Researchers reveal new potential means to suppress tumor growth

Main category: Cancer / Oncology
Also included in: genetics
Article Date: June 5, 2013-0:00 PDT current ratings for:
Researchers reveal new potential means to suppress tumor growth

Researchers at the University of California, San Diego School of Medicine, with colleagues at the University of Rochester Medical Center have identified a new mechanism that seems to remove the tumor growth, opening up the possibility of developing a new class of anti-cancer drugs.

Written in first editions online this week by the proceedings of the Academy national of Sciences (PNAS), Willis X. Li, Ph.d., Professor in the Department of medicine at UC San Diego, reports that a particular form of signaling called STAT5A protein stabilizes the formation of heterochromatin (a form of chromosomal DNA), which in turn removes the ability of cancer cells to give instructions to multiply and grow.

Specifically, Li and his colleagues concluded that the place of STAT form promotes and stabilizes the heterochromatin, which keeps DNA closely packed and inaccessible to transcription factors. "As a result, genes 'buried' in heterochromatin are not expressed," said Li.

Phosphorylation is a fundamental cellular function in which a phosphate group is added to a protein or molecule, the cause to activate or disable or modify its function. A STAT place lack of this phosphate group.

Li said that in previous studies with the fruit flies, the place of STAT caused chromatin form to condense in heterochromatin, while the phosphorylated version prompted the dispersal and loss of the heterochromatin, promoting the expression of genes.

"STAT site promotes and stabilizes the formation of heterochromatin, which in turn removes the gene transcription," Li said. "when we have expressed either HP1 (the central element of the heterochromatin) or place STAT5A in human cancer cells, several genes important for the growth of the cancer are removed." These cancer cells do not grow as fast or as large as their cancer cells parental control in xenograft models mouse."

Most suppressors tumor known, such as p53 or Rb function by inhibiting the progression of the cell cycle or by stimulating cell death or apoptosis. Li said their findings indicate a potential new way to inhibit the expression of the genes of cancer and could constitute a new class of tumour suppressors.

"We are trying to identify drugs to small molecules that can promote the formation of heterochromatin without stopping cell division or causing the death of the cell," he said. "These drugs, if found, may be effective in treating cancer with fewer side effects."

Article adapted by Medical News Today press release original. Click on "references" tab above for the source.
Visit our cancer / Oncology section for the latest news on this subject. Co-authors are Xiaoyu Hu, Amy Tsurumi and Hartmut Land, Department of biomedical genetics, University of Rochester Medical Center; Pranabananda Dutta, Jinghong Li and Jingtong Wang, Department of medicine, UCSD.
Funding of this research came, in part, grants from the National Institutes of Health R01CA131326 and RO1CA138249 and a leukemia & Lymphoma Society Research Scholar grant.
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Potential Therapeutic Target Discovered For Cushing's Disease

Main Category: Cancer / Oncology
Also Included In: Neurology / Neuroscience;??Endocrinology
Article Date: 10 May 2013 - 0:00 PDT Current ratings for:
Potential Therapeutic Target Discovered For Cushing's Disease

Scientists at the Salk Institute for Biological Studies have identified a protein that drives the formation of pituitary tumors in Cushing's disease, a development that may give clinicians a therapeutic target to treat this potentially life-threatening disorder.

The protein, called TR4 (testicular orphan nuclear receptor 4), is one of the human body's 48 nuclear receptors, a class of proteins found in cells that are responsible for sensing hormones and, in response, regulating the expression of specific genes. Using a genome scan, the Salk team discovered that TR4 regulates a gene that produces adrenocorticotropic hormone (ACTH), which is overproduced by pituitary tumors in Cushing's disease (CD). The findings were published in the early online edition of Proceedings of the National Academy of Sciences.

"We were surprised by the scan, as TR4 and ACTH were not known to be functionally linked," says senior author Ronald M. Evans, a professor in Salk's Gene Expression Laboratory and a lead researcher in the Institute's Helmsley Center for Genomic Medicine. "TR4 is driving the growth and overexpression of ACTH. Targeting this pathway could therapeutically benefit treatment of CD."

In their study, Evans and his colleagues discovered that forced overexpression of TR4 in both human and mouse cells increased production of ACTH, cellular proliferation and tumor invasion rates. All of these events were reversed when TR4 expression was reduced.

First described more than 80 years ago, Cushing's disease is a rare disorder that is caused by pituitary tumors or excess growth of the pituitary gland located at the base of the brain. People with CD have too much ACTH, which stimulates the production and release of cortisol, a hormone that is normally produced during stressful situations.

While these pituitary tumors are almost always benign, they result in excess ACTH and cortisol secretion, which can result in various disabling symptoms, including diabetes, hypertension, osteoporosis, obesity and psychological disturbances. Surgical removal of the tumors is the first-line therapy, with remission rates of approximately 80 percent; however, the disease recurs in up to 25 percent of cases.

Drugs such as cabergoline, which is used to treat certain pituitary tumors, alone or in combination with ketoconazole, a drug normally used to treat fungal infections, have been shown to be effective in some patients with Cushing's disease. More recently, mefipristone-best known as the abortion pill RU-486-was approved by the FDA to treat CD. Despite these advances in medical therapy, the Salk scientists say additional therapeutic approaches are needed for CD.

"Pituitary tumors are extremely difficult to control," says Michael Downes, a senior staff scientist in the Gene Expression Laboratory and a co-author of the study. "To control them, you have to kill cells in the pituitary gland that are proliferating, which could prevent the production of a vital hormone."

Previous studies have found that, by itself, TR4 is a natural target for other signaling molecules in the pituitary. Small-molecule inhibitors that have been developed for other cancers could be potentially applied to disrupt this signaling cascade. "Our discovery," says Evans, a Howard Hughes Medical Institute investigator and holder of the March of Dimes Chair in Molecular and Developmental Biology, "might lead clinicians to an existing drug that could be used to treat Cushing's disease."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our cancer / oncology section for the latest news on this subject. Other researchers on the study were Li Du, Marvin Bergsneider, Leili Mirsadraei, Stephen H. Young, William H. Yong and Anthony P. Heaney of the David A. Geffen School of Medicine at the University of California, Los Angeles, and Johan W. Jonker of the University of Groningen.
The study was supported by the National Institutes of Health, the Leona M. and Harry B. Helmsley Charitable Trust, the Samuel Waxman Cancer Research Foundation, the Jonsson Comprehensive Cancer Center at UCLA, and Ipsen/Biomeasure.
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Chemists Demonstrate Nanoscale Alloys So Bright They Could Have Potential Medical Applications

Main Category: Medical Devices / Diagnostics
Also Included In: Cancer / Oncology
Article Date: 16 May 2013 - 0:00 PDT Current ratings for:
Chemists Demonstrate Nanoscale Alloys So Bright They Could Have Potential Medical Applications

Alloys like bronze and steel have been transformational for centuries, yielding top-of-the-line machines necessary for industry. As scientists move toward nanotechnology, however, the focus has shifted toward creating alloys at the nanometer scale - producing materials with properties unlike their predecessors.

Now, research at the University of Pittsburgh demonstrates that nanometer-scale alloys possess the ability to emit light so bright they could have potential applications in medicine. The findings have been published in the Journal of the American Chemical Society.

"We demonstrate alloys that are some of the brightest, near-infrared-light-emitting species known to date. They are 100 times brighter than what's being used now," said Jill Millstone, principal investigator of the study and assistant professor of chemistry in Pitt's Kenneth P. Dietrich School of Arts and Sciences. "Think about a particle that will not only help researchers detect cancer sooner but be used to treat the tumor, too."

In the paper, Millstone presents alloys with drastically different properties than before - including near-infrared (NIR) light emission - depending on their size, shape, and surface chemistry. NIR is an important region of the light spectrum and is integral to technology found in science and medical settings, said Millstone. She uses a laser pointer as an example.

"If you put your finger over a red laser [which is close to the NIR light region of the spectrum], you'll see the red light shine through. However, if you do the same with a green laser [light in the visible region of the spectrum], your finger will completely block it," said Millstone. "This example shows how the body can absorb visible light well but doesn't absorb red light as well. That means that using NIR emitters to visualize cells and, ultimately parts of the body, is promising for minimally invasive diagnostics."

In addition, Millstone's demonstration is unique in that she was able to show - for the first time - a continuously tunable composition for nanoparticle alloys; this means the ratio of materials can be altered based on need. In traditional metallurgical studies, materials such as steels can be highly tailored toward the application, say, for an airplane wing versus a cooking pot. However, alloys at the nanoscale follow different rules, says Millstone. Because the nanoparticles are so small, the components often don't stay together and instead quickly separate, like oil and vinegar. In her paper, Millstone describes using small organic molecules to "glue" an alloy in place, so that the two components stay mixed. This strategy led to the discovery of NIR luminescence and also paves the way for other types of nanoparticle alloys that are useful not only in imaging, but in applications like catalysis for the industrial-scale conversion of fossil fuels into fine chemicals.

Millstone says that taken together these observations provide a new platform to investigate the structural origins of small metal nanoparticles' photoluminescence and of alloy formation in general. She believes these studies should lead directly to applications in such areas of national need as health and energy.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our medical devices / diagnostics section for the latest news on this subject. The paper, “Photoluminescent Gold-Copper Nanoparticle Alloys with Composition-Tunable Near-Infrared Emission,” first appeared online April 3 and later in print April 10 in JACS (Journal of the American Chemical Society). Funding was provided by the University’s Central Research Development Fund and administered by Pitt’s Office of Research and University Research Council.
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