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- All Subjects: medicine
- Creators: Lopez, Angel
Adaptive therapy utilizes competitive interactions between resistant and sensitive cells by keeping some sensitive cells to control tumor burden with the aim of increasing overall survival and time to progression. The use of adaptive therapy to treat breast cancer, ovarian cancer, and pancreatic cancer in preclinical models has shown significant results in controlling tumor growth. The purpose of this thesis is to draft a protocol to study adaptive therapy in a preclinical model of breast cancer on MCF7, estrogen receptor-positive, cells that have evolved resistance to fulvestrant and palbociclib (MCF7 R). In this study, we used two protocols: drug dose adjustment and intermittent therapy. The MCF7 R cell lines were injected into the mammary fat pads of 11-month-old NOD/SCID gamma (NSG) mice (18 mice) which were then treated with gemcitabine.<br/>The results of this experiment did not provide complete information because of the short-term treatments. In addition, we saw an increase in the tumor size of a few of the treated mice, which could be due to the metabolism of the drug at that age, or because of the difference in injection times. Therefore, these adaptive therapy protocols on hormone-refractory breast cancer cell lines will be repeated on young, 6-week old mice by injecting the cell lines at the same time for all mice, which helps the results to be more consistent and accurate.
Tissue engineering is a field of regenerative medicine that integrates the knowledge of scientists, physicians, and engineers into the construction or reconstruction of human tissue. Practitioners of tissue engineering seek to repair, replace, maintain, and enhance the abilities of a specific tissue or organ by means of living cells. More often than not stem cells are the form of living cells used in this technology. Tissue engineering is one of the disciplines involved in translating knowledge of developmental biology into the clinical setting. One focus that this field has taken is the understanding of tissue and organ development during embryogenesis, as this knowledge will open avenues to new applications of this technology.
The purpose of regenerative medicine, especially tissue engineering, is to replace damaged tissue with new tissue that will allow the body to resume normal function. The uniqueness of tissue engineering is that it can restore normal structure in addition to repairing tissue function, and is often accomplished using stem cells. The first type of tissue engineering using stem cells was hematopoietic stem cell transplantation (HSCT), a surgical procedure in which hematopoietic stem cells (HSCs) are infused into a host to treat a variety of blood diseases, cancers, and immunodeficiencies. While there is a standard procedure for the infusion of these cells into a donor, variations in the sources of hematopoietic stem cells, and in the relationship between donor and recipient, do produce some variability in the procedure.
The discovery of hematopoietic stem cells (HSCs) provided a pioneering step in stem cell research. HSCs are a type of multipotent adult stem cell, characterized by their ability to self-renew and differentiate into erythrocyte (red blood cell) and leukocyte (white blood cell) cell lineages. In terms of function, these cells are responsible for the continual renewal of the erythrocytes, leukocytes, and platelets in the body through a process called hematopoiesis. They also play an important role in the formation of vital organs such as the liver and spleen during fetal development. The early biological knowledge obtained from the studies of HSCs established the base of knowledge for understanding other stem cell systems. In addition, these cells have a vital role in furthering stem cell research for clinical applications. Regenerative medicine is a field of medicine that has applied HSCs to the treatment of blood-borne diseases such as leukemia and lymphoma and of cancer patients undergoing chemotherapy.
Umbilical cord blood (UCB) stem cells are hematopoietic stem cells (HSC) that are recovered from the blood of the umbilical cord and placenta after birth. Umbilical cord blood is rich in cells that express the CD34 molecule, a surface protein that identifies cells as stem cells. Prior to the discovery of UCB stem cells, it was standard procedure to discard the umbilical cord and placenta; now much effort is devoted to raising public awareness and to encouraging people to store or donate cord blood. The importance of these cells lies in potential clinical treatments of blood-borne diseases, as well as the possibility of restoring cells of other lineages, such as cardiac and neural cells. These possible uses have given rise to cord blood stem cell banking, both private and public, where cells can be frozen and stored for later use.
prostate cancer is most commonly treated with hormonal therapy. The idea behind
hormonal therapy is to reduce androgen production, which prostate cancer cells
require for growth. Recently, the exploration of the synergistic effects of the drugs
used in hormonal therapy has begun. The aim was to build off of these recent
advancements and further refine the synergistic drug model. The advancements I
implement come by addressing biological shortcomings and improving the model’s
internal mechanistic structure. The drug families being modeled, anti-androgens,
and gonadotropin-releasing hormone analogs, interact with androgen production in a
way that is not completely understood in the scientific community. Thus the models
representing the drugs show progress through their ability to capture their effect
on serum androgen. Prostate-specific antigen is the primary biomarker for prostate
cancer and is generally how population models on the subject are validated. Fitting
the model to clinical data and comparing it to other clinical models through the
ability to fit and forecast prostate-specific antigen and serum androgen is how this
improved model achieves validation. The improved model results further suggest that
the drugs’ dynamics should be considered in adaptive therapy for prostate cancer.