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Showing posts with label Other. Show all posts
Showing posts with label Other. Show all posts

Thursday, June 27, 2013

Tumour "Tweets" Influence Other Cells

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Academic Journal
Main Category: Biology / Biochemistry
Also Included In: Cancer / Oncology;??Neurology / Neuroscience
Article Date: 24 Jun 2013 - 2:00 PDT Current ratings for:
Tumour "Tweets" Influence Other Cells
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Groundbreaking research from Australia reveals that brain tumours release small bits of information, rather like "tweets", that interact with blood vessel cells in a way that causes them to undergo significant changes. The researchers believe the discovery may lead to new treatments.

Writing in the 17 June online issue of RNA Biology, Michael Buckland, associate professor in the University of Sydney's Brain and Mind Research Institute (BMRI), and colleagues, describe how they found brain tumours release microvesicles containing new forms of RNA, and these interact with nearby brain blood vessel cells.

RNA (short for ribonucleic acid), a close cousin of DNA, is a group of long-chained molecules that among other things, control gene expression and help transfer the genetic code held in DNA to make proteins.

Microvesicles are tiny pockets of cell plasma, enclosed in a membrane. They are released by cells and were once considered to be junk, or debris.

Buckland says scientists are just becoming aware of the significance of microvesicles, and how they may be important for health and disease.

For instance, there have been suggestions that microvesicles may have potential as clinical biomarkers for individual cancers.

"It seems that many cells release microvesicles allowing them to communicate and influence other cells nearby and in distant parts of the body in real-time - much like tweeting," Buckland says in a statement.

Tumours thrive in different environments to healthy tissue. As the tumour grows it interacts with its environment, for instance changing the blood supply to suit its own needs.

To do this the tumour must interact with other cells, and modify their gene expression so they make the proteins that suit the tumour rather than those that suit healthy tissue.

The team had a hunch that one way brain tumour cells (gliomas) do this is via the microvesicles.

So they designed a study that took an "unbiased approach to identifying RNAs in glioma-derived microvesicles, and explored their potential to regulate gene expression in recipient cells".

For the study, the team grew brain tumour cells (gliomas) in culture and harvested the microvesicles they released into the culture medium.

When they added the glioma-produced microvesicles to cultures of brain blood vessel cells, they triggered significant changes in the cells, including many changes in gene expression.

On closer examination they found that the glioma microvesicles contained complex populations of coding and non-coding RNA, and the proportions of these populations were different to those from the cells they came from.

Compared to the glioma cells that made them, glioma microvesicles had lower levels of microRNA and higher levels of unusual or new non-coding RNA, most of which "have no known function", write the authors, who conclude:

"Our data suggest that the scope of potential actions of tumor-derived microvesicles is much broader and more complex than previously supposed, and highlight a number of new classes of small RNA that remain to be characterized."

Buckland says their findings suggest microvesicles "likely to play an important role in the changes to blood vessels seen in high grade brain tumours, the most common form in Australian adults".

They present a new target for treatment against brain tumours, he says, adding that:

"Furthermore, they can be detected in the blood of patients with brain tumours, and may be an important diagnostic tool in the future."

A biosciences company has also suggested, at a scientific meeting in 2011, that the fact circulating microvesicles have different RNA profiles highlights their potential use in cancer detection and monitoring.

Written by Catharine Paddock PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

Visit our biology / biochemistry section for the latest news on this subject. "Glioma microvesicles carry selectively packaged coding and noncoding RNAs which alter gene expression in recipient cells"; Cheryl C.Y. Li, Sally Eaton, Paul E. Young, Maggie Lee, Rupert Shuttleworth, David T. Humphreys, Georges E. Grau, Valery Combes, Mary Bebawy, Joyce Gong, Susan Brammah, Michael E. Buckland, and Catherine M. Suter; RNA Biology, Volume 10, Issue 8, published online 17 June 2013; Link to Abstract.
Additional source: University of Sydney press release. Please use one of the following formats to cite this article in your essay, paper or report:

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Paddock, Catharine. "Tumour "Tweets" Influence Other Cells." Medical News Today. MediLexicon, Intl., 24 Jun. 2013. Web.
24 Jun. 2013. APA

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'Tumour "Tweets" Influence Other Cells'

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Thursday, May 30, 2013

Worse Outcomes for Breast Cancer Patients with Other Illnesses

Older breast cancer patients who have additional medical conditions have worse survival than patients without other illnesses.? These findings were recently published in the Journal of the National Cancer Institute.?

According to results from previous studies, illness in addition to breast cancer may shorten survival and increase death rates among older women with breast cancer. Studies to date have assessed the association between other illness as a whole and breast cancer death but have not evaluated specific illnesses independently.??

To better understand how medical conditions in addition to breast cancer may affect survival among older women, researches selected 13 medical conditions to evaluate; these included stroke, chronic obstructive pulmonary disease, chronic renal failure, congestive heart failure, dementia, diabetes, liver disease, heart attack, paralysis, peripheral vascular disease, previous cancer, rheumatoid arthritis, and ulcers. A total of 64,034 breast cancer patients were included in the study. Patients were 66 years old and older and had been diagnosed with breast cancer between 1992 and 2000.??

42% of patients had a history of one or more of the selected illness. ?Patients with selected illnesses experienced shorter overall survival times and increased overall deaths from breast cancer and other conditions compared with patients without another illness.?When patients between 66 and 74 years of age were further analyzed according to age and type of illness other than breast cancer, overall survival was worse or similar among patients with Stage I breast cancer and another illness compared with patients with Stage II breast cancer and no other illness.??

It appears that certain illnesses in addition to breast cancer may decrease overall survival and increase death among older women with breast cancer. These findings may help doctors more accurately predict survival among breast cancer patients. As well, they underscore the importance of balancing treatment for breast cancer with treatment for other conditions.?

Reference: Patnaik JL, Byers T, DiGuiseppi C, et al. The influence of comorbidities on overall survival among older women diagnosed with breast cancer. Journal of the National Cancer Institute [online publication]. June 30, 2011.?

Posted July 21, 2011


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Wednesday, May 29, 2013

Gene-Silencing Activity Discovery Could Lead To Treatment For Viral Infections, Cancers And Other Diseases

Main Category: Infectious Diseases / Bacteria / Viruses
Also Included In: Cancer / Oncology;??Genetics
Article Date: 13 May 2013 - 0:00 PDT Current ratings for:
Gene-Silencing Activity Discovery Could Lead To Treatment For Viral Infections, Cancers And Other Diseases
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A team led by scientists at The Scripps Research Institute (TSRI) has found how to boost or inhibit a gene-silencing mechanism that normally serves as a major controller of cells' activities. The discovery could lead to a powerful new class of drugs against viral infections, cancers and other diseases.

"Learning to control natural gene silencing processes will allow an entirely new approach to treating human disease," said Ian J. MacRae, assistant professor in TSRI's Department of Integrative Structural and Computational Biology and principal investigator for the study, which appears as the cover story in the May 9, 2013 issue of the journal Molecular Cell.

A Scientific Mystery and Technical Conundrum

The gene-silencer in question is Argonaute 2, a molecular machine in cells that can grab and destroy the RNA transcripts of specific genes, preventing them from being translated into proteins. Argonaute 2 and other Argonaute proteins regulate the influence of about a third of the genes found in humans and other mammals - and thus are among the most important modulators of our cells' day-to-day activities. Argonautes' gene-silencing functions also help cells cope with rogue genetic activity from invading viruses or cancer-promoting DNA mutations.

Yet Argonautes' workings are complex and not yet entirely understood. For example, before it starts a search-and-destroy mission against a specific type of target RNA, an Argonaute 2 protein takes on board a target-recognition device: a short length of "guide RNA," also known as a microRNA (miRNA). The miRNA's sequence is mostly complementary to the target RNA's - a sort of chemical mirror-image - so that it can stick tightly to it.

But how do an Argonaute protein and its miRNA guide, having formed their partnership, manage to part company? It has been a scientific mystery and technical conundrum for researchers, who have found it hard to separate Argonaute proteins from miRNAs in the lab dish.

"That problem led us to look for a way to get Argonautes to unload these miRNAs," said Nabanita De, a postdoctoral fellow in MacRae's laboratory who was first author of the new study.

Matches and Mismatches

In an initial set of experiments, the team demonstrated that when an miRNA hooks up with an Argonaute 2, the pair do remain locked together and functioning for an exceptionally long time: days to weeks, whereas solo miRNA normally is degraded within minutes.

Yet prior studies by other laboratories have hinted at the existence of mechanisms that can hasten the separation of miRNAs from Argonautes. Some viruses, for example, produce decoy target RNAs that virtually nullify the activity of the corresponding miRNAs, seemingly by destabilizing the miRNA-Argonaute pairing. A key feature of these decoy target RNAs is that they make an almost perfect complementary match to the miRNAs - especially at one end of the miRNAs, known as the three-prime or 3' end. In this respect, they match the miRNAs much better than the natural gene transcripts that the miRNAs evolved to target.

De confirmed that decoy RNAs designed to match miRNAs this way can greatly hasten the miRNAs' "unloading" from Argonautes, thus effectively dialing down these miRNAs' normal gene-silencing activities. By contrast, mismatches at the 3' end delayed unloading, enhancing the gene-silencing activity.

Why do these matches and mismatches have such effects on the miRNA-Argonaute pairing? The mechanisms aren't obvious. But De noted that mismatches at the opposite end of miRNAs - the 5' end - have the opposite effect. "Targets with 5'-end mismatches are actually better at unloading miRNAs from Argonaute," she said.

"The next thing we're trying to figure out is how all that works," said MacRae. "We have some guesses but no clear answer."

In a study reported last year, MacRae's laboratory used X-ray crystallography to determine the first high-resolution atomic structure of an Argonaute 2-miRNA complex. Now the team is working on a structural study of the complex as it grabs a target RNA. "When we can see the structural details of that interaction, then I think we'll have a much better handle on this loading and unloading process," said MacRae.

Many Potential Applications

Scientists already have begun developing gene-silencing drugs that work like miRNAs; they are taken up by Argonaute proteins as guide RNAs and lead to the silencing of targeted gene transcripts. Pharmaceutical companies also are developing drugs that bind directly to miRNAs to inhibit their activity. The findings here suggest a new and, in principle, more powerful class of miRNA inhibitors/enhancers, aimed at destabilizing or stabilizing the miRNA-Argonaute complex.

"I can think of many applications for these," said MacRae. "One of the most obvious would be against hepatitis C virus, which requires a certain miRNA in liver cells for efficient replication; an RNA-based drug that speeds up the unloading of this virus-enhancing miRNA would be a powerful approach for shutting down the virus."

A better understanding of the miRNA loading and unloading process also should lead to better miRNA-type drugs, he added.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our infectious diseases / bacteria / viruses section for the latest news on this subject. Other contributors to the study, "Highly Complementary Target RNAs Promote Release of Guide RNAs from Human Argonaute 2," were Lisa Young, Nicole-Claudia Meisner and David V. Morrissey of the Novartis Institutes for Biomedical Research, and Pick-Wei Lau of the MacRae laboratory at TSRI.
The study was funded by the National Institutes for Health (grant R01 GM086701).
Scripps Research Institute Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Institute, Scripps Research. "Gene-Silencing Activity Discovery Could Lead To Treatment For Viral Infections, Cancers And Other Diseases." Medical News Today. MediLexicon, Intl., 13 May. 2013. Web.
13 May. 2013. APA

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


'Gene-Silencing Activity Discovery Could Lead To Treatment For Viral Infections, Cancers And Other Diseases'

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.

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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