IUDs safe in population at high risk for STIs

  1. ?In a study population at high-risk for sexually transmitted infections, the rate of pelvic inflammatory disease following intrauterine device placement was low.
  2. The IUD continuation rate at one year was greater than 85 percent.

Evidence Rating Level: 3 (Average)???????

IUD Diagram Jun15 Blog







Image: CC/Wikimedia Commons/Blausen.com?used with license/permission

Study Rundown: Intrauterine devices (IUDs) are some of the most effective forms of birth control, with a failure rate of less than one percent, and have been demonstrated to be safe for a wide range of women, including teenagers and young adults. Despite their high efficacy and safety record, many practitioners and patients still have misconceptions regarding the risk of pelvic inflammatory disease (PID) after IUD placement. PID is an infection of the upper genital tract (endometrium, tubes and ovaries) that commonly occurs when a sexually transmitted infection (STI), such as Chlamydia, gonorrhea, or trhichomonas ascends from the lower genital tract. Complications from PID include infertility and PID as well as an increased risk of ectopic pregnancy. If a woman has an STI at the time of IUD placement, she is at higher risk of contracting PID, but after about 20 days, the risk of PID decreases to the baseline risk among women who use a non-barrier form of contraception. Because of the concern for risk of PID with IUD insertion among women at high risk for STIs, most large studies exclude this population and limited data exists to guide their use in this population. In the present work, researchers retrospectively assessed rates of PID after IUD placement in an urban teaching hospital that did not restrict IUD eligibility based on STI risk factors.

Rates of PID following IUD placement were low and comparable to previous studies. The study population was at high-risk for STIs with a high incidence (nearly 50%) of personal history of STIs, 50% of participants were under the age of 26, and participants identified as being single. Lack of control group limited this study. Replication of findings using an age-matched control cohort would lend credence to the results presented herein.

Click to read the study in Contraception

Relevant Reading: Does insertion and use of an intrauterine device increase the risk of pelvic inflammatory disease among women with sexually transmitted infection? A systematic review

In-Depth [retrospective cohort]: Researchers reviewed charts of all patients undergoing hormonal IUD placement in the resident clinic of a large, urban, academic medical center from July 2007-June 2008 (n = 283). IUD candidates were not restricted by age, parity or STI risk. The primary outcome was diagnosis of PID within twelve months of IUD placement. Secondary outcomes included continuation and adverse outcomes: expulsion, perforation, pregnancy, pain and heavy bleeding.

Prior to IUD placement, 140 patients (49.5%) reported a history of STI and eight (3.02%) tested positive for gonorrhea or chlamydia at the time of placement in this high-risk population. In the 12 months following placement, only two patients (0.7%) were diagnosed with PID, one of which had a positive gonorrheal test at the time of placement. The continuation rate at one year was 85.2%, expulsion rate was low (5.3%) and a minority of women (17.7%) reported adverse effects.

(by Maren Shapiro; Reprinted with license and permission from 2 Minute Medicine)RePubHub Banner



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Halozyme: Update Following Type B FDA Meeting

Recent FDA meeting allows for potential marketing application based on progression free survival in pivotal Phase 3 pancreatic cancer study

Halozyme Therapeutics, Inc.,a biotechnology company developing novel oncology and drug-delivery therapies, today announced it plans to proceed with a Phase 3 clinical study (Study 301) of its investigational new drug PEGPH20 in patients with metastatic pancreatic cancer, using a design allowing for potential marketing application based on either progression free survival (PFS) or overall survival. The use of PFS as the basis for marketing approval will be subject to the overall benefit and risk associated with PEGPH20 combined with nab-paclitaxel (ABRAXANE ?) and gemcitabine therapy, including the:

  • Magnitude of the PFS treatment effect observed;
  • Toxicity profile;?and
  • Interim overall survival data.

The study will enroll patients whose tumors accumulate high levels of?hyaluronan?(HA)?? a?sugar?that?is sometimes more prevalent in the areas surrounding cancer cells. Halozyme recently discussed the study as part of a planned Type B meeting with the U.S. Food and Drug Administration (FDA).

bullseyeData discussed at the meeting focused on interim results from the company’s randomized Phase 2 study in pancreatic cancer, Study 202, which showed a doubling in median PFS in metastatic pancreatic cancer patients with high levels of HA who were treated with Halozyme’s investigational new drug PEGPH20 combined with nab-paclitaxel (ABRAXANE ?) and gemcitabine (9.2 months vs. 4.3 months in patients treated with nab-paclitaxel ABRAXANE ? and gemcitabine alone). The potential risk profile, including rate of thromboembolic events, was also discussed.? Additional?takeaways from the meeting include:

  • Halozyme?affirmed?plans?to enroll and evaluate high-HA patients using a companion diagnostic test; and
  • FDA provided feedback on the current?companion diagnostic approach and confirmed that an approved companion diagnostic strategy is required prior to Phase 3 study initiation.

“We are encouraged by the FDA’s feedback and their willingness to consider a novel primary endpoint such as PFS given the high unmet medical need in high-HA metastatic pancreatic cancer,” said Dr. Helen Torley, President and Chief Executive Officer. “We are committed to rapidly finalizing the Phase 3 protocol and developing the companion diagnostic regulatory filings required to initiate Study 301.” Based on this FDA feedback, the company is targeting the end of first quarter 2016 to initiate the Phase 3 study.

About Study 202 & PEGPH20microscope in laboratory
Study 202 (Halo 109-202) is a Phase 2 multi-center, randomized clinical trial evaluating investigational new drug PEGPH20 as a first-line therapy for treatment of patients with stage 4 metastatic pancreatic cancer. The primary outcome of the trial is to measure improvement in progression-free survival in patients receiving investigational new drug PEGPH20 in combination with gemcitabine and nab-paclitaxel compared to gemcitabine and nab-paclitaxel alone. A second primary endpoint will assess the thromboembolic event rate in the PEGPH20 treatment arm. Secondary endpoints also include objective response rate and overall survival. More information may be found at: http://oncologytrials.halozyme.com/pancreatic/.

PEGPH20 is an investigational PEGylated form of Halozyme’s proprietary recombinant human hyaluronidase under clinical development for the systemic treatment of tumors that accumulate hyaluronan. FDA granted orphan drug designation to PEGPH20 for treatment of pancreatic cancer and fast track for PEGPH20 in combination with gemcitabine and nab-paclitaxel for the treatment of metastatic pancreatic cancer. Additionally, the European Commission, acting on the recommendation from the Committee for Orphan Medicinal Products of the European Medicines Agency, designated investigational drug PEGPH20 an orphan medicinal product for the treatment of pancreatic cancer.

About Halozyme
Halozyme Therapeutics is a biotechnology company focused on developing and commercializing novel oncology therapies that target the tumor microenvironment. Halozyme’s lead proprietary program, investigational drug PEGPH20, applies a unique approach to targeting solid tumors, allowing increased access of co-administered cancer drug therapies to the tumor.? PEGPH20 is currently in development for metastatic pancreatic cancer and non-small cell lung cancer and has potential across additional cancers in combination with different types of cancer therapies. For more information, visit www.halozyme.com.

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FDA Approves Pulmozyme with eRapid Nebulizer

CF Patients See 2 – 3 Minute Treatment Times

The eRapid Nebulizer System (eRapid) from PARI has been approved as the first electronic nebulizer by the Food and Drug Administration to deliver Genentech’s Pulmozyme for cystic fibrosis treatment.? A huge improvement for cystic fibrosis patients, eRapid is able to reduce average treatment times with Pulmozyme from 6-8 minutes down to 2-3 minutes.? Both adult and pediatric patients showed a strong preference for eRapid over conventional nebulizers in a clinical study. FDA-Logo

“We have been pleased with eRapid’s fast treatment times in the lab and are excited that patients now have access to a much faster Pulmozyme therapy.? As the first electronic nebulizer to deliver Pulmozyme, eRapid is a true breakthrough for cystic fibrosis patients who take the therapy daily, often for years,”?said Lisa Cambridge, director of Medical Science and Pharmaceutical Alliances at PARI Respiratory Equipment, Inc.

“PARI was motivated to introduce eRapid to the US market based on encouragement from the Cystic Fibrosis Foundation and their input to have a general-use, electronic nebulizer that could improve therapy adherence. For many years, eRapid has been successfully distributed in Europe (as eFlow Rapid) with favorable feedback from patients with CF. In the Pulmozyme clinical trial, there was a 10:1 preference for eRapid in the pediatric group and a 20:1 preference in the adult group.? That confirmed our decision to bring eRapid to the US,” added Geoff A. Hunziker, president of PARI USA.

“After the successful results of a Phase IV study, we are confident that physicians will see that both pediatric and adult patients favor eRapid based on reduced treatment times, quiet operation, and its small, portable size.? We were also happy to see that patients were more satisfied with treatment and eRapid had a positive influence on adherence ? good for their overall cystic fibrosis management,” added Lisa Cambridge.? eRapid is available today by prescription through a select group of specialty pharmacies.? Visit www.pari.com or call 1-800-FAST-NEB to learn more.

Pulmozyme is indicated for daily administration along with standard therapies for the management of cystic fibrosis to improve pulmonary function.? For more information, visit http://www.pulmozyme.com/.

About eRapid Nebulizer System eRapid is an electronic nebulizer that enables quick and efficient inhalation that can greatly reduce a patient’s treatment burden. ?For more information on eRapid, please visit http://www.pari.com/.

About Cystic Fibrosis Cystic fibrosis, a life-threatening disease affecting 30,000 American patients, involves a genetic mutation that results in poorly hydrated, thickened mucus secretions in the lungs, as well as severely impaired mucociliary clearance.? Get more information about Cystic Fibrosis, visit http://www.cff.org

About PARI Respiratory Equipment, Inc. PARI is a leading, worldwide developer and manufacturer of fast and efficient aerosol delivery systems for patients with asthma, chronic lung disease, cystic fibrosis, RSV, VAP, and HAP.? PARI’s worldwide vision is to improve the lives of those affected by respiratory diseases and those who care for them.?PARI is considered the gold standard for aerosol delivery for nebulizer therapies.? Featured products include the PARI LC PLUS Reusable Nebulizer, Vortex Holding Chamber, and the drug-specific eFlow Technology platform.

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New Treatment Helps 80% Of Kids Overcome Peanut Allergies

In the past several decades, the number of children with peanut allergies has tripled from 0.4 percent in 1997 to 1.4 percent in 2010, according to a Mount Sinai Hospital study. While doctors aren?t certain what caused the increase, it has led schools and airlines to ban peanut products out of fear of causing severe reactions.

By Lecia Bushak? Release Date January 31, 2015

Now, a new study from Murdoch Children?s Research Institute outlines a new treatment that could possibly cure children of their peanut allergies. The researchers gave 60 peanut-allergic children a dose of a probiotic known as Lactobacillus rhamnosus (around 20 kilograms of yogurt) mixed with a peanut protein, and gradually increased the daily amount over the course of 18 months in order to test whether their tolerance would gradually increase. Over 80 percent of the children who received the treatment were no longer severely allergic to peanuts by the end of the 18 months, when compared to four percent of the placebo group.

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For the study, “the combined delivery of probiotic and oral immunotherapy was a safe and effective treatment for peanut allergy; however, it is important to point out that this treatment must be given only under close medical supervision as we are giving peanut to children who are allergic to peanut, and children did have allergic reactions,? said Professor Mimi Tang, an author of the study, in the press release. ?Nevertheless, the likelihood of success was high ? if nine children were given probiotic and peanut therapy, seven would benefit.?

Immunotherapy, more simply known as allergy shots, is a long-term treatment that helps people develop a higher tolerance to allergens, and decreases symptoms of allergic rhinitis, allergic asthma, or conjunctivitis, according to the American Academy of Allergy, Asthma, and Immunology (AAAAI). Allergy shots are similar to vaccines: The body responds to each injection by building up its immunity to the allergen, similar to how vaccines help the body create defenses against viruses.

Previous research has found that oral immunotherapy ? meaning doses of the allergen taken by mouth, not a jab ? proved useful in decreasing symptoms of peanut allergy in children. Also known as desensitization, the treatment is still being studied. Until it’s used more widely, most people with peanut allergies should still avoid peanuts at all costs, and carry an ?Epi-pen,? or a shot of epinephrine, wherever they go to prevent anaphylaxis. Less severe allergy cases involve Benadryl as the only treatment option.

The new study?s results, however, are promising. Eighty-two percent of the children treated with the probiotic mixture were able to include peanuts in their diet after the trial, compared to 3.6 percent of the placebo group. ?It appears that we have been able to modify the allergic response to peanut such that the immune system produces protective responses rather than a harmful response to the peanut protein,? Tang said.

The authors believe that finding a cure for peanut allergies is crucial, since it?s one of the most common and severe allergies ? it can also last a lifetime. Out of the 15 million Americans who have some form of food allergy, peanut, milk, and shellfish allergies are the most prevalent.

?Many of the children and families believe it has changed their lives, they?re very happy, they feel relieved,? Tang told The Guardian. ?These findings provide the first vital step toward developing a cure for peanut allergy and possibly other food allergies.?

Source: Tang M, Ponsonby A, Orsini F, Tey D, Robinson M, Su E. Administration of a probiotic with peanut oral immunotherapy: A randomized trial.?The Journal of Allergy and Clinical Immunology. 2015.

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The Top 5 Recent Breakthroughs in Advanced Lung Cancer Treatment

Ross Camidge MD PHD ATOMICWe might need to look at our back catalogues for treatments we could retrospectively explore for effective predictive biomarkers with our more modern approaches. ?D. Ross Camidge, MD, PhD

A countdown of the top 5 breakthrough therapies in the treatment of advanced lung cancer was presented by D. Ross Camidge, MD, PhD, at the 2014 Chicago Multidisciplinary Symposium in Thoracic Oncology. Dr. Camidge is Director, Thoracic Oncology Clinical and Clinical Research Programs, and Associate Director for Clinical Research, University of Colorado Comprehensive Cancer Center, Aurora. He is also the Director for the newly minted ATOMIC Lung Cancer Consortium. He chose the following molecular therapies as his top choices for illustrating what the future of Lung cancer treatment will involve:

#5. Crizotinib

Dr. Camidge chose crizotinib(Xalkori) as a breakthrough therapy ?because of how it has exemplified the philosophy of one size does not fit all,? he said.

#4. Second-Generation ALK Inhibitors

The second-generation ALK inhibitors werechosen ?not because of their impressive activity post-crizotinib, but because of their progress in accurately defining how we capture data on benefit in central nervous system (CNS) disease,? Dr. Camidge explained.

#3. Third-Generation EGFR Inhibitors

Dr. Camidge identified the third-generation EGFR inhibitors ?because of what they are teaching us about understanding acquired resistance in order to effectively treat it,? he said.

#2. PD-1/PD-L1 Antagonists

Dr. Camidge singled out the inhibitors of programmed death receptor 1 (PD-1) and its ligand (PD-L1) as opening the door to immunotherapy but with the open question of whether they will really be a panacea or whether they have the potential to become a truly personalized medicine.

#1. Three Possible Future Breakthroughs

The?number 1 spot was shared by three ?mini-fantasies? about what future breakthroughs might be, based on the concepts of mining the past, intraoncogene heterogeneity, and affordable incremental benefit.

Explaining his interest in mining the past, Dr. Camidge said, ?We have walked away from a large number of targeted agents because they didn?t work when given to otherwise unselected lung cancer populations. However, in almost all of these cases, no attempt at robustly exploring predictive biomarkers was conducted,? he noted.

?Consequently, the classes of drugs may not truly be ineffective, and there may have been evidence of hypersensitive subpopulations ripe for re-exploration,? he continued. ?We might need to look at our back catalogues for treatments we could retrospectively explore for effective predictive biomarkers with our more modern approaches.?

As an example, he cited the class of drugs known as death receptor agonists. These drugs ?which directly stimulate apoptosis and worked exceptionally well in various preclinical models, were all dropped when a series of randomized phase II studies adding these agents to first-line chemotherapy failed to show an advantage.? But the nonprogressors in the experimental arms approached 15% of the population in several of the studies, he said. ?Unfortunately little or no tissue was collected in these studies so no predictive biomarkers could really be explored at the time.?

Dr. Camidge used KRAS as an example of intraoncogene heterogeneity. The most common mutation among adenocarcinomas of the lung, KRAS has been shown in preclinical and clinical studies to have tremendous heterogeneity. The trial design for the FAK inhibitor VS-6063 in KRAS-mutant lung cancer is ?at least starting to address this heterogeneity by exploring its benefit in four KRAS-mutant cohorts that have also been characterized with regard to their INK4a and p53 status to see if these contexts alter the response to the drug, based on relevant preclinical data,? Dr. Camidge said.

To explain affordable incremental benefit, he cited the REVEL study, which looked at the addition of ramucirumab (Cyramza), an antibody against VEGFR2, to standard second-line docetaxel. ?The addition of ramucirumab increased the response rate from 14% to 30% and the disease control rate from 53% to 64%, increased the progression free survival from 3.0 to 4.5 months, and increased the overall survival from 9.1 to 10.5 months,? Dr. Camidge reported.

?So with an unequivocally positive phase III study, adding a little to all major endpoints, we might want to be using this drug. But only if it, and drugs like it, are affordable, as one recurring problem has been in pricing a breakthrough as if it?s a game-changer and not just a way of offering a little incremental benefit to everyone.? If not affordable, ?these minor breakthroughs will never be practical to use in the real world,? he said.

Disclosures: Dr. Camidge has received honoraria from Pfizer, Genentech/Roche, Clovis, Aria, and Eli Lilly.

Camidge DR: The top five most promising molecular therapies on the horizon. Chicago Multidisciplinary Symposium in Thoracic Oncology. Presented October 31, 2014.

Source/Complete article by Charlotte Bath (The ASCO Post) is available at: http://www.ascopost.com/issues/december-1,-2014/top-5-breakthroughs-in-the-treatment-of-advanced-lung-cancer.aspx

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There May Soon Be A Vaccine For Breast Cancer

A study?on a new breast cancer vaccine developed at Washington University School of Medicine in St. Louis has found the treatment to be safe in patients with metastatic breast cancer. According to the press release,?the vaccine helped patients? immune systems attack breast tumor cells and also slowed the cancer?s progression.

By Dana Dovey? Release date: December 1, 2014

Breast cancer is the second most common cancer among American women, surpassed by only skin cancer. It?s estimated that around one in eight American women will develop some form of breast cancer during their lifetime, and sadly, the American Cancer Society estimates that around 40,000 women will succumb to the disease every year. Breast cancer detection and treatment is constantly improving, but with the possibility of a new vaccine, the day we beat breast cancer may be sooner than imagined.

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The vaccine works by helping a patient?s own body fight off breast cancer cells by pushing the immune system to target proteins called mammaglobin-A. These proteins are only found in breast tissue, and express themselves at abnormally high levels when there’s a tumor.? The vaccine prompts the immune system to target and destroy these proteins, which significantly slows breast cancer?s progression.

?Most physician scientists believe that breast cancer vaccines will be most successful for the treatment of patients with early-stage breast cancer, or for prevention of breast cancer in patients who are at high risk for developing breast cancer,? breast cancer surgeon and senior author of the study Dr. William E. Gillanders told?Medical Daily in an email. Mammaglobin-A is found in as many as 80 percent of breast cancer cases, he said. “In theory, this means we could treat a large number of breast cancer patients with potentially fewer side effects.?

The phase 1 trial was conducted to test the vaccine?s safety, and researchers were pleased to find that it passed with flying colors. Rash, tenderness at the vaccination site, and mild-flu like symptoms were the worst reactions recorded. “Despite the weakened immune systems in these patients, we did observe a biologic response to the vaccine while analyzing immune cells in their blood samples,” said Gillanders.

It?s important to note that this vaccine did not ?cure? the patient?s cancer or cause them to go into remission. ?Cancer vaccines are not currently used as a substitute for other therapies ? they are typically given in addition to other effective treatments,? Gillanders told Medical Daily.

Now that the vaccine has been shown to be safe for human use, the team will move on to a larger clinical trial. This time, they will use volunteers who were only recently diagnosed with breast cancer, and therefore would have much stronger immune systems. It?s believed that the stronger immune systems may provide even more impressive results.

?If we give the vaccine to patients at the beginning of treatment, the immune systems should not be compromised like in patients with metastatic disease,” Gillanders said. “We also will be able to do more informative immune monitoring than we did in this preliminary trial.?

Still, of the 14 volunteers in this most recent trial, about half showed no cancer progression one year after receiving the vaccine, which Gillanders says suggests ?that the cancer growth was slowed ? i.e. the progression-free survival was prolonged.?

The team now has the funding needed for the second phase of their study and will soon begin their new trial.

For more?information on translational research in breast cancer please visit the ABRCC website.
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If You Have Penicillin Allergies, You Should Get Retested

Patients who have been diagnosed with penicillin allergies probably aren?t allergic to it anymore, according to a new finding. The allergy wears off over time, but most people live the rest of their lives believing they’re still allergic, and pay for more expensive, unnecessary medication.

by Samantha Olson? Release Date: November 9, 2014

Mayo Clinic Allergist Dr. Thanai Pongdee, and his team retested 384 patients and found 94 percent of them were not allergic. The patients were scheduled to undergo several different types of surgeries when they were tested. Pongdee said he expected they would find maybe half of the patients still allergic to penicillin, a common medical allergy. However, when almost all of the patients found they weren?t allergic, it more than confirmed a suspicion doctors had for a long time.

Test Tube Penicillin
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“We knew that the majority of people who list penicillin as an allergy actually aren?t allergic when they are reevaluated, so if you can determine they are not, you can avoid using more toxic and more expensive antibiotics,” Pongdee told NBC News. “It doesn?t happen very often that a health care provider challenges the presumption that the patient is still allergic. Many don?t realize that this is something a person may lose over time.”

When a patient walks into the hospital, one of the first questions they?re asked is, “Are you allergic to any medications?” Ten percent of the population report they’re allergic to penicillin, making it the most commonly reported drug allergy, according to the American College of Allergy, Asthma & Immunology?(ACAAI). A patient with an allergy may develop hives, swelling, throat tightening, wheezing, coughing, and difficulty breathing. In severe cases, it can cause a patient to go into sudden anaphylactic shock, which will rapidly worsen and could become deadly.

Penicillin has been around since 1928, and has been used to treat a variety of conditions, such as strep throat, ear infection, or sinus infection. Penicillin is the base of many front-line drugs, and if you can?t take one of those, you?re often forced to take a more expensive alternative with more side effects.

When one Long Island mother, whose son was diagnosed with a penicillin allergy at the age of 8, was asked if she would have him retested, she said, “I definitely would. It would stop us from worrying because he doesn’t wear a bracelet. He broke out in a rash and hives after he was given amocycillin for his strep throat.”

In most cases their sensitivity to penicillin will lessen overtime and can be treated safely with the drug. It?s exciting news for patients with documented penicillin allergies because they can start receiving cheaper drugs, such as the generic penicillin-based amoxicillin used to fight bacterial infections. Most people are diagnosed when they are toddlers due to an adverse reaction, but then live the rest of their lives avoiding a drug allergy with unfounded fears.

?There are two issues: these patients are put on other antibiotics which [are] less effective and potentially have more side-effects,? Family Allergist Dr. James Sublett, the incoming president of the ACAAI told NBC News. ?The other is cost. A very commonly used substitute, for example Levaquin, is seven to eight times more expensive for a 10-day course than a similar course of generic Augmentin, a penicillin drug.?

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Cancer Leaves a Common Fingerprint on DNA

Chemical alterations to genes appear key to tumor development
by Shawna Williams, Johns Hopkins Medicine – Release Date: August 26, 2014
(Displayed with permission from redOrbit.com2014 redOrbit)

Fast Facts:

  • Alterations to chemicals attached to DNA, known as epigenetic changes, affect how genes do their work and have been linked to colon cancer.
  • A new study of six different cancer types found distinctive epigenetic changes in all of them.
  • Conclusion: Epigenetic changes are key to cancer development.
DNA Image Courtesy of Thinkstock via RePubHub
DNA Image Courtesy of Thinkstock via RePubHub

Regardless of their stage or type, cancers appear to share a telltale signature of widespread changes to the so-called epigenome, according to a team of researchers. In a study of a broad variety of cancers, published online in Genome Medicine on Aug. 26, the investigators say they have found widespread and distinctive changes to chemical marks known as methyl groups attached to DNA. Those marks help govern whether genes are turned “on” or “off”, and ultimately how the cell behaves. Such reversible chemical marks on DNA are known as epigenetic, and together they make up the epigenome.

Regardless of the type of solid tumor, the pattern of methylation is much different on the genomes of cancerous cells than in healthy cells,” says Andrew Feinberg, M.D., M.P.H., a professor of medicine, molecular biology and genetics, oncology, and biostatistics at the Johns Hopkins University School of Medicine. Feinberg led the new study along with Rafael Irizarry, Ph.D., a professor of biostatics at Harvard University and the Dana-Farber Cancer Institute. “These changes happen very early in tumor formation, and we think they enable tumor cells to adapt to changes in their environment and thrive by quickly turning their genes on or off,” Feinberg says.

Feinberg, along with Johns Hopkins University School of Medicine oncology professor Bert Vogelstein, M.D., first identified abnormal methylation in some cancers in 1983. Since then, Feinberg?s and other research groups have found other cancer-associated changes in epigenetic marks. But only recently, says Feinberg, did researchers gain the tools needed to find out just how widespread these changes are.

For their study, the research team took DNA samples from breast, colon, lung, thyroid and pancreas tumors, and from healthy tissue, and analyzed methylation patterns on the DNA. “All of the tumors had big blocks of DNA where the methylation was randomized in cancer, leading to loss of methylation over big chunks and gain of methylation in smaller regions,” says Winston Timp, Ph.D., an assistant professor of biomedical engineering at Johns Hopkins. “The changes arise early in cancer development, suggesting that they could conspire with genetic mutations to aid cancer development,” he says.

The overall effect, Feinberg says, appears to be that cancers can easily turn genes “on” or “off” as needed. For example, they often switch off genes that cause dangerous cells to self-destruct while switching on genes that are normally only used very early in development and that enable cancers to spread and invade healthy tissue. “They have a toolbox that their healthy neighbors lack, and that gives them a competitive advantage,” Feinberg says.

“These insights into the cancer epigenome could provide a foundation for development of early screening or preventive treatment for cancer,” Timp says, suggesting that the distinctive methylation “fingerprint” could potentially be used to tell early-stage cancers apart from other, harmless growths. Even better, he says, would be to find a way to prevent the transition to a cancerous fingerprint from happening at all.

Other authors on the paper are Hector Corrada Bravo of the University of Maryland, College Park, and Oliver G. McDonald, Michael Goggins, Chris Umbricht and Martha Zeiger, all of The Johns Hopkins University.

The study was funded by the National Human Genome Research Institute (grant number HG003223), the National Cancer Institute (grant number CA054358), the National Institute of General Medical Sciences (grant numbers GM083084 and GM103552) and the National Center for Research Resources (grant number RR021967).

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A Novel Drug for Treatment of Necrotizing Soft-Tissue Infections

Criterium, Inc., a full-service CRO is proud to be the CRO of record as the supplier of services and support for this important trial. Further study details are provided by the pharmaceutical development sponsor, AtoxBio Ltd. on ClinicalTrials.gov

Clincial Trial Results ReportA complete article detailing the trial and its current progress was highlighted in JAMA’s April 2014 issue in print and online (http://archsurg.jamanetwork.com/article.aspx?articleid=1859986). This is a study to evaluate the safety and pharmacokinetics profile of different doses of AB-103 administered to patients diagnosed with Necrotizing Soft Tissue Infections that are scheduled for an urgent surgical intervention as part of their standard of care. The primary study hypothesis is that AB-103 can be administered safely to the patients presenting with Necrotizing Soft Tissue Infections. Secondary endpoints are efficacy by exploratory descriptive analyses of specific efficacy endpoints from three outcome domains to demonstrate treatment benefit of AB-103 in comparison to placebo in patients with Necrotizing Soft Tissue Infections.

The efficacy domains Lab-Beakersare:

  1. Clinical status domain
  2. Pharmacoeconomics domain
  3. Systemic and local inflammatory biomarker domain

Criterium, with extensive experience in dermatology and infectious disease indications, particularly with wound and burn treatments, provided services for data and project management, clinical and medical monitoring, biostatistics, safety, regulatory support, and medical writing.

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Clinical Trials Monthly Case Study Analysis

Each month, we investigate a different Clinical Trial Case Study that posed us with a challenging question; this month it’s a look at INFECTIOUS DISEASE, regulatory issues and patient enrollment:

We asked ourselves:
A Phase III study required by the World Map Color - NOAM-SOAMFDA for approval was stalled at its North America sites and regulatory processes in South America prevented significant contribution to these studies. There were multiple rejections because this infectious disease study required a placebo control. The study recruitment by another CRO was not met in the previous two seasons.

Criterium offered an experienced team in the Southern Hemisphere to get approval by the regulatory authorities of this placebo-controlled respiratory infection study, to extend the recruitment to 10 months of the year and to enroll at a higher rate per site than the previous seasons’ site enrollment rates.

Criterium’s team averaged more patients per site than the Northern Hemisphere at a high compliance rate for the target micro-organisms.

What If: The client could have continued recruiting patients in the Northern Hemisphere winters, thereby further extending the length of the study.

Results: Criterium managed the regulatory process to receive approval for the study on the first agency reviews and accelerated enrollment with its experienced team in South Africa and New Zealand.

Read more of our successful case studies: https://www.criteriuminc.com/case_studies.php

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