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Application of nuclear magnetic resonance (NMR) in metabolomics and metabonomics of human diseases

Grant number: 18/06510-4
Support type:Regular Research Grants
Duration: June 01, 2018 - May 31, 2020
Field of knowledge:Physical Sciences and Mathematics - Chemistry
Principal Investigator:Ljubica Tasic
Grantee:Ljubica Tasic
Home Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Assoc. researchers:Ana Cristina Victorino Krepischi


The present project aims at metabolomic and metabonomic analyzes by nuclear magnetic resonance techniques applied to studies of childhood and juvenile cancers and glioma (glioblastoma). Information about metabolic changes in cancer cells is known and studied, but studies in younger populations - among children and adolescents aged 1 to 19 years - are scarce because they present a group of very peculiar diseases, where genetic differences and mutations are not the primary causes of cancer occurrence. Moreover, in Brazil, cancer is already the leading cause of death due to illness among children and adolescents (8% of the total) and, also, in developed countries. Cancer affecting the younger population encompasses several diseases, such as central nervous system tumors, lymphomas, neuroblastoma, Wilms tumor, retinoblastoma, osteosarcoma, and sarcomas. Over the past four decades, progress in cancer treatment in childhood and adolescence has been extremely significant. Today, around 80% of children and adolescents with cancer can be cured, if diagnosed early and treated in specialized centers. Most of them will have good quality of life after adequate treatment, however, the effects of treatments received via chemotherapy and/or radiotherapy may compromise longevity, since after 20 to 30 years of anticancer treatment, individuals may have recurrence or cancer of another type. Thus, it is necessary to propose follow-up, personalized treatment and diagnosis - early, accurate, robust, which may allow the correct use of chemo- and/or radio- drugs. In this project, we will have three diseases as study targets: (a) Wilms tumor (TW, or nephroblastoma); (b) osteosarcoma, and (c) liver tumor (hepatoblastoma). Samples from patients with solid tumors will be studied by applying the nuclear magnetic resonance techniques in the semi-solid state (HR-MAS). Also, sera from the same patients will be used and studied by liquid magnetic resonance techniques. It is expected to verify whether metastatic activity and/or resistance to chemotherapeutic treatment can be observed in tumor tissue and/or serum metabolome and to discover possible candidates for prognostic or therapeutic markers. We hope that early detection, follow-up treatment, as well as, better understanding of altered biochemical pathways may be of great importance in increasing clinical efficacy and anticancer therapy in pediatric malignancies. At last but not the least, a part of our research covers studies about glioblastoma in which we hope that metabolic changes in gliomas may provide an overview of tumor development and progression. Gliomas are the malignant tumors that cause the most dangerous and prevalent brain cancers - they are exceptionally resistant to treatment and take away more and more lives from young and middle-aged people. The lack of effective biomarkers for diagnoses and targets for treatment is due to the incomplete understanding of the molecular mechanisms of these highly variable diseases. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ESCOBAR, MELISSA QUINTERO; MASCHIETTO, MARIANA; KREPISCHI, V, ANA C.; AVRAMOVIC, NATASA; TASIC, LJUBICA. Insights into the Chemical Biology of Childhood Embryonal Solid Tumors by NMR-Based Metabolomics. BIOMOLECULES, v. 9, n. 12 DEC 2019. Web of Science Citations: 0.
MONTE, GABRIELA GUILHERME; NANI, V, JOAO; DE ALMEIDA CAMPOS, MARINA ROSSETO; DAL MAS, CAROLINE; NEGRI MARINS, LUCAS AUGUSTO; MARTINS, LUCAS GELAIN; TASIC, LJUBICA; MORI, MARCELO A.; HAYASHI, MIRIAN A. F. Impact of nuclear distribution element genes in the typical and atypical antipsychotics effects on nematode Caenorhabditis elegans: Putative animal model for studying the pathways correlated to schizophrenia. PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, v. 92, p. 19-30, JUN 8 2019. Web of Science Citations: 0.
STANISIC, DANIJELA; FREGONESI, NATALIA L.; BARROS, CAIO H. N.; PONTES, JOAO G. M.; FULAZ, STEPHANIE; MENEZES, ULISSES J.; NICOLETI, JORGE L.; CASTRO, THIAGO L. P.; SEYFFERT, NUBIA; AZEVEDO, VASCO; DURAN, NELSON; PORTELA, RICARDO W.; TASIC, LJUBICA. NMR insights on nano silver post-surgical treatment of superficial caseous lymphadenitis in small ruminants. RSC ADVANCES, v. 8, n. 71, p. 40778-40786, 2018. Web of Science Citations: 1.

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