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Research investigates process that triggers tumor growth

Study opens new possibilities for lymphoma treatment

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Angiogenesis is one of the hottest lines of research in the world for the treatment of cancer. She studies the process of vessel formation within the tumor. To grow and multiply, the tumor needs nutrients and oxygen that it takes from the blood. Some genes are involved in this mechanism for tumor survival. Two of these genes were studied by Angelo Borsarelli Carvalho de Brito, the first student to graduate from the Medical Research Program at the Faculty of Medical Sciences (FCM) at Unicamp.

“Angiogenesis is classically a process seen as harmful because it makes the tumor grow but, at the same time, it plays an important role in delivering chemotherapy to the tumor. It would be like a dispute”, explains Angelo.

Photo: Scarpa
Angelo Borsarelli Carvalho de Brito: “Angiogenesis is classically a process seen as harmful because it makes the tumor grow but, at the same time, it plays an important role in delivering chemotherapy to the tumor”

According to the survey Angiogenesis in diffuse large B-cell non-Hodgkin lymphoma: impact of polymorphisms in the VEGF and VEGFR2 genes on clinical aspects and tumor vascularization, some polymorphisms in these genes may be associated with greater or lesser success in the conventional treatment of patients with the disease. The research was supervised by Professor Carmen Silvia Passos Lima, from the Department of Clinical Medicine and co-supervision by Professor José Vassalo, from the Department of Pathological Anatomy.

"Polymorphisms define the color of eyes, skin, hair type and other physical characteristics transmitted from parents to children. They also determine variations in the metabolism of toxic substances to the body, in the formation of blood vessels to irrigate cells and in the repair of damage to cellular DNA”, explains oncologist Carmen Silvia Passos Lima.

Non-Hodgkin lymphomas are the ninth cause of cancer in Brazil. The most common subtype is diffuse large B-cell lymphoma. It is the most common hematological neoplasm. The main symptoms are enlarged lymph glands in the neck, groin and armpits. They can also appear in the spleen, digestive tract, bones, testicle, lung and other places. At diagnosis, around 50% of patients have an advanced stage of the tumor. The recommended treatment is chemotherapy and around 80% of patients are cured.

The study included 168 patients diagnosed with diffuse large B-cell non-Hodgkin's lymphoma (LDGCB) attended ebetween 2009 e 2014 at the Unicamp Blood Center and from 2013 to 2014 at the AC Camargo Hospital. Ospacfeelesforam avaliaof the cada childês monthes no decorrer do primeiro ano, the cadto whatagive meses in segundo ano, the caby seis monthesapartir from terceiro aNo. awhatuinto aNo, apost otéend of the trainatamento chemotherapy.

Daygnostic of LDGCB was realizado em exame histopatológico nos laboratoryos do Departamento de Anatomia Patológica da FCM and the Hospitaltathere. C. Camargo. Toddas as análisesmolecbeehiveres of DNA and identification of genotypes foram realizadajust not Laborathorium dand GenéticC'sâncer (Lageca) da Facthe wooldand from Ciências Médecas da Unicamp.

Photos: Scarpa
Professors Carmen Silvia Passos Lima and José Vassalo, respectively, research advisor and co-supervisor

According to Angelo, the VEGF is the main protein involved in angiogenesis. To act, the gene needs a receptor on the cell, which is VEGFR2. They work together to form vessels that lead to tumor growth. Some polymorphisms in these genes increase or reduce the production of the VEGF protein and formation of blood vessels.

“Today, there are new therapeutic agents that act on the angiogenesis pathway and are offered by the Unified Health System (SUS)” for patients with some types of tumor, which justifies the interest in the subject, explains Angelo.

After four years, the study revealed that isolated or associated polymorphisms in the VEGF gene were associated with response and toxicity to treatment and survival of patients with the tumor. The next stage of the study is to verify whether these polymorphisms can be used in the practice of caring for these patients.

“If a certain polymorphism makes the patient respond better to chemotherapy, but with greater toxicity, it is plausible to think that the dose can be reduced to avoid toxic effects. This is what we call pharmacogenetics. However, this must be confirmed in a future study”, says Angelo. It is also of great interest to verify whether polymorphisms in the VEGF gene can also alter the response of patients with the tumor to agents that inhibit angiogenesis.

The research resulted in three scientific articles that are under analysis for publication em periodicals with international circulation. Furthermore, while he was in the Researchers in Medicine Program, Angelo won several awards, five of which were international awards at the American Hematology, European Hematology, European Clinical Oncology and Oncohematology Society Congresses. In 2016, Angelo won the Young Scientist Award, offered by the Society of Medicine and Surgery of Campinas (SMCC) and also took second place in the same category for other research on genetic polymorphisms and cancer.

The winning work was Associations of VEGF and VEGFR2 polymorphisms with increased risk and aggressiveness of multiple myeloma, published in 2014, in Annals of Hematology. The work that came second was Association of BAX G(-248)A and BCL2 C(-717)A polymorphisms with outcome in diffuse large B-cell lymphoma patients, published in 2016 on British Journal of Haematology.


Medicine Researcher Program

The Medicine Researcher Program was created in 2012. It allows undergraduate students in the sixth or eighth semester of the Unicamp Medicine course to enroll in subjects in the Postgraduate Programs at the State University of Campinas. At the end, the student receives undergraduate and postgraduate diplomas. Two places are offered each year. The scientific initiation advisor is the one who identifies students who have potential. The model is similar to the North American one. In Brazil, in addition to Unicamp, only the Federal University of Rio de Janeiro (UFRJ) and Escola Paulista de Medicina offer this type of program.

“Overnight, you stop being a medical student and become a postgraduate student and have to learn how to deal with the responsibility of conducting a research project. It's a reality check. You become mature and more autonomous in solving your problems”, says Angelo, who is now in medical residency.

Find out more about the Medicine Researcher Program at https://www.fcm.unicamp.br/fcm/programa-de-pesquisador-em-medicina/documentos-e-procedimentos

 

 

JU-online cover image
Audio description: In the room, bust image and in profile, a man sitting, on the right of the image, points with the index finger of his right hand at the LCD monitor that displays circular illustrations and which clearly reads more advanced stage and larger tumor volumes. Next to the monitor, on the right, there is a computer cpu on the table. He wears glasses and wears a white coat over a dress shirt. Image 1 of 1.

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