The role of serotonin in all cancers of the billiary and GI tracts was well-known in the first half of the 20th century. The term carcinoid syndrome was used to describe the spectrum of such cancers and it was widely acknowledged that most of the patients died as a result of the fibrosis that serotonin caused, and not as a result of the primary cancer.
It was not until the introduction of the poisonous SSRI class of drugs that this role started to get pushed into the background through skewed or directly fraudulent studies whose goal was to promote the use of the SSRI drugs. To add insult to injury, companies like Pfizer sell and openly market as beneficial the SSRI drugs while at the same time quietly running clinical trials with serotonin antagonists like terguride to reverse the fibrosis of various organs that serotonin is known to directly cause.
This new study shows that serotonin and cortisol are directly causative for liver cancer development. The role of serotonin should not be surprising to anybody given the information above, and the fact that fibrosis is an immediate precursor to cancer (as Peat wrote). The more "surprising" finding is that cortisol is also a causative agent for liver cancer. This is arguably a more impactful findings given that glucocorticoids are the most widely prescribed anti-inflammatory agents today, and surpass even the SSRI drugs in terms of widespread use. Virtually all patients enduring a hospital stay or even childbirth (especially through C-section) are prescribed a glucocorticoid to control inflammation. As it often turns out these days, the very drugs prescribed to control an inflammatory condition end up exacerbating it and even turning it deadly.
Finally, I am not convinced that cortisol and serotonin are only causative in males. The same mechanism is at play in both female and male liver cancer development and in fact serotonin levels are (on average) higher in females and non-cancer liver disease is also higher in females (as Peat wrote as well). So, unless I see a study vindicating these two hormones in females I am going to assume their role is equally detrimental for both sexes.
Incidentally, cyproheptadine has recently been found to retard the growth of liver cancer. Given the ability of cyproheptadine to block both serotonin and cortisol I doubt this finding is a coincidence.
Tumor-Associated Neutrophils and Macrophages Promote Gender Disparity in Hepatocellular Carcinoma in Zebrafish | Cancer Research
http://www.cmghjournal.org/article/S2352-345X(17)30004-8/fulltext
https://medicalxpress.com/news/2017-08-non-sex-hormones-sexing-liver-cancers.html
"...However, clinical trials targeting sex hormones did not produce sufficiently convincing results, suggesting that other factors might also be involved. Liver cancer models based on zebrafish also show sex disparity. In particular, two non-sex hormone factors, cortisol and serotonin, appear to play critical roles in the sex disparity of liver cancers."
"...Using a liver tumour model in krasv12 transgenic zebrafish, a research group led by Prof GONG Zhiyuan, including Ph.D. students YAN Chuan and YANG Qiqi from the Department of Biological Sciences, NUS found that some other factors which are not sex hormones play critical roles in the sex disparity of liver cancers. In one study, they found that a glucocorticoid hormone, cortisol, is produced more than usual in male zebrafish with liver cancers. This hormone could trigger two different types of white blood cells, neutrophils and macrophages, which in turn enhance the development of liver cancer. In another study, they found that serotonin, a neurotransmitter, is also produced more than usual in male oncogenic livers. This again can cause the growth of liver cancer through the activation of a major cell type involved in liver diseases (hepatic stellate cells)."
It was not until the introduction of the poisonous SSRI class of drugs that this role started to get pushed into the background through skewed or directly fraudulent studies whose goal was to promote the use of the SSRI drugs. To add insult to injury, companies like Pfizer sell and openly market as beneficial the SSRI drugs while at the same time quietly running clinical trials with serotonin antagonists like terguride to reverse the fibrosis of various organs that serotonin is known to directly cause.
This new study shows that serotonin and cortisol are directly causative for liver cancer development. The role of serotonin should not be surprising to anybody given the information above, and the fact that fibrosis is an immediate precursor to cancer (as Peat wrote). The more "surprising" finding is that cortisol is also a causative agent for liver cancer. This is arguably a more impactful findings given that glucocorticoids are the most widely prescribed anti-inflammatory agents today, and surpass even the SSRI drugs in terms of widespread use. Virtually all patients enduring a hospital stay or even childbirth (especially through C-section) are prescribed a glucocorticoid to control inflammation. As it often turns out these days, the very drugs prescribed to control an inflammatory condition end up exacerbating it and even turning it deadly.
Finally, I am not convinced that cortisol and serotonin are only causative in males. The same mechanism is at play in both female and male liver cancer development and in fact serotonin levels are (on average) higher in females and non-cancer liver disease is also higher in females (as Peat wrote as well). So, unless I see a study vindicating these two hormones in females I am going to assume their role is equally detrimental for both sexes.
Incidentally, cyproheptadine has recently been found to retard the growth of liver cancer. Given the ability of cyproheptadine to block both serotonin and cortisol I doubt this finding is a coincidence.
Tumor-Associated Neutrophils and Macrophages Promote Gender Disparity in Hepatocellular Carcinoma in Zebrafish | Cancer Research
http://www.cmghjournal.org/article/S2352-345X(17)30004-8/fulltext
https://medicalxpress.com/news/2017-08-non-sex-hormones-sexing-liver-cancers.html
"...However, clinical trials targeting sex hormones did not produce sufficiently convincing results, suggesting that other factors might also be involved. Liver cancer models based on zebrafish also show sex disparity. In particular, two non-sex hormone factors, cortisol and serotonin, appear to play critical roles in the sex disparity of liver cancers."
"...Using a liver tumour model in krasv12 transgenic zebrafish, a research group led by Prof GONG Zhiyuan, including Ph.D. students YAN Chuan and YANG Qiqi from the Department of Biological Sciences, NUS found that some other factors which are not sex hormones play critical roles in the sex disparity of liver cancers. In one study, they found that a glucocorticoid hormone, cortisol, is produced more than usual in male zebrafish with liver cancers. This hormone could trigger two different types of white blood cells, neutrophils and macrophages, which in turn enhance the development of liver cancer. In another study, they found that serotonin, a neurotransmitter, is also produced more than usual in male oncogenic livers. This again can cause the growth of liver cancer through the activation of a major cell type involved in liver diseases (hepatic stellate cells)."