Studies showing cancer reversal / shrinking

Mauritio

Very interesting human study on the effect of 60min. exercise (EX) vs. 60min hot bath at 40°C (PH).

Both were comparable in terms of elevating HSP70, but the elevation wasn't drastic and returned to baseline in about 2h.
The pro-inflammatory cytokine IL6 was elevated a lot more from exercise than the hot bath. So overall a hot bath seems to be safer than I thought and safer than exercise.

Interestingly just sitting in a hot bath for an hour increased their resting energy expenditure by 79%! That's what they found.

What makes the bath so good for tumors is the increase in temperature.
Both methods were comparable at raising core temperature.
But the bath was a lot better at increasing skin and muscle temperature compared to exericse!
https://pmc.ncbi.nlm.nih.gov/articles/PMC5605168/
@cs3000 @DavidPS

cs3000

replied with more discussion on HSP at https://bioenergetic.forum/post/32387

cs3000

B-lapachone and breast cancer reversal when Nqo1 is expressed, (used 2 lines that dont have nqo1 then made them express nqo1, like a lot of cancers do maybe most)

https://www.researchgate.net/publication/260151326_Tumor-Selective_Futile_Redox_Cycle-Induced_Bystander_Effects_Elicited_by_NQO1_Bioactivatable_Radiosensitizing_Drugs_in_Triple-Negative_Breast_Cancers

Breakthrough dose was 70mg/kg every other day for just 5 uses (65mg/kg slowed a lot but didnt reverse interestingly). In one of the types (B) the cancer basically didnt even grow at all.

(would more treatments work for smaller doses?)

~(the effect relies on cells having NQO1 activity,
Cancer cells expressing >100 U of NQO1 enzyme activity are killed, while normal tissues that lack, or express low levels of, NQO1 are spared,
because high NQO1 metabolises the quionine into an unstable compound that causes a big surge in superoxide which generates h2o2 overload and kills the cell, shown at 4uM.
but the effect is somewhat selective on cancer cells vs healthy human cells which have less NQo1, at least up to 10 uM it doesnt kill at least some healthy cells measured. but does drastically inhibit proliferation of healthy cells >1uM.)

in human breast cancer tissue microarrays,*60% (12/20) of breast cancer tissue samples showed strong NQO1 expression, while low to no signiﬁcant expression wasnoted in adjacent normal breast tissue

NQO1 is a ﬂavoprotein that is over-expressed approximately 5- to 200-fold compared with normal adjacent tissue in various solid tumors, including cancers of the pancreas, lung, prostate, and breast

~~But these are high and possibly toxic doses,
generally only 1mg/kg - 2.5mg/kg (~5mg-10mg human) are used for effects, maybe best at lower doses but regularly, combined with different things,

~~considering the level of toxicity for NQO1 expressing tumors i'd wanna be extra sure there arent healthy tissues somewhere that express elevated amounts close to what cancers do , if using these high doses if theyre even reasonable to get ahold of, some healthy tissues express it to some extent eyes lungs etc https://doi.org/10.1016/S0891-5849(00)00310-5

~~here mice ate 70mg/kg in diet though and it showed beneficial effect on multiple measures in aging , and increased lifespan +17% in stress https://pmc.ncbi.nlm.nih.gov/articles/PMC3469505/#s3 but they didnt look at all tissues to see if theres damage,
I guess in food its less bioavailable mixing with other things so effectively a much lower dose (?)

But here 80mg/kg orally just once showed signs of liver & kidney toxicity https://www.scielo.br/j/jbpml/a/6RX9dwWpVrnCVVFxp5gFjfr/?lang=en

The measured oral bioavailability of β-lapachone was 15.5%.

~~here 50mg/kg, injected i.p, but spaced out 1 day apart, for 10 treatments https://www.pnas.org/doi/10.1073/pnas.96.23.13369#sec-2 significantly lowered ovarian cancer and judging visually and by bodyweight didnt notice significant toxicity during this timeframe

**here ** 50mg/kg twice a day injected I.P increased mortality and was highly toxic https://www.tandfonline.com/doi/pdf/10.4161/cbt.4.1.1382 ,
Unlike the just 5 rounds dosing 1x every other day in the 1st study

β-lapachone given for a dose of 50 mg/kg I.P. twice a day for two weeks was extremely toxic with nearly one-half of animals dying during the treatment.
{this might have been due to what they combined it with but maybe not}
Clearly complexation of β-lapachone with HPβ-CD increases the
bioavailability, efficacy, and toxicity of this active antipancreatic
cancer agent. Future studies to improve solubility with decreased
toxicity are warranted.

and here 10mg/kg daily but injected into the blood for 1 - 2 weeks showed higher death rates https://www.scielo.br/j/bjmbr/a/pf9P7yD9qDP79yV5bDvPjqb/?lang=en

So the first study showed a survival increase doing just 5 treatments with a day apart. I guess you avoid lethal toxicity this way but idk how certain tissues would be affected , theres a tradeoff with that

I would only be happy using low dose for more treatments over time, if that had efficacy will see if i find anything

,
Lower dose 12.5mg or 25mg/kg subcutaneous daily https://www.nature.com/articles/s41598-017-02937-0#Sec2
slowed well but did not shrink alone

Lower doses orally, maybe ~5mg-10mg daily if not ~30mg human equiv, have a preventative effect on generating cancer. has a sedative effect https://www.sciencedirect.com/science/article/abs/pii/S0014299924001997

cs3000

Human trial with methylglyoxal {aka pyruvaldehyde} (william Koch compound)
https://web.archive.org/web/20161017113947/http://www.cancer-therapy.org/CT/v4/B/HTML/17. Talukdar et al, 205-222.html

Long term in a variety of cancers, ~80% of the people had remission or stability @dapose

Its found in mankuna honey but the amounts they used here were high at ~500mg x4 a day (in water, just a little 60ml so dont tip pH too high?, with food) + vit c and some b vits, and over a long timeframe. seeing if i can find how long the effect should take. methylglyoxal levels go up with high blood glucose & finding glyoxalase 1 inhibitors to use should increase the effect for a lower dose needed https://www.cancertreatmentsresearch.com/methilglyoxal/ (nice writeup) looking up toxicity, apparently taking creatine can protect healthy cells so this has a selective effect

No significant toxicity (but can take creatine and vit C to enhance effect and protect healthy cells just in case there's toxicity on the heart without)
https://doi.org/10.1016/j.taap.2005.07.003

Acute toxicity study was done with two species of animals, mouse and rat. The maximum dose of methylglyoxal for each mouse was for oral 2 g, for subcutaneous 1 g and for intravenous 0.3 g

All the animals except those used for biochemical studies (see below) were observed up to 90 days after completion of the treatment and were found to remain healthy. No toxic effect on physical condition and behavioral pattern such as hair texture, food intake etc. and death were observed. However, the subcutaneous injections appeared to be painful for both treated and control groups. {diluted in saline too} The pain appeared to persist for several minutes after injection.
In the animals, which received intravenous injections, swelling appeared in the tail and adjoining regions from 3rd week of the treatment. The swelling remained up to about 10 days from end of the treatment.
Treatment of methylglyoxal had no toxic effect on the
functions of liver, kidney and heart and hemopoietic organs
of the rats

As mentioned before, methylglyoxal had been found to possess strong antitumor activity. Szent-Gyorgyi and his associates and Apple and Greenberg long ago showed remarkable antiproliferative and curative effects of methylglyoxal towards cancer-bearing animals (Szent-Gyorgyi et al., 1967; Egyud and Szent-Gyorgyi, 1968; Apple and Greenberg, 1967).
In in vivo and in vitro studies with animals and in vitro studies with a wide variety of human post-operative malignant tissue samples, we had observed that methylglyoxal acted specifically against malignant cells and ascorbic acid significantly augmented this anticancer effect of methylglyoxal (Ray et al., 1991, 1997a, 1997b; Biswas et al., 1997). Moreover, we had observed that creatine present in cardiac cells completely protected the animal from any possible deleterious effect of methylglyoxal treatment on cardiac mitochondria (Sinha Roy et al., 2003).
So, we tested whether these compounds had any curative effect on mice inoculated with EAC cells. The results are presented in Table 7. It appears that at a particular dose the antiproliferative effect of methylglyoxal is augmented in presence of ascorbic acid and further improved when the mice were treated with methylglyoxal in combination with ascorbic acid and creatine. Nearly 80% of the animals treated with this combination were completely cured.

In mice 30mg/kg methylglyoxal slowed tumor development but 30mg/kg + 50mg/kg vit C + 150mg/kg creatine = 0 tumor development,

and regression into tumor free by day 10 but this was in tumors that just started growing

so gram amounts might not be needed if combined with creatine and vit C, was injected i.p so without food if thats tolerable, bumping up because of i.p ~300mg daily might be effective over time combined with 250mg vit C and 1gram creatine, split into 2 doses 6 days a week, maybe adding a couple more grams creatine would work better too

Creatine supplementation with methylglyoxal: a potent therapy for cancer in experimental models. Amino Acids, 48(8), 2003–2013. doi:10.1007/s00726-016-2224-1
20mg/kg but i.v + vit c + creatine (started on day 7,)

Mauritio

Very interesting . I guess the mechanism would be its oxidizing effects?

Ray talked about it a few times in his newsletter and it didn't sound positive.
Also methylglyoxal is a naturally occuring of glycolysis (not oxidative phosphorylation) so it should be higher in unhealthy people . Plus it can be converted into lactate, which is the body's way of detoxing it.

When you read studies on it, it doesn't sound encouraging, it's seen as cause of diabetes and other illnesses.
Shouldn't it be very good for diabetes if it's so pro-metabolic ? Maybe it rises as a defense mechanism .

"...MGO is linked to the development of diabetes, vascular complications of diabetes, and other age-related diseases."
https://pubmed.ncbi.nlm.nih.gov/31539311/

Methylglyoxal is a major cell-permeant precursor of advanced glycation end-products (AGEs), which are associated with several pathologies including diabetes, aging and neurodegenerative diseases.
https://pubmed.ncbi.nlm.nih.gov/25709564

Then there's this quote by Peat.
https://raypeatexplained.com/ray-peat-on-oxidation/#152124319605143112494046561751189594877

And this study showing dietary intake being associated with less low grade Inflammation.
https://pubmed.ncbi.nlm.nih.gov/36055771/

cs3000

@Mauritio its an aldehyde so doesnt sound like a healthy compound / pro metabolic outside of specific use nah (probably best not to take generally outside of cancer) so its one of those things that has an outweighing effect on cancer cells, the anti-cancer dose didnt show toxicity though so i guess healthy cells can deal with that amount well enough but probably some extra burden

apparently low amounts can stimulate cancer growth but higher amounts triggers the apoptosis process (thats normally lacking because of damage making it inefficient, and pH change, needs to be more acidic inside the tissue for apoptosis to happen optimally, cancers are acidic nearby but higher end pH inside - maybe methylglyoxal accumulation makes the tumor more acidic?)

Also it has two carbonyl groups , koch and reinstorff back in the day thought these can be used to take out things with strong bonds that are sticking around blocking mitochondria respiration and enable healthy processes again. maybe @dapose has more to to say on that

Following Glo1 inhibition, cancer cells switch from glycolysis to tricarboxylic acid (TCA) cycle to avoid apoptosis induced by MGO accumulation.

for some reason cancer cells are more sensitive to MGO overload than normal ones even though they have higher glutathione (which sounds to me like the effect is less about damage and more about re-enabling apoptosis unless for some reason they accumulate extreme amounts) https://www.science.org/doi/10.1126/science.160.3832.1140.a

Mauritio

@cs3000 ok thanks.