Cells govern their internal processes through highly complex signaling systems. A recent City of Hope study published in the journal Science Signaling shed more light on how cells control this system — and how diabetes can cause a malfunction that leads to kidney disease.
The study’s senior author, Rama Natarajan, Ph.D., director of the Division of Molecular Diabetes Research at City of Hope, explained the science published in their paper, “TGF-β Induces Acetylation of Chromatin and of Ets-1 to Alleviate Repression of miR-192 in Diabetic Nephropathy.”
What’s the main finding of this study?
MicroRNAs (miRNAs) are recently discovered small, noncoding RNAs that have been shown to affect the expression of genes and play pivotal roles in physiological and pathological processes. However, the mechanisms by which miRNAs are regulated are not fully understood. » Continue Reading
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The Islets of Langerhans may sound like an exclusive tropical retreat, but they’re closer to home than you might think. These isles are found in the pancreas and hold precious treasures for researchers bent on finding cures for diabetes.
Commonly referred to as islets, they’re clusters of cells in the pancreas, containing 1,000 to 3,000 cells each – resembling small islands in the pancreatic tissue. The average healthy, adult pancreas contains about 1 million islets, and they make up about 3 to 4 percent of the organ. As treatments for diabetes advance, these cells are becoming a focus of procedures lauded as potential keys to curing the disease.
The islets are named after Paul Langerhans, a German physician who discovered in them 1869. They include four major types of cells working together to regulate blood sugar, which is why they’re an important factor in diabetes.
The most plentiful are the insulin-producing beta cells and the glucagon-producing alpha cells. In diabetes, the immune system attacks the beta cells, destroying them. Diabetic patients cannot produce insulin, the hormone which lowers blood glucose levels. » Continue Reading
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Since 1995, more than 133,000 Californian teachers have contributed to one of the most powerful, ongoing epidemiological studies in cancer, appropriately named the California Teachers Study.
Using survey data and medical records of the participants, it has made numerous important discoveries linking cancer risk to lifestyle factors – including physical activity, alcohol consumption and using hormone replacement therapy.
Now, an effort funded by the National Cancer Institute (NCI) and spearheaded at City of Hope will take this study one level beyond surveys and health records – it will start collecting blood and saliva from its participants, with the goal of identifying biomarkers tied to cancer risk. This can hopefully lead to earlier detection, better treatments and perhaps even the prevention of certain cancers.
In the video above, James V. Lacey Jr., Ph.D., associate professor at City of Hope’s Division of Cancer Etiology, talks about the significance of the California Teachers Study and its next steps to collect biological samples. He is the principal investigator of a NCI-funded effort to collect more than 21,000 samples for analysis and evaluation. » Continue Reading
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A gene may play as large a role in the cause of obesity as the foods we eat, according to new research from City of Hope.
The study, published in the Journal of Biological Chemistry, found that a protein, called RLIP76, produced by a specific gene, plays a significant role in obesity. Mice lacking the protein were resistant to gaining weight on a high-fat diet and had reduced blood sugar, cholesterol and triglyceride levels. In fact, they gained 40 percent less weight than mice that produced the protein after 12 weeks on a high-fat diet.
Sanjay Awasthi, M.D., a professor of Division of Molecular Diabetes Research and of medical oncology at City of Hope, is one of the study’s lead authors. “The American Medical Association recently defined obesity as a disease, but it’s long been viewed as a syndrome with many contributing factors and no single gene we can pin down — until now. This is conclusive evidence that a single protein dramatically affects development of obesity.”
Of course, such observations are based on animal data, which may or may not apply to humans, but they are undeniably provocative.
With about two-thirds of the U.S. population weighing in as overweight or obese, obesity is one of the nation’s most serious health problems and a global epidemic affecting 300 million people worldwide. Pinpointing this gene’s potential role offers new insights into the mechanism behind obesity — and why it’s so tough to fight, said Sharad Singhal, Ph.D., a research professor in the Division of Diabetes, Endocrinology & Metabolism at City of Hope.
In addition to being thinner after the high-fat diet regimen, the mice without the protein had lower levels of cholesterol and insulin in their blood streams. » Continue Reading
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RNA interference, or RNAi, is a relatively young but important field of study in genetics research that is leading to new treatment options for cancer, diabetes, HIV/AIDS and other serious illnesses. City of Hope scientists recently published findings that may advance these efforts in the journal Nucleic Acids Research.
Study first author Nicholas Snead, Ph.D., a recent graduate of the Irell & Manella Graduate School of Biological Sciences at City of Hope, explains the significance of the study results that appear in the paper, titled “Molecular basis for improved gene silencing by Dicer substrate interfering RNA compared with other siRNA variants.”
What’s the main finding of this study?
The study revolves around a process in our cells called RNA interference, which is a way to suppress the level of any protein we want. We, as researchers, initiate RNAi by administering a small double-stranded RNA. Different researchers use different lengths and shapes of these small double-stranded RNA when initiating RNAi, with some researchers claiming that certain lengths and shapes work better than others. Most researchers, however, only look for the end-result of RNAi.
Our study focused on trying to understand some of the intermediate steps in the RNAi process with these differently shaped small double-stranded RNA. The main finding was that slightly longer and asymmetric double-stranded RNAs called Dicer substrate RNA (dsiRNA) — which were pioneered in Dr. [John] Rossi’s lab several years ago — perform better than the “classically” shaped double-stranded RNAs in early, intermediate and late stages of the RNAi pathway. » Continue Reading
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Arti Hurria, M.D., director of the Cancer and Aging Research Program at City of Hope, feels strongly that too little attention has been paid to the needs of older people with cancer. She’s working to change that.
She recently presented an overview of her work – and the context for it – at the annual meeting of the American Society of Clinical Oncology (ASCO), where she was honored as the 2013 recipient of the B.J. Kennedy Award for her contributions to the research, diagnosis and treatment of cancer in the elderly. Here, we offer the second in a five-part series on the most important aspects of Hurria’s work – and what doctors and others need to know about treatment of the elderly.
Part 2: We have a workforce shortage
The geriatric competence of the entire workforce needs to be reviewed, the researcher said, with additional skills developed through training.
The first step: Evaluate the expected shortage of geriatricians and health care professionals capable of meeting the needs of older adults. Although the number of elderly cancer patients is increasing, the number of geriatricians is expected to decline. The United States currently has 2,620 75-and-older patients per geriatrician with that ratio set to reach 3,798 patients per geriatrician in 2030. » Continue Reading
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As a veteran Ventura County firefighter, Jeff Maurer was hardwired to respond to emergencies. So, in 1995, when his captain’s 6-year-old daughter was diagnosed with leukemia, he and his colleagues mobilized and took turns donating blood on her behalf to Children’s Hospital Los Angeles. The day Maurer donated, he went upstairs to visit the child’s family.
A nurse interrupted their reunion, escorting him to the hallway with disturbing news: A lab tech had found an abnormality in Maurer’s blood work.
He soon discovered that the disease threatening his friend’s child was rampaging in him, as well.
His platelet counts were dangerously low, and his blood contained “blast” cells, clusters of immature white cells that could crowd out his healthy cells — and kill him.
The improbable diagnosis of acute myelogenous leukemia hit him hard — particularly since he felt fine, was a runner and had not been experiencing symptoms.
“I started thinking of all the things that I would miss in life should I not be around,” recalled Maurer, who was only 35 when he was diagnosed. He thought first of his baby daughter, Rachael, then only 8 months old.
“The realization that I may not be there as a positive influence in her life and as her dad was devastating,” he said. » Continue Reading
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Cells must efficiently pack enormous amounts of DNA into their tiny nuclei. How they do this, and the role this packaging plays in disease development, remains a mystery. But research just published in The Journal of Biological Chemistry provides a few clues that may lead to breakthroughs in disease diagnosis, prevention and treatment.
Co-lead author on the study Dustin Schones, Ph.D., an assistant professor in City of Hope’s Department of Cancer Biology, explains the significance of the paper, “High Mobility Group Protein N5 (HMGN5) and Lamina-associated Polypeptide 2 (LAP2) Interact and Reciprocally Affect Their Genome-wide Chromatin Organization.”
What’s the main finding of this study?
Every cell in the human body contains a copy of the individual’s genome, the genetic blueprint that orchestrates the activities of cells for normal development and function. This genome consists of approximately 3 billion nucleotides, which is equivalent to approximately two meters of chromosomal DNA. This has to be packaged into a nucleus that is on the order of 10 microns. This packaging is analogous to approximately six miles of string being packaged into a golf ball.
This packaging is accomplished by wrapping the genome around collections of proteins to form a structure known as chromatin. The chromatin structure is subject to many chemical modifications, and aberrant modifications accompany the progression of many diseases, including cancer development. » Continue Reading
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For many Americans, the Fourth of July would not be the same without a backyard barbecue filled with steaks, hamburgers and hot dogs. But grill masters beware: research says high-heat grilling can increase cancer risk.
Cooking meats at very high temperatures converts proteins and sugars found in red meat, pork, poultry and fish into heterocyclic amines (HCAs), while dripping fats and juices from meat create polycyclic aromatic hydrocarbons (PAHs). Both compounds are known to cause DNA-altering changes that can increase the risk of cancer.
A study from the University of Minnesota found that eating charred, well-done meat on a regular basis may increase your risk of pancreatic cancer by up to 60 percent. And the American Institute for Cancer Research stated that consuming red and processed meats raises one’s risk of colorectal cancer.
“It is estimated that three-quarters of colorectal cancers, half of breast cancers and one-third of lung cancers could be prevented with healthier diets,” said Peggy Mancini, M.S., R.D., a clinical dietitian at City of Hope.
However, you don’t have to give up grilling completely to stay healthy. Here are a few tips on how you can lower your risk of cancer when hosting a summer barbecue: » Continue Reading
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When facing a cancer diagnosis, patients and their caregivers may have trouble getting the supportive care they need; in fact, they may not even be fully aware of their challenges or the resources available to them.
Thus, it is key to screen patients so that persistent issues impacting treatment – from pain and nausea to depression and anxiety to financial and transportation obstacles – can be addressed in a timely manner. Thanks to a $1.5 million grant from the National Cancer Institute, City of Hope is leading the country’s health systems to do just that.
The grant will fund a series of workshops to educate health professionals nationwide on how to screen patients for treatment-related issues, led by Matthew Loscalzo, M.S.W., L.C.S.W., the Liliane Elkins Endowed Professor in Supportive Care Programs, and program manager Karen Clark, M.S., from City of Hope’s Sheri & Les Biller Patient and Family Resource Center.
“Many cancer patients report that it can be difficult to communicate their ongoing concerns with their doctors and other members of their health care team,” Clark said. “Screening gives patients the opportunity to tell the team about any issues – physical, psychological, family, social, spiritual, financial or others – that may impact their care.” » Continue Reading
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