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!
Scientists learn more about how gene linked to autism affects brain
19.06.2018 | Cincinnati Children's Hospital Medical Center
Overdosing on Calcium
19.06.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.
Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...
Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...
Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.
Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...
The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.
Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.
An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.
Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...
13.06.2018 | Event News
08.06.2018 | Event News
05.06.2018 | Event News
20.06.2018 | Information Technology
20.06.2018 | Materials Sciences
20.06.2018 | Life Sciences