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but we stopped. So the SBA today, um, we're giving you, um, all of Megace SPS at the beginning of our talk on. Then if you can feel them in now on, then we'll give them to you again at the end of the session. Um, after after Megan's, that of speaking. Which is why this is a bit different. Unusual. Okay, so say hi, everyone. I'm Megan today. I'm gonna be going through as you saw. Quite a lot of topics to do with the oncology and cancer. It will be a bit of a whistle stop for today, but I'll do my best. It still explain everything as well as I can. For those of you in Cardiff, these you're learning objectives on bowel. They fit into today's talk. But we'll get going straightaway on. We're going to start off by just going through the terminology of cancer to start off with. So I've got through few definitions for you guys to try, so I'll flash up a definition. And if you could just pop in the chapped for me, what term it's describing. So to start off with, we have an abnormal growth of a tissue that occurs independently to the body's normal homeostatic growth regulating mechanisms. It occurs when the body's own cells divide more than they should or do not die when they should, which is a loss of growth control. This is heritable from South, so can anyone pop in the chapped for me? What is that definition? What is it? Just wiping neoplasm neoplasia. Any other suggestions? You're crazier. Brilliant. Yeah, you guys have got it. Well, don't see it. This is the definition of me. A place here. Be aware and you need this a bit for later on. Remember that new places can be benign or they can meet malignant, so any place is not always the same is cancer, which is we'll see later is always malignant. It's not benign, whereas a neoplasia, as it says here, is this abnormal growth of tissue that's growing kind of out of control. That's the definition of the A pleasure. So our next one it's a pre malignant condition characterized by abnormal development of cells, histologically, often with the replacement of a mature cell type to a less mature cell type, usually in response to a stimulus. Any ideas what this is defining Yeah, but you guys have got the right idea. Yeah, loads of correct answers coming in. Brilliant. Yes, this is dysplasia. So it's really important to remember the dysplasia is this kind of abnormal development of cells, usually in response to his dependents. And it's no, always. Dysplasia is not cancer. It may sometimes develop into cancer. For example, you can have dysplasia of the sail cells of the cervix on that could then become a survival cancer, for example. But dysplasia in itself is not cancer. That's important to remember this for this one. So our next definition, Adam normal change in the structure of the tissue in response to a stimulus. So change in the structure of the tissue. Any ideas of this one is? Yeah. Brilliant. Lots of right answers coming in. Well done. Yeah. So this is my pleasure, but, um, next one and increased production of normal cells in a tissue without an increase in the size of the cells. In response to his to me, this so increase production of cells come in. They're not increasing size. Fabulous. Yeah, Hyperplasia. Really Well done. If it was uncreative in the size of the tissue, but the, um, but the size of the cells was changing rather than the number of cells. What would you call that? Her battery. Pretty A lot of guys. You got your definitions. Correct word. Um, so our next one on abnormal mass or growth of tissue, which may be a benign or malignant. Any ideas what this is defining? Yeah, but you guys on the bull Well done. That's tumor. So a team a, um although, like, neoplasia can be benign or malignant, and this is more like a mass or growth. So, for example, if someone had, um, local leukemia so say a cancer of the blood, you wouldn't necessarily call that a tumor because it's not really a mass per se eso. A tumor is when you have this kind of growth, but it's more of a physical mass. That's how I like to remember it. So it's fun number productive cells of the body, which, when they acquire mutations, cannot be inherited. Buy future generations. Any ideas? What? This is referring to you. There's a type of body cell that non reproductive. Yeah. Perfect. You guys have got it. Well done yet somatic. Next one, The spread of cancer cells into adjacent normal structures. What do we call that? Okay, we got bit of a split I've had. It's quite a few metastases in the chart is also invasion. Invasive? Yeah, well done to all the those of you that put invasion and explain a bit more about this in a second. So next one, the spread of cancer cells from its origin site, the distance sites in the body. What do we think that is? Yeah. Pretty well done. Yet that's metastases. So you can have local invasion, which is when the cancer spreads. As that says two adjacent structures, but then metastases when it travels further by three main methods. Does anyone know the three main methods of metastases? How does accounts this? I'll get from one side to the other? Yeah. Transglottic blood lymph perfect. Yep. So it can either traveling the blood drive in the lymph or travel across like a cavity basically on bats. How it gets to more distant sites. Perfect. And then our final definition solid milligram neoplasm arising from abnormal, unregulated cell division which invades into nearby tissue and can spread to distance sizing the body. Yeah, but in cancer carcinoma. Excellent. With, um you guys have got your definitions done. Really well, which is really good. Um, I know I personally really struggled with definitions. I found this diagram really helped me a lot to understand these different cellular changes because sometimes the words could be a bit confusing. So what I want you to remember is in comparison to a normal cell, you have atrophy, which is when there's a decreased size and function of the cells. You have hyperplasia, which is when the number of cells increases. So you can see we've gone from 46 but then you have her purchase be, which is an increase size of themselves. So we've still got four cells, but they just increased in size. You have to be really careful with these two here hyperplasia and hope I but free because both of them will cause organ or tissue enlargement. But as you can see, there's different mechanisms underlying that. So that's really important to know the difference between the two. Then we have met pleasure as you guys know, which is the change in the structure of the cells and finally dysplasia, which is the abnormal development of cells. So this is kind of a summary diver and hopefully make it easier to learn those definitions. Then I've just popped on here a little image for you guys to look at maybe in your in time, but just so you can understand how normal cells can go through these cellular changes to develop into a cancer. So we start off with our normal cells, and then, as you guys know from your oncology physiology, that will go through a bit later. The cell cycle in the cells becomes unregulated, which can then cause cells to divide more, more rapidly so that causes are hyperplasia Has we have more and more cells developing? And then, from there these cells begin to develop Abnormally. Something goes wrong with mutation, that kind of thing that causes the dysplasia and then that can lead to on neoplasm or, in this case or cancer as theseventies begin to invade the basement membrane. But you can look at that as a bit of a summary in your in time. So next wanted to cover kind of the naming convention in oncology, because if you can get run, get your head around this, this could help you a lot with your SPS. A swell. Um so to start off with start with are benign. So if you see a word and it is a tissue plus oma on that is a benign neoplasm off the origin tissue that's named in the name of the word that you see. So, for example, in adenoma is a benign neoplasm of glandular tissue because adult or usually represents, it's kind of the prefix for glandular tissue or lipomas is the same. But for adipose fat tissue, can anyone putting the chapter may What would be a fibroma using that logic? If I say somebody has a fibroma, how would you define a fibroma? Yeah. Brilliant. Benign neoplasm off fibrous tissue. Fabulous. So that's your tissue. Pass over, then. If we go into tissue for sarcoma. This this basically is a malignant neoplasm this time of connective tissues. So a liposarcomas we saw before lipo meaning adipose or fat. This time we have a malignant neoplasm of adipose of fat. So can anyone tell me if you had a wrapped? Oh rhabdomyosarcoma, What would that be? Erupted? My psych oma. Perfect. Yeah, So it would be a malignant neoplasm of specifically skeletal muscle. But you guys have got the idea. Then we have our tissue plus carcinoma. That's a malignant neoplasm of epithelial to shoot. And I've got a couple of definitions here for you to read in your own time. But can anyone tell me what would be a squamous cell carcinoma? What's that suggesting? What's the definition of a squamous cell carcinoma using this? This mechanism here, this convention? Yeah. Perfect. Yeah, lots of rounds is coming through, so yeah, it's just a malignant neoplasm of squamous epithelium. So you can see using these name and conventions could be really useful because you can gain a lot of information about what? To she was affected on what kind of cellular changes are happening just by the name of the near present that you see, Um, some other important ones be to know are lymphomas and leukemias. Lymphoma is a malignant neoplasm of immune cells on that's normally associated with the lymph nodes. Up a little lymph node diagram. To help you remember that auras A leukemia is a malignant neoplasm off excuse the double off off the blood and the mean cells mainly in either the bone marrow or in the blood itself, so these two can be quite confusing. Have problem has hopefully you'll be able to remember the more with these diagrams in the future. And obviously with anything in life, there are exceptions to Israel. So if I told you somebody had a melanoma, well, you would probably think it's a benign neoplasm off melanocytes. The design will know what a melanoma actually is. Can you pop in the chapped for me? What is a melanoma? Yeah, Perfect. Yeah, it's a malignant Yes, it's a malignant neoplasm of Balon asides within the skin. Perfect on. Do another one of you guys to know is hepatocyte little carcinoma. Um, you. It's basically a malignant neoplasm of the best sites, so all kind of functional liver cells that doesn't necessarily fit is mold on, but it's important exception to know radiance. Then we're going to the cell cycle because that's really important in terms off oncology. So what is the cell cycle? Well, it's a coordinated sequence of events by which is sell, duplicates its contents and then divides into two identical cells, basically cells splitting into two. Can anyone pop in the chat? What are some of the functions of the cell cycle. Why do we Why do ourselves go through this whole cycle? Why is it important? Get pretty and grow from repair. Brilliant maintenance of tissue. Perfect replication yet brilliant CIA. It's for development of tissues, replacement of damage tissues if you have a few cells that become damaged, replacing those on Galson so in wound healing as well. So if you've damaged a tissue, that's a really important for you to have the cell cycle to make up new cells again. So I've done a little diagram for you guys off the cell cycle, the which hopefully brings bells. Remember that different cells go through the South cycle, different rates, so you'll have some cells like, for example, the epithelium within our esophagus that is constantly being wet, worn away by the food. We and so the cells there will be going through this cell cycle really, really quickly. Um, whereas you have other cells, the can go through the cell cycle but won't do it very often. They might need quite a strong stimulus to do it, for example, like the alveolitis in our lungs, they need quite a strong stimulus before they go through the South cycle. They won't kind of do it very regularly. And then you also have permanent cells which don't go through the cell cycle. They're very specialized. Ondas We'll talk about. They just kind of sit in this gene or phase. So just remember, even though the cell cycle was quite a kind of fixed, So call if you like, know every cell goes through in exactly the same way. So let's talk through the different stages, so we start off with GI. Note. This, as I say, is where the kind of terminally difference is differentiated cells sit on. That's basically where cells are when they're not undergoing so replication. So I kind of think that this is like a pause phase, that kind of pause. They're not not going around the cycle, they're just sitting outside of it. Then we go to GI one. This is the longest phase unending into gear on as I said before is camp is triggered by stimuli said. There's a really strong stimulus. This will kind of kick a sellout of gene or on force it to go into do one, so that could be things that might, uh, gyn is that will go through later. It might be internal signals in the cell Extent of signals in the cell Septra. Um and what's important to know is during the one, basically you're getting ready for our essays, our DNA reputation and ultimately, the so dividing. So we need to make more cytoplasm because if we're making more cells, those cells need to be kind of equal in size to the original. See me to make more side puzzle. Need to make more organelles because both both sides or get a require organelles. Um, you need to make more proteins that you're ready to perform D and a reputation and also the stage. Would you look for any mistakes in the DNA as well ready before gets replicated. Then we have essays. This is when our semi conservative model of DNA replication occurs using DNA primaries. And then we go into G two. So the DNA was replicated, but now we need to get ready to replicate the cell itself. So once again, the cytoplasm increases in size. We make some more enzymes and more proteins, and we do our final checks ready before we make two cells and then finally we go into our emphasis. So I'm sure you guys know the stages of my toesies. But here's a little diagram here. So we've just been through interphase interface being G one s phase and G two, We then go into prophase. This is when the DNA kind of condenses. It forms those two sister chromatid, it's and the mycotic spindles. As you can see here, it stopped for muscle. Well, um, there's also you can't see it on this diagram. There's also kind of a pro pro metaphase in the middle. That's where the nuclear envelope breaks down, that we're ready to move these primitives across the cell because if they're still contained within the nucleus and they're not going to go anywhere, then we have metaphase, which I remember is middle. So we'll the chromosomes align in the middle. And on a phase where the Crimson's pulled away towards post t the phase where they arrive at the polls and we form these new nuclear envelopes on, then finally excited kinesis where the actual side has, um itself. That's so hopefully that's all ringing bells. Hopefully that should be good. So how do we regulate the South cycle? How does it come about? How do we make sure it's performing as it should? Well, the South cycle is regulated by these structures here called C CD case or cycle independent kind. A XYZ Um, what happens is and I've done that, or animation toe. Hopefully help. This make sense is we have these molecules called Might a Jen's. A Mighty genes are basically molecules that stimulate my toast is they stimulate the cell to replicate. So what happens is a mighty gyn binds to my my to gym receptor on. So remembering what that does is that then triggers an interesting your signaling pathway. So signals go from from the outside. From this much Jim is that you're going off two on the nucleus of the cell, and what that does is that activates transcription factors off genes that produce Cyclens as well. Well, yeah, produce the the genes that produce cycling's basically upper curates those transcription factors so that more Cyclens are produced, Um said when we have a much in that increases the amount of seconds that we have so cyclen dependent kind of Karnezis is also produced. A different site in the DNA, but they're produced at a constant rate. They're not affected by the Mighty Jones in that way. They're always around. Whenever we need them, they'll be there. But is this up regulation of the cycles? That's really important. So we've had this mitogen. It's telling ourselves we need to divide so more seconds have been made. The CDK is always there. So then what happens is the cycling on the CDK bind together on that. Well, then go on to stimulate proteins and other components that, um, push on ourselves. I can keep it moving as it should, um, such as go through the reputation, etcetera. And what we need to remember is different parts of the cell cycle. A rep a controlled by different Cyclens like independent kind. A Z combination's basically eso. There's four main checkpoints you need to know eso further progression through G one. We have a cycling called Cyclen D, which helps to control that on that's paired with the CD K for or CDK six on CDK. Then we have the GI one aspect point. That's a second a a CDK to progression through s phase, Second A and CDK to um, progression through G two up to where the spindles and begin to assemble in M phase. It's that could be CDK one. Now, this is obviously something you just got a set of memorized. But the way I like to remember it is just deep if you do them in order. Deep breath isn't It was It just seems to stick in my head and with these ones as well. I like to kind of remember them. Um, especially if you look at 4 to 11. They're kind of multiples of each other, saying half four to get to have to to get to one on that sort of helps. But savvy, this is just something that you got to sit down and remember. Well, hopefully those little tips and tricks help a little bit. So how does this function in the South cycle itself? Well, as well as these seconds is like independent Canase is, we also have checkpoints on these help to provide an extra level of control Basically, in the cell cycle. Um, we have three main checkpoints. Does anyone know what any of the checkpoints a cold do you want s pretty in? I've marked them on the diagrams, hoping they're in. They are in the right place. That might give you a clue as to what I called. Yep. Do you want to ask you to, um perfect? Yep. Spend, uh, some very, really well done yet. So we got Do you want us checkpoint due to inject point and spend assembly or the inject point? That's really good. What I've done is well, as I've marked on on the Cyclens we just talked about, you can see we've got our deeds A d e a A and B. So what do you teach of these checkpoints do? Well, the G one aspect point. At this point, we've gone through the ones we've got our cell ready to replicate. So this checkpoint basically just checks that the cell is in the right position, ready to replicate in the right environment. Everything's favoring cell division. It's got sufficient proteins. It's got sufficient side to pass. Um, except, uh, so that it definitely is ready to replicate his DNA. Our next checkpoint is up here and do two m on that basically checks that there aren't any mutations in the DNA because with mutated are sorry. We've replicated idea and Espace, and it's growing a little bit more. And you, too. So at this point, before we create a whole new cell and if it was wrong creek two cells with a problem, we want to check that we haven't got any problems without delay. So we check here, there's no mistakes. Any DNA that's been damaged has been repaired on D. Um, all the DNA has been replicated before. We then divide, um, during my testes, and then finally we have the spins assembly s. So this is basically where we check that the my topic spindles air attached to the sister committed before they pulled apart so that that process during out of phase, where they're pulled away, goes, goes ahead successfully, basically brilliance. Now we'll go into the histology of cancer. So to start off with tissue processing. So this is quite a long winded set of steps that you need to remember about how, um, a tissue is processed. A cancerous a potentially cancerous tissue is processed. Um, this is really important because it's important for the grading of cancer on. We'll go into later. But the grading is all about looking at the microscopic level of a cancer cell on the cancer cells to look and see what their structure is like, how differentiated they are so that we can understand what treatments we can get the patient and they're prognosis and that certain things that that is really important, that we processed these tissues correctly so that we're able to gather all the information. And the aim of this tissue processing is basically to go from you can see here biopsy. So a kind of bigger mass of cells, that part of a cancer to a very thin slice of that that's adequately process so that we can look at it under the microscope around with the microscope. So we start off with our biopsies. So we've taken a small example of the body tissue that contains the cancer cells on. There's four main areas over cancer and surrounding tissue that we need to take cells from. Does anyone know which bits of the cancer do we need to do? We need to take our samples from what do we need to encompass in our samples, yet? Margins brilliant. That's type of thing I'm thinking off yet margins what else do we need to get yet the core of the cancer itself? Yet we need to look about anything else. Lymph nose perfect. Yet I've just had another message is, Well, yeah, you guys have got all forth and the other one's the background issue because with cancer, a lot of it is comparing the cells to the cells around them that are normal. So we need to compare to the background tissue perfect. So we need to take a biopsy of the cancer itself because we need to look at the cells. And so we take several biopsies of the cancer itself so that we can get a good view of that. We need to get the margins evolved because we need to make sure that we've added quick, adequately excised the tumor. If we were taking it out on these margins shouldn't contain any cancer cells if the tumor has been fully removed. If there are cancer cells in the margin, you need to go back on dmard sure that you exercise more because it suggests that you've left some cancer cells in inside the patient, which then could leave their cancer to regrow on cause issues down the line. Then, as I say, we need the background to shoot. That's really important to compare the cancer cells to the non cancerous ponds on. We also need the nearby lymph oats because we want to know. Has there been any lymph nodes have been affected by this cancer? If it's spread further, brilliant is the next step is fixation with formalin solution. Onda, I'm sure, especially if you're from Cardiff, you'll have heard of formaldehyde. It's often used a tissue preservative, basically from our highest tech here gas. So when you dissolve it, that's what forms the formalin. Um, and that's what this compound is, and it's a tissue preservatives. It prevents the samples from breaking down further because we want to look at the cells and their structure so we don't want them to break down after we taking them out of the body. The move. React the tissue with alcohol and Xiling. So the job of the alcohol is to remove the all the water from the cells because we want to look it on a flat surface on. Then designing basically gets rid of that alcohol. So we just put put loads of our car with and we don't want to leave the alcohol there, So then use designing to dissolve the alcohol. So what we're left with is cells of no water in it. Basically. Then we need to embed the tissue in something called power from works. Basically, the reason why we do this is the works surrounds the tissue, and it allows us to take thin slices of the tissue. You wouldn't be able to do that after you just reacted it with the alcohol is Eileen. You need to put it in a solid structure so that we can take our slices and I'll show you that in a second. And then to take the slices we do you think could sectioning and that's using a microtome machine. So basically, this is a machine that they use a new see a video in a second that they used to get these thin slices. Then we need to stay in it, which I'm sure you will remember from school. So we use the hate any staining. Remember that, um, the marks talk sling stains the cell. New guys boot on the es in stains this side to present pink as you can see in this image. And then finally, after we've made our little slide with a little tissue sample on it, we need to send that to Histopathologist to have a look at under the microscope so that they can braid the cancer. So I thought to bring these to life, I chewed some videos S. So this is what happens when the tissue is embedded in paraffin wax. I'll rewind it because it's quite quick. So the tissue is put in a little cassette, and then the in the liquid in here is kind of a liquid paraffin wax, and they put it on this metal sheet, which is really, really cold on. What that does is that sex sets the work solid. And as you can see, we've gone from having quite a thin slice of tissue to then having something that we'd be able to slice more easily on. Then, here, this is the Microtome machine says you can see a thin song Boys coming out here that's very thin. The wax sample is in this thing that it's moving up and down, and we're able to make a very thin sample off the tissue here, which can then be taken ready to use pop on a slide and use to look at under a microscope. So that's what it looks like in real life. I think it's a bit easier to understand the process if you can see it on what it's actually, um like in real life. Perfect. So we processed are sample and we're beginning to the under the microscope. Can anyone pop in the trap for me? What? You might see what the kind of classic findings that you might find in a tissue sample if it's cancerous. Well, the features of a cancer cell looking at it under the microscope. Pretty in. Oh, yeah. You guys got lots of ideas. Bring it nuclear polymorphism. Brilliant. My toesies crisis hopes is yet hopes other cell your oxy basement membrane breach yet? Yeah, hi Nucleosides President ratio. Yes, you guys are pretty well done. So yes, nuclear PM or physics. This is basically where the nuclear in the cells insoluble are all different sizes. So remember that the nuclear staying kind of blow here you can see that there's somebody small ones. There's some really big ones. They're all different. So that's a sign of cancer that, as you said, a breach of the basement membrane to remember. Epithelium sits on top of our basement membrane, which is on top off any connected tissue organs that are underneath. So if you have a cancer cell that begins to bake, break through that basement membrane, you may see that on on our tissue processing to look out for that one. There's you guys said my toe, see? So if you can see my toesies, as you can see where these white hours appointing on that suggests that the cells are going going through ourselves cycle very quickly. A lot of them are going through the M phrase, which is obviously classic of cancer. So you can see here some cells here, probably at the end of Anaphase. They're being pulled away. We've got metaphase cell here so you can see that the chromosomes of condensed in there I'm undergoing those actions that you see in the cell cycle. Then we have a necrosis. So when the cancer cell grows really quickly, sometimes it can grow so quickly outstrips its blood supply on. That means that the center of the tissue that's furthest away from that blood supply dies on what happens is it becomes this kind of dark pink color that you can see on this slide. Um, and that's a sign of cancer. If you can see that the inner part a dying. And as you guys said, hi percent cellularity and crowding. So if the cancer is replicating really, really quickly, we're gonna get lots of cells were gonna get some of that hyperplasia on. As you can see, I have shown you to slightly you could see the top one looks relatively normal, but the bottom one there are loads of cells. You conceal the nuclei that really squished in That leads to that kind of crowding hyper cellularity cause he lots of cells in one place. Perfect. So I'm gonna wish through the grading and the staging of cancer. So what is grating? So grading is the severity of a malignant tumor according to its degree differentiation from background normal tissue in the area using histological analysis under a microscope. So, in a nutshell, it's how differentiated is the cancer in comparison to the normal cells, which is why we need to compare it to our background tissue as we talked about when we were doing Our tissue processing and grading is all about how it looks under the microscope. It's not necessary where it is, it's not necessary. Anything like that, it's all about What did the cells look like when they are looked at under a microscope on what you need to remember is as a cell. Oh, as a cancer grows and becomes more developed. Generally it tends to undifferentiated. It tends to go back towards more undifferentiated stem cells. Eso to grade it. We use different grades. Commonly, a three grade system is used, but you may have a different cancers, different grading systems to use. I don't have time to go to every single one. But generally the higher the grade, the less differentiated the cells are and therefore kind of the worst prognosis. The more developed the cancer is, so you can see here that grade one is well differentiated. The cancer is tissues quite similar to the background tissue on. This has the best prognosis and then we have great to poorly differentiated. The cancerous tissue has a low resemblance to the background to shoot, but you can kind of tell it looks similar and then we have great three, which is undifferentiated. Looks nothing like the background issue at all. On this has the worst prognosis because it's growing fast, it's going through. My toast is really quickly. It's invading, and it is a greater chance of metastasizing. So that's grading. That's in comparison to staging. Can anyone tell me what the definition of staging is? Got to define what staging is in comparison grading. What would you say? Staging is, Yeah, profits. Really good definitions coming. Three guys? Yes, perfect. So it's the size of the tumor, brilliant on how far it's anatomically spread. That's the idea with staging. So the definition I put down is an anatomical description of the science. When, say extent of a pro me tumor and it's in lymphatic, Mr Metastatic, spread them. Get the words out. So it's basically anatomically. How big is the the tumor itself? Has it gone to the lymph nodes and has it metastasized to a distance I on. Because of that definition, we tend to use something called TNM staging to summarize all three of those points. So that stands for tumor, which is the size of the Prometrium itself. How much. It's grown at the original site and how much it's invaded into nearby organs. Lymph nodes. How many lymph nodes are involved where those lymph nodes and those are the ones containing the cells from the primary tumor? And then we have metastases. So how far those cells spread from the primary cancer site to a distance? I basically on with staging where not necessarily looking under the microscope because that's not a lot more grading. This is looking at clinical findings. So the patient's kind of examinations of symptoms except, uh, we're also looking at the imaging, so you might get a CT scan, a pet scan, etcetera to see if you can pick up cancer cells elsewhere in the body. Um, and staging is more important for prognosis than grading is because once something is metastasized, it's a really high stage that completely alters what treatment you can give to a patient. Um, that's really important to remember I popped here The definitions off, um, for the kind of descriptions of the different abbreviations for tnm staging, I won't go through the mole, But what I think is most important to remember is if you see an X That basically means that that measure the tumor, the nose or the metastases can't be measured. So it's not. It's not there. You just can't measure it. For whatever reason. The scan is inadequate, cetera. It can't be measured. Well, if you see a zero, it means that the thing that's being measured, the tumor that influence the metastases is not actually present. So you've looked for it. You could find it, but it's not there. So, for example, if someone was in ex, it means that you can't measure the lymph nodes. For whatever reason, you can't see there's a cancer there. If they're ends ear. Oh, then you've looked in the lymph nodes. You've adequately looked. It should have worked it. It would have picked something up if there was something there. But there isn't something there. That's the difference between an X and the road or extends a row in. But all three of these categories on that something that comes up on exams really, really often to make sure you understand that difference. Um, and I'll let you read through the exact definitions of all of these in your own time. So really quick. The difference between nine and Millikan. So I've popped here a few definitions. So benign, meaning a tumor that doesn't doesn't invade or destroy its origin tissue. And it, more importantly, doesn't spread too distant sites in the body on benign is a non cancerous tumor. So we said before that cancer was a malignant neoplasm. Therefore, relying benign things that you have finding the body. You know, they're not cancerous, basically, whereas malignant is a tumor that invades and destroys the tissue that it's in. It conspired to distant sites, as we said before on it may also affect the lymph nodes. So can anyone pop in the chapped for me? Any features of the line on DMiller? Clin gross that you can think off any of the differentiating factors between the two? Yeah. Yep. Benign as well. Defined margins. Brilliant milligram, poorly defined, benign stays. Local know. Mets less invasive. Better prognosis. Excellent. Benign Doesn't invade basement membrane. Anything else? Any other ideas? Not so good ideas coming through slow growth in benign, malignant rappers. Yeah, perfect. This is a summary table that you guys can use for your vision. Just detail in the main group of main differences between the two. So benign is local malignant congrats where the nine is very defined in its margins. It's very, you know, exactly which sells a country. Sorry, which cells are benign and this abnormal growth, which cells normal, whereas in malignant it's a bit harder to tell. Benign things you said grow more slowly. Resume ligament is very rapid, the hot they go through cell cycle very quickly. Undergo mitosis very quickly as well, when I intends to strongly resemble the tissue of origin, whereas Millikan things tend to know as well. And then I, um And so I was called metastasize. Whereas malignant cells have the potential to which is, as we know, main cause of some of the deaths that we have in cancer on benign generally has a good prognosis where, as malignant, sadly, does not ridean. So then we're going to the difference between oncogene untrue suppressive genes. So to start off with tumor suppressor jeans. These are genes that involved in slowing down cell division, repairing damaged DNA on a proptosis so that controlled, uh, death of the cells. Basically, if a tumor suppressor gene becomes mutated, we call that in activating mutation. So Basically what that mutation does is that inactivates or turns off a tumor suppressor DJing. So we're turning off a gene that would be suppressing a tumor from forming. So what happens then is, if we're not stopping a tumor, forming it is more likely that the tumor will grow. There's no limitation on the cellular growth whatsoever, and that's how cancer can occur. I'm sure you guys have heard the kind of analogy of a car, So if you think if we have a mutation in a to Mr Pressure Gene that the break or the parachute, or whatever you like to think all that's slowing the car down get smaller, so it's more likely that the car is going to speed up. It's gross. Gonna get quicker, and it's gonna go really, really fast. If the cause of the cancer is from a mute mutation in the tumor suppressor gene, you need to mutated coffees for the cancer to develop. If you only have one copy, that's enough for you to prevent the cancer from occurring. You need both of them knocked out before you can get cancer to occur, and I'll explain that more in a second we compare this to a proton codeine, which is a gene that's involved in normal cell growth. So the making sure that ourselves do grow and they go through this out cycle, but they go through the correct rate when this becomes mutated. This converted from a proton, codeine, Tylenol, codeine, and we call these mutations activating mutations cause they turn these jeans on. So we go from a cell that's just regulating normal cell growth. Normal rate on, then you activate it, and it goes into overdrive on that causes that uncontrolled, uncontrollable cellular gross. So going back to our car, this means that the frontal force, the accelerator, is now being pushed down as hard as it will go on, the car is going to speed up really, really fast and grow really quick as well. Because of its effects. You only need one mutated copy for cancer to potentially occur, because if you're speeding that car up, no matter if you have one copy or two, you're going to speed that car up anyway. So that could then develop into a cancer is I hope that makes sense that leads us onto Knudsen's to hit hypothesis of tumor suppressor genes. So, as I said before, a single cell needs to lose two copies of it's tumor suppressor gene for a near pleasant to develop, says they said Before, if you lose one copy of a tumor suppressor gene through a little activated mutation, there's still enough tumor suppression for accounts not to develop Onda. This is really important to know for the difference between sporadic and inherited cancers. So if, um, somebody has, um, a sporadic cancer developing when they're born, they they're gene that to Mr Prosser, Gene on a crime his own here. So that's a It's about here in this chromosome in a spread of cancer. They're born with two normal copies of the tumor suppressor gene in both their maternal and paternal reels. Over time, if they develop mutations, then in this diagram, the chromosome is going to turn, you know, move. But next, so you need this toe happen twice before you can get a cancer to develop. So we need to somatic mutations to a cup. This is in comparison to an inherited cancer, where when somebody's born, they've already had a germline mutation. So, um, you take in that they've inherited from their parents reproductive cells off one copy of the allele already being mutated. So we've already had one it. If you like to the tumor suppressor gene during life, they then only require one more mutation of that tumor suppressor gene in that cell for a cancer, then to develop on. Because of this, you can see why inherited people that have inherited cancer syndromes develop their cancers a lot earlier in life because it doesn't take much time for these mutations to accumulate in the same cell because you've only got to hit it once, as opposed to hitting it twice. Um, you take shins are quite rare anyway, so the chance of it happening twice is quite slim, but obviously can happen. As we know, if someone has an inherited cancer, this can happen a lot more quickly. You've only got half. It happened once, so brilliant on to our last section. We nearly done. So I'm gonna go through the types of DNA damage on so about inherited counts is and joins. So what can cause DNA damage from anyone putting the chapped for me? What different things could cause DNA to become damaged chemicals brilliant sunlight. Radiation smoking. Perfect. That's a good ideas. I realizing radiation. Yeah. Brilliant. Okay, so what I've done is I've route this into exogenous on endogenous so exogenous meaning outside and endogenous meaning kind of internal. So you guys came up with loads of these? Well done, sir. Exogenous. I'm thinking you the radiation from the sun. Um, ionizing radiation is You guys said some things that x rays on tobacco smoke. Well, we know that that's a carcinogen that can cause damage to our DEA. Internally, we can have reactive oxygen species, eso different reactions. They may create some of these reactive oxygen species which can then attached to the DNA damage it. Well, we may have a swell dealing memory's failing to be payroll for basis during DNA replication. So we know DNA play MRIs is role is to add on the complimentary nucleotides to theory Jinling DNA strand. If it adds on the wrong base, that is technically a mutation. So if the DNA memories fails to do its job, that could be an indigenous cause of DNA damage, especially for is, um, repaired. So there are seven different types of DNA damage. If there is DNA damage. It causes the cell cycle two stone if it's being regulated correctly, and if that don't midges ever parable them, the cell will undergo apoptosis. So it's, we said, before that controlled cell death. So I popped on here the seven different types of DNA damage that can occur. So we have a single strong breaks says that says and 10, a break in one of the strengths and a basic sights of a site where there's no base, a double strong break breakthrough, two strands an interest. Wrong Crosslink. So that's to curve a little bonded nucleotides in different strands of the jury in a But because it's interstromal, it's between the toe. Then we have Ms Pairing. So, like I said before, you know, primaries doesn't do its job, but it pairs the wrong base. It doesn't give us a complimentary pair. Then we have intra strand crosslink, so that's when to nucleotides in the same DNA strand. Currently, bond together as you can see by the started lines on then we have bulky Adoxa, so that's when, like chemicals you guys had before can attach onto the D A distorted shape because leads a different problems as well. So can anyone tell me, what's the mechanism off DNA repair? If we have a single strand break or a a basic side, does anyone know I would test you on all of these and just quizzing one or two? What's the mechanism? Yeah, I've had a few ounces come to me. Yeah, really good. So this one is basics Asian repair. So if there is DNA damage that's detected, that's either a single strong break on a basic site. We have basics. Vision repair, really well done for Double Strand, break into strong cross. Think this is something called homologous recombination on nonhomologous and joining for Ms Pairing. It's Ms Much repair that was quite easy to remember. I'm finally for the other two. We have a nucleotide excision repair. So these are things you sadly have to remember. You don't at your stage need to know really how they work or anything like that. But if in exams they say, Oh, there's a a basic site. How is it repaired? Need to be able to recall those basics it in repair on. Hopefully, this diagram will make it a lot easier to remember. Remember that if deal a damage occurs on these pathways are lost or they're not working the DNA well, then obviously not be repaired on. That can cause mutations to accumulate in ourselves on. Eventually, that increases the chance of us having either a Proton cojean activating into an Uncle Jean or a tumor suppressor gene having a new doctor, gated mutation and then that causes the cancer to develop. So that's why this is relevant. We damaged DNA, and then we get the mutations accumulate because it's not being repaired properly. And then that causes makes it more likely that those mutations are ones in proto-oncogene or tumor suppressor jeans on that, then causes are cancer. Million. So then a little bit about inherited cancer syndromes. So can anyone putting the chapped really quick. What are some features off inherited cancer syndromes? They're features that would make you think this is inherited cancer and not one that has occurred by somatic cells By all two hits. A Z spoke earlier. Let's follow this Brilliant. So yeah, young age pretty in family history. Perfect. Multiple cancer is rare. Cancer. Yeah, You guys have got it Well done. Yes, multiple counts is sorry multiple cases of the same or related cancers in the family. So, for example, breast or ovarian, that's really good young age. So, as we said before, it shouldn't take. If someone has an inherited cancer, it doesn't take as long for them to get two hits of a tumor suppressor DJing or two developed one mutation in and proto-oncogene so younger age seems to point towards it, um, rare cancer types of things that retinal blastoma is things that that that rare er they tend to be inherited if the cancer's have any abnormal features. So what? This images alluding to is a right sided colon cancer. Generally colon corrective lenses. The left side. It's if it's right sided, you might see. Think that's a bit abnormal. Um, also, if you have triple negative breast cancers, so where the Eastern progesterone and her two receptors a real negative. That's quite irregular as well. And if there's more than one type of cancer in the person, either synchronous that at the same time or metachromatic so at different times in their life, brilliant. And then finally, what I've done is I put together a little summary side off some of the three main inherited cancer syndromes that can affect the bowel. It's obviously we have a menial adenomatous polyp poses or F A P. Listen, this is a mutation in APC Gene, which is a tumor suppressor gene on what happens, is, as you can see here, people develop thousands of these small polyps on polyps. A little kind of adenoma is so benign, neoplasms off landed a tissue that developed in the colon quite early in life. So about 8, 30 or 40. And even though these are belonging there kind of the first step to developing a cancer eso it's more likely that a cancer is mutation. Will developing these on then go on to cause colorectal cancer? So it's estimated we both have 100% chance of developing colorectal cancer. So many of these patients have a prophylactic colectomy, so removing the code on ahead of time in their twenties. Then we have lynch syndrome, So mutation and mismatch repair genes. That's really important to note. It's the most common cause of inherited colorectal cancer on this could be quite aggressive. It's not. It's not a very good one to have it all on what you really need to know for SBA is is is it's association with other types of cancers as well. So colorectal, endometrial, ovarian and the main other types that you see with lynch syndrome. So if you hear that someone's got kind of two of these or they've got a family history of these anything like that Pink Lynch syndrome and they just put here funding map. So this is a mutation in the much way HG in this one is also more recessive, the old one out. It's quite similar. It's description to F A P, but the cancer risk is later on in life. So you would want this identified. You do a colectomy and do an ileoanal pouch. So where the terminal ileum is, um, anastomosis to the anus. Basically, um, and this is also associated with breast cancer brilliance. That's all my slides or electrical while to go through. Um, so what we're gonna do is we're gonna go through the SBA is that you dip a force. It should be nice and quick, but hopefully you find them easier to answer this time. And so would I be able to get someone to launch the polls for me. Sorry. I can't get them to work on my laptop. So, Hannah, could you let me know when you started and stopped the pole? Sorry. I can't see it. Start it. Sorry. No, that's five. That's five. Let me know when you stopped it. Sorry. My computer's having a funny five. Mandatory. Um, Flick. 2.5 minutes. Should be a good and point commanded air. Is that okay? We really got about, like, 30 responses, and I think it's picking up right now, actually. Okay. Let me know when it's get that seconds. Maybe, um, they were officially at 35% but 60 responses. That's a because of time. I'm just going to move on. So if you guys answer these quick as you can that be super helpful. This is probably the hardest one. So the answer to this one was papilloma. So what I was trying to get out with this question is getting you to think about the definitions of each of these. So remember, if you have a tissue plus oma, that's a benign neoplasm in you, um, melanomas or exception to that tissue plus home a rule. So we talked about before leukemias, that malignant neoplasm of the blood on immune cells from the bone marrow that then goes into the blood. As he said, Melanomas. The exception. That's a malignant neoplasm of the melanocytes squamous cell carcinoma. So remember, carcinoma is a malignant neoplasm of, in this case, squamous epithelium. So that's malignant. That's gonna have a worse prognosis. Rhabdomyosarcoma. So that's a malignant neoplasm of the skeletal issue. So papilloma is the only benign lesion here. Therefore, that one is most likely to have the best prognosis. Next question could really launched whole, uh, make. Basically, I launched all of them maxed. Okay, don't worry, that's fine. Then call. I will just talk through these, then. No worries. No, we've got 64 responses. That's fine. That's fine. No worries. Want that's okay. So the answer to this one is B. That's because we're talking through. We're talking about Cycling is responsible for progressive progression. Three seed to GI to. Sorry. So if we look back at our table from earlier, that was our last cyclen, which you remember by the Deep Pneumonic and would be be in this case. So that's why it's like them be on Then we had this question, which was the 61 year old female. She's had a hemicolectomy, um, on she's had it processed by histopathologist. Which of these is, um no, a histological silent malignancy that may be seen in her sample. So the correct answer here was metastases. So I'm sure you guys, you all got these early in the chapter on these are the different size that you might see of a cancer on tissue sampling. Remember, metastases. Even though it is a sign of cancer, you wouldn't see it on a single tissue sample. You need to look at things that scan. So that's why that's the incorrect on. That's the correct answer here. But it's not what you would see on her histological sample on, then. Finally, this is quite a tricky one is well, the tnm staging off. Um, this tnm So she is ah t two n zero m x. So the answer to this one was a So remember X means that something cannot be measured. It could be Look, it cannot. They measuring hasn't worked basically and's ear Oh, means that it's not present. So you've looked for it. It's the looking has worked, but there is nothing there. So in this case is T two. So I didn't expect you to know what ti waas for. Breast cancer. So T is tumor measuring 2.25 centimeters. It's zero. So it's not present. We've looked for it. We've measured it, but it's not less. There's no lymph node involvement on MX mean it cannot be measured to the metastases. Can't be measured. That's why the answer to that one is a And that's my an end of my presentation. I hope that was helpful. Thank you so much. I pass over to Toby. Yeah, Um, thank you. Make. That's really good. Really comprehensive. Um, just got with me and my men digestive of next lecture while I try and show my screen. Let me know what? You want me to launch the bulls, Toby? Yeah. So we can if we lost the post of the start. We can do that now. Okay, Do it now, then. Okay. Cool. And people see that. I would hope so. Yeah, we can. We can say Oh, other people couldn't see okay work only at 30 responses, and it's picking up. So another 30 seconds or so it just let me know. Sauna. Yeah. Um, okay. I see this is all right. Actually, um, 64. 65 86 Missus submitting. I have been ended there now. And is it? Yeah, it's three. Um, Right, then. So my section I'm gonna be going through the whole marks That cancer on some treatment, including phone quality. Yeah. So you might see this on image before this is just relaying different. Who must cancer, whom ox comes up being, um, elements or traits of cancer, which a lot of cancers share. Um, and initially, these were put down to six traits. Um, which I've labeled here and then recently. More recently, um, four more being added which are going to you later. So fastly sustaining curl effective signal. This is basically just maintaining growth. Um, kids as a cancer. So you want to just to buy this much you can grows quickly as possible. So you probably remember neck talking about my Tradjenta on D in health. He's a years to start. So, cycle, man, ever. The side wants to divide, and it's appropriate. However, encounter cells on the development, a shins, and they're much in receptors, Um, or at the time of great factor receptors say that's like tires and kind a XYZ or had to receptors That should be hard to know. Has to, um, on me. As a result, it means that the cells can start this whole cascade on proliferate without the need Been lights gentle bind initially, um and then ultimately that leads to activation of Raz To think I want to activate slightly d It combines Deanna and stop the whole set of cycle pre sex just water on the topic of tyrosine kinase is, um imatinib is a drug which is used to treat chronic myeloid leukemia. When there's a BCR a be out tyrosine kinase is on this dress, it inhibits that so country so juices this ties in kind of which can activate without the need for my surgeon. Then mass nip just comes along on blocks that okay, number 30 evading of great suppresses. So normally in health, you have a team of suppressive such as our be on D happen is when and this I will want to divide a cycling dependent kind of come along, bind to the gym suppressor force for a later on, then, cause it's changing shape. So there's no longer any inhibition and as a result, uh, in the South and going to devise. However, in Kansas case, um, the gym, a suppressor might be irritated, and that means it's a shape is never complimentary to the trend to the transcript from back there on. There's never any impression on the South and just gross motor once whenever it wants. Yeah, there enabling replication in mortality. So you may know that DNA contains 10. Till, um, is on every time eso divides the Tela May will get shorter on this means that sells have a limited number, um, divisions until eventually TV. And there would be so sure that there's not enough useful Team A left on Do the So trick out a cocktail sis. So this means the healthy cells have around 40 divisions in their life cycle, and then that so we'll eventually undergo apoptosis. And obviously, every time the cell divides, it produces a new door to sell. So it's not like the body is that was just keep losing tissue like you did your reproducing that, um, in cancer. However, um, you produce the telomerase enzyme. And that means you can regenerate your team. Um, ears. So you end up never having in the mayor's, which is too short. She never undergo that apoptosis on you can, um, replicate indefinitely. And that's how you in a blue, um, replication in mortality. Next up, his invasion of metastasis. So obviously with cancer. The thing But the worst prognosis is metastases on Megan quite neatly went over. How, um, cancer can spread your invasion or in the lymph for the blood. Um, um, that's how you end up getting the other symptoms away from the primary site of the cancer on normally. So you have a cancer, but at the dermatitis, you abdominus oh, epidemic tissues unable to move. So it's not motel, and it's unable to metastasize how the mesenchyme would tissue is able to move, and it's very tall. So the undergo metastases. This these cells have teo um, undergo epidemic. Oh, hasn't kind of transition rich and a bruise them to metastasize. So just another form different station to enable cells to may become nasty metastases. So can anyone tell me, um, cancer? It has, ah, high rate of metastasis. Just put it into the shop. So Okay, so people are sending me lots of different cancers. Order which metastasized like lung cancer, is due after metastasize about cellular cast. Name is these Oh, cancers that can metastasize. How the the one I was thinking of was melanomas. So metal name is well known for easily metastasizing. Andi frequently decell d so and then on the country. Basic cell casts. Name is another type of skin cancer, but they don't metastasize very easily. And then I was about pat scan on her. Please don't tell me where this CT Scan is taken off. What is it showing? Just the general regions? Fine. I wouldn't expect you to know the exact location, but you could give a day. Okay. Getting quite few masters in quite a few people says spinal mats. Spinal matter actually be within the spine. So you can see the white shade of of the spinal column In there on the PAP scan shows the area of high activity. Um, just to the size of the spinal column. Say it's not spinal mats. Um, it's not the kidney. Okay, so this is actually the the neck X, and it's the left internal jugular node. Often you get metastases to lymph nodes because it's draining from the lymph is often the first day she would get any metastasis. And this is just a cross section someone's neck. Another front. Um, you can see that tricky area. So I've done these two together, um, seven achievement graze, and you end up getting this massive cells on it. Once it gets bigger and bigger, you end up with these cells, and then inside the cells aren't going to get any nutrients because you don't have any blood vessels supplying their cells on. And then that causes this local area of hypoc CIA on in health on that area of hypoxia might undergo apoptosis on the cells could die. How the cancer cells, which is fed, um on this will cause angiogenesis. So then, Kansas, our often happen own blood vessels. Um, and then example of this in clinical practice might be if you have a lung cancer and you go to take a biopsy. Often it could be difficult, because soon should biopsy that cancer. You could end up bursting one of those blood vessels so you can get lots of bleeding into the lung. Um, and that's just for MRIs And why my difficult party lung cancer is? Yeah, and next up is resisting apoptosis, so you might recognize this from the one the polls earlier on. It's normally your so we should be able Teo identified. Manage to do today on this damage is detected by the P 53 um, protein on that because B C o off proteins of the B cell family to be transcribed and now activated cast basis would do then cause itself undergo apoptosis. So obviously, if the cancer cell mutates the P 53 gene, you don't get a functioning people re protein say that any DNA damage isn't recognized and then you end up on with cancer cells, avoiding this apoptosis. And that's why we're 50% of camps is have people, if t three mutations. Okay, so this is the, um, other hallmarks, which I didn't mention earlier. They've been added so Jimmer promoting information. This is just recognizing that when there's long periods of inflammation, you're more risk of getting cancer. So if you think about um, having lots of gastric ulcers, so from HP Laurie infections, then you end up getting continuous information. So you're more risk of gastric cancer and then backs itself for guests. An example. Get reflux interest off. A guess on that reflux causes acidity to damage the tissue. Cause the information and then you're more risk off soft job cancer. Okay, Okay, then, Jenna. Genome instability on mutation. So that just shows that some people predisposed cancer due to various medications like the break and mutations. The classics, Uncle um, link syndrome with the, um shh. Dean on these often mutations. And she misses presses. Um, because if you have mutations in those genes, then you can't protect yourself from cancer. Increased glucose uptake on. So normally your body cells will expire. Every bickley. So you're getting three by cholecystitis. Then use Pipi pyruvate against the crap cycle. How about the in cancer cells? You end up taking pyruvate and then perspiring and aerobically to produce lactate on. The reason for doing that is so you get, um, more materials. That sounds confused. Then, um, like, make their in cell components. So that takes a lot more useful stent in there. Products of glycolysis. Um, so that's why best a lot of cells cancer cells so perspire Annamarie between and then that means they need a lot more glucose, the normal cells. And that's why one reason why they have a lot more glucose uptake. We also did that dividing lot more rapidly, saying, You need more glucose and that's how past and it worked. Text cans work cause they can show I be increased, um, metabolic rate from glucose uptake than avoiding in mean destruction. It's the last one. So and health again, your immune system recognizes any foreign cells. Um, just like bacteria or virus hours and cancer cells and a different if they're different changes or not to be different from the normal cells than CD eight sounds recognized in this foreign on end up causing sound that to themselves on the cancer cells. Get around this by having fewer, and they see one receptors. So there's just fewer places where CDA says combined, and also they some cancers express the program Death like and one and then that sends signals CD eight. So I was I'm telling them not to kill them. No. Okay, so that's sort of days and then just attached to slide here to show you how lots of drugs can act at all these different hallmarks to cause on death of cancers. Because interrupting the red evade, um, death. Then you can use inhibitors of those mechanisms, um, turned up treating cancer, But I'm not gonna go into one of them now. So many different treatments would be time. Why? I'm gonna fix and breast cancer, so has to be receptive to receptors. Um, normal cells. Do you have her to receptors on That used, um, similar to the way my surgeon's buying Teo epidemic. Great. Um, similar look to right much. And by March, your receptors, um, has to need it for some of the device. Other country cells you can have, um, instances where you have nose of hers. Her receptors on this means the cancer cells divide 40 much Herceptin or trustees. The map is way of getting around this. So they're just antagonists, um, off the her to the receptors. So as a result, the mice change can't bind on you Don't get this uncontrolled proliferation of cells. I'm sure you know that that some cells her positive on some cells hurting next to, and you also got these two receptor positive cells now least in receptor positive cells could be treated with tamoxifen or letrozole. Tamoxifen could be used in pre and post menopausal. I went in, Um, and that's the eastern receptor antagonists. So they just block the Eastern, receptive much in the same way as Herceptin will block. Had two receptors okay each time were block so tamoxifen will block the estrogen receptors. Um however, once you're in menopause, your body on stuff producing, um, eastern for your ovaries, which means you can end up blocking estrogen straight from its production rather than smoking. It's receptors say Estrogen's also produced from fat cells area right, Mattei's um, and it's also produce in a in a your adrenal glands. You bet. If you block the action of the aromatase, then you stop Eastern on production in France's. So I've tried to explain that here it's a post menopausal. You block ovaries producing estrogen, so now you're only producing its gyn from your fat cells, so you only need to block that, and that's where you can you use letrozole. Um, and I mentioned tamoxifen. Can you be used on pre and post menopausal women left? Result is only used on post menopausal women I'm, um if for any reason a doctor did one toe treated. Remember the letrozole in that pre menopausal? You actually have to induce menopause in those patients for it to be, um um, for you to be able to use it because it just might be a factor about twice but bit more on Herceptin. So, um, her two receptors are important in repairing heart tissue. Okay, so you patients must have an ejection fraction of over 50% before starting on Herceptin so that patients have oh, sounds scan ox on scans for hearts before they end up having on Herceptin prescribed. So I've been more other treatments now, Um, Brady therapy. I'm sure you know is used by firing radiation. I've said X rays, but you can also use same raise. That flight a cancerous I was kill was 1000 that region on. Do you end up having some of the side effects are listed below? Um, that he is just a picture. Long maps, um, more just a show. X rays than anything else. It's It's a cannonball lung. If anyone was interested, um, then chemotherapy. So, um, chemotherapy is the use of chemical substance. Is to kill cells again. It's not specific to cancer cells, but it does have more of an effect on cancer cells than healthy cells just because it acts during my Tosis. Some cells on cancer cells are more likely to be going on undergoing my taste this than any healthy cell. So that's why they are going to be more effective. Doxorubicin is an example of it on. It has very similar, um, effects to radiotherapy. Um, that it's important to note that you also get my legs suppression and chemo that immunotherapy is easing balance. Could therapy to fight, um, cancer cells by using your own immune system So you might use monoclonal antibodies, or Carty, which, when you take your T cells out, make that, um, program to attack cancer cells and then put back into the body. And then T cells should be able to find cancer cells on immunotherapy, unlike chemotherapy is specific to cancer. Yeah, So, um, I didn't make this, but, um, it's a nice a nice way of remembering with the difference on side effects of the different drugs, so I'm going into a base trucks. But using a toxicity bear, you can draw out, um, the different drugs on day, then say, well, the side effects are so d there for the 10. Best heart. That's doctor repeats in to show the cardio toxicity. Um, methotrexate's, um you can see that, um, in their kidneys have nephrotoxicity and then in the feet, You got a preference for the on. Yeah, that's lost. Just lots of different things there. Which you could go over in your in time. Okay, Thinking coming to the end. So I wasn't gonna go over this slide, be convicted in your in time on. Um, it's just some examples of, um, drugs. She's to treat different cancer is on. Do some of that class. Is is Well, okay, So, um, I'm back Teo. The SBA is I don't know how you want to run its honor if you want to give them the polls again. Daddy, I do what I do with maybe read on like the entire pole. That's okay. Yeah, sure. You don't use that hand to be. Some was raised their hand and I was going back down. Dorie Okay? Yeah, we had about 60. Response is pretty. Can you see it? Uh, yeah, I can see the pope. Okay, Weight throughout it. But, uh, you control it. Um, if you had to, I could end it. Yes. Okay. Just can't actually, but up waiting for about 60. Ideally, I know, like not many people after the cold, but I did the, like, 40 to 60. Okay, okay. Let me know if you have to leave, and I'll under otherwise Okay, Thank you. They're up to 41 now, So, um okay, push it. Think people still answering? Okay, if you want to explain the answers, go for it. Yeah, and heard people, didn't she? Um I'm gonna leave now, but, um, end it whenever you want to change that. Here. I under here and people can't see. The answer is okay. Sick. Thank you. I give people five seconds. Okay. Yeah. No. Uh, so p 53 is common in mutation cancer. Have you ever read these questions? So the answer waas to avoid apoptosis. If you remember back to this slide p 53. It's a protein which detects DNA damage. Um, so, um, you take it in? That means DNA, um, damage won't be dissected. So, so, So good. Apoptosis. So that's to your your old man on Treated for his Hodgkin's lymphoma is bright about cardio toxic backs. Which treatments could he be talking about? Um, this is, um does it ever red herring in here? I just talked about Herceptin on accepting Could be cardio toxic of the answers doxorubicin on Herceptin could have been. The answer, however, is not used to treat Hodgkin's lymphoma. It's used to treat um, her her two positive breast cancer on. In fact, the only two things there are used to treat her skin. Some Famer is bleomycin on D doxorubicin that Allah periodo is used to prevent on, um, collagen emergency Could Jima lysis syndrome. Um, you What treatment did prescribe off the surgery to reduce her current right of cancer? Say, I think may see you got this right. It's letrozole because it's post menopausal has a pacemaker. Pozo 80 post menopause. You get lectures. Oh, um, Philadelphia chromosome. I was really impressed with how many people got this before the lecture, and I didn't really go over it in a lecture, but it was on one other slides to start on day. The Philadelphia chromosome results from translocation three in the ninth on the 22nd crimes. Same. It's annoying, Alleged, Because doesn't have much kind of clinical relevance. But it is something you could be asked in your pre clinical exams. There you go. On, just some other other bits on there, um, about different lesions. Uh, what is the role of pee program? Death like and one and receptor. So correct. Answer. Well, this evasion of the immune system, Because if you remember it, have CD eight cells not to kill cancer cells on. Yeah, concludes my section of the lecture. Thank you for everyone here. Hung about. Um I hope you enjoyed their on good luck with any example of coming up on. Hopefully see you see it. Thanks to be that was really, really good on this. A really, really helpful. Um, I've popped be feedback link a few times in the chap. If anyone has any difficult to get into the metal form or doesn't wish to fill out the form, then just let me know