that's a good list, most of these if not all aren't specific nor potent tgf alpha inhibitors (which I think is good because that target can be two-edged) and may work against cancer through a wide range of mechanisms. One strategy is to look for substances that overlap several important targets e.g. curcumin, apigenin, egcg, etc. For example, grape seed extract and thymoquinone inhibit angiogenesis, very important in GBM. HSP90 is important (see attachment), ammonia needs to be addressed IMO, etc.
that's a good list, most of these if not all aren't specific nor potent tgf alpha inhibitors (which I think is good because that target can be two-edged) and may work against cancer through a wide range of mechanisms. One strategy is to look for substances that overlap several important targets e.g. curcumin, apigenin, egcg, etc. For example, grape seed extract and thymoquinone inhibit angiogenesis, very important in GBM. HSP90 is important (see attachment), ammonia needs to be addressed IMO, etc.
@jdubw Sorry, I meant TGF-beta
@j Cissus Quadrangularis. I think that God lead me to this one. It seemed to help my wife’s cognitive ability shortly after taking it tonight.
It is a plant steroid with some cognitive effects. I had been using it recently to deal with injuries. Things just seemed to move me towards it for her, so I looked it up. Here it shows potential to fight glioblastoma
https://academic.oup.com/rpsppr/article/2/2/rqad014/7100332
@jdubw That's wonderful to hear. Very interesting study, CQ inhibits both MAPK/ERK and STAT3 expression.
@j the Cissus effect seems to have waned, and I also am uneasy with using Cissus too long as it seems to cause some kind of imbalance after around a month or so (in my personal experience). That is also a problem with GBM, it seems to wax and wane, and it is hard to tell is something is really having an effect. On top of that is the fact that a patient may appear to get worse even while the tumor is shrinking or the immune system is reacting against the tumor.
Anyway, what do you think of magnesium threonate? This is a magnesium that crosses the BBB, and may improve cognition. I am wondering if this might help fight the GBM. Although my wife is definitely not magnesium deficient.
@jdubw I know it can be useful for pain management.
Oral application of magnesium-L-threonate enhances analgesia and reduces the dosage of opioids needed in advanced cancer patients—A randomized, double-blind, placebo-controlled trial
https://onlinelibrary.wiley.com/doi/full/10.1002/cam4.4922
@j thanks for sharing that study. On a side note, I found that I can overcome the hurdle of “too many pills to swallow” by emptying multiple capsules into a sweetend/flavored solution (preferably stevia), and administering by a 30 ML oral syringe. This means I can add more CAM for additional benefit, and it leaves more pill swallow-ability for things that don’t go well into solution (encapsulated raw garlic and cayenne). Now I am trying to really zero in on the most promising CAM’s. I am looking to research more on R-ALA and PSK mushroom. We have been taking Theobromine and Magnolia Extract. Would you mind sharing what you think are some of the top tier herbs/supplements for GBM?
@jdubw That's a great idea, using powders is very useful, and often the best way to keep using the supplements is by mixing in juices or like your idea administering by oral syringe.
I'd also take the supplements you mention but magnolia extract I'd replace with pure magnolol as the extract doesn't have sufficient amounts of it.
Magnolol
https://liftmode.com/magnolol-powder/
Add to that pure Honokiol for synergy and Artemisinin for even more synergistic anticancer power.
Boswellia (inflasanum MCSformulas, has 180mg AKBA)
Ornithine or ornithine-L-aspartate, for ammonia scavanging.
Butyrate
AHCC (with fucoidan for synergy)
Ellagic acid
Melatonin 10 to 20 mg (intermittent use)
@jdubw That's a great idea, using powders is very useful, and often the best way to keep using the supplements is by mixing in juices or like your idea administering by oral syringe.
I'd also take the supplements you mention but magnolia extract I'd replace with pure magnolol as the extract doesn't have sufficient amounts of it.
Magnolol
https://liftmode.com/magnolol-powder/Add to that pure Honokiol for synergy and Artemisinin for even more synergistic anticancer power.
Boswellia (inflasanum MCSformulas, has 180mg AKBA)
Ornithine or ornithine-L-aspartate, for ammonia scavanging.
Butyrate
AHCC (with fucoidan for synergy)
Ellagic acid
Melatonin 10 to 20 mg (intermittent use)
And add a few more supplements that have shown in vivo anticancer efficacy against GBM and also aid in ammonia detoxification, such as Baicalein.
Metabolic Interaction between Ammonia and Baicalein
"In conclusion, this study confirmed that baicalein, a flavonoid with a vic-trihydroxyl structure on the A-ring, has the potential to detoxify ammonia and treat ammonia-associated chronic diseases."
@j hey thanks for sharing your insights. We have been doing the raw garlic from McGraws book. My wife hates garlic, so press it into mush and mix it with a bit of oil and sugar substitute. We can do a clove in a couple spoonfuls this way with little complaint.
Unfortunately, she appears to have part of the tumor bleeding out, so I have been going through all the supplements to see what might be contributing. Basically anything that could potentially interact with a blood thinner, and this is a lot of them.. even garlic. I am trying to work down to minimal doses of essential things like Boswellia and Curcumin and garlic. Getting rid of high dose Niacin and Hesperidin. I plan on swapping out Baicelein for Fisetin. Might get rid quercitin or just lower the dose. There are others too, and I am looking to add in some more CAM that does not interfere with blood clotting. I think mushrooms and anything immune boosting will be good.
There seems to be a weird tie-in with her immune system and the GBM. Any small viral illness like a cold makes the GBM symptoms get five times worse. The when the virus clears she bounces back.
right, many anti-cancer compounds possess blood-thinning properties, from mild to potent. This characteristic likely contributes to their efficacy, particularly in the prevention of metastasis. The mushrooms are great.
A good air purifier in rooms she spends most of her time can be helpful in reducing exposure to airborne viruses and germs.
[Proliferation inhibition of glioma cells by vitamin K2]
Abstract
The antitumor effects of vitamin K2 were studied using three glioma cell lines: C6 (rat glioma cell), RBR17T and T98G (human glioma cell). The antitumor effects were estimated by count assay. The results was that vitamin K2 induced growth inhibition in a dose-dependent manner. The RBR 17T cells exposed to vitamin K2 for 72 hours resulted in oligonucleosomal DNA fragmentation and formed a ladder on agarose gel electrophoresis. Furthermore, the RBR17T cells exposed to vitamin K2 for 24 hours were significantly accumulated in the G0G1 phase of the cell cycle. Those results suggested that vitamin K2 can inhibit the proliferation of cells through the induction of cell cycle arrest and apoptosis for tumor cells. The combined treatment of vitamin K2 with ACNU or 5-FU or INF-beta or 1,25-dihydroxyvitamin D3 enhanced growth inhibition significantly. In conclusion, vitamin K2 can be a useful drug for the treatment of glioma.
https://pubmed.ncbi.nlm.nih.gov/10065443/
Vitamin K can counteract some of the blood thinning effects (and as always, consult her oncologist first).
right, many anti-cancer compounds possess blood-thinning properties, from mild to potent. This characteristic likely contributes to their efficacy, particularly in the prevention of metastasis.
Hence, concurrent use of natural products with blood-thinning properties and anticoagulants may result in prolonged bleeding times and should be avoided.
https://www.sciencedirect.com/science/article/abs/pii/B9780128116555000064
Abstract
Artemisia annua is a commonly used Chinese herbal medicine, which is bitter in taste and cold in nature. Assigned to hepatic, biliary, and renal meridians, it has the traditional functions of clearing summer heat, removing hectic heat and antimalaria. Clinically, it is used for the treatment of symptoms such as fever due to Yin deficiency, affection due to exogenous summer heat, and malaria and jaundice due to dampness heat. Its functions and uses have been documented in historical works about Chinese materia medica. Pictorial Classic of Herbal described that “Artemisia annua is the best medicine for treating bone-heat syndrome and fever in chronic consumptive diseases and was used alone in ancient prescriptions.” A. annua can also be used for treating “ulcer,” as documented in Shennong’s Herbal Classic. According to the Newly Compiled Materia Medica of the Tang Dynasty, “crude stalks of Artemisia annua can be applied to incised (metal-inflicted) wounds, and effectively stop bleeding, promote tissue regeneration and alleviate pain.” In addition, Peaceful Holy Benevolent Prescriptions and Miraculous Emergency Prescriptions also mentioned that A. annua had been used for treating “unstoppable purulence in ears” and “dental swelling and pain.”
@j thanks, very much needed. I have a feeling that she is deficient in Vitamin K based on a recent XRay showing bone weakness. I probably need to add calcium along with it.
@j piperlongumine looked good at first, but it is touted as an autophagy inducer by the Life Extension company.
@j took a long break from Arteminsin, but recently started it up again. From what I read I am thinking running it for only 2 - 3 days per week.
@j took a long break from Arteminsin, but recently started it up again. From what I read I am thinking running it for only 2 - 3 days per week.
Sounds good
You've probably seen this but just in case you haven't: "Inhibition of autophagy by chloroquine potentiates synergistically anti-cancer property of artemisinin by promoting ROS dependent apoptosis"
https://pubmed.ncbi.nlm.nih.gov/25308836/
Abstract
Artemisinin (ART) is a well-known anti-malarial drug, and recently it is shown prospective to selectively kill cancer cells. But low potency makes it inappropriate for use as an anticancer drug. In this study, we modulated the ART-induced autophagy to increase Potency of ART as an anticancer agent. ART reduced the cell viability and colony forming ability of non-small lung carcinoma (A549) cells and it was non-toxic against normal lung (WI38) cells. ART induced autophagy at the early stage of treatment. Pre-treatment with chloroquine (CQ) and followed by ART treatment had synergistic combination index (CI) for cell death. Inhibition of autophagy by CQ pre-treatment led to accumulation of acidic vacuoles (AVOs) which acquainted with unprocessed damage mitochondria that subsequently promoted ROS generation, and resulted releases of Cyt C in cytosol that caused caspase-3 dependent apoptosis cell death in ART-treated A549 cells. Scavenging of ROS by antioxidant N-acetyl-cysteine (NAC) inhibited caspase-3 activity and rescued the cells from apoptosis. Similar effects were observed in other cancer cells SCC25 and MDA-MB-231. The appropriate manipulation of autophagy by using CQ provides a powerful strategy to increase the Potency of selective anticancer property of ART.
Dual Role of WISP1 in maintaining glioma stem cells and tumor-supportive macrophages in glioblastoma
Abstract
The interplay between glioma stem cells (GSCs) and the tumor microenvironment plays crucial roles in promoting malignant growth of glioblastoma (GBM), the most lethal brain tumor. However, the molecular mechanisms underlying this crosstalk are incompletely understood. Here, we show that GSCs secrete the Wnt-induced signaling protein 1 (WISP1) to facilitate a pro-tumor microenvironment by promoting the survival of both GSCs and tumor-associated macrophages (TAMs). WISP1 is preferentially expressed and secreted by GSCs. Silencing WISP1 markedly disrupts GSC maintenance, reduces tumor-supportive TAMs (M2), and potently inhibits GBM growth. WISP1 signals through Integrin α6β1-Akt to maintain GSCs by an autocrine mechanism and M2 TAMs through a paracrine manner. Importantly, inhibition of Wnt/β-catenin-WISP1 signaling by carnosic acid (CA) suppresses GBM tumor growth. Collectively, these data demonstrate that WISP1 plays critical roles in maintaining GSCs and tumor-supportive TAMs in GBM, indicating that targeting Wnt/β-catenin-WISP1 signaling may effectively improve GBM treatment and the patient survival.
https://pubmed.ncbi.nlm.nih.gov/32541784/
Carnosic acid (Carnosic acid biosynthesis and accumulation take place exclusively in young rosemary leaves at the branch apices, with the diterpene molecule being partially consumed during leaf development and aging ref )
Pyroptosis, ferroptosis, and autophagy cross-talk in glioblastoma opens up new avenues for glioblastoma treatment
https://biosignaling.biomedcentral.com/articles/10.1186/s12964-023-01108-1
"Guo’s research lab spent more than a decade conducting research to understand how more aggressive forms of cancer – specifically glioblastoma (brain), breast, skin, lung, liver and pancreatic – can rapidly produce lipids. Their early research published in the journal Cancer Cell in 2015 found that glucose was necessary for lipid production, not just because glucose is converted to lipids, but also because it needs to be present for SREBPs to activate. However, glucose alone could not trigger lipogenesis. Through extensive, long-term research they found that ammonia from glutamine (a building block of protein) was also required.
In fact, it was ammonia that actually activates the SREBPs that tell the cell to make lipids. The team’s newly published data details how tumor cells use glutamine to produce ammonia. Together with glucose, this activates lipid production and aggressive tumor growth."
and here's a link to the study in Nature: https://www.nature.com/articles/s42255-022-00568-y
A few months ago I posted this research:
Glutamine-released ammonia acts as an unprecedented signaling molecule activating lipid production
https://www.sciencedirect.com/science/article/pii/S2352304222002148
In astrocytes: Melatonin detoxifies the excess ammonia by activating the Arginase I and II enzyme that prevents glutamine synthesis and glutamate accumulation in extracellular fluid.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137547/
