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TNBC / testing strategies in a NED situation

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(@rosed)
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@j Thank you, Johan, for such a detailed response. Your kindness goes beyond my ability to adequately thank you through my keystrokes.  To think a complete stranger cares enough to take this time.... it makes me think that part of my cancer journey is learning about the goodness in humanity (while dealing with some of the worst in the oncology doctors). Thank you so much. I will reread all this information and digest it.


   
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(@rosed)
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@laika Thank you so much for your response.  I did get 3 doses of pembro before my surgery.  My PDL-1 status is almost 0, but I did read that it could still work..... I especially read about Ivermectin and Pembro working together.... I believe the City of Hope was doing research on that.....     You are inspirational to me to think that you could achieve this status. I look forward to conversing with you in the future. This journey can be so lonely but isn't it absolutely amazing to be able to connect with a stranger on something so deep as our very survival. It is all mind-blowing. Thank you again for taking the time to respond to me....


   
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(@rosed)
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@j Does CCL5 have anything to do with CCR5, like what Maraviroc or leronlimab works with?


   
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(@rosed)
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@j What a phenomenal resource. Thank you for sharing this with me.


   
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(@j)
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Posted by: @rosed

@j Does CCL5 have anything to do with CCR5, like what Maraviroc or leronlimab works with?

@rosaleend

Indeed Rosaleen, these receptors are related 

https://pubmed.ncbi.nlm.nih.gov/16807236/

 


   
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(@j)
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Posted by: @j

For example, using the tool I mentioned previously, for 10mg/kg in mice the human equivalent dose for a 75kg person would be 60.81 mg.

To ensure that there are no misunderstandings regarding the dosage I mentioned above, it's 60,81 mg (almost 61 mg). I asked someone who's very knowledgeable about this product and he says that animal studies show good effects from emodin doses in the range of 30mg-50mg daily (human equivalent dose).

 


   
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(@j)
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Here's a very interesting study on the use of taxol in combination with lapachone: Potent inhibition of tumor survival in vivo by β-lapachone plus taxol: Combining drugs imposes different artificial checkpoints

https://www.pnas.org/doi/10.1073/pnas.96.23.13369


   
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(@rosed)
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@j What a phenomenal resource. Thank you for sharing this with me. Quick question... do you think it is okay to be on berberine and metformin together.  I have seen that many people take both.


   
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(@j)
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Posted by: @rosed

@j What a phenomenal resource. Thank you for sharing this with me. Quick question... do you think it is okay to be on berberine and metformin together.  I have seen that many people take both.

I think it's a very good idea to take both. Berberine protects against metformin-associated lactic acidosis:

https://pubmed.ncbi.nlm.nih.gov/28656086/

Note that berberine has powerful blood-sugar-lowering effects so when combined with metformin just make sure to check you're not going too low on blood sugar. 

 


   
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jens
 jens
(@jens)
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@laika Hi Laika

Thanks for all the links and posts. My wife( Lourdes) is struggling with TNBC with mets to the lungs  She was NED in 2019 but metastasized in 2021. Initially on  Olaparib until it became resistant. Our oncologist wanted to put her on Gemcitabine and Carboplatin. We decided to hold off and try an Oncolytic virus combined with a PD-1 immunotherapy. She is on her second dosage of an OV. I wanted to say thanks to the Immunotherapy protocol link. Very informative.

Lourdes also has a tumor under her arm. Did you have any radiation on any areas? Before or after chemo?

Would mind telling me the dose of Ivermectin you were taking or are taking? I am just not confident she is taking the right amount. Also did you take Hydroxychloroquine  with the Ivermectin at any time?

I couldn't open your TNBC protocol that you posted for Chris. Can you post the link again or email please? [email protected] 

Thanks again.

Jens


   
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laika
(@laika)
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Hi @jens

I'm so sorry to hear about Lourdes. Can you try accessing the spreadsheet here and let me know if it still doesn't work? That's great you found access to an OV-- are you getting that through a clinical trial or somewhere else? 

I did have radiation to my spine when I went metastatic, 19 days before starting chemo. I was in terrible pain, and it helped almost immediately. On the one hand, I think radiation can be synergistic with immunotherapy because it induces immunogenic cell death, which is immunostimulatory. On the other hand, I worry that the scar tissue it produces may be areas that are difficult for immune cells to penetrate, so any cancer cells that survive radiation might 'hide' there. If you can convince them, I think doing radiation while on immunotherapy (rather than before, as I did) would be best. 

My ivermectin dose varies. It makes me a little fatigued if I take too high a dose, so it depends on what I have the next day. My usual dose is around 20mg. I use the 1% injectable solution from amazon (10 mg / mL). I use a syringe to pull out ~2 mL and put it in two size 000 empty gel caps so I don't have to taste it. I usually take it for the first two weeks or so of a four week cycle.

I started hydroxychloroquine with ivermectin for a short time but stopped after I read something that suggested hydroxychloroquine could reduce the efficacy of ivermectin-- I can try to dig it up later.

IMO, a very important lifestyle factor you can work on to synergize with immunotherapy is the microbiome. Plenty of exercise and a high fiber diet with a lot of variety of fruits and vegetables. Frozen berries are an easy way to up your fiber intake. Many studies show a correlation between a healthy microbiome and good outcomes with immune checkpoint inhibitors.

Please keep us posted and let me know if you have any questions.

Take care


   
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(@chris48)
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Topic starter  

Posted by: @laika

@chris48

Apologies for the long delay. I'm always happy to share my story. I'm attaching my protocol, the spreadsheet format is better, but I don't want to post my personal Gmail publicly. My protocol is more optimized for synergy with immune checkpoint inhibitors since that's what I'm on.

Did her oncologist offer any adjuvant therapy after the recurrence? Off labels are good, but I think you need as much in the arsenal as possible.

I think you should push strongly for a PDL-1 inhibitor in this situation. Recent RCTs are showing significant benefit regardless of PDL-1 status. If onc says no, try getting a second opinion. If cost is an issue, see if there are any clinical trials you could enroll in that would offer it.

Sending you best wishes

 

 

Those files are awesome! Thank you so much!

In that spirit I have translated a PPT that I have created during the past 2 years. I contains a lot of information on various meds, supplements and therapy options for cancer (special focus on TNBC). I hope you can also find something useful in there. @rosaleend @jens maybe this could be interesting for you too.

Unfortunately, her docs won't give her immunotherapy because she does not have a genetic mutation (BRCA1, 2 etc). They did not even test for PDL-1 status. Anyway, due to the side effects I am unsure if this would be the right path in a NED situation. We are now doing the COC protocol (plus some supplements) and hope that her CTCs go quickly down to 0.

Laika, reaching NED status after having TNBC mets is absolutely amazing! I am so happy for you!!! 

All the best,

Christian

 


   
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(@j)
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Ammonia mediates mitochondrial uncoupling and promotes glycolysis via HIF-1 activation in human breast cancer MDA-MB-231 cells

https://www.sciencedirect.com/science/article/abs/pii/S0006291X1931681X


   
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jens
 jens
(@jens)
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Hi Johan.

 

Thanks for that. HIF-1 signaling pathway is a key in many different ways it seems.

jens


   
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(@j)
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Posted by: @jens

Hi Johan.

 

Thanks for that. HIF-1 signaling pathway is a key in many different ways it seems.

jens

Hi Jens, I am very sorry to hear Lourdes is not getting better. I agree with the changes you are making.

Here are a few suggestions:

 

TAMOXIFEN
+EGCG(synergistic cytotoxicity https://pubmed.ncbi.nlm.nih.gov/15457130/)
+ursolic acid: https://ecommons.cornell.edu/handle/1813/59279?show=full
+caffeic acid (sensitize cancer cells to tamoxifen https://aacrjournals.org/clincancerres/article/21/8/1877/79074/Caffeine-and-Caffeic-Acid-Inhibit-Growth-and
+baicalein (sensitize cancer cells to tamoxifen + HIF1α inhibition: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567056/
+luteolin (sensitize cancer cells to tamoxifen https://www.jocpr.com/abstract/synergistic-inhibition-of-drug-resistant-breast-cancer-cells-growth-by-the-combination-of-luteolin-and-tamoxifen-involve-6169.html
+Melatonin
+Berberine

PHENYL BUTYRATE Increase dosage e.g 6 grams in 3 divided dose or 9 grams in 3 divided doses. I'd make sure to get the cofactors at the same time, glycine 400-500mg, vitamin B2 100mg, L-Ornithine 500mg

HONOKIOL
MAGNOLOL ( https://liftmode.com/magnolol-powder/#10g)
ARTEMISININ

BICARBONATE 4 grams in 2 divided doses (AM/PM)

I've attached a screenshot with compounds to address HIF1. And will attached a few more screenshots below regarding other mechanisms.

Kind regards,

 

 

 


   
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(@j)
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STAT3


   
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(@j)
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INFLAMMATION


   
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(@j)
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GLYCOLYSIS


   
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(@j)
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HDAC


   
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(@j)
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LACTIC ACID


   
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(@j)
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AMMONIA


   
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(@j)
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Posted by: @j

AMMONIA

I'd start with Selenium, Magnesium, Zinc, B1/B6, Naringin, Citrulline, and Ornithine.

 

 


   
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(@j)
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Posted by: @j

Posted by: @j

AMMONIA

I'd start with Selenium, Magnesium, Zinc, B1/B6, Naringin, Citrulline, and Ornithine.

 

 

@jens Probiotics can also be useful to further reduce ammonia:

Lactobacillus bulgaricus

Lactobacillus acidophilus

Bifidobacterium longum

Saccharomyces boulardii
https://csef.usc.edu/History/2017/Projects/S1612.pdf

 


   
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(@j)
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Posted by: @j

Posted by: @jens

Hi Johan.

 

Thanks for that. HIF-1 signaling pathway is a key in many different ways it seems.

jens

Hi Jens, I am very sorry to hear Lourdes is not getting better. I agree with the changes you are making.

Here are a few suggestions:

 

TAMOXIFEN
+EGCG(synergistic cytotoxicity https://pubmed.ncbi.nlm.nih.gov/15457130/)
+ursolic acid: https://ecommons.cornell.edu/handle/1813/59279?show=full
+caffeic acid (sensitize cancer cells to tamoxifen https://aacrjournals.org/clincancerres/article/21/8/1877/79074/Caffeine-and-Caffeic-Acid-Inhibit-Growth-and
+baicalein (sensitize cancer cells to tamoxifen + HIF1α inhibition: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8567056/
+luteolin (sensitize cancer cells to tamoxifen https://www.jocpr.com/abstract/synergistic-inhibition-of-drug-resistant-breast-cancer-cells-growth-by-the-combination-of-luteolin-and-tamoxifen-involve-6169.html
+Melatonin
+Berberine

PHENYL BUTYRATE Increase dosage e.g 6 grams in 3 divided dose or 9 grams in 3 divided doses. I'd make sure to get the cofactors at the same time, glycine 400-500mg, vitamin B2 100mg, L-Ornithine 500mg

HONOKIOL
MAGNOLOL ( https://liftmode.com/magnolol-powder/#10g)
ARTEMISININ

BICARBONATE 4 grams in 2 divided doses (AM/PM)

I've attached a screenshot with compounds to address HIF1. And will attached a few more screenshots below regarding other mechanisms.

Kind regards,

 

 

 

https://www.frontiersin.org/articles/10.3389/fphar.2022.796763/full

Honokiol Inhibits HIF-1α-Mediated Glycolysis to Halt Breast Cancer Growth

 

 


   
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(@j)
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Posts: 2160
 

Posted by: @j

Posted by: @j

Posted by: @j

AMMONIA

I'd start with Selenium, Magnesium, Zinc, B1/B6, Naringin, Citrulline, and Ornithine.

 

 

@jens Probiotics can also be useful to further reduce ammonia:

Lactobacillus bulgaricus

Lactobacillus acidophilus

Bifidobacterium longum

Saccharomyces boulardii
https://csef.usc.edu/History/2017/Projects/S1612.pdf

 

Lactobacillus bulgaricus https://www.metabolics.com/lactobacillus-bulgaricus-powder-pot-of-100g.html

 


   
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(@j)
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https://pubmed.ncbi.nlm.nih.gov/23771315/

"In this study, we used MDA-MB-231 and MDA-MB435 breast cancer cells for experiment. Both cell lines are
triple-negative breast cancer (TNBC) cells, lacking expression of estrogen receptor, progesterone receptor, and HER2 proteins [43]. Effective therapies for TNBC are limited [44]. Therefore, additional therapeutic approaches are required. Here, we find that the combination of curcumin and emodin decreases breast cancer cell viability and induces apoptotic cell death more strongly than either drug alone"


   
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(@j)
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Posted by: @j

Posted by: @rosed

@j What a phenomenal resource. Thank you for sharing this with me. Quick question... do you think it is okay to be on berberine and metformin together.  I have seen that many people take both.

I think it's a very good idea to take both. Berberine protects against metformin-associated lactic acidosis:

https://pubmed.ncbi.nlm.nih.gov/28656086/

Note that berberine has powerful blood-sugar-lowering effects so when combined with metformin just make sure to check you're not going too low on blood sugar. 

 

Hi Rosaleen, to clarify, I think Berberine is a good addition to Metformin because of the protection against metformin-associated lactic acidosis. Not that I think it's a good anticancer combination. That wasn't clear from my response.

 


   
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(@j)
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Posts: 2160
 

@jens

Celecoxib and luteolin suppress breast tumor xenograft growth doi:10.1007/s13277-015-3322-5 

"To confirm our in vitro results, we tested the synergistic anticancer effect of celecoxib and luteolin in a nude mouse xenograft model. As shown in Fig. 4a, at the end of the overall treatment period, treatment with celecoxib alone, but not luteolin alone, reduced MDA-MB-231 tumor volumes relative to those in vehicle-treated mice. However, the celecoxib and luteolin combination treatment significantly reduced MDA-MB-231 tumor volumes relative to those in mice subjected to other treatments (p<0.05). As tumor growth is regulated by both reduced apoptosis and increased proliferation, we assessed the levels of cleaved PARP and PCNA (Fig. 4b,
c). The levels of cleaved PARP were markedly decreased, and those of PCNA were markedly increased in the MDA-MB231 tumors (p<0.05). These results indicate that the celecoxib and luteolin combination treatment increased tumor apoptosis and decreased tumor proliferation."

In the mice model, they used 30mg/kg celecoxib and 30mg/kg luteolin intraperitoneal twice a week (Monday, Thursday)

Conversion using https://dosecal.cftri.res.in/index.php results in approx 180mg celecoxib and 180mg luteolin for a 75kg person. Since they used i.p. treatment I don't know how this converts to oral dose, that's probably more difficult to determine but this dosage seems a good starting point, one could try 5 days of this combination at these dosages. 200mg celecoxib is just the regular dose, Daniel has 150mg liposomal luteolin in store.

Celecoxib should not be combined with metformin or with cimetidine, because of the increased risk of lactic acidosis.

 

 

 

 

 


   
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(@j)
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Apigenin and Luteolin Attenuate the Breaching of MDA-MB231 Breast Cancer Spheroids Through the Lymph Endothelial Barrier in Vitro

https://www.frontiersin.org/articles/10.3389/fphar.2018.00220/full


   
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(@j)
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Recap:

Apigenin + Luteolin https://www.frontiersin.org/articles/10.3389/fphar.2018.00220/full

Celecoxib + luteolin suppress breast tumor xenograft growth doi:10.1007/s13277-015-3322-5

Apigenin + metformin https://www.nature.com/articles/s41598-021-93270-0/figures/7

EGCG + Tapentadol https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754998/

 


   
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