Banca de DEFESA: Dileep Kumar

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : Dileep Kumar
DATE: 29/02/2024
TIME: 08:30
LOCAL: Auditório 02 do Instituto de Ciências Biológicas - IB
TITLE:

"Effect of Low-dose Chemotherapy in a Metastatic Pre-clinical Breast Cancer Model".

KEY WORDS:

Breast cancer model, Tumor micro-environment, Metastasis, Immunosuppression, Chemotherapy, Low-dose treatment, Cyclophosphamide, 5-fluorouracil

PAGES: 37
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Breast cancer develops differently in each patient. Metastasization happens when cancer cells from the primary tumor develop the ability to establish new tumor spots in other organs, such as the liver, lungs, or bones. 4T1 mouse mammary tumor cell line, which is a cell line used in preclinical breast cancer tumor models in mice, can spread to distant locations, including lungs, bones, and bone marrow. One interesting point related to the 4T1 cell behavior is the ability to affect hematopoiesis. For instance, the 4T1 cells can induce the production of aberrant myeloid cells to the detriment of normal lymphoid cells. Thus, the balance between these two lineages is disrupted in 4T1 tumor-bearing mice, creating an immunosuppressor phenotype that allows tumor growth. Among the myeloid cells produced, one specific immature subtype, the myeloidderived suppressor cells (MDSCs) are produced in higher proportion in tumor bearing mice in comparison to healthy animals. These MDSCs are a heterogeneous population of immature myeloid cells that accumulate in lymphoid organ, especially in spleen which can expands during cancer progression, and has a remarkable ability to suppress T-cell responses, thus creating an immunosuppressive phenotype. This study aimed to evaluate the presence of these MDSCs after the treatment of 4T1-tumor-bearing mice with low-dose chemotherapy. We opted for a low- dose therapeutic approach based on previous works demonstrating the potential of low-dose chemotherapy with cyclophosphamide (CP) and 5-fluorouracil (5-FU) in reducing the number of immunosuppressive cells. CY with 5-FU reduced breast cancer tumor growth and lung metastasis. In addition, lowdose therapy modified both the counts and phenotypes of leucocytes when compared to the positive control – tumor without treatment mice. Moreover, it was also observed a reduction of MDSCs counts when compared to the positive control group. In conclusion, low-dose chemotherapy modified the leucocyte populations, and these modifications co-related with the systemic response to the therapy, including distant lung metastasis control.

COMMITTEE MEMBERS:
Externa à Instituição - Amanda Alencar Cabral Morais - MS
Presidente - 1929494 - JOAO PAULO FIGUEIRO LONGO
Externa ao Programa - 2171029 - MARIA DE FATIMA MENEZES ALMEIDA SANTOS - nullInterna - 2220195 - MONICA PEREIRA GARCIA
Externa à Instituição - Maria de Sousa Brito Neta