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Gut bacteria from amphibians and reptiles achieve tumor elimination in mice

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Re: Gut bacteria from amphibians and reptiles achieve tumor elimination in mice

#101
post #40

I have been working with my dad on his cancer treatment since last year. My interest in the topic has only peaked ever since. (Disclaimer- I am an engineer and not a microbiologist/doctor) Mutations and wrong copying of genome happens all the time in the body and some enzyme has the job of correcting the mutated genes so it doesn’t get into the system. Level 2 defence is T cells killing it as identified as foreign bo…

I know this is a bit off topic, but have you ever thought about why steroids and other forms of doping are not a free lunch? Why can't we just inject an external chemical to boost our strength for free without any side effects?

If steroids worked, everyone would be constantly injecting them. It would be like drinking coffee.

And that is the reason why steroid injections are harmful. If there is a free lunch, the human body will simply produce the optimal amount of steroids on its own until the Pareto frontier is reached and a tradeoff needs to be made.

Where does the body get the materials to form the steroids? From your diet. So the primary intervention is always a healthy diet and an active lifestyle. You know, the boring things that parents drill into their children.

It's valid but "medicine" that has only upsides and no downsides isn't medicine, it's diet.

Re: Gut bacteria from amphibians and reptiles achieve tumor elimination in mice

#102
post #40

I have been working with my dad on his cancer treatment since last year. My interest in the topic has only peaked ever since. (Disclaimer- I am an engineer and not a microbiologist/doctor) Mutations and wrong copying of genome happens all the time in the body and some enzyme has the job of correcting the mutated genes so it doesn’t get into the system. Level 2 defence is T cells killing it as identified as foreign bo…

> To me it sounds a tough problem given the permutation and combination of mutation— roughly few trillions.

You are right. There is a very good explanation in this comic https://phdcomics.com/comics.php?f=1162

Re: Gut bacteria from amphibians and reptiles achieve tumor elimination in mice

#103
post #73
post #40

I have been working with my dad on his cancer treatment since last year. My interest in the topic has only peaked ever since. (Disclaimer- I am an engineer and not a microbiologist/doctor) Mutations and wrong copying of genome happens all the time in the body and some enzyme has the job of correcting the mutated genes so it doesn’t get into the system. Level 2 defence is T cells killing it as identified as foreign bo…

Our L1 defense is actually incredibly good. A human will undergo about 10^16 cell divisions over the course of their lifetime. Around 10^3 to 10^6 of those divisions will result in a mutation that gets past the L1 defenses and need to be eliminated by the T cells. It's not generally easy to make dramatic improvements to something with a 99.9999999% success rate. The immune system is pretty good too, which means any g…

Thanks for these insights! Do you have any material or sources for a layman to learn more about this and where these numbers come from?

Re: Gut bacteria from amphibians and reptiles achieve tumor elimination in mice

#104
post #93

Earlier quoted context omitted.

The catch is that there are thousands of promising therapies in animal models/pre-human testing. A very very tiny fraction of them will ever make it to market for a variety of both good and not-good reasons.

From what I saw, there are very few experimental therapies that claim 100% efficacy, no side effect, no patent on complex engineering process to produce the drug. I agree with GP that it is very notable. I mean if it works on humans, which is not a stretch, colorectal cancer is done. It's huge.

Yes there are few that claim 100% efficacy and no side effect at this stage, but there are far, far, far fewer who make it to human availability.

I wouldn't describe it working in humans as "a stretch" per se. I'm not identifying a specific reason it shouldn't work in humans. I'm just saying that's true of thousands and thousands of really great looking treatments (per year!) that, nonetheless, end up not working in humans, or not being convincing enough to even warrant putting them in humans once.

Re: Gut bacteria from amphibians and reptiles achieve tumor elimination in mice

#105

Earlier quoted context omitted.

Prevalence of the disease - if it only impacts 1/100 million, going to be hard to ever find sufficient patient population to test and recoup your investment. Existing quality of treatments - if there are already efficacious drugs on the market - how sure are you that this new therapy will be best in class? Only being as good as the status quo is not an ideal competitive position. Conversely, if there is an unmet need…

I guess I'm not being clear. Are these examples of "good" or "bad" reasons to not go to market? I assume "good"? If so, what would be an example of "bad"? Or vice versa if your meaning was opposite.

I responded below already but since writing that, I've come up with a few more great bad reasons not to bring a drug to market (sorry for the parseability of that one...)

Best bad reason: it would cannibalize an inferior drug currently in your portfolio that's still under patent protection.

I think this behavior is at the far "evil" end of the spectrum of behaviors that drug developers systematically engage in (which I believe is far more banal + less evil than what they're accused of), but it does happen and it's a really nasty

Where it gets especially nasty is when companies buy drugs in development or pre-development from other companies in order to squash (or at least delay) a potentially competitive asset before it reaches the market.

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Another great bad reason, but mostly applies to devices/procedures: the device/procedure is fantastic but for various structural reasons outside of the control of the device/procedure developer, there is insufficient incentive for healthcare providers to actually deploy said device/procedure.

A trivial example would be a pacemaker that requires fewer leads than the competitors and has fewer complications. Great for patients, but potentially totally uninteresting to the electrophysiologists who install it and would get paid less due to the less complex procedure.

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Best good reasons all fall under: making a therapy is unfathomably difficult and most efforts are destined to fail OR (separately) proving a therapy works is unfathomably expensive and most efforts can't produce a positive ROI after that process.

Re: Gut bacteria from amphibians and reptiles achieve tumor elimination in mice

#106
post #46

Sorry, as someone in this field, this is bullshit. It is in mice. Several things trigger my bullshit meter. Quote: "This dramatically surpasses the therapeutic efficacy of current standard treatments, including immune checkpoint inhibitors (anti-PD-L1 antibody) and liposomal doxorubicin (chemotherapy agents)" PD-L1 monoclonal antibodies are only effective against cancers that are, you guessed it, PD-L1 positive. At h…

> Sorry, as someone in this field, this is bullshit. It is in mice.

Nice to hear an expert opinion. Let's hope your comment goes back to black. I have a lot of question!

> This is a nothing burger.

Is it enough for a bread-mayo-bread sandwich? Lettuce?

IIUC the bacteria makes the cancer disappear for two weeks, until they end the study and kill the mice. (IIUC this is timeline is usual for very early studies.) They tried other bacterias and one of them made the cancer disappear for a few days, so I'm worried about the long time efficiency of this method.

Is injecting the bacterias a second time as efficient as the first time, or the inmune system kills the bacteria before they hurt the cancer?

What happen in case of metastasis? Each one must be injected with the bacterias or they will jump and make all of them disappear?

Does the bacteria infect other organs and kill you? Is there a good antibiotic in case the bacteria cause problems?

They used cancers that were 200mm3 (i.e. like a sphere of 7mm = 1/4 inch). What happens in bigger cancers? Does bigger cancer have better irrigation and make it more difficult for the bacteria to survive? What happens to tiny hidden metastasis (that probably still have good enough irrigation)?

Re: Gut bacteria from amphibians and reptiles achieve tumor elimination in mice

#107
post #65

Earlier quoted context omitted.

Prevalence of the disease - if it only impacts 1/100 million, going to be hard to ever find sufficient patient population to test and recoup your investment. Existing quality of treatments - if there are already efficacious drugs on the market - how sure are you that this new therapy will be best in class? Only being as good as the status quo is not an ideal competitive position. Conversely, if there is an unmet need…

Also the ethically in blind studies, can't just let some random patients die just to prove that your drug works.

Yes, you can. The problem with testing is that a candidate treatment may make things worse for patients, not that it may improve things.

If your treatment works, that’s an improvement of what you had before. Once you know that, you can treat all patients. For some, that will be too late, but without your tests, it would be too late for them, too.

If your treatment doesn’t do anything at all, it keeps things the same, but the patients in the test group likely will have had some inconveniences (having to visit a doctor, getting an injection, etc), so you shouldn’t do the test.

If your treatment makes things worse, you of course shouldn’t do the test.

Problem is that you typically only can only know in hindsight which of these applies.

So, you think carefully on whether a treatment could fall in category 3, and, if so, first do it on a group of patients who consent to be Guinea pigs and, often, are already terminally ill, as any negative outcomes will cause less harm to such patients.

Then, as soon as during the test your stats tell the drug does or doesn’t work, you stop the test and either treat all patients or stop treating the test subjects.

Re: Gut bacteria from amphibians and reptiles achieve tumor elimination in mice

#108
post #40

I have been working with my dad on his cancer treatment since last year. My interest in the topic has only peaked ever since. (Disclaimer- I am an engineer and not a microbiologist/doctor) Mutations and wrong copying of genome happens all the time in the body and some enzyme has the job of correcting the mutated genes so it doesn’t get into the system. Level 2 defence is T cells killing it as identified as foreign bo…

> But I was curious if there is working happening on L1 defence — fixing the enzyme that fixes the wrong copy paste mechanism. Or making the enzyme get more efficient and powerful. Is that line of thought even valid?

Mutations in general are not the defining quality of cancer. It's mutations in these very L1 safeguards. There are several such safeguards and a cell needs several mutations in those to become malignant. Eg. https://en.wikipedia.org/wiki/P53

Correcting genes only works in certain conditions (e.g. limited single strand breaks), in a narrow time frame during cell division, safeguards rather trigger cell suicide, or if that fails they mark the cell for destruction by immune cells. A cell can't fix DNA which made it through cell division once, because it got nothing to proof-read against.

After the safeguards are gone, everything goes and genetic diversity increases quickly within each tumor. This diversity is what's making cancer treatment hard. At some point there won't be a shared vulnerability in all malignant cells. The repair mechanisms are working in favor of the cancer now. For example, with radiation therapy you preferably want to induce DNA double strand breaks, because cancer cells can't repair those. Otherwise you need to increase the radical burden enough to overwhelm repair, but migrating radicals may damage distant cells, too.

I presume you could hypothetically inject mRNA of a working safeguard gene (eg. P53) into all cells (at some point cancer cells can't be selected exclusively, since they lost identifying marks and present as stem cells), so the functional enzyme or transcription factor is forced to be built inside. I am sure people are trying this right now. However, the inner workings of cells on a molecular level are insanely complex and our understanding is only scratching the surface. As with P53, you have a transcription factor, which means it's modifying gene expressions elsewhere. It's only a small part of a complex regulatory cascade. I doubt there is a safeguard target, which can easily be injected without considering the precise timing and environment within that safeguard cascade in the cell. Of course, the rest of the safeguard system needs to be present in the cell to begin with. Mind you, you don't want to cause cell suicide in healthy cells, so you want to restore the function of whole selective complex.

Then there is the question of delivery. Can you deliver eg. the mRNA to every cell without raising suspicion of the immune system? With the COVID vaccine, the enabling breakthrough was the delivery vehicle, not as much the mRNA part. Can you even reach the cancer cells at all? Cancer cells are frequently cloaked, shadowed or cut of by senescent, or necrotic cells, or acquired unique ways of metabolic adaptations. A bit similar to bacterial persistence, like M. tuberculosis, which can evade bodily and chemical defenses for decades.

The take-away: Life is complex beyond comprehension! Despite simplifications taught in schools and reductionist zeitgeist, we actually know very, very little about what's going on in genetics and molecular biology, most medical knowledge is empiric guessing instead of explanatory understanding.

Re: Gut bacteria from amphibians and reptiles achieve tumor elimination in mice

#109

Earlier quoted context omitted.

A lot of potential treatments are too easily available and can't be patented. If a big pharma company can't make massive profit from it, they won't bother bringing it to market. Consider that a not-good reason. Other treatments may eventually prove to have too many serious negative side effects. That's a good reason to abandon them.

> A lot of potential treatments are too easily available and can't be patented. This isn’t really an obstacle, at least not as much as it’s made out to be. There are numerous examples of drugs being brought to market at high prices despite having been generic compounds. Even old drugs can be brought back at $1000/month or more at different doses or delivery mechanisms. One example: Doxepin is an old antidepressant th…

About Doxepin. As many seniors do, I also suffer from extreme inability to stay asleep at night. I have trialed through all the known prescription and non prescription possibilities, only eszopiclone and baclofen seem to show some promise, however, eszopiclone is DEA listed, requires higher and higher doses, and if I take it more than say 2 weeks, it has rather serious side effects attempting to withdraw, addictive, serious anxiety, trying to wean oneself off it. Doxepin is prescribed as an antidepressant in large doses, one of the most potent H1 histamine antagonists known. The H1 system in our bodies promotes wakefulness. In very low doses, doxepin acts against the H1 to promote sleep. To avoid the upcharges of low dose doxepin, I am prescribed the high dose version, which I have to break the capsules to administer about 5 to 10 mg. placed in an empty gelatin capsule (it's bitter). It really works well, however you are fairly tired and useless the next day.

Re: Gut bacteria from amphibians and reptiles achieve tumor elimination in mice

#110
post #16

Earlier quoted context omitted.

I know hearing this gets old, however, please review sources outside of LLMs for accuracy. LLMs take a whole bunch off stuff from all over the internet and distill it down to something you can consume. Those sources include everything from reddit to a certain de-wormer that folks still think treats COVID (side note: I've a few long COVID victims in a support group I am in, and they are not happy about the disinfo tha…

I have significant experience in polymer chemistry, as an experiment, I decided to ask gemini some very specific questions to try and back it into a corner, so to speak. It blew me away with the answer, discussing quite a bit of info I was not even aware of.

Cool story, bro.
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