Wednesday, September 4, 2013

Doctor Shares Simple steps for women to keep the young breasts

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Doctor Shares Simple steps for women to keep the young breasts -

Aging affects the breasts as the rest of the body. Skin stretches over time and the breasts begin to sag, while sun exposure causes age spots and wrinkles of the neckline. Women often spend time and effort the fight against facial aging, but often neglect to take care of their breasts properly, resulting in premature aging of the breast, says Dr. Price.

"The breast skin needs daily care as the face done," says Dr. Price. "It is also vitally important to wear a well-fitting bra to support the breasts, particularly during exercise."

Dr. Price action women can take simple steps to keep their breasts look as young as possible:

  1. Get a professional bra fitting Support bra fits properly can help keep the juvenile form. breasts. If a woman maintains a stable weight, it should have a professional fitting at least once a year to ensure that her breasts are properly supported; more frequent connections are recommended if a woman has undergone significant weight loss or gain, been pregnant, or had breast cosmetic procedure like breast augmentation or a breast lift.
  2. wear a good sports bra. When caring for breasts, it is particularly important to have adequate support during exercise, particularly high impact activities such as running. The breasts are made of soft tissues connected to the chest wall by ligaments, and over time these ligaments can stretch, causing sagging. Physical activity is important for overall health - and exercise is thought to help lower the risk of breast cancer -. but wear a bra during exercise is crucial for maintaining a youthful profile within
  3. Moisturize and protect the breasts and cleavage. As women learn to use a moisturizer and sunscreen on their faces to keep them looking young and healthy, they must follow the same practices for breasts and cleavage. Creams and lotions designed for use at night generally have the right balance of ingredients to help protect the delicate skin in this area. Women should also regularly apply sunscreen to exposed areas of the chest to protect against sun damage.
  4. Practice good posture. Poor posture can exacerbate drooping breasts while sitting right some advantages: it creates a more youthful profile and makes the breasts appear larger than if a woman was slumped. Incorporate exercises to strengthen the chest, shoulders and back into an exercise routine can be easier to maintain good posture throughout the day.
  5. Maintain a stable weight. Weight gain causes the skin of the breasts to stretch, and it may or may not reduce to its original size after weight loss. Yo-yo should be avoided to maintain the breasts in their optimal state.

Although the aging process is inevitable, following these 5 tips can help maintain the elevation of the breasts and keep skin healthy breasts.

When considering a breast enhancement procedure
If the breasts show unwanted effects of aging, loss or weight gain or pregnancy, there are a variety cosmetic procedures can improve their appearance. sagging breasts can be lifted and reshaped with a lift or breast reduction, and breast augmentation can help restore fullness to the breasts that have lost volume.

Dr. Price recommends that a woman interested in making such improvements consult an experienced plastic surgeon in cosmetic breast procedures that may suggest aesthetic enhancement options.

Tuesday, September 3, 2013

HCV reactivation can not worsen survival outcomes for lymphoma patients with HIV

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HCV reactivation can not worsen survival outcomes for lymphoma patients with HIV -

More than a quarter of HIV patients are also infected with the virus hepatitis C (HCV), which can complicate treatment and care decisions after a diagnosis of cancer. Details of these complications has been well documented in the past. The results of a new Fox Chase Cancer Center study of this patient population can begin to fill this gap

Fox Chase hematologist and medical oncologist Stefan K. Barta, MD, MS, MRCP -., Who led study - analyzed the HIV patient data + lymphoma diagnosis, collected over 17 years, to better understand how HCV infection influences survival results. Mr. Barta collaborators will present the group's findings at the 50th annual meeting of the American Society of Clinical Oncology.

Reactivation of HCV, in which the virus is detectable symptoms but not necessarily the origin, is common in HIV + patients. Notably, Dr. Barta and his team found that reactivation of hepatitis C does not seem worse survival outcomes for patients with lymphoma who also had HIV.

"Many patients do experience some reactivation of hepatitis C, but in most patients it seems to be self-limited and does not affect the results for the treatment of cancer" said Dr. Barta.

he noted that the treatment of patients co-infected with HIV lymphoma and HCV requires caution and care. HIV more than triple the risk of liver failure in people also infected with HCV, according to the Centers for Disease Control and Prevention. And among cancer patients, HIV patients infected with HCV can fall into a feedback loop that can decrease the effectiveness of treatment.

"patients undergoing chemotherapy may experience reactivation of herpes virus C, which in turn can lead to liver failure," said Dr. Barta. "This means that we have to reduce the dose of chemotherapy, which could adversely affect the results."

In addition, HIV patients often take a variety of other drugs, including antiretroviral drugs, which makes them particularly vulnerable to side effects such as toxicity. However, Dr. Barta said the new study suggests that the potential risks should not deter oncologists to treat these patients with chemotherapy.

"People should not be afraid to treat patients with HIV and HCV aggressive," said Dr. Barta. "At the same time, we must be careful to monitor these patients because reactivation occur and could potentially lead to severe liver failure."

He and his colleagues analyzed the medical records of 10 HIV patients who had been diagnosed with lymphoma at the Albert Einstein Cancer Center in the Bronx, New York, from 1997 to 2013. Patients with primary lymphoma central nervous system have been excluded. The researchers found that 53 patients, or 28 percent of eligible patients were also infected with HCV. The virus reactivated in 17 of these patients, about one third of the population of patients infected with HCV during treatment.

Patients infected with HCV were overall survival 59.7 months compared to 88.6 months for patients or HCV or hepatitis B (HBV). However, this survival advantage disappeared when the researchers adjusted for variables including age, sex, race, CD4 count, the presence of cirrhosis, type of lymphoma, and levels of lactate dehydrogenase (LDH , an enzyme). Multivariate analysis showed that co-infection with HCV was not associated with a lower overall survival in patients with lymphoma. At the same time, researchers have seen the overall survival results worse associated with low CD4 counts (below 100 cells / cubic millimeter), a diagnosis of non-Hodgkin lymphoma, the disease in an advanced stage, the levels LDH more than 10, or cirrhosis.

Dr. Barta said he hopes the new study opens clinical cancer trials to a little studied patient population. HIV patients with HCV are often excluded from clinical trials of cancer because of concerns about liver failure and drug toxicity, resulting from the interaction of retroviral drugs with chemotherapy. Barta said he hopes the new results suggest that these patients can tolerate chemotherapy without side effects, will help to reverse this trend.

"This is very important for a large proportion of patients," he said. "We want to assure researchers that these patients, as long as they have adequate liver function should also be enrolled in trials clinical. "

The co-authors Dr. Barta include Ashwin Sridharan, Santiago Aparo, Susanna A. Curtis and Justin D. Kaner.

Patients with advanced colorectal cancer respond well to the new combined therapy

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Patients with advanced colorectal cancer respond well to the new combined therapy -

In an aggressive disease known for low response rate, researchers from the University of Texas MD Anderson cancer Center found patients with advanced colorectal cancer responded well to a combination of vemurafenib therapy drugs, cetuximab and irinotecan.

The Phase I trial presented Saturday, May 31 in a discussion poster at the American Society 2014 Annual Clinical Oncology meeting in Chicago, examines a specific mutation in the BRAF gene, which is present in 5 to 10 percent of patients with colorectal cancer.

previous research identified this mutation as a target for therapy, but response rates with single agent vemurafenib were poor, leading researchers to learn more about the combination with different drugs.

"Patients with BRAF mutation in colorectal cancer are known to have aggressive disease that generally do not respond to standard chemotherapy," said David Hong, MD, associate professor, Investigational Cancer Therapeutics and principal. "So when BRAF inhibitors initially started there was excitement which could become the new standard of care, but we found they did not work very well."

in the study, the researchers combined increasing doses of vemurafenib (V) and cetuximab (C) and irinotecan (I), two drugs already used to treat metastatic. Twelve patients colorectal cancer were enrolled in both dose levels including seven at the dose of one (V-480 mg, 250 mg and C-I-180 mg) and five at the two dose with vemurafenib increased to 720 mg.

radiographic images were evaluated every four cycles in a cycle of 14 days of treatment. Patients were evaluated for adverse events with the most common, including rashes, diarrhea and nausea.

The results show better responses

Of the nine evaluable patients, partial responses or stable disease was seen in eight patients with colorectal cancer having undergone restaging examinations following the start of treatment. The rate for colorectal eight patients response was 50 percent, while response rates with single agent vemurafenib is less than 10 percent.

"What is promising is that we see these high response rates in early studies suggesting this could become a new standard of care in line," said Hong. "There is clearly a kind of synergistic activity with the combination."

US A randomized cooperative trial phase II of this association in colorectal cancer BRAF mutated begin later this summer led by Scott Kopetz, MD, Ph.D., In Gastrointestinal Medical Oncology is the lead author of the phase I.

"Although early, the exciting aspect is that we see significant response rates, but questions remain as to the duration of these responses and mechanisms resistance are "Kopetz said. "By expanding our initial findings and move to cooperative group network, we will be able to quickly conduct studies that could lead to get this approved combination."

Nonadherence triple risk of relapse in African-American and Asian children with ALL in remission

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Nonadherence triple risk of relapse in African-American and Asian children with ALL in remission -

nonadherence triple risk of relapse, more common in African American and Asian children

an estimated 25 percent of children in remission from acute lymphoblastic leukemia (ALL) are missing too many doses of essential maintenance medication that minimizes the risk of relapse according to a study published online today in Blood , the Journal of the American Society of Hematology. The study also indicates that maintenance medication adherence was lower among African-American and Asian children in remission from ALL than in non-Hispanic white children, with 46 percent of African Americans and 28 percent of Asians not taking enough to prevent relapse, compared with 14 percent of non-Hispanic whites.

acute lymphocytic leukemia (ALL), a cancer of white blood cells, is the most common form of cancer in children. While more than 95 percent of children with ALL enter remission within a month of receiving the initial treatment of cancer, one in five people will relapse. In order to remain cancer free, children in remission from ALL must take oral form of chemotherapy every day for two years (known as 6-mercaptopurine or 6MP) that protects the body against the re-emergence of the disease.

Despite the proven benefits of 6MP, previous studies have suggested that children with ALL have difficulty taking the drug regularly. Other studies have reported that pediatric ALL survival rates vary widely between racial groups. These two ideas have prompted researchers to begin studying specific models to race in 6MP adherence in children with ALL.

"Although we do not yet know why the children of different races have significantly different survival rates for all we know they joined their maintenance drugs is a key factor in their survival," said lead study author Smita Bhatia, MD, MPH, of City of Hope in Duarte, Calif. "in this spirit, we sought to investigate potential links that may exist between several specific key sociodemographic race of these children and their adherence to 6MP. "

Dr. Bhatia and a team of investigators began their research to study the differences 6MP adhesion between the different racial groups of children in remission of ALL in 2012, reports that Hispanic children were not following maintenance regime as prescribed 6MP consistent than non-Hispanic whites. to examine 6MP membership African-American, Asian and non-Hispanic white children in remission of all, the research team enrolled 298 patients 77 institutions in a study that followed 6MP drug levels in the bloodstream, the answers of a questionnaire administered to their families and, perhaps more importantly, an electronic method for tracking maintenance. Each patient included in the study, which was prescribed 6MP, came with a pill bottle fitted with a microprocessor chip in the cap that recorded each date and time of the bottle has been opened for a period six months.

for the three groups, African-American children took their 6MP least often, with 46 percent of them taking 0 percent or less of their medication, nonadherence during threshold which the relapse risk became statistically significant. While Asian children in the study group took their medication more consistently, 28 percent of them did not take at least 0 percent of their drugs. non-Hispanic white children were more adherent to their maintenance treatment regimen than any other group; However, 14 percent still did not 6MP enough to meet the criterion of researchers to adherence. Taken together, about 25 percent of children enrolled in the study did not take their 6MP at least 0 percent of the time, tripling their risk of relapse.

To better understand the socio-demographic factors that have influenced the drug nonadherence in children, the researchers asked their families to complete questionnaires to provide more information on race, income, the structure of the family, and the level of parental education. Responses to the questionnaire revealed that African American kids came largely from low income family households with lower education level parent (less than college training / professional degree). Conversely, Asian children in general have come to high-income nuclear families with educated parents (college diploma / vocational or postgraduate degree). Despite representing two demographic extremes, neither group adhered to their medication consistently as non-Hispanic white children, who reported a moderate income, relatively nuclear family structure, and the average parental education compared to other groups, in part because the specific demographics race played an important role in respect of 6MP.

researchers observed that 6MP adherence rates were significantly higher in Asian children and African-American who came from households where their mother acted as their full-time caregiver and supervisor drugs . Furthermore, according to the research data, African American children whose mothers had relatively low levels of education, as well as children living in a single parent, multiple-children households were less adherent to their medications. The researchers also noted that Asian children were more vulnerable to medication nonadherence if they were from low-income households and non-Hispanic whites did not take their medications as always if their fathers had a low level of education.

Regardless of race, families have reported that the most common reason for children not taking their medications 6MP was forgotten.

"Our data show that one in four children in remission from ALL do not take the drugs needed to stay cancer free, and overwhelmingly, the main reason why they forget to take their pills every day, "said Dr. Bhatia. "These results are the basis for other studies that examine how physicians can intervene successfully using technology, for example, that children do not know an increased risk of relapse because they take their chemotherapy oral. "

UIC is conducting clinical trials to evaluate the three-drug combination therapy for advanced pancreatic cancer

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UIC is conducting clinical trials to evaluate the three-drug combination therapy for advanced pancreatic cancer -

Researchers at the University of Illinois at Chicago are leading a clinical trial to evaluate a new, three -drug combination therapy for advanced pancreatic cancer.

ductal carcinoma of the pancreas has a five year survival rate of less than 5 percent and is the fourth leading cause of cancer death in the United States, claiming nearly 40,000 lives each year.

scientists pace have made progress in the last decade to understand the biology of the disease at the cellular level, but progress in the clinical results are not kept.

"There is an urgent and unmet need for effective treatments for patients with advanced pancreatic cancer after first-line chemotherapy fails," said Dr. Neeta Venepalli, UIC assistant professor hematology and principal investigator of the study.

patients in the Phase 1 study will give three drugs that are considered to attack the cancer cells in different ways. First, gemcitabine is a chemotherapy drug approved by the FDA that works by slowing or stopping the growth of tumors. It has been the standard treatment for advanced pancreatic cancer for the past decade.

A second medicament, a monoclonal antibody which recognizes a protein called mucin 1 which prevents the death of cancer cells and is superabundant in ductal carcinoma of the pancreas, is administered to patients to stimulate an immune response. The antibody also attracts the third drug, PGG, which moves to the site of the tumor to activate an immune response and kill the targeted cancer cells

"Our Phase 1 trial combining gemcitabine with two new immunotherapies cancer -. A regime that has not been tried before, "said Venepalli, member of the IU Cancer Center.

" We are optimistic and pleased to provide a new approach for the treatment of this devastating disease. "

The study will evaluate the combination of drugs to determine the highest dose of the monoclonal antibody which can be tolerated without unacceptable side effects.

monoclonal antibody and PGG are experimental drugs and will be provided by Biothera, a US biotechnology company.

The sequencing of the tumor offers new perspectives for the management of lung cancer

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The sequencing of the tumor offers new perspectives for the management of lung cancer -

sequencing of tumors in several different lung cancer and surrounding tissue complicates the dominant theory linear progression of lung cancer and offers new perspectives for the management of this deadly cancer, according to a new study from the Mayo Clinic. The sequencing results allow, for the first time, molecular solid evidence of the progress of phenotypic indolent components to more aggressive disease and also show that the two components can move independently, even if they originate from the same precursor, according the study. The paper appears online in Cancer Research .

"This study highlights the potential changes in our understanding of the molecular pathogenesis and better treatment of adenocarcinoma of the lung," said George Vasmatzis, Ph. D., lead author of the study and co -Director of the Biomarker Discovery program at the Mayo Clinic Center for individualized Medicine. "The heterogeneity of lung cancer we repeatedly said that the natural history of tumors and routes of progression vary by case, and several models are possible in certain cancers."

Lung cancer accounts for nearly 0,000 deaths each year in the United States, more than the three most common cancers combined, according to the American Lung Association. The treatment of cancers at an early stage can be adapted to the type of genomic alterations observed explains Dr. Vasmatzis. In some cases, this could mean less: aggressive treatment and observation periods nearby, while other situations may require more immediate interventions, such as surgery or radiation.

"As suggested by clinical studies demonstrating improved disease-free and overall survival for the treatment of lesions containing components of adenocarcinoma in situ [noninvasive lung cancer], it is possible that this represents a distinct clinical entity which can be treated less aggressively or by resection sub-lobar or even watchful waiting periods with almost following up imaging before treatment, "says Dr. Vasmatzis.

future lung cancer genome studies and tumor progression are under the Dr Vasmatzis team in Biomarker Discovery program. Their goal is to develop a series of predictive biomarkers that can help patients and doctors separate cancers potentially aggressive lung and threatening those indolent based molecular signatures found in the patient's tissue.

ASTRO publishes new policy model for proton therapy beam

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ASTRO publishes new policy model for proton therapy beam
-

The American Society for Radiation Oncology (ASTRO) has released a new model policy for by proton beam therapy (PBT) that details which cancer diagnoses meet standards based on ASTRO data and should be covered by private insurers and Medicare. Developed by leading radiation oncologists and medical physicists, including the significant contribution of expert representatives in proton therapy, this model policy supports PBT cover for appropriate patients and identifies areas where coverage with the development of evidence and further research is needed.

PBT is neither a new nor an experimental technology for treating cancer with radiation. It uses proton particle radiation to deliver radiotherapy highly conformal to a specific target area of ​​the tumor while giving a much lower dose in normal tissue in the path of the input and output proton beam. reduced radiation dose to healthy tissue PBT is attractive because it can reduce side effects for patients, potentially increasing their quality of life. To date, the scientific evidence exists confirming that PBT is particularly useful in a number of pediatric cancers, especially those in the brain, as well as certain adult cancers such as ocular melanoma. Further research on other sites of disease cancer, such as breast, prostate and lung, is underway with the NCI clinical trials currently supported from patients in three sites of disease in the centers therapy treatment over 14 protons across the country. PBT has attracted much attention because of its relative cost, which may be considerably more than traditional therapy to external beam radiotherapy because of the heavy load of the construction and maintenance of proton therapy centers.

"proton therapy beam (PBT) is demonstrating promise in our ongoing efforts to improve survival and cure rates for cancer patients while reducing side effects," said Colleen AF Lawton, MD, Fastro, president of the board of ASTRO. "as leading experts in radiation oncology, it is important for ASTRO to provide guidelines based on evidence-balanced payers which ensures access to PBT for . cancer patients while being wise stewards of our nation and the financial resources of our patients "

This model policy recommends two cover groups for PBT: 1) patients with specific diagnoses for which PBT been proven to be effective; and 2) patients with a diagnosis of cancer where the evidence of the effectiveness of PBT is still emerging, and thus cover the development of evidence is recommended for patients s they are enrolled in clinical trials or multi-institutional registry to collect data and to inform a consensus on the role of proton therapy. This model policy is consistent with the previous reporting ASTRO on the use of PBT for prostate cancer, as well as ASTRO Choose wisely published last September list. In addition, ASTRO urges private insurers and Medicare to cover PBT for cancer patients with difficult to treat, rare or very complex for which the PBT characteristics offers advantages over other forms of treatment .

ASTRO Model Policies are developed to communicate this ASTRO believes are correct coverage policies for radiation oncology. The model ASTRO policies do not serve as clinical guidelines and are subject to review and periodic review. The ASTRO model policy may be reproduced and distributed without modification for non-commercial purposes. ASTRO has already issued political models on the cover for brachytherapy, intensity modulated radiation therapy (IMRT), stereotactic radiotherapy body (SBRT) and stereotactic radiosurgery (SRS) and are available online at www.astro.org/ModelPolicies .

Rice, MD Anderson researchers refine the technique to attack hard to reach tumors

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Rice, MD Anderson researchers refine the technique to attack hard to reach tumors -

Short, custom carbon nanotubes have the potential to provide drugs to pancreatic cancer cells and destroy them from within, according to researchers at Rice University and the University of Texas MD Anderson cancer Center.

nanotubes Pristine products through a new process in moss can be modified to carry drugs to tumors through gaps in the walls of blood vessels that larger particles can not not get through

nanotubes can then target and infiltrate the nuclei of cancer cells, where drugs can be released by sonication - .. that is, shaking

directed research rice chemist Andrew Barron has been reported in the Royal Society of Chemistry Journal of Materials Chemistry B .

cancer patients most of the pancreas die within a year of diagnosis and have a five year survival rate of 6 percent, partly because there is no method for early detection, according to the American Cancer Society. The tumors are often inoperable and pancreatic cancer cells are also difficult to reach with chemotherapy, said co-author Jason Fleming, professor of surgical oncology at MD Anderson.

"These results are encouraging because they offer a potential delivery solution for patients with cancer of the pancreas with tumors resistant to standard chemotherapy," said Fleming. "There are molecular and biological barriers the effective delivery of chemotherapy for tumors of pancreatic cancer, and these nanotubes may be able to do some of those irrelevant. "

the rice scientists made sufficiently pure nanotubes to change profit and small enough to slip through the defenses of the body, Barron said the researchers knew of previous work that the nanotubes could be modified. - a process called functionalization. - When carrying chemotherapy agents and release at a controlled rate by sonication

"This time, we tried to work on the length of the tubes should be and the extent of functionalization maximize absorption by the cells," said Barron.

Several discoveries were the key, he said. First, the rice graduate student, former student and co-author Alvin Orbaek purified iron catalysts of carbon nanotubes need to grow by rinsing with chlorine. "Iron particles Leftover damage the tubes by oxidation," Barron said. "This makes it difficult for future use."

The next step was to cut the nanotubes to size. Very long nanotubes are floppy and difficult to treat, Barron said. Enrico Andreoli, a postdoctoral research associate in the group and the Barron lead author of the paper, used a thermal process to chop an average length of 50 nanometers. (A human hair is about 100,000 nanometers wide.)

"Instead of experiencing a nanotube powder fluffy, we get something that looks like a hockey puck," said Barron. "It's very dense - it looks like a sponge washer - .. But you can cut it with a razor blade can weigh and make accurate chemistry with her"

Laboratory Barron added polyethyleneimine (PEI) to the nanotube

surfaces. in laboratory tests, the tubes were modified easily dispersed in a liquid and able to pass through the barriers in living cancer cells to infiltrate the nuclei. a small molecule variant of PEI turned out to be less toxic to cells than larger versions, Barron said.

"This research shows that the particles are small enough to penetrate inside cells where you want them and they may have increased benefit kill - but it is still unknown, "said Fleming

Fleming, whose work focuses on improving the administration of medication for pancreatic cancer, has warned that more research is needed .. "the next step will be to test this approach in mice that have allografts taken from human tumors," he said. "The architecture of these tumors look more like that of human pancreatic cancer."

Scientists are developing a new molecule to monitor the drug concentration

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Scientists are developing a new molecule to monitor the drug concentration -

Monitoring of drug levels in patients is essential for effective treatment, particularly in cases of cancer, heart disease, epilepsy and immunosuppression after organ transplants. However, current methods are expensive, time consuming and require dedicated staff and the patient's distance infrastructure. Publishing in Nature Chemical Biology , scientists from EPFL introduce new light emitting sensor proteins that can quickly and easily show how the drug is in the blood of a patient by changing the color their light. The method is so simple that it could be used by the patients themselves.

Effective treatment drugs based on the balance between efficacy and toxicity of the drug, which is at the heart of personalized medicine. But as every patient is different from another, which requires constant monitoring to customize the best dose of the drug and prevent side effects or even poisoning. medical methods based on current monitoring techniques that require specialized and expensive devices personnel, and must be performed in diagnostic laboratories far from the patient's point of care. Development, rapid inexpensive methods could improve drug treatment at the bedside or in the patient's home, especially in areas with poor medical infrastructure.

A new molecule to the concentration of drug monitoring

[1945002l'équipe] Kai Johnsson at EPFL has developed a new molecule biosensor that can rapidly and accurately measure the concentration of drug in a patient's system without requiring anything more complicated than a regular digital camera. The molecule is the result of engineering innovative proteins and organic chemistry, and has been shown to work over a range of current drugs for cancer, epilepsy and immunosuppression.

The probe molecule functions by binding the drug circulating in the bloodstream of the patient and changes color accordingly. The molecule itself is comprised of four components. A component is a receptor protein which can bind to target molecules of the drug. The second component is a small molecule similar to the target molecule, which can bind to the drug receptor. The third component is a light producing enzyme called luciferase, and the fourth is a fluorophore molecule which can modify the color of the light of luciferase when it comes close to it.

When there is no drug around the receiver and the like drug molecule to bind together. This brings the fluorophore close to the luciferase enzyme, and the system produces a red light. But in the presence of a medicament, for example in the blood of a patient, the drug molecules bind to the receptor more efficiently and therefore "push" the analogous drug molecule outside. The entire probe molecule system opens, taking the fluorophore away from the luciferase. As a result, light emitted gradually changes from red to blue in proportion to the concentration of the drug.

The physician or patient can record the signal easily by placing a drop of sample, such as blood on a piece of paper, placing in a dark box and photograph with a camera classic. The photograph can then be analyzed by a color measurement software to generate an average measure. By comparing this measurement to a standard drug concentration curve, it is easy to calculate the concentration of drug in a sample or the blood stream of a patient. The detection molecule can be used with virtually any type of medicament, because it is necessary simply to change the receptor protein at one end and the like drug molecule to the other.

successfully tested against the anti-cancer and other drugs

EPFL researchers have called their new class of biosensors "based Indicators drugs luciferase "or LUCIDs. to test their versatility, they developed LUCIDs against six drugs commercially available, including three immunosuppressants, anti-seizure, anti-arrhythmic, and an anti-cancer drug. drugs have been tested with success in vitro, and anti-cancer antibody has also been tested with real samples human blood plasma. the signal every six LUCIDs has been shown to be accurate and very stable, with a duration of more than 10 minutes.

"This system is a cheap, effective solution to the drug dosage customization patients across a range of diseases," said Rudolf Griss, one of the authors. the successful implementation he and co-author Alberto Schena encouraged to develop a startup company to streamline and market innovation. "We envision a simple detector, hand held where the patient can take a pinprick of blood and can have an immediate reading of the concentration of free drug in their system - much like diabetics for glucose are now in blood. "

Antiviral treatment can prevent hepatitis B to develop hepatocellular carcinoma

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Antiviral treatment can prevent hepatitis B to develop hepatocellular carcinoma -

The researchers found that antiviral therapy may be able to prevent virus hepatitis B to develop under the most common form of liver cancer, hepatocellular carcinoma (HCC).

This was the conclusion of a study published in the May issue of Clinical Gastroenterology and Hepatology. Henry Ford Health System in Detroit investigators, Geisinger Health System in Danville, Pa., And Kaiser Permanente in Honolulu, Hawaii and Portland, Oregon. participated in the study, as well as researchers from the Centers for Disease Control and Prevention in Atlanta.

According to the first of -its-kind analysis of more than 2,0 adult participants with hepatitis B, those treated with antiviral therapy had a significantly lower occurrence of HCC five-year follow-up period. Overall, 3 percent of patients developed HCC during the study period. But patients who received antiviral therapy were 60 percent less likely to develop HCC than untreated patients.

"The results of this study allow us to reassure our patients that we're not just treating their viral levels, but that antiviral therapy can effectively reduce their risk of developing liver cancer," said the principal investigator of the study, Stuart C. Gordon Henry Ford Health System, MD, who worked closely with Henry Ford chief scientific Mei Lu in Detroit.

HCC is most liver cancers in the United States, usually occurs in people 50 years or more and is more common in men. If cancer can not be removed, it is usually fatal within three to six months. In most cases, HCC is caused by scarring in the liver - cirrhosis -. Which may be the result of alcohol abuse, hepatitis B or C, chronic liver inflammation or iron overload

"This study was the first to approach therapy and antiviral efficacy in the prevention of hepatitis B develop liver cancer, "said Joseph Boscarino, Ph.D., principal investigator and researcher for the site Geisinger. "With this information, clinicians can begin to prescribe an antiviral treatment for patients with hepatitis B in order to prevent a common and dangerous form of cancer."

Monday, September 2, 2013

Mammography has helped reduce the incidence of breast cancer at an advanced stage 37%

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Mammography has helped reduce the incidence of breast cancer at an advanced stage 37% -

Over the last 30 years, since mammography was introduced, breast cancer incidence end of the line decreased by 37 percent, a new study from the University of Michigan Comprehensive cancer Center found.

analysis reflects a trend underlying the increased incidence of breast cancer has since the 1940s, a kind of inflation rate for breast cancer.

researchers examined at an early stage and late stage breast cancer diagnoses between 1977-1979, before mammography became popular, and compared with diagnoses between 07-09. Based on the trends observed during the pre-mammography period from the 1940s to 1970s and the continuing trends over time, the researchers took into account an estimated center increased incidence of breast cancer 1 3 percent per year. This is called an annual percent change or APC

Think of the APC as the inflation rate. $ 1 1977 does not go as far in 07. As the cost of money increases, the number of breast cancer diagnoses increases, regardless of the efforts to detect it earlier.

in this document, published in Cancer, the researchers studied data the late 1970s and projected impact of early and breast cancer at an advanced stage in 07 -09 on the basis of APC. They then compared the projected rates to actual rates.

the incidence of breast cancer late phase decreased by 37 percent compared to the expected rate, and the incidence of early stage breast cancer has increased accordingly by 48 percent in 1977-1979 07-09. They also performed similar analyzes with other APC values ​​ranging from 0.5 percent to 2 percent. All estimates have shown a significant reduction of the disease at an advanced stage.

"When we take into account this time trend, our analysis shows that there has been a change in the advanced stage of breast cancer at an early stage on the last 30 years. This is what you expect an effective screening program. we not only detect cancer more at an early stage, but we are reducing the number of cases in advanced stages that tend to be more difficult to treat and more deadly, "said lead author of the study Mark Helvie, MD, professor of radiology and director of breast imaging at the UM Comprehensive cancer Center.

There are many reasons why the incidence of breast cancer increases over time, including breeding, feeding and environmental factors. previous estimates showed an annual increase of 1 percent to 3 percent in the US and Europe before the start of screening mammography. in countries Africa, Asia and Eastern Europe without routine screening mammogram, breast cancer rates increase as much as 3 percent to 5 percent annually.

Importantly, the study also found that since mammography was introduced, there was an overall decrease of 9 percent in invasive breast cancer, when considering a annual percentage increase of 1.3 percent. This was offset by an increase in ductal carcinoma in situ, called stage 0 breast cancer, which are not invasive.

"While we have seen an increase in the overall incidence of breast cancer over the last 30 years, the decline advanced diagnostics is a positive benefit of mammography and our increased awareness early detection. the reduction of the disease in an advanced stage, and improved treatment, contributes to the decrease in mortality in the United States of cancer in the last 20 years, "said Helvie.

The investigators isolated the protein that is responsible for the fungus' ability to cross the blood-brain barrier

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The investigators isolated the protein that is responsible for the fungus' ability to cross the blood-brain barrier -

In a remarkable series of experiments on a fungus that causes meningitis cryptococcosis , a fatal infection of the membranes covering the spinal cord and brain, UC Davis researchers have isolated a protein that appears to be responsible for the fungus' ability to cross the blood circulation in the brain

discovery - published time:. June 3 in MBIO, open access, peer-reviewed journal of the American Society for Microbiology - has important implications for the development of more effective treatment for Cryptococcus neoformans, the cause status, and other brain infections, and for brain cancers are difficult to treat with conventional drugs.

"This study fills an important gap in our understanding of how C. neoformans crosses the blood-brain barrier and causes meningitis, "said Angie Gelli, associate professor of pharmacology at UC Davis and principal investigator of the study. "We hope that our results will lead to improved treatment of this fungal disease and other central nervous system diseases."

Normally, the brain is protected against bacterial, viral and fungal pathogens in blood by a tightly packed layer of endothelial cells lining the capillaries of the central nervous system - called the blood-brain barrier. Relatively few organizations - and drugs that could fight against brain infections or cancers. - Can violate this barrier

The fungus studied in this research causes meningoencephalitis cryptococcosis, a usually fatal infection of the brain that affects every year about 1 million people worldwide, mostly those who have an immune system weakened. People usually first develop an infection in the lungs after inhalation of fungal spores of C. neoformans in soil or droppings pigeons. The pathogen then spreads to the brain and other organs.

single protein identified

In an effort to discover how C. neoformans exceed the blood-brain barrier, researchers candidate proteins isolated cryptococcosis the cell surface. One was an uncharacterized metalloproteinase they named MPR1. (A protease is an enzyme - a specialized protein - which promotes a chemical reaction ;. A metalloprotease contains a metal ion - in this case, zinc - which is essential for its activity) The M36 class of metalloproteases which belongs MPR1 is unique to fungi and does not occur in mammalian cells.

researchers then artificially generated a strain of C. neoformans which do not have MPR1 on the cell surface. Unlike normal C. neoformans wild type, strain without MPR1 could not cross an artificial model of the human blood-brain barrier

They then took a common baker's yeast strain -. Saccharomyces cerevisiae - that cross the blood-brain barrier and does not normally express MPR1 and modified to express MPR1 on its cell surface. This strain was then acquired the ability to cross the blood-brain barrier model.

mouse investigators then be infected with C. neoformans that lacked MPR1 or the wild type strain by injecting organisms in their blood. Comparing the mouse brain pathology 48 hours later, they found numerous cryptococcal filled cysts around the brain tissue of mice infected with wild-type strain; these lesions were undetectable in people infected with the strain lacking MPR1. In another experiment, after 37 days of infection by the inhalation route, 85 percent of mice exposed to wild C. neoformans had died, while those given the fungus without MPR1 were alive.

"Our studies are the first clear demonstration of a specific role for a fungal protease invade the central nervous system," Gelli said. "The details of exactly how it crosses is an important new field under investigation . "

new targeted therapies possible

According to Gelli, their discovery has important therapeutic potential in two important mechanisms Either MPR1 -. or aspect of the mechanism by which it crosses the blood-barrier brain - could be a target for new drugs for the treatment of meningitis caused by C. neoformans in a person who develops a pulmonary cryptococcosis infection, such treatment would ideally make the fungus less likely to enter the brain and lead to. a rapidly fatal meningitis.

Second, MPR1 could be developed as part of a drug delivery vehicle for brain infections and cancers. Antibiotic drug or fight against cancer which is unable to cross the blood-brain barrier on its own could be attached to a nanoparticle containing MPR1, allowing him to hitch a ride and deliver products to where it is needed .

"the greatest obstacle to the treatment of many cancers of the brain and infections becomes good drugs across the blood-brain barrier," said Gelli. "If we could design an effective distribution system in the brain, the impact would be huge for the treatment of some of these terrible diseases. "

The group of Gelli is currently pursuing such a nanoparticle drug delivery system using MPR1. They also study further the molecular mechanism by which exact MPR1 violates the blood-brain barrier.

Investigators are studying a new cancer immunotherapy to help patients with advanced pancreatic cancer

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Investigators are studying a new cancer immunotherapy to help patients with advanced pancreatic cancer -

medical investigators at Virginia G. Piper Cancer Center at Scottsdale Healthcare study a new immunotherapy cancer to see if it can successfully help patients with advanced pancreatic cancer.

The trial of Phase 2B of CRS-207 and GVAX Pancreas Vaccine is open at Virginia G. Piper Cancer Center at Scottsdale Healthcare Clinical Trials, a partnership with the Translational Genomics Research Institute (TGen), where cancer patients are treated with promising new drugs

participants in the study, called ECLIPSE (effectiveness of the combination Listeria / GVAX immunotherapy in pancreatic cancer Framework) will be randomized so that patients receive . single CRS-207 vaccine, or that the combination vaccine with the vaccine GVAX Pancreas and low dose cyclophosphamide. A third group of patients will receive standard chemotherapy.

"This is a very innovative approach using immunotherapy to treat pancreatic cancer," explained Dr. Erkut Borazanci, MD, MS, medical oncologist and development of drugs Scholar at Virginia G. Piper Cancer Center clinical trials at Scottsdale Healthcare and lead investigator of the study.

CRS-207 vaccine is a weakened form of the bacterium Listeria monocytogenes, which has been genetically modified to be safe for human consumption, while maintaining its ability to stimulate the immune system. Specifically, CRS-207 was designed to stimulate an immune response against the antigen mesothelin associated with a tumor, which is present at high levels on the cells of pancreatic cancer.

The GVAX vaccine is made, pancreatic cancer inactivated genetically modified cells that have been shown to stimulate the anticancer activity of the immune system. The vaccine is administered with a low dose of a drug against the common cancer called cyclophosphamide to enhance the effectiveness of the vaccine.

In a Phase 2A trial recently completed in 93 patients with advanced pancreatic cancer, survival was improved in patients who received the combined treatment of CRS-207, GVAX and cyclophosphamide (6 , 1 month), compared to 3.9 months for those who received only GVAX and cyclophosphamide. Immunotherapies were well tolerated, with no serious side effects associated with undesirable side processing.

Virginia G. Piper Cancer Center Clinical Trials is among the top 11 centers in the United States participating in the study. The drug was developed by Aduro BioTech, Inc., a clinical stage immunotherapy company located in Berkeley, California. A total of 240 patients should be treated at more than 20 clinical trial sites in North America.

"If this study is successful, we hope that this form of immunotherapy will become widely available across the country to treat patients with advanced pancreatic cancer," added Dr. Borazanci.

pancreatic cancer is difficult to treat and is the fourth leading cause of cancer deaths in the United States tumors can develop in the pancreas without any symptoms at first, which means that the disease is often an advanced stage when diagnosed, and survival remains low.

Virginia G. Piper cancer Center clinical trials is known worldwide for its expertise in the study of new treatments for pancreatic cancer .

people looking for information on eligibility to participate in clinical trials at cancer Center at Virginia G. Piper Scottsdale Healthcare may contact the coordinator of cancer care at 480-323-1339; toll free at 1-877-273-3713 or by email at clinicaltrials@shc.org. Additional information is available at http://www.clinicaltrials.gov (NCT004262).

Study: Most doctors do not recommend active surveillance of prostate cancer at low risk

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Study: Most doctors do not recommend active surveillance of prostate cancer at low risk -

Instead, they recommend treatment by their specialty suggests the investigation in medical care

specialists who treat prostate cancer agree that active surveillance is an option, yet most do not recommend it, as appropriate for their own patients, according a study in the July issue of Medical Care effective. The journal is published by Lippincott Williams & Wilkins, part of Wolters Kluwer Health.

On the contrary, urologists are more likely to recommend surgery and radiation oncologists are more likely to recommend radiation therapy treatments provided by their own specialties. "Given the growing concerns about the overtreatment of prostate cancer, our study has important policy implications of possible obstacles to the promotion of surveillance and specialty assets prejudices about the optimal treatment regarding prostate cancer localized "comments Dr. Simon P. Kim of Yale School of Medicine.

most experts prostate rate Effectiveness active surveillance

the researchers surveyed urologists and oncologists regarding their views on options for "low risk" prostate cancer. the study focused on the perception of active surveillance as a first approach.

prostate cancer usually progresses slowly most elderly men diagnosed with the disease at an early stage will not actually die from prostate cancer. for these low-risk cases, there is a growing interest in active surveillance, in which patients are monitored closely for signs of disease progression.

Active surveillance has emerged as an approach to avoid "over-treatment" of prostate cancer. In many cases, it can avoid surgery or radiation which would cause a risk of complications and side effects without actually benefiting the patient.

Dr Kim and coauthors analyzed survey responses from 717 US urologists and radiation oncologists. According to research data, 72 percent of experts agreed that active surveillance is an effective alternative for men with cancer of low risk prostate. In addition, 80 percent agreed that active surveillance has been underutilized in the United States.

-But do not recommend it for their own patients

"However, 71 percent of physicians reported that their patients are not interested in active surveillance" the researchers write. the rate was over 80 percent for radiation oncologists, compared to 60 percent for urologists.

When asked what treatment they recommend a hypothetical 60 the man with prostate cancer at low risk, only 22 percent of the doctors said would approve active surveillance. instead, 45 percent would recommend surgery (radical prostatectomy), while 35 percent would recommend some form of radiation therapy.

in general, the recommendations divided along the respondents-the lines most specialized recommended treatment under their specialty. After adjustment for other factors, urologists were four times more likely to recommend surgery, compared to radiation oncologists. Urologists are also much less likely to recommend a form of radiotherapy.

urologists were twice as likely to recommend active surveillance compared with radiation oncologists. The doctors who worked in academic medical centers were also more likely to recommend active surveillance.

The survey adds to recent evidence that physicians consider active surveillance as a "reasonable approach" for initial therapy in appropriate patients with low risk prostate cancer. The two specialist groups recognize the growing concern about overtreatment of prostate cancer.

However, "that does not always translate into their self-reported treatment recommendations patterns," Dr. Kim and colleagues write. "Our study suggests that there are still key attitudinal barriers to active surveillance among specialists in prostate cancer, especially given radiation oncologists and urologists can see their treatment as superior."

The researchers discuss options to better incorporate patient preferences into treatment decisions such as decision aids provide men with evidence on the benefits and disadvantages of the treatment options. Coordinated, multidisciplinary care involving the patient's primary care providers and specialists can also provide a better balance between the risks and benefits of different approaches. "By doing so, active monitoring can become a more acceptable disease management strategy for cancer of low risk prostate patients and newly diagnosed specialists," Dr. Kim and coauthors conclude.

La Jolla Institute researchers advance the work towards a vaccine for heart disease

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La Jolla Institute researchers advance the work towards a vaccine for heart disease -

search to the first vaccine in the world for heart disease continues to advance the Institute's Jolla for allergy and immunology, with researchers that demonstrate a significant reduction of arterial plaque in concept testing in mice.

Klaus Ley, MD, a pioneer in vascular immunology, vaccine leads the effort, which aims to reduce the buildup of plaque in the arteries by targeting inflammation. In his latest discovery, recently published in the journal Frontiers in Immunology , Ley used two mouse peptides identified by Harley Tse, Ph.D., of Wayne State University, which he built to test the vaccine approach. In the study, the vaccinated mice had arterial plaque about 40 percent less than the mice that did not receive the vaccine.

"Diseases of the heart remains the number one killer of our nation," said Mitchell Kronenberg, Ph.D., La Jolla Institute president and scientific director. "We are excited by the studies of Dr. Ley, who show the promise to create a vaccine that could one day reduce the incidence of this terrible disease. "if successful, the vaccine could be administered to help prevent heart disease and also to stop or reduce the progression of the disease. Besides heart disease, the vaccine could target shots, which are also powered by the buildup of plaque in the arteries.

the research drew praise from several experts in cardiology. Stanley Hazen, MD, Ph.D. .D., head of preventive cardiology section at the Cleveland Clinic, one of the best cardiology hospitals in the nation, called the research "elegant and terribly exciting."

"This lays the foundation for one day be able to prevent or even eradicate heart disease by providing a vaccine. Really remarkably significant advance, "says Hazen, also chairman of the Department of Cellular and Molecular Medicine.

Eric Topol, MD, academic director of Scripps Health and professor of genomics at the Scripps Research Institute, stressed the importance of Ley work. "If successful, the potential for development of a vaccine to prevent atherosclerosis would be a monumental advance in medicine," said Topol.

About 0,000 Americans die of heart disease each year, an amount of 1 every 4 American deaths. most people know that cholesterol is a major factor in the creation of the artery-clogging plaque leading to heart disease. However, many people may not be aware that inflammation is also a very important contributor to arterial plaque buildup. "numerous studies over the past 15 years have demonstrated the critical role of inflammation in heart disease," says Ley. "By creating a vaccine to reduce inflammation in the arteries, we hope to significantly reduce plaque buildup that accompanies it."

The Ley study was published December 27th in a document "atheroprotective vaccination with MHC-II restricted peptides ApoB- 100" Frontiers in Immunology

Ley said the type of vaccine, he explores is different from these people for the flu and other infections. " the goal of a vaccine against the flu is to teach the immune system to launch an attack if it encounters the virus, "he said. "Our vaccine works more like the desensitization process used in allergy shots Allergy shots are designed to teach the immune system of the individual to tolerate the allergen Our vaccine could work on the same principle - in this case .. What we would teach the immune system to tolerate certain molecules of our own body mistakenly attacks, which causes inflammation. "

in an earlier study, published August 13, 2012 in the Journal of Clinical Investigation, Ley identified a specific kind of immune (CD4 T cells) orchestrate the inflammatory attack on the wall artery receiving specific signals from the antigen from other inflammatory cells in the vessel wall. in addition, it was discovered that these immune cells behave as if they have already seen the antigen that causes them to start the attack. an antigen is a peptide derived from a virus, bacteria or, in the case of autoimmune diseases, one of our own proteins that the immune system mistakenly viewed as foreign and attack.

Ley said the discovery was particularly exciting because it means the immune cells have "memory" of the molecule brought out by antigen presenting cells. "immune memory is the underlying basis of effective vaccines, "he explains. "This means that conceptually, it was possible to envisage the development of a vaccine for heart disease."

Ley collaborated with fellow La Jolla Institute scientist Alessandro Sette, Ph.D. and Dr. Tse from Wayne State University in Michigan, to identify specific peptides, which invites high blood attack in mice - the sub-product which is inflammation. Mouse peptides were used in the test vaccine to teach the body, through gradual exposure, tolerate rather than attack these proteins.

Alongside this research Ley worked with Sette, a biologist vaccine internationally recognized, identified several candidate peptides in order to eventually create a vaccine against heart disease for people. "The next step is to test promising candidate peptides in mice specially designed with an immune system more similar to humans," he said. If successful, the vaccine could begin human clinical trials in as little as three years, says Ley.

The vaccine effort reflects the power to top immunologists together in an institution, Ley note. "This shows what can happen when you have an institute like ours dedicated to immunology," says Ley. "Sette is a world renowned expert on vaccines and I have knowledge in specialized cardiovascular immunology. It is the combination of our two areas of expertise that allows this vaccine initiative to continue. I do not think it could have happened anywhere else. "

Corneal prosthesis restores vision in patients blinded by corneal disease

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Corneal prosthesis restores vision in patients blinded by corneal disease -

A new review article in the June issue of Focal Points a monthly publication of the American Academy of Ophthalmology, calls keratoprosthesis a viable alternative to standard cornea transplants to help people with corneal blindness. Co-written by R. Rony Sayegh, MD, a surgeon with the Eye Institute University Hospitals, the document states that if the standard corneal transplantation is effective in treating many of the 8 million cases worldwide of corneal blindness, keratroprosthesis is an important alternative when standard treatment fails.

"There is no doubt that Keratoprosthesis helped restore vision in many patients blinded by corneal disease," said Dr. Sayegh, who is also assistant professor of ophthalmology Case Western Reserve University School of medicine, who co-authored the paper with Natalie A. Afshari, MD, Professor of ophthalmology and head, Division of cornea and refractive surgery of the Shiley Eye Center, University of California , San Diego, La Jolla, Calif. a corneal prosthesis is a surgical device that is assembled with a given cornea and transplanted to replace corneas severely damaged or diseased. the surgery is relatively rare and is performed to restore vision in patients corneas severely damaged due to congenital birth defects, infections, inflammation, injury and chemical burns.

the most widely used device for this procedure in the US is the prosthesis Boston (Boston KPro). It consists of a front plate with a clear plastic rod, which houses the optical part of the device, a rear plate, and a titanium locking ring. Each year, only about 0 patients in the US receive KPro compared to 36,700 corneal transplants nationwide.

"The KPro is reserved to a small but significant number of people who are blinded by severe cornea conditions," said Dr. Sayegh. "If a patient undergoes several standard cornea transplants, blood vessels unhealthy can develop leading to a rejection of the transplanted cornea, making it impossible to keep the grafts clearer standards for vision. the Boston KPro and other prostheses can give these people a last chance to have his sight and be able to function independently again. "

Dr. Sayegh has recently begun testing a new design for the K-Pro that has a titanium back plate that joins via a new trigger mechanism for the rear plate to fit on the front plate, which avoids the need for an additional locking ring.

"the new design eliminates added piece and makes it easier for the surgeon to assemble the device," said Dr. Sayegh. "More importantly, fewer components can result in improved the overall safety of the procedure, and it is likely that this design update will become the new standard. "

many members of the cornea service at university hospitals studied and helped the development of keratoprosthesis Boston. the availability of this technique for residents of Northeast Ohio has helped a number of patients regain vision after many years of blindness.

Dr. Sayegh said that there are other types available keratoprostheses, and we chose a surgeon must depend on the patient's needs and the severity of his condition.

"the most effective devices tend to have a more wide range of indications, are less expensive and are easier to surgically implant, preferably in a single step by a single surgeon, employing techniques familiar to most surgeons. Good anatomical retention and ability to restore the best achievable visual potential are other important factors for the success of corneal prosthesis. Lastly, a favorable safety profile with a low occurrence of complications, particularly those threatening the view is of the essence. clinicians should be able to identify appropriate candidates for the procedure, and the choice corneal prosthesis used must be adapted to the patient's specific condition, "he said.

New concept of organs on a chip may help study cancer metastasis

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New concept of organs on a chip may help study cancer metastasis -

The recent development of the concept of organs on a chip opens the possibility to study realistically human organs without the use of patients or animal testing. Professor Jaap den Toonder, who gave his inaugural lecture at the University of Technology Eindhoven (TU / e) June 20, goes even further: he intends to microsystems in which several "bodies" are connected by "blood vessels". It will for example allow a precise investigation of how cancer spreads. This could possibly make the development of medical drugs much cheaper and faster. TU / e started a special microfabrication laboratory to develop the necessary technology.

Breast cancer usually spreads to the bone marrow, brain or lungs. But it is difficult to track exactly how this process - it can not be observed directly in the human body. This is exactly the question Jaap den Toonder, Professor of Microsystems, wants to help answer, in collaboration with other Dutch institutes. Den Toonder was involved early on in the development of organs on a chip, in collaboration with other researchers, including Donald Ingber of the Wyss Institute at Harvard.

Metastasis
The TU / e professor working to develop a microsystem in which the organs are represented as an "organ on a chip", connected by a system of "blood vessels". Breast tissue sample contains the primary tumor. Because the microsystem is totally transparent, researchers can see with great precision when and how cancer cells spread, or metastasize, to other organs. For a sense of how it will work, please see this video: https://www.youtube.com/watch?v=DOvDMut0Vx4

individual organs on a chip are tiny pieces of tissue live grown with artificial blood. The goal is to allow the tissue to study, for example to study how the disease develops and how the tissue responds to medication. However the disease and drugs often involve interaction between multiple organs. A typical example is the interaction between different drugs in the liver, through which the substances are produced which can be toxic to other organs. This is the reason to move a body on a micro chip with several organs. A microsystem typically several centimeters and contains a network of channels and microchambers with sizes varying from 1 to 100 micrometers.

No animal testing
systems of this type can help to get a great reduction in the cost of the development of medical drugs. The test is now often done on human cells in petri dishes, but these do not provide a realistic natural environment. In addition, animal tests are carried out, but they often react differently humans. In addition, in animals, it is impossible to observe in real time exactly what is happening. And the fact that a drug does not work as expected is often not discovered until it was actually tested on humans, in which a lot of expensive work may already have been done. Using a micro with organs on a chip, researchers will be in the near future be able to carry out tests more quickly and realistically, without the need to use animals or humans. Den Toonder believes that the first applications will be ready for use within four to eight years.

Microsystems must provide an environment is present in the human body to ensure the validity of test results, Den Toonder explains. The environment of the cell must produce such bioactive signals right, so that the cells display true (pathogenesis) physiological behavior. In addition, the deformation and the rigidity of the environment are very important. "There is strong evidence that increasing the rigidity of the environment can make cancer cells trigger invasiveness, which is the first phase of metastases."

Not expensive cleanroom
To make microsystems, Den Toonder uses a technique derived from the production of semiconductor chip: lithography. He refers to this as "everyday lithography", because the smaller dimensions are much larger than those in the production of microchips. "Our smaller dimensions are 1 to 10 micrometers. At this scale, you do not need an expensive clean room, and there is no need to use smaller dimensions than that. The smaller scale in which we work is that of red blood cells and micro blood vessels size and these are of the order of a few micrometers. "in addition, the fluid flow in these narrow vessels is laminar by definition, so that it can be easily controlled.

TU / e will be in the near future to build a "laboratory MICROFAB" specially for the development of microsystems and research with these systems. The 700 square meter laboratory will be the best equipped center of its kind in the Netherlands, and represents an investment of over one million euros.

Discovery provides scientists with a better understanding of limiting uncontrolled cell growth

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Discovery provides scientists with a better understanding of limiting uncontrolled cell growth -

Biologists at UC San Diego have found the "missing link" in the chemical system that allows to animal cells to produce ribosomes -the thousands of protein "factories" contained in each cell that produce all the proteins necessary for tissue building and maintaining life.

Their discovery, detailed in the June 23 issue of Genes & Development, will not only force a revision of basic textbooks on molecular biology, but also to provide scientists a better understanding of how to limit the uncontrolled cell growth, such as cancer, which may be adjusted by controlling the release of ribosomes.

ribosomes are responsible for the production of wide variety of proteins including enzymes; structural molecules, such as hair, skin and bones; hormones such as insulin; and components of the immune system such as antibodies. Considered the most important molecular machinery of life, ribosomes have been extensively studied by scientists (the 09 Nobel Prize in chemistry, for example, was awarded for the study of structure and function). But until now, researchers had not discovered the details of how proteins that are used to build ribosomes themselves are produced.

Among the multicellular animals, such as humans, the ribosomes are composed of about 80 different proteins (humans have 79 while other animals have a slightly different number), and four different kinds of molecules RNA. In 1969, researchers discovered that synthesis of ribosomal RNA is carried out by specialized systems using two key enzymes: RNA polymerase I and RNA polymerase III. But until now, scientists did not know whether a complementary system was also responsible for the production of 80 proteins that make up the ribosome.

This is essentially what the UC San Diego researchers led by Jim Kadonaga, biology teacher, set out to examine. What they found was the missing link-specialized system that allows ribosomal proteins themselves to be synthesized by the cell.

"We found that the ribosomal proteins are synthesized via a novel regulatory system with the enzyme RNA polymerase II and a factor called TRF2" said Kadonaga. "In the production of most proteins, RNA polymerase II works with a factor called TBP, but for the synthesis of ribosomal proteins, it uses TRF2".

"The discovery of this system based on specialized TRF2 for ribosome biogenesis," he added, "provides a new way to study ribosomes and control of cell growth, and should lead to understanding and potential treatment of diseases like cancer. "

Small antioxidant molecules suppress colon cancer associated with colitis

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Small antioxidant molecules suppress colon cancer associated with colitis -

Researchers at Case Western Reserve University and Dartmouth showed that a class of small antioxidant molecules carries a huge potential for suppressing cancer associated colitis colon. These results, published in early June edition of Journal of Clinical Investigation offers hope that eventually doctors will be able to significantly reduce the number of people suffering from this inflammatory disease of intestine (IBD) who will develop colon cancer.

The molecules, called synthetic triterpenoids, appear to reach their positive effect in two ways. Firstly, they prevent inflammation, often a flash point which contributes to the development of colon cancer. On the other hand, they increase 15 hydroxyprostaglandin dehydrogenase (15-PGDH), a gene product that is known for a high level of protection against colon cancer. Oral administration of synthetic triterpenoids has shown such success in mice that researchers believe that clinical trials could demonstrate their efficacy in chemoprevention -. That is, the administration of drugs to stop or delay the onset of cancer rather than treat

"Patients with inflammatory bowel disease were 10 times more risk of cancer colon, placing it among the top three high-risk conditions for colorectal cancer, "said lead author and hematologist / oncologist John Letterio, MD, Professor of Pediatrics, Case Western Reserve University school of Medicine and director of the Angie Fowler adolescent and young adult Cancer Institute, Rainbow Babies & Hospital Hospitals University children. 'common epithelial cancers develop over a period of years or decades, in populations at high risk because of genetic predisposition, of so that chemoprevention strategies could delay or even halt the onset of clinically evident colon cancer. "

Join Letterio in this survey was Michael B. Sporn, MD, Professor of pharmacology and toxicology, Dartmouth Medical School, who first coined the term "chemoprevention" there almost four decades and investigated triterpenoids synthesized since 1995, demonstrating their effectiveness against epithelial cancers. Sporn collaborating on scientific research with leading physicians around the country, and collaboration with Letterio Sporn was natural because the two worked together when Letterio was a postdoctoral researcher. Colleague Sanford Markowitz, MD, PhD, Genetics Ingalls Professor of Cancer Case Western Reserve School of Medicine, served an important role in the investigation because of its expertise as the innovator who first characterized 15-PGDH, significant tumor suppressor and anti-inflammatory natural.

"We were intrigued by recent results that inflammatory cytokines, such as TNF-alpha, inhibit the expression of 15-PGDH" Letterio said. "We found that the triterpenoids may reverse inflammatory process by allowing the expression 15-PGDH to resume. Triterpenoids also inhibit the expression of cyclooxygenase-2 (COX-2), an enzyme known to feed inflammation. Between reverse the effects of TNF-alpha and COX-2, this class of small molecules could remove the colon cancer associated colitis. "

In genetically modified to proneness to inflammation-driven mouse on intestinal neoplasia, triterpenoids administered orally increased the survival of mice. triterpenoid molecules also deleted neoplasia intestinal epithelial reducing production of inflammatory mediators and increase the expression of the colon, the suppression of cancer 15 -PGDH.

the investigators also found that the triterpenoids administered to normal mice prevented their development of inflammation and colon cancer, despite their exposure to carcinogens known to cause both conditions. in addition, they discovered that triterpenoids trigger responses of epithelial cells to TGF-beta, a signaling pathway known to activate the 15-PGDH.

"Two points are particularly important in this study," said Letterio. "First of all, our studies in mice showed a cancer chemopreventive effect with triterpenoids. Second, our data also show that the production of 15-PGDH in mice was dependent on the presence of a signaling pathway intact TGF-beta. This path ensures that internal conditions remain relatively constant in the intestinal mucosa, both in the regulation of epithelial cell differentiation and development of inducible regulatory T cells to repel cancer. "

The following research team will focus on assessing the effect of triterpenoids for models of IBD and colon cancer that are not related to colitis. Investigators also want to explore whether triterpenoids natural plant derivatives with similar properties to synthetic triterpenoids laboratory products might offer a comparable benefit.

"the argument is strong for further human trials in cancer chemoprevention with triterpenoids," said Letterio . "There are many questions about safety, effectiveness, intermittent versus continuous administration, and synthetic vs. triterpenoid natural. clinical trials designed with care and a collaborative approach between industry and academia are needed to answer these questions. "

Markowitz agrees and further discusses the importance of the findings in the latter investigation.

"colon cancer is among the most feared consequences of ulcerative colitis in the long term," he said. "Even with intense monitoring of the colon by colonoscopy and random biopsies, cancer development are not always taken in time. The conclusion that synthetic triterpenoids can prevent colon cancer in the mouse model is the first breakthrough in this area and opens a novel opportunity to develop new drugs for use in human patients. "

Inovio evaluates the responses of immunotherapy in the treatment of HPV-related cancer head and neck

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Inovio evaluates the responses of immunotherapy in the treatment of HPV-related cancer head and neck -

Inovio Pharmaceuticals, Inc. (NYSE Amex: INO) announced today ' hui that it has launched a Phase I / IIa clinical trial to evaluate the safety, immunogenicity and clinical responses of its immunotherapy product, INO-3112 in the treatment of human papillomavirus (HPV) - associated head and neck cancer. INO-3112 is a lead product mix of active immunotherapy, VGX-3100 Inovio and its proprietary immune activator expressing interleukin-12 (IL-12). VGX-3100 is currently being evaluated in a randomized phase II efficacy for the treatment of dysplasia high grade cervical (pre-cancer).

In a phase I study of VGX-3100, Inovio has shown that immunotherapy produced high levels of durable immune responses of T cells, including CD8 + "killer" in 78% of patients in the study. These CD8 + T cells showed the functional capacity of killing target cells presenting the E6 and E7 antigens. In preclinical animal models, HPV immunotherapy Inovio demonstrated 100% protection against the HPV E6 and E7-expressing tumors and preventing or delaying the growth of these tumors. IL-12 immune enhancer owner, INO-012, has already been shown to improve specific immune responses of the CD4 antigen + and CD8 + T cells PENNVAX Inovio ® HIV DNA vaccine in a clinical trial. The inclusion of this immune activator based DNA in INO-3112 is designed to increase the production of specific HPV CD8 + T cells for the treatment of HPV-related cancers.

In this open study, called HPV-005, up to twenty adults with HPV-positive head and neck squamous cell carcinoma (ECCC) will be treated with INO-3112 and followed for safety and immune responses clinics. In a part of the study, up to ten patients will be treated with INO-3112 before and after resection of the tumor. In the second part of the study, up to ten patients will be treated with INO-3112 after the end of chemotherapy and radiotherapy. Each INO-3112 treatment will be administered using Inovio's CELLECTRA® delivery system.

In addition to assessing safety, the study will analyze the immune responses of T cells to INO-3112. Pre and post-immunotherapy tumor tissue will be analyzed to assess infiltration of T cells in the bed of the tumor and the tumor. Clinical responses characterized by anti-tumor effects, according to RECIST criteria, progression-free survival will also be measured.

The study will be conducted at the Abramson Cancer Center (ACC) at the School of Medicine Perelman (of PSOM) at the University of Pennsylvania, one of the cancer treatment center the first in the world and led by senior researcher Charu Aggarwal, MD, MPH, assistant professor of medicine in the division of hematology-oncology at the PSOM and ACC.

Dr. J. Joseph Kim, President and CEO of Inovio, said: "Initiating this head and neck cancer study is just the tip of the iceberg in our development plans immune therapy in oncology Onco-immunotherapy is all about T cells -. The same as our products have been shown to stimulate extremely well. We look forward to our next data cervical dysplasia unblinded phase II study on the efficacy and T-cell responses this summer. "

" We will also launch clinical studies on additional cancer to further characterize and expand the potential of our DNA immune therapy products and immune activators with their powerful capacity to generate and enable the highest levels of specific killer cells of the T antigen These include assays for INO-5150 for the prostate cancer with our pharmaceutical partner Q3 and INO-1400, our immunotherapy encoded for hTERT in the breast, cancer patients lung and pancreas later this year. our goal is to have the best and largest immunotherapies for cancer portfolio assets with the potential to find and destroy cancer cells, "said Dr. Kim.

human papillomavirus (HPV) is the most common sexually transmitted disease in the United States, infecting 79 million Americans. HPV infection can lead to cervical dysplasia and cancer as well as cancers of the anogenital tract. head and neck cancer causing HPV is the fastest growing cancer in men and is expected to exceed the impact of HPV cervical cancers caused by the end of this decade. If proven effective INO-3112 could increase current therapeutic approaches to head and neck. the therapy today for oropharyngeal (head and neck) cancer is a combination of chemotherapy, radiotherapy and surgical resection. treatments have many potential side effects, including damage to the throat, which can impede the ability to speak and swallow.

VGX-3100 and INO-3112 for the treatment of diseases related to HPV Caused

lead product, VGX-3100 Inovio's immunotherapy based ' DNA for precancerous lesions and cancers caused by HPV. This product without an immune activator, is currently double-blind randomized, phase II evaluating its efficacy and immune responses against HPV-caused cervical dysplasia. INO-3112 combines this immunotherapy with IL-12 immune activator based DNA to further stimulate the immune response against head and neck cancer, cervical cancer and other cancers.

Inovio immune activators

immune enhancers can play a vital role in increasing antigen-specific immune responses such as those generated by DNA vaccines Inovio. Inovio the portfolio of patents granted, DNA-based immuno vary in their ability to activate and enhance the therapeutic T cells or preventing antibodies to modulate the type of immune responses generated by the vaccine, the impact of durability of the immune response, and drive immune responses towards sites of infection, such as mucosal surfaces. different immune enhancers can play a unique role in achieving desired immune responses generated by DNA immunotherapies and vaccines. In addition, while it has been shown certain cytokines and chemokines protein based for severe toxicity, probably because of their dosage levels and systemic administration, DNA and immune activators based immunotherapies Inovio come together to an injection site in order to allow local production by the body of cytokines or chemokines, as well as antigens which stimulate immune responses with modifiers advantages and toxic systemic effects disease.

Sunday, September 1, 2013

Study results suggest growing support for the management of care focused on patient

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Study results suggest growing support for the management of care focused on patient -

primary care physicians practicing in a coordinated care model in team operates the health information technology are more likely to give patients recommended preventive screening and appropriate tests that doctors working in other contexts, according to a study published today in the Annals of Internal Medicine . The study comparing the quality of care by physicians using a model known as home medical benefit patient-centered (PCMH) care physicians in non-PCMH practices provides evidence that the model previously unproven but popular effectively provides care for patients.

"The study showed that primary care physicians participating in PCMHs improved their quality of care over time to a significantly higher rate than non-PCMH peers," said lead author Dr. Lisa Kern, associate professor of health policy and research at Weill Cornell Medical College. "the PCMH model combines electronic health records (EHRs) to organizational changes, including changes in the roles and responsibilities of clinicians and staff It was the combination of EHR and organizational changes that have been associated with greater improvement in quality ;. DSE alone are not enough. "

The PCMH is an organizational model that has attracted more attention since the Affordable Care Act encouraged, and in some cases, providers incentives to improve the quality of care they provide while reducing its cost. It is based on a personal relationship between being a patient, the doctor and the patient care team, which coordinates care across the health system, specialized practices in hospitals, skilled nursing facilities, the community health and home care services. Electronic health records (EHRs) and other technologies to monitor the health of patients over time to ensure that patients receive appropriate and necessary care. In 2012, there were over 0 commercial health plans, 42 states and three federal initiatives test the PCMH model.

Although PCMH could function without EHR technology has been shown to improve communication among providers, patients and their care teams. It keeps patients better informed about medical choices about their health providers and guides. To become a PCMH, medical practice must undergo a rigorous certification and demonstrate competence in a wide range of performance standards.

"This is an important study of a model of delivering health care that has been widely distributed, but has not been widely proven to improve health care. Practices that turn in PCMHs can be well positioned for additional changes to the delivery of health care, such as participation in responsible care organizations and other forms of health management of the population, "said the lead author, Rainu Dr Kaushal, Chair of the Department of policy of health care and research and Frances and John L. Loeb Professor of medical informatics at Weill Cornell.

the prospective cohort study evaluated health Hudson Valley of New York, where providers and payers operate independently. the researchers looked at how the quality of care has changed over three years (08-2010) in 13 primary care practices using EHRs and became PCMHs during the study, compared to 64 practices using EHRs, but are not PCMHs and 235 non-PCMH practices the paper-based system that is used to store patient health information.

The researchers compared the medical claims of more than 140,000 patients commercially insured through 10 quality measures, such as eye exams, hemoglobin A1C tests to monitor levels of blood glucose, and lipids tests for patients with diabetes; breast cancer and colorectal cancer screening; and tests recommended for children with sore throat. They found that, over time, doctors practices using the PCMH model scored between 1 and 9 percentage points higher than non-PCMH practices on four of the 10 measures. Overall, the likelihood of receiving recommended care in PCMHs was 6 percent higher than in the group that used EHRs and 7 percent more than in the group that used the paper documents.

The PCMH effect was independent of EHR technology, which, itself, appeared to be insufficient to achieve improved care. The authors suggest that changes in organizational culture required by the PCMH appear to play a role in improving the quality of care. PCMHs require suppliers to take responsibility for their performance, build teams by defining roles and responsibilities, and manage groups or patient populations rather than individuals. Although none of these changes specifically focus on information technology, it is at least the management of two people and the most easy-responsibility performance for providers to achieve.

Goserelin can help reduce the risk of early menopause in young women with breast cancer

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Goserelin can help reduce the risk of early menopause in young women with breast cancer -

Among young women treated for breast cancer, one of the most distressing side effects of chemotherapy is early menopause.

But a large clinical trial showed that the risk of early menopause can be significantly reduced by adding a drug called goserelin to chemotherapy. In addition, women who took goserelin and wanted to have children were more likely to get pregnant and give birth to a healthy baby.

The results were released during the 2014 American Society of Clinical Oncology 50th Annual Meeting in Chicago. Kathy Albain, MD, of Loyola University Medical Center is the lead author of the study.

The overall objective of goserlin is temporarily put ovaries "at rest" during chemotherapy. "We found that, in addition to reducing the risk of early menopause and all the symptoms that are associated with menopause, goserelin was very safe and may even improve survival," Albain said. "I think these our results will change clinical practice. "

the multi-center phase 3 trial included premenopausal women under 50 who had certain types of breast cancer early (estrogen and progesterone receptor negative) . one hundred thirty-one patients were randomized to receive standard chemotherapy and 126 were assigned to receive a goserelin chemotherapy.

After two years, 45 percent of women receiving standard chemotherapy had stopped menstruation or had high levels of a hormone known as FSH name, an indication of reduced production of estrogen and egg supply. by comparison, only 20 percent of women receiving goserelin had stopped menstruating or had high FSH. The pregnancy rate was almost twice as high in the goserelin group (21 percent against 11 percent).

After four years, 89 percent of patients who received goserelin had no signs or symptoms of cancer, compared to 78 percent of those receiving standard chemotherapy. Overall survival at four years was 92 percent in the goserelin group and 82 percent in the standard chemotherapy group.

"Premenopausal women starting chemotherapy for early breast cancer should consider this new option to prevent premature ovarian failure," Albain and colleagues concluded.
Goserelin (trade name, Zoladex®) is similar to a natural hormone produced by the body. It is approved by the FDA for prostate cancer, certain benign gynecological disorders and certain breast cancers.

Goserelin is administered by injection. In the clinical trial, women assigned to the goserelin group was hit once every four weeks during their chemotherapy treatment. The side effects of goserelin were rare, and mostly included more symptoms associated with reduced activity of the ovaries during chemotherapy.

Approximately 25 percent of breast cancers occur in women under 50 years of breast cancer chemotherapy can trigger early menopause in women in their 20s, 30s and 40s. After completing chemotherapy, some women return to menstruation and are able to have children should they choose to do so. But for many women after chemotherapy, menopause is permanent.

menopause induced by chemotherapy tends to appear suddenly, and therefore, the symptoms are much more intense. These symptoms include irregular periods and cessation of periods completely; vaginal dryness; hot flashes; night sweats; sleep problems; mood changes; weight gain; hair thinning; dry skin; and loss of breast fullness. "Early menopause in patients younger breast cancer can be very debilitating," said Albain.

The clinical trial is called "Prevention of early menopause studies (POEMS) S0230." It is sponsored by national cooperative group research SWOG cancer and employees of SWOG groups, including the Cancer Study Group, Eastern Cooperative Oncology Group and the Alliance for International Breast oncology clinical trials. First author is Halle CF. Moore, MD, of the Cleveland Clinic. The study was funded in part by the National Cancer Institute

Study suggests new targets for the treatment of rare genetic disorder and cancer

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Study suggests new targets for the treatment of rare genetic disorder and cancer -

The combined action of two enzymes, and Srs2 EXO1, prevents and repairs common genetic mutations in cells yeast growth, according to a new study by scientists at NYU Langone Medical Center.

Because such mechanisms are generally preserved throughout evolution, at least in part, researchers say the results suggest that a similar DNA repair kit may exist in man and could be a target for controlling certain cancers and treatment, a genetic disorder linked to a rare enzyme called Aicardi syndrome-Goutieres. Syndrome, an often fatal neurological condition, is found in only a few families in small towns in Italy, Algeria and Japan, and among the Cree Indians in North America.

In a report to be published in the journal Nature Online June 1, NYU Langone researchers, aided by colleagues from Yale University, found that the action of the paired enzyme prevents and repairs the errors made during the DNA replication, when molecular subunits called rNMPs is inserted into the DNA. The rNMPs are RNA building blocks chemical cousin of DNA, which is the key intermediate involved in making all the proteins from DNA

The researchers propose that some misguided rNMPs occur naturally -. And are repaired - that DNA is replicated during cell growth, enzymes quickly recognize these foreign intruders like lesions. If not removed, these lesions increase the probability of mutations in the DNA code, which if allowed to accumulate, create genomic instability in yeast and human cells, and may lead to cell death and immune responses promote cancer.

"Taking our cue from the yeast, which shares a third of its genetic makeup with humans, our study shows for the first time a robust safeguard mechanism of DNA repair is in place to deal with common RNMP induced mutations, "says senior study investigator and NYU Langone yeast geneticist Hannah Klein, PhD." Without a robust backup system for DNA repair, the cells will die. "

Among the key findings of the study was that one of the enzymes, Srs2, helps open the scale yeast DNA structure resembling closely linked so that another enzyme, EXO1, can cleave on rNMPs astray. These bad RNMP insertions during replication, scientists say, contaminating DNA and often fatal structural alterations. both enzymes were previously known to play a role in DNA replication and repair, but scientists say this is the first evidence of their role in the prevention and correction of derivative RNMP mutations.

Furthermore, the research team found that the Srs2 Exo1cell-repair mechanism prevents mutations of the acceleration in the already deficient yeast in a third enzyme encoded by the gene RNaseH2. This enzyme is the primary removal mechanism for rNMPs during cell growth, a major role in DNA repair. But in the deficient yeast as the RNaseH2 and Srs2 enzyme, the number of mutations, loss of chromosomes, and chromosome breaks increase of 10 times.

According to Dr. Klein, acting president of biochemistry and molecular pharmacology at NYU Langone, the study team is also the first to show how Srs2 and EXO1 backup service routine function RNMP RNaseH2 of the enzyme, highlighting the constant need nature to balance cell growth, genetic mutation and DNA repair in preventing disease and cell death.

Dr. Klein warned that if no known human counterpart Srs2 exists EXO1 is in human cells, it is likely that a repair safeguard mechanism similar DNA exists in people. And if further testing shows that its repair function can be manipulated in humans, the enzyme mechanism can be used as a basis to block or reverse derivatives cancers RNaseH2 mutations. Dr. Klein said decomposing how tumors develop in yeast cells deficient RNaseH2 is essential to develop and test potential treatments for people.

overproduction

Other research has involved RNase H2 as one of several genetic aspects of many cancers, including cancers of the bladder, brain, breast, head and neck squamous cell carcinoma and leukemia (T- and B acute lymphoblastic leukemia cells and acute myelogenous leukemia), melanomas, and seminomas.

Even more specifically, she said, the enzyme repair mechanism could be used to decrypt and address the root causes of the enzyme RNaseH2 deficit, which in humans is known to be the one of the main hereditary signatures behind Aicardi syndrome -Goutieres. The syndrome causes inflammation of the spinal cord and brain shrinkage inevitably stall the physical and mental development in early childhood. Although rare and currently incurable, the disease affects hundreds in isolated communities where inbreeding within the family took place and when both parents have RNaseH2 or other Aicardi -Goutieres related mutations.

For the study, lead investigator and yeast geneticist colleague Catherine Potenski, PhD, monitored how various mutant yeast strains grew in the laboratory, including the deficient enzyme RNaseH2 and Srs2. (Dr Klein's lab in the late 1980s was the first to isolate RNaseH2 mutations in yeast.)

Dr. Potenski, a postdoctoral researcher at NYU Langone, said yeast strains deficient in both enzymes accumulated mutations and thrive, while those only depleted the RNaseH2 enzyme were able to minimize the changes and continue to grow. However, in experiments with EXO1, disposal doped mutations in RNaseH2 deficient strains, whereas depletion Srs2 had no aggravating effect. This evidence confirmed that researchers Srs2 EXO1 and acted together to avoid mutations in cells deficient RNaseH2.

Analysis by Yale colleagues later confirmed, action linked between Srs2 and EXO1 showing how Srs2 EXO1 stimulated to act on the yeast DNA, allowing cleavage and repair RNMP lesions.

Dr. Potenski said its latest studies of Srs2, EXO1 RNaseH2 enzymes and should also serve as a reminder to other researchers that the known enzymes can have many roles in the life cycle of the cell, some are not yet known, and that more backup roles can be found.

Dr. Potenski said the team next plans to investigate what other biological factors can influence EXO1 as a third repair mechanism possible backup, and to study the factors that could trigger RNaseH2 mutations most likely to lead to cancer.

Changes in BRCA2 and CHEK2 genes may increase the risk of lung cancer, according to a study

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Changes in BRCA2 and CHEK2 genes may increase the risk of lung cancer, according to a study -

Genetic causes of lung cancer explored in the overall project of the genome

new research confirms vulnerability to lung cancer can be hereditary and involves the BRCA2 gene as harboring genetic mutations involved. An international consortium of scientists, including researchers from the Institute for Research on Cancer in London, the International Agency for Research on Cancer in Lyon, the National Cancer Institute in Bethesda, Harvard and Dartmouth used the integrated results project 1000 Genomes with the genetics of lung cancer studies to complete the survey published June 1, 2014 Nature genetics .

study scanned the genomes of more than 11,000 people of European descent to look for common variations associated with non small cell carcinoma, a common form of lung cancer. The analysis showed that variations in the gene BRCA2 and CHEK2 can significantly increase the risk of an individual for lung cancer. The chances of a smoker developing lung cancer may be doubled if he or she carries the BRCA2 variation. In addition, the TP63 gene, which was previously only associated with a risk of lung cancer in Asian populations, has been associated with a risk for adenocarcinoma, a form of non-small cell cancer, in those of European origin .

The study four associations (GWA) studies genome-wide opportunity for the UT MD Anderson Cancer Center, the Institute for Research on Cancer, the National Cancer Institute, and the International Agency for Research cancer. The scientists used imputation, a statistical form of inference, in which data from a group of individuals who were sequenced reference is used to fill in missing values ​​on the genome for participants to 'study. The study validated the use of this approach in the search for common genetic variations between different data sets and genotyping many other Harvard participants, the International Agency for Cancer Research, University of Toronto , the Institute for research on cancer and the German cancer research Institute.

Chris Amos, PhD, lead author of the paper and director of the Center for Genomic Medicine at Dartmouth said: "This variant confers the strongest associations found to date for cancer among those identified by genome - wide association studies, and identifies a subset of people who are particularly vulnerable to the adverse effects of smoking. "

The BRCA2 gene for a large protein that functions primarily to coordinate the activities of many different genes involved in DNA repair. DNA cells accumulate damage due to environmental toxins such as those in tobacco smoke. Mutations in BRCA2 can affect the ability of cells to respond to DNA damage, which increases the chance that a cell becomes a cancer.

Previous studies did not detect a link between BRCA2 and lung cancer. All four GWA all data analysis in this study showed a significant association of the BRCA2 gene (of rs11571833) with non-small cell carcinoma, especially squamous cell carcinoma. In addition, the results of previous studies linking validated CHEK2 (rs17879961) with squamous cell carcinoma. The results of the variation TP63 (rs13314271) in individuals in the European ancestry provides strong evidence for its connection to adenocarcinoma.

"Our study showed that mutations in two genes, BRCA2 and CHEK2, have a very important effect on lung cancer risk in the context of smoking. Mutated BRCA2 in particular, appears to increase the risk about 1.8 times, "said study leader Richard Houlston, professor of molecular and population genetics at the Institute for research on cancer (ICR). "Smokers generally have nearly a 15 per cent chance of developing lung cancer, much higher than among nonsmokers Our results indicate that some smokers with BRCA2 mutations are at a huge risk of cancer lung -.. Somewhere in the region of 25 percent in their life lung cancer claims more than a million lives a year worldwide and is by far the biggest cancer killer in the UK. We know that the main thing we can do to reduce mortality is to persuade people not to smoke, and our new results clearly indicate that this is even more critical in people with a genetic risk underlying. "

the results of this study may influence how individuals are examined and treated for lung cancer. Those with genetic mutations who smoke may be candidates for lung cancer screening with low dose CT. Given that individuals with mutations in the germline BRCA1 or BRCA2 respond to a specific chemotherapy PARP inhibition, it is possible that individuals with this mutation BRCA2 and lung cancer may well respond more favorably to inhibition of PARP as other cases of lung cancer.