Pharmacogenetics of ugt genes in North African populations

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]. [...

Natación artística en niñas: antropometría, genotipo y rendimiento deportivo.

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.post-print680 K

A catalogue of Spanish archaeomagnetic data

International audienceA total of 58 new archaeomagnetic directions has been determined from archaeological structures in Spain. Together with five previous results they allow the compilation of the first archaeomagnetic catalogue for Spain, which includes 63 directions with ages ranging between the 2nd century BC and the 20th century AD. Characteristic remanence directions have been obtained from stepwise thermal and alternating field demagnetization. The hierarchical structure has been respected in the calculation of the mean site directions. Rock magnetic experiments reveal that the main magnetic carrier is magnetite or titanomagnetite with different titanium contents. The age estimate of the studied structures is generally well justified by archaeological constraints. For six structures the proposed date is also supported by physical methods. The data are in close agreement with the French secular variation (SV) curve. This catalogue represents the first step in the construction of a SV curve for the Iberian Peninsula, which will be of much use in archaeomagnetic dating and in modelling of the Earth's magnetic field in Western Europe

Newer generations of multi-target CAR and STAb-T immunotherapeutics: NEXT CART Consortium as a cooperative effort to overcome current limitations

Adoptive T cellular immunotherapies have emerged as relevant approaches for treating cancer patients who have relapsed or become refractory (R/R) to traditional cancer treatments. Chimeric antigen receptor (CAR) T-cell therapy has improved survival in various hematological malignancies. However, significant limitations still impede the widespread adoption of these therapies in most cancers. To advance in this field, six research groups have created the “NEXT Generation CART MAD Consortium” (NEXT CART) in Madrid’s Community, which aims to develop novel cell-based immunotherapies for R/R and poor prognosis cancers. At NEXT CART, various basic and translational research groups and hospitals in Madrid concur to share and synergize their basic expertise in immunotherapy, gene therapy, and immunological synapse, and clinical expertise in pediatric and adult oncology. NEXT CART goal is to develop new cell engineering approaches and treatments for R/R adult and pediatric neoplasms to evaluate in multicenter clinical trials. Here, we discuss the current limitations of T cell-based therapies and introduce our perspective on future developments. Advancement opportunities include developing allogeneic products, optimizing CAR signaling domains, combining cellular immunotherapies, multi-targeting strategies, and improving tumor-infiltrating lymphocytes (TILs)/T cell receptor (TCR) therapy. Furthermore, basic studies aim to identify novel tumor targets, tumor molecules in the tumor microenvironment that impact CAR efficacy, and strategies to enhance the efficiency of the immunological synapse between immune and tumor cells. Our perspective of current cellular immunotherapy underscores the potential of these treatments while acknowledging the existing hurdles that demand innovative solutions to develop their potential for cancer treatment fully

Differential expression of PMCA2 mRNA isoforms in a cohort of Spanish patients with breast tumor types

© 2018 The Authors. Published by Spandidos Publications. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3892/ol.2018.9540© Romero-Lorca et al. 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<0.028). Furthermore, PMCA2z expression was significantly associated with PR status (P<0.024, compared with in PR-negative tumor tissues), and PMCA2w expression was significantly associated with ER status (P<0.048, increased in ER-positive tumor tissues, compared with ER-negative tumor tissues). Finally, PMCA2b was overexpressed in HER2-positive tumor tissues, compared with in HER2-negative tumor tissues (P<0.014). The data demonstrated the differential mRNA expression of a number of splice site A and C variants of PMCA2 in breast tumor and adjacent tissues, depending on tumor hormone receptor status and histological classification. In agreement with previous data, PMCA2b was overexpressed in HER2-positive tumor tissues, indicating that high mRNA levels of this variant could be a marker of poor prognosis.The present study was funded by the Universidad Europea de Madrid (project 2014/UEM005).Published versio

Pharmacogenetics of ugt genes in North African populations

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]. [...

Pharmacogenetics of ugt genes in North African populations

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]. [...