--- Log opened Mon Sep 16 00:00:53 2024
00:01 < fenn> the oxidative stress is probably how radiation therapy works too
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01:01 < hprmbridge> Eli> Chemo is pretty indiscriminate and kills everything.
01:03 < jrayhawk> via oxidative stress
01:08 < jrayhawk> the inverse relationship between glutathione and chemotherapy effectiveness is written about extensively
01:08 < jrayhawk> https://www.sciencedirect.com/science/article/abs/pii/S014296122100466X
01:10 < hprmbridge> Eli> Ok that’s very interesting. Yes, the antioxidants seem to rapidly progress lung cancer and possibly other types of cancer. There is some evidence that beta carotene impacts the nrf2 pathway. So, these antioxidants work via filtering to prevent ROS from forming, direct neutralization of ROS non enzymatically, and then up regulation of the bodies internal enzymatic ROS neutralization. I’m thinking a
01:10 < hprmbridge> Eli> basic elimination diet could increase oxidative stress in the body, resulting in preferential destruction of stressed cancer cells.
01:10 < hprmbridge> Eli>
01:10 < hprmbridge> Eli> The speed with which mice tumors grow when given antioxidants is pretty incredible. Inverting this might slow cancer progression. Im wondering if there are any off the shelf drugs that modulate nrf2
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01:16 < hprmbridge> Eli> Oh wow, an entire glutathione depletion strategy.
01:16 < hprmbridge> Eli>
01:16 < hprmbridge> Eli> I sort of stumbled across the nrf2 hypothesis today. So, i haven’t had an opportunity to read the literature on using oxidative stress against cancer. I’m thinking someone needs to write a paper on the nrf2 pathway wrt lung cancer, and possibly other cancers, if there’s a research gap. Might be my next project
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01:33 < hprmbridge> Eli> Interesting. Cancer cells seem to produce a large amount of ROS. This initiates a cytoprotective response from the body. GSH responds. If we deplete GSH, nrf2 responds. Massive ROS generation is one of the side effects of rapidly growing cells. We could potentially get the rapidly growing cancer cells to self destruct via stress. This should force the surviving cancer cells to evolve towards a
01:33 < hprmbridge> Eli> slow growing cancer that generates less ROS. It’s not necessarily a cure, but it’s an interesting attack vector to slow it down. Could be done for free via dietary changes. Could potentially be modulated via xenobiotics.
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01:37 < hprmbridge> Eli> It’s sort of like how keto can slow down cancer via starving it of products needed for growth. The fact that cancer wants to grow so much more rapidly than other cells has historically been its weakness. In a sense, I guess keto, chemo, and antioxidant deprivation all slow cancer progression via that underlying fact.
01:37 < hprmbridge> Eli>
01:37 < hprmbridge> Eli> Sorry if I’m monopolizing the chat. Sometimes it helps me think to talk this stuff out.
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02:10 < hprmbridge> Eli> Ok, I think there’s a chance we just discovered why the 18,000 person caret trial failed. That had been a big mystery for years and a lot of cancer people had all sorts of hypotheses for why it happened. I need to look through the literature to see if there’s really no one who has published this. It seems so obvious in retrospect. Fenn, jrayhawk, do you guys want to be listed in a paper?
02:23 < jrayhawk> that and, due to heterodimerization of VXR and RDR, it is spectacularly stupid to not co-administer vidamin D with retinoids if you're trying to treat cancer
02:23 < jrayhawk> er, VDR and RXR
02:28 < jrayhawk> retinoids simultaneously increase vitamin-D demand by releasing calcium and compete with vitamin-D for RXR receptors, undermining myeloid differentiation
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02:35 < jrayhawk> i would want to see a draft of the paper before attaching my name to it, but maybe!
02:54 < jrayhawk> one of those situations where if you have a deficiency of both, you can create dose-dependent pathology using either. RCTs don't do you any good if you norm on pathology.
02:58 < hprmbridge> Eli> yeah of course
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08:14 < hprmbridge> nmz787> Heads out to the farm pickup truck that I've been keeping the ozone generator in to de-scent of mold and mouse pee... This is now the official oxidative therapy chamber!
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08:38 < docl> I know there's been some pseudoscience around hydrogen peroxide therapy, but what actually happens if you inject H2O2 (dilute/isotonic) close to the cancer site? it's not like lasts very long in the body, but could last long enough to push cancer cells over the edge if all they need is a bit more ROS to kill themselves
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14:41 < hprmbridge> kanzure> oops I meant https://www.neurology.org/doi/full/10.1212/WNL.0000000000201578
15:25 < jrayhawk> it's misleading ot say that cancer is riding the edge of oxidative stress to grow as fast as possible; cancer is highly mutagenic and employing many strategies simultaneously. the fastest-growing, most noticable portions of a cancer are the ones riding the edge of oxidative stress, but killing those will just select for more robust, slower-growing cancer cells.
15:26 < jrayhawk> It is very normal for an experimental treatment to reduce cancer size by 75% but only slow down the time-course of the disease progression rather than resolve it.
15:36 < jrayhawk> kanzure: wtf that shit's crazy https://www.ncbi.nlm.nih.gov/pmc/articles/instance/9990427/bin/WNL-2022-201417f1.jpg
15:49 < hprmbridge> nmz787> Folks, my kid can open my phone and see that adult content fwiw
15:49 < hprmbridge> nmz787> (j/k .. j/k )
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17:16 < docl> do cancer cells tend to prey on / kill each other? perhaps a more robust cancer line could be seeded into an existing one, with a suicide gene present
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17:32 < L29Ah> cancer cells aren't immune cells, they don't have much capability to kill, they mostly compete with each other at acquiring nutrients, stimulating blood supply expansion and multiplying as fast as possible
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17:33 < L29Ah> well there are immune cell cancers, not sure if they keep/utilize their killing capability as they're usually underdifferentiated
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17:34 < jrayhawk> well, it's possible all cancers eventually metasticize by getting endocytosed into macrophages, which then proliferate everywhere
17:35 < jrayhawk> at which point all bets are off
17:36 < jrayhawk> but i haven't seen that hypothesis well-validated
18:42 < docl> the dependency on blood oxygen might be exploitable, if you have a red blood cell substitute that you can control. at any rate, respirocyte research could be classified as cancer research. you could have the respirocyte mechanism (a MOF probably) switch from releasing to absorbing O2 when it's in the cancer.
19:36 < docl> wikipedia suggests heme gets released from hemoglobin under oxidative stress. apparently it just gets really cytotoxic and makes a bunch of free radicals when that happens. but if you could get it to act like the heme in muscle tissue, it could in principle pull O2 from the solution. so then anti-cancer blood might be possible to achieve by lab evolution.
19:40 < docl> .wik Heme
19:40 < saxo> "Heme (American English), or haem (Commonwealth English, both pronounced /hi:m/ HEEM), is a ring-shaped iron-containing molecular component of hemoglobin, which is necessary to bind oxygen in the bloodstream." - https://en.wikipedia.org/wiki/Heme
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20:07 < docl> .wik Myoglobin
20:07 < saxo> "Myoglobin (symbol Mb or MB) is an iron- and oxygen-binding protein found in the cardiac and skeletal muscle tissue of vertebrates in general and in almost all mammals." - https://en.wikipedia.org/wiki/Myoglobin
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20:23 < hprmbridge> Eli> As cancer grows there are a lot of mutations. So different parts of a tumor have different mutations. This is why a treatment may kill a lot of cancer cells but not all. The remaining cancer cells can then survive and progress. It’s like fighting the bad guy in terminator 2
20:45 < docl> if you can scrub the oxygen from the blood locally to the tumor in a way that's triggered by oxidative stress, I think that's going to kill the cells fairly indiscriminately based on their proximity. survors won't be selected for low oxidative stress, more the opposite, as the rapid-oxidizer cells are protected from their own excesses.
20:47 < docl> just adding antioxidants would encourage the tumor to evolve in the suicidal direction, but unfortunately the tumor would then grow. limiting available oxygen altogether does the same thing while slowing growth, I think
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--- Log closed Tue Sep 17 00:00:54 2024