Case Report Stage IV Endometrial Cancer: Good News from Marcos

During this holiday, I was very happy to read good news from Marcos (a visitor of this website) regarding the treatment outcomes of his wife, suffering from stage IV endometrial cancer.

Here is a short summary extracted from the e-mails Marcos sent to me:

Status before the treatment, before May 28:
–  My wife’s tumors are found in the vertebra L2, bone and soft tissues around them.Size 6x4x5 cm.Lungs: about 14 very small nodules,the largest 1.2 cm, another 0.9, rest less than 0.4 cm
–  The tumor that gives problems is that of the vertebra L2 by its growth toward the spinal canal
In the analysis of tumor tissue (similar to foundation one)the mutations found were PI3K, PTEN, ESR1, and CTNNB1
– The state of my wife is very good, can travel, walking, cycling, does not appear to have this terrible disease, her capacity for fight and her desire to live are incredible. Despite the setting of 5 vertebrae in his back from the last operation.

Results reported on July 26:
–  The intensive treatment is giving a good result. reduction of tumor markers of 240 to 80. Destruction of half of the 14 lung nodules, with size reduction of the two largest. reduction in size of the lesion of the vertebra L2.

The treatment:
Part of the implemented treatment schedule was shared by Marcos here. The idea of his approach was to build an extensive treatment approach in order to increase the chance of success of the chemotherapy. This was done together with a medical doctor and they succeeded. Next to the chemotherapy, the treatment schedule included a few other substances expected to exert a strong pressure on the cancer cells, including glycolisis inhibitors such as 2DG intravenous and Salinomycin intravenous, but also diet approaches such as 3 days fasting before chemotherapy and Ketogenic Diet.
Marcos allowed me to publish his complete treatment schedule, but in order to mantain the safety of this website, if anyone is interested in knowing the details I think it’s best that you contact Marcos.

In my opinion the key of this success were the following aspects:

  • Attitude: Positive behavior, belief and expectation of Marco’s wife is essential
  • Coherent intravenous treatment: Correct type, dose and timing of additional intravenous treatments next to chemo
  • Coherent support for core treatments: Fasting before chemo, keto diet, and several other drugs and supplements used

Disclaimer:

This site is not designed to and does not provide medical advice, professional diagnosis, opinion, treatment or services to you or to any other individual. Through this site and linkages to other sites, I provide general information for educational purposes only. The information provided in this site, or through linkages to other sites, is not a substitute for medical or professional care, and you should not use the information in place of a visit, call consultation or the advice of your physician or other healthcare provider. I am not liable or responsible for any advice, course of treatment, diagnosis or any other information, services or product you obtain through this site. This is just my own personal opinion regarding what we have learned on this road.

Please read an extended version of the Disclaimer here: https://www.cancertreatmentsresearch.com/?page_id=1794

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94 thoughts on “Case Report Stage IV Endometrial Cancer: Good News from Marcos

  1. Marcos- I am very happy to hear of your success, may your battle continue to be successful. Daniel, thank you for providing the resources to make successes possible!

  2. I am impressed by the good stuff that Marcos was able to buy for his wife, but I have a couple of observations, just to clarify the targets of the treatment, and maybe a couple of suggestions:
    – mutation PI3K means PI3K (part of the classic oncogenic pathway PI3K/AKT/mTOR) is aberrantly activated; the compounds listed there in theory can inhibit PI3K, even in synergetic combinations, but may not be enough, in comparison with a dedicated inhibitor; from my experience, Apigenin can worsen the blood formula, in my father’s case it didn’t help against the cancer; if you want to use Vit E, then use the Tocotrienol form, not the common Tocopherol, which may antagonize chemo;
    – liposomal Tetrandrine is a very good choice, Tetrandrine (new to me) inhibits many oncogenic signals, including beta-catenin, which is linked to the CTNNB1 mutation; Itraconazole may also inhibit beta-catenin; but there may be a problem, by inhibiting beta-catenin, the osteoclasts are stimulated; while Tetrandrine seems to act against osteoclasts, you might want to consider adding Zoledronic acid, against the spinal metastasis, if it is deemed osteolytic; there are a couple of articles about the use of Zoledronic acid against metastases of endometrial cancer; BTW, it would be nice to know, for other readers of the site, where to buy liposomal Tetrandrine from, and how expensive it is;
    – ESR1 is Estrogen receptor alpha, mutated means aberrantly activated, and Anastrazole should be inhibiting it;
    – PTEN tumor suppressor, just above PI3K, mutated means silenced, Tetranderine may upregulate it if it’s not silenced; if silenced, it may not help much; there are possible treatments against PTEN null (silenced) cancers;
    – the alternation of chemo and Salinomycin is a good choice, but I’m not sure about alternating 3BP and Salinomycin; maybe it would be worth trying simultaneous 3BP and Salinomycin, with lower doses; the reason is that Salinomycin is more cytotoxic under glucose starvation and hypoxia; I noticed that to counter the adverse effects from Salinomycin you use Amiodarone, I strongly suggest to switch to something else that would do the job; Amiodarone has a long half-life, and leads to the accumulation of several chemo agents, with potential lethal consequences;
    – instead of Avastin (Bevacizumab) you might want to consider Nintedanib; in various cancer trials it proved superior to Bevacizumab;

    1. Hi Ovidiu.
      Than you for your opinion,I very much appreciate your expert opinion.
      The problem you see in the administration of 3BP and SALINOMYCIN, is to increase the oxygenation for 3BP to be effective, may decrease the effectiveness of salinomycin?. Such as separarias in the period of 21 days?.Normally it is said that 3BP would serve to make effective salinomycin.That is to say there is that prime salinomycin with chemotherapy or with 3BP.The protocol of Daniel on 3BP and Salinomycin is the one that i have done.
      1.Nintedanib is not approved in Spain,your purchase in Sigma Aldrich is too expensive
      2.I don’t have access to protease inhibitors PI3K/AKT/mTOR pathway.DoYou know of one cheap and effective?.
      3Zoledronic acid. Don’t you think that its use could aggravate anemia which my wife presents almost constantly?.I’m scared of the osteonecrosis of the jaw. Could be used intermittently ,a month yes and a month no?.
      4.Already taking anastrozole two years ago I did not mention it in the protocol.
      5.Amiodarone will be deleted.
      6.Tetrandrine purchased powder to 98% purity in naturemmfg.com and mixed with high quality Empty liposomes of Enoch Solution.
      7.Please send me the studies of the use of zoledronic acid in endometrial cancer?.
      Please any other suggestions or possible treatment let me know.Your help is critical

      1. @marcos: 3BP has a short half-life of only 77 minutes, so applying Salinomycin the next day might be too late to benefit from the synergy with 3BP;
        The antitumor agent 3-bromopyruvate has a short half-life at physiological conditions. PMID: 25152397
        With 3BP the problem is that, besides the short half life, by now (2+ months of treatment) the cancer may have downregulated MCT1…

        1. Nintedanib might be approved for pulmonary fibrosis, but not for cancer, this may change, so keep an eye on it;
        2. new synthetic inhibitors of PI3K/Akt/mTOR (not necessarily protease inhibitors like Nelfinavir or Ritonavir), tend to activate other survival pathways when used for some time; I still have to do more reading to understand the problem, so I can’t recommend one now; you are already using Metformin (sometimes only mTORC1 inhibitor, but in endometrial cancer full PI3K/Akt/mTOR inhibitor) and Tetrandrine for this purpose;
        Metformin is associated with reduced cell proliferation in human endometrial cancer by inbibiting PI3K/AKT/mTOR signaling. PMID: 29182407
        Involvement of PI3K/AKT/GSK3beta pathway in tetrandrine-induced G1 arrest and apoptosis. PMID: 18437054
        You might want to replace Resveratrol with Pterostilbene, but you’ll have to import it from the USA, it’s scarce and more expensive in the EU;
        Pterostilbene, a natural phenolic compound, synergizes the antineoplastic effects of megestrol acetate in endometrial cancer. PMID: 28986550
        3. About ZOL, I don’t know, I suppose it might worsen anemia; you could check for low vitamin B12 levels, because of high dose Metformin, as a cause for anemia; osteonecrosis of the jaw is a more frequent for those with lots of teeth problems;
        4. I saw Anastrazole listed by you, and is probably doing its job;
        5. Pharmacokinetic interaction between taxanes and amiodarone leading to severe toxicity. PMID: 27868228
        6. I tried searching with Google for naturemmfg.com and Enoch Solution Liposomes, but found nothing; so after some tweaking, came up with http://www.naturemfg.com/products/plant-extract/tetrandrine/ and http://www.enocpharma.com/?lang=en
        7. An Unusual Solitary Metatarsal Metastasis from an Endometrioid Endometrial Adenocarcinoma. PMID: 26193447

        Last, you might want to try Telmisartan, a cheap tumor stroma disrupting agent and a PI3K/Akt inhibitor, it synergizes with liposomal Docetaxel against a lung cancer Kras mutant in a mouse model. It may also synergize with the liposomal Tetrandrine, if Metformin hasn’t already disrupted tumoral stroma;
        Tumor stromal disrupting agent enhances the anticancer efficacy of docetaxel loaded PEGylated liposomes in lung cancer. PMID: 27171485

        1. Hi Ovidiu.
          I will try to apply salinomycin half an hour after 3BP,and to prevent the closure of the MCT1 line with paracetamol,EWOT etc.
          Can i replace itracozanol by a statin as lovastatin that increases the expression of Pten.
          In fact the two links to the pages of sale of tetrandrine and Empty liposomes are correct.
          I can access easily pterostibeno.
          Telmisartan will work just as well without the addition of doxorubicin?.
          I do not think it is wise to apply together lovastatin and zoledronic acid,according to your experience which it would be more appropriate?.
          I have access to celastrol known inhibitor of HSP90, we use together with Phlorizin to enhance the effects of hyperthermia that we are going to apply soon. What do you think?..
          Thank you for your opinions

          1. @marcos: Daniel made his point, that 3BP can inhibit glycolysis for a longer time than suggested by the short half-life, and that’s why doctors use the alternate day regimen, so better keep the current schedule;
            Telmisartan was suggested because the tumoral stroma could impede the delivery of many chemos, including the liposomes loaded with Tetrandrine;
            About the simultaneous application of ZOL and a statin, I wish I had a sure answer… there are pros and cons…
            A HSP90 inhibitor should be synergetic with hyperthermia, but the response to HSP90 inhibition is upregulation of HSP70;

            Last, do you have a way to check that the stuff you bought is really what you paid for, and that it was stored and transported properly, so it is still >90% effective when used by the patient?

            1. Hi Ovidiu.
              With regard to 3BP ,salinomycin and phlorizin i have total confidence were bought in SA. With regard to tetrandrine I bought at other times to this provider and accompanied by a certificate which includes storage temperatures that do not exceed 5 degrees.

            2. Hello Marcos.
              I’m very interested to use tetrandrin. I’m looking it for my dad since some time and I haven’t find a supplier. I have checked the web site where you bought it : thank you very much for this advice, I will write to them.
              But before, I want to ask you about the dose you use, when in the day (at what time), during or after meals…
              I have tried to understand how you encapsulate it in lyposomes, but I can’t understan: please can you explain me this step ? It’s mandatory or it can be used like this (even if it would be less effective)?
              Thank you in advance for this valuable information and good luck to you. I hope with all my heart that your wife’s condition will improve.
              Best regards,
              Dess

        2. Ovidiu, there is a difference between half-life of a drug and it’s intracellular action. Once inside the cancer cell, 3BP will act for several days. I’ve seen that on CT scan. So in my view, there is no problem with using other drugs the next day when targeting synergy between 3BP and the second drug. It may even be better to use the second day and not first in order to give time to some process in the cell to take place. That is why others such as US doctors using the combo of Sal and 3BP and reporting good results, used the combo in alternative days. Instead, I would better combine 3BP with 2DG during the same day and Sal and 2DG the other day. Kind regards, Daniel

  3. Hi guys!

    I have kept in touch with Daniel for months and my friend Marcos. My lack of time has prevented me from participating in the forum.
    My mother is having new growth of glioblastoma (diagnosed in 2015)
    We are using the same 2DG metronomic protocol as Marcos. Currently it seems that everything is stable.

    I will share our treatment line. Any suggestions will be appreciated:

    – Nanothermia 2 times a week at 120w
    – 2DG Metronomic once a week at 3grs. (3ml / h.) Combined one day with nanothermia
    – 80mg temozolamide combined the two days of 2DG
    – 600 mg of ribavirin every day
    – 200 mg celecoxib every day
    -1700 mg metformin every day
    – 10 ml empty liposomes all days (20ml in nanothermia days)
    – 100mg canagliflozin combined 1 day with nanothermia
    (distanced 48 hours from 2DG)

    I am studying taurolidine …. and a peptide vaccine directed to the PTEN mutation

    Daniel suggested me:

    – Besentabs but they can also help reduce the acidity around the tumor and that may be good for glyoblastoma that are highly acidic. Just that we need to clarify the impact on the absorption of temozolamide.

    – Add another cycle of metronomic 2dg in the week

    -Add another mitochondria inhibitor next to Metformin like Atovaquone

    -Add an MCT1-MCT4 inhibitor like Ibuprofen if possible, to reduce the lactic acid export that may result following the use of Metformin

    -Use other glycolysis inhibitors during the days my mom is not on 2DG. One that is accessible is Vitamin C in high dose, but you can try to search for other glycolysis inhibitors.
    If not, maybe you extended the use of canagliflozin to a time closer to 2DG admin but not overlapping that ……………………….. ……….

    I hope to participate in the forum!

    Best regards to all

    1. Hi Manuel,

      Thank you so much for taking the time to write this comment. I understand how difficult it is as you have so much to take care of, including taking care of your dear mom and working full time as the same time. So please use your time for that instead of spending time discussing on this website. What i only ask from you and others with whom I communicate by e-mail is that when there are general questions (not personal), please ask them on this website from time to time so that others can benefit from the related discussion. This is because lately I spend most of my time answering e-mails and calls, and as a result I have no more time to reflect the learnings here on the website so that others benefit.

      I would also like to add again that all the ideas and knowledge I share with you or others (including that going through private communications) goes with the Disclaimer on this website. Everyone has to use that as input only while discussing with their medical doctor the best approach in line with patient’s status, and should not replace the medical advice.

      Beyond that, I am happy to hear about the fact that your mom is doing better and she is now in a stable situation since you implemented approaches to support chemo, which as I understood was not anymore effective prior to that. I very much think 2DG metronomic plays a major role in that outcome.
      Indeed, I think Taurolidine is a treatment approach that is relevant for glioblastoma, but it requires an intensive treatment.
      Increasing slightly the frequency of 2DG metro may be an easier approach that could help.

      Kind regards,
      Daniel

    2. Hi Manuone, my father-in-law is a long term GBM survivor, for almost 16 years. In his case Tamoxifen + CCNU worked (after regrowth during temodar). He’d also take Melatonin(15mg) and antineoplastons orally. This supplement isn’t for sale any longer but phenylbutyrate is basically the same thing. Royal Jelly has some phenylbutyrate btw.

      1. Thanks Johan! Very helpful! I am glad to hear your father in law is well following these combos! Very good reminder regarding Phenylbutyrate which I also like it. It’s very expensive. A cheaper option could be from China but its challenging for most to find a trusted source. Do you have a specific source that its both fair quality and cheaper?

      2. Thanks Johan, for your response via the e-mail. I do not know why your comment is not published. I checked the spam and your post is not there. So here I will post your response and I hope in the future you will be able to post your comments (maybe you need to login first):

        “Hello Daniel, I’ve been trying to post a response on the forum but can’t get it to go through. So I’m sending it here. Have a great day! J

        Hi Daniel, here’s a good source to buy S. Phenylbutyrate: http://www.spb11.com/order/
        Note this is for “research only”.

        An alternative is to have the drug prescribed off-label, for Urea Cycle disorder.
        Some health insurance companies consider the drug necessary for treatment of malignant glioma, for example Aetna.
        http://www.aetna.com/cpb/medical/data/200_299/0240.html

      3. Hi Johan! Thanks for your comment. I find interesting tamoxifen adjuvant to temodal or lomustine with an “acceptable” toxicity …..
        Glutamine´s inhibition with sodium phenylbutyrate seems to me very important and would be synergistic to 2DG metronomic
        Does the natural glucosamine supplement perform the same function?

        https://www.mistrys.co.uk/ammonaps-tablets-500mg-250-pack-94273.html <<<<<<<<<<<< buy online sodium phenylbutyrate

        Could you tell me the doses your father-in-law use please?

          1. Hi Johan – Not sure if what I posted below was as a reply to you, so I’ll repeat.

            Can you clarify the dosing of antineoplaston for your dad? Would you guess a similar dosing of sodium phenylbutyrate would have comparable effects? For example, if your father in law could not access antineoplaston, what dose of sodium phenylbutyrate would you expect he would use?

            Thank you!

            Jessica

            1. Hi Jessica,

              A10 antineoplastons is a 4:1 mixture of phenylacetylglutamine(PG) and iso-phenylacetylglutamine(Iso-PG)

              Sodium Phenylbutyrate(SP) is metabolized to phenylacetylglutamine, however I don’t know how much PG you get
              from one gram of SP.

              My father in law took 18 A10 pills a day, which amounts to a dose of a 3.15 gr/day of A10. There was never a
              need to reassess the dose because after one month an MRI showed a small decrease in the tumor. So he just
              continued taking A10, with the chemo(CCNU), tamoxifen(40mg/day) and melatonin(15mg/day), until the gbm was
              gone (6 months).

              My guess is that 4 to 6 grams of SP could be a good (starting)dose.

              A recent study found that in Glioblastoma “inhibition of caspase-3 causes the microglia to stimulate the tumour
              cells instead of attacking them”. (Nature Immunology, September 2016 DOI: 10.1038/ni.3545).

              Interestingly, SP is a Caspase 3 activator.

              Since I mentioned Melatonin I have to add that Mel can inhibit caspase 3 activity. Meaning melatonin could
              potentially make matters worse. In spite of this, several studies show the benefits of using melatonin in treatment
              of gbm. One recent study suggests melatonin alters gbm stem cells (Chen et al. (2016) Melatonin Inhibits Tumorigenicity of Glioblastoma Stem-like Cells via the AKT-EZH2-STAT3 Signaling Axis).

              Hence the importance of combination therapies, and chosing the right combos. The result of using both an inhibitor
              and activator simultaneously can be either zero, inhibition or activation. Some drugs or natural compounds may be
              beneficial in one way and detrimental in another way. If you can cancel out the negative by combining with another
              compound, that could potentially make all the difference.

              All the best!

  4. Hi Johan – I’ll post my question here at the end as well, since it flows better. Can you clarify the dosing of antineoplaston for your dad? Would you guess that a similar dose of sodium phenylbutyrate would have comparable effects? For example, if your father in law could not access antineoplaston, what dose of sodium phenylbutyrate would you expect he would use?

    1. Hi Marcos,

      I just replied to your e-mail with some feedback and questions on the new protocol. If I find time I will also add them here on the website. Great to hear that your wife continues to see tumour reduction as you wrote in the e-mail. After you answer the questions, I will try to reply asap – if I can today – during the next days will be more challenging as I will be travelling for several days.

      Kind regards,
      Daniel

  5. marcos this is remarkable!
    You have been able to incorporate many of the ideas that have been discussed on this forum over the last few months.

    The first thing that caught my attention was how you have been able to adapt your original treatment plan. Over the last few months there has been an emergent awakening on the forum of what can actually be helpful in treating cancer. I think that D is totally correct when he says that this really belongs to no individual person though it is a result of a collective group effort.

    Your latest plan clearly improves on your first effort. You have been able to learn from the postings and incorporate these ideas into your plan. What I can clearly see is the idea of the metabolic approach, metronomics, and chaos. It has taken us quite some time to appreciate these concepts, so it is highly encouraging to see that you have finally been able to put it all together.

    Starting with the metabolic perspective, it is impressive to see how many glycolytic/ OXPHOS inhibitors that you have worked into the plan. Vitamin C, methylglyoxal, 3-BP, 2-DG, salinomycin, tocotrienol … Have I missed any? This is very impressive! Developing a comfort level with a wide range of them prevents resistance escape. With such a broad net of protection, one could certainly wonder how it would be even possible for cancer to actually find a path around such a formidable blockade.

    The integrative health concept of polypharmacy is proven to be successful strategy. It is quite surprising to see how often mainstream medicine will announce a powerful mono-therapy only for resistance to emerge. Yet, with metabolics there is a very constricted range of paths of resistance available to cancer. Closing them all off gives a very encouraging feeling.

    Metronomics is also highly visible in your latest plan; while it was not clearly visible in your first plan. It is great to see this front and center! Our forum apparently is one of the first to formally and explicitly talk in terms of metabolic metronomic dosing. We do have the Vitamin C trials from Scotland in the 1970s as a point of reference. However, for whatever reason, metabolic metronomics is from what I can tell nearly absent from the scientific literature. When I have read about metronomic dosing it is almost exclusively in reference to metronomic chemo. The only reference I have found is https://www.ncbi.nlm.nih.gov/pubmed/?term=30170097

    In your updated plan you mention metronomic 2-DG, metronomic Vitamin C and metronomic Methylglyoxal. It seems that you might even be open to dual metronomic vitamin C and methylglyoxal. This is such a tremendous conceptual step forward that this forum has innovated. D has noted in the past that most clinics would tend to stay away from such a dosing approach not because it does not make sense, but more that it would not make business sense. More chair time is less cash flow. When you do it yourself, that consideration completely disappears; all you want is a treatment that is effective.

    I like how you added in bolus dosing as well as metronomic dosing. So perhaps you could do a 100 gram IV vitamin C over about 2 hours and then perhaps move down to 10 grams per hour for another 5 hours. There are numerous variations that you could try.
    Earlier on the thread I posted the formula for what the vitamin C concentration would be using different dosing. It might be very helpful to pull out this formula and see what concentration would result by changing dosing variables.

    Clearly I really liked the Methylgloxal and Vitamin C combo ( I am glad that you remembered about adding in the creatine for cardiac protection). Perhaps you could contact the Indian researchers to see what their opinion of the plan might be. Combining a glycolytic and a selective OXPHOS inhibitor appears to be a strong choice, especially considering that human clinical research has confirmed this combo, even when it was used in what might be suboptimal dosing.

    Finally on top of metabolics and metronomics , you have added chaos! Basically what we are working with now is a chaotic metabolic metronomic dosing approach. This yet another incorporation of the ideas of the forum into a coherent treatment plan.
    Congratulations! I am glad that you were able to find my post and find a way to add it to the plan. I think that the color scheme that you have for the plan is almost the only way to handle this new feature.

    At first when I saw others with what I thought were overly convoluted treatments I thought I should post that it would be best to make things simpler. I like having all my paperclips in a straight line! It was only when I saw the video that lullabyman posted that I realized that simple treatments are exactly what cancer finds easy to work around. What you want is to constantly adding complexity to the plan. This probably will be an ongoing feature now of further treatment plans that you post to the forum: a constant introduction of new treatments, with variations of the existing treatments in terms of dosing, combinations and scheduling. By definition, those cancer cells that are still present are the ones that already survived the previous treatment. Why not present a new challenge to these surviving cells?

    Your current treatment plan is a great update! It is not entirely clear where the future might guide us to for your next update, though here are a few suggestions:

    1. One consideration could be to strengthen the combinations. Taking the research that has already found synergism in in vitro and or in vivo research would be a great move. While you likely have very well considered reasons for all your combinations in your plan, this observation could be of help to others who are also thinking of using a similar treatment protocol. The vitamin C, Methylgloxal, and creatine combo is very solid and clinically established. Perhaps other combos that focused on the paired Glycolysis and OXPHOS inhibition could be added (check d’s list of OXPHOS and glycolysis inhibitors). Here is a rough list that I have been compiling of combinations that have been noted in the research. Of course one would want to carefully review them and search for yet others that might be of help. I recently found combinations of alpha-tocopherol and tocotrienol had was synergistic as well as a combination of tocotrienol and statins that also magnified effectiveness. Enhancing effectiveness while increasing safety seems like a sure winner. The one thing obviously to be aware of is not to load up so many treatments at the same time that they wind up cancelling each other out. Possibly only 2 or 3 treatments at a given time should be understood to be the limit. Adding in DCA and Omeprazole (#5 below) would add yet another dimension of complexity to the treatment and might be a good choice.

    1. DCA and Salinomycin 30531808 in vitro 15 milliM DCa, 0.25 microM Sal increase dose?
    Not good dosing. Human dosing only gives .4 milliM DCA. Could try nanoparticles or other analogs.
    2. DCA and Propranolol PMID:30513596
    3. DCA and Metformin 27449090
    4. DCA and Curcumin 30396945
    5. DCA and Omeprazole 22740984

    20. Vitamin C and Auranofin PMID:30462268
    21. Vitamin C and Mendione PMID:15004519
    22. Vitamin C and Doxycycline PMID:28978032
    23. Vitamin C and lipoic acid and Vitamin K3 PMID:11384106
    24. Potassium Ascorbate with Ribose PMID:29290903
    25. Sub-Apoptotic Vitamin C, Alpha-tocopheryl succinate (aTOS), and vitamin K3 PMID:26427039
    25a. 15 combined with KRN7000
    26. Vitamin C and fenofibrate https://jeffreydachmd.com/fenofibrate-anti-cancer-drug/

    30. 2-DG and 3-BP 23076497
    31. 2-DG and N-dodecylimidazole (NDI) 27587392
    32. 2-DG and metformin 27825799
    33. 2-DG and Berberine 27796611 23872355
    34. 2-DG (metro) and fenofibrate 27183907
    35. 2-DG mito-CP 23872912

    40. Methylglyxoxal Nano 24368179

    50. Honokiol Nano

    70. Delta Tocotrienol 29769046 29330434 Nano 28972460 Nano 27993600 Nano 25622049
    Nano 24813390 Nano 22271424 Nano 22826870 Nano 20189780 Nano 20823492 Nano 20123009
    MCT-1 26328490
    IV Tocotrienol?

    2. Trying to find a way to introduce nanoformulations would almost certainly greatly intensify treatment power. Many of these are highly safe chemicals such as honokiol etc. that can become much much more potent in a nanoparticle form. Chitosan is awidely used coating agent that is considered to be very safe.

    We will no doubt find yet more innovations and insights in the months ahead, though perhaps for the time being we will need to consolidate what we have already learned.

    I hope my comments are useful to you.
    Best Wishes, Jcancom

  6. {I have trouble with this as a longer post, so I will break it up into smaller posts.}

    marcos this is remarkable!
    You have been able to incorporate many of the ideas that have been discussed on this forum over the last few months.

    The first thing that caught my attention was how you have been able to adapt your original treatment plan: You are learning! Cancer is relentlessly learning, if we want to be successful we also need to adapt. Over the last few months there has been an emergent awakening on the forum of what can actually be helpful in treating cancer. I think that D is totally correct when he says that this really belongs to no individual person though it is a result of a collective group effort.

    Your latest plan clearly improves on your first effort. You have been able to learn from the postings and incorporate these ideas into your plan. What I can clearly see is the idea of the metabolic approach, metronomics, and chaos. It has taken us quite some time to appreciate these concepts, so it is highly encouraging to see that you have finally been able to put it all together.

    Starting with the metabolic perspective, it is impressive to see how many glycolytic/ OXPHOS inhibitors that you have worked into the plan. Vitamin C, methylglyoxal, 3-BP, 2-DG, salinomycin, tocotrienol … Have I missed any? This is very impressive! Developing a comfort level with a wide range of them prevents resistance escape. With such a broad net of protection, one could certainly wonder how it would be even possible for cancer to actually find a path around such a formidable blockade.

  7. The integrative health concept of polypharmacy is proven to be successful strategy. It is quite surprising to see how often mainstream medicine will announce a powerful mono-therapy only for resistance to emerge. Yet, with metabolics there is a very constricted range of paths of resistance available to cancer. Closing them all off gives a very encouraging feeling.

    Metronomics is also highly visible in your latest plan; while it was not clearly visible in your first plan. It is great to see this front and center! Our forum apparently is one of the first to formally and explicitly talk in terms of metabolic metronomic dosing. We do have the Vitamin C trials from Scotland in the 1970s as a point of reference. However, for whatever reason, metabolic metronomics is from what I can tell nearly absent from the scientific literature. When I have read about metronomic dosing it is almost exclusively in reference to metronomic chemo. The only reference I have found is https://www.ncbi.nlm.nih.gov/pubmed/?term=30170097

    In your updated plan you mention metronomic 2-DG, metronomic Vitamin C and metronomic Methylglyoxal. It seems that you might even be open to dual metronomic vitamin C and methylglyoxal. This is such a tremendous conceptual step forward that this forum has innovated. D has noted in the past that most clinics would tend to stay away from such a dosing approach not because it does not make sense, but more that it would not make business sense. More chair time is less cash flow. When you do it yourself, that consideration completely disappears; all you want is a treatment that is effective.

    However, I am glad that you have steered clear of metronomic 3-BP. 3-BP is an extremely powerful treatment that needs to be given with some caution. Metronomic dosing with clearly safe natural medicines such as Vitamin C etc. is a great strategy. Interestingly, vitamin C appears to upregulate MCT-1 through ROS generation. So, continuing to dose with 3-BP is a rational strategy as it would be effective against this subset of cancer cells.

    I like how you added in bolus as well as metronomic dosing. Perhaps you could do a 100 gram IV vitamin C over about 2 hours and then perhaps move down to 10 grams per hour for another 5 hours and then perhaps rotate into metronomic 2-DG or tocotrienol. Lullabyman introduced a very point when noting that it is duration and not necessarily dose that is important with metabolic approaches. There are numerous variations that you could try. Earlier on the thread I posted the formula for what the vitamin C concentration would be using different dosing. It might be very helpful to pull out this formula and see what concentration would result by changing dosing variables.

  8. I especially admire the Methylgloxal and Vitamin C combo that you have added ( I am glad that you remembered about adding in the creatine for cardiac protection). This is based on solid science and it apparently confirms our intuition about Glycolysis + OXPHOS inhibition. You might consider contacting the Indian researchers to hear their opinion of your plan.

    Finally on top of metabolics and metronomics , you have added chaos and complexity! Basically what we are working with now is a chaotic metabolic metronomic dosing approach. This is yet another incorporation of the ideas of the forum into a coherent treatment plan. Congratulations! I am glad that you were able to find my post and find a way to add it to the plan. The color scheme that you have added greatly helps. In future updates you might need to specify all the treatments as a color and then just show us a color scheme.

    At first when I saw others with what I thought were overly convoluted treatments, I thought that order should be brought to their plans. I like having all my paperclips in a straight line! It was only when I clicked the link to the video that Lullabyman posted that I understood that simple treatments are exactly what cancer finds easy to work around. Treatment complexity results in success (eg. HIV, antibacterial treatment). This complexification probably will be an ongoing feature now of further treatment plans that you post to the forum: a constant introduction of new treatments, with variations of the existing treatments in terms of dosing, combinations and scheduling. By definition, those cancer cells that are still present are the ones that already survived the previous treatment. Why not present a new challenge to these surviving cells?

  9. Your current treatment plan is a great update! It is not entirely clear where the future might guide us to for your next update, though here are a few suggestions:

    1. One consideration is to consult existing literature to strengthen the combinations. Taking the research that has already found synergism in in vitro and or in vivo research would be a great move. While you likely have very well considered reasons for all your combinations in your plan, this observation could be of help to others who are also thinking of using a similar treatment protocol. The vitamin C, Methylgloxal, and creatine combo is very solid and clinically established. Perhaps other combos that focused on the paired Glycolysis and OXPHOS inhibition could be added (check D’s list of OXPHOS and glycolysis inhibitors).

    Here is a rough list that I have been compiling of combinations that have been noted in the research. Of course one would want to carefully review them and search for yet others that might be of help. I recently found combinations of alpha-tocopherol and tocotrienol had was synergistic as well as a combination of tocotrienol and statins that also magnified effectiveness. Enhancing effectiveness while increasing safety is a sure winner. The one thing obviously to be aware of is not to load up so many treatments at the same time that they wind up cancelling each other out. Adding in DCA and Omeprazole {a proton pump inhibitor} (#5 below) would add yet another dimension of complexity to the treatment and might be worth considering. The list is not exhaustive and is meant more as a starting point to investigate potential combinations available. Many of the metabolics inhibitors that we focus on are included in the list below. As D has mentioned some caution is warranted when contemplating these combos as the synergy noted for 2-DG and 3-BP (#30) could risk TLS. This risk likely would be magnified when using 2-DG metronomically.

  10. 1. DCA and Salinomycin 30531808 in vitro 15 milliM DCa, 0.25 microM Sal increase dose? Human dosing only gives .4 milliM DCA.
    2. DCA and Propranolol PMID:30513596
    3. DCA and Metformin 27449090
    4. DCA and Curcumin 30396945
    5. DCA and Omeprazole 22740984

  11. {I’ll try to post the rest of the list when the software allows me to.}

    2. Trying to find a way to introduce nanoformulations would almost certainly greatly intensify treatment power. Many of these are highly safe chemicals such as honokiol etc. that can become much much more potent in a nanoparticle form. Chitosan is awidely used coating agent that is considered to be very safe.

    We will no doubt find yet more innovations and insights in the months ahead, though perhaps for the time being we will need to consolidate what we have already learned.

    I hope my comments are useful to you.
    Best Wishes, Jcancom

  12. Thank you very much J for your contributions and reflections
    I also benefit from these reflections
    I have very clear metronomic metabolic approaches:
    -2 dg metronomic + cytotoxic chemo (tmz or lomustine)
    -salinomycin iv
    -Vitamin c iv metronomic 1.5 gr / h in 33 hours

    The theory of metabolic chaos alternating treatments seems to me excellent. It would even allow me to use more therapies and drugs by reducing drug interactions.
    I will make 2 or 3 treatment plans and I will share them with you.
    I think very hard to fight GBM … we do not surrender easily

  13. Manuone, we can all learn from the treatment plan proposed by Marcos.

    He has done a very admirable job in integrating the knowledge of the forum into a coherent plan. His approach is very much in line with my current understanding of what a metabolic plan should look like.

    He took a metabolic treatment (e.g. vitamin C) and then considered the different treatment dimensions that could be manipulated. For instance, he considered time, dose, and combinations. Specifically, he identified a 100 g rapid high dose strategy, while also being open to extending this out metronomically. Dosing up towards 50 mM provides the opportunity to stress a wide range of cancer cells. With a safe treatment such as vitamin C, it is very wise to take full advantage of the treatment potential available (including the recognition that high dosing is feasible).

    We talked on the vitamin C thread of how powerful such a dosing approach likely would be. Duration becomes a powerful tool against cancer. Possibly so much so that we would need to be careful about TLS. Considering this, I think that Marcos has it right: at this time probably think in terms of vitamin C dosing for possibly 2 days, and then move onto some other metabolic approach. As he became more comfortable with metronomic vitamin C, perhaps he could work up towards a full 2 week metronomic vitamin C protocol as was done in Scotland. I am also concerned that intense vitamin C treatment might condition the tumor environment for rapid growth ( through ROS generation leading to MCT-1 upregulation etc.), though with a combined metabolic approach other treatments (e.g., 3-BP ) could then counteract such eventualities.

    Marcos also identified strong vitamin C combinations: Methylgloxal and alpha lipoic acid/ vitamin K3. Through time even more of these well researched combos could be added into the mix. Yet, this is a very reasonable starting point. By carefully contemplating how each of the treatments can be used to maximal effect, Marcos has created a very impressive plan.

    He was then able to add in several additional metronomic metabolics treatments off the same template which could continue to provide yet more energy stress to the cancer. I think this is a very well considered plan and might almost be too powerful. Perhaps adding in more treatment power on top of the 2-DG will need to be done somewhat gradually. Having more frequent labs (possibly daily or more often) during these treatments would be reasonable. There might also be a home monitor that could be bought that could that measurements even more often. With this level of intensity of therapeutic pressure (in particular, continuous metabolic stress) one can understand why there has been such a notable amount of success this year on the forum.

    Manuone, there is a great deal to learn form the plan constructed by Marcos. Methylgloxal is a specific OXPHOS inhibitor and has been shown in clinical studies to be a good combiner with vitamin C (also add in creatine). Putting a glycolytic and OXPHOS inhibitor together metabolically could produce very powerful results. One wants to look out for these strong combinations. MG and vitamin C are a strong combo even when they are given non-metronomically!

    Salinomycin is another very strong metabolic treatment, so metronomic dosing likely should be avoided.
    Of note, the Dayspring Cancer Clinic website found that 3-BP can cause edema problems with brain tumors, so it would be best to steer clear of it for GBM.

    1. Dear J,

      I’m enthusiastic about Marco’s plan but every patient is a world and the clinical conditions and the type of tumor make the difference.
      -My mother shows a special sensitivity to vitamin C iv ….. I think it does not work well in her case. Yesterday we tried the metronomic dosage and she felt especially bad. After 16 hours the infusion it was stopped. It will take me time and blood tests to find a possible cause.

      -On the other hand MG is not recommended at this time like 3BP and the potential risk of cerebral edema ….

      -DCA iv is another good option in the cocktail but my mother does not tolerate well with skin reactions

      – I can consider alpha lipoic acid iv it can work similar to DCA

      The moment plan looks like this:

      INFUSIONS

      -2dg metronomic 3 grs x 2 days
      -salynomycin iv once a week
      -vitamina c iv ????????
      -alpha lipoic acid iv ?????

      DRUGS

      –lomustine 40mgx3 days 1 time every 6 weeks or follow with TMZ
      – Liposomal tetrandine
      -metformin
      -celebrex
      -acetozolamide
      -simvastatin
      -tamoxyphene
      -fenbendazole
      -mebendazole
      -thalidomide
      -sodium phenylbutyrate
      -mebendazole + fenbendazole
      -Omega 3
      -vitamin d3
      -complex vitamins b
      -80mg aspirin …
       
      I would like to receive opinions about ERLOTINIB. Johan recommended me this based on this study:
      https://www.curetoday.com/articles/looking-ahead-combination-offers-new-hope-for-glioblastoma
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018931/

      Erlotinib has not been highly effective in monotherapy (as nothing until now). It seems toxic to the skin and diarrhea … I can cycle with thalidomide looking for synergy. It seems directed to EGFR but it has been shown that its action is independent of the mutation. This worried me because gliosarcoma unlike glioblastoma does not usually express EGFR

      kind regards

        1. Thanks for the recommendation Daniel,

          You are absolutely right and I prefer to be cautious although alpha lipoic iv would be similar to DCA inhibiting glycolysis.
          At the moment I will only use 2dg metronomic and salinomycin iv

          Kind regards

      1. Hi Manuel,

        I notice you haven’t decided on CCNU or to continue with TMZ.

        Note there’s the option of doing TMZ/CCNU in combination, a phase 3 trial
        of this combination has shown good results in terms of overal survival.
        Median reported survival was 46.9 months for CCNU + TMZ versus 30.4 months
        for TMZ alone!

        Dosing in this trial was:

        Day 1: CCNU 100 mg/m2
        Day 2-6: TMZ 100 mg/m2
        during 6 week (42 day) cycles

        Here’s a study(in vitro) on combined TMZ/CCNU, suggesting synergistic activity of this
        combination:

        “Acquired temozolomide resistance in human glioblastoma cell line U251 is caused
        by mismatch repair deficiency and can be overcome by lomustine.”
        https://www.ncbi.nlm.nih.gov/m/pubmed/28825189/

        Phase II trials of lomustine/tmz:

        1) https://www.ncbi.nlm.nih.gov/pubmed/27006176
        2) http://ascopubs.org/doi/full/10.1200/jco.2006.06.9104

        Regards,
        Johan

        1. Thanks Johan!

          I am considering it but I am concerned about toxicity and not being able to use lomustine in a metronomic way. Lomustine is only used once every 6 weeks.
          The risk of leukopenia thrombocytopenia, sepsis, anemia … will be elevated along with other drugs.
          My mother is in palliative care and does not receive active medical monitoring for this reason I will have to pay for private analytics to monitor all the parameters

          regards

      2. Manuone,

        You would want to follow the Riordan protocol for vitamin C treatment, if possible . They have had a vast experience in vitamin C treatment. So, you should carefully read through their protocol and notice their comments about treatment safety.

        For example,
        “2. Tumor necrosis or tumor lysis syndrome has been reported in one patient after high-dose IVC (Campbell & Jack,1979).
        For this reason, the protocol always begins with a small 15 gram dose.”
        https://www.cancertreatmentsresearch.com/good-news-from-marcos/#comment-8066

        As a general guideline you would never want to start up any treatment aggressively.
        With metronomic dosing the plan would actually be more to provide ongoing treatments that are well tolerated and could potentially be given essentially around the clock. So, metronomic would be more of a gentle style of treatment that is constantly pressing the cancer mass. Jess gradually increased 2-DG as it was seen to be well tolerated.

        From the chart posted on Jess’s page, we can see what happens when aggressive chemotherapy treatment is interrupted to give the patient time to recover from the treatment: The tumor growth almost goes vertical! Patients basically become addicted to chemo for their survival! While it might appear as though the chemo is working, as soon as treatment stops or resistance emerges, the tumor growth can become overwhelming.
        https://www.cancertreatmentsresearch.com/case-report-stage-iv-pancreatic-cancer-good-news-from-jess/

        {This is also noted in the video that was posted about chlorine dioxide recently. You will need to think about this one by yourself, though it does appear promising. Notice that 2 GBM patients have reportedly benefited. However, this treatment is apparently illegal in several nations https://www.cancertreatmentsresearch.com/community/forum-to-discuss-treatment-protocols-and-drugsupplement-cocktail/chlorine-dioxide-metabolic-treatment/#post-817 }

        I am unsure what to suggest to you, as GBM truly is a world to itself as you expressed it. marcos’s plan really leapt off the page for me and felt so in tune with my current understanding. I am not being critical of you (it is more the restrictions that are imposed by the specific circumstances that you face), though I feel somewhat stymied that you are having trouble with or are advised against vitamin C, MG, 3-BP, DCA etc. Fortunately, there are many other metabolic inhibitors that we have found that perhaps could be incorporated into your metronomic metabolic plan. Just as with marcos, if you can see that initial success with the MMD concept, then you will be enthusiastic to add in the chaotic complexity etc. that could further enhance its effectiveness. Hopefully, metro 2-DG will give you this first taste of treatment success.

        GBM has been noted as a particularly active metabolic style cancer. As you are likely aware there are at least 2 GBM patients who have been reported to the literature who have done surprising well following a ketogenic diet with caloric restriction etc. Given your particular circumstances finding a way to include metronomic metabolic dosing could be difficult, though there is a growing list of metabolic blockers that we have compiled (for example, tocotrienol, honokiol etc.).

        You will need time to gain experience and comfort with different treatments (as marcos did). Metronomic 2-DG is a good starting point. Hopefully, you will (through time) be able to add in others and find combinations that you are comfortable with.

        I am interested in seeing how you will be able to integrate the metabolic ideas of our forum into our plan..
        Best Wishes, Jcancom

      3. Manuone,

        You would want to follow the Riordan protocol for vitamin C treatment, if possible . They have had a vast experience in vitamin C treatment. So, you should carefully read through their protocol and notice their comments about treatment safety.

        For example,
        “2. Tumor necrosis or tumor lysis syndrome has been reported in one patient after high-dose IVC (Campbell & Jack,1979).
        For this reason, the protocol always begins with a small 15 gram dose.”
        https://www.cancertreatmentsresearch.com/good-news-from-marcos/#comment-8066

        As a general guideline you would never want to start up any treatment aggressively.
        With metronomic dosing the plan would actually be more to provide ongoing treatments that are well tolerated and could potentially be given essentially around the clock. So, metronomic would be more of a gentle style of treatment that is constantly pressing the cancer mass. Jess gradually increased 2-DG as it was seen to be well tolerated.

        1. From the chart posted on Jess’s page, we can see what happens when aggressive chemotherapy treatment is interrupted to give the patient time to recover from the treatment: The tumor growth almost goes vertical! Patients basically become addicted to chemo for their survival! While it might appear as though the chemo is working, as soon as treatment stops or resistance emerges, the tumor growth can become overwhelming.
          https://www.cancertreatmentsresearch.com/case-report-stage-iv-pancreatic-cancer-good-news-from-jess/

          {This is also noted in the video that was posted about chlorine dioxide recently. You will need to think about this one by yourself, though it does appear promising. Notice that 2 GBM patients have reportedly benefited. However, this treatment is apparently illegal in several nations https://www.cancertreatmentsresearch.com/community/forum-to-discuss-treatment-protocols-and-drugsupplement-cocktail/chlorine-dioxide-metabolic-treatment/#post-817 }

          I am unsure what to suggest to you, as GBM truly is a world to itself as you expressed it. marcos’s plan really leapt off the page for me and felt so in tune with my current understanding. I am not being critical of you (it is more the restrictions that are imposed by the specific circumstances that you face), though I feel somewhat stymied that you are having trouble with or are advised against vitamin C, MG, 3-BP, DCA etc. Fortunately, there are many other metabolic inhibitors that we have found that perhaps could be incorporated into your metronomic metabolic plan. Just as with marcos, if you can see that initial success with the MMD concept, then you will be enthusiastic to add in the chaotic complexity etc. that could further enhance its effectiveness. Hopefully, metro 2-DG will give you this first taste of treatment success.

        2. From the chart posted on Jess’s page, we can see what happens when aggressive chemotherapy treatment is interrupted to give the patient time to recover from the treatment: The tumor growth almost goes vertical! Patients basically become addicted to chemo for their survival! While it might appear as though the chemo is working, as soon as treatment stops or resistance emerges, the tumor growth can become overwhelming.
          https://www.cancertreatmentsresearch.com/case-report-stage-iv-pancreatic-cancer-good-news-from-jess/

          {This is also noted in the video that was posted about chlorine dioxide recently. You will need to think about this one by yourself, though it does appear promising. Notice that 2 GBM patients have reportedly benefited. However, this treatment is apparently illegal in several nations https://www.cancertreatmentsresearch.com/community/forum-to-discuss-treatment-protocols-and-drugsupplement-cocktail/chlorine-dioxide-metabolic-treatment/#post-817 }

        3. From the chart posted on Jess’s page, we can see what happens when aggressive chemotherapy treatment is interrupted to give the patient time to recover from the treatment: The tumor growth almost goes vertical! Patients basically become addicted to chemo for their survival! While it might appear as though the chemo is working, as soon as treatment stops or resistance emerges, the tumor growth can become overwhelming.
          https://www.cancertreatmentsresearch.com/case-report-stage-iv-pancreatic-cancer-good-news-from-jess/

          1. {This is also noted in the video that was posted about chlorine dioxide recently. You will need to think about this one by yourself, though it does appear promising. Notice that 2 GBM patients have reportedly benefited. However, this treatment is apparently illegal in several nations https://www.cancertreatmentsresearch.com/community/forum-to-discuss-treatment-protocols-and-drugsupplement-cocktail/chlorine-dioxide-metabolic-treatment/#post-817 }

            I am unsure what to suggest to you, as GBM truly is a world to itself as you expressed it. marcos’s plan really leapt off the page for me and felt so in tune with my current understanding. I am not being critical of you (it is more the restrictions that are imposed by the specific circumstances that you face), though I feel somewhat stymied that you are having trouble with or are advised against vitamin C, MG, 3-BP, DCA etc. Fortunately, there are many other metabolic inhibitors that we have found that perhaps could be incorporated into your metronomic metabolic plan. Just as with marcos, if you can see that initial success with the MMD concept, then you will be enthusiastic to add in the chaotic complexity etc. that could further enhance its effectiveness. Hopefully, metro 2-DG will give you this first taste of treatment success.

          2. {This is also noted in the video that was posted about chlorine dioxide recently. You will need to think about this one by yourself, though it does appear promising. Notice that 2 GBM patients have reportedly benefited. However, this treatment is apparently illegal in several nations https://www.cancertreatmentsresearch.com/community/forum-to-discuss-treatment-protocols-and-drugsupplement-cocktail/chlorine-dioxide-metabolic-treatment/#post-817 }

          3. {This is also noted in the video that was posted about chlorine dioxide recently. You will need to think about this one by yourself, though it does appear promising. Notice that 2 GBM patients have reportedly benefited. However, this treatment is apparently illegal in several nations

            1. I am unsure what to suggest to you, as GBM truly is a world to itself as you expressed it. marcos’s plan really leapt off the page for me and felt so in tune with my current understanding. I am not being critical of you (it is more the restrictions that are imposed by the specific circumstances that you face), though I feel somewhat stymied that you are having trouble with or are advised against vitamin C, MG, 3-BP, DCA etc. Fortunately, there are many other metabolic inhibitors that we have found that perhaps could be incorporated into your metronomic metabolic plan. Just as with marcos, if you can see that initial success with the MMD concept, then you will be enthusiastic to add in the chaotic complexity etc. that could further enhance its effectiveness. Hopefully, metro 2-DG will give you this first taste of treatment success.

      4. Hi Manuel,

        People with brain tumors often have high copper levels, which might explain your mother felt so bad on the vitamin c IV, because of copper detox symptoms. https://drlwilson.com/articles/copper%20elimination.htm

        “Missing immune cells that could fight lethal brain tumors”
        A mysterious lack of T-cells has hindered the immune system’s ability to fight glioblastoma
        Date:August 13, 2018 Source:Duke University Medical Center
        https://www.sciencedaily.com/releases/2018/08/180813125239.htm

        I think this new information tell us that gbm treatments shouldn’t only focus on what can cross the brain barrier.
        Some natural compounds are very effective at boosting the immune system:

        melatonin (Action of melatonin on bone marrow depression induced by cyclophosphamide in acute toxicity phase.:remarkable countering activity towards leukopenia and anemia)
        astragalus
        panax ginseng
        echinacea
        mushroom extracts
        zinc + a natural zinc ionophore such as molybdenum or EGCg
        selenium (sodium selenite)
        and others.

        Regards
        Johan

  14. Manuone, I recently bought an electronic pH monitor. It was quite cheap as it only cost about $10. I was motivated to buy this from the posts made by Don on this forum. He reported being very focused on moving up his urine pH values, especially through the use of diet. The url below talks of how pH and oxygen levels are highly correlated.

    According to the below research this might be a very wise investment especially for those interested in monitoring their risk of cancer of their response to cancer treatment. This would give you an inexpensive biomarker that you could measure frequently and manipulate through lifestyle interventions.
    http://myplace.frontier.com/~felipe2/id18.html

    1. {This post continues from the post one above.}

      GBM has been noted as a particularly active metabolic style cancer. As you are likely aware there are at least 2 GBM patients who have been reported to the literature who have done surprising well following a ketogenic diet with caloric restriction etc. Given your particular circumstances finding a way to include metronomic metabolic dosing could be difficult, though there is a growing list of metabolic blockers that we have compiled (for example, tocotrienol, honokiol etc.).

      You will need time to gain experience and comfort with different treatments (as marcos did). Metronomic 2-DG is a good starting point. Hopefully, you will (through time) be able to add in others and find combinations that you are comfortable with.

      I am interested in seeing how you will be able to integrate the metabolic ideas of our forum into our plan..
      Best Wishes, Jcancom

      1. Thank you for your opinions J are always very constructive for me!

        Regarding iv treatments these are the difficulties:
        – 3BP: risk of cerebral edema in patients with brain tumors
        – MG: I do not think it’s time to use it, even Daniel does not recommend it to me
        – Vitamin C iv metronomic: I tried this but my mother reacted badly … it is possible that a deficiency of copper or magnesium or other minerals are the cause of my mother’s bad reaction. Administer it without sodium chloride and this may also be a cause but diluting it would reduce effectiveness in a dose administered for many hours

        – DCA: my mother seems allergic to him, it causes itching

        My options are: to extend the schedule of 2 dg metronomic, salinomycin IV and some cycles of taurolidine

        Thanks once again 🙂

        kind regards

  15. Happy new year.I still have some things to finish my protocol between them find out the dose of REVERSINE in humans, and on the other hand my supplier of chemotherapeutic agents will be out of service for some time,someone on this blog knows a reliable source for cyclophosphamide and paclitaxel in Europe?.Thanks

    1. Hi Marcos,

      The dose of Reversine that was typically used intravenous by those I know was 1.5mg regardless of weight of the patient. I have to contact and see what were the higher doses they used as I think they tried to increase the dose. Regarding the other question, chemo can be ordered from German pharmacies with prescription. Here u can search for what u need https://www.medizinfuchs.de/wirkstoff/Cyclophosphamid-1189.html?sac=1

      Kind regards,
      Daniel

  16. Happy New Year marcos!

    Might you give us an update on your wife?
    The last report from Daniel, mentioned that 7 of the 14 lung nodules had been destroyed and the main L2 lesion had decreased in size, while the markers had decreased from 240 to 80. I would love to hear how things are going now. I do not recall D’s report mentioning how long you have been battling this for. Best Wishes, Jcancom

  17. happy new year J.
    This struggle takes 3 years and 5 months,in the diagnosis had 54 lung nodules, and a lesion of the vertebra L2 that made it hard for her to walk,the current situation is that the tumor marker is in 61,has dropped from 280 and the nodules are 6, and the size of the tumor of the L2 has gone from 5.5 X 4.5 X 3.8 to 3.5 X 3X 2.7.In all this time a relentless struggle against the tumor,with all kinds of applications and treatments,official and a search of the triumph over the monster

  18. marcos, this is great news!

    What are the dates for the 5.5 x 4.5 x 3.8 and 3.5 x 3 x 2.7 readings?
    Was the only change that you made from May 28 to July 26 from your first report was the addition of the metabolic protocol (i.e., did the chemotherapy stay the same from before May through till the end of July)?
    What is the current schedule for the metronomic dosing? (i.e. how many days a week (and for how long) are you using fasting/ 2-DG/Vitamin C/ MG/ etc.).
    Do you continue to see improvements in markers and tumor reductions since the July 26th report?
    Glad that this is helping you! Best Wishes!

  19. D, MG is just too good of an anti-cancer drug to miss out on!
    It is quite remarkable in that it selectively inhibits OXPHOS subunit 1 NADH in cancer cells.
    This is almost magical!
    There are not that many substances that readily spring to mind that are that specific to cancer cells.

    If there are concerns with MG iv, probably the best would be to go oral.
    There would seem to be no reason why this could then be used metronomically.
    MG is a naturally occurring substance found for e.g. in honey, so oral metronomic MG should be understood to be reasonably safe.

    1. J, thanks, I totally agree from a scientific point of view. As I mentioned in my post on MG there is also an option for IV based on my discussions with prof Manju. Just that when I saw the solution it appeared a little too aggressive compared to others I used and this is what triggered some concerns. But this is just my perception … nevertheless, if I would go for IV, I would proceed carefully and increase the dose towards the target dose in smaller steps.

    2. @Jcancom: MG has been tried as an anti-cancer drug over 40 years ago, but high toxicity to normal cells could not be overcome. So IMO it’s a bad idea to be enthusiastic about it. It has been proven that at lower doses MG promotes tumor growth, while only at higher doses it strongly inhibits tumors.
      Hormetic potential of methylglyoxal, a side-product of glycolysis, in switching tumours from growth to death. PMID: 28916747

      There is one article about metronomic MG, acting as a chemosensitizer, but the article is not yet free, so I can’t comment more.
      Methylglyoxal at metronomic doses sensitizes breast cancer cells to doxorubicin and cisplatin causing synergistic induction of programmed cell death and inhibition of stemness. PMID: 30170097

      If the cancer cells have high levels of GLO1 (Glyoxalase 1), or other detoxification mechanisms, they may be able to overcome the stress caused by MG. So finding out the GLO1 basal expression (and potential to increase) in the cancer cells from a specific tumor should be performed, in order to ensure that they are sensitive to MG. Another approach would be to use a GLO1 inhibitor (it seems several flavonoids, like Scutellarein, and Metformin are such inhibitors) together with exogenous MG.
      Synergistic inhibition of colon cancer growth by the combination of methylglyoxal and silencing of glyoxalase I mediated by the STAT1 pathway. PMID: 28903386

      1. Hi Ovidiu
        Then what happens to the clinical trial of Dr. Manju Ray, I’m a little confused no longer if you apply it not even orally,Ovidiu you could send me the link of the clinical trial where it was determined that the dose to cause damage to the cancer was toxic to normal cells.Another inhibitor of GLO1 is curcumin intravenously,my thinking was to use it orally but liposomado.Please someone to resolve my doubt.

      2. ovidiu,

        I do not understand all these claims about toxicity that arise in the literature. The toxicity caused by chemotherapy is truly profound, yet many of the metabolic chemicals that we have explored through the years have shown a near absence of such effects. The research that has accumulated over the last few decades and the human clinical trials that have been conducted have provided considerable evidence that MG is largely non-toxic. This can be collaborated by the very high concentrations of MG that occur in Manuka honey. Of relevance was the experience of a poster to the compass thread. The patient took a very large oral overdose of MG due to a dosing miscalculation and was able to recover from this problem quite rapidly. A piece of good news with MG is that it has an antidote that could be on hand if there were any acute signs that occurred after dosing.

        It is of further note that the nanoformulation might be used to dose the MG directly to the tumor. When this formulation was used down dosing of almost 100 fold was possible while maintaining efficacy. Also of interest is that MG is a specific inhibitor of cancer cell OXPHOS subunit 1. I found this highly impressive. Typically cancer drugs will have a wide range of effects on normal cells, yet with MG it appears that the mitochondrial effect is very specific. With our current therapeutic focus on metabolism and depleting energy, it could be very handy to have MG on hand. It could be imagined that MG could simply stress cancer cells beyond viability.

        I am glad that you mentioned this concern and it is a good idea to be open to new evidence, though the totality of the MG research appears to be quite favorable.

  20. D, sorry for all of my recent posts! It’s embarrassing for me! It’s just that I have so much energy and I want to help people.
    The problem with all these posts is that sometimes there can be too much unprocessed information for people to cope with.
    One idea to cope with this would be to have a “playground” where people could toss around ideas without the software reporting the posts. When an idea was more fully formed it could then be posted to the normal forum. This could help cut down on the thread clutter and keep things better organized.

    One of the ideas that I am excited about now is percutaneous injections in particular acetic acid, ethanol etc.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1774888/pdf/gut05401151.pdf
    https://www.ncbi.nlm.nih.gov/pubmed/?term=19086330

    D, are they serious just stick a needle into the patient hit the hepatic artery and then inject acetic acid/Ethanol?
    Subcutaneously? Outpatient procedure?

    I wonder if that could work for Jess?
    Could they simply stick a needle through the stomach and hit a pancreatic artery and get the pancreatic tumor as well?
    Wow! The articles talk about this being a highly successful procedure of perhaps 90% complete response rates for the tumors targeted. Does this actually make sense in a metastatic setting?
    Getting rid of targetable existing masses might give metabolic approaches a better chance.

    1. Hi J.
      I’m going to produce the compound couple.D-Ribose+ascorbic acid but liposomado +potassium bicarbonate i read the whole article that posted but what are the doses of each of the compounds in humans ?since the article is in vitro.

      1. marcos, this is fantastic!

        We have been waiting years and years for someone to take the first step toward synthesizing compounds.
        It is urgently important to think in this way because few if any chemicals do that much good without proper formulation.

        Yet when synthesis are done the enhancement in efficacy can be truly dramatic.
        Moving to mito-DCA enhances efficacy by 1000 fold! Almost any compound will become more effective witht the proper formulation. One sticking point about these formulations is they often do not have even in vivo results. It makes it very difficult to make any informed opinion.

        Just to be clear, we are talking about this article?
        https://www.ncbi.nlm.nih.gov/pubmed/29290903

        Your choice of PAR would thus seem truly truly inspired!
        The method given in the article below:

        “The mixture was prepared by dissolving potassium bicarbonate, ascorbic acid, and ribose powders in culture medium in the dark (because they are light-sensitive), using nonmetallic spatulas (to avoid oxidation of ascorbic acid).”

        This is perhaps the most basic synthesis I have ever seen! Almost all the meals I cook up are more complicated than that!
        This is such a great place to start some basic chemistry.

        Take a look at the ingredients! They are essentially regarded as GRAS! Potassium? A daily intake of roughly 5 GRAMS is recommended and maximal intake of roughly 18 grams when kidney function is intake mentioned online. Most people are potassium deficient! Potassium’s regulation of cellular pH clearly caught my attention; this might have been an aspect of cancer that we have neglected to date. Ascorbic acid as we have seen can be taken in truly overwhelming doses. d-Ribose can be taken as a multi-gram daily supplement.

        Look at Figure 4! only 2 mM of PAR almost stopped the melanoma cell proliferation! Ascorbic acid can require 50 mM or more!

        Regarding dosing I will leave it you, however, from what I can see you have quite a good range of dosing available.
        The obvious suggestion would be to simply titrate up. The study quoted above did not mention in vivo research, which is disappointing.

        Lullabyman!!! Can you help us out on this one?

  21. This is the resolution of the formulation of 3BP ,of the dR Ko,i put the calculation that i’ve done,with invaluable assistance.
    Component 1 solution .(more buffer) Phosphate Buffer PH 7.4 disodium and monosodium 0.5 molar,which includes the 40 % of the mixture,rest of the solution, glycerol 1%, inositol 4% and sorbitol 55% to this solution more buffer is added the component 2 . 3bromopyruvate Molecular weight 166.96 g/mol,in an amount of 120 mg max, and to give a final concentration of 0.5 Molar. The buffer calculations on the basis of monosodium phosphate disodium ph 7.4 and 0.5 MOLAR.(This is good insurance).

    .Disodium phosphate 42.6 grams, monosodium phosphate 24 gr ,total weight 66.6 gr
    buffer concentration 40%—— 40%=66.6 buffer=mass/mass of the dissolution x100 —- clearing mass of the dissolution=166.5 gr.
    Now we cleared the rest of the components. Sorbitol—- Sorbitol 55%=mass/166,5×100 sorbitol —-91.58 gr,so on inositol=6.66 gr and glycerol 1.66 gr this for a liter of deionized water.Let’s now with the 3BP 120 mg and 0.5 molar.
    Molecular Mass 3 bromopyruvate=166.96 0.5 MOLAR.—- 83.48 g=0,120 gr /volume dissolution, VOLUME DISSOLUTION =1.44 ml Now the quantities of buffer ,sorbitol,inositol and glycerol which were calculated for a one liter , we calculate for 1.44 ml Results:disodium phosphate 61.34 mg,monosodium phosphate 34.58 mg sorbitol 131.04 mg inositol 9.59 mg glycerol 2.39 mg.a little help I think it is a good thing.

    1. marcos, what is your wife’s glucose level?

      The first step in an ketogenic anti-cancer is to raise ketone levels. This is the hard part.

      The second part is to lower glucose levels. This is supposedly the easy part. Reducing food intake and exercise are some approaches that could be useful for glucose lowering. The lower glucose levels are the higher is survival, and the lower is tumor size.

      Think of cancer as a metro system with many interconnecting lines.
      Typical modern populations would have a network state defined by high glycolysis, high glucose levels, high fat levels, low exercise levels, low ketone levels, and almost no gluconeogenesis. By changing the network state into a ketogenic one, there would be lower glycolysis, lower glucose levels, high fat levels, perhaps higher exercise levels, high ketone levels, and high gluconeogenesis.
      What is particularly interesting is that one could imagine a range of other metabolic network states that could be achieved. For example, lowering glucose levels could lead to lower lactate levels. Lower lactate levels have substantial potential for significant anti-cancer effects. In addition, anaerobic exercise can rapidly lead to another state of high lactate levels. There could be potential benefits for integrating this into a comprehensive anti-cancer plan. Another network state changer could be pulsing different state changes through the system. For example, there is mention that pulsing ketogenic diets can be helpful. The idea here might be that simply maintaining one steady state requires no adaptive skill by the cancer cells: they just keep on doing what they were doing. Changing the network state would require cancer cells to reconfigure their metabolism which is not always an easy task for them.

      Thinking about things in this way could be quite useful for you.
      Driving down lactate levels to a low level might have large anti-cancer effects even by itself.
      You might need to manipulate the system a while to see how everything responded, though you would quickly see whether this would be of help to you.

      As an aid to capture the benefit you might consider buying glucose, ketone and lactate monitors. These monitors could clearly demonstrate to you what effect different interventions had on the network state. You would also have quantitative results for how fast different measures changed. For example, what rate the liver could convert lactate to glucose while under ketosis etc. .

      Best Wishes, Jcancom

  22. Hi J.
    I already have blood glucose meter,levels range between 70 and 80 mg/dl.Get the ketosis after the days of fasting even though it is not maintained for more than 10 days.She follows a ketogenic diet from three years ago,this is another of the reasons for his evolution.

  23. marcos, what is your opinion of moving down the glucose levels below 70 mg/dL?
    D has recently posted about an article that I found that talked about potentially greatly moving down glucose perhaps down to ~30 mg/dL using a protocol that has been already tested and approved in healthy people. However, this approach could only be tried if someone were fully ketoadapted, otherwise coma might result even at the ~45 mg/dL glucose level. A previous article talked about maximal glucose decrease which apparently has also already been done with humans in which they achieved a remarkable 9 mg/dL without compromising cognitive status.

    Bringing down glucose levels that low would have to capture the tumors attention.

    My idea would then be to see what happens to lactate levels. With glucose levels that low, the body would be expected to draw down lactate levels. Lactate is a prime driver of many features of cancer. This could have significant clinical relevance.
    What are your feelings about this approach?

    1. marcos, it might not apply in your instance, though what would your opinion be on a strategy to move down glucose with the intent of lowering lactate levels? Once someone were ketoadapted (stage IV starvation after 2 weeks) then glucose could be lowered below 50 mg/dL.

      https://arxiv.org/pdf/1407.7622.pdf
      Also https://www.cancertreatmentsresearch.com/community/forum-to-discuss-treatment-protocols-and-drugsupplement-cocktail/a-hypothetical-method-for-controlling-highly-glycolytic-cancers/#post-827

      One easy way to lower glucose levels is to engage in aerobic exercise. As the glucose levels were to respond, then it would b expected that the lactate levels would also eventually fall. Lactate has so many negative effects including promoting metastasis, suppressing immune response, shuttling energy to other cancer cells, etc.. Further given cancer’s large appetite for energy, glucose lowering is known to cause considerable stress for them.

      This is might be an idea to consider and research further. First you might determine if such a lactate lowering effect could in fact be achieved.

    1. marcos,

      lullabyman posted some references that showed that ultrasound could substantially increase (5 times or more!) release the contents of nanoformulations. This might be of help to you when applying any nanoformulations you synthesize.

  24. This week begins my wife with the treatment of IPT,we are going to include DMSO 2ml in the bag of chemotherapy with low doses of paclitaxel chemotherapy,IPT will be preceded by a fast of 48 hours,instead of including glucose in the bag,we have thought of including 50 ml of 2DG,because to enter at the same time that chemotherapy,will not have time to slow down the division of cancer cells and if you will reach the tumor chemotherapy with greater ease.What do you think about this?

    1. Hi Marcos,

      Sounds very interesting. I know you are very careful, but I would only add one change at a time just to reduce any risk. So if I would want to do what you suggest, I would first time add DMSO, and if everything goes well, next time I would add 2DG instead of glucose.

      Kind regards,
      Daniel

  25. Hi .
    I tried IPT with Taxol (paclitaxel) and with prolonged fasting 48 hours before.In addition use DMSO 5 ml in the bag of taxol and in addition 40 ml of 2DG replacing the glucose solution.No side effects worthy of everything well. There is a neurosurgeon that now sees possible the surgical operation with complete resection,need to please anyone with suggestions ,for before and especially after the operation, the share here.Oncothermia before the intervention,Mozobil after etc,ideas of this typ

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