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A new study published in the journal Cell Stem Cell, describes how scientists have developed a way of producing highly sought populations of a pure tissue-specific cell from human pluripotent stem cells.

Human pluripotent stem cells (hPSCs) are precursor cells than can produce over 200 distinct cell types in the human body. They hold great promise for regenerative medicine and drug screening. The idea is to be able to generate a range of pure tissue types by manipulating these precursor cells.

However, it is proving very challenging to obtain large numbers of pure, untainted, tissue-specific cells from hPSCs. Part of the problem is how to ensure they receive highly specific signals, that do not coax them down paths that lead to a range of other tissue types.

Now, a team led by the Genome Institute of Singapore (GIS) in the Agency for Science, Technology and Research (A*STAR) has developed a new way of coaxing hPSCs to produce highly pure populations of endoderm, a valuable cell type that gives rise to organs like the liver and pancreas, bringing closer the day when stem cells can be used in clinical settings.

One of the study leaders is Dr. Bing Lim, senior group leader and associate director of Cancer Stem Cell Biology at the GIS. He and his colleagues developed a highly systematic and novel screening method.

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Scientists make pure precursor liver and pancreas cells from stem cells

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29/01/2014 - 15:56:06Back to World Home

A revolutionary new approach to creating stem cells in the laboratory could open up a new era of personalised medicine, it is claimed.

Scientists have shown it is possible to reprogramme cells into an embryonic-like state simply by altering their environment.

It means in principle that cells can have their developmental clock turned back without directly interfering with their genes something never achieved before.

The cells become pluripotent, having the potential ability to transform themselves into virtually any kind of tissue in the body, from brain to bone.

Reprogramming a patients own cells in this way is seen as the Holy Grail of regenerative medicine, raising the prospect of repairing diseased and damaged organs with new healthy tissue that will not be rejected by the immune system.

Current methods of performing the same trick involve genetic manipulation, which carries with it a serious risk of triggering cancer.

But the new method described in the journal Nature requires no genetic tweaking. Scientists simply bathed immature white blood cells from mice in an acidic solution for 25 minutes.

Tests showed that, stressed in this way, some of the cells lost their blood identity and produced gene markers typical of early embryos.

When these cells were transferred to a special growth-promoting culture medium they began to multiply and acquired features typical of embryonic stem cells.

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Stem cell breakthrough may herald age of personalised medicine

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Haruko Obokata / Nature

Japanese researchers have created a new type of stem cell just by pressuring normal cells in the body. This image shows a mouse embryo created using these cells, which are genetically engineered to glow green.

Scientists have made a whole new type of stem cell using little more than a little acid, and they say it may represent a way to skip all the complex and controversial steps that it now takes to make cells to regenerate tissues and organs.

The team in Japan includes some of the foremost experts in making what are called pluripotent stem cells master cells that have the power to morph into any type of cells, from blood to bone to muscle. These master cells look and act like an embryo right after conception and, like a days-old embryo, have the power to generate new tissue of any type.

Making these powerful cells usually requires the use of embryos something many disapprove of or tricky mixtures of genes to turn back the clock.

While theres not an immediate use for the discovery, it could add to the arsenal of tools that scientists can use in trying to find ways to repair the human body, the team reports in this weeks issue of the journal Nature.

It is also exciting to think about the new possibilities this finding offers, not only in areas like regenerative medicine but also perhaps in the study of senescence and cancer as well, Haruko Obokata of the RIKEN Center for Developmental Biology in Kobe, Japan, told reporters in a conference call.

Obokatas team worked with mice, and found they could get ordinary cells from baby mice to turn into pluripotent stem cells by bathing them in a slightly acidic solution. They call them stimulus-triggered acquisition of pluripotency, or STAP, cells.

Other stem cells experts praised the work. These breakthroughs are so impressive and potentially powerful truly another dramatic game-changer, said Dr. Gerald Schatten, a stem cell and genetic engineering expert at the University of Pittsburgh.

If reproducible in humans, this will be a paradigm changer," said Dr. Robert Lanza of Massachusetts-based Advanced Cell Technology, a company developing stem cell-based treatments.

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Scientists make a new type of stem cell, using a little acid

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In experiments that could open a new era in stem cell biology, scientists have found a cheap and easy way to reprogram mature cells from mice back into an embryonic-like state that allowed them to generate many types of tissue.

The research, described as game-changing by experts in the field, suggests human cells could in future be reprogrammed by the same technique, offering a simpler way to replace damaged cells or grow new organs for sick and injured people.

Chris Mason, chair of regenerative medicine bioprocessing at University College London, who was not involved in the work, said its approach was "the most simple, lowest-cost and quickest method" to generate so-called pluripotent cells - able to develop into many different cell types - from mature cells.

"If it works in man, this could be the game changer that ultimately makes a wide range of cell therapies available using the patient's own cells as starting material - the age of personalized medicine would have finally arrived," he said.

The experiments, reported in two papers in the journal Nature on Wednesday, involved scientists from the RIKEN Center for Developmental Biology in Japan and Brigham and Women's Hospital and Harvard Medical School in the United States.

Beginning with mature, adult cells, researchers let them multiply and then subjected them to stress "almost to the point of death", they explained, by exposing them to various events including trauma, low oxygen levels and acidic environments.

Within days, the scientists found that the cells survived and recovered from the stressful stimulus by naturally reverting into a state similar to that of an embryonic stem cell.

These stem cells created by this exposure to stresses - dubbed STAP cells by the researchers - were then able to differentiate and mature into different types of cells and tissue, depending on the environments they were given.

"If we can work out the mechanisms by which differentiation states are maintained and lost, it could open up a wide range of possibilities for new research and applications using living cells," said Haruko Obokata, who lead the work at RIKEN.

Stem cells are the body's master cells and are able to differentiate into all other types of cells. Scientists say that, by helping to regenerate tissue, they could offer ways of tackling diseases for which there are currently only limited treatments - including heart disease, Parkinson's and stroke.

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Scientists create embryonic-type stem cells without embryos

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In a step that has implications for stem cell research, human biology and the treatment of disease, researchers in Japan and at Harvard University have managed to turn adult cells back into flexible stem cells without changing their DNA.

The researchers discovered that they could put cells in various challenging circumstances ?? including in acidic solutions and under physical pressure ?? and turn mature blood cells into cells that were capable of turning into virtually any cell in the body.

The research, published today in the journal Nature, was in mice. If it can be repeated in people, it has the potential to transform research using stem cells to treat disease, and it may lead to a new understanding of how the body heals from injury, said Charles Vacanti, the Harvard Medical School stem cell and tissue engineering biologist who led the research.

Biology textbooks say that once a cell matures to serve a specific role, like, say a red blood cell, it can never go back into a less mature state. Vacanti and his colleagues say their new research upends that dogma.

"This study demonstrates that any mature cell when placed in the right environment can go back, become a stem cell, which then has the potential to become any cell needed by that tissue," said Vacanti, also of Brigham and Women's Hospital in Boston.

He believes that that process happens naturally in the body after injury, and the more significant the injury, the farther back these cells will revert. "With a very significant injury, you will cause it to revert clear back to what is basically an embryonic stem cell," he said.

In an early embryo, all cells are stem cells, capable of turning into any cell in the body. As the fetus develops, those cells differentiate into cells with specific functions in muscles, blood, organs, etc. Some of those mature cells develop diseases and injuries. The promise of stem cells ?? as yet largely unrealized ?? is to provide patients with healthy versions of their own cells that can then repair damage and reverse disease.

Most people are familiar with stem cell research because until 2006, embryos had to be destroyed to study them.

Then, Japanese researcher Shinya Yamanaka developed a strategy for tinkering with adult cells, reverting them to stem cells. This has led to dramatic advances in the field, but because his approach required changes to the genetic material in a cell's nucleus, researchers have been anxious about using these cells in patients.

If stem cells can be created simply by bathing adult cells in a low-pH solution or putting them under physical pressure, that would make research simpler and more applicable to the real world, according to several researchers not involved in the new work.

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Researchers turn adult cells back into stem cells

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By Amy CorderoyJan. 30, 2014, 3 a.m.

People who need hip replacements could be able to use cells taken during the procedure to help heal their damaged bones, researchers say.

People who need hip replacements could be able to use cells taken during the procedure to help heal their damaged bones, researchers say.

A ground-breaking study has found that parts usually discarded when people with arthritis have hip replacements can actually be used to collect stem cells that could help regrow bone, cartilage and fat.

Tens of thousands of Australians have hip replacements each year, with numbers rising by more than 37 per cent over the past 10 years to more than 36,500 last year.

Melissa Knothe Tate, the Paul Trainor chair of biomedical engineering at the University of NSW, said her team had shown for the first time that the previously discarded tissue has the potential to be put to good use.

"There is a lot of potential for stem cells to be used to harness the body's own healing capacity for all sorts of illnesses," she said. "Arthritis is the leading cause of disability in ageing adults and the increasing number of hip replacements opens up a new, easy way of getting stem cells."

Her international research team collected samples from the periosteum, connective tissue in the ball at the very top of the thigh bone, of four people with arthritis who had hip replacement.

"These patients are aged and they have disease, so this study was quite out of the box," Professor Knothe Tate said.

But on comparing the stem cells they derived with commercial cells taken from bone marrow they found "remarkable similarities". The cells were similar to bone marrow in terms of their ability to develop into other cells in the lab, according to the research published in Stem Cells Translational Medicine. Professor Knothe Tate said patients could potentially bank their cells for future use, to help heal bones seriously damaged by things like car accidents or cancer surgery, by wrapping them in a cover that could deliver the cells to the injured area.

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It's good to the bone: hip surgery 'waste' could become healing cells

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This is big.

Scientists have found a way to create embryonic stem cells without using an embryo or without introducing genetic material. The discovery could revolutionize medicine by giving doctors a way to repair diseased and damaged tissue think heart disease, blindness, skin burns with organs and tissue grown from the patients own cells.

Cloning Creates Human Embryonic Stem Cells

The researchers, led by Haruko Obokata from the Riken Center for Developmental Biology in Kobe, Japan, found that by when they applied various stresses to white blood cells, such as bathing them in acid or putting them in a low-oxygen environment, nearly bringing them to the brink of death, some of the cells lost their blood identity and reverted to a state equivalent to an embryonic stem cell.

They call these cells STAP, for stimulus-triggered acquisition of pluripotency.

When the scientists transferred the STAP cells to a special growth-promoting solution, they began to multiply and look like embryonic stem cells, which can grow into any type of cell skin, bone, organ depending on the environment into which they were placed.

And when the cells were injected into mice embryos, they contributed to the overall tissue of the baby mice, something that researchers didnt think would be possible.

Not only is the approach faster and far cheaper than current methods, but it eliminates the controversy surrounding embryonic stem cell research, which requires the destruction of an embryo, raising ethical concerns. The new approach also avoids the genetic risks associated with the alternative to the embryonic method, called induced pluripotent stem (iPS) cells. That technique requires the introduction of genetic material into a cell, and has lead to tumor growth in some cases.

Stem Cell Treatment Cures Blindness

Inspiration for the research came from techniques already used in labs and in gardening, where a change in the physical environment can alter a cells identity. In the lab, for example, frog skin cells can be switched to brain cells if exposed to a solution with a low pH. And botanists can grow a new plant by creating a plant callus, a node of plant cells created from a physical injury to an existing plant.

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Groundbreaking: Embryonic Stem Cells Made With Acid

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Malcolm Ritter, The Associated Press Published Wednesday, January 29, 2014 10:57AM EST

NEW YORK -- A simple lab treatment can turn ordinary cells from mice into stem cells, according to a surprising study that hints at a possible new way to grow tissue for treating illnesses like diabetes and Parkinson's disease.

Researchers in Boston and Japan exposed cells from spleens of newborn mice to a more acidic environment that they're used to. In lab tests, that turned them into stem cells, showing enough versatility to produce the tissues of a mouse embryo, for example.

Cells from skin, muscle, fat and other tissue of newborn mice appeared to go through the same change, which could be triggered by exposing cells to any of a variety of stressful situations, researchers said.

Scientists hope to harness stem cells to replace defective tissue in a wide variety of diseases. By making stem cells from the patient, they can get around the problem of transplant rejection.

Human cells are now routinely turned into so-called "iPS" stem cells. That involves reprogramming an ordinary cell by slipping genes or substances into its nucleus. The new method, in contrast, lets the cell change its own behaviour after researchers have applied an external stress.

"It's very simple to do. I think you could do this actually in a college lab," said Dr. Charles Vacanti of Brigham and Women's Hospital in Boston, an author of two papers published online Wednesday by the journal Nature.

Vacanti also acknowledged that if the technique works with human cells, it could conceivably provide a new potential route for cloning people. He has no interest in doing that, he said, but "it is a concern."

Another author, Haruko Obokata of the RIKEN Center for Developmental Biology in Kobe, Japan, said researchers are now studying whether the technique works with human cells. She also said it's premature to compare it to iPS technology in terms of potential medical uses.

Experts not connected to the study said the results are surprising, and that it's too soon to know their practical implications.

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Simple technique produces stem cells in mice

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PARIS: Scientists on Wednesday reported a simple way to turn animal cells back to a youthful, neutral state, a feat hailed as a "game-changer" in the quest to grow transplant tissue in the lab.

The research, reported in the journal Nature, could be the third great advance in stem cells -- a futuristic field that aims to reverse Alzheimer's, cancer and other crippling or lethal diseases.

The latest breakthrough comes from Japan, as did its predecessor which earned its inventor a Nobel Prize.

The new approach, provided it overcomes safety hurdles, could smash cost and technical barriers in stem-cell research, said independent commentators.

"If it works in man, this could be the game-changer that ultimately makes a wide range of cell therapies available using the patient's own cells as starting material," said Chris Mason, a professor of regenerative medicine at University College London.

"The age of personalised medicine will have arrived."

Stem cells are primitive cells that, as they grow, differentiate into the various specialised cells that make up the different organs -- the brain, the heart, the kidney and so on.

The goal is to create stem cells in the lab and nudge them to grow into these differentiated cells, thus replenishing organs damaged by disease or accident.

One of the obstacles, though, is ensuring that these transplanted cells are not attacked as alien by the body's immune system.

To achieve that, the stem cells would have to carry the patient's own genetic code, to identify them as friendly.

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Stem cells in "revolutionary" boost

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A University of Colorado Cancer Center study published today in the International Journal of Radiation Oncology Biology and Physics shows that patients taking crizotinib for ALK+ non-small cell lung cancer may safely and durably use up to three courses of targeted radiation therapy to eradicate pockets of drug-resistant disease. Eliminating these pockets of resistant disease allows patients to continue treating the overall condition with crizotinib, leading to improved 2-year survival rates compared with patients forced to discontinue the drug sooner.

ALK+ lung cancers are caused by the aberrant reactivation of the ALK gene, and comprise about 3-5 percent of all cases of non-small cell lung cancer. In these cases, clinical studies have shown that the drug crizotinib is highly effective and the drug was rapidly approved by the FDA in 2011. Unfortunately, at around 8 -- 10 months after the initiation of treatment, the cancer tends to acquire resistance to crizotinib. Earlier work at CU Cancer Center and elsewhere showed that resistance occurs through a change in the biology of the cancer. At this point, patients have generally been switched to another drug.

However, it may not be the entire cancer that develops resistance to the drug. Instead, as the change in biology is an evolutionary event only pockets of the cancer may become immune. Previous work from the CU Cancer Center described the use of a single course of radiotherapeutic local ablative therapy to eliminate these isolated pockets of resistant disease.

"The traditional paradigm for cancer patients has been to switch your systemic therapy to another agent if you progress, even though a majority of your cancer may still be controlled by the original drug. But what if we could use targeted radiation therapy to eliminate those sites of errant disease so a person could stay on a specific drug longer?" says Gregory Gan, MD, PhD, a chief resident in the University of Colorado School of Medicine Department of Radiation Oncology and the paper's first author. "Using stereotactic body radiotherapy, we can ablate these limited sites of progressive disease so patients can continue on the drug they are on -- a technique we refer to as 'weeding the garden'."

The current study reports median two-year follow-up results of up to three courses of local ablative therapy to control resistant, progressive disease in ALK+ lung cancer patients.

Specifically, the group followed the experience of 38 ALK+ non-small cell lung cancer patients. Of these 38 patients, 33 progressed during the study, meaning the disease gained resistance to crizotinib. Fourteen of those patients progressed in a way that allowed for local ablative therapy. These eligible patients received 1-3 rounds of radiotherapeutic local ablative therapy to "weed the garden" of resistant pockets of disease. Examples of sites that were treated included metastases to the lung, liver, abdominal lymph nodes, and adrenal glands.

"With this long follow up, we can now see that on average it took 5.5 months from the first use of local ablative therapy until further evidence of progression on crizotinib occurred -- a duration of disease control that is highly competitive with what any new drug-based therapy might be expected to achieve in the acquired resistance setting. In addition, we found that you can use radiotherapeutic local ablative therapy in the same patient multiple times with excellent control of these sites of resistant cancer and minimal to no side-effects. By keeping these patients on crizotinib for longer periods of time and/or because of the direct effect of the local ablative therapy, there was a suggestion that patients may also being enjoying a significant survival benefit," says Ross Camidge, MD, PhD, director of the Thoracic Oncology Clinical Program at the CU Cancer Center and the senior author of the study. However, Camidge cautions that this apparent overall survival benefit will need to be studied formally in a prospective clinical trial currently being established at the University of Colorado.

Among the 38 ALK+ patients, the overall survival at 2 years was 57 percent, but among those who stayed on crizotinib for more than a year it was 72 percent compared to 12 percent in those who discontinued crizotinib earlier.

"Not only does this study raise very important questions, but the pulling together of all the different analyses is part of a string of impressive achievements by Dr. Gan, who is emerging as a young leader in the field of radiation oncology," says Brian Kavanagh, MD, MPH, CU Cancer Center investigator and vice-chair of radiation oncology at the University of Colorado School of Medicine.

"We've been using radiotherapeutic local ablative therapy to control pockets of drug-resistant cancer not just in ALK+ lung cancer patients but in other types of cancer in patients on targeted therapy or chemotherapy. Radiotherapy has shown great success controlling these sites of resistant disease but more work needs to be done to fully determine when it is best to use local therapies versus a change in systemic therapy. The next step will hopefully be a prospective clinical study," says Dr. Kavanagh.

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'Weeding the garden' lets anaplastic lymphoma kinase-positive lung cancer patients continue crizotinib

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1 hour ago

While grain yield is economically important in field corn production, there are other metrics more important in sweet corn grown for processing, said Marty Williams, a USDA-ARS ecologist and University of Illinois crop sciences researcher.

In a study recently published in Field Crops Research, Williams questioned whether the crop yield responses that have been previously reported in sweet corn research are actually helpful to the industry.

"What has been done in the past is analogous to predicting someone's height based on their shoe size, as opposed to actually measuring their height," Williams said.

After collecting and studying sweet corn data representing 31 hybrids across 22 locations in Illinois over an 8-year period, Williams said he sees a disconnect in what researchers are measuring in the field and what processors and seed companies need to know in order to make improved production decisions.

In other words, Williams said researchers need to start speaking the same language as the sweet corn industry.

Williams explained that the two variables that affect processor decisions most include recovery (percentage of kernels that can be canned or bagged from the green-ear mass) and case production (cases per acre of processed kernels).

However, he added that nearly all historic and recent field research in processing sweet corn reports neither of these variables, regardless of whether the studies pertained to plant pathology, fertility management, pest control, or sweet corn breeding and genetics.

"Ear number or green-ear mass are often the only crop responses reported in research on field productivity of processing sweet corn. Sometimes, other crop responses are reported, including plant traits such as height or canopy density, or ear traits such as ear length or ear width," he said.

In his study, Williams looked for relationships between processor variables and 17 crop traits (5 plant traits, 8 ear traits, and 4 yield traits). He determined that none of the crop traits predicted recovery.

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Better sweet corn research, better production

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1 hour ago MSU scientists have identified how a single gene in honey bees separates the queens from the workers. Credit: Courtesy of Zachary Huang

Scientists have identified how a single gene in honey bees separates the queens from the workers.

A team of scientists from Michigan State University and Wayne State University unraveled the gene's inner workings and published the results in the current issue of Biology Letters. The gene, which is responsible for leg and wing development, plays a crucial role in the evolution of bees' ability to carry pollen.

"This gene is critical in making the hind legs of workers distinct so they have the physical features necessary to carry pollen," said Zachary Huang, MSU entomologist. "Other studies have shed some light on this gene's role in this realm, but our team examined in great detail how the modifications take place."

The gene in question is Ultrabithorax, or Ubx. Specifically, the gene allows workers to develop a smooth spot on their hind legs that hosts their pollen baskets. On another part of their legs, the gene promotes the formation of 11 neatly spaced bristles, a section known as the "pollen comb."

The gene also promotes the development of a pollen press, a protrusion also found on hind legs, that helps pack and transport pollen back to the hive.

While workers have these distinct features, queens do not. The research team was able to confirm this by isolating and silencing Ubx, the target gene. This made the pollen baskets, specialized leg features used to collect and transport pollen, completely disappear. It also inhibited the growth of pollen combs and reduced the size of pollen presses.

In bumble bees, which are in the same family as honey bees, queens have pollen baskets similar to workers. In this species, Ubx played a similar role in modifying hind legs because the gene is more highly expressed in hind legs compared to front and mid legs.

Besides honey bees, which aren't native to North America, there are more than 300 species of other bees in Michigan alone. These include solitary leaf cutter bees, communal sweat bees and social bumble bees.

"The pollen baskets are much less elaborate or completely absent in bees that are less socially complex," Huang said. "We conclude that the evolution of pollen baskets is a major innovation among social insects and is tied directly to more-complex social behaviors."

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Single gene separates queen from workers

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A group of researchers from Mexico's General Hospital, Health Secretariat, Medicine Faculty and the Institute of Cellular Physiology of the National Autonomous University of Mexico (UNAM) identified a therapeutic target for cervix cancer: gene CDKN3.

The researched performed at the lab indicates that when this gene is blocked in culture cancerous cells, the neoplastic proliferation greatly diminishes.

Jaime Berumen Campos, who coordinates the research said that this gene is blocked by a "siRNA" (small interference RNA), molecular technique applied to several strands of cervix cancer cells making them incapable of proliferating, and confirmed that tumors in mice stopped growing.

To achieve this, researchers first analyzed eight thousand and 638 genes in 43 samples of cervix cancer cells, identifies six suspect of making cervical cancer grow.

One of these genes is CDKN3, which apparently is the most important, given that its activity was highly elevated in most of explored cancers.

Later, clinical evolution of 42 patients was studied during five years, and was found that when CDKN3 is very active, patients have little survival, Berumen Campos explained, who because of this research won the Award of Medical Research "Dr. Jorge Rosenkranz" 2013, in the clinical area.

"70 per cent of the patients with a high activity of this gene, died less than two years of developing the illness, meanwhile only 15 per cent of patients with a low activity of this indicator died while the study was being performed."

Experimentation in culture cells and observation in women with cancer, indicate that this gene is linked to the aggressiveness and malignant growth of the tumor. Besides, the findings indicate that this gene could be a good therapeutic target, meaning, that overriding its primary function (promoting cellular growth), it would be possible to diminish the proliferation of tumors in women.

Cervical cancer is treated by surgery, chemo and radiotherapy or a combination of all the above, according to the clinical stage. The success and survival diminish as the disease advances.

The percentage of women who survive five years is reduced by 93 percent in the first stage, and to 15 percent in the fourth stage. Contrary to other types of cancer, for which drugs against specific molecular targets exist, this have not been developed for cervical cancer.

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New technique developed to control cervical cancer

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