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Researchers Investigate New Treatments for Leading Cancers

WASHINGTON — January 02, 2017 12:56 AM Carol Pearson Scientists are investigating new ways of treating people with liver cancer. The methods range from developing an artificial liver, to seeing if genetically-modified pigs can produce organs compatible with humans. For those who have liver cancer, their only cure lies in a liver transplant or removal of the cancerous part of the organ. Both require major surgery. And, patients who get a transplant will need to take immuno-suppressant drugs for the rest of their lives. However, scientists are working on a new approach that is minimally invasive. With both chemotherapy and radiation, healthy cells around the tumor are damaged. But this approach involves the use of natural, non-toxic chemical compounds from plants. Kattesh Katti, a professor at the University of Missouri School of Medicine, led a study that used nanotechnology to target and destroy precancerous tumor cells in the livers of mice and in in-vitro human cells. “It sounds like a fairy tale, but we are really in advanced stages in terms of tumor treatment, in terms of disease diagnostics," said Katti. Katti's work involved very small particles of gold encapsulated in a protective stabilizer from an acacia tree. The particles attract precancerous and malignant cells, which are far more susceptible to lower levels of heat than healthy cells. “The patient will be administered with these nano particles. Within a couple of hours, the patient will be treated with lasers, and then the patient can go home. So, there is no radioactivity. There is no toxic waste. There is no toxicity, systemic toxicity, to the patient,” said Katti. Katti said the cost of treatment will be low because one gram of gold can be used to treat 50 [...]

Cellular immunotherapy targets a common human cancer mutation

December 7, 2016 In a study of an immune therapy for colorectal cancer that involved a single patient, a team of researchers at the National Cancer Institute (NCI) identified a method for targeting the cancer-causing protein produced by a mutant form of the KRAS gene. This targeted immunotherapy led to cancer regression in the patient in the study. The finding appeared Dec. 8, 2016, in the New England Journal of Medicine. The study was led by Steven A. Rosenberg, M.D., Ph.D., chief of the Surgery Branch at NCI’s Center for Cancer Research, and was conducted at the NIH Clinical Center. NCI is part of the National Institutes of Health. More than 30 percent of all human cancers are driven by mutations in a family of genes known collectively as RAS, which has three members: KRAS, NRAS, and HRAS. Mutations in the KRAS gene are thought to drive 95 percent of all pancreatic cancers and 45 percent of all colorectal cancers. A mutation called G12D is the most common KRAS mutation and is estimated to occur in more than 50,000 new cases of cancer in the United States each year. Because of their importance in cancer causation, worldwide efforts to successfully target mutant RAS genes are being pursued. Such efforts have met with limited success to date. In attempting to develop more effective approaches to targeting RAS, Rosenberg’s team isolated tumor infiltrating lymphocytes (TILs) that targeted the KRAS G12D mutation from tumor nodules in the patient’s lungs that developed after colorectal cancer cells had spread to the lungs. TILs are white blood cells that migrate from the bloodstream into a tumor. The isolated TILs were grown in the laboratory to large numbers and then infused into [...]

Nanotechnology a ‘green’ approach to treating liver cancer

November 29, 2016 (Nanowerk News) According to the American Cancer Society, more than 700,000 new cases of liver cancer are diagnosed worldwide each year. Currently, the only cure for the disease is to surgically remove the cancerous part of the liver or transplant the entire organ. However, an international study led by University of Missouri School of Medicine researchers has proven that a new minimally invasive approach targets and destroys precancerous tumor cells in the livers of mice and in vitro human cells (Journal of Photochemistry and Photobiology B: Biology, "Photothermal therapy mediated by gum Arabic-conjugated gold nanoparticles suppresses liver preneoplastic lesions in mice"). "The limitations when treating most forms of cancer involve collateral damage to healthy cells near tumor sites," said Kattesh Katti, Ph.D., Curators' Professor of Radiology and Physics at the MU School of Medicine and lead author of the study. "For more than a decade we have studied the use of nanotechnology to test whether targeted treatments would reduce or eliminate damage to nearby healthy cells. Of particular interest has been the use of green nanotechnology approaches pioneered here at MU that use natural chemical compounds from plants." Kattesh Katti, Ph.D., University of Missouri-Columbia The study was conducted in the United States and Egypt, and it involved the use of gold nanoparticles encapsulated by a protective stabilizer called gum Arabic. The nanoparticles were introduced to the livers of mice intravenously and were heated with a laser through a process known as photothermal therapy. "Gum Arabic is a natural gum made of the hardened sap from acacia trees," said Katti, who also serves as director of the MU Institute of Green Nanotechnology and is the Margaret Proctor Mulligan Distinguished Professor of Medical Research [...]

New topical immunotherapy effective against early skin cancer

Combination of two drugs reduces precancerous skin lesions By Julia Evangelou Strait November 21, 2016 Washington University dermatologist Lynn Cornelius, MD, (left) conducts a skin exam with patient Robert Manchester. Manchester is a participant in a clinical trial testing the effectiveness of a new topical immunotherapy against precancerous skin lesions called actinic keratosis, often found on sun-damaged skin. (Photo: Robert J. Boston/Washington University School of Medicine) A combination of two topical drugs that have been in use for years triggers a robust immune response against precancerous skin lesions, according to a new study. The research, from Washington University School of Medicine in St. Louis and Harvard Medical School, shows that the therapy activates the immune system’s T cells, which then attack the abnormal skin cells. The study, which involved patients with actinic keratosis, a precursor to a type of skin cancer called squamous cell carcinoma, is published Nov. 21 in The Journal of Clinical Investigation. “We looked at precancerous lesions on patients with sun-damaged skin,” said Washington University dermatologist and study co-author Lynn A. Cornelius, MD, director of the Division of Dermatology. “Most commonly found on the face, scalp and arms, these lesions appear abnormal by visual examination and under the microscope but are not full-blown skin cancers. But because these lesions have the potential to develop into a true skin cancer, they are commonly treated. Our study shows this combination therapy is more effective and better tolerated than current treatment practices.” On average, the investigational therapy reduced the number of precancerous skin lesions on the face by almost 88 percent compared with a 26 percent reduction using the standard chemotherapy. While some side effects such as skin scaling and itching were similar with both [...]

Lab-Grown Human ‘Mini Lungs’ Successfully Engraft in Mice, a Respiratory Research Breakthrough

Shantell M. Kirkendoll November 07, 2016 6:00 AM Scientists can now grow 3-D models of various organs from stem cells, creating new ways to study disease. More than a year ago, scientists made studying lung cells in a petri dish appear old-fashioned. A team led by University of Michigan Medical School researchers coaxed stem cells to grow into three-dimensional miniature lungs, which mimic several aspects of the structure and complexity of human lungs. Now, the researchers have transplanted the 3-D mini lungs into immunosuppressed mice and have shown that the mini lungs can survive, grow and mature. The milestone is published in the Nov. 1 issue of eLife. “In many ways, the transplanted mini lungs were indistinguishable from human adult tissue,” says senior study author Jason Spence, Ph.D., associate professor in the Department of Internal Medicine and the Department of Cell and Developmental Biology at the U-M Medical School. Respiratory diseases account for nearly 1 in 5 deaths worldwide, and lung cancer survival rates remain poor despite numerous therapeutic advances during the past 30 years. These numbers highlight the need for new, physiologically relevant models for translational lung research. Lab-grown lungs can help because they provide a human model to screen drugs, understand gene function, generate transplantable tissue and study complex human diseases, such as asthma. And they’re not the only tissues in development. As a developmental biologist, Spence has been tinkering with creating other tissues from stem cells, termed “organoids.” Researchers in the Spence Lab have had remarkable success with what some have called “intestines in a dish,” for example, which may help with the study of inflammatory bowel disease. "In just eight weeks, the resulting transplanted tissue had impressive tube-shaped airway structures similar to [...]

Making Every Cell Matter

October 31, 2016 A new method for encapsulating single cells within tunable microgels could boost efficacy of cell-based therapies and tissue engineering (CAMBRIDGE, Massachusetts) – Alginate hydrogels – which are derived from the polysaccharide found in brown seaweed – have emerged as an effective material for manipulating cells and tissues due to their biocompatibility and the ability to tune their mechanical and biochemical properties to match physiological conditions found inside the body. Already they have been demonstrated to influence the differentiation of stem cells, incite immune attacks on cancer cells, and weaken tumors’ resistance to chemotherapy, but as of yet, hydrogels have mostly been useful for controlling groups of cells at large rather than individual cells. For example, alginate capsules filled with hundreds of pancreatic islet cells can be implanted in diabetic patients. However, these capsules are millimeters in size and eventually become surrounded by thick scar tissue that blocks the biological signals of islet cells and renders the implant ineffective. This image shows an encapsulated single cell rendered in three dimensions. The greenish-blue colored part in the middle is the cell nucleus; the yellow color represents the cell’s cytoskeleton; and the purple on the outside is the thin hydrogel layer that encapsulates the cell. The new microfluidic-enabled method for encapsulating single cells could pave the way for more effective cell therapies and precise tissue engineering capabilities. Credit: Wyss Institute at Harvard UniversityNow, thanks to the joint efforts of a team from the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), a new and highly effective microfluidic method for encapsulating single cells in microscale hydrogels sets the stage for a dramatic [...]

Achilefu receives inaugural breast cancer research award

$4.5 million from U.S. defense department funds innovative light therapy October 26, 2016 ROBERT BOSTON PHOTO Samuel Achilefu, PhD, (shown) a scientist at Washington University School of Medicine in St. Louis, is the first recipient of the Breast Cancer Research Program Distinguished Investigator Award, from the U.S. Department of Defense. As part of the award, Achilefu will receive $4.5 million to support his work to use light to activate drugs and the immune system in the body. Samuel Achilefu, PhD, a scientist and inventor at Washington University School of Medicine in St. Louis, has been recognized as the first recipient of the Breast Cancer Research Program Distinguished Investigator Award, from the U.S. Department of Defense. The award comes with $4.5 million to support his innovative work to use light to activate drugs and the immune system in the body. He is developing the approach as a safer and more effective way to treat breast cancer than currently available chemotherapy drugs. So-called photoimmunotherapy also has the potential to help those with breast cancer that has spread, which typically evolves to become resistant to chemotherapy. Metastatic disease is responsible for more than 90 percent of the 41,000 breast cancer deaths in the U.S. each year. Washington University scientists led by Samuel Achilefu, PhD, have devised a way to apply light-based therapy to deep tissues never before accessible. They delivered light directly to tumor cells, in the form of an imaging agent frequently used in positron emission tomography (PET) scans. This light source, along with a novel cancer-targeting product and a chemotherapy drug, selectively kill cancer cells. “The goal is to harness the power of light and cancer-specific tumor targeting strategy to effectively treat tumors while minimizing or even eliminating damage [...]

Iron nanoparticles make immune cells attack cancer

Stanford researchers accidentally discovered that iron nanoparticles invented for anemia treatment have another use: triggering the immune system’s ability to destroy tumor cells. SEP 26, 2016 A mouse study found that ferumoxytol prompts immune cells called tumor-associated macrophages to destroy tumor cells. Amy Thomas Iron nanoparticles can activate the immune system to attack cancer cells, according to a study led by researchers at the Stanford University School of Medicine. The nanoparticles, which are commercially available as the injectable iron supplement ferumoxytol, are approved by the Food and Drug Administration to treat iron deficiency anemia. The mouse study found that ferumoxytol prompts immune cells called tumor-associated macrophages to destroy cancer cells, suggesting that the nanoparticles could complement existing cancer treatments. The discovery, described in a paper published online Sept. 26 in Nature Nanotechnology, was made by accident while testing whether the nanoparticles could serve as Trojan horses by sneaking chemotherapy into tumors in mice. “It was really surprising to us that the nanoparticles activated macrophages so that they started to attack cancer cells in mice,” said Heike Daldrup-Link, MD, who is the study’s senior author and an associate professor of radiology at the School of Medicine. “We think this concept should hold in human patients, too.” Daldrup-Link’s team conducted an experiment that used three groups of mice: an experimental group that got nanoparticles loaded with chemo, a control group that got nanoparticles without chemo and a control group that got neither. The researchers made the unexpected observation that the growth of the tumors in control animals that got nanoparticles only was suppressed compared with the other controls. Heike Daldrup-Link Getting macrophages back on track The researchers conducted a series of follow-up tests to characterize what was happening. [...]

Cancer killers: C dots show ability to induce cell death in tumors

By Tom Fleischman Nanoparticles known as Cornell dots, or C dots, have shown great promise as a therapeutic tool in the detection and treatment of cancer. Now, the ultrasmall particles – developed more than a dozen years ago by Ulrich Wiesner, the Spencer T. Olin Professor of Engineering – have shown they can do something even better: kill cancer cells without attaching a cytotoxic drug. A study led by Michelle Bradbury, director of intraoperative imaging at Memorial Sloan Kettering Cancer Center and associate professor of radiology at Weill Cornell Medicine, and Michael Overholtzer, cell biologist at MSKCC, in collaboration with Wiesner has thrown a surprising twist into the decadelong quest to bring C dots out of the lab and into use as a clinical therapy. Their paper, “Ultrasmall Nanoparticles Induce Ferroptosis of Nutrient-Deprived Cancer Cells and Suppress Tumor Growth,” was published Sept. 26 in Nature Nanotechnology. The work details how C dots, administered in large doses and with the tumors in a state of nutrient deprivation, trigger a type of cell death called ferroptosis. “If you had to design a nanoparticle for killing cancer, this would be exactly the way you would do it,” Wiesner said. “The particle is well tolerated in normally healthy tissue, but as soon as you have a tumor, and under very specific conditions, these particles become killers.” “In fact,” Bradbury said, “this is the first time we have shown that the particle has intrinsic therapeutic properties.” Wiesner’s fluorescent silica particles, as small as 5 nanometers in diameter, were originally designed to be used as diagnostic tools, attaching to cancer cells and lighting up to show a surgeon where the tumor cells are. Potential uses also included drug delivery and environmental [...]

New immunotherapy for leukemia shows promise in small clinical trial

'Training' immune cells boosts effectiveness in patients with AML By Julie Evangelou Strait September 21, 2016 A new type of immunotherapy shows promise against cases of acute myeloid leukemia (AML) that recur after treatment or that never respond to therapy in the first place. A small clinical trial at Washington University School of Medicine in St. Louis provides evidence that the immune system’s “natural killer” cells can be dialed up in the laboratory, trained to recall that activation and then effectively unleashed to destroy cancer cells in some patients. The findings are published Sept. 21 in the journal Science Translational Medicine. Responses to the treatment were observed in five of the nine patients that could be evaluated. Four patients achieved complete remission; there was no evidence of leukemia for at least one month after treatment. One patient achieved a partial remission, with some abnormal cells reappearing at the one-month mark. The remaining four patients did not respond to the therapy. The longest complete remission lasted about six months, according to the researchers. In contrast, the average life expectancy for patients with active AML that does not respond to therapy is about three months. “This is a small study, but a 50 percent response rate is promising since these are patients with very poor prognoses and very few options,” said senior author Todd A. Fehniger, MD, PhD, co-principal investigator of the study and an associate professor of medicine. “Many of these patients are older and are not candidates for traditional bone marrow transplants because of the side effects associated with such an aggressive treatment.” The treatment, part of a phase I trial, was developed at Washington University. The researchers said a response to therapy in five of nine [...]