In order to evaluate our patients, progress and if our methods of treatment are working we will be performing PET scans. This will give us an image regarding the patient’s response to the treatment and whether the tumor has progressed or not. It will give us the molecular activities within the patient. This is a great way since the patient will not be harmed and it will illustrate whether we are targeting the correct pathway or of modifications will be needed. Pet scans also have the ability to measure an individual’s blood flow, glucose, and oxygen use. This will also help us see if organs surrounded the tumor are working. Overall, we will be obtaining molecular info with the use of nuclear medicine imaging.
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ML385 would be another great inhibitor to use to target the trans activation of NRF2, transcription factor. This all works by ML385 finding a potential binding domain within NRF2 and in these case it will be the cap and collar or Neh1. Neh1 is also a region in which DNA binding occurs. Once it finds the potential binding domain it doesn't allow for the binding of the Nrf2-MAFG complex to ARE. MAFG is just a kind of sMaf, which are basic regions for leucine zipper type transcription factors. They act on gene regulation. This all results in a decrease in the rate of transcriptional activity. In a Keap1 mutation it will result in the levels of GSH being reduced and GSH is composed of cysteine, glutamate and glycine.
The way it's doing this is by guiding glutamine which we know is the addiction and directing it towards a pathway in which small molecules will be converted to large molecules. This will enhance purine synthesis and have an effect on pentose phosphate pathway to further the progress of cell proliferation and division. Essentially, Nrf2 when not disturbed and plays its role and regulated it helps in the removal of carcinogens. When hyperactive the malignant tumorous cells can tolerate reactive oxidative species and will avoid programmed cell death.
The Keap1-Nrf2 pathway is a regulator of providing protection to cells from harmful agents like peroxide or singlet oxygen. In this pathway, Nrf2 is bound to Keap1 and is kept it in the cytoplasm unless stressors come in which then means that they dissociate from each other. This leads to Nrf2 entering the nucleus through phosphorylation. Ubiquitination and degradation of Nrf2 occurs when bound to Keap1. Once in the nucleus Nrf2 binds to ARE (antioxidant response element) and sMaf. When there is a loss of function in Keap1, it leads to Nrf2 to continue and not be regulated. Nrf2 in malignant cells will provide an increase in chemoresistance and this will then facilitate cell growth of the tumor. When there is the overactivation of Nrf2 it is essentially affecting cell proliferation.
In image 22 there are some similarities and differences between the two multi panel figures. They had the same plants for the three labeled panels (A, B, C). The ruler is depicted in both multi-panels. However, there are some differences in the position of the ruler in the images. The type of ruler used was different and the detail of the images is different as well. Some factors that could have resulted in the differences are the specificity of how far the technological device should be in regard to the plant. Another is how detailed the image should be and what to include. In addition, in the left multi-panel one could observe that each image is a close-up to the plant and illustrates more details versus the right multi-panel figure.
An exampe of an observation and inference situation is watching somone cry and inferring they might be sad. However, the individual could be crying of excitment and joy. They could have received good news that they were so happy they shed tears. Another situation could be where they are sad and might be overwhelmed or stressed.
I went to Morrill III building and entered the greenhouse. I was walking through the greenhouse observing the variety of plant species that surrounded me. However, my attention was drawn to a particular plant species. It stood out form all other types of plant species. It was a red plant. I usually see my mom always buy this type of plant around Christmas time. It reminded me of family and unity. It had such a vibrant color and stood out to me from all the other plants. I immediately decided to choose this as my figure to illustrate to others.
A chemotherapy drug that would link with CB-839, a glutiminase inhibitor would be docetaxel. Docetaxel is known as a antimicrotubule agent. This means that it inhibits the formation of microtubules. Microtubules are highly involved in replicating and pulling apart chromosomes and sister chromatids throughout various stages of the cell cycle. Microtubules are known to be unstable. They contain a plus and minus end. The plus end is referred to as beta and the minus end as alpha. Tubulin is the building blocks of microtubules. Tubulin assembly can happen at either end of the microtubule. When outside the cell it is most favorable at the plus end and depolymerization happens on the minus end. Inhibition of the formation of microtubules will collapse and will result in cell death. Overall, the use of docetaxel with Cb-839 will be a great contribution to targeting KRAS-driven lung adenocarcinoma.
The lungs are already in close contact with the circulatory system. Our concern is whether the drug will reach the circulation and won’t be reduced along the way. The lungs already have a high rate of blood flow. Since delivery to the lungs is rather complex we will need a way for our drug to be enhanced without losing its ability or a reduction in concentration. One way is through a C and R uptake pathway. This will make our drug be amplified in a sense and delivery of our drug will be improved. We will need to enter the vascular tissue and a way to do this is through vascular permeability in which blood vessels permit for the flow of molecules and in this instance, it will be our drug.
Docetaxel is known as a antimicrotubule agent. This means that it inhibits the formation of microtubules. Microtubules are already unstable, and they are known to contain a plus and minus end, beta and alpha respectively. Tubulin assembly can happen at either end but is most favorable at the plus end when outside the cell and depolymerization happens on the minus end when outside the cell. Microtubules are highly involved in replicating and pulling apart chromosomes and sister chromatids throughout various stages of the cell cycle. Inhibition of the formation of microtubules will collapse and will result in cell death.