Posted on by Daniel

Heparin: Great Value in Cancer Treatment

Background:

blood clotHeparin is a widely used injectable blood thinner. It is typically administrated as an injection IP (anyone can do it at home) or Intra Venous. It is used to treat and prevent deep vein thrombosis and pulmonary embolism (collectively known as venous thromboembolism).

According to Wikipedia, Heparin’s normal role in the body is unclear. Heparin is usually stored within the secretory granules of mast cells and released only into the vasculature at sites of tissue injury. It has been proposed that, rather than anticoagulation, the main purpose of heparin is defense at such sites against invading bacteria and other foreign materials. In addition, it is observed across a number of widely different species, including some invertebrates that do not have a similar blood coagulation system. (Ref.)

Heparin as a Cancer Treatment

Anti-Coagulant Slows Down Tumor Growth And Spread: A research group at University of Hull and Hull’s Castle Hill Hospital has revealed that Heparin can reduce the levels of a tissue factor (a protein that contributes to clotting) being secreted by tumors.

While tissue factor’s role in healthy people is to promote blood clotting in wounds and aid repair, tumors secrete tissue factor as an inflammatory response to their interaction with growth factors in the blood, which they hijack to help them grow and spread. High levels of tissue factor are known to cause thrombosis, which is one reason why cancer patients are particularly at risk of developing lethal deep vein blood clots.

Same researchers have previously shown that tumor cells which express high levels of tissue factor are more invasive, and other reports show that they metastasize rapidly and are resistant to therapy. As a result they concluded that finding new ways to suppress the expression of tissue factor are crucial.

Using Heparin to treat pancreatic, breast, melanoma, colorectal and ovarian cancer cells, they shown that this suppressed the cell’s interaction with growth factors, preventing tissue factor from being secreted, ” raising the possibility of a universal treatment strategy that could benefit all cancer patients.”

Same researchers conclude: “What we have here is experimental evidence that a drug that is already known to be safe in humans as an anti-coagulant may also suppress tumor growth directly and reduce resistance to treatment. I think this would also be a very useful way of lowering the risk of tumor regrowth in between chemotherapy and radiotherapy sessions.”

The Anticoagulant Heparin: A Possible New Cancer Treatment?

“… A potentially more significant issue, however, is whether taking heparin to treat blood clotting problems may have somehow slowed down the growth of Mrs. Benchley’s lung cancer. Based on cases like hers, doctors have begun to wonder if the human body’s blood clotting mechanism may somehow play a role in the growth of cancerous tumors. If that is so, then it would explain why a drug like heparin that fights blood clotting might actually stop or slow down tumor growth.”

“The possible reasons for this are not completely understood. To put them as simply as possible, cancerous tumors are usually surrounded by a substance called fibrin. Fibrin promotes the growth of the tumor and the growth of new blood vessels that supply the tumor with necessary nutrients. Heparin interferes with fibrin formation and perhaps directly inhibits the formation of new blood vessels. Both heparin and LMWH may also inhibit tumor growth in other ways.”

Heparin-like compounds inhibit breast cancer metastasis to bone

Researchers have discovered a novel mechanism regulating the development of breast cancer bone metastases and showed that heparin-like compounds can potentially be used to inhibit breast cancer metastasis to bone.

2016: Application of a Persistent Heparin Treatment Inhibits the Malignant Potential of Oral Squamous Carcinoma Cells Induced by Tumor Cell-Derived Exosomes

Exosomes are 30–100 nm-sized membranous vesicles, secreted from a variety of cell types into their surrounding extracellular space. Numerous studies have showed that tumor cell-derived exosomes play important roles in tumor growth and progression. The uptake of exosomes by oral squamous cell carcinoma (OSCC) cells and subsequent tumor progression was abrogated in the presence of heparin. Taken together, these data suggest that OSCC cell-derived exosomes might be a novel therapeutic target and the use of heparin to inhibit the uptake of OSCC-derived exosomes by OSCC cells may be useful for treatment.

2016: Anti-heparanase activity of ultra-low-molecular-weight heparin produced by physicochemical depolymerization

Heparanase is an endo-β-D-glucuronidase that plays an important role in cancer progression, in particular during tumor angiogenesis and metastasis. Inhibiting this enzyme is considered as one of the most promising approaches in cancer therapy. Heparin is a complex glycoaminoglycan known as a strong inhibitor of heparanase.

2016: Metastasis stimulation by hypoxia and acidosis-induced extracellular lipid uptake is mediated by proteoglycan-dependent endocytosis

Here, we provide evidence of a novel role of heparan sulfate proteoglycans (HSPGs) in the adaptive response of tumor cells to hypoxia and acidosis through increased internalization of lipoproteins, resulting in a lipid storing phenotype and enhanced tumor forming capacity. We show that stress mediated lipoprotein uptake is highly dependent on intact HSPG expression. The functional relevance of HSPG in the context of tumor cell stress was evidenced by HSPG-dependent lipoprotein cell signaling activation through the ERK/MAPK pathway, and by reversal of the LD-loaded phenotype by targeting of HSPGs. We conclude that HSPGs may have an important role in the adaptive response to major stress factors of the tumor microenvironment with functional consequences on tumor cell signaling, and metastatic potential.

Indeed it is known that the inhibition of lipid droplet (LD) formation may represent a serious anti cancer solution: https://www.cancertreatmentsresearch.com/?p=1447

Very good discussion on Heparin anti cancer effects: “Data from epidemiologic studies and clinical trials demonstrate a protective and therapeutic effect for heparin treatment on tumor growth and metastasis [64]. In certain tumors, such as small-cell lung cancer, a portion of the survival benefit can clearly be ascribed to antithrombotic effects [65]. However, the benefits of heparin treatment exceed the effects of anticoagulation, suggesting that other mechanisms are involved [66]. Multiple mechanisms likely contribute to the therapeutic effects of heparin, including inhibition of selectin binding [66], inhibition of heparanase [51] and sulfatases [67], decreased platelet signaling to suppress tumor angiogenesis [45], and enhanced terminal differentiation of cancer cells [27].” For more, go to http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065786/#S6title

Notes:

  • enzymatic depletion of mast cell heparin by injection of heparinase enzyme into tumor implants accelerated tumor growth and increased blood clotting within the tumors (Ref.)
  • NDST-2 knockout mice are unable to synthesize mast cell heparin –  tumor cells implanted into NDST-2 knockout mice grew faster than tumor cells implanted into wild-type mice that synthesized normal heparin (Ref.)
  • “our observation that mast cells are abundantly present within the fibrous regions of tumors raises the intriguing possibility that a growth inhibitory mechanism similar to the one that we observed in our in vitro studies could also be naturally operative within tumors in vivo … we acknowledge, however, that this possibility seems to be at odds with the accumulating evidence that mast cells promote rather than inhibit tumor growth … In this regard, it should be emphasized that mast cell granules contain numerous biologically active compounds in addition to heparin, such as histamine, tryptase, and chymase. Some of these mast cell compounds and metabolites are likely to have significant effects on fibroblasts that remain to be defined. In addition, a number of other mediators from fibroblasts and mast cells could potentially influence tumor growth through a variety of mechanisms such as cyclooxygenase metabolites, heparanases, etc. The net effect on tumor growth, therefore, is likely to be the result of multiple complex interactions between the various components of mast cell granules and adjacent stromal cells such as vascular endothelium and fibroblasts.” (Ref.) The whole point of thsi is that heparin (produced by mast cells) has anti cancer effects while mast cells overall lead to tumor progression – therefore using Heparin as injection while if possible inhibiting mast cells may be best approach.
  • NDST2 (N-Deacetylase/N-Sulfotransferase-2) Enzyme Regulates Heparan Sulfate Chain Length (Ref.)
  • NDST-2 having a role in the formation of fully sulfated heparin – central role for NDST-2 in MC heparin synthesis – targeting of the NDST-2 gene was previously shown to result in strongly defective synthesis of heparin (Ref.)
  • Mast Cell (MC) degranulation also caused an up-regulated expression of certain CS sulfotransferase genes, accompanied by a corresponding down-regulation of NDST-2. These results suggest that activated MCs predominantly synthesize CS over heparin and, indeed, the biosynthetic35S-sulfate labeling experiments supported an increased secretion of CS (Ref.)

Conclusion:

Heparin is a great tool to help dissolve blood clots and thus enhance the penetration of treatments to the tumor site. Due to this property it may make sense to often use it just before starting the administration of other IV therapies. In addition to that, Heparin seems to have anti cancer action too and this strengthen the idea of using Heparin as a part of any anti cancer treatment.

Source:

Heparin can be found at any pharmacy and is very affordable. Here is an example: https://www.medizinfuchs.de/preisvergleich/heparin-natrium-25000-rati-5×5.0-ml-ratiopharm-gmbh-pzn-3029843.html

Dose, Administration, Safety:

Here info that we need to have references on what is safe in terms of administrated dose https://www.medicines.org.uk/emc/medicine/9796

Other references:

P1-206: Optimization of small cell lung cancer (SCLC) treatment by heparin plus chemoradiotherapy: report of an exhaustive retrospective study of 239 patients in a single specialized center

Intensified chemotherapy and simultaneous treatment with heparin in outpatients with pancreatic cancer – the CONKO 004 pilot trial

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.

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25 thoughts on “Heparin: Great Value in Cancer Treatment”

    1. Curcumin IV is “widely” available at pharmacies in Germany, for example here http://apotheke-koenigstein.de/
      For Quercetin IV, I only have one source on the other hand. In one country it is used as a drug in hospitals for other health issues but not cancer. To protect that source I will only share the info by email. If you need the info just send me an email.

  2. I keep a supply of 500usp/5ml heparin lock flush, last step for our home infusions. I guess I should give at the beginning too. Perhaps I should tell the chemo nurses to do same.

    1. Thanks Ovidiu! This is a nice one indeed and as a result will added to the text above.
      I was not aware about the heparanase role.
      For many cancer patients its anti coagulant function is actually good as well, so Heparin as is is already very helpful. But I agree that lowering its anti coagulant function will enable us to use higher doses and consequently achieve stronger anti-heparanase activity.

  6. As far as i read and searched,heparin must be added to any cancer protocol.
    It exactly improves survival in every clinical trials.
    But there are lots of derivatives of heparin.
    Which one will be choose?
    Ultra low molecular weight,low molecular weight or non-anticoagulant heparin?
    Is there any idea?

  7. Thank you very much Daniel.I am going to begin tinzaparin.
    But afraid of bleeding.When there is a cut in her hand,finger etc.,bleeding does not stop easily.

    1. Dear Ergin, please check with a doctor if based on the status of the blood results of your mom using tinzaparin is safe. It should not be difficult to find a doctor that can advise you on that.

  8. Hi Daniel,
    You will kill me after too many questions.But i need help.I am still working on Tinzaparin.

    May be this is our novel drug:
    It is not expensive like salinomycin,,can be easily find on pharmacies.And there are clinical trials with heparin but not tinzaparin.
    I think the dosages should be the same.On lab results,It totally depletes resistivity.I like it very much and want to use it.
    Tinzaparin is different than its derivatives.
    https://www.researchgate.net/publication/280693552_Low_molecular_weight_heparin_tinzaparin_antagonizes_cisplatin_resistance_of_ovarian_cancer_cells
    You can download it from upper right as you know:)
    Kind Regards
    Ergin

  10. I have the chance to get the heparin, but don`t know: is there a difference between Innohep (Tinzaparin-Natrium) or Fraxiparin (Nadroparin-Calcium)? I asked the Pharmazis and he said, both are low-moleculare heparins.
    I would be happy, to get an answer. Thank you, whoever is competent…

  11. Dear Daniel,

    Another valuable article of yours that got very little attention. I like the idea of heparin injection. Do you mean ip, i.e. intraperitoneally? I wonder if patients can do that themselves? Also, do doctors prescribe it for cancer, what do you think? As I said in my other comment in Ergin’s thread I am treating my mom’s tumour in the peritoneum with both heparin and diclofenac, but in ointment forms (creams). The doc said he can prescribe diclofenac tablets but it will hurt my mom’s stomach. Maybe the cream is a better solution as the tumour is palpable under the skin anyway.

    However, intraperitoneal injection of heparin would make sense in her case but I wonder if doctors prescribe it off-label.

    1. Hi Helga,

      Heparin-like compounds can be indeed given as IP injection. For tumors located close to the surface we can always try substances combined with DMSO, such as the 3BP solution I discussed on the 3BP page. But we can also consider mixtures of DMSO with other substances including natural substances such as Curcumin, to be applied at the tumor location.

      Kind regards,
      Daniel

    2. So sorry to hear your mother has this thing called cancer. I know how it feels. Truly shocked.
      When did you find out about this?
      If it can be felt, going at it from outside should give some results. Heat, light, drugs etc.

      Warm hugs, Alex

  12. Dear Daniel & Alex,

    Thanks for responding. When I came to my mom’s place around Xmas, she was already doing very badly, hardly able to put one foot before the other to walk. After Xmas her ascites became so severe that she woke up saying “this may be the end”. I was devastated. We called the doctor, and he prescribed anti-diuretic combined with potassium. It helped very little. She made it to her appointment on January 15th at a heart clinic where the doctor actually recognised my mother as she used to work in health care 40 years ago for a while and he remembered her. She was a very attractive woman at the time, perhaps the reason he remembered her. He was truly shocked by my mother’s condition and apparently by her GP’s lack of interest in her medical condition as she visited him many times over the years but he never took the time to physically examine her.

    She was referred to the internal ward of the hospital for Jan 30. However, her condition worsened when she ran out of the antidiuretic, my sister called the doctor and she was taken to the hospital promptly. She ended up in a room for 4 patients and was kept there for a week. Just to illustrate her case, she was taken to a room of moribunds. Three of her roommates died while my mother was there. Her ascites water was taken out from her belly, after which she felt a bit relieved. Nevertheless, she was so weak upon leaving the hospital that I had to help her with getting up from her bad, even with sitting up. The food was awful there, hardly any calories most of the time and definitely no vitamins. We visited her every day and took her nutritious food but she didn’t take her cimetidine, maybe once a day.

    Now she takes 3×400 mg cimetidine, 2×200 mg beta-glucan, cat’s claw, freshly made rose hips drink, artemisia drink, 1000 mg vitamin C and continues to take her anti-diuretic. Amazingly, her circumference measured around the belly decreased from the worst 103 cm to 91 cm (as of yesterday). Her weight is 51 kg now. What made the most difference I feel are the Diclofenac and heparin creams we apply both on her belly, on separate occasions . She can walk around now, even walked up today twice to the 2nd floor! I may try DMSO if I can find it but her improvement is already quite visible. She also takes Budwig’s mixture (cottage cheese, flaxseed oil, yogurt and some honey). She also stopped craving sweet foods, which is a typical sign of cancer I’ve read.

    Alex, how is your mom doing, both physically and mentally? I can hardly describe the pain I felt when I heard my mom over the phone when I left her on her own for 3 days in mid-January because I wanted to prepare for a job interview for a job in London. I ended up cancelling the interview because I felt so horrible and rushed to my mom’s place. No job could compensate for the pain and guilt I suddenly felt over her condition and her impending death (which she was so close to I feel).

    Warmest hugs,
    Helga

    1. HI Helga,

      I did not had the chance to read all the comments due to the tech issues I had to deal with next to everything else, but would like to help in anyway I can – if you like we could brainstorm in a Skype call – just let me know if that’s a good idea.

      Kind regards,
      Daniel

      1. Dear Daniel,

        Thanks so much, that would be great. I just recently started to get back to some kind of normalcy, resuming work on my paper. It is so close to submission but recently it was guilt that prevented me from finishing it. Guilt about not doing any work – a vicious circle. When would you have time to skype – what time of the day? My mom’s condition is kind of stable now – not very well but still functioning on a basic level. Best, Helga

        1. Hi Helga,

          Great to hear that your mom is stable. Tomorrow evening or Sunday evening could be suitable. Also next week in the evenings. Just let me know what you prefer so that I reserve the time.

          Kind regards,
          Daniel

          1. Hi Daniel,

            Thanks a lot. Probably next week would be better, one of the evenings if that agrees with you. I’ll send you an email so that we can specify the time.

            Thanks,
            Helga

        2. Dear Helga,
          You have a very good opportunity if the tumor is palpable.Please read for tinzaparin and ovarian ca.It works different than ordinary heparin.
          DMSO,a great idea with Pyrivinium pamoate. (We used iv DMSO with iv curcumin and it was worked)
          If the tumor is palpable:you can reach a great immunity reaction by heating more than 40 degree for 2 hours with a good fasting+phlorizin+DMSO.
          Kind Regards
          Ergin

          1. Dear Ergin,

            Thanks a lot. Where did you get the pholirizin? And how much does one need? I found this site: http://www.adooq.com/phlorizin-phloridzin.html But it is very expensive, it seems. Are you suggesting to put it on the belly, mixed with DMSO? Phlorizin is coming from the apple tree root bark if I understand correctly. I remember there was a lot of discussion about it, I’ll try to find it. Now I don’t find the tumor palpable, probably because the ascites decreased but it cannot be very deep if it is on the peritoneum.

            Kind regards,
            Helga

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