Newswise — There are two common approaches to protecting humans from infectious disease: Targeting pathogens and parasites with medicines like antibiotics, or dealing with the conditions that allow transmission. A paper published today in the journal Nature Scientific Reports demonstrates the effectiveness of a third strategy: Adjusting the landscape of the human body to remove the mechanism that allows pathogens to cause disease. The discovery is the result of serendipity and collaboration between high-level scientists in different fields. "It was pure luck that I ended up on this paper," says Dan Theodorescu, MD, PhD, director of the University of Colorado Cancer Center. "Bill Petri and I had been social friends for years – Christmas parties, that kind of thing. When I was at Virginia it happened that we were on a recruitment committee together and the candidate was late, so we started talking." His conversation with William A. Petri, Jr., MD, PhD, chief of the Division of Infectious Diseases & International Health at the University of Virginia led to the idea of applying an innovative cancer science technique to the study of infectious disease. With first author Chelsea Marie, PhD, postdoctoral researcher in the Petri Laboratory at Virginia, the group decided to silence genes in human cells to discover if the loss of any single gene would confer immunity to the parasite E. histolytica, which infects 50 million people and causes 40,000-110,000 deaths via severe diarrhea worldwide. "Chelsea is a fearless experimenter. She took a library of cells that Dan had developed in his work with bladder cancer and then sequentially killed them with E. histolytica parasites," Petri says. Specifically, the group used the technique called RNAi to create a library of bladder cancer cells with thousands of independent, silenced genes. Then they challenged these cultures with the parasite E. histolytica. "We do this all the time in cancer research," Theodorescu says. "Commonly, we're looking for genes that, when silenced, will make cells more susceptible to chemotherapy." In this case the analogue of chemotherapy was the infectious, dangerous pathogen. "This amoeba is a cluster bomb – a voracious killer. In the back of my mind I was thinking the parasite was going to decimate the host cells no matter what we did with their genetics," Marie says. For the vast majority of cells in this genome-wide screen, Chelsea Marie was correct; E. histolytica decimated many thousands of these independent cell cultures. However, a small number of cells seemed to resist the parasite. Was this the random chance of lucky survival or had silenced genes somehow offered immunity to these cells? To find out, Marie discarded the killed cells and retested the cells that had survived; again she infected these survivor cells with E. histolytica. "It wasn't a fluke," says Marie. "We did this over nine generations of cells, each time selecting the cells that survived and then re-applying the parasite. Over these generations of selection, we saw the cultures becoming more and more enriched for cells lacking specific genes." Using next generation sequencing, Marie identified the genes that conferred resistance and found that many were involved in managing the flow of potassium into and out of human cells. Specifically, the identified genes KCNA3, KCNB2, KCNIP4, KCNJ3, and SLC24A3 are involved in what is called potassium transport. A follow-up experiment showed that new intestinal cells treated with E. histolytica showed potassium efflux – the flow of potassium from inside a cell out through the cell wall – directly before cell death. "We started to see a pretty clear line of reasoning," says Theodorescu. "The parasite was causing potassium efflux right before cell death and cells that happened to be unable to transport potassium didn't die." To ensure that lack of potassium transport was, in fact, causing resistance to the parasite, the group reversed the direction of their experiments. Marie started with new cells and used drugs to block their ability to transport potassium. Blocking potassium efflux created cells that were resistant to E. histolytica. "There is a clear need for new drugs targeting E. histolytica," Petri says. "Right now there is a single antibiotic that works against this parasite. We know that eventually the parasite will develop resistance to the antibiotic and at that point there's no plan B. This could be the plan B – targeting the human genes that enable the parasite to cause disease." Marie is pushing forward. She recently learned from a mentor at John's Hopkins how to isolate stem cells from human tissue to grow what she calls "mini guts" to test therapeutics that may be useful in human patients. And technological advances make this study's general technique more efficient, allowing the use of what are called CRISPR libraries instead of RNAi screens. "This is a major finding with translational implications for this infection that causes so many deaths worldwide, but also proof that this cancer-science approach can be used to explore genetic mechanisms of resistance in the field of infectious disease," Theodorescu says. The field of infectious disease has been focused on the infection, targeting pathogens and their transmission. This study shows that in addition to characteristics of the parasite, mortality due to disease can be prevented by manipulating characteristics of the host.
RUTGERS CANCER INSTITUTE ONE OF FEW CENTERS ON EAST COAST TO OFFER IMMUNOTHERAPY CLINICAL TRIAL TARGETING LEUKEMIA/LYMPHOMA
Newswise — New Brunswick, N.J., September 8, 2015– Rutgers Cancer Institute of New Jersey is one of a few East Coast sites to offer a clinical trial investigating an experimental drug known as REGN1979 in the treatment of non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL). The drug – designed to use the body’s own defenses to fight illness – targets a specific protein (called CD20) found in these particular types of cancer and targets another protein (called CD3) found on T-cells, a type of cell in the immune system. REGN1979 is designed to help T cells find and destroy B cells, including those cancerous B cells found in NHL and CLL. The goal is to determine how much of the drug can be given safely to patients who have the CD20 protein on their lymphoma or CLL cells. “By harnessing the body’s own natural defenses, there is an opportunity to provide alternate therapies for patients with NHL and CLL whose disease has stopped responding to standard treatments,” notes Rajat Bannerji, MD, PhD, medical oncologist and principal investigator of the trial at Rutgers Cancer Institute of New Jersey and associate professor of medicine at Rutgers Robert Wood Johnson Medical School. Participants are expected to be involved in the study for at least one year. Patients enrolled into the study will receive an infusion of the study drug through a vein. Participants also will be asked permission for scientists to study tissue samples taken from tumors or bone marrow collected during certain clinic visits. Adults aged 18 and older who are diagnosed with NHL or CLL and have had prior treatment with a particular antibody therapy (anti-CD20) are eligible to take part in the trial, provided they meet additional entry criteria. Prior to being enrolled into the study, participants would be required to undergo a number of tests including blood work and a physical exam. For more information on how to take part in this trial, sponsored by Regeneron Pharmaceuticals, Inc., individuals should call the Cancer Institute’s Office of Human Research Services at 732-235-8675 or e-mail firstname.lastname@example.org. Clinical trials, often called cancer research studies, test new treatments and new ways of using existing treatments for cancer. At the Cancer Institute, researchers use these studies to answer questions about how a treatment affects the human body and to make sure it is safe and effective. There are several types of clinical trials that are currently underway at the Cancer Institute, including those that diagnose, treat, prevent, and manage symptoms of cancer. Many treatments used today, whether they are drugs or vaccines, ways to do surgery or give radiation therapy, or combinations of treatments, are the results of past clinical trials. As New Jersey’s only National Cancer Institute-designated Comprehensive Cancer Center, the Cancer Institute offers patients access to treatment options not available at other institutions within the state. The Cancer Institute currently enrolls more than 1,200 patients in clinical trials annually, including approximately 17 percent of all new adult cancer patients and approximately 70 percent of all pediatric cancer patients. Enrollment in these studies nationwide is fewer than five percent of all adult cancer patients. About Rutgers Cancer Institute of New JerseyRutgers Cancer Institute of New Jersey (www.cinj.org) is the state’s first and only National Cancer Institute-designated Comprehensive Cancer Center. As part of Rutgers, The State University of New Jersey, the Cancer Institute of New Jersey is dedicated to improving the detection, treatment and care of patients with cancer, and to serving as an education resource for cancer prevention. Physician-scientists at the Cancer Institute engage in translational research, transforming their laboratory discoveries into clinical practice, quite literally bringing research to life. To make a tax-deductible gift to support the Cancer Institute of New Jersey, call 848-932-3637 or visit www.cinj.org/giving. Follow us on Facebook at www.facebook.com/TheCINJ. The Cancer Institute of New Jersey Network is comprised of hospitals throughout the state and provides the highest quality cancer care and rapid dissemination of important discoveries into the community. Flagship Hospital: Robert Wood Johnson University Hospital. System Partner: Meridian Health (Jersey Shore University Medical Center, Ocean Medical Center, Riverview Medical Center, Southern Ocean Medical Center, and Bayshore Community Hospital). Major Clinical Research Affiliate Hospitals: Carol G. Simon Cancer Center at Morristown Medical Center and Carol G. Simon Cancer Center at Overlook Medical Center. Affiliate Hospitals: JFK Medical Center, Robert Wood Johnson University Hospital Hamilton (CINJ Hamilton), and Robert Wood Johnson University Hospital Somerset.
3D Printing is reaching new heights according to sources from the FDA as well as WebMD, and the clinical trials of a new medication being tested for epilepsy. In a recent report from Aprecia Pharmaceuticals, the agency has developed a 3D printed tablet for epilepsy that rapidly disintegrates with a sip of liquid. The tablet is called Spritam and is the first 3D printed drug to be approved for sale in the U.S. and it is expected to be available early next year, in 2016. “For the last 50 years we have manufactured tablets in factories and shipped them to hospitals and for the first time this process means we can produce tablets much close to the patient,” Dr. Mohamed Albed Alhnan, a lecturer in pharmaceutics at the University of Central Lancashire in the United Kingdom, explained in an interview with BBC News. Nearly 3 million Americans have been diagnosed with epilepsy, including 460,000 children according to WebMD.com and the numbers continue to rise. The financial expense and physical care some patients need can be overwhelming to the family and/or the caregiver, 3D printing can make the frustration of being able to obtain prescriptions easier and possibly even approach new, more effective medication technology. 3D printing is already a leading technology in the development of medical devices. There is still a long road ahead for 3D printing pharmaceuticals. From developing printers that can print a higher quantity pharmaceuticals at a time all the way down to the specific benefits of 3D printing like drugs that can be personalized using different layers to create a more effective release of the medication into the body, a more person specific medication experience. “The uniformity of dosage control with this type of manufacturing method is at least as good, if not far better, than conventional manufacturing” said Michael J. Cima, PhD., Massachusetts Institute of Technology.
Dental Tips from Texas A & M can help you encourage healthy dental habits away from home. 1. Eat healthy foods at home A healthy diet won’t just improve your child’s growth and physical health; it will also improve their dental health. Most natural foods contain lower amounts of sugars and aren’t as damaging to the teeth. One of the easiest things you can do to ensure your child will make healthy, tooth-conscious decisions at school is to eat healthy foods at home. Aim to serve your child a balanced diet, including fruits, vegetables, whole grains, dairy products and protein. “Parents need to serve these foods at home so their children will imitate those eating habits when they are elsewhere,” Pace said. 2. Pack fruits and dairy Natural is usually better when it comes to foods in general, and the same goes for snacks. Instead of popular snacks that may lead to unhealthy teeth or dental habits, try going the au naturel route. Packing fruit will satisfy your child’s sweet cravings and help them gain all the proper nutrients they need to grow healthy. Milk doesn’t just help their bones grow stronger, it can also help their teeth stay healthier as well. One of the best snacks you can pack in your child’s lunch is a dairy product. Try throwing in a string cheese or a carton of milk to their lunchbox. “Cheese or other dairies are a great way to end meals,” Pace remarked. “They can help protect tooth enamel, which is key to preventing decay.” 3. Avoid sticky and sugary foods “In general, any food that is sticky, crunchy or has sugar can promote cavities,” Pace warned. Sticky foods like candy or gummies are not only loaded with sugar, but they can also be difficult to dislodge later. Anything that sticks to the teeth can potentially damage them or cause decay. “Frequent sugar consumption is one of the worst things for your teeth that can cause tooth decay. Unfortunately, sugar is in almost everything,” Pace said. Avoid packing food with extra sugar like cookies, sugary beverages or candy in children’s daily lunches. Sugary, prepackaged snacks may be convenient short term, but they may also help a cavity thrive later on. Check all the sugar content on any prepackaged foods or snacks, and opt for more natural or low-sugar foods instead. Switch out your kid’s sugar-bomb applesauce for the no sugar added variety. If you’re having trouble thinking of appropriate snacks, fruits with peels can satisfy your little one’s sweet tooth without promoting cavities. 4. Be active in their dental care Participate in your child’s morning and nightly teeth cleaning rituals, and teach them the tools to keep those pearly whites healthy and happy. You can also take it a step further by acting as a dental advocate yourself to promote healthy habits in your children. “Children love to imitate, so let them watch you brush your teeth and floss. Or even better, do it with them,” Pace suggested. “Really try to have your kids brush their teeth after breakfast.” Healthy habits start at home, so try to make your child’s formative years fun and memorable. While brushing teeth, sing a favorite song or play a catchy tune on your phone to make it enjoyable, and always serve them healthy foods at home. These are habits they’ll take with them throughout their lifetime. Report by Texas A & M
Newswise — ST. LOUIS — In research published inCancer Cell, Thomas Burris, Ph.D., chair of pharmacology and physiology at Saint Louis University, has, for the first time, found a way to stop cancer cell growth by targeting the Warburg Effect, a trait of cancer cell metabolism that scientists have been eager to exploit. Unlike recent advances in personalized medicine that focus on specific genetic mutations associated with different types of cancer, this research targets a broad principle that applies to almost every kind of cancer: its energy source. The Saint Louis University study, which was conducted in animal models and in human tumor cells in the lab, showed that a drug developed by Burris and colleagues at Scripps Research Institute can stop cancer cells without causing damage to healthy cells or leading to other severe side effects. The Warburg EffectMetabolism – the ability to use energy – is a feature of all living things. Cancer cells aggressively ramp up this process, allowing mutated cells to grow unchecked at the expense of surrounding tissue. “Targeting cancer metabolism has become a hot area over the past few years, though the idea is not new,” Burris said. Since the early 1900s, scientists have known that cancer cells prefer to use glucose as fuel even if they have plenty of other resources available. In fact, this is how doctors use PET (positron emission tomography) scan images to spot tumors. PET scans highlight the glucose that cancer cells have accumulated. This preference for using glucose as fuel is called the Warburg effect, or glycolysis. In his paper, Burris reports that the Warburg effect is the metabolic foundation of oncogenic (cancer gene) growth, tumor progression and metastasis as well as tumor resistance to treatment. Cancer’s Goal: To Grow and DivideCancer cells have one goal: to grow and divide as quickly as possible. And, while there are a number of possible molecular pathways a cell could use to find food, cancer cells have a set of preferred pathways. “In fact, they are addicted to certain pathways,” Burris said. “They need tools to grow fast and that means they need to have all of the parts for new cells and they need new energy.” “Cancer cells look for metabolic pathways to find the parts to grow and divide. If they don’t have the parts, they just die,” said Burris. “The Warburg effect ramps up energy use in the form of glucose to make chemicals required for rapid growth and cancer cells also ramp up another process, lipogenesis, that lets them make their own fats that they need to rapidly grow.” If the Warburg effect and lipogenesis are key metabolic pathways that drive cancer progression, growth, survival, immune evasion, resistance to treatment and disease recurrence, then, Burris hypothesizes, targeting glycolysis and lipogenesis could offer a way to stop a broad range of cancers. Cutting off the Energy SupplyBurris and his colleagues created a class of compounds that affect a receptor that regulates fat synthesis. The new compound, SR9243, which started as an anti-cholesterol drug candidate, turns down fat synthesis so that cells can’t produce their own fat. This also impacts the Warburg pathway, turning cancer cells into more normal cells. SR9243 suppresses abnormal glucose consumption and cuts off cancer cells’ energy supply. When cancer cells don’t get the parts they need to reproduce through glucose or fat, they simply die. Because the Warburg effect is not a feature of normal cells and because most normal cells can acquire fat from outside, SR9243 only kills cancer cells and remains non-toxic to healthy cells. The drug also has a good safety profile; it is effective without causing weight loss, liver toxicity, or inflammation. Promising ResultsSo far, SR9243 has been tested in cultured cancer cells and in human tumor cells grown in animal models. Because the Warburg pathway is a feature of almost every kind of cancer, researchers are testing it on a number of different cancer models. “It works in a wide range of cancers both in culture and in human tumors developing in animal models,” Burris said. “Some are more sensitive to it than others. In several of these pathways, cells had been reprogramed by cancer to support cancer cell growth. This returns the metabolism to that of more normal cells.” In human tumors grown in animal models, Burris said, “It worked very well on lung, prostate, and colorectal cancers, and it worked to a lesser degree in ovarian and pancreatic cancers.” It also seems to work on glioblastoma, an extremely difficult to treat form of brain cancer, though it isn’t able to cross the brain/blood barrier very effectively. The challenge for researchers in this scenario will be to find a way to allow the drug to cross this barrier, the body’s natural protection for the brain, which can make it difficult for drug treatments to reach their target. And, in even more promising news, it appears that when SR9243 is used in combination with existing chemotherapy drugs, it increases their effectiveness, in a mechanism apart from SR9243’s own cancer fighting ability. Other researchers on the study include Colin A. Flaveny, Kristine Griffett, Bahaa El-Dien M. El-Gendy, Melissa Kazantzis, Monideepa Sengupta, Antonio L. Amelio, Arindam Chatterjee, John Walker, Laura A. Solt and Theodore M. Kamenecka. Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious diseases.
The no-diet approach to weight control By adopting sensible eating habits and practicing portion control, you can eat nutritious foods so that you take in as many calories as you need to maintain your health and well-being at your ideal weight. Often, weight loss occurs on its own simply when you start making better food choices, such as avoiding processed foods, sugar-laden foods, white bread and pasta (substitute whole-grain varieties instead), foods with a high percentage of calories from fat, alcoholic drinks. While nothing is absolutely forbidden, when you do succumb to temptation, keep the portion size small and add a bit more exercise to your daily workout. By replacing some unwise food choices with healthy ones, you'll be cutting back on calories. If you add some moderate physical activity, you have the perfect weight-loss plan without the need for special or inconvenient (and often expensive) diet plans. An example of a successful no-diet weight loss program A 45-year-old woman complains that she has gradually put on 12 pounds over the past year. In the last month, she's faced a stressful work deadline and added another 4 pounds to her frame. This individual's goal is to lose the 16 pounds she has gained. Since her weight has been gradually increasing, she knows that she is consuming more calories than she is burning, especially with her sedentary job. She decides that a weight loss of 1 pound per week (equal to a deficit of about 3,500 calories, or cutting 500 calories per day) would be acceptable and would allow her to reach her goal in about four months. She decides to make some changes that will allow her to cut back an average of 250 calories per day. Skipping a large glass of sweetened iced tea will save about 200 calories. Substituting mineral water for the cola she regularly drinks during meetings can save another 150 calories. Foregoing her morning muffin snack (or eating only half a muffin) can also save 250 calories or more. To reach her goal of a 500-calorie-per-day savings, she adds some exercise. Getting up early for a 20-minute walk before work and adding a 10-minute walk during her lunch break add up to a half hour of walking per day, which can burn about 200 calories. On weekends, she plans to walk for 60 minutes one day and spend one hour gardening the next day for even greater calorie burning. If walking for 60 minutes is too much, two 30-minute walks one day would burn the same number of calories. Twice per week she plans to stop at the gym on the way home from work, even if only for a half hour of stationary cycling or swimming (each burning up to 250 calories). By making just some of the dietary cutbacks mentioned and starting some moderate exercise, this individual can easily "save" the 3,500 calories per week needed for a 1-pound weight loss, leading to a healthy rate of weight loss without extreme denial or deprivation. Furthermore, her changes in diet and lifestyle are small and gradual, modifications that she can maintain over time. Superfoods Quiz: Test Your Diet IQTake our Superfoods Quiz! Get to know how unprocessed, raw, organic foods and healthy drinks are rich in nutrients and dietary...learn more » Childhood Obesity Quiz: Test Your Medical IQChildhood obesity has reached epidemic proportions. Take the Childhood Obesity Quiz to test your knowledge of the facts and...learn more » Belly (Abdominal) Fat Quiz: Test Your Belly Fat IQDid you know there is a medical term for belly fat? Find out what it is and learn why getting rid of belly fat may be the best...learn more » Fat and Fats Quiz: Test Your Diet IQTake this online Fat & Fats Quiz to learn if you really are what you eat!...learn more » Food Portion Distortion Quiz: Test Your Diet IQAre your portions deceiving you? Take the Food Portion Distortion Quiz to find out how and why gigantic portions trick you into...learn more » Healthy Eating at Restaurants Pictures Slideshow: Don't Abandon Your DietSee how to recognize the dangers and stay on your healthy diet when eating out. Watch this slideshow to learn about healthy...learn more »