Florina Iulia Bura
@imibic.org
Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain
GE09 Research in peritoneal and retroperitoneal oncological surgery, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain
RESEARCH, TEACHING, or OTHER INTERESTS
Biochemistry, Genetics and Molecular Biology, Cancer Research, Oncology, Drug Discovery
Scopus Publications
Scholar Citations
Scholar h-index
Scopus Publications
Lidia Rodríguez-Ortiz, Mari C Vázquez-Borrego, Florina I Bura, Melissa Granados-Rodríguez, Francisca Valenzuela-Molina, Blanca Rufián-Andújar, Ana Martínez-López, Rosa Ortega-Salas, Juan José Espejo-Herrero, Antonio Romero-Ruiz,et al.
Oxford University Press (OUP)
Mari C. Vázquez-Borrego, Melissa Granados-Rodríguez, Florina I. Bura, Ana Martínez-López, Blanca Rufián-Andújar, Francisca Valenzuela-Molina, Lidia Rodríguez-Ortiz, Sergio Haro-Yuste, Ana Moreno-Serrano, Rosa Ortega-Salas,et al.
Springer Science and Business Media LLC
AbstractPseudomyxoma peritonei (PMP) is a rare disease characterized by a massive accumulation of mucus in the peritoneal cavity. The only effective treatment is aggressive surgery, aimed at removing all visible tumors. However, a high percentage of patients relapse, with subsequent progression and death. Recently, there has been an increase in therapies that target mutated oncogenic proteins. In this sense, KRAS has been reported to be highly mutated in PMP, with KRASG12D being the most common subtype. Here, we tested the efficacy of a small-molecule KRASG12D inhibitor, MRTX1133, in a high-grade PMP xenograft mouse model carrying a KRASG12D mutation. The results obtained in this work showed a profound inhibition of tumor growth, which was associated with a reduction in cell proliferation, an increase in apoptosis, and a reduction in the MAPK and PI3K/AKT/mTOR signaling pathways. In conclusion, these results demonstrate the high potency and efficacy of MRTX1133 in KRASG12D-PMP tumors and provide a rationale for clinical trials.
A. Arjona-Sanchez, A. Martinez-López, M.T. Moreno-Montilla, J. Mulsow, P. Lozano-Lominchar, B. Martínez-Torres, B. Rau, E. Canbay, A. Sommariva, M. Milione,et al.
Elsevier BV
Francisca Valenzuela-Molina, Florina I. Bura, Mari C. Vázquez-Borrego, Melissa Granados-Rodríguez, Blanca Rufián-Andujar, Sebastián Rufián-Peña, Ángela Casado-Adam, Juan Manuel Sánchez-Hidalgo, Lidia Rodríguez-Ortiz, Rosa Ortega-Salas,et al.
Frontiers Media SA
IntroductionPseudomyxoma peritonei (PMP) is a rare malignant disease characterized by a massive multifocal accumulation of mucin within the peritoneal cavity. The current treatment option is based on complete cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy. However, the recurrence is frequent with subsequent progression and death. To date, most of the studies published in PMP are related to histological and genomic analyses. Thus, the need for further studies unveiling the underlying PMP molecular mechanisms is urgent. In this regard, hypoxia and oxidative stress have been extensively related to tumoral pathologies, although their contribution to PMP has not been elucidated.MethodsIn this manuscript, we have evaluated, for the first time, the intratumoral real-time oxygen microtension (pO2mt) in the tumor (soft and hard mucin) and surrounding healthy tissue from five PMP patients during surgery. In addition, we measured hypoxia (Hypoxia Inducible Factor-1a; HIF-1α) and oxidative stress (catalase; CAT) markers in soft and hard mucin from the same five PMP patient samples and in five control samples.ResultsThe results showed low intratumoral oxygen levels, which were associated with increased HIF-1α protein levels, suggesting the presence of a hypoxic environment in these tumors. We also found a significant reduction in CAT activity levels in soft and hard mucin compared with healthy tissue samples.DiscussionIn conclusion, our study provides the first evidence of low intratumoral oxygen levels in PMP patients associated with hypoxia and oxidative stress markers. However, further investigation is required to understand the potential role of oxidative stress in PMP in order to find new therapeutic strategies.