Germans Trias i Pujol Research Institute IGTP

Barcelona, Spain

Germans Trias i Pujol Research Institute IGTP

Barcelona, Spain

Time filter

Source Type

PubMed | Catalan Institute of Nanoscience and Nanotechnology, Germans Trias i Pujol Research Institute IGTP, Germans Trias i Pujol Hospital and Idibell Campus In Hospitalet Of Llobregat
Type: | Journal: Scientific reports | Year: 2017

We wanted to implement an NGS strategy to globally analyze hereditary cancer with diagnostic quality while retaining the same degree of understanding and control we had in pre-NGS strategies. To do this, we developed the I2HCP panel, a custom bait library covering 122 hereditary cancer genes. We improved bait design, tested different NGS platforms and created a clinically driven custom data analysis pipeline. The I2HCP panel was developed using a training set of hereditary colorectal cancer, hereditary breast and ovarian cancer and neurofibromatosis patients and reached an accuracy, analytical sensitivity and specificity greater than 99%, which was maintained in a validation set. I2HCP changed our diagnostic approach, involving clinicians and a genetic diagnostics team from panel design to reporting. The new strategy improved diagnostic sensitivity, solved uncertain clinical diagnoses and identified mutations in new genes. We assessed the genetic variation in the complete set of hereditary cancer genes, revealing a complex variation landscape that coexists with the disease-causing mutation. We developed, validated and implemented a custom NGS-based strategy for hereditary cancer diagnostics that improved our previous workflows. Additionally, the existence of a rich genetic variation in hereditary cancer genes favors the use of this panel to investigate their role in cancer risk.


PubMed | Gustave Roussy Cancer Campus, Marie Lannelongue Hospital, Autonomous University of Barcelona, Institute Hospital del Mar Investigacions Mediques IMIM and 5 more.
Type: Journal Article | Journal: Hepatology (Baltimore, Md.) | Year: 2016

Identification of new treatments for relapsing pediatric cancer is an unmet clinical need and a societal challenge. Liver cancer occurrence in infancy, 1.5 for million children per year, falls far below the threshold of interest for dedicated drug development programs, and this disease is so rare that it is very difficult to gather enough children into a phase II clinical trial. Here, we present the establishment of an unprecedented preclinical platform of 24 pediatric liver cancer patient-derived xenografts (PLC-PDXs) from 20 hepatoblastomas (HBs), 1 transitional liver cell tumor (TCLT), 1 hepatocellular carcinoma, and 2 malignant rhabdoid tumors. Cytogenetic array and mutational analysis of the parental tumors and the corresponding PLC-PDXs show high conservation of the molecular features of the parental tumors. The histology of PLC-PDXs is strikingly similar to that observed in primary tumors and recapitulates the heterogeneity of recurrent disease observed in the clinic. Tumor growth in the mouse is strongly associated with elevated circulating alpha-fetoprotein (AFP), low rate of necrosis/fibrosis after treatment, and gain of chromosome 20, all indicators of resistance to chemotherapy and poor outcome. Accordingly, the ability of a tumor to generate PLC-PDX is predictive of poor prognosis. Exposure of PLC-PDXs to standards of care or therapeutic options already in use for other pediatric malignancies revealed unique response profiles in these models. Among these, the irinotecan/temozolomide combination induced strong tumor regression in the TCLT and in a model derived from an AFP-negative relapsing HB.These results provide evidence that PLC-PDX preclinical platform can strongly contribute to accelerate the identification and diversification of anticancer treatment for aggressive subtypes of pediatric liver cancer. (Hepatology 2016;64:1121-1135).


Teniente-Serra A.,University of Barcelona | Teniente-Serra A.,Autonomous University of Barcelona | Grau-Lopez L.,University of Barcelona | Mansilla M.J.,University of Barcelona | And 6 more authors.
Autoimmunity | Year: 2016

Objective: The objective of this study is to characterise the functionally relevant minor lymphocyte subpopulations in whole blood of multiple sclerosis (MS) patients and their potential utility as biomarkers for treatment follow up. Material and methods: Peripheral blood from 40 healthy donors (HD) and 66 MS patients [23 relapsing–remitting (RRMS) without treatment, 27 RRMS undergoing treatment (16 IFN-β, 11 natalizumab), and 16 progressive forms (eight secondary progressive and eight primary progressive)] was analysed by multiparametric flow cytometry. Results: Untreated MS patients showed a decrease in early effector memory (CD45RA−CCR7−CD27+) CD4+ and CD8+ T cells and an increase in Th17 lymphocytes in peripheral blood compared with HD. Regarding the effect of treatment, whereas no differences in relative percentages of cellular subpopulations were observed in patients under IFN-β treatment, those under treatment with natalizumab had an increased percentage of early effector memory CD4+ (CD45RA−CCR7−CD27+), central memory CD8+ (CD45RA−CCR7+CD27+) T cells, recent thymic emigrants (CD4+ CD45RA+CCR7+CD27+CD31+PTK7+) and transitional B cells (CD19+CD27−CD24hiCD38hi). Conclusions: Multiparametric flow cytometry analysis of whole blood is a robust, reproducible, and sensitive technology to monitor the effect of MS treatments even in minor lymphocyte subpopulations that might represent useful biomarkers of treatment response. © 2016 Informa UK Limited, trading as Taylor & Francis Group.


PubMed | University of Barcelona, Germans Trias i Pujol Research Institute IGTP and e Blood and Tissue Bank BST
Type: Journal Article | Journal: Autoimmunity | Year: 2016

The objective of this study is to characterise the functionally relevant minor lymphocyte subpopulations in whole blood of multiple sclerosis (MS) patients and their potential utility as biomarkers for treatment follow up.Peripheral blood from 40 healthy donors (HD) and 66 MS patients [23 relapsing-remitting (RRMS) without treatment, 27 RRMS undergoing treatment (16 IFN-, 11 natalizumab), and 16 progressive forms (eight secondary progressive and eight primary progressive)] was analysed by multiparametric flow cytometry.Untreated MS patients showed a decrease in early effector memory (CD45RA(-)CCR7(-)CD27(+)) CD4(+) and CD8(+) T cells and an increase in Th17 lymphocytes in peripheral blood compared with HD. Regarding the effect of treatment, whereas no differences in relative percentages of cellular subpopulations were observed in patients under IFN- treatment, those under treatment with natalizumab had an increased percentage of early effector memory CD4(+) (CD45RA(-)CCR7(-)CD27(+)), central memory CD8(+) (CD45RA(-)CCR7(+)CD27(+)) T cells, recent thymic emigrants (CD4(+) CD45RA(+)CCR7(+)CD27(+)CD31(+)PTK7(+)) and transitional B cells (CD19(+)CD27(-)CD24(hi)CD38(hi)).Multiparametric flow cytometry analysis of whole blood is a robust, reproducible, and sensitive technology to monitor the effect of MS treatments even in minor lymphocyte subpopulations that might represent useful biomarkers of treatment response.

Loading Germans Trias i Pujol Research Institute IGTP collaborators
Loading Germans Trias i Pujol Research Institute IGTP collaborators