18AnnaI – CA Work Experience Program

Day 8

Today in the lab I got to work with the MDs and Sarah to create a gel that stores the drugs that we want to test on the mice so that it is ready for use and ready to be tested. Additionally, we continued monitoring the growth of the organoids in the tissue culture lab which we’ll need to develop for the next few weeks before they’re ready to be injected into the mice. Overall, today was a pretty relaxed day as the 119 drug was ready to be tested and all we could do was monitor the organoid growth to make sure that they were multiplying without the dilution of fibroblasts. Ultimately, for the next few weeks the lab will be moving at a pretty slow pace until the mice come and the drug tests can be carried out. Sarah and I finished most of the pre-lab data analysis yesterday, so today we just observed organoid growth under the microscope and made gels to store drugs before they get tested on the mice.

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Day 7

Today I mainly worked with Sarah to continue growing organoids in the tissue culture lab to be able to insert them into mice to observe their growth and test different drugs on them to observe their responses. Sarah and I finished up plating the organoids that were left and after that was finished, we began to log data (a lot of what we did was digital data analysis) for the organoids before testing her drug—labeled 119 on the mice. I also got to go with Dr. Hsu to order thirty mice for this next wave of experiments with them. Today was mainly a research and data analysis day to finish up any pre-requisite steps to testing the mice. But for the past few days, we’ve mainly been working on the same thing— growing organoids and plating them to be ready for the mice. The reason why we have to do this over several days is because organoid growth doesn’t occur slowly, but it doesn’t occur rapidly either. If we put the organoids in an environment where they would rapidly grow, they would be diluted with fibroblasts (I talked about these in a previous post), and thus the sample wouldn’t be usable for the purpose of our research outside of the mouse. So it’s a little bit of a lengthy and slow process while there’s not much we can do other than pre-lab data analysis.

Day 6

Today was a pretty relaxed day since both of the MDs weren’t in the lab today. I continued working with Sarah on our organoid project to observe their development in mice. What we got to do today was plate the organoids so that they’re ready to be injected into the mice. I also spent some of my time with Dr. Hsu in the clinic since he spends his Tuesdays and Fridays there. Unlike last Friday, he saw almost thirty patients yesterday, but I only stayed to come meet the ones that I met last week so that I could observe their progress. One of the patients with pancreatic cancer that I met last week came back in today and made the decision to start chemotherapy despite the possible risks because of his severe weight loss. With this patient specifically, it was interesting to note the behind the scenes work of the oncologist. Dr. Hsu was discussing with other oncologists what they would do in situations like that. Dr. Hsu explained to me that he rarely refuses treatment to his patients because he believes that cancer shouldn’t be viewed solely through an objective lens. When I was observing Dr. Hsu’s interactions with his patients I particularly noticed that unlike many other doctors I’ve shadowed, he takes a very holistic and engaging approach with his patients. Often times he’ll ask them questions to see how they’ll personally answer before he provides his own medical opinion. It was so interesting to see how flexible he was with his patients making it feel like they had the power in their own hands. As we were walking from the research building to the clinic building he explained to me that especially with cancer patients psychology plays a crucial role. He talked about how positively empowering the patient to be able to answer questions and make their own decisions (to some extent) is extremely important in cancer work.

Day 5

Today I got some one on one time working with Dr. Hsu in the lab. We spent a few hours making organoids in the tissue culture lab to be transferred to the mouse laboratory to be injected into the mice and developed into complete cancer cell lines to observe their growth. Tomorrow, we have to work on plating the organoids to make sure they’re ready to be injected into the mice. What happens after they are injected is that upon observing the natural growth, different drugs are tested, and our job is to observe whether the mice respond to the drug or not. And a response to the drug isn’t necessarily positive as the mice can respond poorly to the drug causing other medical symptoms, or the cancer cells could continue to duplicate. But, how did we make the organoids? What we did was take a piece of tumor delivered from the OR and we soaked it in a solution at room temperature over the weekend. This allowed parts of the tumor to dissociate into the solution. What we had to do then was remove the surrounding liquid without removing any of the floating cancer tissue. After this process was completed multiple times (a cycle of pipetting), the organoids were left in the tube and ready to be distributed to petri dishes to be observed under the microscope. Upon observing the organoids, you could see that they looked like a group of clumped cells.

Day 4

Today I got to work in the clinic alongside Dr. Hsu which meant that I went a couple buildings over to the medical center. I got to meet five cancer patients that day with ages ranging from 42 to 81 with cancers ranging from colorectal cancer to anal cancer to pancreatic cancer to even lung cancer. I couldn’t take many pictures because by law, you’re not allowed to take pictures within the clinical facility, but the picture below is of the office space that I sat in while Dr. Hsu showed me different CT scans and showed me how to identify cancer or abnormal spotting on a patient. The first patient that we saw had colorectal cancer and had already gotten most of his colon removed in surgery; however, what we saw on the CT scans was a little disheartening as we found an abnormal spot on his lungs not because the cancer had spread from his colon, but because he was a heavy smoker. So Dr. Hsu ordered more scans and tests to continue with treatment. Another patient that we saw that day was in the terminal stages of his cancer. Dr. Hsu explained to me that his cancer started out as colorectal cancer and then spread to his pancreas where the cancer cells multiplied so quickly that it completely compressed his stomach (you could see the dramatic decrease in the size of his stomach on the scan) so that he needed a feeding tube to consume food. His cancer, unfortunately, was completely untreatable, but Dr. Hsu saw that he was healthy enough and strong enough (despite losing more than twenty pounds) to undergo another round of chemotherapy just to contain the cancer enough to give him a few more good living months. Another patient we saw that previously had anal cancer came in because of an arterial clot. What Dr. Hsu explained to me is that venal clots are common, easier to detect and treat, and sometimes occur without another factor or cause influencing it. However, arterial clots are much rarer and can easily be fatal, and they are primarily caused by some other disease or outside influencer. What Dr. Hsu was worried about was that his cancer had returned and that was what was causing the clot, so he ordered more scans be completed to check for any signs of recurring cancer.

The experience in the clinic was totally different than all of my other days in the lab. And what struck me most about my experience in the clinic was the general disposition of all of the cancer patients. The relationship that the cancer patients have with their doctors is absolutely spectacular. Because the oncologist sees them regularly for long periods of time, they become extremely attached; I was really fascinated and comforted by the positive relationships that the oncologists formed with their patients and vice versa.

Day 3

Today I got to get more hands on in the lab. The first thing that I got to do was go into the tissue culture lab which is a room full of incubators keeping cancer cells alive at normal body temperatures. One of the MDs explained that after extracting cancer cells from a patient in the OR, they are taken to the tissue lab where they are incubated and cultured for growth. Upon growth, they are injected into the lab mice where active cancer growth is observed to be treated with different types of test drugs using computational biology. I got to observe colorectal cancer cells under a microscope while assorting them in different petri dishes under the fume hood. The second thing that I got to do in the lab today was extract DNA from the collected cancer cells. It was interesting to note that extracting the DNA was not at all an arduous task. And yesterday, when I got to observe one of the MDs deal with buffer solutions, I realized that this was the aftermath to what I got to do today. Essentially, to discover the proteins in the RNA of the cancer lines, they first extract the DNA from the cancer cell lines which is converted into RNA, then placed in a buffer solution where, in a two day process, we can determine the existing proteins and pick different drugs to test on these proteins to see which drug weakens them most. But after extracting the DNA and using the incubator to cultivate it, I got to put it on a small slide and observe its architecture under a microscope. It was interesting to see the stark differences but also the subtle similarities between the different cancer cells under the microscope. I got to observe some cancer cells that had been in the incubator for weeks and were flourishing while I also got to observe fresh cancer cells, not yet grown. I also got to observe colorectal cancer cells and kidney cancer cells and noted the differences between those two as well.

Today I also got to take a paraffin block containing cancer cell tissue, slice it, soak it, and put it in a slide for analysis. What I got to do was dye the sliced piece of cancer tissue so that its architecture and makeup is observable under a microscope. And then it can be delivered to the tissue culture lab to be kept in an incubator so that we can visibly see its makeup and whether it is primarily comprised of organoids or fibroblasts. What Dr. Hsu came in and explained to me was that fibroblasts often grow in cancer cell tissue and overtake the organoids inhibiting their growth. This is a big problem when it comes to developing cancer cell lines because the cancer cell lines aren’t pure enough to evaluate for research, and even when they try and purify the lines to allow more pure cancer cells to grow, the fibroblasts still invade the organoids and often make it difficult to see the organoids. What’s nice though is that the makeup of organoids vs. fibroblasts are very different. Fibroblasts are long, weed-like organisms whereas organoids look like clumps of cells. It’s very difficult to get a pure cancer cell line of organoids, so Dr. Hsu has assigned Sarah and I the task of constructing pure organoid cancer cell lines. It’s difficult because as soon as you cut up the cancer tissue and attempt to grow it in separate petri dishes, we create a comfortable environment for the fibroblasts to grow also. So starting today we began to work in the tissue lab to design a procedure to properly construct organoid cancer cell lines without fibroblasts getting in the way. What Dr. Hsu did explain to me though is that the reason why not much research has been diverted to being able to construct these organoid cancer cells without the fibroblasts is that since fibroblasts grow with the growth of cancer cell lines when injected into mice, this in fact helps research how to treat the cancer considering the growth of other cells also. Fibroblasts are key in determining what types of drugs are potent enough to defeat cancer cells because they grow inside of the human body also.

Day 2

So today I actually got to go to the lab and do some research along two MDs and one undergraduate from Duke. Today was mainly an observing day to get a feel for the lab and all of the protocols. I observed the two MD students conduct research while I sat with the undergraduate student (Sarah) who explained to me her data analysis on the potency of different types of drugs on colorectal cancer. One of the MD students that I was working with showed me some of his work with pipetting tumor cells to be tested for what types of proteins are in them. He explained to me that they transfer tumor cells directly from the OR to the lab to create buffer solutions and test them for what proteins they have inside of them in order to assign different drugs to each solution to test which drug is most effective at dismantling the proteins existing in those solutions. This was particularly interesting especially after learning about buffer solutions in chemistry; seeing one of the MDs put my chemistry knowledge to use was spectacular. I actually got a feel for what I was learning out of a textbook– it was the tangible aspect of all the calculations that I did throughout this year. It’s so fascinating to me that the other side of what seems intangible, almost theoretical numbers are physical appliances with very visible applications. The other MD took me around the lab for a tour to show me its basic functions and the equipment used to conduct respective experiments. But they also explained to me that most of their research isn’t actual, tangible lab work. Rather, most of their time is spent analyzing the data that they collect evaluating cancer drugs and different mechanisms to approach cancer cures. Again, my chemistry and math knowledge was laid out on a practical level as I observed the MDs and the undergraduate (Sarah) calculate standard deviation when determining the potency of each drug; such practical application with data analysis reminded me a lot of pharmaceutical work, so it was interesting to draw a similarity between those two professions. In general, today was a pretty hands off day, but in the next few days, I’ll be observing drug effects on actual cancer patients that have come through the office, and I’ll be actually going into the clinic and meeting cancer patients with Dr. Hsu.

Day 1

Today, since Dr. Hsu had to work in the clinic with patients, I did research about what Dr. Hsu actually does on a daily basis. Dr. Hsu pursued an MD PhD so that he could practice medicine with cancer patients while still conducting research in a lab. He explained that 70% of the time he conducts research, writes thesis papers, collaborates with other oncologists while he spends the other 30% of his time working at the Duke Medical Center with cancer patients suffering from gastrointestinal cancers. Most of his clinical work deals with patients with colorectal cancer, and most of his research is conducted on mice where he explores genomics and computational biology. His lab focuses on the use of genomic based technologies to identity and develop novel therapeutic targets for the treatment of gastrointestinal cancers. His lab also develops preclinical models using patient derived xenographs and early passage cell lines in GI cancers. Dr. Hsu has in fact developed this technique further so that it has been used to treat lung, breast, renal, bladder, melanoma, sarcoma, and other cancers. His primary focus however, is on colorectal cancers. He has done a lot of work with drug effects on cancer cell lines exploring the most potent drugs to combat the growth of these cell lines, and the way that he does this is by observing and analyzing cancer growth in mice. And though most of his work consists of working hands on with mice and live cancer cells from the OR, he spends some of his time conducting data analysis to evaluate the potency of certain drugs on different types of cancers.