I'm back to posting. I realized that I was involving myself in too many ways on the forum, and have decided to scale back to discussing fundamentals of new treatments.
A critical part of PCa CAR-T treatment is leukodepletion just prior to reinjecting modified T cells. I had thought that this was to create a richer environment of modified T cells, but in speaking with Dr Dorff, it is done to remove immunosuppressive components. I decided to dig into this a bit more and would like to share a couple of recent research articles.
The first is hidden behind a paywall, but discusses the relationship between immunosuppressive macrophages and PARP inhibitors in BRCA+ breast cancer in mouse models
My current thinking is that targeting immunosuppressive components in the tumor microenvironment will have more widespread and effective treatment for PCa than checkpoint inhibitors.
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Javelin18
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The immune system is ridiculously complex. The immune system is partly responsible for prostate cancer progression. Among the reasons for poor results for immunotherapy in prostate cancer are:
• poor infiltration of effector T cells into tumors
• anti-inflammatory cytokines and chemokines
• pro-inflammatory cytokines and chemokines
• high regulatory T cells (Tregs)
• high infiltration of tumor-associated macrophages, neutrophils and myeloid-derived suppressor cells
• Low expression of PD-L1 and CTLA-4
This is why patients should not take "immune system builders," large amounts of anti-inflammatories, or anti-oxidants. They may be inadvertently encouraging cancer progression.
This is fascinating to me. My husbands doctors have suggested he receive Evusheld. He is receiving chemo, carbazitaxel / carboplatin, and his WBCs drop to 0.9 between treatments, even with Neulasta on board. He already has a highly aggressive cancer, so we certainly don’t want to worsen it. Would you include monoclonal antibodies as being a treatment to avoid?
We can continue living in a bubble if that is necessary. We haven’t made a final decision on the Evusheld.
I am not intending to hijack this discussion, with a personal question, so I can make a separate post if preferred.
Huge sigh of relief! We really need to enjoy life more, so hopefully this is approved this week. I appreciate your prompt answer. I learn so much from you!
Evushield looks like a good choice for right now during the remains of the Omicron in the community. Lasts at least six months so that certainly seems worthwhile for the immunocompromized.
The Japanese have been prescribing PSK, polysaccharide K or Turkey Tail mushroom for decades for those receiving chemo because PSK boosts the immune system of patients on chemo as chemo also attacks their immune systems.
The link below from our US guv acronym agencies is dated 2021--I do not like "old research".
Medicinal mushrooms are considered an unlimited source of polysaccharides (mainly β-glucans) and polysaccharide-protein complexes and possess various immunological and anticancer
Apr 21, 2021 · Higher mushroom consumption is associated with a lower risk of cancer, according to a new study. The systematic review and meta-analysis examined 17 cancer studies
It is always a mistake to lump all cancers together. For the reasons I gave above, PCa is immunologically different. There have been no prospective clinical trials in prostate cancer patients that I'm aware of.
LOL- you may not like old research, but you would be foolish to ignore it - for example, the 2003 trial that established docetaxel for mCRPC
Why go off point? Mushrooms strengthen the immune system. That is the point. The guv acronym agencies acknowledge the effectiveness of mushrooms. If you want old research, not even research, you will find that the Japanese have been prescribing PSK for chemo patients for decades, beginning I think in the 1980's. It is on the net if you wish to look.
I do know how adverse you are to anything that isn't synthetic. I worked in pharmaceutical manufacturing for 14 years. One of the drugs the company manufactured was a synthetic version of a plant. I spent the greater part of a summer on small scale batches of a new cancer drug for which there were high hopes of success --it failed. Out of about 125 new drugs being formulated, run through testing for the market, only one will be successful. The test subjects were beagles.
Perhaps you should pay more attention to the QUALITY of the research than the date it was done. Rather than make useless statements like that the Japanese have used it for a long time, I invite you to delve into "levels of evidence" and "GRADE." You may find few studies worth the paper they are printed on.
It isn't even the result of a trial - it is just those doctor's opinions, based on nothing. That's level 5 evidence - it doesn't get anymore useless than that.
I worked in pharmaceuticals. Why do you think a company will spend hundreds of thousands, maybe millions to develop a new drug that is essentially dried whatever? How do those salaries get paid? Bonuses and benefits? 401k and free cars complete with insurance as well as employee sick time, vacation, leave, educational assistance and so on get paid? The addition to the plant I worked in --just the addition--cost 117 million dollars over 20 years ago. That building also needs to be heated and energy costs for the utilities aren't cheap either. Humongous boilers and chillers with oil as the cooling and heating medium. Electricity to turn pumps for transfers and agitators in reactors from 100 gallons to 4,000 gallons, some high grade stainless, some glass lined. A tank farm with tanks holding as much as 10,000 gallons. A dedicated flammable storage area. Training and equipment for 80 plus employees to be emergency responders for HAZ-MAT incidents and Confined Space Rescue Operations. All the numerous supporting departments.
Ask a company like that to till their lawn over, grow mushrooms and do studies on the mushrooms.
The National Center for Biotechnology Information and the National Institutes of Health did post that info. They don't associate their acronyms with folklore.
If someone wants to do their own sleuthing fine and I encourage it.
There are substantial costs, revenues and profits in developing new drugs. There is also substantial risk because most new drugs fail to meet safety and efficacy goals in clinical trials.
There is also a multi-billion dollar supplement industry that spends a lot of money supporting candidates in Washington and state elections. They have, so far, kept the supplement industry unregulated. They do not have to show safety or efficacy for any of the drugs they develop. They do not even have to prove that the drug they claim is in the bottle, is actually in it. In fact, it is not in their best interest to test anything.
There have been clinical trials of supplements. Almost all have failed to show any benefit and some have shown to be harmful.
Just because a study gets published, doesn't mean that what is published is clinically useful. Most published studies are only for hypothesis generation. One has to assess each study.
The fact is--had the managing VP at the company I worked for suggested that the R&D group dedicate it's time and resources to do a mushroom study I'm sure he would have had a surprise visit from the HR department head -- from the company's main headquarters!
If you do not believe that the pharmaceutical manufacturers spend more money in lobbying than some supplement company--these pharmaceutical companies can EAT the supplement companies for a snack.
That is old ground. I know you are biased. Any studies to show that the supplement isn't in the bottle?
Studies to prove a supplement's effectiveness or ineffectiveness are usually done with one supplement at a time. Diet doesn't work that way and neither do natural supplements. Synergy is important.
To get back on point--the Japanese studies show that PSK is beneficial for those on chemo. PSK is prescribed by Japanese doctors for patients receiving chemo to help preserve their immune system's strength as chemo also weakens the immune system.
Anyone with a keyboard can access that info if they wish to do so. Anyone who wishes to disparage these studies can also do so. Just remember the NCBI and NIH don't lend their initials without consideration.
I haven't seen any RCTs from Japan or anywhere else proving that mushrooms help immune systems during chemo. If you had it you would have shown it.
The supplement industry must love you - one supplement does nothing, one needs to take ten to observe an effect. When someone comes up with excuses like that to defend what in their heart of hearts they know to be true, they are doing "pseudoscience." In fact, you check almost all of the boxes in the link below:
You asked for an example that what is in the bottle may not be what the label says. Here is one of many examples:
A study looked at 28 popular brands of red yeast rice and analyzed them for monacolin K (the active ingredient in lovastatin). Here's what they found:
• Monacolin K was not detected in two brands.
• In the 26 brands that contained monacolin K, the quantity ranged more than 60-fold from 0.09 to 5.48 mg per 1200 mg of red yeast rice.
• Following the manufacturers’ recommendations for daily servings, the quantity of monacolin K consumed per day would range more than 120-fold from 0.09 to 10.94 mg.
An accompanying editorial points out the safety hazard...
"The adverse effects that were reported relate to muscle symptoms, liver enzyme abnormalities, allergic, skin and gastro-intestinal reactions...Uncertainties related to safety issues also exist when it comes to the composition of these products; some may also contain monacolins other than monacolin K, which may also influence the lipid profile. These supplements may also contain saturated and unsaturated fatty acids, pigments, minerals, plant sterols and citrinin. The precise content of the supplements is generally not labelled; methods to measure the composition are insufficiently standardized; the absence of mycotoxins such as citrinin should be measured with great precision."
Even when the labels are correct, we have to be cautious about taking supplements. There is nothing "natural" about supplements. Our bodies evolved to process foods, not isolated and concentrated ingredients. We, and our microbiomes, can extract what we need and handle the limited amounts of toxins that occur naturally. The internet is full of sites like "Life Extension" and daytime TV is full of shows like "Dr Oz" that promote supplements while playing fast and loose with medical evidence. They spin research to make it sound scientific, but it is usually fake medical news.
As for the unchecked power of the Supplement Industry to deceive patients, there is this:
"Former Senator Orrin Hatch from Utah, was the author of the DSHEA law in 1994 and profited greatly for it. His family is invested in supplement companies, including Herbalife, among others. Between 1989 and 1994, Herbalife International gave Hatch $49,250; MetaboLife, $31,500; and Rexall Sundown, Nu Skin International, and Starlight International a total of $88,550. In addition, according to his financial disclosures for 2003, Hatch owned 35,621 shares of Pharmics, a Utah-based nutritional supplement company. In the early 1990s, Hatch's son Scott began working for lobbying groups representing vitamin and supplement makers. Kevin McGuiness, Hatch's former chief of staff, was also a lobbyist for the industry.
The supplement industry has thrived in the state of Utah, and thanks to Senator Hatch, the industry has grown unchecked -- all while patients continue to be misled and possibly harmed. In fact, the corridor of 1-15 in Utah is known as the silicon valley of the supplement industry."
You don't understand why some studies are useless and some are valuable. I showed you how to learn that. If you want to stay ignorant, that's your choice.
I wish you wouldn't tell me that I am ignorant. I am polite to you even when we disagree.
Your other message just came. From my response to Campsoups:
An excerpt from the NCBI and NIH post:
"their use in integrative medicine leads to a clear reduction of side effects in patients undergoing chemotherapy or radiotherapy"
PSK lessens the side effects of chemo and radiotherapy. What is wrong with that if that even if that is all it does? If someone doesn't want to lessen the side effects of their treatment--fine. I put the info out there.
Do men with prostate cancers have chemo and radiation for their cancers? Wouldn't you like this information available to them?
I was polite. I said you are willfully ignorant of levels of evidence. (And you take things out of context). You still haven't provided a link that works.
"want to stay ignorant", means that you view me as presently ignorant.
Again--from one of the links I supplied posted by agencies funded with our tax dollars
In addition, their use in integrative medicine leads to a clear reduction of side effects in patients undergoing chemotherapy or radiotherapy.
Wouldn't you want men having chemo or radiation to know about this? I think you would T_A. I don't think you wouldn't. You'd want those having chemo and radiation for their cancer to suffer less from the treatments. I believe you would want those having these treatments to be aware of this.
You shouldn't have any problem with the links. I clicked on them. They worked for me.
Consideration is consideration. Studies are studies. Proper trial evidence is evidence.I hope you are ok. I don't see a bio on your home page.
Your steadfast vehement backing and presentation of this doesn't seem out of concern or compassion for better treatment. It just seems you have a strong grievance towards the scientific worlds lack of confirmation of the beliefs you develop based on your "internet" searches.
I am not "vehemently" backing anything. Maybe the Japanese doctors are all wrong?
What I have said is that everyone reading this has a keyboard. Each do their own search and make their own decision. I don't like making things personal or going off point. Immunity and mushrooms have taken quite a few diversions. Why do you think the NCIB and NIH have attached initials to this? We both paid federal taxes for this to be on the net. It wasn't posted by some mushroom farmer who lives in a rainy area.
If you don't like it fine. I believe in a mix of conventional and adjuvant --whatever it takes. The mushrooms are used as an adjuvant to enhance the treatment. Why do you assume what I believe and link those beliefs to me?
An excerpt from the NCBI and NIH post:
"their use in integrative medicine leads to a clear reduction of side effects in patients undergoing chemotherapy or radiotherapy"
PSK lessens the side effects of chemo and radiotherapy. What is wrong with that if that even if that is all it does? If someone doesn't want to lessen the side effects of their treatment--fine. I put the info out there.
A link:
In 1994, a study in Japan followed 262 patients who had successful surgery for gastric cancer and were given chemotherapy with or without PSK. Patients who received chemotherapy and PSK were less likely to have recurrent cancer and lived longer than those who did not. Treatment with PSK caused few side effects.
Medicinal Mushrooms (PDQ®)–Patient Version - National ...
Another link which if you go into it has studies with --people! They say the results are clinically significant. This was posted by the NIH's, National Cancer Institute.
There was and is a cultural belief in Japan of medicinal effects of mushrooms that began three thousand years ago. The stories passed down from generation to generation.
Then around the 1970’s the public pushed hard enough for mushroom supplements that the government gave into studies backed by manufactures and further political pressure from citizens brought mushroom supplements into the government’s health care plan’s SOC during chemo treatments.
My father-in-law (Japanese) discussed this with me years ago when he was still alive.
Nothing too science based (no sound evidence) about its development in Japan. Mostly public/political pressure to bring it onboard as part of Japan’s National Healthcare System SOC due to cultural beliefs passed down thru the generations.
NCBI--National Center for Biotechnology Information
NIH--National Institutes of Health
The abstract below--
Abstract
Medicinal mushrooms are considered an unlimited source of polysaccharides (mainly β-glucans) and polysaccharide-protein complexes and possess various immunological and anticancer properties. In addition, their use in integrative medicine leads to a clear reduction of side effects in patients undergoing chemotherapy or radiotherapy. The literature reports a number of beneficial effects of using mushrooms as health supplements in patients affected by high-grade glioma. The effects of medicinal mushrooms on side effects in patients with brain cancer and a case study report are also described in this review.
NCBI and NIH do not publish info based on folklore that I know of. If you look on the net you will find much info.
So the Shar of Iran had a son "the Shan of Iran" who suffered from epileptic seizures. The Shar ordered the strongest man in his kingdom to watch the Shan of Iran 24 X 7 to insure nothing happens to his son. So this Strong man guard watched the Shan of Iran every minute of the day for 4 years. One day the Strong man guard was so bored that he went to see a movie all by himself. As fate would have it the Shan of Iran had an epileptic fit and died while the guard was in the movie theater. With that the Shar of Iran was furious at the guard and called the strong man guard into the throne room and demanded to know from the guard "where were you when the fit hit the Shan?"
Good thoughts. How could this be implemented? Perhaps low dose Rapamycin at non immunosuppressive doses (2-3 mg weekly) which have immune enhancement shown in older human trial of response to vaccines.
I think we all want a magic bullet, but I don't think there's one. The immune system interactions aren't understood, so I think there's more basic research needed. The first article seems to show the best attempt st implementation. Breast cancer seems to be closely related to PCa, so that looks to me where something may be learned.
I think it will probably be a few years to translate findings from breast cancer to PCa, I've started talking about the idea with Dr Dorff, hoping to stimulate thoughts in her more attuned mind.
I can access journals at the local college library, so I'm going to look up the article. The only difficulty will be understanding the article.
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