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Head and neck squamous cell carcinoma: identification of molecular markers and compounds for therapeutic use
Brazil (IFMSA-Brazil) - Faculdade de Medicina de Sao Jose do Rio Preto, Sao Jose do Rio Preto
Departament of Molecular Biology – Laboratory of Molecular Markers Av. Brg. Faria Lima, 5416 - Vila Sao Pedro, São José do Rio Preto - SP, 15090-000
Profª. Dra. Eloiza H. Tajara
Profª. Dra. Eloiza H. Tajara
English, Portuguese, Italian and Spanish
Type of Research Project
- Basic science
What is the background of the project?
Head and neck squamous cell carcinoma (HNSCC) is one of the most common types of neoplasms and its main etiological factors are smoking, alcohol consumption and human papillomavirus (HPV) infection. The metabolic profile of HNSCC is heterogeneous and related to mutations in several tumor suppressor genes and oncogenes. Altered metabolic patterns include increased levels of lipids in biofluids, a finding confirmed by previous data from our group.
What is the aim of the project?
The aims of this project are (a) to determine in plasma and tumor samples the concentration and structure of lipids by mass spectrometry imaging (MSI) and/or capillary electrophoresis technique coupled to time-of-flight mass spectrometry (CE-TOFMS), (b) to evaluate whether changes in lipid profile correlate with clinical and histopathological characteristics and response to treatment, (c) to investigate, at the level of transcripts and proteins, the concentration of enzymes of the choline phosphorylation pathway (d) to evaluate the role of potential protein markers identified using functional in vitro studies, (e) to identify natural compounds that efficiently target selected HNSCC markers.
What techniques and methods are used?
* Mass spectrometry to determine the concentration and structure of lipids in plasma and tumor samples * Cell culture for functional in vitro studies *Polymerase Chain Reaction and Western blot to investigate the expression of enzymes of the lipid pathway in tumor cells and inflammatory mediator expression * Bioinformatic tools to identify compounds that target selected markers * Molecular docking to evaluate compound and target interactions.
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
The student’s tasks will involve all the laboratory work. The student will initiate the work with blood samples withdrawing supervised by the tutor. The next phase will include the cell culture and slides preparation, all the instructions will be provided by the tutor or the laboratory responsible. Will be required the student make functional studies applying techniques as immunohistochemistry. Polymerase Chain Reaction will also be part of the process and will be performed by the student. All the data collected from the results will be organized in Microsoft Excell tables and crossed with another studies data, making a discussion and possible improvements in the outcomes.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Articles about head and neck carcinomas, lipid metabolism including phosphatidylcholine and sphingomyelin metabolism in cancer will be provided to the student previously.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will prepare a poster
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
Ability to work with basic laboratory techniques, be able to work in group, be organized. Subjects passed: Biochemistry
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Students in biomedical fields
- 1. Leemans CR; Braakhuis BJ; Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer. 2011 Jan;11(1):9-22. doi: 10.1038/nrc2982
- 2. Leemans CR; Snijders PJF; Brakenhoff RH. The molecular landscape of head and neck cancer. Nat Rev Cancer. 2018 May;18(5):269-282. doi: 10.1038/nrc.2018.11
- 3. Ogretmen B. Sphingolipid metabolism in cancer signalling and therapy. Nat Rev Cancer. 2018 Jan;18(1):33-50. doi: 10.1038/nrc.2017.96
- 4. Glunde K; Bhujwalla ZM; Ronen SM. Choline metabolism in malignant transformation. Nat Rev Cancer. 2011 Nov 17;11(12):835-48. doi: 10.1038/nrc3162
- 5. Li Z; Kang Y. Lipid Metabolism Fuels Cancer's Spread. Cell Metab. 2017 Feb 7;25(2):228-230. doi: 10.1016/j.cmet.2017.01.016
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