More "miscellany" PART ONE: more on nasty cancer (General)

by David Turell @, Thursday, May 25, 2023, 18:54 (7 days ago) @ David Turell
edited by David Turell, Thursday, May 25, 2023, 19:25

Trying to damage the liver from a distance:

"Cancers often release molecules into the bloodstream that pathologically alter the liver, shifting it to an inflammatory state, causing fat buildup and impairing its normal detoxifying functions, according to a study from investigators at Weill Cornell Medicine.

"This discovery illuminates one of cancer's more insidious survival mechanisms and suggests the possibility of new tests and drugs for detecting and reversing this process.

"In the study, published in Nature, the researchers found that a wide variety of tumor types growing outside the liver remotely reprogram the liver to a state resembling fatty liver disease via secretion of extracellular vesicles and particles (EVPs) containing fatty acids. The scientists found evidence of this process in animal models of cancer and in the livers of human cancer patients.


"In their work published in 2015, for example, the team discovered that pancreatic cancers secrete molecules encapsulated in extracellular vesicles that travel through the bloodstream, are taken up by the liver and prepare the organ to support the outgrowth of new, metastatic tumors.

"In the new study, the researchers uncovered a different set of liver changes caused by distant cancer cells which they observed in animal models of bone, skin and breast cancer that metastasize to other organs but not to the liver. The study's key finding is that these tumors induce accumulation of fat molecules in liver cells, consequently reprogramming the liver in a way that resembles the obesity- and alcohol-related condition known as fatty liver disease.

"The team also observed that reprogrammed livers have high levels of inflammation, marked by elevated level of tumor necrosis factor-α (TNF-α), and low levels of drug-metabolizing enzymes called cytochrome P450, which break down potentially toxic molecules, including many drug molecules. The observed reduction in cytochrome P450 levels could explain why cancer patients often become less tolerant of chemotherapy and other drugs as their illness progresses.

"The researchers traced this liver reprogramming to EVPs that are released by the distant tumors and carry fatty acids, especially palmitic acid. When taken up by liver-resident immune cells called Kupffer cells, the fatty acid cargo triggers the production of TNF-α, which consequently drives fatty liver formation.


"'One of our more striking observations was that this EVP-induced fatty liver condition did not co-occur with liver metastases, suggesting that causing fatty liver and preparing the liver for metastasis are distinct strategies that cancers use to manipulate liver function," said co-first author Gang Wang, a postdoctoral associate in the Lyden laboratory. Jianlong Li, a scientific collaborator in the Lyden laboratory, is also a co-first author of the study.

"The scientists suspect that the fatty liver condition benefits cancers in part by turning the liver into a lipid-based source of energy to fuel cancer growth.

"'We see in liver cells not only an abnormal accumulation of fat but also a shift away from the normal processing of lipids, so that the lipids that are being produced are more advantageous to the cancer," said co-senior author Dr. Robert Schwartz, associate professor of medicine in the Division of Gastroenterology and Hepatology at Weill Cornell Medicine and a hepatologist at NewYork-Presbyterian/Weill Cornell Medical Center.

"'There are also crucial molecules involved in immune cell function, but their production is altered in these fatty livers, hinting that this condition may also weakens anti-tumor immunity," said co-senior author Haiying Zhang, assistant professor of cell and developmental biology in pediatrics at Weill Cornell Medicine.

"The researchers were able to mitigate these systemic effects of tumors on the livers by implementing strategies such as blocking tumor-EVP release, inhibiting the packaging of palmitic acid into tumor EVPs, suppressing TNF-α activity, or eliminating Kupffer cells in the experimental animal model."

Comment: the abnormal mutations manage to subvert normal DNA processes into wild uncontrolled growth. One could make the case that an evil designer is running the show, but one can also point out that just a mild switch to the DNA code can unleash these cancer cells which then use normal processes in abnormal ways. One might guess that design processes, hidden in DNA for controlled use are found by the rogue mutations and subverted to uncontrolled use. Cancer cells are only as intelligent as the code they twist through those mutations.

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