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Doxycycline Effective In Human Trial For Breast Cancer

Discussion in 'Scientific Studies' started by haidut, Oct 4, 2018.

  1. haidut

    haidut Member

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    It seems that medicine is finally starting to wake up from its slumber that has now lasted almost a century. I posted a few other studies on the effects of antibiotics used as cancer treatment. Those older studies also used doxycycline but other antibiotics from the same group like tetracyline and minocycline have also been shown to work.
    Tetracyclines (and A Few Other Antibiotics) As A Cure For Cancer

    As I mentioned in that post above, a human dose of about 200mg doxycycline was needed to stop the growth of the most aggressive tumors like pancreatic and brain types.
    Well, this new study below (from the same authors as the one above) shows that using the same 200mg dose of doxycycline was effective in reducing the "stemness" of breast cancer cells and thus arrest proliferation. The treatment lasted just 14 days and was combined with surgery but the study says the surgery cannot explain the benefits seen since the placebo group that got only surgery as treatment did not respond positively at all.
    Interestingly, this study also mentions that the same 200mg dose was able to induce complete remission in people with lymphoma. I bet the infamous fraudster Martin Shkreli knew about these results when he bought the exclusive rights for doxycycline in the US and jacked up its price a few thousand percent.
    Credit goes to Dr. Lisanti, one of the authors, for admitting that the anti-cancer effects of doxycycline has been obvious for more than 50 years. I hope that information is used one day for massive class-action lawsuits against Big Pharma and the medical industry in general under the legal premise of "knew or should have known".

    @aguilaroja @Such_Saturation

    Doxycycline, an inhibitor of mitochondrial biogenesis, effectively reduces cancer stem cells (CSCs) in early breast cancer patients: A clinical pilot study

    "...Previously, doxycycline has been used clinically to target cancer-associated infections, with promising results, leading to a complete pathological response (CPR) or “remission” in patients with MALT lymphoma [15, 16]. Interestingly, this CPR did not correlate with the presence of micro-organisms, possibly suggesting that doxycycline might be acting on the tumor cells themselves."

    "...In contrast to our results with the doxycycline treated patient population, patients in the untreated control group did not show any statistically significant changes in the expression of CD44, when tumor tissue sections were compared before and after surgery (Supplemental Figure S1). The results of multi-variate analysis are included as Supplemental Information (Tables S11 to S15) and showed that CD44 remained unchanged (See Table S13; ANOVA; P < 0.7707). Therefore, surgery itself was not sufficient to significantly change the expression levels of the tumor markers examined, including CD44."

    "...Remarkably, CD44 levels were reduced between 17.65% and 66.67%, in 8 out of 9 patients treated with doxycycline. Representative images of this reduction in CD44 immuno-staining are illustrated in Figure 4 for two patients. In contrast, only one patient showed a rise in CD44, by 15%. Overall, this represents a positive response rate approaching 90%. It is worth noting that the levels of cleaved caspase-3 were most strikingly elevated in the two patients (Cases 8 & 14) that showed the largest reductions in CD44 expression (Figure 5). Therefore, a certain threshold level may need to be reached to augment the activation of caspase-3."

    "...Here, we conducted a clinical pilot study with doxycycline, to assess its effects in early breast cancer patients. Importantly, most biomarkers tested remained unchanged, with the exception of CD44, which was reduced on average by nearly 40%, in a period of only two weeks of treatment. Analysis of waterfall plot data revealed that in 8 out of 9 patients treated with doxycycline, CD44 levels were reduced between 17.65% and 66.67%. In contrast, only one patient showed a rise in CD44, by 15%. Two patients of the HER2(+) sub-type, also showed positivity for another stem cell marker, namely ALDH1. In these HER2(+) patients, ALDH1 levels were reduced by nearly 60% in one patient, while ALDH1 levels were reduced by 90% in the other patient, in response to doxycycline. Thus, oral doxycycline treatment effectively reduced the expression of two CSC markers, in early breast cancer patients. Our current in vivo results are consistent with recent findings in MCF7 and MDAMB-468 cells, two human breast cancer cell lines in culture, which showed significant reductions in the CD44(+)/CD24(-/low) CSC population, after treatment with doxycycline [17]. In addition, the expression levels of other “stemness” markers (Oct4, Sox2, Nanog and CD44) were also reduced by >50%, in response to doxycycline, as assessed by mRNA levels and independently confirmed by immuno-blot analysis [17]"


    https://medicalxpress.com/news/2018-10-antibiotic-effective-breast-cancer-clinical.html
    "...Scientists fighting cancer have carried out the first successful trial of the effects of the antibiotic Doxycycline on cancer recurrence in patients after surgery. Breast cancer patients were given the orally-administered antibiotic for 14 days before surgery and almost all saw a significant drop in cancer stem cells, the aggressive cells that drive tumour recurrence. Although small – restricted to 15 patients at the University Hospital in Pisa, Italy – the trial is highly significant, giving hope for the efficacy of cheap, over-the-counter drugs being used alongside standard treatments to prevent cancer regrowth. Doxycycline is one of the most commonly-prescribed antibiotics, effective in treating pneumonia, sinusitis, chlamydia, syphilis, cholera and Lyme disease."

    "...Professor Lisanti added: "Our ability to treat cancer can only be enhanced by utilising drugs that are not only cheap but also widely available. Since Doxycycline first became clinically available in 1967, its anti-cancer activity has been right under our nose, for more than 50 years."
     
  2. Fractality

    Fractality Member

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    So inhibiting mitochondrial biogenesis is now a good thing? Or is that just a mistaken cause for the benefit? I thought antibiotics are anti-cancer since they are anti-endotoxin.
     
  3. OP
    haidut

    haidut Member

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    This study and the previous one say it only happens in fast-proliferating cells, such as cancer. Normal cells are unaffected.
     
  4. Texon

    Texon Member

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    So 200 mgs per day is the dose to treat cancer? Does this dose in humans negate the anti inflammatory effects of the low dose 20-40 mgs protocol? How long could 200 mgs/day be taken before being in danger of serious secondary infections, I.e., yeast overgrowth, c. dificile etc.
     
  5. Texon

    Texon Member

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    Thanks by the way
     
  6. Texon

    Texon Member

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    I just found this. Looks like abstracts on every study ever done on doxycycline.

    subantimicrobial dose doxycycline: Topics by Science.gov
     
  7. managing

    managing Member

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    I had same question. I may ask Dr P.
    I thought this was a great question, so I asked Dr. Peat.

    "I think that’s safe; the person should avoid prolonged sun exposure, because it creates photosensitivity. Other safe and helpful things are acetazolamide, transdermal CO2, aspirin and lidocaine."
     
  8. aguilaroja

    aguilaroja Member

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    I am still thinking on the recent research ideas about cancer stem cells (CSCs), and angiogenic endothelial stem cells. My preliminary guess is these are local conditions of metabolic decline, causing corresponding cells to be more troublesome.

    Doxycycline induces apoptosis via ER stress selectively to cells with a cancer stem cell-like properties: importance of stem cell plasticity. - PubMed - NCBI
    "those CSC-like properties could reversibly change depending on the culture conditions, suggesting some kinds of CSCs have plasticity in tumor microenvironments. The sphere-forming cells (i.e. cancer stem-like cells) showed increased contact between mitochondria and mitochondrial associated-endoplasmic reticulum (ER) membranes (MAM). Mitochondrial targeting doxycycline induced activating transcription factor 4 (ATF4) mediated expression of ER stress response and led to p53-upregulated modulator of apoptosis (PUMA)-dependent apoptosis only in the cancer stem-like cells. We also found that doxycycline effectively suppressed the sphere formation in vitro and blocked CD44v9-expressing tumor growth in vivo."
    "monolayer cancer cells acquire CSC-like properties in a reversible manner."

    Cells with stemness features are generated from in vitro transformed human fibroblasts
    "Sphere cells engrafted into NSG mice more rapidly than adherent cells, but both cell populations were tumorigenic. These results indicate that, during transformation, human somatic cells can acquire CSC properties, confirming the high plasticity of tumor cells. However, CSC-like cells are not the only tumorigenic population in transformed cells, indicating that the CSC phenotype and tumorigenicity can be uncoupled."

    Doxycycline induces apoptosis via ER stress selectively to cells with a cancer stem cell-like properties: importance of stem cell plasticity
    "...under sphere-forming assay conditions, prostate cancer cells acquired CSC-like properties: promoted mitochondrial respiratory chain activity, expression of characteristic CSC markers and resistance to anticancer agents. Furthermore, those CSC-like properties could reversibly change depending on the culture conditions, suggesting some kinds of CSCs have plasticity in tumor microenvironments. The sphere-forming cells (i.e. cancer stem-like cells) showed increased contact between mitochondria and mitochondrial associated-endoplasmic reticulum (ER) membranes (MAM)."
    "...doxycycline effectively suppressed the sphere formation in vitro and blocked CD44v9-expressing tumor growth in vivo."
     
  9. aguilaroja

    aguilaroja Member

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    I view some Lisanti group work as paralleling William F. Koch's "electronic activation" of quinones. Dr. Peat has long noted the resemblance of the tetracyclines to quinones. That is, respiration, and oxidation, are necessary to go well in selected contexts. Mitochondrial dynamics are important in restorative function, but their disordered response may also worsen decline, like the cancer state.

    @haidut and others have extensively discussed quinone physiology in other threads, including references under the Panquinone and Kuinone discussions.

    (props to the Search site for organizing transcripts.)

    Mitochondrial fission as a driver of stemness in tumor cells: mDIVI1 inhibits mitochondrial function, cell migration and cancer stem cell (CSC) signalling
    "Disruption in mitochondrial dynamics plays a role in cancer. Therefore, proteins involved in regulating mitochondrial dynamics are potential targets for treatment. mDIVI1 is an inhibitor of the mitochondrial fission protein DRP1, which induces i) mitochondrial oxidative stress and ii) effectively reduces mitochondrial metabolism. We show here that mDIVI1 is able to inhibit 3D tumorsphere forming capacity, cell migration and stemness-related signalling in breast cancer cells, indicating that mDIVI1 can potentially be used for the therapeutic elimination of cancer stem cells (CSCs)."

    https://light.sx/transcript-358
    "There is a series that actually starts with vitamin K. It's a quinone structure that has been studied from about 1910 on as an anti-cancer, antiviral, energy-promoting, respiration- improving, anti-inflammatory, anti-fibrotic substance. For example, vitamin K is now used to strengthen bones, prevent osteoporosis and prevent calcification of arteries. That's a basic, vital function that does have tremendous range of functions. The emodin in cascara substance and the tetracycline is a four-ring substance, but they are all quinones that are intensified by adding the extra ring. So from vitamin K all the way up to tetracycline, it's a similar biological effect. It extreme sounds too good to be true, to be able to stimulate respiration, be anti-inflammatory, germicidal, anti-cancer and so on."

    Cascara, energy, cancer and the FDA's laxative abuse.
    William F. Koch, came to believe that cellular respiration involved free radicals, and experimented with the metabolic effects of many organic molecules, quinones of several kinds, that can form free radicals, looking for the most useful ones. "
    "Anthraquinones, because of the presence of several oxygen molecules, had low electron densities and were stable. The tetracyclines, with related structure, have some similar properties, and are antiinflammatory, as well as antibiotic."

    Ray Peat
    "Since I think Koch and Szent-Gyorgyi were right in believing that electronic activation is the most important feature of the living state, I think the very specific electronic interaction between vitamin E and ubiquinone must play an important role in the respiratory function of ubiquinone. Ubiquinone is known to be a part of the electron transport chain which can leak electrons, so this might be one of the ways in which vitamin E can prevent the formation of toxic free-radicals. If it can prevent the "leakage" of electrons, then this in itself would improve respiratory efficiency."
     
  10. tankasnowgod

    tankasnowgod Member

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    Very cool. I was thinking that antibiotics or antifungals combined with an iron reduction strategy (like phlebotomy or an iron chelator) would work especially well against cancer, maybe even injected into a tumor. But it looks as if that wouldn't even be necessary, as the oral route worked pretty well. I still don't know why a full iron panel isn't routine when ANY sort of cancer is suspected (other than the fact that Medical Mafia really does want people to suffer so they can sell their overpriced, ineffective treatments). Substances like IP6 and Lactoferrin could also be useful to improve effectiveness of antibiotics, and reports indicate that they seem to have anti cancer effects on their own.
     
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