While drugs like statins and bempedoic acid have been shown to have a positive impact against coronary artery disease and cancer, the common link is better understood courtesy of science. A new target was found called LOX-1 and is involved with both the clogging of arteries and cancer metastasis. A future target for drug research:
Next, a new blood test that can guide treatment options in prostate cancer for better results. The test is courtesy of the Vancouver Prostate Centre and may be able to detect resistance before it happens allowing for a change of treatment.
Lastly, research at the Moffit Center ( place where greatjohn was under treatment ) identifies a potential target to overcome castrate resistance and block the evolution of that resistance.
Thanks for the appreciation and reply.... Science edges ever closer to some real answers for PCa patients.... eliminate castrate resistance and people could be fine on ADT for the rest of their lives... need to get there and sooner rather than later...
I wish j-o-h-n would come over here and hang out, but maybe he just wants to focus on other things. He has been sending out humor for years, and laughter really is the best medicine. A special 2 scoops salute for all he did to make people laugh, because darn it, we are cancer patients and sometimes we need a laugh. I will see if I can get my comedy routine up and running, or at least walking fast... I'll shoot you a response on the serious one a bit later.
j-o-h-n is as free as a bird for sure... Chatted with him a bit today... as always, he wants 2 scoops....chocolate chip, of course... Now I can't tell you how many times I partied to that song....
I totally agree, l loved your LOX-1 joke! I've got a wicked sense of humor that sometimes gets me in trouble, but music and humor is what gets me through. Best always...🕊️🤣🎶✌️
Well, then I vote that you be designated as the FPC director of musical humor - and any other endeavors that bring some levity to the often dry and dreary content that predominates. 🤩🎼 👏🎵 👌🥇🎶🤣
Very unofficially been there and done that, apparently you missed out on the whole en.wikipedia.org/wiki/Urech.... thread a while back. My sense of humor is not everyone's cup of 🍵! 😁
That's why I now sit back in the corner with headphones on and behave. LOL!
I did see it, but I forgot because darn it, that's what we do on ADT....the dreaded brain fog... Good behavior is overrated, but good humor is underappreciated... pull off the headsets and you go girl....
Bring that humor and music....we need to laugh... I'll second that nomination... As the K9 Comedian says, sometimes it is all too dreary and laughter is the best medicine...
Make that 2 days to go.... I can not wait to be done with them. As for LOX-1 with cream cheese, I will take the Anti LOX-1 on a bagel since that would be better for me... I do like the Muttley laughing youtube video....I use to watch Dick Dasterdly and Muttley on saturday cartoons.
Thanks very interesting. Really appreciate all the research you dig up from a great variety of areas.. Do you know of any supplements that target Lox1 ?
It seems that black soybean hull, propolis, grape seed, and apple condensed tannin are around the best. So a good grape seed extract and bee propolis should be helpful and not too pricey.
Hi Fish. The Geiger are quiet now.Thanks for making me aware of LOX-1. Very interesting. Appears can be a bad actor when activated. Interesting Berberine appears to suppress it. My hunch is it may play a role in the beneficial effects seen from statins.
I’ve been paying more attention recently to two areas: cellular senescence (including PC treatment emergent senescence) and senolytics. Those most well established and available now are dasatinib, Quercetin and fisetin. The last two being readily available plant derived supplements.
And secondly the gut microbiome. Previously not fully appreciated by me. And now am all over it, as per my recent posts. Easy changes to improve it seem a no-brainer. Involved in the mechanisms of benefit of antioxidants, anti inflammatories and metabolism mediators. Even of how Metformin confers benefits. But not fully explored. Josh also deeply exploring this arena along with K-9.
In the meantime, I keep my high dose statin, resveratrol (added back in), Quercetin, fisetin, probiotics, inulin/FOS with psyllium and high fiber diet.
The long cycle modified BAT is also going well. Love that high T!
Thanks for the added info. I agree with your thoughts on the statin benefits. My real questiion is what is the most optimal?? Is it statins, statins with zetia or bempedoic acid? Drugs like inclisiran work differently than statins and so I would love to see a study comparing the various cholesterol fighting drugs and effects on PCa progression. Like you, I have been on Atorvastatin 80 mg and can find no reason to change. I take fisetin, resveratrol, quercetin, and berberine as well as others.
Fishing this summer?? Absolutely !!! I have been busy with work, but quitting my job, and will use COBRA to get to Medicare. I plan to take time with my son to go fish in Canada for bass, walleye, and musky for a week soon.
Glad to hear that BAT is going well... Ride the T tide and go with the flow...
I have struggled for years to get a solid read on lipids and cancers, since in my case, I have found some evidence that cholesterol and/or its components can fuel cancer progression in both PCa and CLL. At different points I have seen indications that Total Cholesterol and each major component individually were the bad actors in both of these cancers and many others. I have previously reported that when my historically low HDL dropped out of the normal range in 2020 that I later started using the Cholestene lovastatin equvalent derived from red yeast rice. The effects were immediate and my last labs produced results that were nothing short of amazing (see attached graph), especially considering I had been taking the Cholestene for only 3 months. (@ 1200 mg, twice a day - I have recently cut that in 1/2 to 600mg x 2.) Note that with a near 100% WFPB diet, I am producing all my cholesterol internally and getting near zero, if any, from food intake.
However, I still have some lingering suspicions about the low HDL, as it could have been low because it was being used/converted by one or both of the cancers to fuel their progression. Since other than my low platelets and depleted immunoglobulins (the latter somewhat concerning for COVID), my blood work had reached normal ranges prior to starting Cholestene. Therefore, it seems any issue with lipids (to cancer directly) would probably be confined to PCa. So, the one issue I have yet to answer is: Since I have now boosted my HDL well into the normal range, is that a positive or negative for my current/future PCa status? A major hurdle in unraveling such things is the question of causation vs correlation, so in watching for a "durable" response, now that I am off treatment, one of the things I will consider if things go south (er, PSA goes north) is to drop the Cholestene and let the lipids run free again. As I now frequently like to say, whether we are on SOC or N=1-care, we are all forever medical works in progress. Or as Rosanne Rosanadana was fond of saying on SNL, "It's Always Something".
Influence of serum total cholesterol, LDL, HDL, and triglyceride on prostate cancer recurrence after radical prostatectomy - Cancer Management & Research - 2019; 11: 6651–6661. Published online 2019 Jul 16. doi: 10.2147/CMAR.S204947
In reviewing this and many other similar research, this recent commentary & video on MedPage Today offer some focused insights on the devil-in-the-details nature of all observational studies and meta-analysis. (Note: video would not work for me on Firefox, but a full transcript is provided)
Making Observational Studies More Reliable— Harlan Krumholz, MD, discusses a new path to less bias, more transparency by Emily Hutto, Associate Video Producer July 17, 2022
And here is a link to the study Dr. Krumholz is referring to in his discussion:
Large-scale evidence generation and evaluation across a network of databases for type 2 diabetes mellitus (LEGEND-T2DM): a protocol for a series of multinational, real-world comparative cardiovascular effectiveness and safety studies - BMJ Open. 2022 Jun 9;12(6):e057977. doi: 10.1136/bmjopen-2021-057977.
And on Topic Two: I keep thinking how much better we would understand the evolution of our hormone-driven disease, if we monitored all major sex hormones over time. I expect we would not only see individualized responses to ADT, BAT, RT, etc. and be able to anticipate well in advance the subtle evolution in our disease states, but could/would be able to adjust treatments to respond to those changes. It seems the historical genetic mapping of CTCs could also provide similar early warning signs that treatments need to be changed or escalated/reduced, essentially personalizing drug combos and dosing amounts to the individual response. The science is most definitely way ahead of the clinical practice - and our patient community is paying the heaviest price one can pay for that: inevitable disease progression, increasingly poor QOL, and, eventually, an early grave. Maybe in a parallel universe the medical practitioners are leading and not following the developments of science.
Topic Three: This looks like Moffitt expanding their PCa knowledgebase and continuing the challenges to SOC started by Gatenby at the Center of Excellence for Evolutionary Therapy and Alexander at his Alexander Lab. Definitely a place to watch for major treatment developments over time.
Thanks for posting and for your continued efforts to keep us up to date on the developing science related to our common disease.
2 days and a bit more - and then on to the chain saw and the fishing gear. Keep it safe, Bro'
Plenty to address from your response. In my opinion, Topic One--controlling LDL is essential with LOX-1 and so I looked at your labs and your HDL and LDL are essentially 1:1. Good job on the cardiac risk. I might consider driving LDL down further with Atorvastatin 10 mg twice a week or so to give PCa less building blocks. MB may wish to weigh in here as well. The concern is dropping your LDL too low. Otherwise, I think what you are doing now is solid. It is always something....
Topic two-- indeed, knowing your hormone levels is essential in my opinion. Control your hormones and control your destiny... I think Josh has proven this to be true. I should have done better on my last vacation. Also, the partying... Bad Fish, Bad...
Indeed, I agree that the science is outstripping the practice, but part of it is the speed at which it is progressing. I do like the APCCC and that leading minds are voting and coming to a consensus of how treatment should be done. The issue is that so many Urologists are out there treating people the same way they have for 20 years, and patients are paying the price. We all want the progress to be faster, but in 2018, there was Lupron and abiraterone for initial treatment, and abiraterone was just being offered to HSPCa. We've come a long way in a few years, K9 Wonder...
Topic Three-- Moffit and everyone else is stepping up their game. Find a way to block castrate resistance and the death toll goes way down... I keep my peepers open and watching to see if Osteodex gets a partner for Phase III. In the meantime, CCS1477 goes into Phase III as the first bromodomain inhibitor to make it this far. If approved, it will provide a new class of drugs for late stage PCa in 3-5 years.
Thanks for the input. On the lipids, Patrick actually clued me into PCa targets to shoot for with lipids several years back. I shared my lipids from 2019 and these were his insightful comments:
My concern with the Tri:HDL ratio isn't cardiovascular - it's PCa-related. I have zero-tolerance towards insulin resistance because I feel that it is related to aggressive PCa. With insulin resistance, the body produces more as it tries to overcome the resistance. It's a growth promoter.
The irony is that the beta cells that produce insulin eventually burn out as a man becomes diabetic. A year later, the diabetic has reduced his risk of PCa. Not an ideal solution, but it points to the dangers of high insulin.
So, when a year later my HDL dropped out of the normal range, I started the Cholestene which caused the rapid improvement across the board, even hitting Patrick's ideal T/HDL ratio right on the nose at 1.0. As you may have picked up in his posts, Patrick really thinks insulin resistance is a major factor in PCa progression and the T/HDL ratio is one of many indicators that measure it.
And when you look at my LDL numbers historically, the drop in the latest post-Cholestene lab was a significant drop out of that consistently elevated range. Also, FWIW, the labs came back with a note that my total C was low at <150. (I see other places that <120 is the bottom of the range.) At the most recent 147, it is over 100 points below what it was back in 2003.
As I mentioned in the reply, I have cut back to a 1/2 daily dosage on the Cholestene to see how much my numbers will change when I do lipid labs again in December.
In the meantime, I'll continue to leave the "drugs in development" to you and Don Pescado to research. Both of you will definitely have more time for that sort of research after tomorrow.
Oh, and to optimize LOX, in addition to toasted bagel and cream cheese, I believe in a slice of tomato, capers, shreds of red onion and sprinkle of lemon pepper. 👍🥯
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. Thanks again 👍
