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5. Pharmacogenetics of Neoadjuvant MAP Chemotherapy in Localized Osteosarcoma: A Study Based on Data from the GEIS-33 Protocol.

Author

Salazar, Juliana, Arranz, María J., Martin-Broto, Javier, Bautista, Francisco, Martínez-García, Jerónimo, Martínez-Trufero, Javier, Vidal-Insua, Yolanda, Echebarria-Barona, Aizpea, Díaz-Beveridge, Roberto, Valverde, Claudia, Luna, Pablo, Vaz-Salgado, María A., Blay, Pilar, Álvarez, Rosa, and Sebio, Ana

Subjects
*ADJUVANT chemotherapy, *ATP-binding cassette transporters, *NEOADJUVANT chemotherapy, *PROGNOSIS, *GENETIC variation
Abstract

Background: Osteosarcoma is a rare disease, but it is the most frequent malignant bone tumor. Primary treatment consists of preoperative MAP (methotrexate (MTX), doxorubicin and cisplatin) chemotherapy followed by surgery and adjuvant chemotherapy. Pathological response to preoperative chemotherapy is one of the most important prognostic factors, but molecular biomarkers are lacking. Additionally, chemotherapy-induced toxicity might jeopardize treatment completion. We evaluated variants in genes involved in DNA repair and drug metabolism pathways as predictors of response to MAP-based treatment. Material and Methods: Germline polymorphisms in MTHFR, SLC19A1, ABCB1, ABCC2, ABCC3, ERCC1, ERCC2 and GSTP1 genes were determined for association studies in 69 patients diagnosed with localized osteosarcoma who enrolled in the prospective GEIS-33 trial. P-glycoprotein expression in tumor tissue was also analyzed. Results: In the multivariate analysis, the ABCC2 rs2273697 (odds ratio [OR] 12.3, 95% CI 2.3–66.2; p = 0.003) and ERCC2 rs1799793 (OR 9.6, 95% CI 2.1–43.2; p = 0.003) variants were associated with poor pathological response. P-glycoprotein expression did not correlate with pathological response. The ABCB1 rs1128503 (OR 11.4, 95% CI 2.2–58.0; p = 0.003) and ABCC3 rs4793665 (OR 12.0, 95% CI 2.1–70.2; p = 0.006) variants were associated with MTX grade 3–4 hepatotoxicity. Conclusions: Our findings add to the evidence that genetic variants in the ABC transporters and DNA-repair genes may serve as predictive biomarkers for MAP chemotherapy and contribute to treatment personalization. [ABSTRACT FROM AUTHOR]

Published
2024
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6. CXCR4 Expression as a Prognostic Biomarker in Soft Tissue Sarcomas

Author

Virgili, Anna C., primary, Salazar, Juliana, additional, Gallardo, Alberto, additional, López-Pousa, Antonio, additional, Terés, Raúl, additional, Bagué, Silvia, additional, Orellana, Ruth, additional, Fumagalli, Caterina, additional, Mangues, Ramon, additional, Alba-Castellón, Lorena, additional, Unzueta, Ugutz, additional, Casanova, Isolda, additional, and Sebio, Ana, additional

Published
2024
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12. ERCC1 and ERCC2 Polymorphisms Predict the Efficacy and Toxicity of Platinum-Based Chemotherapy in Small Cell Lung Cancer.

Author

Barba, Andrés, López-Vilaró, Laura, Ferre, Malena, Majem, Margarita, Martinez-Recio, Sergio, Bell, Olga, Arranz, María J., Salazar, Juliana, and Sullivan, Ivana

Subjects
SMALL cell lung cancer, GENETIC variation, GENETIC polymorphisms, STATISTICAL significance, PROGRESSION-free survival
Abstract

Standard first-line chemotherapy in small cell lung cancer (SCLC) is based on the platinum plus etoposide combination. Despite a high objective response rate, responses are not durable and chemotherapy-induced toxicity may compromise treatment. Genetic variants in genes involved in the DNA-repair pathways and in etoposide metabolization could predict treatment efficacy and safety and help personalize platinum-based chemotherapy. Germline polymorphisms in XRCC1, ERCC1, ERCC2, ABCB1, ABCC3, UGT1A1 and GSTP1 genes were investigated in 145 patients with SCLC. The tumor expression of ERCC1 was determined using immunohistochemistry, and the tumor expression of ERCC1-XPF was determined via a proximity ligation assay. Survival analyses showed a statistically significant association between the ERCC1 rs11615 variant and median progression-free survival (PFS) in patients with limited-stage (LS) SCLC (multivariate: hazard ratio 3.25, [95% CI 1.38–7.70]; p = 0.007). Furthermore, we observed differences between the ERCC1-XPF complex and median PFS in LS-SCLC, although statistical significance was not reached (univariate: positive expression 10.8 [95% CI 4.09–17.55] months versus negative expression 13.3 [95% CI 7.32–19.31] months; p = 0.06). Safety analyses showed that the ERCC2 rs1799793 variant was significantly associated with the risk of grade ≥ 3 thrombocytopenia in the total cohort (multivariate: odds ratio 3.15, [95% CI 1.08–9.17]; p = 0.04). Our results provide evidence that ERCC1 and ERCC2 variants may predict the efficacy and safety of platinum-based chemotherapy in SCLC patients. LS-SCLC patients may benefit most from ERCC1 determination, but prospective studies are needed. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Clinical Relevance of Tumour-Infiltrating Immune Cells in HER2-Negative Breast Cancer Treated with Neoadjuvant Therapy

Author

Arqueros, Cristina, primary, Gallardo, Alberto, additional, Vidal, Silvia, additional, Osuna-Gómez, Rubén, additional, Tibau, Ariadna, additional, Lidia Bell, Olga, additional, Ramón y Cajal, Teresa, additional, Lerma, Enrique, additional, Lobato-Delgado, Bárbara, additional, Salazar, Juliana, additional, and Barnadas, Agustí, additional

Published
2024
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17. Genetic biomarkers of methotrexate response and safety in Crohn's disease: Data from the Spanish ENEIDA registry.

Author

Salazar, Juliana, Garcia‐Planella, Esther, Fernández‐Clotet, Agnès, Esteve, Maria, Gisbert, Javier P., Busquets, David, Lucendo, Alfredo, Márquez, Lucía, Guardiola, Jordi, Martín‐Arranz, María Dolores, Iglesias, Eva, Monfort, David, Villoria, Albert, Cañete, Fiorella, Bell, Olga, Ricart, Elena, Zabana, Yamile, Chaparro, María, Domènech, Eugeni, and Gordillo, Jordi

Subjects
*CROHN'S disease, *METHOTREXATE, *BIOMARKERS, *DISEASE remission
Abstract

Aims: Methotrexate (MTX) is used to induce and maintain remission in patients with steroid‐dependent Crohn's disease (CD). Despite its proven efficacy, its use is limited due to associated adverse events. Polymorphisms involving folate pathway genes might influence MTX efficacy and toxicity. We aimed to assess the impact of certain polymorphisms on the therapeutic outcomes of MTX in CD. Methods: Patients with CD who exclusively followed MTX monotherapy and fulfilled inclusion criteria were identified from the GETECCU ENEIDA registry. Variants of ATIC, DHFR, MTHFR, SLC19A1, ABCB1 and ABCC3 genes were analysed and their association with efficacy and toxicity was assessed. Results: A total of 129 patients were included in the analysis. MTX was used at a median weekly dose of 25 mg (interquartile range, 15–25 mg) and a median time of 14 months (interquartile range, 4–52 months). Thirty‐seven percent of the patients achieved disease remission with MTX monotherapy, while 34% were nonresponders (MTX failure). MTX‐related toxicity occurred in 40 patients (30%), leading to MTX discontinuation in 19%. DHFR rs408626 (odds ratio [OR] 3.12, 95% confidence interval [CI] 1.22–7.69; P =.017) and MTHFR rs1801133 (OR 2.86, 95% CI 1.23–6.68; P =.015) variants, and smoking (OR 2.61, 95% CI 1.12–6.05; P =.026) were associated with a higher risk of MTX failure. Additionally, the MTHFR rs1801131 variant was associated with a higher risk of MTX‐related adverse effects (OR 2.78, 95% CI 1.26–6.13, P =.011). Conclusion: Our study shows that variants of MTHFR and DHFR genes may be associated with MTX efficacy and adverse events in patients with CD. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Secreted Protein Acidic and Rich in Cysteine (SPARC) Polymorphisms in Response to Neoadjuvant Chemotherapy in HER2-Negative Breast Cancer Patients

Author

Arqueros, Cristina, primary, Salazar, Juliana, additional, Gallardo, Alberto, additional, Andrés, Marta, additional, Tibau, Ariadna, additional, Lidia Bell, Olga, additional, Artigas, Alícia, additional, Lasa, Adriana, additional, Ramón y Cajal, Teresa, additional, Lerma, Enrique, additional, and Barnadas, Agustí, additional

Published
2023
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27. Narración e interacción social en el recurso Espacio de Lectura: ejes para reconocer, interpretar y reconstruir la realidad

Author

Uribe Hincapié, Richard, Salazar, Juliana, Marín, Ángela, Uribe Hincapié, Richard, Salazar, Juliana, and Marín, Ángela

Abstract

This article presents a perspective regarding the importance of narratives in education, not only from the point of view of recognizing the structures of language, but also from their possibilities to recognize, interpret, and reconstruct reality. Therefore, this work establishes the capabilities of narration to establish links with students’ individual and social realities by providing sensory and cognitive tools for understanding, as well as their possibilities to promote interaction practices, which, in addition to contributing to linguistic training, are transcendental in teaching and learning processes with regard to reading, writing, and orality. Finally, based on an experimental exercise with the web resource titled Espacio de Lectura, its implications for developing students' linguistic and social skills through the use of multimedia and multimodal tools are described, as well as its potential to rethink the use of the narration in schools and their forms of interaction, En este artículo se presenta una perspectiva acerca de la importancia de las narraciones en la formación escolar, no solo desde el punto de vista del reconocimiento de las estructuras de la lengua, sino de las posibilidades que estas tienen para reconocer, interpretar y reconstruir la realidad. Por ello, se argumenta la capacidad de la narración para establecer vínculos con las realidades individual y social de los estudiantes al proveer herramientas sensoriales y cognitivas para la comprensión del mundo; asimismo, se establecen las posibilidades que tiene la narración para fomentar prácticas de interacción que, además de coadyuvar en la formación lingüística, son trascendentales en los procesos de enseñanza y aprendizaje de la lectura, la escritura y la oralidad, Finalmente, a partir de un ejercicio experimental con el recurso web Espacio de Lectura, se describen las implicaciones de este para desarrollar las habilidades lingüísticas y sociales de los estudiantes a partir del uso de herramientas multimediales y multimodales, así como su potencial para repensar el uso de la narración en la escuela y sus formas de interacción

Published
2023

32. Consensus of experts from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology for the genotyping of DPYD in cancer patients who are candidates for treatment with fluoropyrimidines

Author

García-Alfonso, Pilar, Saiz-Rodríguez, M., Mondéjar, R., Salazar, Juliana, Páez, David, Borobia, A. M., Safont, M. J., García-García, I., Colomer, Ramon, García-González, Xandra, Herrero Cervera, María José, López-Fernández, L. A., Abad-Santos, Francisco, Universitat Autònoma de Barcelona, UAM. Departamento de Farmacología, and UAM. Departamento de Medicina

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Genotyping Techniques, Medicina, Genotypes, Polymorphism, Single Nucleotide, 5-fluorouracil, Capecitabine, Dihydropyrimidine dehydrogenase, Genotypes, Pharmacogenetics, Toxicity, Capecitabine, Breast cancer, Neoplasms, Internal medicine, medicine, Dihydropyrimidine dehydrogenase, Humans, 5-fluorouracil, Genotyping, Dihydrouracil Dehydrogenase (NADP), Toxicity, business.industry, Patient Selection, Cancer, General Medicine, medicine.disease, Pharmacogenetics, Pharmacogenomics, DPYD, Fluorouracil, business, medicine.drug
Abstract

5-Fluorouracil (5-FU) and oral fluoropyrimidines, such as capecitabine, are widely used in the treatment of cancer, especially gastrointestinal tumors and breast cancer, but their administration can produce serious and even lethal toxicity. This toxicity is often related to the partial or complete deficiency of the dihydropyrimidine dehydrogenase (DPD) enzyme, which causes a reduction in clearance and a longer half-life of 5-FU. It is advisable to determine if a DPD deficiency exists before administering these drugs by genotyping DPYD gene polymorphisms. The objective of this consensus of experts, in which representatives from the Spanish Pharmacogenetics and Pharmacogenomics Society and the Spanish Society of Medical Oncology participated, is to establish clear recommendations for the implementation of genotype and/or phenotype testing for DPD deficiency in patients who are candidates to receive fluoropyrimidines. The genotyping of DPYD previous to treatment classifies individuals as normal, intermediate, or poor metabolizers. Normal metabolizers do not require changes in the initial dose, intermediate metabolizers should start treatment with fluoropyrimidines at doses reduced to 50%, and poor metabolizers are contraindicated for fluoropyrimidines, This project has been financed with SEOM and SEFF resources

Published
2021
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33. CES1 and SLC6A2 Genetic Variants As Predictors of Response To Methylphenidate in Autism Spectrum Disorders

Author

Hernandez, Marta H, primary, Bote, Valentin, additional, Serra-LLovich, Alexandre, additional, Cendros, Marc, additional, Salazar, Juliana, additional, Mestres, Conxita, additional, Guijarro, Silvina, additional, Alvarez, Aida, additional, Lamborena, Cristina, additional, Mendez, Iria, additional, Sanchez, Bernardo, additional, Hervas, Amaia, additional, and Arranz, Maria J, additional

Published
2022
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40. Caracterización de los recién nacidos con síndrome de down según condiciones de salud, demográficas y sociales en Medellín del periodo 2015 a 2019

Author

Noreña Gómez, Sara Isabel, primary, Quintero Salazar, Juliana, additional, Posada Mazuera, Mariana, additional, Reyes Iriarte, Martha Mónica, additional, Velez Leal, Sara, additional, Arboleda Gómez, Carolina, additional, Gómez Gonzalez, Andrea, additional, Fernandez Laverde, Mauricio, additional, and Bareño Silva, José, additional

Published
2022
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42. Pharmacogenetic Interventions Improve the Clinical Outcome of Treatment-Resistant Autistic Spectrum Disorder Sufferers

Author

Arranz, Maria J., primary, Salazar, Juliana, additional, Bote, Valentin, additional, Artigas-Baleri, Alicia, additional, Serra-LLovich, Alexandre, additional, Triviño, Emma, additional, Roige, Jordi, additional, Lombardia, Carlos, additional, Cancino, Martha, additional, Hernandez, Marta, additional, Cendros, Marc, additional, Duran-Tauleria, Enric, additional, Maraver, Natalia, additional, and Hervas, Amaia, additional

Published
2022
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44. CES1 and SLC6A2 Genetic Variants As Predictors of Response To Methylphenidate in Autism Spectrum Disorders

Author

Hernandez,Marta H, Bote,Valentin, Serra-LLovich,Alexandre, Cendros,Marc, Salazar,Juliana, Mestres,Conxita, Guijarro,Silvina, Alvarez,Aida, Lamborena,Cristina, Mendez,Iria, Sanchez,Bernardo, Hervas,Amaia, Arranz,Maria J, Hernandez,Marta H, Bote,Valentin, Serra-LLovich,Alexandre, Cendros,Marc, Salazar,Juliana, Mestres,Conxita, Guijarro,Silvina, Alvarez,Aida, Lamborena,Cristina, Mendez,Iria, Sanchez,Bernardo, Hervas,Amaia, and Arranz,Maria J

Abstract

Marta H Hernandez1,2 *, Valentin Bote3 *, Alexandre Serra-LLovich,1 Marc Cendros,1,4 Juliana Salazar,5 Conxita Mestres,2 Silvina Guijarro,3 Aida Alvarez,3 Cristina Lamborena,3 Iria Mendez,3 Bernardo Sanchez,3 Amaia Hervas,3 Maria J Arranz1,2 1Research Laboratory Unit, Fundació Docència i Recerca Mútua Terrassa, Terrassa, Spain; 2School of Health Sciences Blanquerna, University Ramon Llull, Barcelona, Spain; 3Department of Child and Adolescent Psychiatry, Hospital Universitari Mútua Terrassa, Terrassa, Spain; 4EUGENOMIC Genómica y Farmacogenética, Barcelona, Spain; 5Translational Medical Oncology Laboratory, Institut de Recerca Biomèdica Sant Pau (IIB-Sant Pau), Barcelona, Spain*These authors contributed equally to this workCorrespondence: Maria J Arranz, Research Laboratory Unit, Fundació Docència i Recerca Mútua Terrassa, c/Sant Antoni, 19, Terrassa, 08221, Spain, Tel +34 937 36 50 50, Fax +34 93 736 50 21, Email mjarranz@mutuaterrassa.esPurpose: Autistic spectrum disorders (ASD) children and adolescents usually present comorbidities, with 40– 70% of them affected by attention deficit hyperactivity disorders (ADHD). The first option of pharmacological treatment for these patients is methylphenidate (MPH). ASD children present more side effects and poorer responses to MPH than ADHD children. The objective of our study is to identify genetic biomarkers of response to MPH in ASD children and adolescents to improve its efficacy and safety.Patients and Methods: A retrospective study with a total of 140 ASD children and adolescents on MPH treatment was included. Fifteen polymorphisms within genes coding for the MPH target NET1 (SLC6A2) and for its primary metabolic pathway (CES1) were genotyped. Multivariate analyses including response phenotypes (efficacy, side-effects, presence of somnolence, irritability, mood alterations, aggressivity, shutdown, other side-effects) were performed for every polymorphism and haplotype.Results: Single

Published
2022

46. Pharmacogenetic Profiling in High-Risk Soft Tissue Sarcomas Treated with Neoadjuvant Chemotherapy

Author

Virgili Manrique, Anna C., primary, Salazar, Juliana, additional, Arranz, María Jesús, additional, Bagué, Silvia, additional, Orellana, Ruth, additional, López-Pousa, Antonio, additional, Cerdà, Paula, additional, Gracia, Isidre, additional, Majercakova, Katarina, additional, Peiró, Ana, additional, Trullols, Laura, additional, Fernández, Manuel, additional, Valverde, Sandra, additional, Quintana, María Jesús, additional, Bell, Olga, additional, Artigas-Baleri, Alícia, additional, and Sebio, Ana, additional

Published
2022
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