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Alicia Romero-Lorca,1 Apolonia Novillo,1 María Gaibar,1 María Fuencisla Gilsanz,1 Miguel Galán,1 Laura Beltrán,1 Beatriz Antón,2 Diego Malón,2 Amalia Moreno,2 Ana Fernández-Santander1 1Biomedical and Health Sciences Faculty, Universidad Europea de Madrid, Madrid, 28670, Spain; 2Department of Oncology, University Hospital of Fuenlabrada, Madrid, 28942, SpainCorrespondence: Ana Fernández-SantanderBiomedical and Health Sciences Faculty, Universidad Europea de Madrid, c/ Tajo s/n, Villaviciosa de Odón, Madrid, 28670, SpainTel +34 912 115 288Fax +34 916 168 265Email ana.fernandez@universidadeuropea.esPurpose: Bevacizumab is a monoclonal antibody that binds to vascular endothelial growth factor A. It is currently used in combination with chemotherapy to treat metastatic colorectal cancer. This therapy is not equally effective in every patient; in some, mechanisms of resistance arise that remain poorly understood. The aim of the present work was to determine whether the expression of 26 miRNAs could be associated with the effectiveness of bevacizumab plus chemotherapy, with progression-free survival (PFS), and with overall survival (OS) in metastatic colorectal cancer.Patients and Methods: Paraffin-embedded biopsies from 76 patients with metastatic colorectal cancer were collected to isolate miRNAs. The expression of 26 miRNAs was analyzed by quantitative RT-PCR. For the purpose of analysis, patients were classified as either “responders” (PFS ≥ 6 months since beginning treatment) or “non-responders” (PFS < 6 months). For the analysis of PFS and OS, patients were classified into two groups using the median gene expression value as the cut-off point (“high” [≥ 50% percentile] or “low” [< 50% percentile]). Time-to-event data were analyzed using the Kaplan–Meier method and compared by the log rank test. Cox regression was used to estimate hazard ratios (HR) and their 95% confidence intervals.Results: miR-7-5p and miR-10a-5p were more strongly expressed in non-responders than responders (p=0.049 and p=0.043, respectively), and OS was poorer in patients showing these higher expression levels (HR=2.54, 95% CI 1.42– 4.55, p=0. 001, and HR=1.81, 95% CI 1.02– 3.20, p=0.039, respectively). The overexpression of miR-143-3p, however, was associated with a better prognosis and significantly better PFS (HR=0.57; 95% CI: 0.33– 0.96; p=0.033).Conclusion: High expression values for miR-7-5p and miR-10a-5p might be considered markers of a poorer prognosis in patients with metastatic colorectal cancer treated with bevacizumab plus chemotherapy, while the same for miR-143-3p might be a marker of better outcomes.Keywords: miRNAs, colorectal cancer, bevacizumab, paraffin-embedded biopsies, progression free survival, overall survival

En cada deporte es importante optimizar peso y composición corporal y la genética y los datos antropométricos pueden influir en rendimiento deportivo y salud, sobre todo en deportistas menores. Este estudio analiza 60 nadadoras artísticas entre 9 y 17 años, divididas en tres grupos de edad: ≤12, 13-15 y 16-17 años. Se realizó un análisis de medidas antropométricas, edad de menarquia, genotipo relacionado con rendimiento (gen ACTN3) y resultados deportivos, con objetivo de relacionar estos parámetros entre sí en los grupos de edad. Las nadadoras de mayor edad mostraron tendencia a portar el genotipo heterocigoto RX de ACTN3. En este estudio, la práctica de este deporte podría tener impacto en índice de masa corporal, pliegue tricipital, peso y edad de menarquia. La mayor prevalencia del genotipo heterocigoto ACTN3 R577X podría ofrecer una ventaja, pero el rendimiento en competición de las nadadoras artísticas tuvo poca relación con sus medidas antropométricas. In sport, optimizing weight and body composition is important for performance although an excessive drive for thinness can lead to diminished performance and health problems. This is especially important in the youngest athletes. This study examines 60 national competition-level Spanish artistic swimmers aged 9-17 years. Participants were divided into 3 categories: 12 years and under, 13-15 and 16-17 years. The data analysed were anthropometric measures, menarche age, genotype related to performance (gene ACTN3) and athletic performance. Relationships between athletic performance and anthropometric or genetic data were compared among the three age groups. Swimmers showed a tendency to carry the heterozygous genotype RX of the ACTN3 gene in the older age group. In this study, this sport could have an impact on body mass index, triceps skinfold, weight, menarche age, and selection of one genotype, but the performance in competition of the artistic swimmers had little linking to anthropometric measures. 2016UEM15 1.406 JCR (2020) Q4, 76/88 Sport Sciences 0.335 SJR (2020) Q3, 118/210 Physical Therapy, Sports Therapy and Rehabilitation 1,311 IDR (2020) C1, 7/43 Deporte UEM

The addition to chemotherapy of anti-HER2 drugs such as trastuzumab or pertuzumab has improved outcomes in HER2-positive breast cancer patients. However, resistance to these drugs in some patients remains a major concern. This study examines the possible association between the response to neoadjuvant anti-HER2 treatment in breast cancer patients and the presence of 28 SNPs in 17 genes involved in different cell processes (PON1, CAT, GSTP1, FCGR3, ATM, PIK3CA, HER3, BARD1, LDB2, BRINP1, chr6 intergenic region, RAB22A, TRPC6, LINC01060, EGFR, ABCB1, and HER2). Tumor samples from 50 women with early breast cancer were genotyped using the iPlex®Gold chemistry and MassARRAY platform, and patients were classified as good responders (Miller–Payne tumor grades 4–5) and poor responders (Miller–Payne tumor grades 1–3), as assessed upon surgery after 6 months of treatment. Proportions of patients with the HER2Ala1170Pro (rs1058808) SNP double mutation were higher in good (58.62%) than poor (20%) responders (p = 0.025). Similarly, proportions of patients carrying the synonymous SNP rs2070096 (BARD1Thr351=) (wv + vv) were higher in patients showing a pathological complete response (46.67%) than in those not showing this response (15.15%) (p = 0.031). The SNPs rs1058808 (HER2Ala1170Pro) and rs2070096 (BARD1Thr351=) were identified here as potential biomarkers of a good response to anti-HER2 treatment. Universidad Europea de Madrid (2020/UEM15) Foundation of the Universidad Europea, (FGUE001804 and FGUE001805 6.575 Q1 JCR 2021 1.349 Q1 SJR 2021 No data IDR 2021 UEM

Chromodomain-helicase-DNA-binding protein 4 (CHD4) is an epigenetic regulator identified as an oncogenic element that may provide a novel therapeutic target for the treatment of breast cancer (BC). CHD4-the core component of the nucleosome remodeling and deacetylase (NuRD) complex-may be mutated in patients with this disease. However, information on CHD4 mutants that might allow their use as biomarkers of therapeutic success and prognosis is lacking. The present work examines mutations in CHD4 reported in patients with breast cancer and included in public databases and attempts to identify their roles in its development. The databases revealed 81 point mutations across different types of breast cancer (19 of which also appeared in endometrial, intestinal, nervous system, kidney, and lymphoid organ cancers). 71.6% of the detected mutations were missense mutations, 13.6% were silent, and 6.2% nonsense. Over 50% affected conserved residues of the ATPase motor (ATPase and helicase domains), and domains of unknown function in the C-terminal region. Thirty one mutations were classified in the databases as either 'deleterious', 'probably/possibly damaging' or as 'high/medium pathogenic'; another five nonsense and one splice-site variant were predicted to produce potentially harmful truncated proteins. Eight of the 81 mutations were categorized as putative driver mutations and have been found in other cancer types. Some mutations seem to influence ATPase and DNA translocation activities (R1162W), while others may alter protein stability (R877Q/H, R975H) or disrupt DNA binding and protein activity (R572*, X34_splice) suggesting CHD4 function may be affected. In vivo tumorigenecity studies in endometrial cancer have revealed R975H and R1162W as mutations that lead to CHD4 loss-of-function. Our study provides insight into the molecular mechanism whereby CHD4, and some of its mutants could play a role in breast cancer and suggest important implications for the biological comprehension and prognosis of breast cancer, identifying CHD4 as a novel therapeutic target for BC patients. PG-A is supported by Ministry of Science and Innovation of Spain MICINN (grant no. SAF2016-77816-P). AN, AF-S, MaG, and AR-L are supported by the Fundación de la Universidad Europea (project numbers XSAN001907 and XFGU001903). FA-S is a recipient of a fellowship from the MICINN (no. BES-2017-080629). Sí

Angiogenesis pathway genes show substantial genetic variability causing inter-individual differences in responses to anti-angiogenic drugs. We examined 20 single nucleotide polymorphisms (SNPs) in 13 of these genes to predict tumour response and clinical outcome measured as progression free survival (PFS) and overall survival (OS) in 57 patients with metastatic colorectal cancer (mCRC) given bevacizumab plus chemotherapy. SNPs were detected (iPLEX&reg, Assay) in genomic DNA extracted from formalin-fixed paraffin-embedded tumour specimens. The variant allele CD39 rs11188513 was associated with a good tumour response (p = 0.024). Patients homozygous for the wild-type allele FGF2 rs1960669 showed a median PFS of 10.95 months versus 5.44 months for those with at least one variant allele-A (HR 3.30, 95% CI: 1.52&ndash, 7.14, p = 0.001). Patients homozygous for wild-type MMP9 rs2236416 and rs2274755 showed a median PFS of 9.48 months versus 6 and 6.62 months, respectively, for those with at least one variant allele (p = 0.022, p = 0.043, respectively). OS was also lengthened to 30.92 months (p = 0.034) in carriers of wild-type ANGPT1 rs2445365 versus 22.07 months for those carrying at least one variant allele-A. These gene variants were able to predict clinical outcome and tumour response in mCRC patients given bevacizumab-based therapy.

HER2-positive breast cancer (BC) is an aggressive subtype that affects 20–25% of BC patients. For these patients, neoadjuvant therapy is a good option that targets a pathological complete response (pCR) and more breast-conserving surgery. In effect, the outcomes of patients with HER2-positive BC have dramatically improved since the introduction of anti-HER2 antibodies such as trastuzumab (TZ) and/or pertuzumab (PZ) added to chemotherapy. This study sought to examine whether correlation exists between copy number variations (CNVs) in several genes related to the PI3K/AKT pathway (HER2, FGFR1, PIK3CA, AKT3 and MDM2) and the efficacy of anti-HER2 neoadjuvant treatment in patients with early HER2-positive BC. Forty-nine patients received TZ or PZ/TZ and chemotherapy as neoadjuvant treatment. Gene CNVs were determined by quantitative polymerase chain reaction on paraffin-embedded biopsy specimens. The response to 6 months of therapy was assessed by Miller–Payne grading of the tumor on surgical resection; grades 4 and 5, indicating >90% tumor reduction, were defined as a good response. A good response was shown by 64.5% and a pCR by 31.2% of patients. When stratified by anti-HER2 antibody received and gene CNV, it was found that patients with FGFR1 gene amplification or those with FGFR1 amplification treated with TZ alone showed a poor response (p = 0.024 and p = 0.037, respectively). In the subset of patients treated with TZ/PZ combined, the pCR rate was significantly lower among those showing FGFR1 amplification (p = 0.021). Although based on a small sample size, our findings suggest that patients with FGFR1 amplification might benefit less from anti-HER2 antibody therapy.

In one of every four or five cases of breast cancer, the human epidermal growth factor receptor-2 (HER2) gene is overexpressed. These carcinomas are known as HER2-positive. HER2 overexpression is linked to an aggressive phenotype and a lower rate of disease-free and overall survival. Drugs such as trastuzumab, pertuzumab, lapatinib, neratinib, and the more recent afatinib target the deregulation of HER2 expression. Some authors have attributed somatic mutations in HER2, a role in resistance to anti-HER2 therapy as differential regulation of HER2 has been observed among patients. Recently, studies in metastatic ER + tumors suggest that some HER2 mutations emerge as a mechanism of acquired resistance to endocrine therapy. In an effort to identify possible biomarkers of the efficacy of anti-HER2 therapy, we here review the known single-nucleotide polymorphisms (SNPs) of the HER2 gene found in HER2-positive breast cancer patients and their relationship with clinical outcomes. Information was recompiled on 11 somatic HER2 SNPs. Seven polymorphisms are located in the tyrosine kinase domain region of the gene contrasting with the low number of mutations found in extracellular and transmembrane areas. HER2-positive patients carrying S310F, S310Y, R678Q, D769H, or I767M mutations seem good candidates for anti-HER2 therapy as they show favorable outcomes and a good response to current pharmacological treatments. Carrying the L755S or D769Y mutation could also confer benefits when receiving neratinib or afatinib. By contrast, patients with mutations L755S, V842I, K753I, or D769Y do not seem to benefit from trastuzumab. Resistance to lapatinib has been reported in patients with L755S, V842I, and K753I. These data suggest that exploring HER2 SNPs in each patient could help individualize anti-HER2 therapies. Advances in our understanding of the genetics of the HER2 gene and its relations with the efficacy of anti-HER2 treatments are needed to improve the outcomes of patients with this aggressive breast cancer. Sin financiación 4.375 JCR (2020) Q2, 115/242 Oncology 1.228 SJR (2020) Q2, 110/354 Oncology No data IDR 2020 UEM

BACKGROUND In metastatic colorectal cancer (mCRC), the anti-vascular endothelial growth factor drug bevacizumab (BVZ) plus chemotherapy significantly improves progression-free survival compared to chemotherapy (CT) alone. This benefit is not, however, observed in all patients. While increased chemokine CXCL5 gene expression promoting angiogenesis has been proposed as a prognostic mCRC biomarker, few studies have examined its relationship with drug efficacy. This study sought to analyze tumor CXCL5 gene expression in six patients with different efficacy of BVZ-containing CT in terms of the tumor response to treatment. CASE SUMMARY We report six cases of stage IV KRAS-mutated mCRC. Patients were given first line treatment with BVZ-containing chemotherapy in University Hospital of Fuenlabrada. The six patients differed in terms of primary tumor location (right/left side), tumor burden (mostly hepatic and peritoneal disease) and clinical disease course. Before treatment onset, total RNA was isolated from paraffinated tumor biopsy specimens and CXCL5 gene expression quantified through conventional RT-qPCR procedures. Our main finding was that CXCL5 expression levels were several times higher in three patients with lower progression free survival (under 6 mo) from the start of treatment. CONCLUSION A higher expression of CXCL5 was observed in the three patients showing worse tumor response to treatment. Fundación UEM FGUE001804, FGUE001805 2015/UEM12, 2016/UEM13 5.742 JCR (2020) Q2, 28/92 Gastroenterology & Hepatology 1.427 SJR (2020) Q1, 26/144 Gastroenterology No data IDR 2020 UEM

In one of every four or five cases of breast cancer, the human epidermal growth factor receptor-2 (HER2) gene is overexpressed. These carcinomas are known as HER2-positive. HER2 overexpression is linked to an aggressive phenotype and a lower rate of disease-free and overall survival. Drugs such as trastuzumab, pertuzumab, lapatinib, neratinib, and the more recent afatinib target the deregulation of HER2 expression. Some authors have attributed somatic mutations in HER2, a role in resistance to anti-HER2 therapy as differential regulation of HER2 has been observed among patients. Recently, studies in metastatic ER + tumors suggest that some HER2 mutations emerge as a mechanism of acquired resistance to endocrine therapy. In an effort to identify possible biomarkers of the efficacy of anti-HER2 therapy, we here review the known single-nucleotide polymorphisms (SNPs) of the HER2 gene found in HER2-positive breast cancer patients and their relationship with clinical outcomes. Information was recompiled on 11 somatic HER2 SNPs. Seven polymorphisms are located in the tyrosine kinase domain region of the gene contrasting with the low number of mutations found in extracellular and transmembrane areas. HER2-positive patients carrying S310F, S310Y, R678Q, D769H, or I767M mutations seem good candidates for anti-HER2 therapy as they show favorable outcomes and a good response to current pharmacological treatments. Carrying the L755S or D769Y mutation could also confer benefits when receiving neratinib or afatinib. By contrast, patients with mutations L755S, V842I, K753I, or D769Y do not seem to benefit from trastuzumab. Resistance to lapatinib has been reported in patients with L755S, V842I, and K753I. These data suggest that exploring HER2 SNPs in each patient could help individualize anti-HER2 therapies. Advances in our understanding of the genetics of the HER2 gene and its relations with the efficacy of anti-HER2 treatments are needed to improve the outcomes of patients with this aggressive breast cancer.

Background: Genetic variation in glucuronosyltransferases (UGT) is crucial in drug metabolism and risk of some diseases. Aim: To examine genetic variation in UGT in North African populations. Subjects and methods: Allele frequencies of SNPs UGT1A424Thr, UGT1A448Val, UGT2B1585Tyr, UGT2B15523Thr and UGT2B17 CNV deletion from Morocco, Algeria, Tunisia and Libya were compared to European and Sub-Saharan populations. Results: North Africans are the group with the highest genetic heterogeneity given by internal differences in the occurrence of UGT2B17 deletion, UGT1A448Val and UGT1A4 haplotypes. UGT2B15 SNPs differentiate Sub-Saharans from the rest of the populations. Conclusion: North African populations show a high frequency of carriers of UGT2B15523Thr, a variant linked to an increased risk of prostate cancer. High Atlas Moroccans and Algerians show low frequency of UGT2B17del, a variant associated with high concentrations of testosterone and oestradiol. This work was financed by the grant ‘Ajut per potenciar sin􀀁���ergies en recerca’ awarded by the Faculty of Biology, University of Barcelona (2016 and 2017), the project 2016/UEM 39 of the Universidad Europea de Madrid, and by the 2017 SGR 1630 Grup de Recerca en Antropologia Biol􀀁���ogica (GREAB). 1.588 JCR (2018) Q2, 26/90 Anthropology; Q3, 84/164 Public, Environmental & Occupational Health, 51/87 Biology 0.616 SJR (2018) Q2, 208/562 Public Health, Environmental and Occupational Health; Q3, 67/106 Epidemiology, 112/188 Physiology, 226/351 Genetics, 23/36 Aging No data IDR 2018 UEM

El aprendizaje de nuestros estudiantes parte de una necesidad profunda de entender los fenómenos del mundo real que les rodea de una manera holística. Una de las metodologías activas más versátiles es el “Phenomenon- Based learning” (PhBL), que permite integrar y mejorar conocimientos a través de casos reales. En el Departamento de Ciencias Biomédicas Básicas, planteamos una actividad que les promueve a trabajar de forma multidisciplinar desde diferentes asignaturas (Bioquímica y Genética), realizada en dos Grados diferentes (Medicina y Biotecnología) para que se complementen. El formato es una investigación con presentación de resultados científicos en un congreso de estudiantes sobre enfermedades poco frecuentes. Impulsamos de este modo la sensibilización hacia la problemática económica y social de estas enfermedades, así como el compromiso de los alumnos con asociaciones de pacientes y el fomento de la investigación y la innovación para mejorar las condiciones de vida e inclusión de los pacientes. Nuestros resultados reflejan un aumento de la motivación hacia las materias básicas y una percepción muy positiva hacia la actividad. Los estudiantes entienden la importancia de abordar los problemas desde equipos multidisciplinares y recomiendan la consolidación del Congreso, por los excelentes resultados académicos de la actividad y por lo que les supone de motivación y sensibilización social. SIN FINANCIACIÓN No data 2019 UEM

The aim of this study is to describe the diversity of four cytochrome and four sulfotransferase polymorphisms in six north African samples. Scarce data have been compiled for these samples despite the rich genetic background of north African populations. CYP3A4*1B, CYP3A4*17, CYP3A4*3, CYP3A5*3, SULT1A1*2, SULT1A2*2, SULT1A2*3 and SULT1E1*2 polymorphisms were explored in 556 individuals from Morocco, Algeria, Tunisia and Libya. Allele frequencies in our samples largely exceeded the variation ranges described for European populations, especially for CYP3A4*1B, SULT1A1*2 and SULT1A2*3. North African populations are heterogeneous, genetically diverse and show a considerable sub-Saharan African contribution for markers associated with increased risk of prostate cancer and with differential drug metabolism. UEM (2015/31) 2.350 JCR (2016) Q3, 132/257 Pharmacology and Pharmacy UEM

Cytochrome P450 (CYP450), sulfotransferase (SULT), and glucuronidase (UGT) enzymes play roles in the phase I and phase II metabolism of most clinically prescribed drugs. As polymorphisms in these genes may alter enzyme activities, most prescribed drugs will differ in their efficacy and side effects. In prior work, we showed that besides polymorphisms in CYP450, those in SULT and UGT also give rise to different serum levels of some drug metabolites than detected in wild-type carriers of the genes [1]. [...]

The present study examined the mRNA expression levels of different isoforms of the plasma membrane calcium ATPase 2 (PMCA2) gene generated by alternative splicing at the first intracellular loop (site A) and C‑terminal region (site C) in 85 human breast cancer tumor and 69 adjacent non-tumor tissues. Associations were identified between the expression of PMCA2 splice isoforms and the following clinical variables: Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status, tumor size, staging and histological classification, and lymph node status. Transcripts including splice site A or splice site C were amplified by reverse transcription-quantitative polymerase chain reaction using PMCA2 isoform‑specific primers. Tumor and adjacent tissues were determined to express the different PMCA2 splice isoforms 2w, 2x and 2z (site A), and 2b (site C). The mRNA levels for these variants indicated high biological variability, but increased expression was observed in breast tumor tissues, compared with in adjacent tissues. Significantly increased PMCA2x/b expression levels were detected in breast tumor tissues histologically classified as lobulillar, compared with in ductal-types breast tumor tissues (P

Introducción: Desde el Departamento de Ciencias Biomédicas Básicas de la Universidad Europea de Madrid optamos por el diseño de actividades que fomenten un entorno de aprendizaje activo e integrador, centrado en el alumno y contextualizado en un entorno profesional. El objetivo es favorecer la asimilación de conceptos fundamentales, motivando al alumno y facilitando el aprendizaje extracurricular. Sujetos y métodos: Dentro de nuestras actividades de valor añadido hemos diseñado una dinámica a través del juego con estudiantes de los primeros cursos de los grados de Medicina, Farmacia y la doble titulación de Farmacia-Biotecnología. Utilizando como hilo conductor un caso clínico relacionado con una enfermedad cardiovascular, se diseñó una yincana con un carácter integrador de disciplinas básicas con diferentes estaciones de trabajo. Se premió la correcta resolución de las tareas incluidas en las estaciones de trabajo en un tiempo establecido. Resultados: Los estudiantes encuestados mostraron su satisfacción con la utilidad de estas sesiones integradas frente a las no integradas, así como con la inclusión de contenidos de diferentes materias (el 54% respondió favorablemente). El 58% de los grupos participantes afirmó que la actividad les acercó a contenidos nuevos. Conclusiones: Con esta actividad se ha aumentado el interés y la motivación de los alumnos por los conceptos más básicos de las ciencias biomédicas, a través de la integración real y la aplicación directa a un caso clínico auténtico. Asimismo, hemos conseguido que los alumnos trabajen competencias necesarias para asumir sus futuros roles como integrantes de equipos multidisciplinares, gracias a la participación de alumnos de grados distintos. Introduction: The Department of Basic Biomedical Sciences at the Universidad Europea de Madrid is committed to design activities that foster an environment of active and inclusive student-centered learning and contextualized in a professional environment. The aim is to ensure, through an integrated assimilation of fundamental concepts, the student motivation to learn and facilitate the extracurricular knowledge. Subjects and methods: Within our added-value activities, we have designed a play-based activity with students from the first course of the degrees of Medicine, Pharmacy and the double degree Pharmacy-Biotechnology. Using a clinical case related to a cardiovascular disease as a thread, a gymkhana was designed following a workstations working model. The correct resolution of all tasks included in each workstation without delay was finally rewarded. Results: Respondents found the integrated sessions more useful than the traditional seminars and also remarked that they bring up a variety of contents from different subjects successfully (54% positive answers). 58% of the survey participants expressed that the activity approached them new content not covered through the traditional master class. Conclusions: We have ensured that students develop skills required to take their future roles as members of multidisciplinary teams, thanks to the participation of students from different degrees. Moreover, the activity managed to increase motivation and the interest for the most basic concepts of Biomedical Sciences through real integration and direct application to a real clinical case. The experience was evaluated as very positive by all participants.

Esta actividad, diseñada desde el Departamento de Ciencias Biomédicas Básicas, se apoya en: 1. la integración de materias básicas (para contextualizar la experiencia clínica desde la perspectiva de sus fundamentos); 2. la formación interprofesional al trabajar con alumnos de diferentes Grados de nuestra Facultad y 3. el aprendizaje a través del juego, para facilitar un abordaje motivante y divertido a los destinatarios de la acción. Esta nueva experiencia consiste en una gymkhana por equipos en base a un caso clínico, en la que por primera vez se trabajan el aprendizaje y la docencia en diversas disciplinas básicas integradas, a través del juego y la competición entre grupos de alumnos (TBL). SIN FINANCIACIÓN No data 2016 UEM

This review is focused on the genetic variation of sulfotransferases (SULTs) and cytochromes (CYPs) genes among different ethnic groups, mainly focusing in variation in North African populations. Polymorphisms of SULTs and CYPs proteins are associated with altered enzymatic activity and physical characteristics. Single nucleotide polymorphisms (SNP) in these genes have shown relevant ethnic differences among Sub-Saharan African and European groups that might contribute to understand the variability in drug metabolism and risk to certain cancers that has been described among these two groups. Taking into account that North African populations have been scarcely described for these genes, and considering the rich genetic past of this region with a noticeable Sub-Saharan African contribution to their original background, it is interesting a revision and description of some relevant polymorphisms. UEM (2015/31) No data (2015) UEM

Las asignaturas básicas impartidas en los primeros cursos de los grados suelen resultar arduas para los estudiantes pues ven poca relación con sus futuras profesiones. Esto resulta en una tasa baja de asistencia a clases. Por otra parte, los alumnos están poco acostumbrados al estudio continuado y suelen preparar los exámenes con poca antelación. Para invertir estas tendencias, los profesores de las asignaturas Bioquímica I y II del Grado en Medicina hemos diseñado un método de evaluación complementario al de los exámenes, que consiste en la realización en clase de tests de respuesta múltiple al final de cada tema mediante el método del Clicker. El 5% de la nota media de estos tests se suma a la nota de los parciales. Nuestros resultados demuestran que se favorece a aquellos alumnos que asisten regularmente a clase y que llevan un estudio continuado a lo largo del temario, puesto que obtienen un incremento en su calificación. Además, aumenta la motivación hacia la asignatura y, sobre todo, los resultados académicos han mejorado considerablemente. SIN FINANCIACIÓN No data 2015 UEM

En la clase inversa el profesor proporciona al alumno (on-line) los materiales necesarios que deberán estudiar fuera de clase y dedica el tiempo designado en el aula a ser tutor, orientador y guía del aprendizaje y puede dedicar una atención personalizada a cada alumno. Nuestra hipótesis se basó en que la modificación de nuestras clases prácticas de la asignatura de Bioquímica I, “volteándolas” para que el alumno tome la iniciativa antes y durante el desarrollo de los experimentos en el laboratorio redundaría en un mayor y más significativo aprendizaje en comparación con los métodos tradicionales. Como conclusiones destacamos que el hecho de tener que preparar determinadas tareas previas a la clase práctica aumenta la cantidad de alumnos que tienen conocimientos sobre la misma y reduce el tiempo de realización. Al tener que diseñar sus propios experimentos y decidir qué material usan, el estudiante aumenta sus conocimientos sobre el trabajo de investigación, el material y los métodos de trabajo de los laboratorios. Además se reduce la probabilidad de copias de ejercicios aunque, por otra parte, la complejidad de los ejercicios que entregan al profesor dificulta la tarea de corrección. SIN FINANCIACIÓN No data 2014 UEM

Objective This study examines the lipid profile change produced in response to tamoxifen (TAM) treatment, and its possible relationship with both apolipoprotein E genotype and menopausal state in patients with breast cancer. Methods: Blood samples were collected from 86 Spanish women with breast cancer before initiating TAM treatment and in the following 6, 12 and 18 months of treatment. Plasma lipid levels (total cholesterol, triglycerides, HDL-cholesterol and LDL-cholesterol) were determined using an automatic analyzer. Genotypes for apolipoprotein E (ApoE) were identified by PCR-RFLP using the HhaI enzyme. Results In all patients, significant reductions in total cholesterol and LDL-cholesterol concentrations and a significant increase in triglyceride concentrations were observed after 6, 12, and 18 months of TAM treatment compared to baseline (pConclusions TAM treatment induced similar plasma triglyceride increases in patients with positive or negative APOE genotype. Compared to premenopausal patients, postmenopausal breast cancer patients showed a more beneficial lipid profile change in response to treatment.

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SIN FINANCIACIÓN No data 2013

Los estudios de Ciencias Biomédicas tienen una fuerte carga experimental y conexión con el mundo de la investigación que a muchos alumnos les cuesta reconocer, especialmente entre los de primer curso. Por ello, los autores hemos diseñado una actividad práctica integrada y evaluable para la asignatura Bioquímica II del Grado de Medicina, impartida en primer curso. Se pretendía conectar la asignatura con el mundo profesional de la investigación en Ciencias Biomédicas. El trabajo de los alumnos consistió en buscar la máxima información sobre el grupo que les hubiera correspondido, preparar una entrevista para realizar al investigador responsable del laboratorio y analizar su publicación más relevante, centrándose en la parte de su investigación que tiene que ver con nuestros estudios. El resultado ha sido satisfactorio a todos los niveles: los alumnos han obtenido buenas calificaciones y han valorado la actividad con un 3 sobre 4, los investigadores puntuaron mayoritariamente con la máxima calificación a los alumnos y los profesores estamos satisfechos con el aprovechamiento de los alumnos así como con la interacción con los investigadores y la integración con el resto de nuestros compañeros docentes. Entendemos que la actividad debe mejorarse de cara al futuro, sobre todo en relación al ítem peor valorado por los alumnos: la conexión entre lo explicado en clase y lo aprendido en el laboratorio. SIN FINANCIACIÓN No data 2012

Tesis inédita presentada en la Universidad Europea de Madrid. Escuela de Doctorado e Investigación. Programa de Doctorado en Biomedicina y Ciencias de la Salud En los últimos años se han incrementado los estudios orientados a la búsqueda de marcadores biológicos y genéticos que permitan la optimización del tratamiento farmacológico del cáncer, desde la investigación básica hacia la medicina personalizada. El objetivo del trabajo de investigación desarrollado en esta tesis doctoral fue encontrar biomarcadores de eficacia del tratamiento y de supervivencia del cáncer colorrectal metastásico con quimioterapia suplementada con bevacizumab, analizando la expresión de genes de proteínas relacionados con la angiogénesis y de genes de miARNs. Se consideraron buenos respondedores al tratamiento a aquellos pacientes que presentaron una supervivencia libre de progresión superior a 6 meses y malos respondedores a aquellos con una supervivencia libre de progresión inferior a 6 meses. El origen de las muestras fueron tumores o biopsias parafinados procedentes de pacientes con cáncer colorrectal metastásico del Hospital Universitario de Fuenlabrada. Se encontraron diferencias de expresión en varios genes de proteínas y de miARNs entre ambos grupos de pacientes, buenos respondedores y malos respondedores. Con respecto a los genes de proteínas se observó una mayor expresión de CXCL5 y TGFBR1 en pacientes malos respondedores, aunque esta relación no pudo ser comprobada estadísticamente debido al bajo número de pacientes en los que se obtuvieron resultados. Con respecto a los genes de miARNs, se observó una expresión significativamente mayor de miR-7 y miR-10 en pacientes malos respondedores frente a los buenos respondedores. Dado que se encontró una asociación entre la mayor expresión de miR-7 y miR-10 y una baja supervivencia global, se proponen estos miARNs como biomarcadores de mala respuesta al tratamiento de cáncer colorrectal metastásico con quimioterapia suplementada con bevacizumab. En relación a la supervivencia libre de progresión, la expresión de miR-143 fue superior o igual a la expresión génica mediana en el grupo de pacientes con supervivencia libre de progresión mayor, de una forma estadísticamente significativa. Se plantea la utilidad de estos estudios de expresión génica en pacientes con cáncer colorrectal metastásico tratados con quimioterapia suplementada con bevacizumab y con diferente respuesta al tratamiento como línea de investigación adecuada en las estrategias de búsqueda de biomarcadores de eficacia y supervivencia. [Resumen Teseo] UEM