TAG: "Colon"

Small RNA plays big role in suppressing cancer

UC Davis research could potentially lead to new cancer therapies.

Yu-Jui Yvonne Wan, UC Davis

By Dorsey Griffith, UC Davis

The micro RNA miR-22 has long been known for its ability to suppress cancer. However, questions remain about how it achieves this feat. For example, which molecules are regulating miR-22, and which are miR22 targets?

Researchers at UC Davis have unraveled some of these relationships, identifying several interactions that directly impact liver and colon cancer. The work provides new insights into how miR-22 operates and could potentially lead to new cancer therapies. The study was published in The Journal of Biological Chemistry.

“There are quite a few molecules present in the gastrointestinal (GI) tract that regulate miR-22,” said Yu-Jui Yvonne Wan, vice chair for research in the Department of Pathology and Laboratory Medicine and senior author on the paper. “If so many chemicals in the GI tract can regulate miR-22, it must be physiologically significant. We needed to better understand the molecules that regulate miR-22 in cancer, as well as the pathways miR-22 controls.”

Micro RNAs, like miR-22, play a major role in gene expression by selectively silencing particular genes. To understand the role of miR-22 in liver and colon cancer, Wan and her colleagues studied mice that lacked the bile acid receptor, farnesoid x receptor (FXR), which balances bile acid and cholesterol. Without FXR, mice spontaneously develop liver cancer. They also examined the expression of miR-22 in human liver cancer and colon cancer specimens.

The researchers found that the journey begins with bile acids, such as hydrophilic chenodeoxycholic acid, which activates FXR. In turn, FXR increases miR-22, which reduces the expression level of Cyclin A2, a protein that influences cell division and protects liver and colon cells from excessive proliferation.

The team confirmed these results using different models and found there is an inverse relationship between miR-22 and Cyclin A2 expression levels in liver and colon cancer cells.

The research also showed that miR-22 can be activated by vitamin D3, which can reduce the toxicity of hydrophobic bile acids. These pieces of information highlight the potential impact of diet and vitamins on GI cancer formation.

“People who are obese, or eating a high-fat Western diet, tend to have dysregulated bile acid synthesis,” said Wan. “When that happens, FXR can be inactivated, potentially decreasing the level of miR-22, increasing the expression of Cyclin A2 and disrupting the cell cycle. So this pathway may play a role in Western diet-associated carcinogenesis.”

In addition, miR-22 has a complicated relationship with a number of cancers, including breast and lung, and may offer promise as a cancer therapeutic target. In addition to targeting Cyclin A2, miR-22 also inhibits the expression level of histone deacetylases (HDACs), proteins that control gene expression by modification of histone structure. A number of HDAC inhibitors are FDA- approved anti-cancer drugs, and miR-22 can potentially be used to treat cancer.

“I’m not so sure miR-22 is all good,” said Wan. “We don’t know what it will target in normal cells. Our next step is to identify more miR-22 effects.”

Other researchers on the paper were Fan Yang, Ying Hu and Hui-Xin Liu.

This research was supported by NIH grants DK092100 and CA53596.

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Diverticulosis much less risky than previously thought

Study contradicts common wisdom on rate of progression from diverticulosis to diverticulitis.

Brennan Spiegel, UCLA

Brennan Spiegel, UCLA

People who have diverticulosis, pouches in the lining of the colon, often worry that they will develop a painful and sometimes serious condition called diverticulitis. After all, previous research showed that up to one in four, or 25 percent, eventually would.

Now, in a 15-year study that contradicts the common wisdom on the rate of progression from diverticulosis to diverticulitis, UCLA researchers demonstrate that the risk is significantly lower than previously thought — about 1 percent over seven years. The researchers also found that those diagnosed with diverticulosis at a younger age are more likely to progress to diverticulitis than those diagnosed at an older age.

The study will help inform patients with diverticulosis — particularly those diagnosed at a younger age — and their physicians about the risks of developing acute diverticulitis, said study senior author Dr. Brennan Spiegel, an associate professor of medicine at the David Geffen School of Medicine at UCLA.

“These colon pouches are commonly detected during colonoscopy, and patients wonder if they are important and what to do with them,” Spiegel said. “In short, diverticulosis is not something to worry much about. Chances are low that something will happen.”

The study appears in the December edition of the peer-reviewed journal Clinical Gastroenterology and Hepatology.

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Non-invasive test could improve colon cancer screening rates

Study explores best ways to reach uninsured patients.

Samir Gupta, UC San Diego

Organized mailing campaigns could substantially increase colorectal cancer screening among uninsured patients, a study published in the Aug. 5 online edition of JAMA Internal Medicine reveals. The research also suggests that a non-invasive colorectal screening approach, such as a fecal immunochemical test (FIT) might be more effective in promoting participation in potentially life-saving colon cancer screening among underserved populations than a colonoscopy, a more expensive and invasive procedure.

The study was led by Samir Gupta, M.D., M.S.C.S., an associate professor of clinical medicine and gastroenterologist at the UC San Diego School of Medicine and Veterans Affairs San Diego Healthcare System, and conducted by UT Southwestern’s Division of Digestive and Liver Diseases, Simmons Cancer Center, and the Moncrief Cancer Institute, in close collaboration with John Peter Smith (JPS) Hospital in Fort Worth, Texas.

As part of the study, uninsured patients not up-to-date with screening between the ages of 54 to 64 years and cared for by a safety-net health system were sent mailed invitations to use and return a no-cost FIT, or encouraged to undergo a colonoscopy through a mailed invitation to schedule one at no cost. In addition, both groups received telephone follow-up to promote test completion.

The study showed that FIT participation tripled, and colonoscopy participation doubled in the study sample of nearly 6,000 patients, when compared to usual care strategy for colorectal screenings. According to Gupta, the difference was much bigger than expected, and the findings could have health policy implications.

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New alternative to surgery lets doctors remove suspicious polyps

Minimally invasive procedure keeps colon intact.

James Yoo, UCLA

Millions of people each year have polyps successfully removed during colonoscopies. But when a suspicious polyp is bigger than a marble or in a hard-to-reach location, patients are referred for surgery to remove a portion of their colon — even if doctors aren’t sure whether the polyp is cancerous or not.

Since only 15 percent of all polyps turn out to be malignant, many patients are unnecessarily subjected to the risks of this major surgery. Now there is an alternative.

A UCLA team of surgeons and gastroenterologists has been performing a new, minimally invasive procedure to remove large and hard-to-reach polyps while keeping the colon intact. The procedure, which combines two minimally invasive techniques, has currently been performed at only a handful of medical centers in the United States.

In the June issue of the journal Surgical Endoscopy, the UCLA researchers present their experiences using the new technique — known as CELS, for combination endoscopy and laparoscopy surgery — and offer the first comparison of the new technique and standard surgery.

“The CELS approach combines the best of minimally invasive techniques and may prove to be a viable option for select patients,” said senior author Dr. James Yoo, an assistant professor of surgery and chief of the colon and rectal surgery program for the UCLA Health System and the David Geffen School of Medicine at UCLA.

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