“Roach Motel” cancer trap

[snoraste]

Just saw this post on Inspire:

uta.edu/news/releases/2018/...

Anyone knows anything about it?

[rococo]

More hope possible. Rococo

[CalBear74]

I can only respond on a conceptual level: Dr. Tang at UTA has a very exciting project going. The new "Right to Try" Law Congress just passed will get activated I suspect by Stage 4 prostate cancer patients as soon as there is a working model to inject.

CalBear74

[pjoshea13]

It seems to be aimed at circulating cancer cells. That's a good thing, I believe, even when there are mets.

My own approach is to avoid/eliminate microclots, which can facilitate metastasis. The body is very efficient at cleaning up mobile cancer cells, but they can avoid detection by attaching to microclots.

I take 12000 FUs nattokinase each night & my D-Dimer as of Wednesday was below the range measurable by LabCorp.

{Some rely on Modified Citrus Pectin to gum-up the region used for docking.}

-Patrick

{I switched from Warfarin to nattokinase over 5 years ago & it has worked out well. I did have a met at L5, which was radiated.}

[snoraste in reply to pjoshea13]

Patrick-

Is nattokinase for blood clots? Or you suggesting that metastasis and blood clots have a similar mechanism?

[pjoshea13 in reply to snoraste]

Nattokinase is an enzyme with a structure similar to plasmin. Plasmin breaks down the fibrin structure of a clot, but does so slowly. Warfarin, which does not dissolve clots, inhibits further clotting by increasing clotting time, so that plasmin can do its job - which can take many weeks. With nattokinase - depending on the dose - clots can be dissolved much faster than they are accreting, so Warfarin is not needed.

Nattokinase also lowers elevated fibrinogen levels. Fibrinogen can be high when there is inflammation. In fact, it is sometimes used as a marker of inflammation. Fibrinogen circulates in case a clot is needed. Fibrinogen is converted by thrombin to fibrin at clotting sites.

Cancer is not only an inflammatory disease, but it also interferes with coagulation. Some papers claim that altered coagulation is important to the metastatic process.

Studies are somewhat mixed. In my view this is because many men develop DVTs in advance of a cancer diagnosis. In the short term, men on warfarin have increased risk for metastatic PCa. However, long-term users have lower risk.

-Patrick

[snoraste in reply to pjoshea13]

Thanks Patrick. Two questions for you if you will:

- is the agent responsible for coagulation process leading to vascular clots the same one that cancer cells need in order to metastasize?

- when you said cancer “interferes with coagulation”, do you mean it increases or inhibits the coagulation?

[pjoshea13 in reply to snoraste]

I'll respond with a few papers (there are many on the subject, but doctors seem oblivious).

[1] The clinical observation that thrombosis in some patients heralds the onset of malignancy has been recognized for over a century. Thrombin the key terminal enzyme of coagulation also promotes angiogenesis and stimulates tumor-platelet adhesion, adhesion to endothelium, tumor implantation, tumor cell growth and metastasis. The thrombin receptor, a member of the protease-activated receptor family, is expressed on many tumor cell lines and on breast tumor biopsy specimens. In addition to mitogenic effects on fibroblast, smooth muscle cells and endothelial cells, thrombin also exerts direct effects on cancer cells by activation of the cell cycle through downregulation of p27(Kip1) and induction of Skp2, and cyclins D and A. MicroRNA 222, which inhibits p27(Kip1), is upregulated by thrombin. In the transgenic TRAMP mouse model of prostate cancer inhibition of endogenous thrombin by hirudin retards spontaneous tumor growth. Inhibition of thrombin may lead to tumor dormancy and could explain inhibition of tumor growth and metastasis by anticoagulants observed in animal models and a beneficial effect on survival observed in some clinical trials of anticoagulants in cancer patients.

[2] - Results:

Our final sample consisted in 58 control patients and 147 patients with urological cancer. We found specific patterns of increased coagulation factors in the different cancers that were statistically significant. Renal cancer showed increased levels of D-dimers, partial thromboplastin time and fibrinogen. D-dimers and fibrinogen were increased in prostate cancer; whereas in bladder cancer, only fibrinogen was elevated. Correlations were found between certain factors and tumor stage and grading, with D-dimers being independently associated with higher tumor grade. Thrombin-antithrombin complex was associated with Gleason score. Furthermore, D-dimers, fibrinogen and F1 + 2 were associated with higher tumor stages (II-IV).

[3] Tumor progression is associated with aberrant hemostasis, and patients with malignant diseases have an elevated risk of developing thrombosis. A crosstalk among the vascular endothelium, components of the coagulation cascade, and cancer cells transforms the intravascular milieu to a prothrombotic, proinflammatory, and cell-adhesive state. We review the existing evidence on activation of the coagulation system and its implication in genitourinary malignancies and discuss the potential therapeutic benefit of antithrombotic agents. A literature review was performed searching the Medline database and the Cochrane Library for original articles and reviews. A second search identified studies reporting on oncological benefit of anticoagulants in genitourinary cancer. An elevated expression of procoagulatory tissue factor on tumor cells and tumor-derived microparticles seems to stimulate cancer development and progression. Several components of the hemostatic system, including D-dimers, von Willebrand Factor, thrombin, fibrin-/ogen, soluble P-selectin, and prothrombin fragments 1 + 2 were either overexpressed or overactive in genitourinary cancers. Hypercoagulation was in general associated with a poorer prognosis. Experimental models and small trials in humans showed reduced cancer progression after treatment with anticoagulants. Main limitations of these studies were heterogeneous experimental methodology, small patient numbers, and a lack of prospective validation. In conclusion, experimental and clinical evidence suggests procoagulatory activity of genitourinary neoplasms, particularly in prostate, bladder and kidney cancer. This may promote the risk of vascular thrombosis but also metastatic progression. Clinical studies linked elevated biomarkers of hemostasis with poor prognosis in patients with genitourinary cancers. Thus, anticoagulation may have a therapeutic role beyond prevention of thromboembolism.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/201...

[2] ncbi.nlm.nih.gov/pubmed/280...

[3] ncbi.nlm.nih.gov/pubmed/288...

[snoraste in reply to pjoshea13]

So in theory, different mechanism of action than modified citrus pectin. Is there a reason for using nattokinase in particular and not just aspirin (for example)?

[pjoshea13 in reply to snoraste]

Low-dose aspirin inhibits the aggregation of platelets & can limit clots. But nattokinase removes clots. And it does also lower clotting potential.

I prefer not to use aspirin. Even low-dose can cause stomach bleeding & kidney damage.

-Patrick

[erjlg3]

Wow!