Study proves the cells can send out Eph ephrins and to transmit signals

Study proves the cells can send out Eph ephrins and to transmit signals -

Eph receptors and their partner proteins, ephrins are essential for intercellular communication. In the developing brain, they guide the young neurons to cells by repulsion right partners. They also play an important role in cell migration, regeneration, neurodegenerative diseases and the development of cancer. Until recently, scientists assumed that ephrin / Eph signal transmission can occur through direct contact from cell to cell. However, Rüdiger Klein and his team at the Max Planck Institute of Neurobiology have shown that cells can also pack and release ephrins assets and Eph receptors by extracellular vesicles. Not only is this discovery to improve our understanding of this communication system, it can also pave the way for new therapeutic strategies.
The human body contains up to 100 billion cells. As they grow, migrate, replicate and move, these cells come into contact with countless other cells and exchanging information with them. One way of this communication is done by the system of ephrin / Eph-receptor, which is capable of guiding the cell migration and growth of neuronal extensions. Moreover, the Eph-ephrin system also plays a role in plastic processes, such as learning and regeneration, as well as in tumor growth, and neurodegenerative diseases.
Eph receptors and their binding partners, ephrins, are found on the surface of almost all cell types. When ephrin meeting the Eph receptor of another cell, they join to form an ephrin-Eph complex. This triggers processes in one or both cells that generally lead to internalization of the complex and repulsion of a cell away from another. The cell repulsed moves or grows in another direction, then. In the nervous system, many of these interactions guide young extensions of neurons to their right destinations.
"This is why it is so fundamentally important to understand how cells use this system to communicate," says Rüdiger Klein, whose Department at the Max Planck Institute of Neurobiology and studying ephrins Eph receptors . It had always seemed obvious that ephrins and Eph could trigger direct contact by signaling process between two cells Recently, however, the ephrin and Eph receptors have also been found in extracellular vesicles / exosomes. - small fat droplets released by the cells, used as transport vehicles, transmitters of signals or to remove cellular components. "this laid the interesting question of what business and Eph ephrins have in exosomes," says Klein.
Intrigued, the team based in Martinsried developed an experimental study developed to purify exosomes from different cell types, including neurons, and analyze their contents. They showed that many of these exosomes contain ephrin and Eph, and decoded the cellular mechanism by which they were packed in exosomes. Interestingly, further analysis showed that Eph receptors had not been dumped as waste, but remained active on exosomes. The eph receptors on exosomes were able to bind to ephrin molecules on the surface of developing neurons and neuronal repel. This proves for the first time that cells can send ephrin and Eph off for transmitting signals over a distance. "It opens up a range of new possibilities," says Rüdiger Klein. Ephrin and Eph receptors have also been found in the exosomes of cancer cells. "This could mean that strategies to control the release of exosomes could be used to interrupt the way signaling and ephrin-Eph thus disturbing the tumor growth ", it conjecture.

A new blood diagnostic test may offer hope for transplant recipients by analyzing cfDNA

A new blood diagnostic test may offer hope for transplant recipients by analyzing cfDNA -

When the cells die, either by apoptosis or necrosis, DNA and other molecules present in these cells Don 't just disappear. They are found in the blood stream, where degraded bits and pieces can be extracted.
This DNA without cell (cfDNA) is degraded due to its exposure to enzymes in the blood, but is nevertheless a powerful tool for monitoring cancer, pregnancy and organ transplantation. A fairly recent breakthrough prenatal screening for conditions such as Down syndrome, like fragments of fetal cfDNA can be detected in the blood of the mother.
Now, borrowing a genomic technique used in the study of the ancient past, a Cornell graduate student came with a diagnostic tool that can open a window to the immediate future of the transplant recipient by analysis cfDNA.
Philip Burnham, a doctoral student in the lab of Iwijn Vlaminck, Robert N. Noyce assistant professor of life sciences and technology, proposed to use the preparation of the DNA library short strand for sequencing cfDNA in plasma of lung transplant recipients. A DNA library is a collection of DNA fragments were cloned into groups so that researchers can isolate desired fragments for the study.
The laboratory paper, "preparing the single-stranded DNA library discovers the origin and diversity of ultrashort DNA -free cells in plasma," was published online June 14 in Nature scientific reports. Burnham, a graduate student of third year physics and biomedical engineering, is the lead author for the work first published laboratory
The identification of the source of the cfDNA -. Some of them from the mitochondria, the energy producer in cells - can help determine if the transplanted organ is injured or rejected.
"mitochondrial donor sequences are different from those of the recipient, thus making this sequence analysis, you can tell them apart," Vlaminck said. "When cells are injured, they release mitochondrial DNA, and given that you can distinguish the patient's DNA donor, you can actually quantify the injury by these measures."
In 2012, the German anthropologist Matthias Meyer published an article on the study of denisovan - man there about 40,000 years -. and the use of a DNA bank of single-stranded preparation method to sequence the genome of Denisova hominid
nucleosomal DNA - the DNA found in cells - can be adapted for sequencing using double-stranded adapters DNA, but this is not an option for 40,000 years of genetic material. The collected DNA from old bones deteriorates and short strands -the same that many types of cfDNA.
"So Phil has decided to apply these concepts to the DNA in the blood," said De Vlaminck. "And when he did, we discovered a variety of short molecules DNA. "
the group took 40 samples from plasma cfDNA six double-lung transplant recipients and tested with both single-stranded and double-stranded library preparation. the single strand method was much more effective than the conventional method of double-stranded in identifying ultrashort cfDNA (shorter than 100 base pairs), which indicates that it would be better equipped for fetal surveillance and growth, as well.
Ideally, with this method, a transplant recipient could get an idea of ​​how the new body responds with a simple blood test Currently, the only way to know is a biopsy -.. in some cases up to 10 of them in the first year, de Vlaminck said
"you could obviously afford to [a blood test] more often, and if it is more sensitive, the hope is that you can intervene early if problems arose, "he said.
the group hopes their methods will lead to more widespread use of cfDNA analysis, not only in the case of transplantation.
"At present, we are working in a nice model system - if we see the donor's DNA in lung transplant recipient
, then we know that it comes from the lung," said Burnham said. "But what we really push hard is the ability to start watching any tissue DNA derived without prior knowledge of what we are looking at and coupled with the ability to identify potential microbial pathogens cfDNA."
This method should also be effective for the detection of infections, which are a concern for transplant patients. immunosuppressive drugs reduce the risk of organ rejection, but leave a patient vulnerable to infection.

A new study identifies four subtypes of human insulin producing beta cells involved in diabetes

A new study identifies four subtypes of human insulin producing beta cells involved in diabetes -

A new study by the eminent scientist nationwide stem cell Markus Grompe, MD, has determined the existence of at least four distinct subtypes of beta human insulin-producing cells that may be important in understanding and treating diabetes. The results were published online today in the journal Nature Communications .
"This study is the first description of several different types of human insulin-producing beta cells," said Grompe, principal investigator, director of the Oregon Stem Cell Center at OHSU and the Pediatric Research Institute Pape family at OHSU Doernbecher children's Hospital. "Some of the cells are better at releasing insulin than others, while others can regenerate faster. Therefore, it is possible that persons with different percentages of subtypes are more prone to diabetes . a better understanding of the characteristics of the cells could be the key to discovering new treatment options, as well as why some people are diabetics and others are not. "
diabetes affects more 29 million people in the United States. It is caused by the malfunction or loss of beta cells producing insulin, which help the body to achieve sugar levels in normal blood. Previously, a single variety of beta cells is known to exist. However, using human pancreatic islets, or clusters of cells until 4000, Grompe and colleagues have discovered a process to identify and isolate four distinct types of beta cells. They also found that hundreds of genes were differentially expressed between subtypes of cells and produce different amounts of insulin. All type 2 diabetes have abnormal percentages subtypes, suggesting a possible role in the disease process
Further research is needed to determine how the different forms of diabetes -. And other diseases - affects new subtypes of cells and how researchers can take advantage of these differences for medical treatment.

Some substances prohibited by WADA may have potential medical applications

Some substances prohibited by WADA may have potential medical applications -

While the world awaits the start of the 2016 Summer Olympics, doping in athletes remains a hot topic.

doping, or the use of a compound or a procedure that was banned by the sports governing body, since it provides an unfair competitive advantage, is governed by the WADA. WADA sets guidelines that most international sports associations follow.

Christopher Mendias, Ph.D., ATC, assistant professor of orthopedic surgery and of molecular and integrative physiology at the University of Michigan, why WADA regulates certain substances, how things change and how some these drugs can help rehabilitate injuries every day and elite athletes alike.

What are some drugs or athletes use drugs to improve performance?

Mendias: In general, you can break down the compounds and technical athletes use into three categories :. medicines that increase endurance athletes, drugs that make them faster and stronger athletes and drugs that help athletes recover after competition

for endurance, compounds typically work for doping increase the amount of oxygen you can carry in your blood. These range from drugs such as erythropoietin or EPO, which increases the production of red blood cells that carry oxygen circulating in the body athletes, transfusion, where you inject more physically red blood directly into veins 'an athlete. This type of doping is more often seen in sports where athletes must run or cycle long distances with little or no breaks during the competition.

When it comes to making stronger athletes, many drugs fall into the category of anabolic agents, working as the hormone testosterone and trigger the production of new proteins in the muscle. These proteins are the "engine" of the largest muscle cells and can generate more force. You see this type of doping use in sports that involve a lot of sprinting, or in collision sports such as football or rugby.

The third class of drugs, those for recovery, can accelerate the normal process of recovery of athletes' injured cells and help load faster fuel stores. Most drugs of this class are growth factors and compounds which are similar to hormones in the body that aid in tissue repair.

They are increasingly used in all different types of sports. Take swimming or athletics, where athletes must perform in the qualifying rounds of rounds before making it to the final. The ability to recover quickly can allow athletes to perform at a higher level in the qualifying rounds so they make it to the finals, and then do their best in the final too. For collision sports such as football or rugby, the faster you repair the damage caused by damaged muscle cells faster you can compete at a high level again.

Elite athletes who use these substances are breaking the rules of their sports. But there are times when these substances can be helpful

Mendias: While certain medications and substances on the prohibited list of WADA have no medical use legitimate, many do. Drugs that increase the red blood cells are often used in patients with kidney disease or recovering from certain types of cancer. The compounds that make muscle cells bigger and stronger approved the use in the fight against diseases of the severe muscle atrophy, as is observed in some types of myopathies and in men with exceptionally low rates androgenic hormones.

Sometimes these drugs have effects on the body that are different from their normal medical use. Take, for example, beta-blockers, which are drugs that are used to treat high blood pressure. Beta blockers may calm nervous nerves and increase accuracy for sports where accuracy is important, such as golf and archery.

Can you talk more about your research in this area?

Mendias :. My lab conducts research on both the biochemical and genetic side muscle weakness and providing therapies to patients in the clinic suffering from injuries that have profound muscle atrophy

the vast majority of patients we treat in sports medicine, almost all, in fact, are not elite athletes and professionals. We are talking about patients who are physically active supporters injury while playing recreational sports. Sports medicine clinicians and researchers are increasingly attentive to the long-term effects of sports injuries. If an injury is sufficiently serious to prevent a patient for a month or two, there's a good chance that there will be long-term consequences of that damage which will extend many years, sometimes decades, in their lives later.

In patients with ACL tears, for example, even after surgery and rehabilitation of the injured leg muscles are often around 30 percent lower than they were before the injury . Over time, this weakness slowly eroding the cartilage in the knee. My laboratory is studying the possibility that growth hormone - a banned substance by WADA - could help address this weakness in a clinical trial approved by the FDA. We chose growth hormone based on numerous laboratory and clinical studies that have shown it can help protect muscles from injury, although it has not been studied in patients with tears ACL.

This is just a potential medical application of WADA -banned substances. WADA and made offers exemptions for legitimate medical use of certain drugs. Before it can approve the use of the drug, WADA considers the benefits of improved performance potential and weighs this against medical use.

We do not know yet whether growth hormone can help restore the strength closer to normal levels in patients with ACL tears, but if our study and others are successful and the growth hormone is approved by the FDA for the treatment of this condition, WADA should assess in each case whether an athlete would be allowed to take growth hormones if they suffered a major knee injury. For growth hormone, most data show that in adults, it has little or no performance enhancing effects on healthy muscle, so we do not anticipate "doping" effect in our current study . But other drugs as anabolic agents that increase muscle strength in healthy could give athletes a long-term benefit in improving performance, even after they have recovered from their injuries.

Are there other drugs with legitimate medical uses in sick patients but no medical benefit in healthy athletes

Mendias: one of the most high profile doping cases involved a new drug recently banned meldonium. The drug, which has been around for decades, is used in some countries in Eastern Europe to treat patients with heart disease, in which low levels of oxygen to the heart causes tissue damage. But for athletes, meldonium seems to favor the recovery and delivery of oxygen to muscles and improve endurance performance.

Maria Sharapova, a famous tennis player, received a two-year suspension for testing positive for the drug. A recent documentary reported that nearly a fifth of Russian athletics athletes meldonium taking. It is a difficult stretch to justify the use of a heart failure drug in people who have some of the best cardiovascular systems of anyone in the world.

How do you think that this research will impact on professional sport in the future

of Mendias :? We are at a very exciting time in the field of sports medicine. There have been many advances in our understanding of how the biochemical and genetic factors control the function of muscle cells, bone, cartilage and tendon. Now we can use our knowledge of these processes to improve the treatment of injuries to these tissues. Unfortunately, some of the technologies that show great promise in regenerative medicine may also be used for doping purposes. WADA continues to develop new technologies and tests to detect doping, but the list of potential doping compounds and technologies seems beyond our ability to detect it in athletes.

Anti-Doping policies are in place not only to help ensure fairness in competition but also for the health and safety of athletes. Although there have been unscrupulous doctors and scientists involved in numerous doping scandals in recent times, the vast majority of clinical sports medicine and researchers are interested in finding ways to help restore injured athletes back to their pre-injury and not to engage in therapies that give athletes benefits that go beyond what they could achieve through technical and accredited training practices.

Study shows how increasing BMI contributes to multiple myeloma growth and progression

Study shows how increasing BMI contributes to multiple myeloma growth and progression -

In a new study published in Cancer Letters researchers from the American University show how, as BMI increases, so does the growth and spread of multiple myeloma blood cancer, representing approximately 10 percent of all blood cancers in patients .
"once a person with cancer is out of normal weight, BMI contributes to the growth of multiple myeloma and progression," said Katie DeCicco-Skinner, associate professor of biology at American University and lead author of the study.
DeCicco-Skinner and his colleagues examined the normal BMI, overweight patients, obese and morbidly obese, and the effects on myeloma . multiple Little research in multiple myeloma looks different patient weight to see how cells promote cancer growth Even studies examine less cancer and morbid obesity -.. a fourth weight class DeCicco-Skinner said was important to study, as overweight people today have the condition
obesity is considered a risk factor for many cancers, and each increase / m2 5 kg in BMI associated with an increase of 10 percent of cancer deaths, studies show. In multiple myeloma study, normal weight is defined as a BMI greater than 25 kg / m2, and suffering from morbid obesity is in the range of 35 to 40 kg / m2.
Growing stem cells
researchers obtained stem cells from the fat discarded liposuction patients who have undergone elective surgery. They turned them into fat cells and fat cells cultured with multiple myeloma. In the bone marrow, wherein the multiple myeloma is often rooted, fat cells play an important role in the proliferation, survival, progression and resistance to cancer cells drug.
As BMI increases a patient, fat cells communicate with multiple myeloma cells, the researchers found. Fat cells grow, gaining additional fat and secrete proteins related to cancer. The researchers also found a correlation between BMI and angiogenesis and adhesion, key indicators of progress.
"We know multiple myeloma cells will anchor in the bone marrow and fat cells in the bone marrow will support the growth and spread of cancer. In our study, BMI increased, we started to see an increase in the ability of multiple myeloma cells to adhere, causing cancer to better anchor, "said DeCicco-Skinner." with angiogenesis, cancer cells can not exist without their own supply blood. We also found the amount of blood vessels that developed was directly proportional to the BMI of the patient. "
DeCicco-Skinner and his colleagues assumed the proliferation of cancer more benefit than the normal BMI due to the epidemiological link between obesity and cancer. But the relationship between multiple myeloma and BMI in obese patients suffering from morbid obesity was drastic.
"We found that fat cells obese or morbidly obese secreted large amounts of inflammatory proteins, which contributed to the progression of the tumor, "said DeCicco-Skinner.
Implications for treatment
looking DeCicco-Skinner suggests a new approach for the treatment of multiple myeloma. Physicians may consider adjusting medications based on BMI for a patient because a drug may not be as effective in obese patients or morbidly obese.
"Most people think that if you develop multiple myeloma, you go to the doctor, find out the most effective drug cocktail is and how it will affect you," said DeCicco-Skinner. " a patient may need to receive drugs to block inflammatory or other specific proteins in obesity, in addition to standard anti-cancer drugs they receive. "
Whether investigating fat cells, immunotherapy, or the use of CRISPR-Cas 9 gene-editing tool, which a federal commission recently approved a number of patients with three types of cancers, including multiple myeloma, approaches beyond attack cancer cells are needed in the fight against many cancers. With multiple myeloma, most patients live four to seven years from the date of diagnosis, and most become resistant to chemotherapy drugs over time.
"Obesity plays a role in cancer as the number of those who are obese increase. Improving our understanding of how cells and cancer cells greases communicate with each others, and how communication changes in obesity, is critical, "said DeCicco-Skinner.

New opioid use in older people with COPD associated with increased risk of breathing-related death

New opioid use in older people with COPD associated with increased risk of breathing-related death

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Older people with chronic obstructive pulmonary disease begin to use opioids have more than twice as likely to die from a complication related to breathing compared to non-opioid users, researchers at St. Michael's hospital found.
When the researchers specifically examined the stronger opioids, they found the risk of death from breathing was five times higher for new opiate users compared with non-opioid users.
study, published today in the European Respiratory Journal , raises safety issues on the new use of opioids in the elderly with chronic diseases obstructive pulmonary disease or COPD, a progressive lung disease that causes breathing difficulties, said Dr. Nicholas Vozoris, pulmonologist author and leader St. Michael the study.
COPD affects approximately four to 10 percent of the Canadian population, the rate of five mortality between 40 and 70 percent, depending on the severity. The two-year mortality rate for people with severe COPD is approximately 50 percent.
The researchers examined the records of more than 130,000 Ontario adults 66 and older with COPD, using several administrative databases on the provincial health care at the Institute for Clinical Evaluative Sciences.
"previous research has shown that about three quarters of older people with COPD were prescribed opioids, which is an incredibly high rate of new use in a population that is potentially more sensitive to drugs "said Dr. Vozoris. "Our new results show that there is not only an increased risk of death associated with breathing associated with a new opioid use, but also an increased risk, visits to emergency rooms, hospital admissions and need antibiotics or steroid pills. "
Dr. Vozoris found that 68 percent of older people with COPD living in the community received a new prescription opioids between April 07 and March 2012. opioids such as codeine, oxycodone and morphine are commonly prescribed in elderly people with COPD to help treat chronic muscle and bone pain, persistent cough and shortness of breath despite inhalation therapy, and insomnia.
"This is a population that has a chronic lung disease with symptoms that can sometimes be difficult to manage," said Dr. Vozoris. "This class of drugs may offer some relief, but there is also evidence suggesting that opioids may impair breathing and lung health in people who have chronic lung compromise."
To lower the risk of adverse events in this population, the thought was to prescribe less powerful or less dosage of opioids. However, Dr. Vozoris and his team still found a significantly increased risk of complications and death among new consumers of respiratory related opiates, regardless of dose. "This finding is important because it has been thought that low doses of opioids may be safe for patients with COPD," said Dr. Vozoris.
Dr. Vozoris hope that clinicians take these findings into account when prescribing opioids for COPD patients. current guidelines recommend their use to manage respiratory symptoms difficult to control who can often compromise the quality of life of a patient, but the current data do not take not support the use of opioids for chronic pain.
"Sometimes patients are looking for a quick solution to the issues and chronic pain or respiratory physicians may believe opioids can offer them some relief, "said Dr. Vozoris." the compromise is explaining that there are risks for patients and ensure that they understand that potentially relieve their symptoms could come at a high cost to their health. "

E-cigarettes may provide benefits to public health, according to a study

E-cigarettes may provide benefits to public health, according to a study -

A modeling study by leading experts in tobacco control is that e-cigarettes may provide public health benefits on a "conservative estimate" of the probable adoption of vaping and smoking among adolescents and young adults.
The study, published in Nicotine & Tobacco Research, suggests that "the recent allegations of some scientists that e-cigarettes are likely to act as a gateway to the use of tobacco products are exaggerated" says lead study author, scientist population David Levy, Ph.D., professor of oncology at Georgetown Lombardi Comprehensive Cancer Center.
If used instead of smoking, e -Cigarettes offer the potential to reduce harm and improve public health, said Levy. But they also have the potential to increase bad if young people who would not otherwise have smoked cigarette smokers become as a direct consequence of the first try e-CIGARETTES- the hypothesis called "gateway" which won the favor of some, he said.
"Our study shows that, given a wide range of reasonable scenarios, e- cigarettes can reduce cigarette consumption and will not lead to offset the increased damage caused by the use of e-cigarettes and more deadly cigarettes, "Levy said. "When considering the positive and negative aspects of using plausible e-cigarette, we find that vaping is likely to have a net positive impact of public health."
The team that developed the model - the US researchers, Australia and Canada - have projected a 21 percent of deaths attributable to smoking and 20 percent in the years of life lost as a result of the use of e-cigarettes among people born in 1997 or later, compared to what would have happened if e-cigarettes were not an option.
"Our model is consistent with recent evidence that, while the e-cigarette use has increased markedly, smoking among youth and young adults has dropped dramatically," Levy said.
Levy supports the decision taken recently by the Food and Drug administration of the United States to ban the use of e-cigarettes to young people under 18 "because we always want to discourage the use of all products of nicotine and cigarettes, "he said.
Levy also said that, despite their estimates of overall public health benefit of e-cigarettes, the use of youth these products should be constantly monitored, as use patterns are likely to change as the product and awareness of product changes.
While supporting FDA regulation cautious of e-cigarettes, Levy said he fears that the regulation of e-cigarettes in the same way that cigarettes will pose a burden to small businesses that lack the resources to obtain marketing approval for their products. "Overregulation e-cigarettes could actually stifle the development and commercialization of safer products that could effectively replace cigarettes," he said.

New tool helps researchers establish links between proteins, genes, drugs and diseases

New tool helps researchers establish links between proteins, genes, drugs and diseases -

Every day, more than 3,000 new summaries are uploaded on PubMed the reference database of the main biomedical literature. Even in the closely defined area of ​​a researcher, it is impossible to stay on top of the bands changing interconnections between these documents. For example, a new gene is described - can it be useful to the specialty of a researcher? It could take many painstaking hours of research to find the answer. Now a new tool developed in Tan alternative laboratory at the University of Colorado Cancer Center and described today in the journal Bioinformatics helps researchers make these connections. The free tool HiPub, is available for download as a plugin for Chrome Web browser.

"HiPub looks through all text and tries to recognize what is called the genes, proteins, drugs, and diseases. It extracts this information and displays in a network. Especially in molecular biology or the biology of cancer, it is helpful to see the links between these things in their biological context, "said Aik Choon Tan, Ph.D., a researcher at the CU cancer Center and associate professor at the CU School of Medicine.

Tan gives the example of a hypothetical researcher who reads a paper exploring the KRAS gene and MEK, known to influence the development of certain cancers. "the researcher wants to know if these genes have any relevance to his specialty, can -being something like p53 [another gene known to influence cancer]. "

queries researchers" p53 "with the new section and HiPub shows how the researcher's interest is connected to the genes of the new paper. If the connections appear convincing, researchers could design experiments to test these linkages.

"The idea of ​​text mining is not new," said Tan. "Computer scientists have done for ten or twenty years. But the real application of text mining in biomedical research is very limited. HiPub is a way to use text mining to simplify the knowledge discovery process. "

The research could help develop better therapies for the new subtype of adenocarcinoma patients

The research could help develop better therapies for the new subtype of adenocarcinoma patients -

Lung cancer is the most common cause of cancer death this represents about a third of all deaths related to the tumor. Adenocarcinoma, a cancer non-small cell lung (NSCLC) represent approximately 40 percent of cancer diagnoses, but few treatments are available for the disease.

A team of researchers led by Elena Levantini, PhD, a research associate in hematology-oncology at Beth Israel Deaconess Medical Center (BIDMC), medical instructor at Harvard Medical School and member of the Institute of cells Harvard strains identified a subtype of human adenocarcinoma. The research could help determine who is most at risk of developing lung tumors that can lend itself to a new therapy to inhibit their progress. The results - in collaboration with the Institute of Cancer Sciences at the National University of Singapore (NUS CSI) - were published today in the journal Science Translational Medicine

"Advances in treatment lung cancer require a better understanding of. molecular origins of this deadly disease, "said corresponding author last Levantini, who is also a researcher at the Institute of biomedical technologies of the National research Council (CNR-ITB). "Understanding the differences between lung cancers could also lead to innovations in treatment strategies and allow us to overcome drug resistance, relapse and progression of the disease."

Levantini and colleagues previously showed that NSCLC tumor cells often express too little or none of a transcription factor called C / EBP 伪, a protein that regulates gene expression and cell proliferation in the lung tissue. It is also known to play involved in a form of leukemia and liver cancer, squamous skin carcinoma cells, squamous cell cancers of the head and neck and other cancers. in their earlier work, scientists suspected that C / EBP伪 can act as a tumor suppressor in normal cells, but the mechanism by which the absence promoted lung cancer tumors are not clear.

In a series of in vitro experiments, the researchers demonstrated that C / EBP 伪 indeed works as a tumor suppressor by limiting the expression of another molecule known to play a role in triggering and the maintenance of tumor growth. This molecule, Bmi1 is an oncogenic protein that has been implicated in colon cancer, a form of leukemia and breast and gastric cancers.

To determine the relationship between the suspected tumor suppressor (C / EBP 伪) and the oncogenic protein (BMI1), researchers first modified a line of human adenocarcinoma cells to overexpress C / EBP伪. This led to a marked reduction in the expression of BMI1. When the team analyzed tissue from 261 patients with NSCLC, they found an inverse correlation between the two molecules; more than 80 percent of the tissues of patients with low levels of suppression of C / EBP 伪 were positive for expression BMI1 tumor. Similarly, a sample of tissue for analysis from patients with lung adenocarcinoma with little or no C / EBP phrase found that people with lower levels of BMI1 were more likely to survive, a model that has prognostic value, the researchers wrote.

"Our findings suggest that lung cancer subtype defined by the loss of expression of C / EBP could specifically benefit from therapies that inhibit BMI1," the scientists wrote. "Thus, the identification of factors that modulate its expression sparked a major clinical interest."

The research team was also able to validate its findings in mice. In a series of experiments with mice engineered to express any C / EBP 伪, scientists found an inverse relationship between the transcription factor and BMI1 which was almost identical to its human adenocarcinoma data. By manipulating the expression BMI1 in vivo, the researchers were also able to confirm that the decreased expression of the oncogene protein was sufficient to completely inhibit tumor formation and even stop tumor growth significantly.

"BMI1 plays an important role in many solid tumors, including one of the most aggressive models of lung cancer, and its expression is related to tumor growth, invasion, the metastasis, prognosis and recurrence, "said Levantini." Our findings may help us design better therapies for the subset of patients with adenocarcinoma low C / EBP 伪 and high expression pattern BMI1. "

Watch-and-wait approach may prove fruitful in subset of adults with advanced kidney cancer

Watch-and-wait approach may prove fruitful in subset of adults with advanced kidney cancer -

watch-and-wait approach means that some patients may delay taking highly toxic non-curative cancer drugs that come with significant side effects

some adults with advanced kidney cancer (renal cell carcinoma) who a slow-growing disease can live for months and even years without the disease getting worse with active surveillance, or close monitoring for signs of disease progression, instead of having to undergo immediate treatment with anticancer drugs very toxic, suggests a new study published in the Lancet Oncology .

The approach shows-and-wait was the most successful among adults with limited site of metastatic disease and those with one or less unfavorable prognostic factors such as anemia, thrombocytosis (high platelet ), and greater disability. For example, 29 patients who had two or fewer organs affected and one or no risk factors at baseline remained on average almost three times longer on active surveillance than other patients (22.2 months vs. 8.4 months).

"There is a perception that all cancers must be treated immediately because they are just as deadly. But what we have seen in this small phase 2 study is a subset of adults advanced kidney cancer is a disease that can be managed safely by using active surveillance, which could save them the inconvenience and side effects debilitating effects of aggressive treatment to slow growth about a year, and in some cases several years without worsening anxiety and depression, "says lead author Professor Brian Rini Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA." with only 50 people involved in our trial, the risks and benefits the approach should be studied in a larger group of patients "

Each year about 62,700 new cases of kidney cancer are diagnosed in the United States and about 14,240 people die from the disease. UK there are approximately 11,873 new cases and 4,421 deaths from the disease. Survival varies greatly from as short as 5 months in patients with poor prognosis without systemic therapy, to 43 months in patients with a good prognosis with a systemic treatment.

When kidney cancer has spread to other body parts, the objective of systemic treatment is to slow the cancer down with anti-angiogenic drugs such as sunitinib and sorafenib are designed to prevent the formation of new blood vessels, thereby stopping or slowing the growth or spread of tumors. But these treatments are expensive, not curative, and have serious side effects, including increased risk of stroke and heart attack.

disease

Some people with advanced kidney cancer have very slow growth, and small case studies suggest that active monitoring and delayed treatment could be a safe and effective alternative to an immediate systemic treatment without compromising the response to subsequent processing.

In this Phase 2 study, Rini and colleagues enrolled 52 adults (aged 18 years or over) with advanced cancer who have not received prior systemic treatment in five hospitals in the United States kidney , Spain and the UK. Participants had a CT scan of the chest, abdomen and pelvis at the beginning of the study and at regular intervals to assess the burden and time to tumor progression. Patients were closely monitored and could decide with their doctor to start systemic treatment at any time. Changes in quality of life, anxiety and depression were also measured at baseline and on the monitoring period. Participants were followed for an average (median) of 38.1 months.

In the 48 participants included in the analyzes, the (median) average time on active surveillance prior systemic treatments from was 14.9 months and overall survival of the start of the monitoring was 44.5 months.

43 (0%) participants experienced disease progression at some point during the study, most of them (37) began a systemic treatment. However, nearly half (20) of participants chose to continue monitoring for an average of 15.8 more months after disease progression. Six patients remain on active monitoring to date. Three participants have survived without their disease getting worse and two withdrew or were lost to view.

Nearly half (22) of the patients died during the study, but only one patient died (brain metastases) without ever receiving systemic therapy.

Importantly, the quality of life, and anxiety and depression scores did not change significantly during the monitoring period, suggesting that living with untreated cancer has not cause psychological harm to patients with advanced kidney cancer in this study.

authors sound a note of caution about the limits of this process could reduce the wide applicability of the approach. For example, patients included in the trial were a very small group selected by the physician, rather than based on the characteristics of the disease, such as tumor burden or the pace of growth of the disease. Furthermore, the decision to end the surveillance was left to the discretion of the patient and physician

According to Professor Rini :.

With the development of new immunotherapy in renal carcinoma cells more work is needed to understand the risks and benefits of this initial observation approach. However, our data provides guidance on how to select patients who may delay treatment and instead be monitored safely with active surveillance.

Writing in a linked comment, Dr Paul Russo Memorial Sloan Cancer Center, Weill Cornell College of Medicine, New York, USA said:

This document provides guidance to both medical and surgical oncologists who, when faced with a newly diagnosed patient with metastatic renal cell carcinoma cells that has a good performance and limited metastatic disease, may offer a period of close supervision with the prolonged survival potential before progression of the disease and the initiation of systemic therapies. There is no evidence from this study that this close supervision for the security or survival of the patient. It remains to be seen whether the current genomics research can identify genes that can be used together with the selection factors described above to better select appropriate patients for initial active surveillance.