélite (MSI) en tumores esporádicos tanto de origen colorectal (CC) como endometrial (CE). Los CC con MSI y MLH1 metilado ocurren en pacientes con más edad que los CC sin estas alteraciones moleculares. Sin embargo, en CE esta relación es controvertida. En este trabajo hemos estudiado la relación entre la edad y el estado MSI y de metilación de MLH1, en una serie amplia de pacientes con CE. El MSI se estableció usando tres marcadores de inestabilidad (BAT-26, BAT-25 y APA3). Para determinar la hipermetilación del promotor MLH1 se usó el MS-SSCA (methylation-sensitive single-strand conformation analysis). El 20% de las muestras de CE eran MSI, y el 80% de estas tenían MLH1 metilado. La edad en el diagnóstico de las pacientes con tumores MSI fue significativamente más elevada que la de las pacientes con tumores que presentaban estabilidad de microsatélites (MSS). (edad±SD: 67.1±9.6 años vs 63.4±10.0 años, p=0,034, test de Fisher). Los tumores MSI con MLH1 metilado ocurrieron en pacientes de más edad que los que presentan MLH1 no metilado o MSS. (68.5±9.5 años vs 61.4±8.0 años vs 63.4 ± 10.0 años, respectivamente, p=0,008, test de Chi-cuadrado). Estos resultados sugieren la existencia de diferencias epidemiológicas en pacientes con CE con diferentes estados de inestabilidad de microsatélites y de metilación del promotor MLH1.

Agregación plaquetaria en perros con cáncer

[ES] Los trastornos psicopatológicos tienen una alta prevalencia (15-25%) y se asocian a numerosas variables. Por otro lado, el envejecimiento poblacional cada vez es mayor y los ancianos constituyen una población de riesgo donde a los factores que afectan a la población adulta se les asocian otros específicos. En este trabajo se evalúa la prevalencia de ansiedad y depresión en la población mayor de 65 años de Las Palmas de Gran Canaria y su relación con variables sociodemográficas y psicosociales. Para ello hemos estudiado en una muestra representativa de esta población: variables sociodemográficas, salud general percibida, hábitos de vida, nivel funcional, rasgos de ansiedad y depresión, acontecimientos vitales estresantes y apoyo social percibido.

Los estrógenos ambientales en Canarias: Posible relación con el cáncer de mama

[ES] El concepto de estrógenos ambientales (EA) incluye un gran número de compuestos químicos de estructura química diferente y que sólo comparten su capacidad para afectar al sistema endocrino de los diferentes organismos vivos al mimificar total o parcialmente la acción de las hormonas estrogénicas fisiológicas.

Factores genéticos y ambientales relacionados con la génesis de cáncer vesical

[ES] Antecedentes: La exposición a sustancias químicas es uno de los factores de riesgo más conocidos y relevantes del cáncer vesical (CaV). Asimismo los factores reguladores de la proliferación celular (como los Insulin-like growth factors- IGF) y la expresión de genes involucrados en la transformación de xenobióticos y en la angiogénesis y proliferación celular, parecen ser factores relevantes en la etiología del CaV. Objetivo: Evaluar la relevancia de los hábitos de vida, la exposición a contaminantes ambientales (y factores de crecimiento celular relacionados) y las características genéticas de la población canaria como factores de riesgo de cáncer vesical en un estudio de casos y controles hospitalarios desarrollado en el Complejo Hospitalario Insular Materno Infantil de Gran Canaria.

Clasificación molecular del cáncer de mama y su impacto en el control inducido por el hipofraccionamiento.

Programa de doctorado: Cáncer: Biología y clínica.

Radioterapia hiperfraccionada en cáncer de mama: resultados clínicos en relación con estudios moleculares y la calidad de vida

Programa de doctorado: Salud pública (Epidemiología, planificación y nutrición)

Biopsia selectiva del ganglio centinela con 99mTc-nanocoloides en el cáncer de mama : validación de la técnica, implantación y análisis del impacto sobre el pronóstico de la enfermedad

Programa de doctorado: Avances en Medicina Interna.

L'epatite E nei suidi: epidemiologia, diagnosi e filogenesi

Hepatitis E is an infectious viral disease with clinical and morphological features of acute hepatitis. The aetiological agent is the Hepatitis E virus (HEV). The disease represents an important Public Health problem in developing countries where is frequently epidemic and primarily transmitted by fecal-oral route. In the last few years, a certain number of sporadic cases have been also described in industrialized countries, Italy included. A swine HEV was first identified in 1997 and is now considered an ubiquitous virus. Human and swine strains from the same geographical region have shown to have a high level of nucleotidic omology and in experimental infections, the possibility of interspecific transmission of swine strains to humans and of human strains to non-human primates has been demonstrated. Furthermore, some seroepidemiological studies have demonstrated that people working in contact with swine have a higher risk to get infected than normal blood donors. Recently, cases of HEV hepatitis have been directly associated to the ingestion of uncooked tissues from pigs, wild boar or deer and today the disease is considered an emerging zoonosis. The aims of this thesis were: evaluate HEV prevalence in Italian swine herds (both in fattening and in breeding animals); investigate the possibility of finding HEV in livers used for human consumption; investigate if there is any correlation between HEV infection and the presence of macroscopical lesions; investigate HEV prevalence in a demographic managed wild boar population; phylogenetically analyse viral strains identified. During an internship period at Veterinary Laboratories Agency (Weybridge, UK), furthermore, swine samples at different stages of production and slurry lagoons have been analysed. Six swine herds located in North Italy have been sampled at different stage of production. The overall prevalence resulted 42%, and both breeding and fattening animals were positive for HEV infection. A longitudinal study has been conducted in a herd across all stages of production until the slaughtering age. Livers have been collected from the animals at the abattoir and 11.8% of them were positive for HEV infection. No correlations have been identified between HEV infection and macroscopical lesions in pigs affected by different pathological conditions. Of 86 wild boars tested 22 (25%) were positive for HEV. Of the swine tested in UK 21,5 % and 2 of the 9 slurry lagoons (22,2%) were positive for HEV infection. All the strains identified belonged to genotype 3 and showed high percentages of nucleotidic identity with humans and swine strains identified in Europe. The high prevalence detected in these studies confirms the widespread diffusion of HEV in swine populations in Italy and in UK. Phylogenetical analysis of identified strains, similar to those identified in autochthonous human hepatitis E cases of the same geographical area, confirm the hypothesis that pigs can be a font of zoonotical infection. The finding that a fraction of the livers inserted in the food chain are positive for HEV infection it’s of some concern for Public Health. The finding of a high HEV prevalence in all examined farms, together with the observation that infection may be sub-clinical and affect animals at slaughtering age, raise concern because of the possible risk of transmission of HEV to humans by either direct contact with infected pigs, indirect contact with environment and working instruments contaminated with pig feces, or ingestion of contaminated undercooked meat.

Microsatélites polimórficos : estudio de su posible papel en el cáncer de mama y la resistencia a insulina

Programa de doctorado: Cáncer: Biología y clínica

Patologia ed epidemiologia molecolare delle infezioni associate all'impianto

Staphylococcus aureus and Staphylococcus epidermidis are leading pathogens of implant-related infections. This study aimed at investigating the diverse distribution of different bacterial pathogen factors in most prevalent S. aureus and S. epidermidis strain types causing orthopaedic implant infections. In this study the presence both of the ica genes, encoding for biofilm exopolysaccharide production, and the insertion sequence IS256, a mobile element frequently associated to transposons, was investigated in relationship with the prevalence of antibiotic resistance among Staphylococcus epidermidis strains. The investigation was conducted on 70 clinical isolates derived from orthopaedic implant infections. Among the clinical isolates investigated a dramatic high level of association was found between the presence of ica genes as well as of IS256 and multiple resistance to all the antibiotics tested. Noteworthy, a striking full association between the presence of IS256 and resistance to gentamicin was found, being none of the IS256-negative strain resistant to this antibiotic. This association is probably because of the link of the corresponding aminoglycoside-resistance genes, and IS256, often co-existing within the same staphylococcal transposon. Moreover we investigated the prevalence of aac(6’)-Ie-aph(2’’), aph (3’) IIIa, and ant(4’) genes, encoding for the three forms of aminoglycoside-modifying enzymes (AME), responsible for resistance to aminoglycoside antibiotics. All isolates were characterized by automated ribotyping, so that the presence of antibiotic resistance determinants was investigated in strains exhibiting different ribopatterns. Interestingly, combinations of coexisting AME genes appeared to be typical of specific ribopatterns. 200 S. aureus isolates, categorized into ribogroups by automated ribotyping, i.e. rDNA restriction fragment length polymorphism analysis, were screened for the presence of a panel of adhesins genes, accessory gene regulatory (agr) polymorphisms and toxins. For many ribogroups, characteristic tandem genes arrangements could be identified. Surprisingly, the isolates of the most prevalent cluster, enlisting 27 isolates, were susceptible to almost all antibiotics and never possessed the lukD/lukE gene, thus suggesting the role of factors other than antibiotic resistance and the here investigated toxins in driving the major epidemic clone to the larger success. Afterwards, .in the predominant S. aureus cluster, the bbp gene encoding bone sialoprotein-binding protein appeared a typical virulence trait, found in 93% of the isolates. Conversely, the bbp gene was identified in just 10% of the remaining isolates of the collection. In this cluster, co-presence of bbp with the cna gene encoding collagen adhesin was a pattern consistently observed. These findings indicate a crucial role of both these adhesins, able to bind the most abundant bone proteins, in the pathogenesis of orthopaedic implant infections, there where biomaterials interface bone tissues. Moreover a PCR screening for the ebpS gene, conducted on over two hundred S. aureus clinical isolates from implant related infections revealed the detection of six strains exhibiting an altered amplicon size, shorter than expected. In order to elucidate the sequence changes present in these gene variants, the trait comprised between the primers was analyzed in all six isolates bearing the modification and in four isolates exhibiting the regular amplicon size. From nucleotide translation, the corresponding encoded protein was found to lack an entire peptide segment of 60 amino acids. These variants, missing an entire hydrophobic region, could actually facilitate current structural studies, helping to assess whether the absent domain is strictly necessary for a functional adhesin conformation and its contribution to the topology of the protein. This study suggests that epidemic clones appear to pursue different survival strategies, where adhesins, when present, exhibit diverse importance as virulence factors. A practical message arising from the present study is that strategies for the prevention and treatment of implant orthopaedic infections should target adhesins conjointly present in epidemic clones. Furthermore, the choice of reference strains for testing the anti-infective properties of biomaterials should focus on a selection of the most prevalent clones as they exhibit distinct profiles of adhesins.