CDK6 represents a promising target for anti-cancer therapy

Main Category: Cancer / Oncology
Also Included In: Genetics
Article Date: 15 Aug 2013 - 0:00 PDT Current ratings for:
CDK6 represents a promising target for anti-cancer therapy

Cell division is tightly controlled by a number of genes and because of the importance of ensuring that the process stays in check - mistakes frequently lead to cancer - mammalian cells often have several inbuilt layers of security. The two cyclin-dependent kinases CDK4 and CDK6 are widely believed to have almost identical functions, so either one of them can compensate for problems with the other. New work at the University of Veterinary Medicine, Vienna challenges this view and shows that, unlike CDK4, CDK6 also promotes the growth of blood vessels. This explains why CDK6 is so frequently misregulated in certain types of cancer. The results are published in the current issue of the prestigious international journal Cancer Cell.

Cancer in humans is frequently associated with unusually high amounts of one or more proteins responsible for controlling the rate at which cells divide. As an example, excessive amounts of the cyclin-dependent kinase CDK6 are often found in types of cancer such as lymphoma. Together with a number of collaborators within Vienna and beyond, Karoline Kollmann of the University of Veterinary Medicine, Vienna (Vetmeduni) has now shown that CDK6 is part of a multiprotein complex that stimulates the production of one of the so-called INK4 family members (confusingly termed p16INK4a), which suppresses tumour growth. In other words, the cell has an inbuilt mechanism to help it cope with excessive amounts of CDK6.

The problems really start when p16INK4a is missing, as is frequently the case in lymphomas or leukaemias. Now the high levels of CDK6 are unchecked and so can lead directly to a stimulation of cell division. Furthermore, Kollmann and her colleagues showed that another CDK6-containing complex can also promote the production of an additional factor, known as VEGF-A, that increases the growth of blood vessels and thus ensures that the cells in the growing tumours are supplied with sufficient energy and oxygen to multiply. CDK6 is the first factor to be shown to be involved in regulating tumour growth while simultaneously helping to supply tumours with blood.

As its name implies, CDK6 is a kinase, i.e. it adds phosphate groups to other proteins and thereby alters their activity. In a further twist to the tale, the Vetmeduni scientists have shown that CDK6 can still exert its effects on p16INK4a and VEGF-A when it lacks its kinase activity: a mutant form of the CDK6 protein with the kinase function inactivated retains the ability to regulate expression of the p16INK4a and VEGF-A genes.

Veronika Sexl, Head of the Vetmeduni's Institute of Pharmacology and Toxicology, where the work was performed, notes the medical importance of her group's findings. "Because it is known to be involved in so many cancers, CDK6 represents a promising target for anti-cancer therapy and lots of labs are trying to design specific inhibitors. But their efforts are focused on inhibiting CDK6's kinase function. We have shown that CDK6 has an additional, kinase-independent mode of action that is responsible for the uncontrolled cell growth and increased production of blood vessels that are a hallmark of cancer. CDK6 inhibitors will also need to block this new function if they are to be effective in treating cancer."

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.

The paper - A new kinase-independent function of CDK6 links the cell cycle to tumor angiogenesis by Karoline Kollmann, Gerwin Heller, Christine Schneckenleithner, Wolfgang Warsch, Ruth Scheicher, Rene G. Ott, Markus Schäfer, Sabine Fajmann, Michaela Schlederer, Ana-Iris Schiefer, Ursula Reichart, Matthias Mayerhofer, Christoph Hoeller, Sabine Zoechbauer-Mueller, Dontscho Kerjaschki, Christoph Bock, Lukas Kenner, Gerald Hoefler, Michael Freissmuth, Anthony R. Green, Richard Moriggl, Meinrad Busslinger, Marcos Malumbres and Veronika Sexl; Cancer Cell, Volume 24, Issue 2, 167-181, 12 August 2013; 10.1016/j.ccr.2013.07.012

University of Veterinary Medicine -- Vienna

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

University of Veterinary Medicine -- Vienna. "CDK6 represents a promising target for anti-cancer therapy." Medical News Today. MediLexicon, Intl., 15 Aug. 2013. Web.
15 Aug. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'CDK6 represents a promising target for anti-cancer therapy'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

Potential new anti-cancer target: 'dark-horse' molecule

Main Category: Colorectal Cancer
Also Included In: Cancer / Oncology;  GastroIntestinal / Gastroenterology
Article Date: 14 Aug 2013 - 0:00 PDT Current ratings for:
Potential new anti-cancer target: 'dark-horse' molecule

Australian researchers have identified a molecule called interleukin-11 as a potential new target for anti-cancer therapies.

Until now, the importance of interleukin-11 in cancer development has been underestimated, but researchers have recently identified this molecule as a 'dark horse' for the development of cancer. Their discovery suggests blocking interleukin-11 signalling could ultimately provide an exciting new approach to the treatment of bowel and stomach cancer, which are two of the most common cancers worldwide.

When a tumour develops, the normal (non-cancerous) tissues around it can become inflamed, and produce many different molecules, including the two related proteins interleukin-11 and interleukin-6. These hormone-like signalling molecules, referred to as cytokines, are thought to promote the growth and spread of cancer cells, but interleukin-11 was thought to have only a minor, if any, role during cancer development.

However Dr Tracy Putoczki and Associate Professor Matthias Ernst from the Walter and Eliza Hall Institute's Cell Signalling and Cell Death division have now shown that interleukin-11 is one of the most important cytokines that stimulate the growth and spread of cancers. Working with scientists at the Melbourne-based pharmaceutical company CSL Ltd, they discovered that blocking interleukin-11 in models of stomach and bowel cancer stopped tumour growth and could lead to tumour shrinkage, making this cytokine a promising potential new target for treating many types of solid cancers.

Dr Putoczki and Associate Professor Ernst made most of their discoveries while working at the Melbourne-Parkville Branch of the Ludwig Institute for Cancer Research, where Associate Professor Ernst is an institute member. Their findings are published online in the journal Cancer Cell.

Dr Putoczki said the team was stunned to discover that interleukin-11 was much more potent in promoting cancer development than interleukin-6. "When considering which cytokines drive cancer development, interleukin-6 has always been in the spotlight," she said. "Despite being very similar to interleukin-6, interleukin-11 has often been overlooked by cancer researchers. Our new research now shows that it might in fact be very important."

Associate Professor Ernst said the team had begun to explore how the discovery could be applied to potential new anti-cancer therapies. "Treating cancers with agents that block cytokine signalling is an exciting new approach that potentially has advantages over current treatment strategies," he said. "Drugs that block the action of cytokines have previously been developed for both inflammatory disease and cancer and, in the case of interleukin-11, our work does not suggest the likelihood of undesirable side-effects. Moreover, agents that inhibit interleukin-6 signalling are already in clinical trials for ovarian, kidney, prostate and breast cancer. Our discovery paves the way for trials of agents that stifle interleukin-11."

Dr Andrew Nash, senior vice president for research at CSL, agreed that the research had identified a potentially important role for interleukin-11 in stomach and bowel cancer. "We have developed a number of potential drug candidates that target the interleukin-11 receptor and this data provides preclinical evidence supporting progression into clinical studies," Dr Nash said.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our colorectal cancer section for the latest news on this subject.

The research was supported by the Ludwig Insitute of Cancer Research, CSL Ltd, the Australian National Health and Medical Research Council, Cancer Australia, Cure Cancer Australia, German Cancer Aid, and the Victorian Government.

Interleukin-11 Is the Dominant IL-6 Family Cytokine during Gastrointestinal Tumorigenesis and Can Be Targeted Therapeutically Cancer Cell, Volume 24, Issue 2, 257-271, 12 August 2013. 10.1016/j.ccr.2013.06.017

Walter and Eliza Hall Institute

Ludwig Institute for Cancer Research

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Walter and Eliza Hall Institute. "Potential new anti-cancer target: 'dark-horse' molecule." Medical News Today. MediLexicon, Intl., 14 Aug. 2013. Web.
14 Aug. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'Potential new anti-cancer target: 'dark-horse' molecule'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

Research suggests neural stem cells may regenerate after anti-cancer treatment

Main Category: Cancer / Oncology
Also Included In: Neurology / Neuroscience;  Radiology / Nuclear Medicine
Article Date: 14 Aug 2013 - 1:00 PDT Current ratings for:
Research suggests neural stem cells may regenerate after anti-cancer treatment

Scientists have long believed that healthy brain cells, once damaged by radiation designed to kill brain tumors, cannot regenerate. But new Johns Hopkins research in mice suggests that neural stem cells, the body's source of new brain cells, are resistant to radiation, and can be roused from a hibernation-like state to reproduce and generate new cells able to migrate, replace injured cells and potentially restore lost function.

"Despite being hit hard by radiation, it turns out that neural stem cells are like the special forces, on standby waiting to be activated," says Alfredo Quiñones-Hinojosa, M.D., a professor of neurosurgery at the Johns Hopkins University School of Medicine and leader of a study described online in the journal Stem Cells. "Now we might figure out how to unleash the potential of these stem cells to repair human brain damage."

The findings, Quiñones-Hinojosa adds, may have implications not only for brain cancer patients, but also for people with progressive neurological diseases such as multiple sclerosis (MS) and Parkinson's disease (PD), in which cognitive functions worsen as the brain suffers permanent damage over time.

In Quiñones-Hinojosa's laboratory, the researchers examined the impact of radiation on mouse neural stem cells by testing the rodents' responses to a subsequent brain injury. To do the experiment, the researchers used a device invented and used only at Johns Hopkins that accurately simulates localized radiation used in human cancer therapy. Other techniques, the researchers say, use too much radiation to precisely mimic the clinical experience of brain cancer patients.

In the weeks after radiation, the researchers injected the mice with lysolecithin, a substance that caused brain damage by inducing a demyelinating brain lesion, much like that present in MS. They found that neural stem cells within the irradiated subventricular zone of the brain generated new cells, which rushed to the damaged site to rescue newly injured cells. A month later, the new cells had incorporated into the demyelinated area where new myelin, the protein insulation that protects nerves, was being produced.

"These mice have brain damage, but that doesn't mean it's irreparable," Quiñones-Hinojosa says. "This research is like detective work. We're putting a lot of different clues together. This is another tiny piece of the puzzle. The brain has some innate capabilities to regenerate and we hope there is a way to take advantage of them. If we can let loose this potential in humans, we may be able to help them recover from radiation therapy, strokes, brain trauma, you name it."

His findings may not be all good news, however. Neural stem cells have been linked to brain tumor development, Quiñones-Hinojosa cautions. The radiation resistance his experiments uncovered, he says, could explain why glioblastoma, the deadliest and most aggressive form of brain cancer, is so hard to treat with radiation.

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.

The research was supported by grants from the National Institutes of Health's National Institute of Neurological Disorders and Stroke (RO1 NS070024), the Maryland Stem Cell Research Fund, the Robert Wood Johnson Foundation, the Howard Hughes Medical Institute, the PROMETEO grant, the Red de Terapia Celular (TerCel) from Instituto de Salud Carlos III, and the Consejo Nacional de Ciencia y Tecnología.

Other Johns Hopkins researchers involved in the study include Vivian Capilla-Gonzalez, Ph.D.; Hugo Guerrero-Cazares, M.D., Ph.D.; Janice Bonsu; Oscar Gonzalez-Perez, M.D.; Pragathi Achanta, Ph.D.; John Wong, Ph.D.; and Jose Manuel Garcia-Verdugo, Ph.D.

Johns Hopkins Medicine

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Medicine, Johns Hopkins. "Research suggests neural stem cells may regenerate after anti-cancer treatment." Medical News Today. MediLexicon, Intl., 14 Aug. 2013. Web.
14 Aug. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'Research suggests neural stem cells may regenerate after anti-cancer treatment'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here

Technique to create better anti-cancer agents, arthritis drugs, and more

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Medical Devices / Diagnostics;  Arthritis / Rheumatology
Article Date: 30 Jul 2013 - 0:00 PDT Current ratings for:
Technique to create better anti-cancer agents, arthritis drugs, and more

Many drugs such as agents for cancer or autoimmune diseases have nasty side effects because while they kill disease-causing cells, they also affect healthy cells. Now a new study has demonstrated a technique for developing more targeted drugs, by using molecular "robots" to hone in on more specific populations of cells.

"This is a proof of concept study using human cells," said Sergei Rudchenko, Ph.D., director of flow cytometry at Hospital for Special Surgery (HSS) in New York City and a senior author of the study. "The next step is to conduct tests in a mouse model of leukemia." The study, a collaboration between researchers from HSS and Columbia University, is in Advance Online Publication on the website of Nature Nanotechnology.

All cells have many receptors on their cell surface. When antibodies or drugs bind to a receptor, a cell is triggered to perform a certain function or behave in a certain manner. Drugs can target disease-causing cells by binding to a receptor, but in some cases, disease-causing cells do not have unique receptors and therefore drugs also bind to healthy cells and cause "off-target" side effects.

Rituximab (Rituxan, Genentech), for example, is used to treat rheumatoid arthritis, non-Hodgkin's lymphoma and chronic lymphocytic leukemia by docking on CD20 receptors of aberrant cells that are causing the diseases. However, certain immune cells also have CD20 receptors and thus the drug can interfere with a person's ability to mount a fight against infection.

In the new study, scientists have designed molecular robots that can identify multiple receptors on cell surfaces, thereby effectively labeling more specific subpopulations of cells. The molecular robots, called molecular automata, are composed of a mixture of antibodies and short strands of DNA. These short DNA strands, otherwise called oligonucleotides, can be manufactured by researchers in a laboratory with any user-specified sequence.

The researchers conducted their experiments using white blood cells. All white blood cells have CD45 receptors, but only subsets have other receptors such as CD20, CD3, and CD8. In one experiment, HSS researchers created three different molecular robots. Each one had an antibody component of either CD45, CD3 or CD8 and a DNA component. The DNA components of the robots were created to have a high affinity to the DNA components of another robot. DNA can be thought of as a double stranded helix that contains two strands of coded letters, and certain strands have a higher affinity to particular strands than others.

The researchers mixed human blood from healthy donors with their molecular robots. When a molecular robot carrying a CD45 antibody latched on to a CD45 receptor of a cell and a molecular robot carrying a CD3 antibody latched on to a different welcoming receptor of the same cell, the close proximity of the DNA strands from the two robots triggered a cascade reaction, where certain strands were ripped apart and more complementary strands joined together. The result was a unique, single strand of DNA that was displayed only on a cell that had these two receptors.

The addition of a molecular robot carrying a CD8 antibody docking on a cell that expressed CD45, CD3 and CD8 caused this strand to grow. The researchers also showed that the strand could be programmed to fluoresce when exposed to a solution. The robots can essentially label a subpopulation of cells allowing for more targeted therapy. The researchers say the use of increasing numbers of molecular robots will allow researchers to zero in on more and more specific subsets of cell populations. In computer programming language, the molecular robots are performing what is known as an "if yes, then proceed to X function."

"The automata trigger the growth of more strongly complementary oligonucleotides. The reactions occur fast. In about 15 minutes, we can label cells," said Maria Rudchenko, M.S., the first author of the paper and a research associate at Hospital for Special Surgery. In terms of clinical applications, researchers could either label cells that they want to target or cells they want to avoid.

"This is a proof of concept study that it works in human whole blood," said Dr. Rudchenko. "The next step is to test it in animals."

If molecular robots work in studies with mice and eventually human clinical trials, the researches say there are a wide range of possible clinical applications. For example, cancer patients could benefit from more targeted chemotherapeutics. Drugs for autoimmune diseases could be more specifically tailored to impact disease-causing autoimmune cells and not the immune cells that people need to fight infection.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our lymphoma / leukemia / myeloma section for the latest news on this subject.

The study was funded, in part, by the National Institutes of Health, National Science Foundation, and the Lymphoma and Leukemia Foundation.

Other researchers involved with the study are Alesia Dechkovskaia from Hospital for Special Surgery, and Steven Taylor, Ph.D., Payal Pallavi, B.A., Safana Khan, Vincent Butler, M.D., and Milan Stojanovic, Ph.D., from Columbia University. Dr. Stojanovich is also a senior author.

Hospital for Special Surgery

Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Hospital for Special Surgery. "Technique to create better anti-cancer agents, arthritis drugs, and more." Medical News Today. MediLexicon, Intl., 30 Jul. 2013. Web.
30 Jul. 2013. APA

Please note: If no author information is provided, the source is cited instead.

'Technique to create better anti-cancer agents, arthritis drugs, and more'

Please note that we publish your name, but we do not publish your email address. It is only used to let you know when your message is published. We do not use it for any other purpose. Please see our privacy policy for more information.

If you write about specific medications or operations, please do not name health care professionals by name.

All opinions are moderated before being included (to stop spam). We reserve the right to amend opinions where we deem necessary.

Contact Our News Editors

For any corrections of factual information, or to contact the editors please use our feedback form.

Please send any medical news or health news press releases to:

Note: Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a health care professional. For more information, please read our terms and conditions.

View the original article here