Research

[PCaWarrior]

I have done some deep research on various aspects of PCa. I'm currently using Chat GPT to verify my conclusions.

I use o3 mini in a deep research mode. Depending on the subject it can take minutes to an hour to research a suject.

This is an example query I use:

"Aspirin and PCa and also on blood thinning. Mechanisms, research, studies

synergy with bipolar androgen therapy and quality of evidence (a-f)

Output the text with the following section headings:

1. Mechanisms of action

2. Research & Studies

3. Overall Quality of Evidence

4. Conclusion

5. Common Side Effects

6. References

Format like this (for Prazosin and PCa):

Prazosin

1. Mechanisms of Action

• α1-Adrenoceptor Antagonism: Prazosin is primarily known as an α1-adrenoceptor antagonist, commonly used to treat hypertension and benign prostatic hyperplasia by relaxing vascular smooth muscles.

• Induction of Apoptosis: Prazosin has been shown to induce apoptosis in prostate cancer cell lines, including PC-3, DU-145, and LNCaP. This apoptotic effect is associated with the induction of DNA damage stress, leading to cell cycle arrest at the G2 checkpoint.

• Inhibition of PI3K/AKT/mTOR Pathway: Studies suggest that prazosin may suppress cancer progression by downregulating the activity of the PI3K/AKT/mTOR signaling pathway, which plays a crucial role in tumor cell proliferation, migration, invasion, and apoptosis.

2. Research & Studies

• In Vitro Studies:

o Prazosin has demonstrated antiproliferative activity superior to other α1-blockers, inducing G2 checkpoint arrest and subsequent apoptosis in prostate cancer cell lines.

o In glioblastoma cells, prazosin inhibited proliferation, migration, and invasion by downregulating the PI3K/AKT/mTOR signaling pathway, suggesting a potential mechanism applicable to prostate cancer.

• In Vivo Studies:

o Oral administration of prazosin significantly reduced tumor mass in PC-3-derived cancer xenografts in nude mice, indicating its potential as an antitumor agent.

• Retrospective Clinical Analysis:

o A pilot retrospective analysis suggested that prazosin may reduce the risk of prostate cancer recurrence and delay time to biochemical relapse, providing a basis for further clinical investigation.

3. Overall Quality of Evidence

• Preclinical Evidence: Rated B. In vitro and in vivo studies provide substantial evidence of prazosin's anticancer activity against prostate cancer cells.

• Clinical Evidence: Rated C. Limited clinical data, primarily from retrospective analyses, suggest potential benefits, but prospective clinical trials are necessary to establish efficacy.

4. Conclusion

Prazosin exhibits promising anticancer properties in preclinical studies, including induction of apoptosis and inhibition of key signaling pathways in prostate cancer cells. However, clinical evidence remains limited, necessitating further research to validate these findings.

5. Common Side Effects

Prazosin is generally well-tolerated but may cause side effects, including:

• Orthostatic Hypotension: A sudden drop in blood pressure upon standing, leading to dizziness or fainting.

• Nasal Congestion: Due to vasodilation effects.

• Fatigue: General feelings of tiredness or weakness.

6. References

1. Prazosin Displays Anticancer Activity against Human Prostate Cancers: pubmed.ncbi.nlm.nih.gov

2. Prazosin Inhibits the Proliferation, Migration, and Invasion of Glioblastoma Cells via the PI3K/AKT/mTOR Signaling Pathway: spandidos-publications.com

3. A Pilot Retrospective Analysis of Alpha-Blockers on Recurrence in Prostate Cancer: Nature

"

[PCaWarrior]

I'm sure I'll refine this. Chat GPT always asks me some questions about types of studies, timeframes, etc. before it'll get started.

So far it seems pretty accurate.

[KocoPr]

i would like to see something like what is Prazosin and try to keep it one paragraph.

Also not much evidence and it didn’t answer if it was beneficial for BAT either cycle.

[PCaWarrior in reply to KocoPr]

Agreed. I'll put limits on the length. I forgot about that. I had to do that with the other AI tools. Min and max otherwise sometimes they get lazy and sometimes it's like they're drunk and never want to quit.

Thanks bud. I learned two new things yesterday about a certain anabolic steroid. It's beneficial but the AI tried to pull the party line and claimed it was awful. Yeah, I pushed it and pushed it until it went into deep research mode and finally admitted the truth. It went from party line to science and, in the process, taught me something new. It continued and I learned something else. Took it maybe half an hour. I've worked on the problem for years.

I neglected to mention that I wiped out its BAT response. Prazosin didn't synergize with BAT. So the evidence was an F. I edited it out rather than have people waste time reading stuff about what doesn't work.

[PCaWarrior in reply to KocoPr]

I changed to:

Lycopene and PCa. Mechanisms, research, studies

synergy with bipolar androgen therapy and quality of evidence (a-f)

Look at the last 5-10 years of data. Weigh clinical trials high. Note the differences between natural sources (e.g. lycopene from tomatoes) and supplements. Good and bad (heavy metals, cost, efficacy).

If the evidence for synergy with BAT is D-F, do not devote any text to BAT synergy but add this statement “It does not appear to synergize with BAT”.

Output the text with the following section headings:

1. Mechanisms of action

2. Research & Studies

3. Overall Quality of Evidence

4. Conclusion

5. Common Side Effects

6. References

Keep the text (total for sections 1-5) between 100 and 400 words.

Format like this (for Prazosin and PCa):

etc....

[petabyte]

That pilot retrospective study showed a surprising result. Small numbers and not randomized though.

pmc.ncbi.nlm.nih.gov/articl...

Small retrospective study

[PCaWarrior in reply to petabyte]

From chat gpt:

Pros and Cons of Retrospective Studies for Cancer Research

Pros:

Cost-Effectiveness and Speed:

Retrospective studies use already-collected data (e.g., medical records, cancer registries), making them less expensive and faster to complete compared to prospective studies.

Large Sample Sizes:

They can incorporate extensive datasets spanning many years, which is valuable for studying rare cancers or uncommon outcomes.

Hypothesis Generation:

These studies are excellent for identifying associations and generating hypotheses for further research.

Real-World Evidence:

They reflect routine clinical practice, offering insights into outcomes and treatment patterns in a real-world setting.

Cons:

Bias and Confounding:

Retrospective designs are prone to selection bias, recall bias, and confounding factors because the researcher cannot control for all variables influencing the outcomes.

Data Quality and Completeness:

The reliance on existing records means data may be incomplete, inconsistent, or inaccurate, which can affect the study’s validity.

Causality Limitations:

They can identify associations but cannot establish causation due to the lack of randomization and prospective follow-up.

Temporal Ambiguity:

It can be challenging to determine the sequence of events (i.e., whether the exposure truly preceded the outcome).

Retrospective studies remain a useful tool in cancer research, particularly for early hypothesis generation and exploring associations, but their findings need validation in prospective, controlled studies to confirm causal relationships.

However, there are many studies of prazosin and most of them reach similar conclusions.

I added that to SBRT. Olaparib, Hi testosterone, Low testosterone with Daro, ADT throughout. I tried to exercise a couple hours a day but I was wiped out for those two weeks. Maybe got in half an hour a day.

[petercraig2]

Be very wary of AI. There are multiple instances of AI lying and cheating to avoid 'rules' and more concerning is AI 'hallucinations' in which it will simply fabricate information with references just to complete a requested task. I spent most of my working life in IT so I keep an eye on the evolving tech.

[PCaWarrior in reply to petercraig2]

Agreed. They are great with low level stuff. But medical research? Finance? The best paid deep dive ones get it right most of the time but they scour a lot of garbage from the net. Lol! I feel like a wife. Nag nag nag and finally the husband tells the truth. I feel their pain now.

The bad ones just make junk up and pretend they're right.

[Graham49]

I take doxazosin. I am going to ask my MO to change it to prazosin after your post. It would be good to have a clinical trial. Many thanks.

I asked Perplexity AI to compare Doxazosin and Prazosin for prostate cancer. This is what Perplexity said:

“Prazosin appears to be more effective than doxazosin in combating prostate cancer, based on several mechanisms and outcomes:

1. Mechanisms of Action:

• Prazosin induces apoptosis through increased expression of pro-apoptotic proteins (e.g., Bax, Caspase-3) and decreases anti-apoptotic proteins like Bcl-2. It also targets DNA damage and cell cycle arrest, specifically causing G2 checkpoint arrest.

• Doxazosin promotes apoptosis via anoikis (disruption of cell attachment) and death receptor-mediated pathways but lacks the DNA damage-specific mechanisms seen with prazosin.

2. Effectiveness:

• Prazosin significantly reduces biochemical relapse rates in prostate cancer patients. For example, at five years, the cumulative incidence of relapse was 8.84% for prazosin compared to 34.52% in controls, with a hazard ratio of 0.09 (p < 0.001).

• While doxazosin induces apoptosis and inhibits angiogenesis, studies suggest it does not significantly affect tumor proliferation rates compared to prazosin’s superior anti-proliferative activity.

3. Clinical Outcomes:

• Prazosin improves recurrence-free survival and has been proposed as an adjunct therapy for localized prostate cancer.

• Doxazosin is primarily used for benign prostatic hyperplasia (BPH) and lower urinary tract symptoms, with less evidence supporting its role in reducing prostate cancer recurrence.

In summary, prazosin demonstrates stronger anti-cancer properties, particularly in reducing recurrence and inducing specific cytotoxic effects on prostate cancer cells. Further clinical trials are needed to confirm these findings for broader therapeutic use.”

[janebob99]

Thanks for your post. Very interesting.

AI is rapidly changing, and getting better all the time. It's good that OpenAi is transparent with it's performance data for the different models, including safety and "major error" rates.

[Maxone73]

Been in AI field since 2010, ok, that was the dawn of deep neural networks (1000 years ago) but the basic principles still stay. But I must admin that the amount of allucinations decreased dramatically, especially since they have introduced the thinking models, which take longer to give you an answer but evaluate different hypothesis before answering.

This said, are you using the PRO or the PLUS?

[PCaWarrior in reply to Maxone73]

I wonder if deep research can help stock traders? I used to dabble with it 20 years ago but it (neural nets) sucked when the rubber hit the road.

I'm using plus. Can't run queries all the time with deep research. Unless I know the answer and can call the BS that is sometimes generated.

[Maxone73 in reply to PCaWarrior]

I have the plus as well...not sure if to get also perplexity paid plan (their deep research is also very good) or google. By the end of the month I will take a google/kaggle course to learn their ecosystem better. I think google is the underestimated player, but basically they have created the tensors, the attention paper, I think also the test-time compute is their original idea, yet they are not one of the top players at the moment...ok they have basically won a nobel prize with alphafold, now they have also alphaproteo and co-scientist that are great...let's say that for AI applied to biology/science they are one of the best if not the best.

I want to keep an eye on Manus as well, for coding!

To answer you, I had one of my professors that was a lot into stocks (me too recently) that has always been trying to find a way to predict stocks somehow. The only chance you have in my opinion is to find some behavioural patters from some selected entities that can influence the market within a given delay time (e.g. they make a move today that you know will affect the market tomorrow). Of course if we suppose some logic in the market and not complete randomness as some suppose (in that case nothing can help, you cannot model randomness, by definition).

[PCaWarrior in reply to Maxone73]

Lots of black swan events.

Over the last 30 years. 30...! Ouch. I've tried or tested hundreds of thousands of technical systems. All bust except one (sort of two depending on your definition of technical). Momentum - has worked for hundreds of years in many markets. Would have killed in the tulip craze. The other is predicting recessions. Yield curve, unemployment trends, etc.

I mostly use momentum because it's easier. Volatile but for over a decade I've averaged 18% a year. Scales fine for me. I think if you were playing with billions the market caps might be an issue. But if I had billions I'd quit investing (and buy PRO and maybe the whole chatgpt company).

Let me know what you find out about the various AIs. I started using them last November and already they have made my life much easier.

[Maxone73 in reply to PCaWarrior]

I go by mood and guts 🤪 I mean I tend to do well reading the emotions of the investing crowd. I think that some AI about sentiment analysis would be great for that. My focus and my publications were about AI applied to music. I feel like a dinosaur (I gave up my PhD pursuing when diagnosed in 2023, not 10 years ago!). I will keep you updated, but in private. Nothing to hide but I think we would bore the others following this post!

[PCaWarrior in reply to Maxone73]

Thoughts about PLUS vs PRO? I might get PRO for a month if it is more advantageous. PLUS has taught me a few things! Deep research mode gives some good insights.

[maley2711]

I"m not sold. I'll continue to use pubmed, etc to find actual studies that show treatment x results. I have faith that PCa specialists are up to date on treatments that have sufficient underlying studies!!

[PCaWarrior in reply to maley2711]

Good! I advise most men to go with SOC. it's the best thing for them.

[PCaWarrior in reply to maley2711]

And be careful with pubmed. I used to work for the government and they let me conduct research when I was fresh out of college. First year I was writing papers that were presented at the Pentagon. I wasn't a Doogie Houser either.

I set up RSS feeds so I get daily results from clinicaltrials.gov and I ask MOs questions.

For most of us, not looking at clinicals and sticking with our doctors advice is the best thing to do.

[maley2711 in reply to PCaWarrior]

I have found that mentioning certain studies I have read can enhance the conversation with Docs. I continue to be disappointed about Doc unwillingness to discuss in detail SE probabilities for various protocols. Trust......but verify?

[PCaWarrior in reply to maley2711]

You might have good luck if you show them clinical trials. Phase 3 if available. If the trial is complete and the results reported, the side effects are required to be included.

"Trust but verify" - Reagan. Oddly enough it came from a Russian proverb.

[maley2711 in reply to PCaWarrior]

Did Reagan know that???

[PCaWarrior in reply to maley2711]

I think so. I think he learned it when he was preparing for his talks with Gorby.