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Re-puporsed drugs to treat NSCLC, ROS1-positive

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(@j)
Joined: 6 years ago
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Here are a few suggestions for reducing lactate:

Targeting the enzymes involved in lactate production
=============================================
Sodium bicarbonate, Magnesium carbonate, citric acid, alpha lipoic acid.

Inhibiting the glycolytic pathway, glycolysis, Warburg effect
=====================================
Methylene blue, Phloretin, Berberine

Blocking the Akt/mTOR pathway
====================
Rapamycin

Targeting lactate transporters
===================
Sodium citrate

Targeting lactic acid bacteria.
==================
Caprylic acid, Allicin

Inhibition of lactate dehydrogenase.
=======================
Sodium-Butyrate

Antioxidants
============
Vitamin C, lycopene, catechins, etc.


   
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(@daniel)
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@dng050 Albendazole is another option for HIF inhibition https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-10-143

Kind regards,

Daniel


   
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(@j)
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I wonder if Dr. Max Gerson was right when he claimed that diseased cells contained too much sodium and too little potassium, or if it is really the ammonia displacing the potassium from the cell's interior that is leading to lowered respiration and eventually leading to a shift from cellular respiration to glycolysis.


   
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(@daniel)
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@j Hi J,

A short comment from my side due to time constrains: Sodium has indeed a major role, via Na/H exchange that is known to be overactive in many cancers. I addressed this subject here pH in Cancer & Tumor Acidification: A Top Treatment Strategy - Cancer Treatments - from Research to Application (cancertreatmentsresearch.com)

This leads to the alkalinization of the intracellular space and as a result a shift to glyco.

Kind regards,
Daniel


   
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(@j)
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Posted by: @daniel

@j Hi J,

A short comment from my side due to time constrains: Sodium has indeed a major role, via Na/H exchange that is known to be overactive in many cancers. I addressed this subject here pH in Cancer & Tumor Acidification: A Top Treatment Strategy - Cancer Treatments - from Research to Application (cancertreatmentsresearch.com)

This leads to the alkalinization of the intracellular space and as a result a shift to glyco.

Kind regards,
Daniel

In his clinical practice, David Brownstein, MD has observed that the opposite is the case. In fact, he recommends adding sea salt and Celtic salt to the diet of cancer patients. Those salts are 30 to 40% sodium. Sodium is an essential mineral, necessary for proper insulin regulation in the body, etc. Ammonium/ammonia on the other hand is just plain toxic, which is why the body has complex systems to get rid of it and metabolize it to less toxic forms such as glutamine. But cancer cells have increased levels of glutamine synthase activity and use glutamine as energy source. 

 


   
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(@j)
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Marine life would be plagued with cancer if it was the sodium 😋


   
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(@j)
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I postulate that a) ammonium can replace potassium and b) high ammonia increases sodium in the cell. Thus, you need to get rid of the ammonia, not the sodium.


   
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(@daniel)
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@j Hi J. Thank you for sharing the points above. There are many that have observed many things and have drawn many conclusions, some good some less good. In my comment above I am not discussing specific observations and related conclusions that may or may of represent the real mechanisms behind depending on the "experimental" condition, but the well-established science indicating that Na/H transporter is highly active in many cancers and part of the fuel for that transporter in Na. Inhibition of that is not always but often connected with cell acidification and death. 

Of course, this is one piece of the puzzle from a scientific point of view and can be others that can have a higher weight and impact on the overall outcome.

Regarding marine life, of course we are not discussing the origin of cancer here but mechanisms that facilitate tumor evolution.

Finally, the fact that this mechanism exists (Na/H upregulated, more Na in the cell, more acidity outside the cell) doesn't mean that we should stop the use of Na that is an essential mineral important for the human body, but it does mean that we should not overuse that and that modulation of Na/H in cancer represents an opportunity that can lead to tumor modulation as well.

I agree Ammonium/ammonia is something that is good to address specifically if that jumps up as it can even be lethal, specifically during TLS. I discussed some points on how to address that about 8 years ago here If TLS (Tumor lysis syndrome) occurs - Cancer Treatments - from Research to Application (cancertreatmentsresearch.com)  including Phenylbutyrate to lower ammonia levels and Bumetanide to reduce negative impact of ammonia on brain when that reaches dangerous levels.

Sorry for my rare interventions here but one day I will be back 🙂

Kind regards,
Daniel


   
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(@j)
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Posted by: @daniel

@j Hi J. Thank you for sharing the points above. There are many that have observed many things and have drawn many conclusions, some good some less good. In my comment above I am not discussing specific observations and related conclusions that may or may of represent the real mechanisms behind depending on the "experimental" condition, but the well-established science indicating that Na/H transporter is highly active in many cancers and part of the fuel for that transporter in Na. Inhibition of that is not always but often connected with cell acidification and death. 

Of course, this is one piece of the puzzle from a scientific point of view and can be others that can have a higher weight and impact on the overall outcome.

Regarding marine life, of course we are not discussing the origin of cancer here but mechanisms that facilitate tumor evolution.

Finally, the fact that this mechanism exists (Na/H upregulated, more Na in the cell, more acidity outside the cell) doesn't mean that we should stop the use of Na that is an essential mineral important for the human body, but it does mean that we should not overuse that and that modulation of Na/H in cancer represents an opportunity that can lead to tumor modulation as well.

I agree Ammonium/ammonia is something that is good to address specifically if that jumps up as it can even be lethal, specifically during TLS. I discussed some points on how to address that about 8 years ago here If TLS (Tumor lysis syndrome) occurs - Cancer Treatments - from Research to Application (cancertreatmentsresearch.com)  including Phenylbutyrate to lower ammonia levels and Bumetanide to reduce negative impact of ammonia on brain when that reaches dangerous levels.

Sorry for my rare interventions here but one day I will be back 🙂

Kind regards,
Daniel

 

Aha! PB, indeed. We've come full circle!

https://www.nature.com/articles/pr199131.pdf

A few peptides can cause cancer to go into complete remission. Exceptional cases but still, it's the elephant in the room, Daniel. Even on this forum, we've seen it happen.

https://synergiesforcancertreatments.blogspot.com/p/17-year-glioblastoma-survivor.html

Have a great weekend!

 


   
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(@daniel)
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@j I knew you wanted to get to PB 😀 

Have a very nice weekend!


   
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(@j)
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Posted by: @daniel

@j I knew you wanted to get to PB 😀 

Have a very nice weekend!

Not exactly, but it emphasizes the message or hypothesis  I'm trying to convey

Cheers

 


   
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dng050
(@dng050)
Joined: 4 years ago
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After tapering off the tablet medicine, my brother is not well. While waiting for chemo/immunotherapy, we will try intravenous vitamin C. Are there ways to add synergy to IVC?

Here is our current protocol:

- fenbendazole, 444 mg twice a day
- IVC (50 grams) two to three days per week
- Ginsenosides 
- LDN (low-dose naltrexone)
- Doxycycline, 100 mg once a day 

While on IVC, we are thinking about pausing all supplements which might have an antioxidant, like curcumin, r-lipoic acid and hydrogen gas. 

dng050 


   
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(@j)
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@dng050 

 

 

Anti-inflammation and anti-cancer effects of Naringenin combination with Artemisinins in human lung cancer cells

https://www.sciencedirect.com/science/article/pii/S2452014422000401

Don't get attached to any treatment options, if it's not working you need to switch asap.

I've attached an excel spreadsheet with more ideas.

 

 


   
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(@j)
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Posted by: @dng050

Here is our current protocol:

- fenbendazole, 444 mg twice a day
- IVC (50 grams) two to three days per week
- Ginsenosides 
- LDN (low-dose naltrexone)
- Doxycycline, 100 mg once a day 

While on IVC, we are thinking about pausing all supplements which might have an antioxidant, like curcumin, r-lipoic acid and hydrogen gas. 

dng050 

In this en vivo study (colon cancer), Doxycycline upregulated the expression of NF-κB, MMP-9 & VEGF, downregulated p53, cytochrome-c, caspase-3 & caspase-9 expression.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801417/

Something to be aware of.

 

 

 


   
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(@j)
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Inhibition of autophagy by chloroquine potentiates synergistically anti-cancer property of artemisinin by promoting ROS dependent apoptosis

https://pubmed.ncbi.nlm.nih.gov/25308836/


   
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dng050
(@dng050)
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Topic starter  

@j I think we will do (far-infrared) sauna to increase blood flow before the IVC. Although worried about the heat shock proteins might assist cancer cells, we hope the potential advantage might outweigh the risk. 

We will also be adding magnesium before IVC, thanks for the idea.


   
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(@j)
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Posted by: @dng050

@j I think we will do (far-infrared) sauna to increase blood flow before the IVC. Although worried about the heat shock proteins might assist cancer cells, we hope the potential advantage might outweigh the risk. 

We will also be adding magnesium before IVC, thanks for the idea.

Good luck!

 


   
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(@j)
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Posted by: @j

I postulate that a) ammonium can replace potassium and b) high ammonia increases sodium in the cell. Thus, you need to get rid of the ammonia, not the sodium.

"it appears that the high-protein, high-fat, low-fiber diet typically consumed in America today will result in high concentrations of ammonia in the human colon." {ref}

 


   
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(@j)
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Posted by: @j

Posted by: @j

I postulate that a) ammonium can replace potassium and b) high ammonia increases sodium in the cell. Thus, you need to get rid of the ammonia, not the sodium.

"it appears that the high-protein, high-fat, low-fiber diet typically consumed in America today will result in high concentrations of ammonia in the human colon." {ref}

 

Ammonia can compete with phenylalanine for the enzymes involved in the formation of phenylacetate (PA) and phenylacetylglutamine (PAG), leading to decreased formation of PA and PAG and increased levels of phenylalanine in the body, in line with the levels observed in cancer patients {ref|ref}.

 


   
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(@j)
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Posted by: @daniel

@j Hi J,

A short comment from my side due to time constrains: Sodium has indeed a major role, via Na/H exchange that is known to be overactive in many cancers. I addressed this subject here pH in Cancer & Tumor Acidification: A Top Treatment Strategy - Cancer Treatments - from Research to Application (cancertreatmentsresearch.com)

This leads to the alkalinization of the intracellular space and as a result a shift to glyco.

Kind regards,
Daniel

The results of enzyme activity measurements from rat astrocyte cultures showed that NKA could also use NH+4 in place of K+ as a substrate. https://www.frontiersin.org/articles/10.3389/fnmol.2016.00057/full

 

This post was modified 1 year ago by Daniel

   
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(@j)
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Hi Daniel, I couldn't edit my post, could you? here's the link:

https://www.frontiersin.org/articles/10.3389/fnmol.2016.00057/full


   
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(@daniel)
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@j Hi Johan. Done!


   
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(@j)
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Posted by: @j

This is how I view the basic cancer process:

Stressors => Hypoxia

Hypoxia => increased reliance on glycolysis.

Glycolysis = the primary pathway used by cancer cells to generate energy.

Lactate is a product of glycolysis. Lactate is then used to generate energy.

Increased lactate => increase in ammonia.

An increase in the production of ammonia or a decrease in the ability of the
body to excrete it => interferes with the uptake of oxygen. This can lead to
hypoxia, as the tissues are not able to get enough oxygen.

=> Vicious cycle.

There are many other things going on but in my view, it's crucial to stop

this process. You can kill cancer cells while this process keeps going which then

leads to recurrence.

 

Check this out @daniel. Citric acid resulted in a 40% drop in ammonia at 2mg per day in 4 divided doses. 

Treatment of Hyperammonemia B. LEVIN, MD; ALEX RUSSELL, MD, MRCP 1967

 

 

 


   
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(@daniel)
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@j Very nice finding J!


   
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(@j)
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I created this diagram to demonstrate how ammonia may be involved in the initiation and development of cancer


   
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dng050
(@dng050)
Joined: 4 years ago
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Topic starter  

Interesting. Any recommendations on dosage and brand? 

dng050


   
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(@j)
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Posted by: @dng050

Interesting. Any recommendations on dosage and brand? 

dng050

I'd make sure to get the purest citric acid, maybe a brand like bulk supplements, or sour salt that is 100% citric acid. A year ago I tested different dosages and felt a bit agitated at the higher doses, I think I was taking 4 grams when I felt a bit anxious. But that might have been because of the quality of the product I used.

https://synergiesforcancertreatments.blogspot.com/p/citric-acid.html

 

 


   
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(@j)
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Microenvironmental ammonia enhances T cell exhaustion in colorectal cancer

https://pubmed.ncbi.nlm.nih.gov/36528023/

"We demonstrate that enhancing ammonia clearance reactivates T cells, decreases tumor growth, and extends survival. Moreover, decreasing tumor-associated ammonia enhances anti-PD-L1 efficacy. These findings indicate that enhancing ammonia detoxification can reactivate T cells, highlighting a new approach to enhance the efficacy of immunotherapies."


   
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(@j)
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Glutamine-released ammonia acts as an unprecedented signaling molecule activating lipid production

"Intriguingly, in this paper,Cheng et al1 for the first time reported that ammonia is not a waste product; rather, it is an unprecedented signaling molecule tying glucose and glutamine to lipid production in human cells.
This study revealed that ammonia released from glutamine triggers a cascade of cellular processes
leading to the activation of lipogenesis machinery for lipid production"

https://www.sciencedirect.com/science/article/pii/S2352304222002148

WOW!

 


   
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(@j)
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Posted by: @daniel

@j Hi J. Thank you for sharing the points above. There are many that have observed many things and have drawn many conclusions, some good some less good. In my comment above I am not discussing specific observations and related conclusions that may or may of represent the real mechanisms behind depending on the "experimental" condition, but the well-established science indicating that Na/H transporter is highly active in many cancers and part of the fuel for that transporter in Na. Inhibition of that is not always but often connected with cell acidification and death. 

Of course, this is one piece of the puzzle from a scientific point of view and can be others that can have a higher weight and impact on the overall outcome.

Regarding marine life, of course we are not discussing the origin of cancer here but mechanisms that facilitate tumor evolution.

Finally, the fact that this mechanism exists (Na/H upregulated, more Na in the cell, more acidity outside the cell) doesn't mean that we should stop the use of Na that is an essential mineral important for the human body, but it does mean that we should not overuse that and that modulation of Na/H in cancer represents an opportunity that can lead to tumor modulation as well.

I agree Ammonium/ammonia is something that is good to address specifically if that jumps up as it can even be lethal, specifically during TLS. I discussed some points on how to address that about 8 years ago here If TLS (Tumor lysis syndrome) occurs - Cancer Treatments - from Research to Application (cancertreatmentsresearch.com)  including Phenylbutyrate to lower ammonia levels and Bumetanide to reduce negative impact of ammonia on brain when that reaches dangerous levels.

Sorry for my rare interventions here but one day I will be back 🙂

Kind regards,
Daniel

 

@daniel 

Here's an interesting study: The interactive effects of ammonia exposure, nutritional status and exercise on metabolic and physiological responses in gold fish (Carassius auratus L.)

"This study aimed to elucidate the physiological effects of high environmental ammonia (HEA) following periods of feeding (2% body weight) and starvation (unfed for 7 days prior to sampling) in gold fish (Carassius auratus). Both groups of fish were exposed to HEA (1 mg/L; Flemish water quality guideline) for 0 h (control), 3 h, 12 h, 1 day, 4 days, 10 days, 21 days and 28 days. Measurements of weight gain (%), oxygen consumption (MO2), ammonia excretion rate, ammonia quotient (AQ), critical swimming speeds (Ucrit), plasma and muscle ammonia accumulation, plasma lactate, liver and muscle glycogen, lipid and protein content were done at various time intervals during the experimental periods. Overall, ammonia excretion rates, plasma ammonia accumulation and AQ were significantly affected by food regime in ammonia free water. HEA, the additional challenge in the present study, significantly altered all the studied parameters among fed and starved groups in days-dependent manner. Results show that weight gain (%), MO2Ucrit, protein content in liver and muscle, and glycogen content in muscle among starved fish under HEA were considerably reduced compared to control and fed fish. Additionally a remarkable increase in plasma ammonia level, muscle ammonia, lactate accumulation and AQ was seen. However in fed fish, MO2, ammonia excretion rate, AQ and lactate level augmented after exposure to HEA. These results indicate that starved fish appeared more sensitive to HEA than fed fish. Furthermore, as expected, the toxic effect of ammonia exposure in both feeding treatments was exacerbated when imposed to exhaustive swimming (swum at 3/4thUcrit). Such effects were more pronounced in starved fish. This suggests that starvation can instigate fish more vulnerable to external ammonia during exercise. Therefore, it was evident from our study that feeding ameliorates ammonia handling and reduces its toxicity during both routine and exhaustive swimming."

The other interesting thing I found is that, for fish, the toxic effect of ammonia is higher in low salinity levels. Meaning, higher salinity is protective against ammonia.

 

 

 


   
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