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Posts Tagged ‘Diabetes’


Live 12:00 – 1:00 P.M  Mediterranean Diet and Lifestyle: A Symposium on Diet and Human Health : October 19, 2018

Reporter: Stephen J. Williams, Ph.D.

12.00 The Italian Mediterranean Diet as a Model of Identity of a People with a Universal Good to Safeguard Health?

Prof. Antonino De Lorenzo, MD, PhD.

Director of the School of Specialization in Clinical Nutrition, University of Rome “Tor Vergata”

It is important to determine how our bodies interacts with the environment, such as absorption of nutrients.

Studies shown here show decrease in life expectancy of a high sugar diet, but the quality of the diet, not just the type of diet is important, especially the role of natural probiotics and phenolic compounds found in the Mediterranean diet.

The WHO report in 2005 discusses the unsustainability of nutrition deficiencies and suggest a proactive personalized and preventative/predictive approach of diet and health.

Most of the noncommunicable diseases like CV (46%) cancer 21% and 11% respiratory and 4% diabetes could be prevented and or cured with proper dietary approaches

Italy vs. the US diseases: in Italy most disease due to environmental contamination while US diet plays a major role

The issue we are facing in less than 10% of the Italian population (fruit, fibers, oils) are not getting the proper foods, diet and contributing to as we suggest 46% of the disease

The Food Paradox: 1.5 billion are obese; we notice we are eating less products of quality and most quality produce is going to waste;

  •  growing BMI and junk food: our studies are correlating the junk food (pre-prepared) and global BMI
  • modern diet and impact of human health (junk food high in additives, salt) has impact on microflora
  • Western Diet and Addiction: We show a link (using brain scans) showing correlation of junk food, sugar cravings, and other addictive behaviors by affecting the dopamine signaling in the substantia nigra
  • developed a junk food calculator and a Mediterranean diet calculator
  • the intersection of culture, food is embedded in the Mediterranean diet; this is supported by dietary studies of two distinct rural Italian populations (one of these in the US) show decrease in diet
  • Impact of diet: have model in Germany how this diet can increase health and life expectancy
  • from 1950 to present day 2.7 unit increase in the diet index can increase life expectancy by 26%
  • so there is an inverse relationship with our index and breast cancer

Environment and metal contamination and glyphosate: contribution to disease and impact of maintaining the healthy diet

  • huge problem with use of pesticides and increase in celiac disease

12:30 Environment and Health

Dr. Iris Maria Forte, PhD.

National Cancer Institute “Pascale” Foundation | IRCCS · Department of Research, Naples, Italy

Cancer as a disease of the environment.  Weinberg’s hallmarks of Cancer reveal how environment and epigenetics can impact any of these hallmarks.

Epigenetic effects

  • gene gatekeepers (Rb and P53)
  • DNA repair and damage stabilization

Heavy Metals and Dioxins:( alterations of the immune system as well as epigenetic regulations)

Asbestos and Mesothelioma:  they have demonstrated that p53 can be involved in development of mesothelioma as reactivating p53 may be a suitable strategy for therapy

Diet, Tomato and Cancer

  • looked at tomato extract on p53 function in gastric cancer: tomato extract had a growth reduction effect and altered cell cycle regulation and results in apoptosis
  • RBL2 levels are increased in extract amount dependent manner so data shows effect of certain tomato extracts of the southern italian tomato (     )

Antonio Giordano: we tested whole extracts of almost 30 different varieties of tomato.  The tomato variety  with highest activity was near Ravela however black tomatoes have shown high antitumor activity.  We have done a followup studies showing that these varieties, if grow elsewhere lose their antitumor activity after two or three generations of breeding, even though there genetics are similar.  We are also studying the effects of different styles of cooking of these tomatoes and if it reduces antitumor effect

please see post https://news.temple.edu/news/2017-08-28/muse-cancer-fighting-tomatoes-study-italian-food

 

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BIO 2018! June 4-7, 2018 at Boston Convention & Exhibition Center

LIVE 2018 The 21st Gabay Award to LORENZ STUDER, Memorial Sloan Kettering Cancer Center, contributions in stem cell biology and patient-specific, cell-based therapy

HUBweek 2018, October 8-14, 2018, Greater Boston – “We The Future” – coming together, of breaking down barriers, of convening across disciplinary lines to shape our future

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  1. Lungs can supply blood stem cells and also produce platelets: Lungs, known primarily for breathing, play a previously unrecognized role in blood production, with more than half of the platelets in a mouse’s circulation produced there. Furthermore, a previously unknown pool of blood stem cells has been identified that is capable of restoring blood production when bone marrow stem cells are depleted.

 

  1. A new drug for multiple sclerosis: A new multiple sclerosis (MS) drug, which grew out of the work of UCSF (University of California, San Francisco) neurologist was approved by the FDA. Ocrelizumab, the first drug to reflect current scientific understanding of MS, was approved to treat both relapsing-remitting MS and primary progressive MS.

 

  1. Marijuana legalized – research needed on therapeutic possibilities and negative effects: Recreational marijuana will be legal in California starting in January, and that has brought a renewed urgency to seek out more information on the drug’s health effects, both positive and negative. UCSF scientists recognize marijuana’s contradictory status: the drug has proven therapeutic uses, but it can also lead to tremendous public health problems.

 

  1. Source of autism discovered: In a finding that could help unlock the fundamental mysteries about how events early in brain development lead to autism, researchers traced how distinct sets of genetic defects in a single neuronal protein can lead to either epilepsy in infancy or to autism spectrum disorders in predictable ways.

 

  1. Protein found in diet responsible for inflammation in brain: Ketogenic diets, characterized by extreme low-carbohydrate, high-fat regimens are known to benefit people with epilepsy and other neurological illnesses by lowering inflammation in the brain. UCSF researchers discovered the previously undiscovered mechanism by which a low-carbohydrate diet reduces inflammation in the brain. Importantly, the team identified a pivotal protein that links the diet to inflammatory genes, which, if blocked, could mirror the anti-inflammatory effects of ketogenic diets.

 

  1. Learning and memory failure due to brain injury is now restorable by drug: In a finding that holds promise for treating people with traumatic brain injury, an experimental drug, ISRIB (integrated stress response inhibitor), completely reversed severe learning and memory impairments caused by traumatic brain injury in mice. The groundbreaking finding revealed that the drug fully restored the ability to learn and remember in the brain-injured mice even when the animals were initially treated as long as a month after injury.

 

  1. Regulatory T cells induce stem cells for promoting hair growth: In a finding that could impact baldness, researchers found that regulatory T cells, a type of immune cell generally associated with controlling inflammation, directly trigger stem cells in the skin to promote healthy hair growth. An experiment with mice revealed that without these immune cells as partners, stem cells cannot regenerate hair follicles, leading to baldness.

 

  1. More intake of good fat is also bad: Liberal consumption of good fat (monounsaturated fat) – found in olive oil and avocados – may lead to fatty liver disease, a risk factor for metabolic disorders like type 2 diabetes and hypertension. Eating the fat in combination with high starch content was found to cause the most severe fatty liver disease in mice.

 

  1. Chemical toxicity in almost every daily use products: Unregulated chemicals are increasingly prevalent in products people use every day, and that rise matches a concurrent rise in health conditions like cancers and childhood diseases, Thus, researcher in UCSF is working to understand the environment’s role – including exposure to chemicals – in health conditions.

 

  1. Cytomegalovirus found as common factor for diabetes and heart disease in young women: Cytomegalovirus is associated with risk factors for type 2 diabetes and heart disease in women younger than 50. Women of normal weight who were infected with the typically asymptomatic cytomegalovirus, or CMV, were more likely to have metabolic syndrome. Surprisingly, the reverse was found in those with extreme obesity.

 

References:

 

https://www.ucsf.edu/news/2017/12/409241/most-popular-science-stories-2017

 

https://www.ucsf.edu/news/2017/03/406111/surprising-new-role-lungs-making-blood

 

https://www.ucsf.edu/news/2017/03/406296/new-multiple-sclerosis-drug-ocrelizumab-could-halt-disease

 

https://www.ucsf.edu/news/2017/06/407351/dazed-and-confused-marijuana-legalization-raises-need-more-research

 

https://www.ucsf.edu/news/2017/01/405631/autism-researchers-discover-genetic-rosetta-stone

 

https://www.ucsf.edu/news/2017/09/408366/how-ketogenic-diets-curb-inflammation-brain

 

https://www.ucsf.edu/news/2017/07/407656/drug-reverses-memory-failure-caused-traumatic-brain-injury

 

https://www.ucsf.edu/news/2017/05/407121/new-hair-growth-mechanism-discovered

 

https://www.ucsf.edu/news/2017/06/407536/go-easy-avocado-toast-good-fat-can-still-be-bad-you-research-shows

 

https://www.ucsf.edu/news/2017/06/407416/toxic-exposure-chemicals-are-our-water-food-air-and-furniture

 

https://www.ucsf.edu/news/2017/02/405871/common-virus-tied-diabetes-heart-disease-women-under-50

 

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New Diabetes Treatment Using Smart Artificial Beta Cells

Reporter: Irina Robu, PhD

Researchers from University of North Carolina and North Carolina State University developed a patient friendly option that treats type 1 diabetes and in some cases type two diabetes by using “artificial beta cells, AβCs” to release insulin automatically into the bloodstream when glucose levels rise. These artificial beta cells mimic functions of the body’s natural glucose controllers, the insulin secreting beta cells of the pancreas. The AβCs could be subcutaneously implanted into patients, which would be replaced every few days or by a disposable skin patch. According to the principal investigator, Zhen Gu, PhD at joint UNC/NC State Department of Biomedical Engineering, they plan to optimize the procedure to develop a skin patch delivery system and test diabetes in patients.
Currently, the major problem with the insulin diabetes treatment is that they can’t be delivered efficiently in a pill and the only option is either by injection or a mechanical pump. Delivering the insulin treatments via transplants of pancreatic cells can solve that problem in some cases. Nevertheless, such cell transplants are expensive, require donor cells that are in short supply, require immune-suppressing drugs and fail due to the destruction of the transplanted cells.
Gu’s AβCs are built with a basic version of a normal cell’s two-layered lipid membrane and show a rapid receptiveness to excess glucose levels in lab dish test and diabetic mice without beta cells. The key novelty is what these cells contain insulin-stuffed vesicles. An increase in blood glucose levels leads to chemical changes in the vesicle coating, producing the vesicles to start fusing with the AβC’s outer membrane thus releasing the insulin.

SOURCE

https://news.unchealthcare.org/news/2017/october/smart-artificial-beta-cells-could-lead-to-new-diabetes-treatment

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City of Hope, Duarte, California – Combining Science with Soul to Create Miracles at a Comprehensive Cancer Center designated by the National Cancer InstituteAn Interview with the Provost and Chief Scientific Officer of City of Hope, Steven T. Rosen, M.D.

Author: Gail S. Thornton, M.A.

Co-Editor: The VOICES of Patients, Hospital CEOs, HealthCare Providers, Caregivers and Families: Personal Experience with Critical Care and Invasive Medical Procedures

 

City of Hope (https://www.cityofhope.org/homepage), a world leader in the research and treatment of cancer, diabetes, and other serious diseases, is an independent, biomedical research institution and comprehensive cancer center committed to researching, treating and preventing cancer, with an equal commitment to curing and preventing diabetes and other life-threatening diseases. Founded in 1913, City of Hope is one of only 47 comprehensive cancer centers in the nation, as designated by the National Cancer Institute.

City of Hope possesses flexibility that larger institutions typically lack. Innovative concepts move quickly from the laboratory to patient trials — and then to market, where they benefit patients around the world.

As a founding member of the National Comprehensive Cancer Network, their research and treatment protocols advance care throughout the nation. They are also part of ORIEN (Oncology Research Information Exchange Network), the world’s largest cancer research collaboration devoted to precision medicine. And they continue to receive the highest level of accreditation by the American College of Surgeons Commission on Cancer for their exceptional level of cancer care.

As an innovator, City of Hope is a pioneer in bone marrow and stem cell transplants with one of the largest and most successful of its kind in the world. Other examples of its leadership and innovation include,

  • Numerous breakthrough cancer drugs, including Herceptin, Rituxan, Erbitux, and Avastin, are based on technology pioneered by City of Hope and are saving lives worldwide.
  • To date, City of Hope surgeons have performed more than 10,000 robotic procedures for prostate, kidney, colon, liver, bladder, gynecologic, oral and other cancers.
  • They are a national leader in islet cell transplantation, which has the potential to reverse type 1 diabetes, and also provide islet cells for research at other institutions throughout the U.S.
  • Millions of people with diabetes benefit from synthetic human insulin, developed through research conducted at City of Hope.
  • Their scientists are pioneering the application of blood stem cell transplants to treat patients with HIV- and AIDS related lymphoma. Using a new form of gene therapy, their researchers achieved the first long-term persistence of anti-HIV genes in patients with AIDS-related lymphoma — a treatment that may ultimately cure lymphoma and HIV/AIDS.

 

Additionally, City of Hope has three on-campus manufacturing facilities producing biologic and chemical compounds to good manufacturing practice (GMP) standards.

City of Hope launched its Alpha Clinic, thanks to an $8 million, five-year grant from the California Institute for Regenerative Medicine (CIRM). The award is part of CIRM’s Alpha Stem Cell Clinics program, which aims to create one-stop centers for clinical trials focused on stem cell treatments for currently incurable diseases. The Alpha Clinics Network is already running 35 different clinical trials involving hundreds of patients, 17 of which are being conducted at City of Hope. Current clinical trials include transplants of blood stem cells modified to treat patients with AIDS and lymphoma, neural stem cells to deliver drugs directly to cancers hiding in the brain, and T cell immunotherapy trials.

Located just northeast of Los Angeles, landscaped gardens and open spaces surround City of Hope’s leading-edge medical and research facilities at its main campus in Duarte, California. City of Hope also has 14 community practice clinics throughout Southern California.

COH robotic (1)COH Helford H (1)COH1 Dr__Rosen_Clinic-2 (2)COH8 Janice_Huss-7COH7 COH_1369COH6 GMP_0454COH4 DSC_9279

Image SOURCE: Photographs courtesy of City of Hope, Duarte, California. Interior and exterior photos of the City of Hope, including Dr. Steven T. Rosen and his team.

 

Below is my interview with the Provost and Chief Scientific Officer of City of Hope, Steven T. Rosen, M.D., which occurred in April, 2017.

 

What sets City of Hope apart from other hospitals and research centers?

Dr. Rosen: City of Hope offers a unique blend of compassionate care and research innovation that simply can’t be found anywhere else.

We’re more than a medical center, and more than a research facility. We take the most compassionate patient-focused care available, combine it with today’s leading-edge medical advances, and infuse both with a quest to deliver better outcomes.

I’m proud to say that we’re known for rapidly translating scientific research into new treatments and cures, and that our technology has led to the development of four of the most widely used cancer-fighting drugs, Herceptin (trastuzumab), Avastin (bevacizumab), Erbitux (cetuximab), and Rituxin (rituximab).

City of Hope is a family. Our special team of experts treats the whole person and the family, not just a body, or a case or a disease. In fact, some of our patients have shared their stories of success. It is gratifying for me and our many health professionals to be able to make a positive difference in their lives.

Eleven years ago, Los Angeles firefighter Gus Perez was facing a battle far greater than any he’d ever known. He was diagnosed with CML (chronic myelogenous leukemia). Gus began receiving the drug Gleevec, which put him into remission. Given the drug’s success, he almost resigned himself to staying on it, yet was drawn to another option: undergoing a bone marrow transplant at City of Hope. “I went to my favorite ocean spot,” Gus recalls. “I put on my wetsuit, like I’ve done thousands of times, and paddled out. Every wave was special because I wasn’t sure if I was ever going to be back. And I remember getting out of the water and counting the steps to my car, thinking, ‘I’m going to beat this. I’m going to retrace those steps.’ And I’m happy to say I was able to do it.” Gus and his family recently celebrated the 10th anniversary of his bone marrow transplant. “City of Hope is more than just medical treatment,” Gus says. “They have to put you back together from the ground up. And to me, that’s truly a miracle.”

 

As an active 14-year-old, Nicole Schulz loved cheerleading and hanging out with her friends. Then her whole world changed. Nicole learned that her fatigue and other symptoms weren’t “just the flu,” but the effects of acute myelogenous leukemia (AML), an aggressive disease that rendered her bone marrow 97 percent cancerous. Nicole spent the next three and a half months at City of Hope, fighting the cancer with a daily regimen of chemotherapy and blood and platelet transfusions. “It put me into remission,” Nicole says. “But I wasn’t cured. And I wanted a cure.” Fortunately, Nicole was a candidate for a bone marrow transplant. Her malfunctioning marrow cells would be replaced with healthy marrow from a matching unrelated donor. “I never gave up — and neither did City of Hope,” Nicole says. After two bone marrow transplants and tremendous perseverance, Nicole is back to living the life she once knew and quickly making up for lost time.

 

When Jim Murphy’s doctor called and asked to see him on Christmas Eve, Jim knew it wasn’t going to be good news. And he was right. “The diagnosis was esophageal cancer,” Jim says. “Once they tell you that, there’s nothing you can do but formulate your action plan.” Jim would need to undergo chemotherapy, radiation and surgery to remove the tumor from his esophagus. It would require taking two-thirds of his esophagus and a third of his stomach. Despite the intense treatment, Jim was determined to keep his life as normal as possible. Throughout his chemotherapy and radiation therapy, he never missed a day of work, even riding his mountain bike to and from City of Hope to take his treatments. “I needed to show myself one victory after another,” Jim says. “I know City of Hope appreciated the fact that I was fighting as hard as they were.” Now cancer-free for several years, Jim credits City of Hope with giving him the best chance to fight his disease. “What really impressed me was that the research was right there at City of Hope. If they have something experimental, it goes from the researcher, right to the doctor and right to you. It’s the ultimate weapon — doctors reaching out for researchers, researchers reaching out for doctors. And the patient wins.”

 

City of Hope is a pioneer in the fields of bone marrow transplantation, diabetes and breakthrough cancer drugs based on technology developed at the institution.  How are you transforming the future of health care by turning science into a practical benefit for patients? 

Dr. Rosen: This is a distinctive place where brilliant research moves rapidly from concept to cure. That’s what we do—we speed breakthroughs in the lab to benefit patients in the clinic

Many know us for our leadership in fighting cancer, but fighting cancer is only part of our story. For decades, we’ve been making history in the fight against diabetes and other life-threatening illnesses that can be just as dangerous, and shattering, to patients and their families.

Every year, we conduct 400+ clinical trials, enrolling 6,000+ patients; hold 300+ patents and submit nearly 30 applications to the U.S. Food and Drug Administration (FDA) for investigational new drugs; and offer comprehensive assistance for patients and their families, including patient education, support groups, social resources, mind-body therapies and patient navigators.

We also translate breakthrough laboratory findings into real, lifesaving treatments and cures, and manufacture them at three on-campus facilities. Our goal is to get patients the treatments they need as fast as humanly possible.

We are in the race to save lives – and win. In our research efforts, we are teaching immune cells to attack tumors and Don J. Diamond [Ph.D.], Vincent Chung, [M.D.], and other City of Hope researchers launched a clinical trial seeking ways to effectively activate a patient’s own immune system to fight his or her cancer. The team is combining an immune-boosting vaccine with a drug that inhibits tumor cells’ ability to grow — to encourage immune cells to attack and eliminate tumors such as non-small cell lung cancer, melanoma, triple-negative breast cancer, renal cell carcinoma and many other cancer types.

City of Hope’s Diabetes & Metabolism Research Institute is committed to developing a cure for type 1 diabetes (T1D) within six years, fueled by a $50 million funding program led by the Wanek family. Research is already underway to unlock the immune system’s role in diabetes, including T cell modulation and stem cell-based therapies that may reverse the autoimmune attack on islet cells in the pancreas, which is the cause of T1D. City of Hope’s Bart Roep [Ph.D.], previously worked at Leiden University Medical Center in the Netherlands, where he was instrumental in launching a phase 1 clinical trial for a vaccine that aims to spur the immune system to fight, and possibly cure, T1D. Plans are developing for a larger, phase 2 trial to launch in the future at City of Hope.

 

What makes your recent alliance with Translational Genomics Research Institute (TGen) different from other efforts in precision medicine around the country and within our Government to identify treatments for cancer?

Dr. Rosen: Precision medicine is the future of cancer care. Since former Vice President’s Joe Biden’s Moonshot Cancer program was launched to achieve 10 years of progress in preventing, diagnosing and treating cancer, within five years, federal cancer funding has been prioritized to address these aims.

City of Hope and the Translational Genomics Research Institute (TGen) have formed an alliance to fast-track the future of precision medicine for patients. Our clinical leadership as a comprehensive cancer center combined with TGen’s leadership in molecular cancer research will propel us to the forefront of precision medicine and is further evidence of our momentum in transforming the future of health.

In fact, most recently scientists at TGen have identified a potent compound in the fight for an improved treatment against glioblastoma multiforme (GBM), the most common and deadly type of adult brain cancer. This research could represent a breakthrough for us to find an effective long-term treatment. The compound prevents glioblastoma from spreading, and leaves cancer vulnerable to chemotherapy and radiation.  Aurintricarboxylic Acid (ATA) is a chemical compound that in laboratory tests was shown to block the chemical cascade that otherwise allows glioblastoma cells to invade normal brain tissue and resist both chemo and radiation therapy.

The goal is to accelerate the speed at which we advance research discoveries into the clinic to benefit patients worldwide.

 

As a prestigious Comprehensive Cancer Center, City of Hope was named this year as one of the top 20 cancer centers for the past 10 years. How do you achieve that designation year after year? And what specific collaborations, clinical trials and multidisciplinary research programs are under way that offer benefits to patients?

Dr. Rosen: It’s simple – we achieve this through the compassion, commitment and excellence of the City of Hope family, which includes our world-class physicians, staff, supporters and donors.

We look to find the best and brightest professionals and bring them to City of Hope to work with our amazing staff on research, treatments and cures that not only change people’s lives, but also change the world.

We also have a community of forward-looking, incredibly generous and deeply committed supporters and donors. People who get it. People who share our vision. People who take their capacity for business success and apply it to helping others. They provide the fuel that drives us forward, enabling us to do great things.

City of Hope has a long track record of research breakthroughs and is constantly working to turn novel scientific research into the most advanced medical services.

Right now, we have a number of collaborative programs underway, including: Our alliance with TGen to make precision medicine a reality for patients, The Wanek Family Project to Cure Type 1 Diabetes, and Immunotherapy and CAR-T cell therapy clinical trials, which aim to fight against brain tumors and blood cancers.

More specifically, our research team led by Hua Yu, [Ph.D.] and Andreas Herrmann, [Ph.D.], developed a drug to address the way in which cancer uses the STAT3 protein to “corrupt” the immune system. The drug, CpG-STAT3 siRNA, halts the protein’s ability to “talk” to the immune system. It blocks cancer cell growth while sending a message to surrounding immune cells to destroy a tumor, and it may also enhance the effectiveness of other immunotherapies, such as T-cell therapy.

We could also see a functional cure for HIV in the next 5 to 10 years. Gene therapy pioneer, John A. Zaia, [M.D.], the Aaron D. Miller and Edith Miller Chair in Gene Therapy, the director of the Center for Gene Therapy within City of Hope’s Hematologic Malignancies and Stem Cell Transplantation Institute, as well as principal director of our Alpha Clinic, and researchers are building on knowledge gained from the case of the so-called “Berlin patient” whose HIV infection vanished after receiving a stem cell transplant for treatment of leukemia. The donor’s CCR5 gene, HIV’s typical pathway into the body, had a mutation that blocked the virus. The team launched a clinical trial that used a zinc finger nuclease to “cut out” the CCR5 gene, leaving HIV with no place to go. Their goal: to someday deliver a one-time treatment that produces a lifetime change. Integral to the first-in-human trials are the nurses who understand the study protocols, potential side effects and symptoms.

 

Would you share some of the current science under way on breakthrough cures for cancer?

Dr. Rosen: We are achieving promising results in many innovative approaches – gene therapy, targeted therapy, immunotherapy and all aspects of precision medicine. We are also forging new partnerships and collaboration agreements around the world.

Let me share with you a few examples of our cutting-edge science.

City of Hope researchers identified a promising new strategy for dealing with PDAC, an aggressive form of pancreatic cancer. The bacterial-based therapy homes to tumors and provokes an extremely effective tumor-killing response.

Teams at City of Hope are working to load nanoparticles with small snippets of DNA molecules that can stimulate the immune system to attack tumor cells in the brain. This innovative approach can overcome the blood-brain barrier, which blocks many drugs from reaching the tumor site.

A pioneer in islet cell transplantation for the treatment of diabetes, City of Hope conducted a clinical trial to refine its transplantation protocol. Because this new protocol includes an ATG (antithymoglobulin) induction, the immune system will not harm the transplant. The immune-suppression strategy used in the trial is considered a significant improvement over the protocol used in previous islet cell transplant trials.

City of Hope physicians and scientists joined a multinational team in reporting the success of a phase II clinical trial of a novel drug against essential thrombocythemia (ET). ET patients make too many platelets (cells essential for blood clotting), which puts them at risk for abnormal clotting and bleeding. All 18 patients treated with the drug, imetelstat, exhibited decreased platelet levels, and 16 showed normalized blood cell counts.

Researchers found that the CMVPepVax vaccine — developed at City of Hope to boost cellular immunity against cytomegalovirus (CMV) — is safe and effective in stem cell transplant recipients. Building on this discovery, City of Hope and Fortress Biotech formed a company to develop two vaccines, PepVax and Triplex, against CMV, a life-threatening illness in people who have weakened or underdeveloped immune systems such as cancer patients and developing fetuses. The vaccines are the subjects of multisite clinical trials. These City of Hope vaccines could open the door to a new way of protecting cancer patients from CMV, a devastating infection that affects hundreds of thousands of people worldwide.

 

In what ways does the initial vision of Samuel H. Golter impact the work you are doing today? What does the tagline – “The Miracle of Science with Soul” – mean?

Dr. Rosen: 100+ years ago, Samuel Golter, one of the founders of City of Hope said: “There is no profit in curing the body if in the process we destroy the soul.” For decades, City of Hope has lived by this credo, providing a comprehensive, compassionate and research-based treatment approach.

“The Miracle of Science with Soul” refers to the lives that we save by uniting science and research with compassionate care.

“Miracle” represents what people with cancer and other deadly diseases say they want most of all.

“Science” speaks to the many innovations we’ve pioneered, which demonstrate that medical miracles happen here.

“Soul” represents our compassionate care. We’re an untraditional health system — and our people, culture and campus reflect this.

 

Can you please describe how City of Hope has evolved throughout its 100-year history from a tuberculosis sanitorium into a world-class research-centered institution? 

Dr. Rosen: City of Hope is a leading comprehensive cancer center and independent biomedical research institution. Over the years, our discoveries have changed the lives of millions of patients around the world.

We pioneered the research leading to the first synthetic insulin and the technology behind numerous cancer-fighting drugs, including Herceptin (trastuzumab), Avasatin (bevacizumab), Erbitux (cetuximab), and Rituxin (rituximab).

As previously mentioned, we hold 300+ patents, have numerous potential therapies in the pipeline at any given time, and treat 1,000+ patients a year in therapeutic clinical trials.

These numbers reflect our commitment to innovation and rapid translation of science into therapies to benefit patients.

We are home to Beckman Research Institute of City of Hope, the first of only five Beckman Research Institutes established by funding from the Arnold and Mabel Beckman Foundation. It is responsible for fundamentally expanding the world’s understanding of how biology affects diseases such as cancer, HIV/AIDS and diabetes.

Recognizing our team’s accomplishments in cancer research, treatment, patient care, education and prevention, the National Cancer Institute has designated City of Hope as a comprehensive cancer center. This is an honor reserved for only 47 institutions nationwide. Our five Cancer Center Research Programs run the gamut from basic and translational studies, to Phase I and II clinical protocols and follow-up studies in survivorship and symptom management.

City of Hope’s Diabetes & Metabolism Research Institute offers a broad diabetes and endocrinology program combining groundbreaking research, unique treatments and comprehensive education to help people with diabetes and other endocrine diseases live longer, better lives.

Our dedicated, multidisciplinary team of healthcare professionals at the Hematologic Malignancies & Stem Cell Institute combine innovative research discoveries with superior clinical treatments to improve outcomes for patients with hematologic cancers.

Working closely with the City of Hope comprehensive cancer center’s Developmental Cancer Therapeutics Program and other cancer centers, the Medical Oncology & Therapeutics Research multidisciplinary program includes basic, translational and clinical research and fosters collaborations among scientists and clinicians.

City of Hope’s Radiation Oncology Department is on the forefront of improving patient care, and our staff is constantly studying new research technologies, clinical trials and treatment methods that can lead to better outcomes and quality of life for our patients.

What attracted you to City of Hope? And how do you define success in your present role as provost and CSO?

Dr. Rosen: Helping cancer patients and their families gives me a sense of purpose. I encourage everyone to find a passion and find an organization that fits their passion. City of Hope is a special place. What we do is bigger than ourselves.

I define success as finding cures and helping patients live stronger, better lives. I am focused on leading a diverse team of scientists, clinicians and administrative leaders committed to discovering breakthroughs and specialized therapies.

COH2 Dr__Steve_Rosen_

Image SOURCE: Photograph of Provost and Chief Scientific Officer Steven T. Rosen, M.D., courtesy of City of Hope, Duarte, California.

 

Steven T. Rosen, M.D.
Provost and Chief Scientific Officer

City of Hope
Duarte, California

Steven T. Rosen, M.D., is provost and chief scientific officer for City of Hope and a member of City of Hope’s Executive Team. He also is director of the Comprehensive Cancer Center and holds the Irell & Manella Cancer Center Director’s Distinguished Chair, and he is director of Beckman Research Institute (BRI) and the Irell & Manella Graduate School of Biological Sciences.

Dr. Rosen sets the scientific direction of City of Hope, shaping the research and educational vision for the biomedical research, treatment and education institution. Working closely and collaboratively with City of Hope’s scientists, clinicians and administrative leaders, he develops strategies that contribute to the organization’s mission.

As director of BRI, he works with faculty across the institution to help shape and direct the scientific vision for BRI while leading the vital basic and translational research that is fundamental to our strategic plan and mission. He focuses on opportunities for expanding and integrating our research initiatives; recruiting and leading talented scientists; helping our talented researchers achieve national and international recognition; and promoting our national standing as a premier scientific organization.

Prior to joining City of Hope, Dr. Rosen was the Genevieve Teuton Professor of Medicine at the Feinberg School of Medicine at Northwestern University in Chicago. He served for 24 years as director of Northwestern’s Robert H. Lurie Comprehensive Cancer Center. Under his leadership, the center received continuous National Cancer Institute (NCI) funding beginning in 1993 and built nationally recognized programs in laboratory sciences, clinical investigations, translational research and cancer prevention and control. The center attained comprehensive status in 1997.

Dr. Rosen has published more than 400 original reports, editorials, books and book chapters. His research has been funded by the National Cancer Institute, American Cancer Society, Leukemia & Lymphoma Society of America and Multiple Myeloma Research Foundation.

Dr. Rosen also has served as an adviser for several of these organizations and on the external advisory boards of more than a dozen NCI-designated Comprehensive Cancer Centers. He is the current editor-in-chief of the textbook series “Cancer Treatment & Research.”

Recognized as one of the Best Doctors in America, Dr. Rosen is a recipient of the Martin Luther King Humanitarian Award from Northwestern Memorial Hospital and the Man of Distinction Award from the Israel Cancer Research Fund. He earned his bachelor’s degree and medical degree with distinction from Northwestern University from which he also earned the Alumni Merit Award, and is a member of the Alpha Omega Alpha Honor Society.

Editor’s Note: 

We would like to thank Mary-Fran Faraji, David Caouette, and Chantal Roshetar of the Communications and Public Affairs department at the City of Hope, for the gracious help and invaluable support they provided during this interview.

 

REFERENCE/SOURCE

The City of Hope (https://www.cityofhope.org/homepage), Duarte, California.

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Merck Might End DPP-4 Drug Development Program Due to Serious Adverse Events

Stephen J. Williams, PhD.: Reporter/Curator

As Reported From FiercePharma

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Breakthrough Research on Encapsulated pancreatic cells offer possible new diabetes treatment.

Reporter: Eveline B. Cohn, PhD

No more insulin injections?

Encapsulated pancreatic cells offer possible new diabetes treatment.

It is known that in patients with Type 1 diabetes the immune system attacks the pancreas, and the monitoring of blood sugar becomes really difficult. Lately the research showed a possibility of replacing the pancreatic islets cells with healthy cells to take over glucose monitoring and insulin release. However the immune system attacked the transplanted cells, patients being obliged to take immunosuppressant drugs for the rest of their life.
Now , a new advance in this type of research by Boston Children’s Hospital designed a material that was used to encapsulate human islet before transplanted them. In animal testing it was showed that the encapsulated human cells could cure diabetes for up to six months without provoking an immune response.
This approach “has the potential to provide diabetics with a new pancreas that is protected from the immune system, which allow them to control their blood sugar without taking drugs. That’s the dream” says Daniel Anderson, The Samuel A Goldblith Associate Professor in MIT’s Department of Chemical Engineering, A member of MIT’s Koch Institute for integrative Cancer research and Institute for Medical Engineering and Science (IMES), and a research fellow in the department of Anesthesiology at Boston Children’s Hospital
The JDRF director Julia Greenstein, Anderson, Langer and colleagues explored a chemical derivative originally isolated from brown algae to encapsulate the cells without harming them, allowing sugar and proteins to go through, thus permitted to test the glucose level after transplantation of the encapsulated cells. The research was published in Nature Medicine and Nature Biotechnology. Researchers from Harvard University, University of Illinois at Chicago and Joslin Diabetes Center and University of Massachusetts Medical school also contributed to this research.
Previous research has shown that when alginate capsules are implanted in primates and humans, scar tissue builds up around the capsules, making the device ineffective. MIT/Children Hospital try to modify alginate make it less likely to provoke this kind of immune response.

A stealth material surface, shown here, has been engineered to provide an “invisibility cloak” against the body’s immune system cells. In this electron microscopy image, you can see the material's surface topography.

With The Courtesy of The Researchers

“We decided to take an approach where you cast a very wide net and see what you can catch,” says Arturo Vegas, a former MIT and Boston Children’s Hospital postdoc who is now an assistant professor at Boston University. Vegas is the first author of the Nature Biotechnology paper and co-first author of the Nature Medicine paper. “We made all these derivatives of alginate by attaching different small molecules to the polymer chain, in hopes that these small molecule modifications would somehow give it the ability to prevent recognition by the immune system.”
800 alginate derivatives were screened . Further, the known triazole thiomorpholine dioxide (TMTD) have been chosen to be tested in diabetic mice. They chose a strain of mice with a strong immune system and implanted human islet cells encapsulated in TMTD into a region of the abdominal cavity known as the intraperitoneal space.
The pancreatic islet cells used in this study were generated from human stem cells using a technique recently developed by Douglas Melton, a professor at Harvard University who is an author of the Nature Medicine paper.
Following implantation, the cells immediately began producing insulin in response to blood sugar levels and were able to keep blood sugar under control for the length of the study, 174 days.
“The really exciting part of this was being able to show, in an immune-competent mouse, that when encapsulated these cells do survive for a long period of time, at least six months,” says Omid Veiseh, a senior postdoc at the Koch Institute and Boston Children’s hospital, co-first author of the Nature Medicine paper, and an author of the Nature Biotechnology paper. “The cells can sense glucose and secrete insulin in a controlled manner, alleviating the mice’s need for injected insulin.”
The researchers also found that 1.5-millimeter diameter capsules made from their best materials (but not carrying islet cells) could be implanted into the intraperitoneal space of nonhuman primates for at least six months without scar tissue building up.
“The combined results from these two papers suggests that these capsules have real potential to protect transplanted cells in human patients,” says Robert Langer, the David H. Koch Institute Professor at MIT, a senior research associate at Boston’s Children Hospital, and co-author on both papers. “We are so pleased to see this research in cell transplantation reach these important milestones.”
Cherie Stabler, an associate professor of biomedical engineering at the University of Florida, says this approach is impressive because it tackles all aspects of the problem of islet cell delivery, including finding a source of cells, preventing an immune response, and developing a suitable delivery material.
“It’s such a complex, multipronged problem that it’s important to get people from different disciplines to address it,” says Stabler, who was not involved in the research. “This is a great first step towards a clinically relevant, cell-based therapy for Type I diabetes.”

VIEW VIDEO

VIDEO SOURCE

https://www.youtube.com/watch?v=cw3EbB8DAq8

At this point the researchers are thinking of using their new material in non human primates and eventually performing clinical trials in diabetic patients. “Our goal is to continue to work hard to translate these promising results into a therapy that can help people,” Anderson says.
“Being insulin-independent is the goal,” Vegas says. “This would be a state-of-the-art way of doing that, better than any other technology could. Cells are able to detect glucose and release insulin far better than any piece of technology we’ve been able to develop.”
In their research they found out that the new material works best with molecules containing triazole group- a ring containing two atoms of Carbon and three of N. However, they suspect that in this particular case it may interfere with the immune system’s ability to recognize the material as foreign.

The work was supported, in part, by the JDRF, the Leona M. and Harry B. Helmsley Charitable Trust, the National Institutes of Health, and the Tayebati Family Foundation.
Other authors of the papers include MIT postdoc Joshua Doloff; former MIT postdocs Minglin Ma and Kaitlin Bratlie; MIT graduate students Hok Hei Tam and Andrew Bader; Jeffrey Millman, an associate professor at Washington University School of Medicine; Mads Gürtler, a former Harvard graduate student; Matt Bochenek, a graduate student at the University of Illinois at Chicago; Dale Greiner, a professor of medicine at the University of Massachusetts Medical School; Jose Oberholzer, an associate professor at the University of Illinois at Chicago; and Gordon Weir, a professor of medicine at the Joslin Diabetes Center.

SOURCE

http://news.mit.edu/2016/pancreatic-cells-diabetes-treatment-insulin-injections-0125?elq=6d9b90a822f04183bd0b059d36eb2b7a&elqCampaignId=9&elqaid=14548&elqat=1&elqTrackId=d91b7d01a9d14b199e41b4deb2c10ac6

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Reinforced disordered cell expression

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Diabetes, Alzheimer’s Share Molecular Pathways, Part of Same Vicious Cycle

http://www.genengnews.com/gen-news-highlights/diabetes-alzheimer-s-share-molecular-pathways-part-of-same-vicious-cycle/81252206/

http://www.genengnews.com/Media/images/GENHighlight/thumb_Jan8_2016_Fotolia_30836005_JigsawPuzzleBrainAndHead1904910113.jpg

A molecular-level link has been found that helps explain the poorly understood association between diabetes and Alzheimer’s disease. Both disorders can drive and be driven by the same pathological process, the disruption of a particular kind of post-translational modification called S-nitrosylation. Thus, the disorders can reinforce each other. [© freshidea/Fotolia]

 

Though they appear to be distinct, diabetes and Alzheimer’s disease have much in common at the molecular level. In fact, recent findings indicate that either disease can worsen the other by disrupting the same chemical process—S-nitrosylation, a form of post-translational modification that is necessary for the proper functioning of multiple enzymes.

S-nitrosylation, it turns out, can be disrupted by excess sugar or β-amyloid protein, either of which can wreak havoc by increasing the levels of nitric oxide and other free radical species. Once S-nitrosylation is disturbed and poorly functioning enzymes are produced, the downstream effects include abnormal increases in both insulin and β-amyloid protein.

Thus, diabetes and Alzheimer’s can drive, and be driven by, the same vicious cycle. Furthermore, either can contribute to the other’s progress. These results emerged from a study completed by researchers based at the Sanford Burnham Prebys Medical Discovery Institute and the Scintillon Institute. The research team was led by Stuart A. Lipton, M.D., Ph.D., a physician-scientist affiliated with both institutions.

“This work points to a new common pathway to attack both type 2 diabetes, along with its harbinger, metabolic syndrome, and Alzheimer’s disease,” stated Dr. Lipton.

The researchers published their work January 8 in the journal Nature Communications in an article entitled, “Elevated glucose and oligomeric β-amyloid disrupt synapses via a common pathway of aberrant protein S-nitrosylation.” This article describes how the scientists used a so-called “disease-in-a-dish” model to discover molecular pathways that are in common in both diabetes and Alzheimer’s.

Specifically, the scientists genetically reprogrammed the skin of human patients to make induced pluripotent stem cells, which were then used to derive nerve cells. They also used mouse models of each disease to analyze the combined effects of high blood sugar and β-amyloid protein in living animals.

“[We] report in human and rodent tissues that elevated glucose, as found in [metabolic syndrome and type 2 diabetes] and oligomeric β-amyloid (Aβ) peptide, thought to be a key mediator of [Alzheimer’s disease], coordinately increase neuronal Ca2+ and nitric oxide (NO) in an NMDA receptor-dependent manner,” wrote the authors of the Nature Communications article. “The increase in NO results in S-nitrosylation of insulin-degrading enzyme (IDE) and dynamin-related protein 1 (Drp1), thus inhibiting insulin and Aβ catabolism as well as hyperactivating mitochondrial fission machinery.”

The scientists also found that the changes in enzyme activity led to damage of synapses, the region where nerve cells communicate with one another in the brain. The combination of high sugar and β-amyloid protein caused the greatest loss of synapses. Since loss of synapses correlates with cognitive decline in Alzheimer’s, high sugar and β-amyloid coordinately contribute to memory loss.

“The NMDA receptor antagonist memantine attenuates these effects,” the authors continued. “Our studies show that redox-mediated posttranslational modification of brain proteins link Aβ and hyperglyaemia to cognitive dysfunction in [metabolic syndrome/type 2 diabetes] and [Alzheimer’s disease].”

“[Our work] means that we now know these diseases are related on a molecular basis, and hence, they can be treated with new drugs on a common basis,” stated Dr. Ambasudhan, a senior author of the study and an assistant professor at Scintillon.

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