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saganmypants t1_j4bbnde wrote

Cancer cells are grown in vitro and then injected into the animal at the desired location of the tumor. For most reliable model systems the parameters for what cell subtype to use and how many cells to inject are known and published

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theythembian t1_j4bqyra wrote

Amongst that scientific community, is this considered ethical or a necessary evil?

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saganmypants t1_j4brme8 wrote

I think it depends on who you ask, but most likely the people engaging in this work would believe that it is necessary at the moment to move medicine forward. There are panels that oversee the experimental design of any such study and I can assure you that they take their job very seriously. My PI in grad school was roasted by them during a meeting because he had not adequately outlined a pain management protocol for the mice in our study that were getting an experimental cancer drug. Everything in these studies is done with ethics at heart

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tourniquette2 t1_j4cu2v1 wrote

Ok, the pain management protocol for mice gave me the warm fuzzies. At least they’re not just being tormented. I always considered animal testing only borderline ethical at the best of times, but it’s at least reassuring that their pain is managed and they’re kind of cared for.

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theythembian t1_j4btykt wrote

How interesting! Wow have they always cared to conduct studies while being ethical? Or is this a recent change that scientists intentionally approach these experiments with ethics/compassion in mind?

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itakestressnaps t1_j4ccqe8 wrote

It’s been around for decades now, but i believe they’ve gotten stricter and stricter in the 21st century.

Usually, at least in the US, the institution has an internal committee, which also answers to higher ups outside the university. These internal committees usually have vets, bioethicists, other scientists who can validate that the science is clear and justified, etc. EVERYTHING has to be outlined in detail, prior to procedures, and no deviations can occur. There’s quite literally a strict rule for everything and anything you could think of. And of course, all personnel has to undergo ethics and technical trainings, online and in-person, and get certified and approved to work each protocol.

Any modifications to protocols have to written in detail, with justifications, and has to be approved prior to implementation. At my institution, there are also surprise visits where they drop in and watch you to make sure you’re following everything down to a T. And we have 24 hour animal techs and vets on call.

Animal work is not my favorite, even though I do it for certain things. And there are definitely a lot of people that prefer not to do it themselves, but the biomedical community in general does believe it is necessary. After all, medicine is where it is now because of animal research. It’s saved countless lives and extended our life expectancy by a LOT in many countries.

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_BlueFire_ t1_j4dr0k2 wrote

We're looking for alternatives, but until we'll be able to replicate an entire system in vitro the results won't be as reliable. That would lead to less reliable drugs or a much slower progress, as we would need human testing for more possible drugs.

There are those who see one way or the other as the better, it really depends on your "ethical priorities"

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wakka55 t1_j4clgwr wrote

Can you inject any mouse off the street and give it the cancer? Or are these special genetically matching mice that don't reject the injection immediately as a foreign invader?

What if you inject a human with it? Do the researchers need hazmat suits to handle these mice?

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saganmypants t1_j4craod wrote

You probably could do any old street mouse but there are companies who produce litter after litter of genetic cloned mice so that your results are consistent and not dependent upon genetic variation. There are different mouse models, but in many cases the mice have compromised or differently engineered immune systems to mitigate immune system interference.

Typical experiments use mouse cancer cell lines so if injected into a human it would be rejected by your immune system, but there are some models of mice with humanized immune systems which are capable of acquiring human cell tumors and those cells could theoretically be transplanted into people. Usually no hazmat suits AFAIK, just typical gloves and lab coat. I am merely a synthetic organic chemist so I don't know much more detail beyond that but have learned enough about it through colleagues who go on to test the things we make

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research_guy17 t1_j4cvxlz wrote

You could attempt "any mouse off the street", but primarily tumor xenograph models are established in SCID mice, bred and cloned for the function. SCID means they are immune deficient, otherwise the immune system of the regular mouse would likely generate antibodies to the injected cells and either reject the attempt to grow the tumor or result in poor health or even death of the "regular" mouse.

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captaincumsock69 t1_j4e5hrs wrote

They use mice that are either purchased or bred for the research. They might use genetic knockout mice or just wild type depends on the project. Presumably if you injected a juman with it a tumor would grow but this is not allowed in most countries

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Tasty-Fox9030 t1_j4ffbog wrote

This sounds so cartoonishly evil that it's difficult to believe, but people have actually been deliberately injected with human cancer cells and they generally do NOT get established.

Horrible but true:

Tuskegee syphilis study not America's only medical scandal https://aquila.usm.edu/cgi/viewcontent.cgi?article=1242&context=ojhe

In general it's going to be ok because a healthy immune system is going to recognize the cells as foreign. The problem with getting cancer for the most part is that they ARE your cells. (Ideally your body recognizes your own cancer cells anyway but you get the idea.) If you're immunosuppressed for whatever reason it's possible.

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ElkSkin t1_j4eh28w wrote

If injected cancer can take hold, why doesn’t skin or oral cancer spread person to person?

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sciguy52 t1_j4eyihe wrote

It has to do with our immune systems. For example if you get a kidney transplant (and don't have an identical twin donor), the kidney will have cell markers on them that are used to recognize the tissue as "self". So the donor had a kidney with a certain set of proteins on the cells of all their tissues that their immune system can identify its own tissues as "self" and the immune cells will not attack them while in the donor's body (in a healthy person). The kidney recipient will have their own set of these proteins that do the same thing, however the donor and recipient have differences in these markers between them. Those differences cause the recipients immune system to recognize the donors kidney as not self but "foreign" so the immune system attacks. This is why we give immune suppressing drugs to transplant patients for life to stop the immune system from killing the organ. If you were lucky and had an identical twin, then these "self" markers would be identical too, and you could get a kidney from them and the immune system would not reject it and no immune suppressing drugs needed.

Instead of kidneys, lets say you injected tumor cells from the donor into a non identical twin recipient what happens? The vast majority of the times the immune system will recognize these as "not self but foreign" and immediately attack and kill them. This is why most of the time you can't exchange cancer cells with another person and give them cancer. Again, identical twins? Different situation. Their "self" markers are the same so cancer cells from one twin would not be attacked by the other twins immune system and could grow and give the recipient cancer. This simplified a bit gets the concept across.

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Greyswandir t1_j4bvt9e wrote

You can also administer carcinogens to cause the specimen to develop cancer on its own, without the need to culture and graft the cells. Based on the type of carcinogen and where/how it is administered you end up with different types of cancer.

Back when I was in grad school one of my colleagues injected a carcinogen via catheter to promote bladder cancer for example.

As to your questions about ethics: in my experience at least yes, researchers take the ethics of what they are doing extremely seriously, and the university has an elaborate oversight and approval system which monitors for ethical lapses. We were taught that an animal could only be used if there was no other way to collect the data we needed, and that the study should always be designed to minimize the animal’s suffering

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SlayerS_BoxxY t1_j4cgpqz wrote

In addition to other answers, there are also genetically modified animals that make them predisposed to certain tumors.

In the US, scientists at academic institutions who use animals are required to abide by institutional guidelines as well as local and federal laws governing the care and use of animals (mostly applying to vertebrates only).

While not all animal studies translate to humans, it is important to keep in mind that all of the major breakthroughs in cancer treatment in recent decades (checkpoint blockade, CAR-T, etc) have been discovered in and developed using animal models. They also relied on basic immunology knowledge generated primarily from animal models.

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wheelis t1_j4c2xk3 wrote

A lot of lab cell lines divide happily in flasks because they come from cancer cells cultured from actual people. For example, Nalm6 is a precursor B cell leukemia cell line and Jurkat is a T cell leukemia cell line. So you could inject Nalm6 cells in a mouse and then see if a CAR-19 T cells can clear the cancer.

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_BlueFire_ t1_j4dq8qt wrote

It depends on the cancer: different animals behave in a more or less similar way to the human system, so after you've gone past the mice stage you choose the ones whose system more closely resembles the human one

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sciguy52 t1_j4ewv87 wrote

Depends on what you are trying to do. I gave a mouse line cancer by introducing a (previously unknown human oncogene) into the mouse, then waited to see if they developed cancer. A mouse line is a line of mice that are genetically identical to each other, not like mice you catch in the field which have genetic variation between them, particularly with regards to the immune system and what it recognizes as "foreign". This was a transgenic mouse, meaning we could introduce the gene into the fertilized egg, then implant it into a mom mouse, the mouse grows up, and we watch and wait. The nice thing about this is we could put a human gene in the mouse in this way and not cause immunological rejection. Had we taken human cancer cells from which this gene was derived, injected them into the same mouse type, the mouse immune system would kill those human cells. In my case, 100% of the mice that had the gene got cancer, and quite rapidly at that. That is one way. This is not a fast thing to do, may take a years to set this all up, then when you get some with the gene you need to breed them a bunch to have enough, and also keep an eye on them to check for signs of cancer. For example my experiment took 2 years from start to finish and it was that fast because the cancer gene caused cancer fast.

OK you maybe want to use mice but you need to inject human tumor cells. Like I said in normal mice they have immune systems and they will reject human cells as foreign, with the immune cells killing the human tumor cells (or human non tumor cells). You might say, but they are human tumor cells, how can that be? The cross species immune reaction is pretty strong and it will quickly kill any cells from a different species very quickly, even cancer cells. In fact injection human tumor cells into another human it is highly likely that other persons immune system would kill them too. If that other person was an identical twin? Different situation, those cancer cells may well grow (I say "may" since ethically can not do this experiment, but can do it in animals), might be a darn good chance they will grow in an identical twin. Back to the mice since we don't experiment on people, what can we do? Well we also have mice that were bred to not have immune systems. So when we inject the human cancer cells in them there is no immune cells to kill the human ones. A lot of the times (depending on what you are doing) those human tumor cells will grow, not always (reasons complex, too long to explain), but works pretty good. Now you have a mouse with human tumor cells growing in a mouse and you can do experiments.

There are other ways this can be done but these two are pretty straight forward and easier to do.

This is with a lot of simplification to keep things simple but describes some of the simpler things we can do.

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sawamoha20 t1_j4i05t8 wrote

There are several methods used to induce cancer in animals for medical experimentation. One common method is to use chemicals or substances that are known to be carcinogenic, or cancer-causing. These chemicals can be administered to the animals through their food or water, or applied topically to the skin.

Another method is to use radiation to induce cancer, this can be done by exposing the animals to ionizing radiation such as X-rays or gamma rays.

Another method is to use genetic engineering to create animals that are predisposed to developing certain types of cancer. This can be done by introducing specific genetic mutations into the animal's DNA that are known to be associated with the development of cancer.

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