Mercola: Study Discovers the Mechanism Behind Prostate Cancer Growth by turiya ..... Prostate Cancer Forum
Date: 11/10/2024 8:54:19 PM ( 9 d ago)
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According to the American Cancer Society, about 1 in 8 men will be diagnosed with prostate cancer during their lifetime. It's the second-leading cause of cancer death behind lung cancer.1 But despite its prevalence, a diagnosis is not an automatic death sentence.
Between 1993 and 2013, the death rate of prostate cancer declined by around half, and 3.3 million American men diagnosed with this disease at some point are still alive.2 Furthermore, the National Cancer Institute predicts a 97.5% survival rate after diagnosis.3 But, we're not out of the woods yet — plenty of research is still being done to learn more about treating this disease, and researchers from the University of Michigan have just pushed the frontier.
In a study4 published in Nature Genetics, researchers discovered a key factor in the development of prostate cancer. Specifically, they noted that when the NSD2 (nuclear receptor binding SET Domain Protein 2) binds with the androgen receptor (AR), it leads to rapid cell division and growth that results in prostate cancer.
Before diving further into this, let's define some of the basics. Androgens are essentially hormones that trigger the growth and development of the male reproductive system, and the most prominent example is testosterone. They're responsible for the changes that males go through during puberty, such as thickening of the vocal cords that leads to a deeper voice.5
While androgens are largely associated with males, females produce androgens as well, but in smaller amounts. When androgens are released, they're converted into estradiol, a type of estrogen. In this converted state, estradiol helps regulate menstruation, as well as conception and pregnancy.6
Now, what is the AR? It's essentially a protein produced by the AR gene, which then binds to the androgens produced in your body. As noted by MedlinePlus:7
"The receptors are present in many of the body's tissues, where they attach (bind) to androgens. The resulting androgen-receptor complex then binds to DNA and regulates the activity of certain genes that play a role in male sexual development. By turning the genes on or off as necessary, the androgen receptor complex helps direct the development of male sex characteristics."
Going back to the Nature Genetics study,8 the researchers were able to crack the code, as it were, between NSD2 and AR using an epigenetics-targeted functional CRISPR (clustered regularly interspaced short palindromic repeats) screening. Interestingly, they noted that NSD2 is also an oncogene in hematologic cancers, and "harbors recurrent activating alterations in over 15% to 20% of multiple myeloma and 10% childhood acute lymphoblastic leukemia."
The researchers used different methodologies that comprised human and animal test samples. For human samples, prostate tumor patient tissues were taken from the archives of University of Michigan archives, while mice were provided by the University of Pennsylvania and the University of Michigan, which were kept under humane conditions.9 After completing their assays and analysis, the researchers published these findings:10
"Conventional plasmid-based reporter systems fail to capture intricate epigenetic or chromatin-level regulation of gene expression as they lack the native histone composition or higher-order chromosomal structure. Thus, we engineered an endogenous AR reporter system by using the CRISPR/Cas9 and homologous recombination methodologies.
We edited the KLK3 gene (also known as prostate-specific antigen, PSA) locus in AR-driven LNCaP cells to knock-in the mCherry coding sequence directly downstream of the endogenous promoter and fused in-frame via an endopeptidase sequence to the KLK3 gene …
Using these endogenous AR reporter cell lines, we carried out a functional CRISPR screen, wherein we treated the cells with a custom single guide RNA (sgRNA) library targeting druggable transcriptional cofactors for eight days, stimulated with DHT for 16 h and FACS-sorted into mCherryHIGH and mCherryLOW populations.
Genomic sgRNAs were sequenced and the ratio of normalized counts in mCherryLOW to mCherryHIGH cell populations was used to rank individual sgRNAs. Here, ranked alongside BRD4 and TRIM24, we identified NSD2 as an AR coactivator."
The study is packed with dense information largely meant for oncology researchers, but the findings above summarize how the researchers were able to sift through large swaths of information and methodologies. Undoubtedly, this new breakthrough will be beneficial for all people receiving prostate cancer treatments.
The researchers concluded that NSD2 plays an important role in the development of prostate cancer. Furthermore, they proposed targeting this protein in further experiments to fully confirm the effectiveness of their findings. In a press release, co-author Dr. Arul M. Chinnaiyan elucidates further:11
"By degrading NSD1 and NSD2, we can more directly target cancer and avoid the normal tissue. Our study suggests if we're able to develop NSD1/2-targeting agents, they could potentially be combined with FDA-approved androgen receptor antagonists and have a synergist effect in terms of treatment."
Considering the new information published, I'd like to debunk a medical myth about prostate cancer that's been circulating for a few years now — choline intake and its association with this disease.
The primary study where this notion came from,12 published in 2012, suggested there might be a link between increased choline intake and an increased risk of advanced, lethal prostate cancer. As noted by the authors, "Men in the highest quintile of choline intake had a 70% increased risk of lethal prostate cancer." However, there are several questionable aspects surrounding this conclusion.
To start, the study was observational only, which means it only suggests associations but cannot prove causation. Since there are many factors, both dietary and environmental, that play a big role in predicting prostate cancer outcomes, pinning the disease to a single nutrient is problematic.
Furthermore, the researchers collected dietary information only six times during 22 years of follow-ups, which raises questions about the accuracy of their collated information. Many people can't even recall what they ate several days ago, let alone the foods they consumed within a span of 22 years. Other shortcomings of this study include the following:
In truth, choline is beneficial for your health. Several studies have shown that increasing choline intake has important benefits, such as decreased risk for heart disease,13 cancer14 and nonalcoholic fatty liver disease.15 Based on these findings, you'd be better off increasing your dietary choline intake, and the best sources include grass fed meat and milk, as well as pastured eggs.
I believe that virtually all major diseases like cancer, heart disease and obesity are linked to an inability to produce cellular energy due to impaired mitochondrial function. Without optimal cellular energy, your body cannot properly initiate the repair processes essential to preventing and recovering from disease.
Through the years, I've identified three pernicious toxins that damage your mitochondrial function, mainly by affecting intracellular calcium that subsequently impact your cellular health. In essence, exposure to these toxins raise intracellular calcium, which results in increased superoxide and nitric oxide levels. These combine into peroxynitrite, a potent reactive oxygen species that contributes to poor health. These three primary culprits are:
Addressing these three factors will help repair and return your mitochondrial function back on track to producing optimal cellular energy. Ultimately, this is the crucial first step to warding off all chronic disease that plague Americans today, such as cancer, and the best way to do it is limiting your exposure to them. To start, I recommend minimizing your LA intake below 5 grams from all dietary sources. If you can get it below 2 grams, that's even better.
Next, minimize your EMF exposure by turning off the Wi-Fi and using hardwired connections instead. I also recommend using an analog alarm clock instead of relying on your phone's alarm clock, which most people put beside their bed. The next strategy is reducing your exposure to plastics, which is accomplished by opting for products sold in glass containers and using reusable products over single-use ones.
This is just a preview of the strategies available to restore and repair your mitochondrial function. My newest book, "Your Guide to Cellular Health: Unlocking the Science of Longevity and Joy," goes into great detail about how these three factors affect your mitochondrial function, as well as practical, healthy strategies to address them.
The eBook is now available, while the print edition will be released on December 10, 2024. I encourage you to pick up a copy, as this contains my latest research that corrects many long-held beliefs I've had in the previous years.
In addition to addressing the main factors of mitochondrial function, there are other strategies available to help you prevent cancer. One approach is taking aspirin, a drug well-known for its pain-relieving and anti-inflammatory uses.
In my interview with bioenergetic medicine expert Georgi Dinkov, he discusses research using a combination of B vitamins and aspirin against a highly lethal form of human mantle cell lymphoma. He discovered that while the vitamins stopped tumor growth, adding aspirin into the equation regressed the tumor in the animal test subjects. Below, he explains the theoretical basis:
"One of Ray [Peat]'s main theories was that … cancer cells … [are] metabolically dysfunctional, we all know that, and typically a cell like that commits apoptosis. But in order to commit apoptosis, that mechanism is controlled almost entirely by the intracellular pH. And in order for apoptosis to occur, it needs to be in the acidic range.
But the cancer cells are alkaline due to exporting lactate and hydrogen ions. So, if anything can drop the intracellular pH, those cancer cells, because they're deranged, should actually disappear by themselves.
And one of Peat's suggestions at the time was, 'Why don't you use the drug acetazolamide?' which as a carbonic anhydrase inhibitor, increases carbon dioxide. Carbon dioxide is acidic, and then that should allow cancer cells to commit apoptosis.
There are some studies in vitro and in vivo showing that acetazolamide may work, but it didn't really cure the tumors. It was a slower growth, partial regression, but it showed that the idea was on the right track.
So, I said, 'Let's find something that's much more acidic than carbon dioxide.' And that is this 2,6-dihydroxybenzoic acid, which is just one extra hydroxyl group on top of aspirin. Salicylic acid, really, which is 2-hydroxybenzoic acid. And then this thing is about 10 times more potent than aspirin."
That said, consider adding aspirin into your health routine. But don't just select any aspirin available — opt for immediate-release formulations instead of the coated extended-release varieties. Pay attention to the ingredients as well. Ideally, corn starch should be the only additive listed.
After doing my own research, I identified a product meeting these criteria. The appropriate dosage ranges from 82 mg to 325 mg daily, taken with your largest meal, depending on your individual needs.
In the context of cancer prevention, the dosage and duration of aspirin are crucial factors. Low doses (75 to 300 mg/day) have been shown to be as effective as higher doses in reducing colorectal cancer-related mortality,17 which means there's no need to take large amounts to gain the benefits.
Consistency and long-term use seem to be key, however. Studies indicate that aspirin's benefits increase with duration, with significant reductions in cancer risk observed after five to 7.5 years of consistent use.18
I personally take 111 mg daily using Health Natura's USP grade 60 gram aspirin powder, which costs less than $20. This 99% pure USP aspirin powder appeals to me due to its prometabolic, antilipolytic, anti-inflammatory, anticortisol and anti-estrogen effects. Its safety profile is also well-established.
For the last 50 years, I have been in a relentless pursuit of how to optimize health and wellness and prevent disease. Every year I get closer to the truth. But this time, I am convinced I have finally uncovered the kernels of truth that will help nearly everyone recover from whatever physical illness they are suffering with.
I've uncovered a groundbreaking revelation that has the astounding capacity to transform global health and that is the power of cellular energy. This isn't just another health trend; it's the fundamental key to unlocking your body's innate healing abilities and achieving lasting vitality.
Nearly everyone reading this is only making about one-third of the energy they require to reverse disease and power their body to regenerate and repair damaged cells. Nearly all of us are in the black hole of self-perpetuating destruction of our gut bacteria that are crucial to help us regain our full energy potential.
Here's a startling fact: A very sensitive and inexpensive blood test shows us that over 99% of us have insulin resistance, and as a result, are unknowingly living with compromised cellular energy. This silent epidemic explains why millions struggle with persistent health issues, feeling trapped in a cycle of treatments that never quite solves the problem. But there's hope, and it lies within your very cells.
Imagine a life where your body hums with energy, where healing happens naturally, and where age is just a number. This isn't a far-off dream — it's the reality that I have been experiencing for over a year now and awaits when you master the art of cellular health.
My newest book, "Your Guide to Cellular Health: Unlocking the Science of Longevity and Joy" is not just a manual — it's your passport to a revolution in personal wellness. This comprehensive guide will empower you with life-changing knowledge:
This isn't about quick fixes or temporary solutions. It's about fundamentally transforming your health at its very foundation — your cells.
Article Link: https://articles.mercola.com/sites/articles/archive/2024/11/09/mechanism-behind-prostate-cancer-growth.aspx
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