Experts join MD Anderson to end a cancer

Experts join MD Anderson to end a cancer -

The University of Texas MD Anderson Cancer Center is pleased to announce that one of the leading experts in the world research and breast cancer treatment, V. Craig Jordan, Ph.D., will join the institution's efforts to end cancer. Jordan is considered the "father of tamoxifen," the revolutionary therapeutic drug that has saved countless lives.

As a professor in Breast Medical Oncology and Molecular and Cellular Oncology Jordan will focus on the new biology of the cell estrogen-induced death in order to develop translation approaches to treatment and prevention cancer. He began working at MD Anderson in October.

"This is an exciting time and I am delighted that Dr. Jordan will contribute to the important translational research in breast cancer here at MD Anderson," said Ron DePinho, MD, president of MD Anderson. "His international reputation as a pioneer in translational research and his many achievements and accolades are well deserved. As we progress in our mission to end cancer in Texas, the nation and the world, it is of eminent scientists like Dr. Jordan who will play key roles in this promise. "

long and distinguished executive career positions Jordan included in some of the most prestigious biomedical institutions in the world. Currently he is scientific director of the Comprehensive Cancer Center at Lombardi at Georgetown University in Washington, DC, and Vincent T. Lombardi president of translational cancer research. He is also vice president of the Department of Oncology and professor of oncology and pharmacology at the Medical School of the University of Georgetown. In addition, he is a visiting professor of molecular medicine at the University of Leeds in England, and assistant professor of molecular pharmacology and biological chemistry at Northwestern University in Chicago.

"the election of Dr. Jordan as a member of the National Academy of Sciences in 09 is just one of many honors he received following his incredible contributions to our understanding of biology cancer, "said Ethan Dmitrovsky, MD, MD Anderson provost and executive vice president. "MD Anderson is known for bringing together the best minds in the common goal of ending cancer. Certainly, a scientist of the caliber of Dr. Jordan adds significantly to our global research programs. His arrival is due in large part to the efforts Debu Tripathy, MD and Vicente Valero, MD "

Dr. Tripathy is new president of MD Anderson breast medical oncology. He will begin his work at the institution in September.

In addition to his membership in the National Academy, the Jordan's achievements list, awards and achievements is long, with more than four dozen international awards. The list includes:
• The Price of St. Gallen Breast Cancer (2011)
• The Price Karnofsky David A. American Society of Clinical Oncology (08)
• The George Price and Christine Sosnovsky in Cancer Therapy (04)
• Charles F. Kettering Prize (03)
• American Cancer Society Medal of Honor (02)
• the Dorothy P. Landon Price translational research the American Association for Cancer Research (02)
• Bristol Myers Squibb award (01)
• Cameron Price of the University of Edinburgh (1993)

Jordan received six scholarships or honorary degrees from universities around the world, including an honorary fellowship of the Royal Society of Medicine. In 2010 he was elected president of the Royal Society Foundation Medicine in North America. Jordan was elected as a member of the Academy of Medical Sciences, the equivalent of the UK Institute of Medicine.

He has contributed to over 700 publications, 99 percent relating to cancer research. He published 11 books and more than 26,000 scientific citations. He is the author of the book "Tamoxifen, a pioneer in the medicine of breast cancer."

Jordan, who was born in New Braunfels, Texas and raised in England, has dual British and American nationality. In 02 he received the Order of the British Empire by Queen Elizabeth II for services to international research on breast cancer. He earned a PhD and D.Sc. University of Leeds in 01, received an honorary M.D. of his alma mater.

"I am proud to be joining MD Anderson Cancer Center," said Jordan. "It is indeed an honor to continue my work in this world-renowned cancer center where I look forward to working with my distinguished colleagues."

Jordan is credited with reinventing a failed contraceptive (known as ICI 46474) as a breast cancer treatment. The drug, which has existed since the 1960s, was originally created to block estrogen in the hope of preventing pregnancy. Jordan developed the adjuvant treatment strategy for long-term tamoxifen, and the description and decipher the properties of a new group of drugs called selective estrogen receptor modulators (SERMs). He was the first to discover the preventive capacities of both tamoxifen and raloxifene drug. The drugs have been approved by the FDA to reduce breast cancer incidence in women at high risk.

Advaxis, MedImmune team trial

Advaxis, MedImmune team trial - immuno-oncology

Advaxis, Inc. (NASDAQ: ADXS), a clinical-stage biotechnology company developing cancer immunotherapies, entered into a clinical trial collaboration with MedImmune, the global research and development arm of organic products from AstraZeneca. Phase I / II study of immunotherapy will evaluate the safety and efficacy of anti-PD-L1 immune checkpoint inhibitor MedImmune investigation MEDI4736, in combination with vaccine immunotherapy main cancer Advaxis, ADXS-HPV, as a treatment for patients with advanced, recurrent or refractory human papillomavirus (HPV) -Associated cervical cancer and head and neck associated with HPV.

both MEDI4736 ADXS-HPV and cancer immunotherapies are a new class of treatments that use the body's own immune system to help fight against cancer. MEDI4736 is designed to counter tactical evading immune tumor by blocking a signal that prevents the detection of tumors, while HPV-ADXS strengthens the ability of immune cells to fight against the tumor. Preclinical data suggest that the combination of ADXS-HPV with a checkpoint inhibitor, such as MEDI4736, can enhance the antitumor response overall.

"Our collaboration with Advaxis is further evidence of MedImmune's commitment to explore new combination of approaches as we progress our immuno-oncology portfolio," said Dr. Bahija Jallal, Executive Vice President, MedImmune. "We think there could be a significant clinical benefit of the combination of MEDI4736 with the vaccine against the specific cancer antigen Advaxis."

under the terms of the agreement, MedImmune Advaxis and evaluate the combination as a treatment for cancer associated HPV and cervical squamous cell carcinoma of the head and neck. it is expected that part of the Phase I trial to establish a recommended dose regime with MEDI4736 ADXS-HPV, and the game Phase II will evaluate the safety and efficacy of the combination. the study will be financed and carried out by Advaxis. the results of the study will be used to determine if further clinical development of this combination is justified.

Under the terms of the agreement, MedImmune has a non-exclusive relationship to tumor types led to HPV. MedImmune has the first right of negotiation for future development combinations involving MEDI4736 and ADXS-HPV.

"We are delighted to be in partnership with MedImmune and evaluate our MEDI4736 in combination with immunotherapy," said Daniel J. O'Connor, CEO, Advaxis. "This is the first time a PD-L1 inhibitor checkpoint will be used with a new class of immunotherapies. As more companies vie for a competitive advantage in the future market PD-L1, the ability of our platform immunotherapy to attack multiple tumor targets is an attractive combination therapy. "

The age of sexual maturity is influenced by the "print" genes in girls

The age of sexual maturity is influenced by the "print" genes in girls -

The age at which girls reach sexual maturity is influenced by genes " print "a small subset of genes whose activity differs parent passes the gene, according to a new study published today in the journal Nature .

results obtained from an international study involving more than 180,000 women scientists from 166 institutions worldwide, including medical school of the University of Boston. The researchers identified 123 genetic variations that have been associated with the time when the girls had their first menstrual cycle by analyzing the DNA of 182.416 women of European ancestry from 57 studies. Six of these variants were found to be clustered in the printed regions of the genome

The activity of imprinted genes differs parent the gene is inherited -. Some genes are active when maternally inherited, others are active only if inherited from the father. Both types of imprinted genes have been identified as determining the time of puberty in girls, which indicates a possible conflict between biological parents on their child's development rate. Further evidence of the imbalance in parental inheritance patterns was obtained by analyzing the association between these imprinted genes and puberty in a study of over 35,000 women in Iceland, where detailed information on their family trees were available.

This is the first time it has been shown that imprinted genes may control the rate of development after birth.

senior author Joanne Murabito, MD, MSc, associate professor of medicine at the School of Medicine Heart Study / Framingham Boston University said: "Our results demonstrate a complex network of underlying genetic factors when menarche menarche is associated with the development of health conditions later in life women such as diabetes, cardiovascular disease and breast cancer by studying the genetic factors that we hope .. better understand how the timing puberty in girls is linked to serious health conditions in women. "

Exposure to light at night makes breast cancer completely resistant to drug

Exposure to light at night makes breast cancer completely resistant to drug -

Exposure to light at night, which stops the nocturnal production of hormone melatonin, makes breast cancer completely resistant to the drug tamoxifen against breast cancer widely used, according to a new study by researchers at the school of the Tulane University medical cancer. The study "circadian disruption and melatonin by light exposure at night Drives intrinsic resistance to tamoxifen therapy in breast cancer," published in the journal Cancer Research , is the first to show that melatonin is critical to the success of tamoxifen in breast cancer treatment.

principal investigators and co-managers of Circadian Biology Group of the Tulane Cancer, Steven Hill and David Blask, as well as team members Robert Dauchy and Shulin Xiang, studied the role of melatonin on the effectiveness of tamoxifen in the fight against human breast cancer cells implanted in rats.

"in the first phase of the study, we kept the animals in a daily light day / night cycle of 12 hours of light followed by 12 hours of total darkness (melatonin is high in of the dark phase) for several weeks, "says Hill." in the second study, we exposed them to the same daily light day / night cycle, but during the 12-hour dark phase, animals were exposed to extremely low light at night (melatonin levels are deleted), roughly equivalent to low light under a door. "

melatonin by itself delayed tumor formation and significantly slowed their growth, but tamoxifen caused a significant regression of tumors in animals with either high levels of melatonin at night in complete darkness or those receiving melatonin supplementation during dim light in the night show.

These findings have potentially huge implications for women being treated with tamoxifen and also regularly exposed to light at night because of sleep problems, night work or exposed to light of the screens computer and television.

"high levels of melatonin at night to breast cancer cells to" sleep "by turning off growth mechanisms. These cells are vulnerable to tamoxifen. But when the lights are on and the melatonin is suppressed to awaken "the breast cancer cells and ignore tamoxifen," said Blask.

The study could shed light night a new and serious risk factor to develop resistance to tamoxifen and other anti-cancer drugs and make the use of melatonin in combination with tamoxifen, administered optimal time of day or night, the standard treatment for patients with breast cancer.

The new technology could revolutionize the treatment and prevention of sepsis

The new technology could revolutionize the treatment and prevention of sepsis -

The National Science Foundation has awarded $ 0,000 for engineers at Oregon State University, who have developed a new technology that could revolutionize they believe the treatment and prevention of sepsis.

Sepsis is a "hidden killer" that the United States actually kills more people every year than AIDS, prostate cancer and breast cancer combined.

More commonly known as "blood poisoning", sepsis can quickly turn a modest infection an inflammation of the whole body based on a dysfunctional immune response to endotoxins which are released from bacterial cell walls . In severe cases, this can lead to multiple organ failure and death.

When treatment is started early enough, sepsis can sometimes be treated successfully with antibiotics. But they are not always effective and the mortality rate for the condition is still 28-50 percent. About one in four people in a hospital emergency room is there because of sepsis, and millions of people die worldwide each year, according to reports in the New England Journal of Medicine and other studies.

In the search for avant-garde, the OSU experts used microchannel technology and special coatings to create a small device through which blood could be treated, removing endotoxins and problematic prevention of sepsis. Several recent professional publications have reported on their progress.

"More work is needed, and the support of the National Science Foundation will contribute to that," said Adam Higgins, principal investigator of the grant and an assistant professor in the OSU School of Chemistry , biological engineering and the environment. "Once completed, we believe that this technology will treat sepsis effectively at low cost, or even prevent it when used as a prophylactic treatment."

This technology can finally offer a way to fight against sepsis other than antibiotics, researchers said.

"This does not kill bacteria and leave floating fragments behind, it sticks to and eliminates circulating bacteria and endotoxin particles that could help trigger a sepsis response," said Karl Schilke , Callahan OSU Faculty Scholar in chemical engineering.

"We hope to emboss the cheap polymer device, so it should be cheap enough that it can be used once and then discarded," said Schilke. "The low cost also allow treatment before sepsis is evident Whenever there is a concern about developing septicemia -. Due to injury, injury, surgery or infection -. You could get ahead of the problem "

" Much of the problem with sepsis is that it moves so quickly, "said Joe McGuire, professor and head of the OSU Department of Chemical, Biological and environmental engineering. "as it is clear that the problem is, it is often too late to treat.

" If given early enough, antibiotics and other treatments may sometimes but not always stop this process, "said McGuire. "Once these are bacterial fragments in the blood stream antibiotics still work. You can have succeeded in eradicating the live bacteria even when you are dying."

The approach developed at OSU College genius is to move the blood through a very small processor, the size of a coffee cup, and literally take endotoxins and remove them.

microchannels make this possible. They can provide accelerated heat and mass transfer as the fluids move through tiny tubes width of a human hair. applications are already under consideration in any heat exchangers solar energy. They can be produced in mass quantities at low cost, stamped on a range of metals and plastics, and used to treat a large volume of liquid in a relatively short time.

in the system developed at Oregon State, blood can be pumped through thousands of microchannels that are coated with what researchers call "brush polymer suspension" with repeating chains of atoms . of carbon and oxygen anchored on the surface This prevents proteins and blood cells from sticking or coagulate on the end of the pendant chain is a peptide -. or bioactive agent. - Who binds tightly to endotoxin and removes blood, which then directly to the patient

Sepsis is quite common. It can develop after an injury caused by a car accident, a dirty wound, an extended operation in hospital which carries a risk of infection or infectious diseases in people with a weakened immune system or compromise.

Researchers identify two classes of antidepressants that reduce symptoms of depression

Researchers identify two classes of antidepressants that reduce symptoms of depression

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Two classes of antidepressants improve symptoms. One agent, not available in the United States, proves superior

Depression is common in cancer, up to half of all patients facing the experience of the disease, depressive symptoms ranging from mild to severe. When depression coexists with cancer, patients may be at increased risk of cancer death and suicide.

Antidepressants are commonly prescribed, but evidence of their effectiveness is mixed. The role of antidepressants in treating depression related to cancer has not been rigorously studied. To identify best practices for the treatment of depression in cancer, the Dartmouth researchers have completed a systematic review and meta-analysis of existing research. The document was published in General Hospital Psychiatry in June

The study identified two classes of antidepressants that reduce the symptoms of depression.

• An alpha-2-adrenergic receptor antagonist: mianserin
• Two inhibitors serotonin reuptake: fluoxetine (Prozac) and paroxetine (Paxil)

available data indicate that paroxetine and fluoxetine can improve depressive symptoms, but perhaps less well tolerated.

Miaserin also showed a depression response rate higher compared to placebo, whereas paroxetine and fluoxetine has not. Response rates were low suggesting that modest changes in depressive symptoms.

"All evidence to the alpha-2 adrenergic receptors was based on a single agent, mianserin," said Natalie Riblet, MD, MPH, lead author of the study, Department of Psychiatry, Geisel School of Medicine. "Unfortunately, the agent most promising, mianserin, are not available in the United States. Given that mirtazapine is a pharmacological close cousin mianserin, there may be clinical benefit to further explore the role of mirtazapine in the management of depression associated with cancer. "

In terms of profiles side effects, mianserin seemed slightly more tolerable compared to placebo, paroxetine was the dropout rate slightly higher but not significant because of side effects compared to placebo, fluoxetine had a significantly higher drop than placebo, but this finding became insignificant after removing an outlier of the study.

"adverse drug interactions are possible between chemotherapy drugs and antidepressants," said Riblet. "Specifically tamoxifen, a common chemotherapy agent, may interact with certain antidepressants to increase the risk of serious side effects."

The different classes of antidepressants work on different neurotransmitters. The study indicated that the antagonists of alpha-2 adrenergic receptors show particular promise in cancer patients may be due to their pharmacological profile, increasing norepinephrine and serotonin. antagonists, alpha-2 adrenergic receptors are less likely to cause side effects associated with common serotonin such as headaches, restlessness, nervousness, or sexual dysfunction, but may contribute to sedation.

The review included nine randomized trials conducted between 1985 and 2011 with 4700 eligible records of 1,169 patients from various countries. Overall 83 percent of the subjects were women with an average age of 54 years.

"There is a paucity of evidence to address the role of antidepressants in depression related to cancer," Riblet said. "Our results suggest the need for high quality randomized clinical trials explore the role of antidepressants in treating depression related to cancer. "

New method triple length of time organs can be preserved for transplantation

New method triple length of time organs can be preserved for transplantation -

supercooling and perfusion machine allows the rat liver transplantation preserved up to four days

a system developed by researchers at the Massachusetts General Hospital (MGH) engineering Centre in medicine has enabled the successful transplantation after conservation rat liver during the period of four days, more than triple the length time members currently can be preserved. The team described their protocol - which combines temperatures below the freezing point with the use of two protection solutions and infusion machine of the body - in a document Nature Medicine receive the publication advance online

"in. our knowledge, this is the longest conservation time with after a successful transplant to date," said Korkut Uygun, PhD, of the Center medical engineering MGH ( MGH-CEM), co-lead author of the report. "If we can do that with human organs, we could share organs worldwide, helping to mitigate the shortage of organs in the world."

When the supply of oxygen and nutrients is cut off from any body, it begins to deteriorate. Since the 1980s, the organ donors were kept at or temperatures just above freezing (0˚ 32˚ Celsius or Fahrenheit) in a solution developed at the University of Wisconsin (UW solution), which reduces the metabolism and organ deterioration ten times for a maximum 12 hours. the extension of the shelf life, the authors note, could increase both the distance of a donor organ can safely be transported and the amount of time available to prepare a recipient for the operation.

Keep an organ below freezing temperatures, a process called supercooling, could extend the shelf life by slowing the metabolism again, it could also damage the body in many ways. To reduce these risks the MGH-CEM protocol involves the use of two protection solutions -. Polyethylene glycol (PEG), which protects cell membranes, and a glucose derivative called 3-OMG, who is caught in liver cells

After the removal of donor animals, livers were tied a machine perfusion system - in essence, an "artificial body" that supports the basic body function - where they were first charged with 3-OMG, then rinsed with a combination of UW solutions and PEG while being cooled at 4 ° C (40˚ F). The organs were then immersed in the solution UW / PEG and stored at -6C (21F) for either 72 or 96 hours, whereupon the temperature was gradually increased back to 4 ° C then organs were perfused with the machine UW solution / PEG at room temperature for three hours before being transplanted into healthy rats.

All animals received for 72 hours supercooling organs were healthy at the end of three months of study follow-up period. Although only 58 percent of animals receiving supercooling bodies for 96 hours survived for three months, the analysis of several factors, then, that the bodies were warmed could distinguish between bodies that have been and are successfully transplanted .

"The ability to assess the livers before transplantation to determine if the body is supercooled still good enough for transplantation," says co-author Bote Bruinsma, MSc, of the MGH-CEM. " even among livers preserved for four days, had we used only those in which the oxygen consumption, bile production and flow of the infusion solution were good, we would have reached 100 percent survival. "

Although much work needs to be done before this approach can be applied to human patients, extending the duration of an organ can be preserved safely may eventually allow the use of organs currently deemed unfit transplantation, notes Martin Yarmush, MD, PhD, founding director of the MGH-CEM and co-lead author. "by reducing the damage that may occur during storage and transportation, our supercooling protocol may allow use livers currently considered marginal - something we're investigating. - which could further reduce long waiting lists for transplants " Yarmush Uygun and are both on the faculty of Harvard Medical School.

The principal author of Nature Medicine report Tim Berendsen, MD, formerly of medical engineering MGH Center and now at the University Medical Center Utrecht, the Netherlands -Low. Additional co-authors are Puts Catheleyne, Nima Saeidi, Berk Usta, Basak Uygun, Maria-Louisa Izamis and Mehmet Toner, all of the MGH-CEM. The study was supported by National Institutes of Health grants R01EB008678, R01DK096075, R01DK084053, R00DK080942 and R00DK088962 and funds from Shriners Hospitals for Children. Several patents covering the work described in this document are pending.

New approach can help develop more effective immunotherapy for metastatic melanoma

New approach can help develop more effective immunotherapy for metastatic melanoma -

A new approach has shown that the recognition of the unique cancer mutations appears to be responsible for complete regressions of cancer in both metastatic melanoma patients treated with immunotherapy guy called T cell adoptive therapy. This new approach may help develop more effective cancer immunotherapies, according to a study published in Clinical Cancer Research , a journal of the American Association for Cancer Research.

"This study provides the technical solution to identify mutated tumor targets that can stimulate immune responses, which is one of the main bottlenecks in the development of a new generation of therapy adoptive T cells, "said Steven A. Rosenberg, MD, PhD, chief of surgery at the National cancer Institute (NCI) in Bethesda, Maryland." the two targets identified in this study play an important role in the proliferation of cancer cells.

"Immunotherapy has the ability to successfully treat cancer by targeting tumor mutations. We have moved a step closer because of this study, "said Rosenberg.

Adoptive T cell therapy is a form of immunotherapy in which the immune cells infiltrating the tumor of a patient, so called tumor-infiltrating lymphocytes (TIL which are T cells) are harvested, activated and expanded in the laboratory and transferred to the patient. These activated cells are able to effectively attack tumor cells.

"in a clinical trial, up to 72 percent of patients with metastatic melanoma experienced tumor regression after the transfer of adoptive T cell. However, all patients received. In fact, the specificity of the TIL remains largely uncertain. Our goal was to establish an effective method to identify the specificity of these cells, "said Rosenberg.

The researchers collected tumor samples from two patients who had received therapy and pursued two approaches screening to identify tumor targets recognized by clinically effective T cells. First, they used conventional method of screening called the screening of cDNA libraries to identify non-mutated target. Second, they used a new method called tandem minigene library screening to identify mutated targets that can not be found by the conventional screening method.

for the second approach, the researchers used the new generation of DNA sequencing to sequence the coding regions of DNA from tumors of both patients and the identified mutations. Then, they generated a library of these mutations. instead of the synthesis of all of the mutated gene, they synthesized only a small region surrounding the mutation (hence the name "minigene" library). They then screened the mini-gene library to identify targets in tumors of patients who were recognized by their TIL.

Using the cDNA library screening, the researchers identified three new tumor targets non-mutated, and four previously known non-mutated tumor targets.

Using tandem minigene library screening, they identified two new mutated tumor targets, and KIF2C POLA2, which play an important role in cell proliferation.

With the approach of the library minigene, Rosenberg and colleagues recently reported another novel tumor targets recognized by activated T cells of a patient with cancer of the bile ducts, which responded to adoptive transfer T cell

Seattle magazine names 36 EvergreenHealth doctors to the list "Top Doctors"

Seattle magazine names 36 EvergreenHealth doctors to the list "Top Doctors" -

The latest issue of Seattle The magazine 36 doctors in the network EvergreenHealth to publish annual list "Top Doctors".

every year Seattle demand thousands of local doctors to nominate colleagues they would trust with the health care of a loved one via a line, peer-to-peer survey . The 2014 list includes 437 providers in 70 specialties.

"We are always proud to recognize the contributions of our suppliers are in the health and wellness of our community, and today we celebrate those who have been honored by their peers as" Top Doctors, "CEO Bob EvergreenHealth Malta said. "The recognition by the local medical community of our suppliers is a testament to the hard work and dedication of our suppliers, and shows that the community appreciates their commitment to providing the highest quality, safest and most satisfying to the best care value. "

More than 13,000 suppliers participated in an independent survey that invited all licensed physicians in the Puget Sound region to nominate their peers for the annual recognition. GMA Research and CHCS Internet Development collected data between January 13 and February 7, 2014, which was assessed to help determine the final list.

the finalists are selected once the nominations of all physicians are counted. Those who are appointed time most in each specialty are candidates for inclusion, and other factors are taken into account before the list is finalized, including the total number of doctors in each specialty, consumer demand for specialty, distribution of voting, the candidates standing, geography, education and residence.

Seattle magazine has expanded the list of specialties this year to include non-certified consulting specialties and alternative medicine in response to the interest of more and more learning reader the best practitioners in these areas as a practice recommended by doctors.

Also new this year, doctors can recognize nurse practitioners and physician assistants who set the bar for excellence in health care.

2014 Top Doctors EvergreenHealth and their specialties are listed below in alphabetical order.

• Sheemain D. Azariah, MD, obstetrics
• Maria Chong, MD, diagnostic radiology
• Lynn B. Davis, MD, obstetrics
• Michele A. Delorit, MD, obstetrics
• Christopher L. Fellows, MD, Cardiology
• Michele B. Frank, MD, Hematology and oncology
• Todd M. Guyette, MD , hand surgery
• Kevin Hanson, MD, emergency medicine
• Michael A. Hunter, MD, radiation oncology
• David Y. Kim, MD , anesthesiology
• Edward Kim, MD, Cardiology
• Jason Kim, MD, pain medicine
• Lindy S. Klaff, MD, pulmonary and Critical Care medicine
• Carolyn R. Kline, MD, maternal fetal medicine and
• Samuel S. Koo, MD, Orthopaedic
• Varun Laohaprasit, MD, neurosurgery
• June L. Lee MD, anesthesiology
• Melissa D. Lee, MD, pulmonary and Critical Care Medicine
• Steven N. Lee, MD, anesthesiology
• Matthew Lonergan, MD, hematology and oncology
• Craig M. McAllister, MD, orthopedic surgery
• Aileen A. Mickey, MD, pulmonary and Critical Care Medicine
• George G. Min, MD, plastic surgery
• James J. O'Callaghan, MD, Hospital pediatric medicine
• Kyle J. Oh, MD, physical medicine and rehabilitation
• Pamela J. Paley, MD, Gynecology
• Sanjiv Parikh, MD, Vascular / Interventional Radiology
• Kim R. Pittenger, MD, family medicine
• Francis X. Riedo, MD, infectious diseases
• Derek M . Rodrigues, MD, Cardiology
• Jeffrey S. Roh, MD, orthopedic surgery
• Connie J. Smith, MD, Geriatrics
• Michael A. Towbin, MD, general surgery
• Dan S. Veljovich, MD, Gynecology
• Mark R. Vossler, MD, Cardiology
• Martin P. Walker, MD, Fetal -maternelle Medicine

The analysis of clinical trials revealed an urgent need to increase the development of Alzheimer drugs

The analysis of clinical trials revealed an urgent need to increase the development of Alzheimer drugs -

The analysis of clinical trials shows pipeline therapeutics is low; 99.6 percent of attempts fail drug

Researchers at the Lou Ruvo Cleveland Clinic Center for Brain Health conducted the first analysis of clinical trials for Alzheimer's disease (AD), revealing an urgent need to increase the number of agents within the drug development pipeline AD and move successfully into new treatment therapy. The document, "Disease Drug Development Pipeline Alzheimer: Few candidates, frequent failures", was published today in the journal Alzheimer's Research & Therapy

An overview all clinical trials shows .:

• There are relatively few drugs in development for Alzheimer's disease.
• the failure rate for developing AD drugs was 99.6 percent for the decade 02-2012.
• the number of drugs has decreased since 09.

"Our goal was examine historical trends to help understand why the treatment of the disease of Alzheimer's development efforts fail so often, "said Jeffrey L. Cummings, MD, D.Sc., Director of the Centre Lou Ruvo Cleveland Clinic for brain health. "with approximately 44 million people worldwide with the condition, the study shows that the drug development ecosystem disease of Alzheimer's disease need more support given the magnitude of the problem. "

By using the advanced search mechanisms ClinicalTrials.gov, a government website which records all clinical trials, Dr. Cummings and Kate Zhong, MD, senior director of research and development clinical and Touro University medical student Travis Morstorf built a comprehensive analysis to examine all tests since 02.

"by analyzing both completed and ongoing trials and is currently active compounds, we been able to provide an overview of longitudinal trends in drug development, "said Dr. Zhong. "We found that investment in AD therapies and drugs is relatively low compared to the challenge posed by the disease. The pipeline is almost dry."

This comprehensive analysis illustrates the high failure rate of compounds and the need for a constant supply of new drugs or a higher emphasis on reorientation, which can be evaluated for efficacy in AD. With AD more to the US economy as cardiovascular disease or cancer, Lou Ruvo Center for Brain Health Research team believes the AD drug system must be supported, cultivated and coordinated to improve the rate and successful development of new therapies.

to accelerate the drug development process and reduce the need to constantly invent new drugs, researchers note the need for other repositioning studies, which involve the study of a approved drug in a new or used condition. For example, researchers at the Cleveland Clinic Centre Lou Ruvo Brain Health for conducting a Phase IIa clinical trial of a benchmark to determine whether bexarotene (Targretin-), a currently FDA-approved drug to treat the cancer skin, can remove an accumulation of proteins in the brains of Alzheimer's patients, as he did in a recent animal study.

Researchers develop a new "nanojuice" to help doctors better identify human gut

Researchers develop a new "nanojuice" to help doctors better identify human gut -

Located deep in the human intestine, small intestine is not easy examine. X-rays, MRI and ultrasound images provide instant but each suffers from limitations. Help is on the way.

University at Buffalo researchers are developing a new imaging technique involving nanoparticles suspended in a liquid to form "nanojuice" that patients drank. After reaching the small intestine, doctors would hit the nanoparticles with a harmless laser light, providing an unprecedented view real-time, non-invasive to the body.

Described July 6 in the journal Nature Nanotechnology, advancement could help doctors better identify, understand and treat gastrointestinal disorders.

"Conventional imaging methods show the body and blocks, but this method allows you to see how the small intestine works in real time," said corresponding author Jonathan Lovell, Ph.D. , UB assistant professor of biomedical engineering. "Improved imaging will improve our understanding of these diseases and enable more efficient care doctors for people suffering from them."

The average of the human small intestine is about 23 feet long and 1 inch thick. Sandwiched between the stomach and the large intestine, where it is a large part of the digestion and absorption of food takes place. It is also where the symptoms of irritable bowel syndrome, celiac disease, Crohn's disease and other gastrointestinal diseases occur.

To evaluate the body, doctors usually require patients to drink a thick, chalky liquid called barium. Doctors then use X-rays, magnetic resonance imaging and ultrasound to assess the organ, but these techniques are limited regarding the safety, accessibility and lack of adequate contrast, respectively.

Furthermore, none are very effective in providing real-time imaging of the movement such as peristalsis, which is the muscle contraction that propels food through the small intestine. Dysfunction of these movements may be related to the previously mentioned diseases, as well as the side effects of thyroid disorders, diabetes and Parkinson's disease.

Lovell and a team of researchers worked with a family of dyes called naphthalcyanines. These small molecules absorb much of the light in the near infrared spectrum, which is the ideal range for biological contrast agents.

They are not suitable for the human body, however, because they do not disperse in the liquid, and they can be absorbed through the intestine into the blood stream.

to solve these problems, researchers have formed nanoparticles called "nanonaps" that contain the colored dye molecules and added the ability to disperse in the liquid and move safely through the intestine.

In laboratory experiments with mice, the researchers administered the nanojuice orally. They then used photoacoustic tomography (PAT), which is the pulse laser lights which generate pressure waves that, when measured, providing real-time and a more nuanced view of the small intestine.

The researchers plan to continue refining the technical trials in humans, and move into other areas of the gastrointestinal tract.

Other authors of the study from the Department of UB Chemical and Biological Engineering, POSTECH Korea, Roswell Park Cancer Institute in Buffalo, the University of Wisconsin-Madison, and McMaster University in Canada. The research was supported by grants from the National Institutes of Health, the Ministry of Defense and the Korean Ministry of Science, ICT and Future Planning.

Scientists discover new compounds that may alter the circadian rhythm

Scientists discover new compounds that may alter the circadian rhythm -

Scientists of Florida campus of The Scripps Research Institute (TSRI) have discovered a surprising new role for compounds- pair who have the potential to alter the circadian rhythm, the complex physiological process that responds to a 24-hour cycle of light and dark and is present in most living beings.

at least one of these compounds could be developed as a chemical probe to discover new therapeutic approaches for a range of disorders, including diabetes and obesity.

study, which was printed before published online by the Journal of Biological Chemistry , focuses on a group of proteins called REV-ERB, a superfamily that plays an important role in the regulation of circadian physiology, metabolism and immune function.

The new study shows that the two compounds, cobalt protoporphyrin IX (COPP) and zinc protoporphyrin IX (ZnPP) bind directly to REV-ERB.

REV-ERB are normally regulated by heme, a molecule that binds to hemoglobin, help to carry oxygen from the bloodstream to the cells and plays a role in cellular energy production. While the active heme REV-ERB, and Copp ZnPP inhibit.

"These compounds are as heme, but when you exchange them their functions are different metal centers," said Doug Kojetin, TSRI associate professor who led the study. "This makes us think that the key is the chemistry of the metal ion itself. The modification of the chemistry of this metal center can be a convenient way to target REV-ERB for diabetes and obesity. "

Kojetin and colleagues recently demonstrated that synthetic agonists REV-ERB, as new compounds, reduce body weight in mice that were obese because of the diet.

the first authors of the study, "Structure of REV-ERB_ domain binding ligand bound to a porphyrin Antagonist," is Edna Camacho Matta-McGill University, Montreal and Subhashis Banerjee of the University of Texas Southwestern . Medical Center other authors of the study include Travis S. Hughes and Laura A. Solt of IRST and Yongjun Wang and Thomas P. Burris University School of Medicine St. Louis

work. was supported by the National Institutes of Health (grants DK080201 and DK101871), the biomedical research Program Esther King James and the Florida Department of Health (grant 1KN-09) and the State of Florida.

work can be found here.

About the Scripps research Institute

the Scripps research Institute (TSRI) is one of the most important, independent nonprofit world focusing on research in the biomedical sciences. TSRI is internationally recognized for his contributions to science and health, including its role in the foundation of new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 3,000 people at its campus in La Jolla, CA, and Jupiter, FL, where his famous scientists, y including three Nobel prize work toward their next discoveries. The graduate program of the institute, which doctorate degrees in biology and chemistry prices, ranks among the top ten of its kind in the country. For more information, see www.scripps.edu.

Study on cancer care model provides for a possible decline in expenditure on processing

Study on cancer care model provides for a possible decline in expenditure on processing -

The study, however, has raised questions because while it reduces the costs of a third party and showed no decrease in patient health, spending on chemotherapy drugs increased

the Wall Street Journal :. study on cancer care gives mixed results
a closely watched study to remove the financial incentive for doctors to prescribe expensive drugs cancer delivered contradictory results, with expenditures of lower overall treatment, but rising costs of chemotherapy drugs. The results of the study, which focused on UnitedHealth Group Inc. insurance arm and five oncology practices, raise questions about the most effective way to cut rapidly growing tab for the treatment of cancer. The US spent more on drugs against cancer last year -; $ 37 billion, up 19% in five years-than any other category, according to the Institute IMS Healthcare Informatics, a unit of IMS Health. The overall costs for cancer treatment are well over $ 100 billion per year and installation, according to researchers at the National Cancer Institute (Wilde Mathews, 7/8)

Reuters :. New Plan Doctor of payment of the costs of cancer care Cut, UnitedHealth Says
experience changing the way physicians US cancer are offset cost cutting health care by a third party, without noticeable decrease in health of patients, according to a three-year study by insurer UnitedHealth Group Inc and five medical oncology groups. Cancer treatment is one of the most expensive and most dynamic categories in the US care. Oncologists and insurers have been designing new incentives for physicians to improve patient care while reducing costs. In the last experiment, UnitedHealth, the largest health insurer in the United States, doctors gave participants an upfront payment to cover full course of treatment of a patient, rather than pay them for each individual medical service such as chemotherapy. The results of the study, which lasted from 09 to 2012, were published online Tuesday in the Journal of Oncology Practice (Humer, 7/8).

In addition, the New York Times examines increasing costs of generic drugs

The New York Times :. rapid price increases for certain generic drugs users Catch By Surprise
in recent years, generic drugs slowed the rise in drug prices, but Americans billions of dollars of health care systems. After the patents for Lipitor, the cholesterol drug, and Ambien, a sleeping pill, expired in recent years, for example, generic drugs have entered the market and prices fell. But increasingly, experts say, the cost of certain generic drugs going in the other direction. The prices paid by pharmacies for generic versions of some Fiorinal with codeine (for migraines) and Synthroid (a drug thyroid) and the generic steroid prednisolone have all more than doubled since last year, EvaluatePharma found. In January, the National Association of Community Pharmacists called for a congressional hearing on generic drug prices, complaining that those of many essential medicines has increased as much as "0, 1000 percent or more" in the past years. The price jumps particularly affected the smaller pharmacies that do not have the influence of big chains negotiate discounts (Rosenthal, 7/8).

This article was reprinted from kaiserhealthnews. org with permission from the Henry J. Kaiser Family Foundation. Kaiser Health News, an editorially independent news service, is a program of the Kaiser Family Foundation, a professional health policy research non-partisan organization affiliated with Kaiser Permanente.

New way to a disabling disease: block access of iron bacteria in the body

New way to a disabling disease: block access of iron bacteria in the body -

In an era of growing concern about the prevalence of resistant disease antibiotics, Case Western Reserve researchers. identified a new promising way to a disabling disease: block access of iron bacteria in the body

scientists have shown how bacterial siderophore, a small molecule, iron uptake from two abundant sources supply fan bacterial growth - as well as how the body initiates a chemical counterassault against this infection process. Their findings appear in a recent edition of The Journal of Experimental Medicine .

"bacterial siderophore will be an important therapeutic target for one day because it can be modified to prevent bacteria to acquire iron, but at the same time, it is possible to maintain access to host iron, "said lead author Laxminarayana Devireddy, DVM, PhD, Assistant Professor of pathology, Case Comprehensive Cancer Center.

investigators knew from the start that bacterial siderophore uptake of iron from the host mammal and transformed so that bacteria can absorb and metabolize the mineral. In this survey, Devireddy and his colleagues discovered that human mitochondria, which resemble very closely the bacteria have their own iron-acquisition mechanisms - mitochondrial siderophore. Mammalian mitochondria are membrane subunits enclosed in the cells which produce most of the energy of the cell, and as their bacterial counterparts, mammalian mitochondria have their own siderophore mechanism research, and provides catches iron for use.

A test tube level, the investigators found that the bacteria can feed on iron provided by bacterial siderophore and siderophore mitochondrial. From this overabundance of iron, bacteria proliferate and do very sick mammalian host with an infection.

"It is like the bacteria can use their own capture mechanisms or iron. It does not matter, host" Devireddy said. "They are very good to use siderophores both sources of bacterial siderophores and mammals. This means that the bacteria get more iron."

Researchers at Case Western Reserve also showed that the absence of mitochondrial siderophore in a mammal can improve its ability to resist infection. When investigators exposed mice deficient mitochondrial siderophore to systemic infection E. coli , the animals resisted infection. The reason? E. coli bacteria had less access iron from siderophores mitochondrial deficient mice.

Furthermore, mammals are not totally defenseless of a bacterial siderophore raid on supplies of mitochondrial iron. In another phase of their investigation, the scientists found that normal mice secrete 24p3 ​​lipocalin protein isolates and removes bacterial siderophore synthesis of siderophores mammals.

"The lipocalin action significantly reduces mouse mortality of E. coli infection, and some actually recovered mouse" Devireddy said. "This kind of delay in bacterial growth gave the time of the immune system to identify and neutralize the microbe."

These results highlight the potential for developing effective therapies to reverse a bacterial infection.

"Any approach to eliminate bacterial siderophore either activate or mitochondrial and lipocalin-2 infection would likely slow, allowing the immune system of the host to respond," Devireddy said. "These new approaches could also provide a much needed alternative to treat these infections that have become resistant antibiotics."

Researchers examine why antioxidant actually do more harm than good

Researchers examine why antioxidant actually do more harm than good -

For decades, people health conscious worldwide took antioxidant supplements and consumed foods rich in antioxidants, thinking it was one way to good health and long life.

However, clinical trials of antioxidant supplements have repeatedly dashed hopes that consumers take in hoping to reduce their cancer risk. Virtually all of these trials have failed to show a protective effect against cancer. In fact, in several trials antioxidant supplementation has been linked to increased rates of certain cancers. In one trial, smokers taking extra beta carotene were more, not lower, lung cancer rates.

In a brief article in today The New England Journal of Medicine David Tuveson, MD Ph.D., Cold Spring Harbor Laboratory professor and director of research for the Foundation Lustgarten, and Navdeep S. Chandel, Ph.D., of the Feinberg school of medicine Northwestern University, suggest why antioxidant supplements might not be trying to reduce the development of cancer, and why they can do more harm than good.

Their views are based on recent advances in the understanding of the system in our cells that establishes a natural balance between oxidant and antioxidant compounds. These compounds are involved in so-called redox (reduction and oxidation) reactions essential for cell chemistry.

oxidants such as hydrogen peroxide are essential in small quantities and are made intracellularly. There is no doubt that oxidants are toxic in large quantities, and the cells naturally produce their own antioxidants to neutralize them. It seemed logical to many, therefore, to increase the intake of antioxidants to counter the effects of hydrogen peroxide and other "reactive oxygen species," or ROS similar toxic, as they are called by the scientists. Especially since we know that cancer cells produce higher levels of ROS to help feed their abnormal growth.

Drs. Tuveson and Chandel suggested that taking antioxidant pills or eating large amounts of foods rich in antioxidants can not show a beneficial effect against cancer because they act on the critical site in the cells where ROS are produced tumor-promoting - in cellular energy factories called mitochondria. On the contrary, supplements and dietary antioxidants tend to accumulate remote sites scattered in the cell, "leaving the tumor promoting ROS relatively unfazed," the researchers say

The amounts of both ROS and natural antioxidants are more elevated in cancer cells. - paradoxically the higher levels of antioxidants as a natural defense by cancer cells to maintain their higher levels of oxidants in check, so growth can continue Indeed, such Tuveson and. Chandel, treatments that increase the levels of antioxidants into cells may be beneficial, while those that act as antioxidants may also stimulate cancer cells. Interestingly, the radiotherapy kills cancer cells by significantly increasing the levels of . oxidants the same is true of chemotherapeutic drugs. - They kill tumor cells by oxidation

Paradoxically, the authors suggest that "genetic or pharmacological inhibition of antioxidant proteins" - a concept tested successfully in rodent models of lung and pancreatic cancers - may be a useful therapeutic approach in humans. The main challenge, they say, is to identify proteins and antioxidant pathways in cells that are used only by cancer cells and not by healthy cells. Obstruction production of antioxidants in healthy cells will upset the delicate balance on which redox normal cellular function depends.

The authors propose further research on antioxidants track profile in the tumor and the adjacent normal cells, to identify possible therapeutic targets.

Physical fitness may buffer some adverse health effects of too much sitting

Physical fitness may buffer some adverse health effects of too much sitting -

The physical form may buffer some adverse health effects of too great meeting, according to a new study by researchers from the American Cancer Society, the Cooper Institute, and the University of Texas. The study appears in the journal Mayo Clinic Proceeding s, and found the association between prolonged sedentary time and obesity and blood markers associated with cardiovascular disease is much less pronounced when taking fitness into account.

sedentary lifestyle has been linked to an increase risk of obesity, metabolic syndrome, type 2 diabetes, cardiovascular disease, certain cancers, and premature death. But previous studies of the association are not taken into account the protective impact fitness, a strong predictor of cardiovascular disease incidence and mortality.

For the current study, researchers led by Kerem Shuval, Ph.D., of the American Cancer Society, examined the association sedentary behavior, physical activity and the ability to obesity and metabolic biomarkers among 1304 men seen at the Cooper clinic in Dallas, Texas between 1981 and 2012. sedentary time was composed of the time watching television and self-reported time spent in a self-report on a car 1982. Fitness survey was determined by a treadmill test during the medical examination at the clinic visits.

The study showed that the more sedentary time was significantly associated with higher levels of systolic blood pressure and total cholesterol and triglycerides and lower levels of HDL, the "good" cholesterol . It has also been associated with BMI, waist circumference and body fat percentage. But when the researchers controlled for fitness, they found prolonged sedentary time was not associated significantly with cholesterol triglycerides / HDL higher (an insulin resistance indicator). Sedentary time was not associated with the metabolic syndrome (a cluster of risk factors). In comparison, the highest fitness levels were associated with decreased adiposity and metabolic measures.

The authors say that the interpretation of the results of their study should be tempered by its limitations. For example, sedentary behavior was based on self-evaluation at some point in time, while fitness was assessed objectively during clinic visits.

"[A] hile our results suggest the need to encourage the achievement of higher levels of fitness through adhering to physical activity guidelines to reduce metabolic risk," they conclude, "the effects of reducing sedentary time on cardiometabolic risk biomarkers justify the additional longitudinal exploration using objective measurement."

A new study reveals how genetic defect can make people more likely to develop melanoma

A new study reveals how genetic defect can make people more likely to develop melanoma -

A new study by University of Kentucky researchers shows how a genetic defect in a specific hormonal pathway may make people more likely to develop melanoma, the most deadly type of skin cancer.

people with fair skin who tend to burn (instead tan) from sun exposure have a much higher risk of melanoma than people with dark skin. On the surface, it appears that the amount of melanin, the natural substance in the skin which determines pigment and acts as a skin "natural sunscreen" would be the sole determinant of the risk of melanoma. However, the truth is more complicated.

Published in Molecular Cell , the study focused on the role of melanocortin1 receptor (MC1R), the receptor on melanocytes in the skin which is called in following exposure to ultraviolet action help skin lay over UV melanin to protect itself. people with fair skin are more likely to inherit a defect of this receptor, and therefore, can not make enough melanin to protect itself completely against UV damage.

Since UV from the sun or tanning beds is a major cause of melanoma, inherited problems in the MC1R means that the skin lacks natural protection by melanin, which acts as an organic sunscreen. This leads to more UV light is chronically via the sensitive layers of the epidermis, where it can contribute to cancer.

However, the British study showed that MC1R defects contribute to the development of melanoma means other than the production of melanin. In addition to regulating the amount of melanin that gets made in the skin, MC1R also control how melanocytes can repair their DNA against UV damage. Have defects in the MC1R signaling delays the body's ability to clear the DNA damage in existing skin -. Leading to an increased potential for cancer mutations

"Whether people have a specific genetic predisposition for melanoma could potentially save many lives," says Dr. John Orazio, Associate Professor and Research Chair Drury pediatric Markey Cancer Center at UK. "If you happen to be born with a problem in this hormonally MC1R, then you must be very careful with regard to UV safety."

a good indication of the state of MC1R of a person is what happens to the skin after sun exposure.

"If you tan well, then your MC1R probably good," said Orazio . "If you tend to burn, then you have inherited a problem with your MC1R, and you should probably avoid UV exposure as targeted use of tanning beds or sun exposure without protection."

D'Orazio and his research team found an important molecular link between MC1R signaling and DNA repair in their study. The team hopes to use this information to develop new melanoma preventive treatments, such additives that may be included in sunblocks to ramp up the skin's ability to handle UV damage.

incidence of melanoma has increased steadily over the past few decades - in the 1930s, about one in 1,500 Americans have developed the disease. Today, chances are about one in every 60. Having a problem with the way MC1R increases the lifetime risk of a person of melanoma about four times.

And chemoprevention of colon cancer: an interview with Dr. John Letterio, School of Medicine of Case Western Reserve University

And chemoprevention of colon cancer: an interview with Dr. John Letterio, School of Medicine of Case Western Reserve University -

Interview by April Cashin -Garbutt , BA Hons (Cantab)

Dr. John Letterio THOUGHT LEADERS SERIES ... overview of the world's foremost experts

How is defined chemoprevention?

The basic idea of ​​cancer chemoprevention is to stop or reverse the progression of premalignant cells to full malignancy, using physiological mechanisms that do not kill healthy cells.

approach involves using either pharmacological or natural agents that inhibit the development of invasive cancer, either by blocking the DNA damage that initiates the carcinogenesis or by stopping or reversing the progression of precancerous cells in where such damage has already occurred.

ideal chemoprevention agent will be safe, orally bioavailable and well tolerated, so that it can be acceptable for routine use as an approach to reduce the risk of cancer an individual .

The term "chemoprevention" was invented back nearly four decades. How much progress has been made since then?

Michael Sporn coined the term in an article chemoprevention 1976 Federation Proceedings when writing about the work of his group was done with vitamin A analogues

Dr. Sporn, then a member of Carcinogenesis Program at the National cancer Institute, led the first work with agents that might be used to prevent cancer.

Since then, there has been tremendous progress in the field of preclinical research where many studies by leading researchers in the field have demonstrated the utility of this approach in animals experimental.

Indeed, in these preclinical models, it is now possible to prevent the onset of cancer in almost all public bodies in which human carcinoma occurs. However, this success has not been limited to human disease models as chemoprevention has been validated in people.

For example, the use of selective estrogen receptor modulators (SERMs), granted as much as a five fold reduction in breast cancer incidence in estrogen receptor-positive women

These compounds -. including tamoxifen, raloxifene and lasofoxifene - have the advantage of eliminating osteoporosis. Fenretinide, for which we have data value of nearly 20 years, provides a significant prevention of breast cancer in premenopausal women.

Yet despite these successes, the general acceptance of chemoprevention still an obstacle that must be overcome and it is. real concern that the concept is not only misunderstood by the general public, but not yet fully embraced by the cancer community

Could you please brief introduction to the class of molecules you worked - synthetic triterpenoids?

triterpenoids are a class of biologically active plant metabolites biosynthesized six isoprene units and cyclized in a variety of skeletal scaffolds.

The acid natural triterpenoid oleanolic has been shown to be an effective platform for synthetic derivatization to generate chemoprevention agents that target the antioxidant and factor erythroid 2-factor (NF-E2) concerning nuclear PI 2 (Nrf2) transcriptional cytoprotective path between other pathways involved in inflammation and cancer.

Indeed, the synthetic triterpenoid used in our recently published in JCI study was derived from oleanolic acid. This natural triterpene is representative of a broad class of molecules ubiquitously present in the plant kingdom, with many widely used in Asian medicine and continually isolated and studied for anti-inflammatory, hepatoprotective, analgesic, antimicrobial, immunomodulatory and effects tonics.

Because many plants containing triterpenoids are readily eaten by wild animals and humans, it could be expected that the content of the plant are relatively nontoxic and could serve as platforms as safe for drug discovery.

In preclinical studies, these triterpenoids have also been shown to be neuroprotective. Our own data showed the ability of synthetic triterpenoids selected to completely reverse the clinical signs of neurodegeneration in mouse models of multiple sclerosis. (Http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242013/?tool=pubmed)

It was announced recently that these molecules carry enormous potential to remove colon cancer associated colitis. Why do patients with inflammatory bowel disease have a higher risk of colon cancer?

It is well established that people with Crohn's disease and ulcerative colitis (the most common forms of IBD) are at a higher risk of developing colorectal cancer (CRC) that the population General. Actually, IBD with colon involvement is among the first three conditions at high risk for CRC, which represents nearly 15% of deaths in patients with IBD.

The link between inflammation and cancer is well established and inflammation undoubtedly contributes to other forms of sporadic and hereditary forms of colon cancer.

A number of very elegant studies in preclinical models have shed enormous light on the mechanisms involved. The picture that emerges is that there are distinct roles for specific immune cells, cytokines and other soluble mediators in the initiation, promotion, progression and metastasis of colon cancer.

A proposed mechanism is that the chronic inflammation of the intestine leads to colorectal dysplasia and the optionally colorectal cancer. Chronic inflammation is characterized by the production of proinflammatory cytokines that can induce mutations in oncogenes and tumor suppressor genes (eg., p53, APC ) and genomic instability through various mechanisms.

Chronic inflammation can act favoring CAC activating proliferation and anti-apoptotic (pro-survival) properties precancerous cells, and also enhance their potential for tumor progression and metastasis by influencing the microenvironment in which they grow.

This effect, in part, is related to the ability of inflammatory cytokines as mediators to activate STAT3 and NFkB, which are important in many inflammatory pathways, but also closely involved in the regulation of tumorigenesis.

The critical point is that all these mediators can be modulated in strategies to halt the progression of the disease. CRC is highly treatable at an early stage, it is important not only to understand the risk, but also recognize the signs and symptoms -. And why regular screenings and early detection are essential

However, the potential that we can further reduce the risk through the application of chemopreventive strategies that target these inflammatory mediators is very real and must be exploited to the clinical benefit.

How are synthetic triterpenoids thought to help protect against colon cancer?

When examining the mechanisms of activity for this class of small molecules it is very important to know and understand their nature "multi-functional", ie, their ability to influence several targets within a cell. Indeed, it is this property that may underlie their unique potential as chemopreventive

For example, triterpenoids directly inhibit the function of both STAT3 and NF? B, key intermediates in colon tumorigenesis process .

Dr. Sporn began synthesis triterpenoids in 1995, shortly after leaving the NCI for Dartmouth. Since then, Dr. Sporn was a collaborator on more than 100 publications have described the mediation mechanisms of several synthetic triterpenoids activities and have demonstrated their effectiveness in cancer chemoprevention in numerous preclinical models of epithelial cancers.

When I entered Case Western Reserve University in 06, I began to interact with Dr. Markowitz, who described 15-PGDH as a suppressor large tumor in colon cancer and as a related molecule to "celecoxib nature."

We were intrigued by the finding that inflammatory cytokines, such as TNF-α, could suppress the expression of 15-PGDH and wondered if the triterpenoids may reverse this suppression.

it proved to be true, showing potentially important mechanisms by which this class of small molecules can suppress colon cancer associated colitis, and may improve the response to COX-2 inhibitors.

What are the next steps in your research?

Our current studies focus on the analysis of this triterpenoid (CDDO-Me / bardoxolone methyl) in other models of IBD and in additional models of colon cancer, and the new data these studies are corroborating the results reported in JCI.

We are also very interested in the potential that natural triterpenoids with similar properties could provide a similar benefit. Our efforts in this regard involves both the isolation of the natural product and similar characterization in vitro analyzes and through in vivo Studies of cancer chemoprevention.

As our data with these mature Triterpenes natural, we expect these collective observations will pave the way for human trials in which cancer chemoprevention by triterpenoids may be achieved in patients who are at risk significantly high.

This may be particularly beneficial in patients with IBD, multiple mechanisms of triterpenoid activity (eg suppression of NFkB and STAT3 signaling, induction of TGF signaling -β, activation of antioxidant Nrf2 response), all can work together to achieve improvements in most clinical IBD.

are there plans to continue human trials in cancer chemoprevention with triterpenoids?

The synthetic triterpenoids, including CDDO-Me (bardoxolone methyl) and an analog bound (RTA 408) are currently being studied in clinical development in a wide range of indications by our collaborator Reata Pharmaceuticals.

Notably, Reata is assessing the immuno-oncology RTA 408 applications in the first clinical trials in melanoma and cancer non-small cell lung, and we expect that positive clinical data histologies interest will be expanded in the future.

In addition to this program, we also have an active effort focused on isolating and unique derivatization, natural triterpenoids.

this initiative involves university-industry collaboration has recently established between Case Western Reserve University (CWRU) and Modularix, by which individual candidate molecules and developed CWRU are selected for their potential as immune modulators and their ability to suppress cancer metastasis.

what do you think the future chemoprevention of colon cancer?

The argument for the continuation of these cancer chemoprevention trials is strong, and has been elegantly defended by Dr. Sporn for many decades.

we could say that we have an obligation to patients suffering from diseases such as IBD and other conditions that increase the risk of cancer :. the obligation to develop these safe and multi-functional agents as an approach to minimize their risk of many diseases of clinical manifestations, including cancer

There are many questions that remain unanswered:

• triterpenoid what will be the safest and most effective in this context
• may benefit clinically be achieved with intermittent exposure, rather? by continuous administration? This will likely be one approach to reduce the risk of complications.
• these triterpenoids may be used in combination with other agents for clinical benefit more?

clinical trials designed with care and a collaborative approach between industry and academia are needed to answer these questions, but there is no doubt that the data led us to where we really have an obligation to do so.

where readers find more information?

• http://www.nature.com/nature/journal/v471/n7339_supp/full/471S10a.html
• http://www.nature.com / nrclinonc / newspaper / v2 / n10 / full / ncponc0319.html
• http://www.ncbi.nlm.nih.gov/pubmed/20420949

About Dr. John Letterio

John Letterio is the director of the Institute of cancer Angie Fowler Adolescent & Young adult hematology and head / pediatric oncology in University hospitals Case Medical Center and Case Western Reserve University in Cleveland, Ohio. Dr. Letterio obtained his Ohio University's medical school State University of Medicine in 1984 completed a pediatric oncology fellowship at the National Cancer Institute in Bethesda, Maryland in 1993. NIH, Dr. Letterio became a permanent researcher and head of the Laboratory of Immune.

After 16 years at NIH, he was recruited at the Case Western Reserve University in 06 to lead the development of programs for children, adolescents and young adults with cancer to blood disorders. As a member of the case Comprehensive Cancer Center and president Jane & Lee Pediatric Cancer Innovation, he leads a core team of scientists and clinical investigators whose efforts are focused on the development and application of new agents for the chemoprevention and cancer treatment.

His research is actively supported by several NIH institutes, including the NCI, NHLBI and NIS, and the Ministry of Defence. His research team has provided important information about the mechanisms linking inflammation to cancer and other diseases. Her most recent studies have demonstrated the potential of synthetic triterpenoids in chemoprevention of colon cancer and appear in the Journal of Clinical Investigation in June 2014.

Somatuline Clarinet Phase III study Ipsen published online in NEJM

Somatuline Clarinet Phase III study Ipsen published online in NEJM -

The US subsidiary of Ipsen (Euronext: IPN, ADR: IPSEY) announced aujourd 'hui the New England Journal of Medicine published the results of clinical trials showing that Somatuline ^® Autogel ^® / Somatuline ^® Depot ^® (lanreotide) injection 0 mg (referred Somatuline ^® ) achieved a statistically significant prolongation of progression free survival (PFS) compared to placebo in patients with metastatic neuroendocrine gastroenteropancreatic tumors (GEP-NETs ). Clarinet ^® , an experimental phase III randomized, double-blind, placebo-controlled anti-proliferative effects of Somatuline ^® was conducted in 48 centers in 14 countries. The article "lanreotide in metastatic neuroendocrine tumors Enteropancreatic" is available online at NEJM.org and was published in July 17 edition (N Engl J Med 2014; 371: 224-233 ..)

data collected from 204 GEP-NET patients on the 96-week study showed that patients treated with placebo had a median PFS of 18.0 months and 33.0% has not progressed or died at 96 weeks, while the median PFS for Somatuline ^® of patients was not reached and 65.1% had not progressed or died at 96 weeks (stratified log-rank test, p <0.001 .) This represents a 53% reduction in risk of disease progression or death based on a hazard ratio of 0.47 (95% CI 0.30 to 0.73) These statistically effects. and clinically significant antiproliferative Somatuline ^® were observed in a broad population of patients with grade G1 or G2 (classification of the World Health Organization) GEP-NETs, ​​and independent of tumor volume liver (≤25% or> 25%). Quality of life measures were not different between Somatuline ^{® groups} and placebo. The safety data generated by the study are consistent with the known safety profile of Somatuline ^® .

"The Clarinet ^® The data are convincing because no progression similar GEP-NET there are survival data without a somatostatin analogue in a large population studied multinational" said Dr Martyn Caplin, Professor of gastroenterology and gastrointestinal neuroendocrinology, Royal free Hospital (London, UK) and lead author and principal investigator of the Clarinet ^® study.

"published peer-CLARINET ^® results in the New England Journal of Medicine highlights the robust data that showed an anti-proliferative effect of Somatuline ^® in the treatment of GEP-NETs, ​​"said Claude Bertrand, Executive Vice President R & D and Chief scientific Officer." based on these significant results, Ipsen has launched a registration program in the world and the July 1, 2014, the presentation of a supplementary New Drug Application for Somatuline ^® for the treatment of neuroendocrine tumors gastroenteropancreatic (GEP-NET) to the FDA and the variations marketing authorization in 25 countries EU were announced. "

" These are potentially interesting news for physicians GEP-NET, data have shown anti-tumor activity and a delay in disease progression in patients treated with Somatuline ^® Depot ^® , "said Dr. Alexandria Phan, Clarinet researcher, IM Director medical oncology at Houston Methodist Cancer Center.

the data Clarinet ^® is considered experimental, as Somatuline ^® are not indicated for the anti-proliferative treatment of neuroendocrine gastroenteropancreatic tumors (GEP-NET) in a market. Somatuline ^® is approved for treatment symptoms associated with neuroendocrine tumors, which may include the treatment of GEP-NET patients with symptoms of carcinoid syndrome in many markets where it is marketed as Somatuline ^® Autogel ^® . Somatuline ^® is not approved in the US to treat GEP-NETs or symptoms thereof, where it is marketed as Somatuline ^® Depot ^® of acromegaly.

common genetic variation in the gene may modify cardiovascular benefit of aspirin

common genetic variation in the gene may modify cardiovascular benefit of aspirin -

Aspirin is the gold standard antiplatelet therapy for aspirin and low daily dose is widely prescribed for the prevention of cardiovascular disease.

Now, a new study suggests that common genetic variation in the gene for catechol-O-methyltransferase (COMT) can modify the cardiovascular benefit of aspirin, and in some people, can impart a slight evil . The results, led by investigators at Beth Israel Deaconess Medical Center (BIDMC) and Brigham and Women's Hospital (BWH) appear online in the journal American Heart Association Arteriosclerosis, Thrombosis, and Vascular Biology .

"This is one of the rare cases where you can identify a single gene polymorphism has a significant interaction with aspirin as it affects whether or not it protects against heart disease" says first author Kathryn hall, PhD, MPH, an investigator in the general medicine division and primary care at BIDMC and researcher at Harvard medical School.

COMT is a key enzyme in the metabolism of catecholamines , a group of hormones that include adrenaline, noradrenaline and dopamine. "These hormones are involved in a wide range of disorders, including hypertension," says Hall, "first, we were interested in whether the COMT gene affected the vulnerability to cardiovascular incident such as myocardial infarction or ischemic stroke. "Knowing that aspirin is commonly prescribed for the prevention of cardiovascular diseases of the incident, investigators also wanted whether genetic variation in COMT influence potential benefit of aspirin.

To answer these questions, the researchers used data from genomics women's health study, a cohort of more than 23,000 women who were followed for 10 years in a randomized controlled trial against placebo double-blind, the low-dose aspirin or vitamin E in the primary prevention of cardiovascular disease in the incident. Their analysis included val158met, a common variant in the COMT gene: People who are homozygous for valine highly active form of the enzyme, the "val / vals," have been shown to have lower levels of catecholamines compared to persons who are homozygous for methionine the low activity form of the enzyme, the "met / metastasis." the val / met are heterozygous between.

"When we looked at women in the placebo arm of the test, we found that 23 percent of women who were "val / vals' were naturally protected against cardiovascular disease incident," says lead author Daniel I. Chasman, PhD, genetic epidemiologist in the Division preventive medicine at Brigham and Women's Hospital and associate professor of medicine at Harvard medical School. "This discovery has been replicated in two other studies based on the population, was in itself a significant interest." But, he adds, the investigation also revealed the surprising discovery that when women with the Val / Val polymorphism were allocated to aspirin, this natural protection has been eliminated.

"As we continued to examine the effects of the drug benefit, we found that val / val women who were randomly assigned to aspirin had more cardiovascular events than val / vals that were assigned to placebo, "said Chasman. Of the 28 percent of women who met / met, the opposite was true, and women had fewer cardiovascular events when assigned to aspirin compared with placebo. The benefit of aspirin compared with placebo allowance encountered / Metastases raised to the reduction of cases of incident cardiovascular disease in 91 women treated over 10 years of follow-up studies. However, the harm of aspirin compared with placebo allowance for the val / val women was an increase of one case per 91 treaties.

The researchers also found that rates of cardiovascular disease were also reduced in met / met women assigned to vitamin E compared with those assigned to placebo.

the authors point out that the results will require further research and replication to understand their potential clinical impact. However, they note that, since aspirin is preventive prescribed to millions of people and the COMT gene variant is extremely common, this study highlights the potential importance of individualizing therapy based on genetic profiles.

"What this study suggests is that we can be smarter about groups of patients who would likely benefit from aspirin," says study co-author Joseph Loscalzo, MD, PhD, chair of the Department of medicine and chief physician at BWH. "Rather than give aspirin to all patients with risk factors for heart disease, we need to use genomics and modern genetics to identify persons for whom aspirin has the greatest benefit and the least risk of side effects. "

One possible reason for the val / val protection could lie in the role of COMT in the allocation of adrenaline, the hormone "fight or flight", which is closely related to the regulation of the cardiovascular system.

"When adrenaline levels increase in response to stress, blood pressure rises and blood pressure is a precursor of heart disease, "says hall. "One possibility is that individuals val val / less epinephrine that meets / met individuals because of their COMT is more efficient at decomposing This could help protect the course against cardiovascular disease. - Who is our working hypothesis It is more difficult to explain why. effect is modified by aspirin and that is what we are in the laboratory aggressively try to understand. "

Researchers discover new genetic links to schizophrenia

Researchers discover new genetic links to schizophrenia -

The discovery of more than a hundred genetic risk factors for schizophrenia provides new clues in the vital understanding of what causes the condition and will kick off the search for new treatments, according to scientists from the United Kingdom.

In the largest molecular genetic study of schizophrenia ever undertaken, genetics psychiatric Consortium (PGC), led by Professor Michael O'Donovan of the MRC Centre of Cardiff University for Neuropsychiatric Genetics and Genomics combined all schizophrenia samples available in a new analysis, only systematic.

study is the result of several years of work by the psychiatric Schizophrenia Working Group Genomics Consortium, an international, multi-institutional collaboration of over 300 scientists in 35 countries worldwide.

"We were able to detect genetic risk factors on a massive scale and unprecedented and shed new light on the biological basis of the state", according to Professor O Donovan who led 'study.

a total examination of 80,000 samples from patients with schizophrenia and healthy volunteers worldwide study, published in Nature , has found 108 specific locations in the human genome linked to schizophrenia, 83 were entirely new.

The new findings also suggest new biological mechanisms and pathways. For example, as the authors had expected, the study involves genes expressed in brain tissue, but it also found genes associated with schizophrenia have been particularly active in the immune system.

"These remarkable results have been made possible through collaboration comprehensive approach," according to Professor Sir Michael Owen, Director of the MRC Centre of Cardiff University for Neuropsychiatric Genetics and Genomics.

"Detecting biological risk factors at this level shows that schizophrenia can be treated with the same approaches that have transformed the results for people with other diseases.

" We believe that now they can also do for schizophrenia which has hitherto been so misunderstood, "he added.

schizophrenia is a debilitating psychiatric disorder that affects more than 24M people the world.

the disorder is highly variable, but is characterized by a combination of hallucinations, delusions such as paranoia, mood swings, apathy and social withdrawal, among others, often emerges in teens and early 20s

His lifelong impact on individuals and society is high, both in terms of healthy life years lost to disability and in terms financial cost.

Many respond well to treatment, but for many who do not meet the options are limited largely because biological mechanisms underlying schizophrenia are not included.

The Professor O'Donovan now hope the wealth of new discoveries will help initiate the search for new treatments he added: "While we are very excited by the results, it is important not to exaggerate or misinterpret. "We are still in the early days of trying to understand what causes the disease but collaborations such as this and new genetic tools mean that we are in a unique position.

" Make full use this research to the treatment will be a long game medium, but since some of our findings emphasize already known targets for existing treatments, it is reasonable to expect that others could do the same within a time shorter time.

"The wealth of new discoveries provides a large number of launch pads for the understanding of the disease and will revive the stalled process of developing new treatments for patients and their families who are still today stigmatized and blamed for the condition.

"The main challenge now is to translate this new knowledge about the biological basis of schizophrenia, new diagnostic tools and new treatments for patients and finally put an end to 60 years of waiting for new treatments for people around the world. "

Zilico receives funding to develop the diagnostic device for oral cancer

Zilico receives funding to develop the diagnostic device for oral cancer -

Zilico Ltd began its development work on a medical device that uses electrical impedance spectroscopy (EIS) in the detection and diagnosis of cancer oral Technology Strategy Board funding, the innovation agency of the United Kingdom.

both prices are Feasibility of Biomedical Catalyst funding and smart. The funds will help support a thorough analysis of the UK market, providing a specification for an oral diagnostic device and a protocol for a multi-center trial.

The funding builds on proven concept-study that was recently introduced and is part of a wider development program leading to a multi-center trial. The awards will help support development projects worth £ 0k.

flagship Zilico ZedScan EIS uses its proprietary technology to detect dysplasia and cervical cancer. Oral cancer following neoplastic way similar to the cervix, DIE can be used to detect changes in oral epithelium cells progress from normal to precancerous and then cancerous.

The University of Sheffield Professor of Oral Medicine, Martin Thornhill, presented on the use of EIA in the detection and diagnosis of oral cancer and dysplasia at the most influential group of experts oral medicine in America last year.

presentation of Professor Thornhill, using impedance spectroscopy to detect potentially malignant oral lesions, was delivered at the 67th Annual Meeting of the American Academy of Oral Medicine (AAOM) in San Antonio, Texas . The study on 50 patients was the result of a collaboration between the University of Sheffield, Sheffield Teaching Hospitals NHS Foundation Trust and Zilico Ltd.

The summary of the presentation was published in the oral surgery, oral pathology, oral medicine and oral Radiology Journal in September 2013. The full paper describing the study has been accepted for publication in the Journal Nanomedicine

Zilico chief Sameer Kothari said :.

We are delighted to have secured this funding which will allow us to build on the proof of concept study and positive feedback received data to the AAOM last year.

we are now well positioned to further develop the device and evaluate in a multi-center clinical study. There is a clear clinical need for accurate diagnosis in the patient's course.

Researchers working to develop new drugs for the treatment of chronic inflammatory diseases

Researchers working to develop new drugs for the treatment of chronic inflammatory diseases -

Science and industry work together to develop pharmaceuticals for the coming treatment of chronic inflammatory diseases. The drugs will fight against the immunological processes that have gone awry.

Statistics show that there are 300 million people with asthma worldwide, 0 million more people living with chronic pneumonia and up to 30% of the world population by supporting rhinitis allergic (allergic inflammation of the nasal airways). chronic inflammatory diseases may also affect other organs and parts of the body beyond the respiratory system; they can occur in the intestine (in the form of inflammatory bowel diseases such as ulcerative colitis), joints (rheumatoid arthritis), skin (scleroderma), or heart and blood vessels (arteriosclerosis). What each form of inflammatory disease has in common is that it comes from inflammation centers in the body that are prevented from healing by immunological processes that have gone awry.

This is where a new product manufactured by the Canadian company Nuvo Research Inc. comes in. It is already approved for use in many countries worldwide as a medicine to help the local healing, and Thailand is already punishable as a means to treat a variety of chronic diseases. Scientists at the Fraunhofer Institute for Cell Therapy and Immunology IZI in Leipzig to work now with a German subsidiary of the company Nuvo Research GmbH, and the Translational Centre for Regenerative Medicine at TRM Leipzig University to develop a platform that will enable them to better understand how the substance works. Their goal is to optimize the drug to make it easier to administer and better tolerated. Above all, scientists are eager to develop drug compounds with which it might be possible to mitigate an even wider range of chronic diseases, and prepare the products for approval in the European and Canadian markets. The cooperation project sponsored to the tune of 4.4 million euros, should be completed in June 2014.

regeneration process disrupted in the case of chronic inflammation

"L inflammation is the body's response emergency, but inflammation usually begins to decline when it starts. for the body to calm down and stabilize the immune system is temporarily suppressed. suppresses the body defense mechanisms until the inflamed tissue was able to resume its normal functions. this regeneration process is disrupted in the case of chronic inflammation, "says Professor Jürgen Arnhold, who is based in the Faculty of medicine from the University of Leipzig and also conducts research at TRM. Various complications may occur, such as infections and bacterial or fungal disturbances in the healing process. If such complications develop beyond a certain threshold, the immune system will suddenly jump back into the very violent action. It is this interaction between immunosuppression and immune overreaction that scientists are looking into the project. There is clearly a class of enzymes at work that would normally be activated by immune cells in a very specific time. If this activation occurs in an uncontrolled manner, the last phase of the inflammatory process is interrupted and becomes chronic. This is especially when the little low molecular weight substance, developed by Nuvo in: "The studies we have conducted on isolated immune cells indicate that it should be possible to alter the function of certain enzymes involved," said Professor Arnhold.

When scientists TRM studying how immune cells respond to selected drug in Canada, IZI's researchers are interested in examining its effect on the body as a whole. The result of these investigations is that, for the drug to be approved in Europe and North America, the authorities require complex and time-consuming studies to be conducted in its safety, tolerability and efficacy. "We are testing the drug on mice that have the same kinds of symptoms that patients with chronic inflammatory diseases," says Dr. Franziska Lange, responsible for inflammation and Immunodiagnostics unit models IZI. " my work group focuses on three conditions: .. asthma, lung and scleroderma smoker, a disease of autoimmune connective tissue We have 20 different model systems with which we are able to simulate different aspects of Crohn This allows us to record the effects and side effects of different doses of the drug on mice. We see ourselves as a service unit and offer many ways to perform preclinical testing of potential drugs, "she goes on to explain. Three other IZI working groups are testing the drug on mice that have suffered a stroke or who colitis to see if the symptoms of the animals better. They are also investigating whether the drug could be useful in breast cancer treatment.

the three cooperation partners have already conducted two studies and both proved the efficacy and safety of the basic active ingredient. currently, they hope to develop another project to improve drug application method. in Thailand it is currently administered by infusion, which means that patients have to travel to the clinic five days later for several hours at a time. the trio worked on the preparation of the drug in such a way that it can also be injected by family physicians.

Scientists report first successful step towards a vaccine that targets the mutation in brain cancer

Scientists report first successful step towards a vaccine that targets the mutation in brain cancer -

astrocytomas and oligodendrogliomas are subtypes of brain cancer called "Glioma ". These incurable brain tumors arise from glial cells, a type of support cell in the central nervous system. "Low-grade gliomas," that grow relatively slowly, so diffuse spread throughout the brain and are very difficult to remove completely by surgery. In many cases, the effectiveness of treatment by chemotherapy and radiotherapy is very limited. gliomas can develop extremely aggressive glioblastoma

low-grade gliomas have a common feature :. Over 70% of the cases have the same gene mutation in tumor cells. the same "typo" in the DNA causes the exchange of one specific building block protein (amino acid) in an enzyme called isocitrate dehydrogenase 1 (IDH1) therefore, most cancer cells do not follow the original construction plan for the protein;. to the 132nd position in the sequence of the molecule, they insert amino acid histidine instead of arginine

"This frequent and highly specific mutation immediately aroused our attention to immunologists :. In cancer cells, the amino acid exchange Ready properties of new protein that can be recognized by the immune cells of the body itself, "says Prof. Dr. Michael Platten, who heads the Clinical Unit of cooperation "Neuroimmunology and Brain Tumor Immunology" at DKFZ; he also works as a senior consultant in neuro-oncology department at Heidelberg University Hospital.

No other tumor type appears the same mutation with such frequency. The mutant protein can surely be detected using a highly specific antibody developed by Prof. Dr. Andreas von Deimling, neuropathologist at the University Hospital and the DKFZ. This form of IDH1 is present on the surface of all tumor cells and it is quite specific to the tumor. "This suggests that we might be able to use a vaccine to alert the patient's immune system to IDH1 mutant, the fight against the tumor without damaging healthy cells," explained Platten.

In collaboration with a team of doctors and University Hospital of scientists from Heidelberg, DKFZ and the Universities of Mainz, T-Tübingen and Hamburg Platten and his colleagues have now made the first successful step towards a vaccine that specifically target the mutation in the tumor.

researchers built a synthetic version of IDH1 segment with the characteristic mutation using individual amino acids. This version of the peptide, which has 15 building blocks, exactly in correspondence of presenting molecules on the surface of tumor cells. This is essential because the immune cells respond only to a target that is presented in so-called "MHC molecules" on the cell surface. If there is no such statement of correspondence, the body is a response immune.

to draw conclusions about the human immune system from vaccination experiments, the researchers used mice whose cells were equipped with human MHC molecules. "After the vaccination of animals the peptide, we could detect immune cells and antibodies that specifically recognized the IDH1 altered tumor cells rather than normal form of the enzyme in healthy cells, "says Dr. Theresa Schumacher, first author of the study.

in laboratory animals, this specific immune response induced by vaccination stopped the growth of cancer cells which had the mutation IDH1 feature. As expected, the vaccination did not disrupt the operation of the normal IDH1 enzyme, which plays a role in energy metabolism of all the healthy cells in the body.

"In some patients with low-grade glioma, we also found Spontaneous immune responses against IDH1 changed," says Platten. "This is a good sign, it suggests that the peptide-based vaccines can indeed support the immune system of the body in the fight against cancer cells." This gives a "vaccine therapy" a good chance of success, according to the Heidelberg doctors. In a clinical trial is expected to begin next year, with the support of the German Consortium for Translational Cancer Research (DKTK), they plan to consider the safety of the vaccine against gliomas based on IDH1 mutant in human patients for the first time.

"most low-grade gliomas can not be completely removed by surgery and therefore often return , "said Professor Wolfgang Wick, medical Director of neuro-oncology department and head of the clinical cooperation Unit" neuro-oncology "at DKFZ. "Patients should benefit greatly from a vaccine that prevents this from happening."