Advanced Prostate Cancer
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Use of Tetracyline Or Doxycline in Stage 4 prostate Cancer?

is anyone using Tetracyline or Doxycline in addition to Lupron and Taxotere(Chemotherapy)... I have read some things from the NIH talking about how good it is with bone metastasis .....and advanced prostate cancer. I certainly wouldn't mind adding a 10 day run of an antibiotic into the mix...if it will "hit from a different angle" and maybe wipe out more of this nasty cancer. I'm doing (just diagnosed in June). Lupron and and I do my 4th chemo treatment on Friday... sort of the "stampede trial" protocol. Is ANYONE looking into? using? asking about Tetracyline? Thanks in advance for any info that I might forward to my oncologist to try to get a prescription for the drug.

John

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John,

I wrote something on this a year ago. It is pasted below.

-Patrick

Tetracycline / doxycycline / minocycline

This post is prompted by Ed Miller's:

"Ten days of the antibiotic clendamycin lowered my PSA for 3 months."

I remembered seeing some PCa-tetracycline studies. (No PCa hits for "Clindamycin".)

The matrix metalloproteinase [MMP] family comprise enzymes that break down extracellular matrix proteins. The matrix holds cells in place & MMPs are essential for metastasis. Key MMPs: MMP-2 (gelatinase A) & MMP-9.

The following studies are not complete, but probably sufficient to grasp the possibilities - particularly [2b].

[1] (1997 - Canada)

"Matrix metalloproteinases are implicated in various steps of development of metastasis, through their ability to degrade the extracellular matrix. Increased matrix metalloproteinase activity of tumor cells has been associated with a higher metastatic potential. Inhibitors of metalloproteinases have been shown to effectively reduce or prevent the formation of metastases. The family of tetracyclines is able to inhibit matrix metalloproteinase activity through chelation of the zinc ion at the active site of the enzyme."

"Using tumor cell lines relevant to bone metastases, i.e. PC-3, ..., we showed that tetracycline and derivatives of tetracycline, namely doxycycline and minocycline, also induced cytotoxicity. The effective concentrations are relatively high for plasma, but are clinically achievable in the bone, since tetracyclines are osteotropic."

[2] Doxycycline.

[2a] (1998 - U.S.)

"The matrix metalloproteinases (MMPs) play a significant role in the growth, invasion and metastasis of many tumors, including those of the prostate. We previously demonstrated that doxycycline, a synthetic tetracycline, inhibits MMPs and cell proliferation and induces apoptosis in several cancer cell lines. We also demonstrated that in an in vivo model of metastatic breast cancer in athymic mice doxycycline inhibits tumor size and regrowth after resection. In the present study, gelatinolytic activity in the human prostate cancer cell line, LNCaP, was suppressed and significant inhibition of cell growth occurred after exposure to 5 or 10 microg/ml of doxycycline, while cell growth was normal in untreated cells."

[2b] (2015 - U.K. / U.S.)

"Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: Treating cancer like an infectious disease"

"... doxycycline is relatively attractive as a new anti-cancer agent, as it has a long half-life systemically and has been used successfully for the long-term treatment of patients with urinary tract infections (UTI), prostatitis or acne, for extended periods of time, of up to 4-to-6 months or more (200 mg per day). Doxycycline also encourages the growth of normal stem cells, has anti-inflammatory properties, and even increases lifespan, in certain experimental contexts [12-14]. Thus, the toxic side effects of anti-cancer therapy would be minimized.

"Doxycycline has also been used in human tumor xenografts and other animal models to significantly reduce tumor burden and even metastatic cancer cell growth [15-20]. For example, in pancreatic tumor xenografts (with PANC-1 cells), doxycycline treatment reduced tumor growth by ~80% [20]. In a xenograft model of breast cancer bone metastasis (with MDA-MB-231 cells), doxycycline treatment reduced bone and bone-associated soft-tissue tumor mass by >60% and ~80%, respectively [19]. However, its anti-cancer activity was attributed to the inhibition of matrix-metalloproteinases (MMPs), rather than the targeting of mitochondrial biogenesis, and doxycycline has not been previously implicated in the selective eradication of cancer stem cells [15-20].

"Our results are consistent with the previous finding that metformin, a widely used anti-diabetic drug, which functions as a mitochondrial inhibitor, can also be used to selectively target CSCs [21, 22]. Metformin functionally inhibits OXPHOS by targeting complex I of the electron transport chain and can even induce lactic acidosis, as a lethal side effect [21, 22]. As a result, the use of antibiotics, such as doxycycline, may provide a safer and far more effective alternative to anti-cancer therapy with metformin."

[3] Minocycline.

[3a] (2014 - Germany)

"Minocycline was identified to potently inhibit cell growth, at concentrations within the range of tissue levels readily reached under standard therapeutic conditions."

"Our findings add to the growing body of evidence for the many pleiotropic actions of minocycline. In view of the striking effects of minocycline on cell growth in PCA cell lines in vitro and its relatively safe side effect profile, the use of minocycline for targeting PCA should be timely clinically evaluated."

[4] CMT-3. (Non-antimicrobial Tetracycline analog.)

[4a] (2001 - U.S.)

"Tetracyclines (TCs) and their non-antimicrobial analogs (CMTs) have therapeutic potential to inhibit tissue destructive disease processes, such as cancer invasion and metastasis, by inhibiting certain matrix metalloproteinases. Enhanced matrix metalloproteinase-2 (MMP-2; gelatinase A) activity has been correlated to cancer invasiveness, and membrane type MMP (MT1-MMP) expressed by tumor cells is involved in localizing and activating pro-MMP-2, a pathway believed to mediate cancer induced tissue breakdown."

"CMT-3 ... has been shown to experimentally suppress prostate cancer, colon adenocarcinoma and melanoma invasiveness in cell culture and to inhibit tumor growth and metastasis in vivo and was used in the current in vitro study."

"CMT-3 at final concentrations of 5--20microM inhibited MT1-MMP gelatinolytic and caseinolytic activity, blocked MT1-MMP activation of pro-MMP-2, and decreased invasiveness"

"The inhibition of MT1-MMP by CMT-3 may partially explain the inhibition of cancer cell -mediated tissue breakdown and invasiveness by this non-antimicrobial tetracycline analog."

[4b] (2011 - U.S.)

"Metastatic cancers account for more than 90% of cancer mortality. The metastasis of all cancers is critically mediated by enzymes that degrade extracellular matrix. Aggressive tumors are characterized by an imbalance between enzymes that degrade ECM and endogenous inhibitors of the enzymes. Matrix metalloproteinases (MMPs) make up the majority of ECM degrading enzymes implicated in cancer metastasis. The potent MMP inhibitory activities of tetracyclines, especially their chemically modified analogs, combined with their relatively well tolerated pharmacological profile, led several researchers to investigate their anticancer potential in a variety of cancers, including melanoma, lung, breast and prostate cancers."

"Chemically modified non-antibiotic tetracyclines (CMTs or COL) were tested using tumors of prostate, breast and melanomas. Some of these CMTs, notably, CMT-3 and CMT-308 significantly inhibited not only invasive potential and MMP activity, but also inhibited cell proliferation by inducing cell cycle arrest and apoptosis. CMT-3 and CMT-308 were significantly more potent than doxycycline or minocycline in inhibiting tumor cell-derived MMPs and inducing apoptosis in vitro and in vivo. CMT-3 (COL-3) showed potent inhibition of tumor growth in xenografts and in bone metastatic models of prostate cancer."

"The mechanism by which CMTs kill tumor cells is via generation of hydroxyl free radicals ([OH](-)) which permeate and depolarize mitochondria, which in turn activates caspase mediated apoptosis. Analysis of tumor tissues from CMT-3 treated rats demonstrated reduction in angiogenesis and increase in apoptosis; both emerged as mechanisms of CMT action. These observations led to testing the efficacy of CMT-3 in human clinical trials against several types of cancer with significant outcomes ..."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/994...

[2a] ncbi.nlm.nih.gov/pubmed/961...

[2b] ncbi.nlm.nih.gov/pmc/articl...

[3a] ncbi.nlm.nih.gov/pubmed/243...

[4a] ncbi.nlm.nih.gov/pubmed/111...

[4b] ncbi.nlm.nih.gov/pmc/articl...

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yes, I also saw your post...I'm thought it was older than it is? how did the tetracycline do for you? what was your dosage..? is it same old tetracycline or a special "blend"? did you do it during your chemo with Taxotere? or did you do it after your Chemo treatments were finished? or before? did YOU suggest it to your oncologist? or did HE suggest it? I think you said 10 days of it? I'm trying to figure out how to approach my oncologist with this. Thanks for any help you can add.

John

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John,

I haven't used Doxycycline. Just something in my back pocket.

I wonder if Ed Miller is still in the group?

Newer study:

ncbi.nlm.nih.gov/pubmed/291...

Doxycycline might be good against PCa stem-like cells.

I would certainly pursue it. What's the downside?

Best, -Patrick

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I am also seeing (from the NIH) that using Doxycline and Vitamin C is even better? so confusing...so much information...and (for now) I'm sure my oncologist is going to say NO NO NO...as he's said to any kind of supplements, vitamins..etc..while I am doing the Chemo. I'm figuring I might try this directly afterwards. Let us know if you find out more. Thanks,

John

p.s. how far along the journey are you? I'm (as I said earlier) just diagnosed in June with Stage 4. This was after Radiation, HIFU, and antibiotics as my PSA never went down after any of these to below 2.0...it bounced up to 8 and then they did the bone scans and Pet scans and saw a few spots on my pelvis and a few local lymph nodes.

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John,

My history is a bit strange, I suppose. My prostatectomy failed (13 years ago), as did salvage radiation. I didn't want to rush into Lupron, so I decided to try testosterone [T]. I tested monthly, & for 6 months my PSA was constant.

I was then persuaded to inject B12, because of insufficiency, & the PSA started moving again. I takes quite a while to return to B12 insufficiency. When that happened, the PSA continued to rise, but the doubling time was >2 years. It had been <6 months before starting T.

I had 6+ years with continuous T, but, following lengthy intestinal problems, the PSADT shortened to 3 months. I switched to 3-monthly phases of high T & castrate T. Been doing that for 5-6 years. My PSADT in the 3rd month of the high T phase is 3 months. Haven't a clue how to lengthen that.

I haven't been greatly interested in scans, but I had some pain that might have been due to PCa & had a bone scan in 2014. There was a solitary met at L5 (nowhere near the pain, which eventually disappeared.) I found a radiologist who was willing to treat it.

I use nattokinase to inhibit clots & possible related mets. Polyphenols to inhibit inflammation. Metformin, Avodart, Simvastatin & other stuff.

I still haven't used Lupron. & now there are so many options compared to 13 years ago. But I'm not in a hurry. LOL

-Patrick

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Hi Patrick,

I was reading your post on the T and high and low alternating -- how did you accomplish that without Lupron and do you recommend trying the high t or B12 shots and how much B12 and how frequent ? I have PSA 0.5 and rising probably in lymph nodes not seen on scans yet surgery April 2016 found in 4 of 10 lymph nodes Avadart and Metformin is all I'm doing currently.

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Hi George,

I was using T continuously for about 6 years, but eventually, the PSA rose beyond my comfort level.

So I decided to try a product that was once called Prostasol & then became QuercetinPlus [Q+]. Men had been using it for years without developing resistance. We all suspected that it might be spiked with low-dose DES.

The originator - Dr. Donsbach - was eventually in trouble for promoting another product, & Q+ stopped working for everyone. The active ingredient isn't in it any more. I still have a supply of the old stuff.

Many of the men who were using it found a way to get hold of DES at 1 mg dosage, & are quite happy with the switch.

Denmeade at Johns Hopkins has had some success with monthly T injections (patients continue on Lupron.) This is a more rapid switch between high & low T that I am doing, & I'm considering switching to monthly, from 3-monthly.

The idea is to prevent resistance to ADT.

I stay away from B12 - I got into trouble injecting it.

Best, -Patrick

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Thanks or the reply -- do you think I could hold it off -- with 3 month interval T- injections and Avadart and what was the amount of T injection you were taking. Apparently you were not on ADT correct? just the spike from normal to high and back to normal?

George

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George,

No - the Q+ lowered my T.

-Patrick

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Q+ lowered your T to what level and how much T did you inject every 3 months if I can ask? I was thinking I could take a large dose of T and spike it up and let it drop back to normal -- apparently the overload of T is what does it anyway.

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I could get T to ~50 ng/dL

I was on AndroDerm 4mg patches for about 4 years.

I now inject 0.4cc T cypionate once/week.

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You can get doxycycline as an ongoing treatment for Lyme disease pretty easily. Lyme is not precisely diagnosed, so many doctors will prescribe it. It is very cheap and can be taken for years. It is not a typical antibiotic. I have taken doxy continually for four years.

Dr. Myers told me doxy was great for fighting bone metastises. It both hardens the bones and seems to repel cancer cells. He said it was fine to take with cancer drugs (Zytiga/Lupron), had few side effects, and could be safely taken for years. He thought it was a great addition to mCRPC cancer treatment, like Metformin and Avodart are.

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Sorry mate, I'm only on lupron at present

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I just read "your story"... Thanks & good luck. If you've had pet scans to see if there is any bone involvement...YOU might ask your doctor(oncologist) about what I am asking about...the Doxycyline. It seems to be a "good thing" with minimal bad side effects (see above from "....Bob")...and he sees this "Dr. Myers" who I keep getting the impression from my reading on here is the "bomb" for advanced Prostate Cancer.

Thanks again,

John

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Thanks John, I just made a note about this concept to discuss the options with my Dr.

GMTA ...lol..

Yes I had taken a holiday for 6-8 months from lupron to raise my PSA TO 9.X so I could take the Axumin scan..to no avail...It showed nothing not a dot, which is good I guess but not so good as if a clusterwas found that could be targeted directly..and maybe wipe out this beast. I am definitely going to talk about this on the 27th when my next shot is due. Thanks again and good luck.

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Gents, do not take the failure of your docs to acknowledge the beneficial use of tetra or doxy as negative info, much more likely is that they simply are not aware of them since studies are limited. herb

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I thought I recalled earlier work on tetra and doxy. I found references on other sites going back to the 1990s. Some clearly was to use of these compounds to fight bacterial infection, even prostatitis that might accompany prostate cancer. But there are others where the two are clearly being suggested for prostate cancer OR PSA!! control.

herb

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Hi greatjohn

I am recently diagnosed with PCa on 27.10.17. Read my post. I thought I was on Stage 2 or 3 hence I treated myself using some ideas from "dirt cheap cure for cancer protocols " Basically I want to boost my body's immune system. After a week recovering from my surgery which I had a stent implanted in my right ureter I started on some hand swinging exercise and diet changes. I was feeling fine and I followed up with PSMA pet scan and CT & Bone Scan. Apparently the reports was bad. I am staged at PCa Stage 4 T4 N2-3 M2-3. I feel OK so I decided to use Vitamin C to treat this aggressive cancer straight on. When I saw an article which included doxycycline I then decided to put myself as s lab rat. I am on doxycycline and vitamin c since 1.12.17. I am still feeling ok. My worry is wether the cancer cell is going to mutate and be resistant to the treatment. Like all conventional treatments it comes and goes. That means the cancer cells would have mutated and be resistant if it didn't work. Time will tell . Bye for now.

Anyway tetracycline is active 6-8 hours and doxycycline is active 16-20 hours roughly.

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Is the Doxy and C working?

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Roland, Is the Doxy and vitamine C working?

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Isn’t this what Provenge does in the extracellular matrix.

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