Reporting August 1, 2007 in the journal Gastroenterology, clinical pharmacologist Scott Waldman, M.D., Ph.D., professor and chair of pharmacology and experimental therapeutics at Jefferson Medical College of Thomas Jefferson University, and his co-workers showed that GCC – guanylyl cyclase C, a protein receptor on the surface of intestinal epithelial cells for two hormones, guanylin and uroguanylin, can suppress tumor formation. These hormones regulate the growth of intestinal epithelial cells.
But early in colon cancer development, these growth-controlling hormones are “lost” and not expressed, disrupting GCC’s activity, and, Dr. Waldman believes, contributing to tumor formation. Using two separate mouse models that mimic the development of colon cancer in people, his team showed that GCC signaling blocks such tumors from forming.
According to Dr. Waldman, the group found that GCC stops tumors from forming through two different mechanisms. In one case, it controls cell growth, while in the other, it maintains “regulation of genomic integrity.”
In one mouse cancer model, the animals carried mutations in the APC gene, which causes colon polyps that frequently lead to colon cancer. Mice in the other cancer-development model were exposed to a commonly used experimental cancer-causing agent, azoxymethane. “We modeled both ways that humans develop colon cancer, and studied the effects of a lack of GCC on the incidence of colon cancer development,” he explains.
“We found that in animals that have APC mutations, tumors developed in the colon and small intestine, which is expected,” Dr. Waldman says. “A lack of GCC resulted in both larger tumors and a greater number of tumors in the large intestine.” In the carcinogen model, the absence of GCC caused an increase in both tumor number and size also.
The findings indicate that the mechanism of the increase in tumor development through loss of GCC expression was a combination, in both models, of a loss of genomic integrity and an increase in cell growth. “When you eliminate GCC from cells, they develop a level of genomic instability, where they start accumulating more mutations and lose pieces of genetic material,” he explains.
“Putting those pieces together – exposure to carcinogen or spontaneous mutations in APC – which happens to almost every colorectal cancer patient, and the loss of GCC signaling brought on by a loss of the two hormones in one of the earliest events that occurs in tumor development in the intestine,” he notes, “and it’s a recipe for colon cancer.”
The finding “converts colon cancer from a genetic disease, which is the way we’ve all thought about it, to a disease of hormone insufficiency,” Dr. Waldman says. “It’s a completely different way of thinking about the disease.
“Not only does this give a new paradigm in how we think about the disease, but it gives us a new paradigm for treating the disease – that is, by hormone replacement therapy.
Essentially, this takes the genetic disease and converts it to an endocrine disease, with a hormone solution.” The researchers would like to extend these studies to show that by treating patients with hormone replacement therapy, intestinal cancer formation can either be prevented or treated.
Steve Benowitz | EurekAlert!
NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)
High speed video recording precisely measures blood cell velocity
15.11.2017 | ITMO University
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
17.11.2017 | Physics and Astronomy
17.11.2017 | Health and Medicine
17.11.2017 | Studies and Analyses