We’re on to bio/biochem passage 2 in Blueprint MCAT full-length 1. Today, we dive into the world of cancer, inhibitors, cell proliferation, kinases, and more.
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[07:38] Passage 2 (Questions 6 – 9)
Every year, there are more than 1 million cases of invasive cancer in the United States, with 582,000 deaths and 14,000 cases in patients younger than 20 years old. At its core, cancer is essentially the failure of tissue growth regulation. In order to maintain healthy and regular tissue function, it is necessary for genes (called oncogenes) to promote cell growth and reproduction. Another class of genes, called tumor suppressor genes, inhibits cell survival and division. These two families of genes are designed to work in harmony, cycling cells within tissues through stages of division and death.
Note: Highlight the key terms such as invasive cancer. The main idea is the very first sentence. Cancer is a failure of tissue growth regulation. And then, you could also highlight “tumor suppressor genes, inhibits cell survival and division” and “designed to work in harmony.” (Phrases in bold as seen above). Then you could go back and read the highlights and then move onto the next paragraph.
[09:36] Paragraph 2
A family of serine/threonine protein kinases, called aurora kinases, plays a crucial role in mitosis progression, including centrosome duplication, chromosome condensation, and cytokinesis completion. Aurora C has also been shown to be involved in spermatogenesis and oogenesis. Overexpression of auroras A and B has been observed in many cancers, including colon and breast cancer, and developing powerful aurora kinase inhibitors has become a priority for oncology researchers.
Note: We learned what cancer was in the last paragraph. Now, we’re going to learn what’s specifically involved in that unregulated cell group. You can highlight some stuff there (like the phrases in bold as seen above.) Some people prefer highlighting phrases, some people prefer highlighting words. It just depends on where your eye goes.
So the first paragraph told us it was about cancer, and then Paragraph 2 tells us about the specific kinases involved leading to what researchers are interested in, which is the aurora kinase inhibitors in the second to last sentence.
[12:04] Paragraph 3
Scientists have been investigating a new hydrosoluble multikinase inhibitor, C5M, which has shown promise as an efficient inhibitor of the division of cells from a multiplicity of origins. These researchers first examined the IC50 of C5M in a number of cancers. The IC50, or half maximal inhibitory concentration, is the concentration of drug that is required for 50% in vitro inhibition of a specific biological or biochemical function. Results are shown in Table 1.
Note: That’s a lot of technical stuff. Again, as shown above, we’re putting in bold the words we think you should be highlighting.
[13:51] Analyzing Table 1
Note: One of the more challenging aspects of bio/biochem, in any of the science passages for students, is being able to understand what you’re looking at.“Start by reading the caption.”Click To Tweet
Table 1 Concentration of C5M needed to reduce cell proliferation by 50% after 96h of treatment in a panel of four cell lines
To investigate differential efficiencies across cell lines, the scientists compared C5M treatment in genetically modified Hct116 cells. Results are shown in Figure 1.
Note: You don’t really need to know anything about those four cell lines. You don’t need to freak out about those abbreviations. Maybe know some of them. But they’re different cell lines and different kinds of tissues and cancers. Then look at the last column, which is probably the most important one.
IC50 is the concentration of the drug needed to reduce cell proliferation by 50%. So this is where you look for a pattern. The lower concentration you need, the more efficient that drug must be.
If I need a ton of drugs to reduce it by 50%, that means the drug is not that efficient, and I need lots and lots of it to make the result that I want to happen. So we’re looking for low numbers that indicate high efficiency. And we got that from the passage in determining what it means to have a concentration.
Figure 1 Exposure of four Hct116 cell lines with (+) and without (-) Chk2 and p53 genes to 1 µM C5M
So we can see that the Chk2+ means that it has that gene, and the Chk2- means that we knocked out the gene. There’s not really a difference between those two. And the reason we know that is by looking at the error bars.'The best way to tell if there's a statistic statistically significant difference is to check the error bars and whether or not they overlap.'Click To Tweet
[18:48] Question 6
It is most likely that the difference in percent inhibition is significant between:
- Hct116-Chk2+ and Hct116-Chk2-.
- Hct116-Chk2+ and Hct116-P53-.
- Hct116-Chk2- and Hct116-P53+.
- Hct116-Chk2+ and Hct116-P53+.
Answer choice Chk2- and P53+, those have the overlapping bars there, and then answer choice D is Chk2+ and P53+, again, overlapping bars. So the only one there that was different was that P53-. Hence, the answer is B.
Correct Answer: B
[21:01] Question 7
Suppose that an unusually high degree of aurora kinase activity is observed in the cervix. What could we reasonably conclude about C5M treatment efficacy across all cervical cancer cell lines, using this new information and the data within the passage?
- C5M will significantly inhibit mitotic progression in cancerous cervical cells.
- C5M will significantly inhibit mitotic progression in cancerous cervical cells, but only if p53 gene expression is knocked out.
- C5M will not significantly inhibit mitotic progression in cancerous cervical cells.
- Insufficient information is available to make conclusions about C5M treatment efficacy.
A – It’s a very large logical leap because the question stem is saying all cervical cancer lines, and we’ve only seen one. So we could be suspicious about that because it seems very extreme. And that’s something to always look out for. So we can x that out because it’s too extreme.
B – That gives us no information about cervical carcinoma. So that is completely out of scope for me, that maybe could be true, but they did not give us that information in the passage. So let’s cross that out as well.
C – Again, the same reasoning as we have for answer choice A. We can’t make a complete ruling on what the efficacy of this drug is for all cervical cancer cell lines because we’ve only ever seen one. And so by process of elimination, the correct answer is D.
This could be an answer trap that a lot of students fall into because they’re afraid to say that it’s insufficient information. But it is really that sometimes. So you can use the process of elimination here to quell that anxiety.
Correct Answer: D
[25:14] Question 8
Given the mechanism of C5M action, what is the most likely reason that C5M concentrations greater than 2 µM were NOT used by the scientists for this experiment?
- C5M is expensive to produce; thus, researchers were keeping the solution diluted to conserve their stock.
- C5M was found to be equally efficacious in all cell lines at the same concentration.
- Concentrations less than 2 µM act to increase the efficiency of C5M more than higher concentrations.
- It is possible that higher concentrations of C5M could disrupt normal cellular division and destroy healthy neighboring tissue.
We could probably go back to the passage to see what’s the mechanism because that seems like it’s important. So the mechanism must have something to do with why they chose these lower concentrations.
And in the paragraph right above Table 1, we see its promise as an efficient inhibitor of the division of cells from a multiplicity of origins. So it will inhibit just the division of cells in general. That tells us a lot of cells could be affected by C5M, not just cancer cells. But it said multiplicity of origins is such an efficient inhibitor of the division of cells. And that seems like a broad spectrum ability of C5M.
Maybe the scientists were trying to spare healthy cells from being inhibited too much because that is the side effect. And a deleterious effect of a lot of cancer drugs is they inhibit division, but they inhibit division everywhere. And you end up with a lot of other side effects because healthy cells are being inhibited as well. So let’s try to see which of these answer choices actually matches that prediction that they were just trying to spare healthy cells because this is an inhibitor of all cell division.
Evaluating the Answer Choices:
A – They talk about the cost so we’ll definitely cross this out.
B – We know this is not true based on Table 1.
C – We don’t necessarily have data to support that.
So, we’re automatically left with D before even reading it.
D – This makes sense since most people understand that any sort of cancer drugs is as bad for the body.
Correct Answer: D
A lot of students actually get nervous when we recommend predicting. They feel scared to predict wrong and that they could get biased against the answers.
If you don’t feel confident predicting yet, you can always start with the process of elimination, and make it make sense as you go along.'As you get more comfortable reading science passages, you will learn to predict and you'll start to see that your predictions are a lot more accurate than you think they are.'Click To Tweet
[30:27] Question 9
Why might the researchers have used both Mahlavu and Focus cell lines in their IC50 experiments, considering that both are liver cell lines?
- One cell line is from a healthy liver, while the other is from cancerous liver cells.
- Different cancers may exist within the same tissue and may respond in different ways to possible therapies.
- One cell line came from a human, while the other came from a mouse.
- It was unnecessary; the scientists could have selected only one of the cell lines for use.
A – It said one cell line is from a healthy liver. And we know that’s not true because it said carcinoma in both of them. So we’re crossing out A.
B – It seems like a good possibility so we can leave this on the table. If you want a good cancer drug, you’re probably going to want to test it on multiple cancers within a cell type, as opposed to just one cancer per cell type. That makes logical sense.
C – This is not given to us in the passage anywhere. So we can cross this one out as well.
D – There’s actually a big difference between the two liver lines. And so if they had just used one, they might have come to a completely different conclusion than if they had used the other. So it was necessary to see the difference between how two different liver cancers respond to the C5M treatment. And so, the difference matters. So let’s go ahead and cross D out.
Correct Answer: B
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