3 ms·

And are we sure inflammation is the root cause and not just a bystander? Couldn’t it be pathogens that are kept in check by inflammation, which then also cause

by manmal 1y ago

And are we sure inflammation is the root cause and not just a bystander? Couldn’t it be pathogens that are kept in check by inflammation, which then also cause cancer to develop? HPV and papillomas, and H. pylori and stomach cancer have been such findings. Apparently, sometimes cancer cells contain fungal DNA (not well studied though, could be contaminants as well). Edited the last sentence.

dillydogg 1y ago
Probably not, given the multiple conditions that are "sterile" inflammation that lead to neoplasms. Consider the example of asbestos; the particles lodge in the lungs which lead to a robust immune response that attempts to clear it, which has a strong association with the development of lung neoplasms. I'm not aware that the link between the inflammation and the development of the neoplasm is well understood. Autoimmune diseases and chronic GERD are other examples.
- manmal 1y ago
  Can you provide more context on what question you were addressing? I‘m not sure what point you are making here.
  - dillydogg 1y ago
    >Couldn’t it be pathogens that are kept in check by inflammation, which then also cause cancer to develop? In reference to this question. These conditions with prolonged inflammation lead to cancer in the absence of a primary pathogen. >Apparently, sometimes cancer cells contain fungal DNA (not well studied though, could be contaminants as well). In reference to this, if you are referring to the "tumor microbiome" hypothesis, it has been thoroughly debunked. http://dx.doi.org/10.1128/mbio.01607-23 http://dx.doi.org/10.1128/mbio.01607-23
    - manmal 1y ago
      > in the absence of a primary pathogen And how can absence of a pathogen be determined, in vivo? That sounds a bit overconfident in current tools, no? H. pylori apparently can hide inside Candida cells. Biofilm lets pathogens prosper while hiding them from diagnosis. Who knows what else is going on. I don’t think the microbiome hypothesis can be rejected at this point. Studies were flawed, yes. I personally am not a fan of the status-quo-ism that comments such as yours express. There’s so much that’s not explored here.
      - dillydogg 1y ago
        EDIT: Sorry, this came across rude, I feel poorly about the tone. I think I'll leave it up as is for posterity's sake but I agree there is a lot we don't know about these conditions. They have been sequenced pretty thoroughly without identifying an organism. H. pylori and bacteria in biofilms can be detected this way. In the case of asbestos, it seems clear that it is the asbestos particles and not an organism. As for the tumor microbiome hypothesis, I just find it hard to take a study seriously that suggests that human cancers harbor thermophilic bacteria found in deep sea vents. I try to support my views by the data we have available, and I think these are currently the most well supported models.
jghn 1y ago
> are we sure inflammation is the root cause and not just a bystander? The GP stated that it was *a* cause, not *the* cause
- manmal 1y ago
  True. The question still stands.
jszymborski 1y ago
Part of the reason cancer is such an interesting field of study in my personal opinion is: (1) You get a lot of these chicken-or-egg situations where the answer is more like "chicken-AND-egg". (2) Cancer is almost always the result of a million things going wrong at once... it's a slow unravelling of the bonkers number of safe-guards our cells have to keep them healthy and normal. Inflammation is a normal part of a healthy, functioning body. It can be caused by anything from scraping your knee to getting a cold. It's useful, and as your comment says, it is an important part to fighting off infections which themselves in rare cases cause cancer. It also plays a pathological role in some diseased like auto-immune disorders, IBS, meningitis, etc... Inflammation, both the healthy and pathological sort, can help set the stage for tumour to form by contributing to the formation of what's known as a "tumour microenvironment" [0]. Chronic inflammation, often caused by disease, is more likely to keep up this permissive environment than one-off cases, and therefore more likely to result in a tumour By the way, we understand DNA mutation/damage to work similarly. It happens all the time naturally, and sometimes mutations are fortuitous, but mostly they are ironed out by the cells machinery. Increasing the rate of mutation can overwhelm that machinery and cause tumours to snowball. So, that's how inflammation can contribute to the initialization of tumours or at least environments that are more permissive of tumours. Tumours, however, also might cause inflammatory response to promote cancer progression through hijacking cell signalling, promoting epithelial-mesenchymal transitions, etc... [1]. We've known inflammation has been linked to cancer since at least 1863 [2], so this is pretty well-trodden territory. The immune system and inflammation is extremely complicated (or at least, I always found it to be), so I'm also not surprised that there are a lot of mysteries lurking. Finally, to answer your question: I'm sure in some cases inflammation is just bystander. My understanding is that inflammation is not the primary mechanism by which HPV causes cancer, so it is very easy to believe it to be a bystander in that case. H. pylori is a good example of chronic GI inflammation that raises your risk of cancer by way of inflammation. I'm not familiar with the fungal DNA research, so can't comment. Also disclaimer: It's been a while since I've studied cancer directly, I'm more of a computational biologist these days. Sorry if I made an error here. [0] https://pmc.ncbi.nlm.nih.gov/articles/PMC6831096/ https://pmc.ncbi.nlm.nih.gov/articles/PMC6831096/ [1] https://blog.cellsignal.com/hallmarks-of-cancer-tumor-promoting-inflammation https://blog.cellsignal.com/hallmarks-of-cancer-tumor-promot... [2] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(00)04046-0/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6...

by manmal 1y ago

dillydogg 1y ago

Probably not, given the multiple conditions that are "sterile" inflammation that lead to neoplasms. Consider the example of asbestos; the particles lodge in the lungs which lead to a robust immune response that attempts to clear it, which has a strong association with the development of lung neoplasms. I'm not aware that the link between the inflammation and the development of the neoplasm is well understood. Autoimmune diseases and chronic GERD are other examples.

manmal 1y ago
Can you provide more context on what question you were addressing? I‘m not sure what point you are making here.
- dillydogg 1y ago
  >Couldn’t it be pathogens that are kept in check by inflammation, which then also cause cancer to develop? In reference to this question. These conditions with prolonged inflammation lead to cancer in the absence of a primary pathogen. >Apparently, sometimes cancer cells contain fungal DNA (not well studied though, could be contaminants as well). In reference to this, if you are referring to the "tumor microbiome" hypothesis, it has been thoroughly debunked. http://dx.doi.org/10.1128/mbio.01607-23 http://dx.doi.org/10.1128/mbio.01607-23
  - manmal 1y ago
    > in the absence of a primary pathogen And how can absence of a pathogen be determined, in vivo? That sounds a bit overconfident in current tools, no? H. pylori apparently can hide inside Candida cells. Biofilm lets pathogens prosper while hiding them from diagnosis. Who knows what else is going on. I don’t think the microbiome hypothesis can be rejected at this point. Studies were flawed, yes. I personally am not a fan of the status-quo-ism that comments such as yours express. There’s so much that’s not explored here.
    - dillydogg 1y ago
      EDIT: Sorry, this came across rude, I feel poorly about the tone. I think I'll leave it up as is for posterity's sake but I agree there is a lot we don't know about these conditions. They have been sequenced pretty thoroughly without identifying an organism. H. pylori and bacteria in biofilms can be detected this way. In the case of asbestos, it seems clear that it is the asbestos particles and not an organism. As for the tumor microbiome hypothesis, I just find it hard to take a study seriously that suggests that human cancers harbor thermophilic bacteria found in deep sea vents. I try to support my views by the data we have available, and I think these are currently the most well supported models.

jghn 1y ago

> are we sure inflammation is the root cause and not just a bystander? The GP stated that it was *a* cause, not *the* cause

manmal 1y ago
True. The question still stands.

jszymborski 1y ago

Part of the reason cancer is such an interesting field of study in my personal opinion is: (1) You get a lot of these chicken-or-egg situations where the answer is more like "chicken-AND-egg". (2) Cancer is almost always the result of a million things going wrong at once... it's a slow unravelling of the bonkers number of safe-guards our cells have to keep them healthy and normal. Inflammation is a normal part of a healthy, functioning body. It can be caused by anything from scraping your knee to getting a cold. It's useful, and as your comment says, it is an important part to fighting off infections which themselves in rare cases cause cancer. It also plays a pathological role in some diseased like auto-immune disorders, IBS, meningitis, etc... Inflammation, both the healthy and pathological sort, can help set the stage for tumour to form by contributing to the formation of what's known as a "tumour microenvironment" [0]. Chronic inflammation, often caused by disease, is more likely to keep up this permissive environment than one-off cases, and therefore more likely to result in a tumour By the way, we understand DNA mutation/damage to work similarly. It happens all the time naturally, and sometimes mutations are fortuitous, but mostly they are ironed out by the cells machinery. Increasing the rate of mutation can overwhelm that machinery and cause tumours to snowball. So, that's how inflammation can contribute to the initialization of tumours or at least environments that are more permissive of tumours. Tumours, however, also might cause inflammatory response to promote cancer progression through hijacking cell signalling, promoting epithelial-mesenchymal transitions, etc... [1]. We've known inflammation has been linked to cancer since at least 1863 [2], so this is pretty well-trodden territory. The immune system and inflammation is extremely complicated (or at least, I always found it to be), so I'm also not surprised that there are a lot of mysteries lurking. Finally, to answer your question: I'm sure in some cases inflammation is just bystander. My understanding is that inflammation is not the primary mechanism by which HPV causes cancer, so it is very easy to believe it to be a bystander in that case. H. pylori is a good example of chronic GI inflammation that raises your risk of cancer by way of inflammation. I'm not familiar with the fungal DNA research, so can't comment. Also disclaimer: It's been a while since I've studied cancer directly, I'm more of a computational biologist these days. Sorry if I made an error here. [0] https://pmc.ncbi.nlm.nih.gov/articles/PMC6831096/ https://pmc.ncbi.nlm.nih.gov/articles/PMC6831096/ [1] https://blog.cellsignal.com/hallmarks-of-cancer-tumor-promoting-inflammation https://blog.cellsignal.com/hallmarks-of-cancer-tumor-promot... [2] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(00)04046-0/fulltext https://www.thelancet.com/journals/lancet/article/PIIS0140-6...