As cancer mortality rates generally fall down, doctors have indicated awkward inconsistencies: it seems that deaths of colorectal cancer among people under 55 are spreading. According to the American Cancer Society, deaths in the junior group increased by 1% between 2007 and 2016.
A new study led by scientists Salk Institute suggests that the growth of colorectal cancer is high-fat diets fat by looking after the balance of acids in the bowel and triggering a hormonal signal that allows cancerous cells to thrive. The perceptions, which appeared in Cell on February 21, 2019, explain why colorectal cancer, which can take decades to develop, can be seen in younger people growing up at a time when higher fat diets are common.
"This study provides a new way to reduce inflammation, restoring the bowel health and gradually move forward," said Professor Ronald Evans, director of the Gene Expression Laboratory, researcher Howard Hughes Medical Institute and holder of the Salk Marquee Chair in Molecular and Biology of Development.
The research, conducted in a mouse model, suggests how lifestyle and genetics converge. The researchers found that the animals with an APC bearing, the most common genetic incubation in people with colorectal cancer, had developed cancer faster when they fed a high fat diet.
"It may be that when you are genetically genetically for colon cancer, something like a high fat diet is repeat," said co-author of study Ruth Yu, a staff researcher at the Gene Translation Lab in Salk.
The bowel and bowel (commonly combined as the "gut") are organs that work hard. As you eat, your shuttle needs to be regenerated regularly to undo the damage made by digestive acids. To do this, the cattle are a population of stem cells that can replenish linear cells when needed.
Scientists have found that colorectal cancers often come from mutations in these cell cells. The most common colorectal ovation associated with cancer in a gene of the APC name, which usually acts as a "suppressor tumor" gene because it controls how often cells are share. Mutations in the APC gene can get rid of that control and allow cells to split quickly and become cancerous.
Over the past four decades, Evans and his colleagues have investigated the roles of gap acids. (There are 30 types of box acids flowing around in the cushion to help digest food and absorb cholesterol, fat and fatty fat nutrients). The laboratory finds were the exposure that Acid boxes send hormonal signals to intestine cell cells through a protein of the name Judgment X receptor (FXR). For the new study, researchers discovered how high fat diets affect those hormonal signs.
Study the first author, Ting Fu, a post-doctoral colleague at Salk, started by following an idea in a mouse model with an APC. These mice develop early signs of colorectal cancer, so they decided to monitor the levels of a loophole acid at the same time. He found that the types of box acids known to be interacting with FXR were increasing at the same time as cancer could begin – and the presence of additional gap acids following a rapid cancer increase.
"We have seen a very dramatic increase in cancer growth after boiling acid," said Michael Downes, senior staff scientist in Salk and the co-equivalent author of the study. "Our experiments showed that maintaining the balance of the acids of a gap is key to reducing cancer growth."
The researchers showed that feeding these mice was a high fat diet such as adding fuel to fire: higher levels of two specific bile acids increase high fat diets that weaken FXR activity. The shuttle wants to repair itself, and FXR keeps the process slow, consistent and secure. When gap acids prevent FXR, a group of cell cells begins to grow rapidly and accumulate DNA damage.
"We knew that high fat diets and gap acids were risk factors for cancer, but we did not expect to find that they were affecting FXR in cell cells," said Annette Atkins, a staff researcher in Salk and co- author of the study.
The mice developed with NPA burials developed an unusual growth of the adenomas name. In humans, adenomas are common in the intestine and are routinely removed during colonoscopies. These growths usually take decades to turn malignant adenocarcinomas. Yet, the adenomas in these mice turned rapidly cancerous when high fat diets were put.
Finally, the researchers found a possible cellular mechanism to explain the increase in colorectal cancer deaths in younger people. Their theory is that high fat diets have become more common in the United States, more people with NPA migrants speed up their cancer growth through this diet.
Next, researchers decided for a new cancer fighting weapon. They use a molecule of the FexD name, developed in Salk, to operate FXR in bowel cells. FexD seems to counter the damage made by unbalanced gap acids in both mouse organ models and human colon cancer cell lines.
Although more experiments need to be done before FexD is proven in people, the team says that the drug candidate has some promising features: he can reach the colon and act on FXR, so production should less side effects than other drugs.
"Although colon cancer is considered impractical, Ting's work is opening a completely new boundary in understanding and treating the disease," said Evans.