interesting find - if u target a main 2% subset of melanoma cells the tumor goes in most cases without destroying the other part. if some are left theres potential for the regression to return
(does doxycyline help these ones get destroyed when combined with inhibitors?)

https://www.pnas.org/doi/10.1073/pnas.1009069108

we revealed that established tumor lesions can be efficiently eradicated by targeted elimination of the less than 2% subset of melanoma cells with the CD20+ high molecular weight melanoma-associated antigen (HMW-MAA)+ phenotype without targeting the tumor cell mass, whereas targeted elimination of any minor subset is less effective.
These data provide a strategy for improving the biological therapy of melanomas and, moreover, for redesigning current drug development paradigms used in the treatment of cancer.

HMW-MAA+ cells gave rise to melanomas upon transplantation, whereas sorted HMW-MAA− cells from the same melanoma did not.
indicating that these cells exhibit melanoma-initiating capacities.
T cells with redirected specificity for CD20 eradicated established melanoma lesions in four out of five melanoma biopsies, although the targeted cells represented less than 2% of melanoma cells.
It is noteworthy that transplanted tumors of patient 5, in which no CD20+ melanoma cells were detected, could not be eradicated by a CD20-redirected T-cell attack.

Where tumors were eradicated, no tumor relapse occurred during the observation period of >36 wk.
Because no tumor relapse was observed in any case during the >36 wk observation period, such melanoma eradication is obviously long lasting
We conclude that CD20 is not functionally crucial but marks a specific cell population. The unexpected observation, however, is that targeting the minor CD20+ melanoma cell population is as effective as targeting the majority of tumor cells. A caveat for a broad therapeutic application is that obviously some melanomas, in our cohort one out of five patients, do not harbor CD20+ melanoma cells

The observation that the specific elimination of a minor subset of tumor cells results in eradication of established melanoma lesions is crucial for the understanding of the biology of melanoma. Continuous melanoma growth obviously requires the presence of a minor population of cells, which displays the CD20+ HMW-MAA+ phenotype;Elimination of these cells is obviously required to eradicate the melanoma irrespective of the bulk of tumor cells

Natural compound Physachenolide C (but not commercially available yet) gave complete remission in melanoma. in 1/3 of the mice it stayed regressed. (in the other 2/3, maybe doxycycline could have brought back the effect)
its a highly potent BET inhibitor

https://pmc.ncbi.nlm.nih.gov/articles/PMC8571524/#sec0011

enhanced immunotherapy for regression (enhance with b-glucan?)
https://pmc.ncbi.nlm.nih.gov/articles/PMC8802328/#S19

@16charactersitis
yeah , its a bit more acid than baking soda from what i remember but practically its basically the same. a few grams of each per L water

@cs3000
450mg daily created regression in this persons liver tumor, to half its size. but the effects stalled and it re-grew after around a year
https://pmc.ncbi.nlm.nih.gov/articles/PMC2769275/

Ultrasonography in our outpatient department revealed a large tumour with central necrosis, measuring about 11 cm in diameter,
CT scan of the liver was performed again and revealed HCC regression, with tumour size reduced to about 4.6 cm in diameter, and portal vein thrombosis (Figure 3).
Silymarin 450 mg daily was the only regularly prescribed medicine during HCC reduction.
The tumour size did not contract persistently as shown by abdominal echo. CT scan of the liver was performed prior to the surgery, revealing an HCC size similar to the previous readings and portal vein thrombosis.

@cs3000 said in Studies showing cancer reversal / shrinking:

Another showing regression of existing tumors
human squamous cell carcinoma
Feeding high amounts of silymarin
( note silymarin / milk thistle inhibits thyroid hormone transport, not suitable for general use)
Shrank the pre existing tumors

Another showing regression of existing tumors
human squamous cell carcinoma

Feeding high amounts of silymarin
(note silymarin / milk thistle inhibits thyroid hormone transport, not suitable for general use)

Shrank the pre existing tumors

doi.org/10.1093/carcin/23.3.499

melanoma, 500mg/kg ~ 3g human only using 1 dose every 2weeks slowed
but didnt regress (maybe lower dose more often could have too)
10.1002/mc.22208

200mg/kg 5days a week for 5 weeks , didnt show kidney or liver toxicity 10.1177/1010428318776170
stalled growth in an oral tumor until the end, but didnt get to regression

Can penetrate skin in Propylene glycol and stays in skin cells for long while https://www.sciencedirect.com/science/article/abs/pii/S0378517322009863

glycerol / glycerine increases growth of some tumors so probably not appopriate as to use for entry
https://pmc.ncbi.nlm.nih.gov/articles/PMC8908677/

Propylene glycol is different. maybe some connection but is used as penetration enhancer in anti tumor studies with effect still so
https://pubmed.ncbi.nlm.nih.gov/23186833/

Mct oil might be good if it dissolves well, warmed in a saucepan

1 haidut posted before:

BRAF + MEK inhibition therapy {inhibiting MAPK through selective paths} + the doxycylcine antiobiotic = regression in a person who had metastasised melanoma into liver & bile duct
https://pmc.ncbi.nlm.nih.gov/articles/PMC4699264/
https://rupress.org/jem/article/218/9/e20210571/212494/Activation-of-the-integrated-stress-response

alone didnt do much , but helped delay the eventual resistance seen in the yellow line

In the person it gave full remission as doxycycline + the mapk inhibitors

To assess the relevance of our in vitro and preclinical findings, we followed the clinical course of one 73-yr-old female patient at our clinic. The patient was diagnosed with stage III melanoma in 2011 and with a relapse of her disease in 2016 after an episode of jaundice, which was related to a tumor mass in her gallbladder and bile duct.
the presence of brown pigment associated with these cells was highly suggestive for a melanoma metastasis.
Subsequently BRAF-MEK inhibitor therapy was initiated. Response assessment after four cycles showed that while the liver metastasis had responded to the treatment, the gallbladder did not.
Due to a skin infection (an acne-like rash) the patient received doxycycline during her fifth BRAF-MEK inhibitor cycle for a total of 12 d.
Strikingly, the gallbladder metastasis started to regress after six cycles, as measured by CT scan, and the PET-CT scan after eight cycles showed a complete response. The patient was under BRAF-MEK inhibitor therapy and had a persistent response for >36 mo (Fig. 6 C). This particular case study highlights the potential clinical benefit of using tetracyclines to sensitize intrinsically resistant lesions to MAPK inhibitors.

*Lipoic acid is a mapk inhibitor, and showed decent effects slowing tumors alone i posted in the first post.
https://onlinelibrary.wiley.com/doi/10.1155/2022/1894379

ALA inhibited a variety of mitogen-activated protein kinase (MAPK) signaling pathways in the epithelial cells

So i wonder if a combo of lipoic acid + doxycycline could be good for giving regression of melanoma / metastasised melanoma to other areas
50 - 150uM is too high to hit in vivo probably, its like 20ug/ml blood i think
so maybe for topical applied to melanoma as the combo. lipoic acid can penetrate if absorbs in right thing, propylene glycol or heated mct oil. not sure about doxycycline . But short half life on lipoic so would have to get a lot in
https://pmc.ncbi.nlm.nih.gov/articles/PMC3648887/ here they got 14ug/cm2 to pass through normal skin
but melanoma = melanocytes so i guess easier to penetrate as doesnt have the outer SC layer?
maybe theres something else for systemic use

extra: (not showing remission but metastasis effect)
B-Glucan (particulate) melanoma matastasis prevention
https://www.researchgate.net/publication/327193765_Beta-glucan-induced_inflammatory_monocytes_mediate_antitumor_efficacy_in_the_murine_lung

oat b-gluten best effect at 200kda size
https://www.researchgate.net/publication/320392541_Systemic_Administration_of_bglucan_of_200_kDa_Modulates_Melanoma_Microenvironment_and_Suppresses_Metastatic_Cancer

turkey tail glucan is 100kda https://pmc.ncbi.nlm.nih.gov/articles/PMC10000499/

Feeding inhibition effect (but is anti androgen)
https://pubmed.ncbi.nlm.nih.gov/26408688/

@lobotomize-me thanks , so where it could increase T3 u expect to see more steroids, but the Test increase could be also somewhat from lower conversion to dht by the looks of it then when using certain extracts, from things in ethanol fraction
i dont think its functionally estrogenic by default because the cortisol also dropped a lot in the OP male lamb study. looks to be sex dependant because of stimulating hormone production at gonads? as the lambs shouldnt have had lower cortisol and higher test if it was estrogenic to them right

but theres a lot of mixed results with it maybe because of the extracts

(broadly most studies only give insight on test increase instead of dht, not always insight alone into if net androgenic i guess. e.g
finasteride can raise test a little where its lowering conversion to dht. though it lowers DHT 50% and only gives like a 10% test increase with that drop. so much of a big Test increase wouldnt be the decreased conversion going by that)

if the oils are mostly responsible for downsides u only get low amounts of essential oils when just ingesting the leaves instead of concentrated extract (gotta be powdered unless chewing for humans to break through the cellulose. or doing hot water infusion like u mentioned) https://iwaponline.com/aqua/article/70/5/773/82378/Essential-oil-and-linalool-contents-in-basil
like 0.5% oil and only 5% of that as linalool, of dry leaves, so 5mg total oils per gram

probably why the studies giving them just the leaves showed good results,
not pushing the oil so much?

, the Jumbo 4320 Thai basils water extract showed the highest total phenolic content at the value of 459.62 ± 3.07 mg gallic acid equivalent/100 g

follow by ethanol and ethyl acetate extracts at 179.80 ± 0.55 and 56.95 ± 0.99 mg GAE/100 g, respectively.1

using water only extract showed a nice effect on diabetes. but high amount (17.5% of dried water extract compared to dry powder weight so 6x dose) https://scialert.net/fulltext/?doi=pjbs.2020.1010.1017

@cs3000 said in Holy Basil: Phyto-TESTOSTERONE, Progesterone and thyro-mimetic ?:

But this one, using very high dose of 80% ethanol : 20% water extract, raised testosterone without crashing LH or causing infertility
https://academicjournals.org/article/article1380729420_Khaki et al.pdf from leaves bought in iran. the rabbit study was india

300mg/kg dose of just the oil extract caused infertility and lowered testosterone , 100mg/kg didnt raise or lower testosterone https://dergipark.org.tr/en/pub/jabs/issue/34910/387191
so its probably the water soluble compounds responsible , or leaves from certain locations

@Mauritio i got a powdered one took some time to get. no noticeable improvements so far. in the feeding studies 60d worked better than 30d (both worked well) so there's some time buildup effect. but expected to notice something acute.
this one i have has some black dots mixed into the powder not listed in the ingredients. so some concern considering it can be extracted from a mold. i guess if the mold is dead it could still trigger inflammation?
i tested it in some 6% h2o2 liquid and it fizzed like fuck so the white powder is legit (can do that with some potato slices too much milder response)

Same wondered if it would be good for that, i started putting it on one side of hairline curious to see if it creates regrowth. putting in a bit of glycerine

@CrumblingCookie said in All things Histone Deacetylase (HDAC) and DNA Methyl Transferase (DNMT) inhibitory - reversing epigenetics from metabolic insults:

@cs3000

free-amino-acid starvation of beneficial ileal bacterial species... Due to lack of digestive functions in the more proximal parts of the GI system? Which more BA in the proximal parts would prevent and heal?

However, some reports described
high fecal BA concentrations in CUMS model mice [21]. Some patients with mental disorders
such as depression and autism also exhibit high intestinal BA concentrations.

Where did you derive or read the <200mg Na-But dose from? In that mice study they used 20mg∙kg−1. 

https://pubmed.ncbi.nlm.nih.gov/25240644/ here valproic acid induced autism-like defects when given during pregnancy , but weirdly this or sodium butyrate fixed them when given for 5 weeks a while after birth. (affects folate during pregnancy idk if that applies to butyrate too, but maybe best to avoid HDAC inhibitors during)

np interesting thread & the 20mg/kg dose for HDAC inhibition orally for mice is about 100mg - 150mg for human when u account for metabolism differences. its not exact depends on substance but generally for mice its (3/37) * dose * human weight in kg , or just dose *5 to simplify for 60kg person and add or reduce as needed for weight. for rats 6/37 or dose *10
useful link for different animals conversion https://www.westernu.edu/media/research/iacuc/dose_conversion_between_animals_and_human_-jbcp_2016.pdf

From Protective CO2 and aging:
Prolonged lack of CO2, i.e. also hypoxic states -> epigenetic silencing/hibernation. Got it! That seems sensible to apply!
Speaking methylation: That's an ambiguous mechanism because whilst we don't want excessive methylation of DNA CpG sites which prevent genetic transcription, methylation of the lysine groups on histone bodies either contributes to their unfolding OR to genetic silencing.
On H3K9 tri-methylation (reportedly a stubbornly long-term, transgenerational impact!) acts silencing so directly opposes the effects of acetylation or bOHB. Which makes HDACis like butyrate or beta-hydroxybutyrate direct antagonists to overmethylation. I wish Peat had followed that up. It could be rewarding to find out about the histone demethylation mechanisms for H3K9 specifically.

ah key context there then , here global methylation was actually lower in hibernation https://pubmed.ncbi.nlm.nih.gov/25908059/ with a global transcriptional decrease https://pubmed.ncbi.nlm.nih.gov/19412897/ with increase in HDAC too especially hdac1 and 4.
(hibernation i think reflects as a darkened hellish depression state for humans, humans dont hibernate so the closest thing is creating a drive towards death. sleep isnt hibernation hibernation is closer to death just on the edge)

Reduced BA uptake in the chronically inflamed states. So it'd be better to really blast up the dosage? Perhaps even so much as to provide BA through serum circulation and the basal membrane (from within the body) instead of the apical side (from the intestinal lumen)?

thats what im thinking too the underneath part, gonna try standard butyric acid diluted in water, into circulation and see if helps a small intestine problem at the ileum from the underside. but some will absorb direct too. i think taking it uncoated = you still get it absorbed a lot in small intestine but spread out absorption in duodenum jejenum ileum and diluted with water, instead of overwhelming just the ileum and with the undiluted sodium release too as extra that doesnt release until then otherwise
1g+ looks like high dose used for acute repair boost and general use lower, (for histone acetylation they showed its effective systemically in tissues at low dose <200mg as the sodium, because most of the sodium butyrate wouldnt havent reached that colon tissue sample direct, so if bumping up 50% to make room for absorption issues still <300mg or 2x <500mg generally)

@CrumblingCookie

https://raypeat2.com/articles/articles/protective-co2-aging.shtml

,
For the butyrate forms i think its better to avoid coated forms for general use, the ones that have fats coating them (small intestine is probably vulnerable to increased amounts released there https://pmc.ncbi.nlm.nih.gov/articles/PMC11641654/#sec2-ijms-25-12998, plus the undiluted sodium when coated, normal form gets absorbed higher)
and only small amounts needed < 200mg as sodium butyrate for h3 acetylation
doi.org/10.1111/bph.13637