(Press-News.org) Blocking dietary sugar and its activity in tumor cells may reduce cancer risk and progression, according to researchers from the Icahn School of Medicine. The study, conducted in fruit flies and published in the journal Cell, provides insight as to why metabolism-related diseases such as diabetes or obesity are associated with certain types of cancer, including pancreatic, breast, liver, and colon cancers.
Ross Cagan, PhD, Professor of Developmental and Regenerative Biology at Mount Sinai, has developed a cancer model in the fruit fly Drosophila that allows scientists to evaluate diseases in the context of the whole animal and multiple genetic targets, rather than just looking at the connection of one gene to one disease. In the current study, Dr. Cagan used fruit flies to understand the effects of diet and insulin resistance on cancer progression.
Cells use glucose for energy and to grow. When a cell becomes insulin resistant, glucose builds up in the blood instead of being absorbed by the cell, starving the cell and leading to metabolic diseases like diabetes. Because of this dysfunctional growth, scientists have been puzzled about how tumors can thrive in an insulin-resistant environment.
"Previous research has established a strong correlation between metabolic diseases and pancreatic, breast, liver, and colon cancers, but we have not determined how tumors grow so aggressively in this environment if they do not have the energy provided by glucose," said Dr. Cagan, who is also Associate Dean of the Graduate School of Biomedical Sciences at Mount Sinai. "Using our fruit fly model, we discovered how tumors overcome insulin resistance in the body and turn metabolic dysfunction to their advantage."
Dr. Cagan and his team engineered fruit flies to express Ras and Src, two important oncogenes, resulting in the development of small head tumors. Next, they fed the flies with a high-sugar diet that promoted insulin resistance. They found that high dietary sugar acts together with Ras and Src to increase insulin sensitivity specifically in tumor cells. By ramping up signaling of an important pathway called Wingless/Wnt, they increased tumor cells' insulin receptors to further promote insulin sensitivity. This cascade of activity changed these small, weak tumors and caused them to begin growing aggressively.
Armed with three new drug targets—glucose, the Ras/Src oncogenes, and Wingless/Wnt signaling—Dr. Cagan and his team identified compounds that can block the process. They treated the flies with acarbose, a treatment for diabetes; a compound called AD81; and a drug called pyrvinium. Acarbose blocked sugar conversion to glucose; AD81 cut off Ras/Src and caused cell death; and pyrvinium inhibited Wingless/Wnt signaling. Taken together, this cocktail of drugs substantially reduced tumor size and progression.
"Our study shows that sugar activates oncogenes in the tumor, which then promote insulin sensitivity, meaning that the exorbitant glucose levels in the blood pour into the tumor, having nowhere else to go in the insulin-resistant body," said Dr. Cagan. "We have identified a three-drug combination that stops this signaling activity and tumor growth in its tracks, without affecting normal cell function."
Next, the research team plans to find out whether the same cascade of events is happening in humans with insulin resistance using tumor samples. Based on those findings, Dr. Cagan and his team will test compounds that exploit this oncogene/sugar cascade.
###
This work was supported through multiple grants from the National Institutes of Health.
END
HOUSTON –Scientists at The University of Texas MD Anderson who identified a protein's dual role in cancer promotion have discovered a way to shut it down, opening a potential new avenue for cancer treatment.
Reporting this week in the journal Cell, the researchers describe the first compound that directly binds to and blocks Skp2, a protein they previously showed both turns off a cellular defense against cancer and switches on a cancer-feeding metabolic pathway.
"The beauty of this study is we identified an inhibitor and showed how it functions to block Skp2. Inhibitors ...
A research group led by researcher Shinji Hirata and Professor Koji Eto at CiRA has conducted a study in which iPS cells generated from a patient with congenital amegakaryocytic thrombocytopenia (CAMT) were induced to differentiate into blood cells in vitro and then used to undertake a detailed study of the differences between these and cells from healthy subjects. The researchers found that, in humans, thrombopoietin receptors are essential not only to the maintenance of the multipotent hematopoietic progenitor population and the production of platelets, but also to erythropoiesis ...
Omega-3 fatty acids, contained in oily fish such as salmon and trout, selectively inhibit growth and induce cell death in early and late-stage oral and skin cancers, according to new research from scientists at Queen Mary, University of London.
In vitro tests showed omega-3 fatty acids induced cell death in malignant and pre-malignant cells at doses which did not affect normal cells, suggesting they have the potential to be used in both the treatment and prevention of certain skin and oral cancers.
Omega-3 polyunsaturated fatty acids cannot be made by humans in large ...
Ruth Elliot, Senior Lecturer in the department of Mental Health and Learning Disability at the University of Huddersfield, has published an article discussing the need for a national 'Mental Health Pathway' to enable paramedics to provide the appropriate care for people who present mental health issues.
The Department of Health (DH) (2005a) acknowledges the huge modernisation of the ambulance service in England and faster access to people with immediate life threatening conditions, however the service is also responding to an increasing number of patients who have an ...
London (31 July 2013). New research suggests that failure by junior doctors in their annual changeover period to identify deteriorating patients and poor prioritisation skills are likely to drive a reduction in the quality and safety of patient care. Next Wednesday 7 August thousands of newly qualified doctors will take up their first hospital jobs and junior doctors will become a grade more senior. This period is associated with worse clinical outcomes than the rest of the year. Researchers writing in JRSM Short Reports, the open-access offshoot to the Journal of the Royal ...
A smartphone app that keeps track of your location and distance walked from home or hotel and warns you when you are likely to be caught out after dark has been developed by researchers in Pakistan to help sufferers of the debilitating disease night blindness. The app can also help travellers with the disease pinpoint hotels should they find themselves too far from base to get home safely.
The researchers describe details of the smartphone software in a forthcoming issue of the International Journal Mobile Learning and Organisation.
Kamran Ahsan, Obaid Khan and Abdul ...
Taking a dip in a freshwater lake can quickly lose its appeal on contact with slippery aquatic plants. These might include Elodea nuttallii and Najas marina, better known as western waterweed and spiny naiad, both of which have been spreading rapidly in German water bodies in recent years.
Ecologists are able to use them as indicator plants. Their proliferation allows researchers to draw conclusions on water quality – Elodea nuttallii and Najas marina are particularly common in lakes with rising water temperatures. The rapid spread of such plants over a wide area can ...
VIDEO:
Dr. Jessica Tyrrell talks through her latest research, which has investigated the ways in which chemicals build up in people of different socioeconomic status.
Click here for more information.
A new study published this week has found that the build-up of harmful chemicals in the body is affecting people of all social standings -- not just those from economically deprived backgrounds as previously thought.
The research has been led by Dr Jessica Tyrrell from the University ...
Reston, Va.– A more precise method for determining bone marrow involvement in patients with diffuse large B-cell lymphoma (DLBCL)—a key factor in tailoring patient management plans—has been identified by researchers in a study published in the August issue of The Journal of Nuclear Medicine. Imaging with 18F-FDG positron emission tomography/computed tomography (PET/CT), when compared to bone marrow biopsy, was more sensitive, showed a higher negative predictive value and was more accurate, changing treatment for 42 percent of patients with bone marrow involvement.
DLBCL ...
Bethesda, MD—A new culprit has been identified that likely plays a big role in the severity of asthma—a small protein chemokine called CCL26. These findings were published in the Journal of Leukocyte Biology and represent the first demonstration that CCL26 is a potent regulator of the migration of asthmatic eosinophils, commonly observed in asthmatic airways. Results from this discovery may lead to new drug targets for the treatment of asthma.
"We hope that these studies will help to develop a new treatment that would specifically abrogate bronchial inflammation and ...
