Advanced Prostate Cancer
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CAN DORMANT PCA CELLS BE KEPT DORMANT

This is in follow up to where is our cancer hiding. In my previous post I postulated "Dormancy Equilibrium" as a theory to when we have very low detectable PSA's or Undetectable PSA's. Whereby cells wake and others go to sleep and they keep this equilibrium which we cannot observe because we cannot detect these cells as we do not have tests or scans that can find Dormant Cells or Detect Active Cells when our PSA's are very low. It made sense that sleeping/dormant cells must wake and take in sustenance, before going back to sleep. This became the basis for "Dormancy Equilibrium", because in the animal world where animals hibernate for 6 months, living in very low metabolism states, there bodies are still feeding on stored fat.

So how do Dormant undetectable Pca cells live for years? I cited my friend who went 12 years with Undetectable PSA's, and we had one poster here at 94 years of age and 18 years of Undetectable PSA's having his cancer come back. What could sleeping Dormant cells be living on? They have to come alive to take in sustenance. If not, they are not of this world, or of any known earthly biology.

OK, so if we have an equilibrium taking place of sleep->awake->sleep->awake, something upsets this balance, and the Cells once in Dormancy[Still a Theory], go on a rampage. They no longer wish to sleep, and they plot a plan to kill, us the host, so they can commit suicide. What causes this awakening, that leads to, or back to Castrate Resistance? No one seems to know. So if we do not know, can we find a way to not allow sleeping/dormant cells after TREATMENTS, to awake, or get out of their Equilibrium Phase?? With new information, I would like to take a stab at this.

So lets do some science! RNA carries info of amino acids to make proteins, sequencing from genes to where proteins are assembled on ribosomes, in the cytoplasm. This is done by Messenger RNA[mRNA]. A single strand of DNA is the blueprint for the RNA, which is transcribing on that strand. Forwarding info-> in a Pca cell/or any cell, is from DNA->RNA->Proteins. Thus DNA to RNA makes Proteins. The main thing to take away here is not to study the 4 roles DNA performs in the body or all the roles RNA performs in the body but to concentrate on one role of RNA-> providing information to make proteins. An article in <RealClearScience.com/article> in joint with the BC Cancer Agency in Canada, has done some interesting research. The article indicates Pca cells alternating between Rapid Growth and Dormancy--almost postulating something like my Equilibrium Dormancy Theory[Where did our cancer go]. A poster here put me on to this article, after I posted, and I had to dig into some more research.

But before going on--let me not lose the point of the RNA making Proteins. This will be the proposed modality at the end of this post. So at least, we can stop the growth of Pca with Surgery, Radiation, Drugs and Chemo, putting the Cancer into Dormancy for some Men--not all will achieve Low PSA's or Undetectable PSA's for many reasons. But for those of us that do, the cancer somehow if you live long enough will return. Dormancy can last a week or in the case of the 94 year old man 18 years.

{So here is a thought]---How about attacking the Dormant Cancer Cells we cannot see, so they do not get out of Equilibrium or Dormancy, to go on a rampage to kill us. What happens when we get to having low PSA's or Undetectable PSA's--- we go on surveillance, or vacations, or maintain drug programs.

This new research states that when Pca cells are in Dormancy that this is a crucial time for progression to start from. How do we stop tumor progression? In Dormancy cancer cells still alive, are protecting against the immune system, by deception, protecting against anti cancer therapies, and finding a way to metastasis. They do this I say through the production, and use of New Proteins from our RNA.

Detecting Dormant Cells are not easy. They are small if in tumor form. There are no patient symptoms and our diagnostic tools cannot find them. So how do we detect them? BC Canada Agency has looked at the RNA produced by Dormant Cells--But if we cannot detect Dormant Cells, how can we detect their RNA. Well there is something called Small RNA's[sRNA]. These can be detected in Urine and Blood.

Now early on in this post I spent time as to DNA,RNA, and the Transcribing of Proteins. These new studies indicate RNA/sRNA have weak spots in their Strand. We have known for years that certain enzymes can break into these stands at these weak spots---or in chemistry terms---their reactive sites.

Thus in continuing, the studies are indicating that anti-inflammatory drugs could stop dormant Cells from waking up. The tests are done by giving over the counter and prescription drugs like Celebrex and measuring the sRNA's in the urine and blood. These tests confirm markedly reduced presence of sRNA's.

Again in my thinking we have a slue of anti-inflammatory supplements, which many are also anti-oxidants. There is inference to believe Anti-inflammatory Supplements can have the same effect as Nsaid's--thus preventing the information from the DNA->RNA->sRNA->to the crucially made proteins that gives protection to the Dormant Pca cells, and prevents them from reconfiguring their biological make-up to wake and divide/grow and begin metastasis. If the sRNA's are stopped from transcribing proteins because their strands have been interfered with, can we now create a Durable Remission?

We do not know of the Nsaid's--which ones work best, and if our anti-inflammatory supplements may be even more effective. But this scenario presented above gives thoughts of possibilities. More proofs are obviously necessary, and could take many years, but below is an incomplete list of known supplemental anti-inflammatories.

Alpha Lipoic Acid, Sulforaphane, Curcumin, Fish Oil, Ginger, Resveratrol, Spirulina, Quercetin, Bromelain, Zinc, MSM, 5-Loxin, Melatonin, Green Tea, Rosemary, Holy Basil. Hu Zhang, Chinese Golden Thread, Barberry, Chinese Skullcap, Oregano, and many more. Interesting is that so many of these known to be anti-inflammatories, are also anti-oxidants.

Nalakrats

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Nal,

look at the last paragraph of this article "inflammation not surgery may be awakening dormant cancer cells"...I wonder if it would be prudent to also take an aspirin or ibuprofen tab a day

Gus

statnews.com/2018/04/11/can...

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And/or many of the anti inflamatories Nalakrats listed at the end of his piece, to me are better choices than aspirin, especially when combined. But... no data to say, so why not add the aspirin to daily curcumin, ALA, baswalia et al....

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I do----2 81's in the morning and 2 at night--plus if in any distress--I hit it with Aleve.

Nalakrats

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Without prescribing-- I personally think from what has been learned that Dormant cells need new Proteins made by instructions by RNA, to come alive to kick our ass---that personally I would take every natural strong anti-inflammatory I can. In actuality I take 90% of the list I put in the post plus others. If right we need to deny the RNA the ability to make the Proteins the Pca cells need to get out of their Dormancy and attack us.

Many men never get low enough in their cancer burden, and thus the loading of anti-inflammatories may be too late, but can help with overall health.

Nalakrats

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Good post. Interesting article. BTW my HIFU surgeon prescribed meloxicam to be taken before and after the procedure.

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Great post and the time you put in this.

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Hope the long diatribe is understood to basically find a way to prevent new proteins to be made by the RNA for the Dormant cells so that they can come out of Dormancy to head toward Metastasis.

Nalakrats

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zyflamend capsules - 10 herbs, all anti-inflammatory. the 4 big cancer-fighters are turmeric, ginger, cayenne and garlic - i use the first 3 in a smoothie with fresh aloe vera gel, tomato, lemon, almonds and walnuts and 1/2 tsp black pepper, to protect the curcumin in turmeric.

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Nala,

Here is an interesting extract from a 2016 paper:

"Figure 1

"Stages of cancer cell colonisation of the bone. (A) Tumour cells are attracted to the high levels of chemoattractants in the bone marrow (red), such as Ca2+, CXCL12 (C–X–C motif chemokine ligand 12) and RANKL. In the endosteal niche, hematopoietic stem cells (HSC) and disseminated tumour cells (DTCs) competitively bind to osteoblasts through interactions between CXCR4/CXCL12 and Annexin II/Annexin II receptor. In addition, expression of E-cadherin on the DTC surface can form adherin junctions with N-cadherin expressing osteoblasts as well as form interactions between RANK and RANKL, the latter of which is secreted by osteoblasts and osteocytes. Furthermore, DTCs also express integrins which can interact with a number of factors in the bone marrow (VCAM-1, bone sialoprotein (BSP), osteopontin (OPN), victronectin); (B) Once in the bone marrow, DTCs compete with HSCs for the endosteal niche. DTCs are able to proliferate; although a majority of cells die or remain dormant. The local environment has a significant impact on the fate of these DTCs. Local levels of type I collagen and fibronectin have been demonstrated to repress dormancy. Dormant cells have been reported to be found in the vascular niche, in close proximity to capillaries and within regions rich in CXCL12 and E-selection. The vascular niche is able to secrete thrombospondin-1 (TSP1) and Notch-1, which are important for maintaining dormancy. Several studies also show TGFβ2, can play an important role in the maintenance of dormancy through MAPK signalling, while TGFβ1 secreted from neovascular tips is associated with tumour cell reactivation. Periostin can also be secreted by neovascular tips as well as Cancer Stem Cells (CSCs), leading to DTC reactivation. The endosteal (osteoblastic) niche can also maintain tumour cell dormancy through the secretion of GAS6 by osteoblasts and OPN and angiopoietin-1 by spindle-shaped N-cadherin+ osteoblasts (SNOs). To exit dormancy, osteoclasts are able to release stem cell signals, triggering the NFκB pathway. We also know that the release of Ca2+ from normal bone remodelling can bind to calcium sensing receptor (CaSR) to stimulate PTHrP, leading to tumour cell reactivation; (C) After DTCs are reactivated, they become proliferative and establish macrometastases. Bone matrix derived TGFβ, IGF, PDGF and BMP can promote tumour cell proliferation, as well as Cancer Associated Fibroblasts (CAFs) secreted CXCL12. Once macrometastases are established, the tumour can release factors that drive osteoclasts (M-CSF, TNFα, IL-11 and IL-8) to induce osteolytic lesions through the stimulation of RANKL. Tumour cells have also been shown to release miRNAs that stimulate osteogenesis through the down-regulation of DKK-1 and SOST-1. Finally, association of tumour cells with the endosteal niche has been associated with tumour cell growth."

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

"4.1. Tumour Dormancy

"Several clinical observations showed that DTCs in the bone marrow do not proliferate immediately but enter a state of dormancy, whereby a group of cancerous cells cannot grow beyond a certain size [69]. It is possible that dormant DTCs never develop cancer or they can exit dormancy to form bone metastasis, potentially many years after diagnosis [70]. Several theories exist to explain how DTCs remain dormant, with the bone microenvironment playing a crucial role in this phenomenon. Tumour dormancy can be defined as when the cell arrests and enters a quiescent state (G0) [71]. Dormancy allows DTCs to adapt to the microenvironment while at the same time they are protected from the immune system and different therapies. The bone microenvironment is composed of different cell types important for the survival and maintenance of HSCs and potentially tumour cells [72] (immune surveillance and survival will be discussed in the next section). Growth-arrested DTCs have been found in close proximity to the perivascular niche [48]. Furthermore, dormant or slow-growing prostate cancer cells have been demonstrated to localise to the endosteal niche [68].

"As discussed, the annexin II and its receptor are expressed by osteoblasts and prostate cancer cells, respectively [33]. The binding of prostate cancer cells to annexin II induces the expression of the growth arrest-specific GAS6 receptors Axl, Sky and Mer, which in the hematopoietic system, induces dormancy [45]. In addition, GAS6 produced by osteoblasts prevents prostate cancer cell proliferation and protects prostate cancer cells from chemotherapy-induced apoptosis [45]. Axl, and hypoxia-inducible factor-1α (HIF-1α) were co-expressed in prostate cancer tissue and bone metastases [73]. In hypoxic environments such as tumours and the bone microenvironment, it is suggested that tumour mass is restricted by the lack of sufficient vascularisation [71]. One study showed that stable bone microvasculature maintained a dormant niche by promoting tumour cell quiescence through Notch-1-mediated regulation of neovascular tips and the angiocrine tumour suppressor functions of thrombospondin-1 (TSP-1) [48].

"TGFβ2 is a bone marrow derived factor which promotes DTC dormancy through TGFβ-R3 and MAPK p38α/β signalling [51]. In the same study [51], treatment with TGFβ1 switched off dormancy, leading to rapid tumour growth in vivo, suggesting that TGFβ2 alone is a mediator of dormancy. It is possible that TGFβ regulation of dormancy could act through the bone morphogenetic protein (BMP) pathway. This signalling pathway is well characterised in bone formation [74]. Recently, indolent prostate cancer cells have been reported to secrete SPARC, which can induce BMP7 secretion by bone marrow stromal cells [50], further supporting the role of BMP7 in inducing prostate cancer stem cell senescence [49]."

-Patrick

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Great post, I appreciate the time and thought that you have invested. Thank you.

I want to read it a few more times and think carefully about your ideas, but the basic idea of reducing inflammation is certainly sound.

With that, I'd suggest adding baking soda, 1/2 teaspoon per day in a glass of water, to your list of anti-inflammatory candidates. See some links to new science and discussion at

healthunlocked.com/advanced...

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Have to know how to use the Baking Soda---if just going into the stomach---the stomach acid Immediately neutralizes the Soda to Sodium Chloride, the release of hydrogen gas, and C02, your burping gasses. Alka Seltzer in its original form was basically Sodium Bicarbonate.

There is Chemistry to be performed to have Baking Powder provide a theoretical benefit, not proven as of yet from a scientific point of investigation.

Nalakrats

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If you follow the link, it is to a scientific study, published in April.

Yep, when you swallow 1/2 tsp of baking soda in a glass of water, it is immediately neutralized by the stomach acid.

When the researchers did this on healthy volunteers, after 2 weeks they found the balance of M1 macrophages (regulatory white blood cells) versus M2 macrophages (inflammatory white blood cells) was shifted strongly towards M1.

Apparently a previously unknown layer of cells on the surface of the spleen senses the neutralization of stomach acid, and responds by adjusting the macrophage balance. It's a classic homeopathic response, where an otherwise insignificant dose nevertheless produces a strong response.

They did this in healthy humans and in rats. In rats, just touching the spleen during sham surgery would erase the baking soda benefits, and produce a strong inflammatory response. Think about that - how many surgeries, even laproscopic, disturb the spleen? Are there other surface cells doing similar things on other organs?

There's so much we don't know, so much to learn.

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Alka-Seltzer contains three active ingredients: aspirin (acetylsalicylic acid) (ASA), sodium bicarbonate, and anhydrous citric acid. The aspirin is a pain reliever and anti-inflammatory, the sodium bicarbonate is an antacid, and the citric acid reacts with the sodium bicarbonate and water to form effervescence. (posted by Dr. Google :D )

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Maybe take an acid reducer like omeprazole, available OTC, prior to ingesting baking soda? Not sold on the baking soda benefit. I take omeprazole for GERD due to a hiatal hernia. Maybe taking the omeprazole does the same thing as baking soda?

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Nalakrats, Thank you for taking the time to post this. It really helps the lay person understand the process...

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Helpful, clear writing, Nalakrats. I am grateful!

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Great post ! Microenvironment and inflammation seem to be the key words. Did you layout the link between antioxidants and microenvironment?

Looking at inflammation: seems to start with sentinel cell activation-> signal sent to nucleus of sentinel cells->changes in gene expression->leads to activation of 3 major subsystems ie, 1 recruitment of leukocytes using cytokines and chemokines , 2 effects of histamine 3 lipid inflammation mediators—interesting this is where “other stressors” besides typical pathogen can trigger this important part of immune system and disturb microenvironment of dormant cell. Perhaps where meditation and exercise can help.

“Free radicals are highly reactive chemicals that have the potential to harm cells. They are created when an atom or a molecule (a chemical that has two or more atoms) either gains or loses an electron (a small negatively charged particle found in atoms). Free radicals are formed naturally in the body and play an important role in many normal cellular processes (1, 2). At high concentrations, however, free radicals can be hazardous to the body and damage all major components of cells, including DNA, proteins, and cell membranes. The damage to cells caused by free radicals, especially the damage to DNA, may play a role in the development of cancer and other health conditions (1, 2).

Abnormally high concentrations of free radicals in the body can be caused by exposure to ionizing radiation and other environmental toxins. When ionizing radiation hits an atom or a molecule in a cell, an electron may be lost, leading to the formation of a free radical. The production of abnormally high levels of free radicals is the mechanism by which ionizing radiation kills cells. Moreover, some environmental toxins, such as cigarette smoke, some metals, and high-oxygen atmospheres, may contain large amounts of free radicals or stimulate the body’s cells to produce more free radicals.

Free radicals that contain the element oxygen are the most common type of free radicals produced in living tissue. Another name for them is “reactive oxygen species,” or “ROS” (1, 2).” So now we recognize the myriad toxins from the environment that can disturb the cell microenvironment and specifically cause the cells DNA to be damaged, hence we also take antioxidants.

Nal, given , thank goodness, you have been undetectable while on “vacation “ from ADT. would you add another item in hope of improving your defenses , where on the other hand , you could disturb the perhaps delicate balance you have achieved? That is, if it isn’t broke why fix it, especially as you could inadvertently release “those dogs of war”?

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Thanks for the walk thru molecular biology--my point is still simple--whereby in order for Dormant Cells to get up and go, they need to have certain proteins encoded to them from RNA---if you stop the encoding of these proteins then your Dormant Pca cells cannot Divide, Colonize, and Metastasize. And that the way to stop them is by the use of Anti-Inflammatory's/which many are Anti-oxidants---having an ability to interfere at the Molecular level with the Strands of Messenger/sRNA, and prevent the encoding of certain proteins, that enliven Dormant Pca cells.

Key is the load of Pca must be very low--I do not expect someone with a PSA of 60 doing Chemo, or Zytiga/Lupron/Prednisone--for this idea to be effective.

Nalakrats

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Nalakrats - Great article and post! I am in 100% agreement with you on the dormancy and anti-inflammatory supplements. We have to continue hitting it when its at its weakest point and prevent “RNA protein making” process. I have a very low undetectable PSA and take a good number of the supplements you have listed. I can’t say thank you enough for all the wisdom you share. You da man! Thanks again!

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I do not know if I am the Man---just using what gifts GOD has given me.

Nalakrats

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