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Roswell Park Researchers Identify Key Link Between Stress and Cancer

AHA Publisher — Mon, 08 Nov 2021 08:00:50 +0000

Roswell Park Comprehensive Cancer Center via Newswise – BUFFALO, N.Y. — Stress can have a significant negative effect on health, but our understanding of how stress impacts the development and progression of cancer is just beginning. A team from Roswell Park Comprehensive Cancer Center has identified an important mechanism by which chronic stress weakens immunity and promotes tumor growth. Their findings, just published in Cell Reports, point to the beta-adrenergic receptor (β-AR) as a driver of immune suppression and cancer growth in response to stress, opening the possibility of targeting this receptor in cancer therapy and prevention. Using a preclinical model of triple-negative breast cancer, a research team led by Hemn Mohammadpour, PhD, DVM, a postdoctoral research affiliate in the lab of Elizabeth Repasky, PhD, and Dr. Repasky, who is Co-Leader of the Cell Stress and Biophysical Therapies Program and the Dr. William Huebsch Professor in Immunology at Roswell Park, found that as tumors grow, they become more sensitive to stress signals coming from the nervous system. Specifically, the researchers discovered that a population of immune cells known as myeloid derived suppressor cells (MDSCs) show an increase in the expression of β-AR, a molecule that controls the function of key immune cells. The findings will help researchers better understand why prolonged exposure to stress often makes our immune system less effective, and build on Roswell Park’s pioneering research into the relationship between stress and cancer. “This increase in β-AR expression on myeloid-derived suppressor cells allows these cells to be stimulated by the stress hormone norepinephrine, which fosters an immunosuppressed environment that promotes tumor growth by increasing MDSCs’ ability to generate and process energy and suppress anti-tumor immune response,” says Dr. Mohammadpour, the paper’s first author. “This study provides some very important clues that help explain the specific mechanisms by which prolonged stress stimulates tumor growth and decreases lifespan.” While there has been a longstanding recognition that long periods of stress, or chronic activation of nerves, are harmful to overall health, details about how this occurs are unclear, especially in the setting of cancer. A better understanding of the specific ways in which stress influences cancer, particularly in terms of lowering immunity against tumor cells, could be used to design new drugs or therapies that can help to minimize negative effects of chronic stress and boost cancer immunotherapy. Based on these findings, Dr. Repasky’s team is planning new clinical and laboratory studies to identify therapies — including existing therapies already approved for other applications — that can block these harmful stress signals and stop the negative cycle of cancer growth and metastasis. “This is especially important for cancer patients, who frequently endure greatly increased levels of stress after their diagnosis, including anxiety, depression and worry about factors like finances and family interactions,” adds Dr. Mohammadpour. Several clinical trials are planned or underway to investigate which interventions are most effective at mitigating the effects of stress in patients with cancer. Roswell Park is currently studying the effects of combining the β-AR blocker propranolol, which is traditionally used to treat migraine headache and various heart problems, with immunotherapy. The study, “β2-adrenergic receptor signaling regulates metabolic pathways critical to myeloid-derived suppressor cell function within the TME,” was supported by the National Institutes of Health and National Cancer Institute (grants R01CA205246, R01CA099326, R01CA172105, F32CA239356, K99 HL155792, T32CA085183 and F30CA265127 and P30CA016056, Roswell Park’s core grant from the NCI) and by the Roswell Park Alliance Foundation. Co-authors include Philip McCarthy, MD, Professor of Oncology and Internal Medicine and Director of Roswell Park’s Transplant & Cellular Therapy Center; Scott Abrams, PhD, Co-Leader of Roswell Park’s Tumor Immunology and Immunotherapy Program; and Cameron MacDonald, a predoctoral trainee in immunology. To read the original article click here.

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Protein in Prostate Cancer May Inhibit Tumor Growth

AHA Publisher — Wed, 16 Jun 2021 07:00:57 +0000

University of Georgia via EurekAlert – Prostate cancer is the second most common cancer among men, according to the American Cancer Society. It’s also one of the trickiest cancers to diagnose and treat. But new research from the University of Georgia has identified a protein that appears to prevent the cancer from spreading to and colonizing the bone, providing a new target for future therapeutics. “Unfortunately, prostate cancer that has spread to the bone is very aggressive, often lethal and very difficult to treat,” said Brian Cummings, corresponding author of the study and head of the College of Pharmacy’s pharmaceutical and biomedical sciences department. “Even in cases of successful treatment, the patient’s quality of life is severely lessened due to bone loss.” Prostate cancer that hasn’t spread beyond nearby organs has nearly a 100% survival rate, meaning almost all of these patients will live at least another five or more years after their initial diagnosis and treatment. But for men whose cancer has spread to other organs or the bone, that five-year survival rate plummets to 30%, according to the American Cancer Society. In the U.S., about one in every eight men will be diagnosed with prostate cancer and more than 34,000 men die each year from the disease. The new study, published by Scientific Reports, focused on cancer-associated fibroblasts, which are the most abundant type of cell in tumors and are responsible for cancer growth and spread. The researchers found that knocking out a specific protein, called glypican-1, could prevent tumor cells from spreading into nearby bone. The study supports a previous report from Cummings’ laboratory suggesting that this protein may prevent tumor growth. The researchers found that the protein doesn’t alter the cancer cells themselves. Instead it affects a group of neighboring cells called fibroblasts. Fibroblasts are cells that help make up connective tissues in people and animals. But fibroblasts can also be present in cancerous tumors, where they facilitate cancer growth and spread. To determine the glypican-1 protein’s role in helping cancer spread, the researchers combined human prostate cancer cells and human bone-derived cells to examine how the cancer cells transformed the fibroblast. Then they genetically modified the cancer cells and the fibroblast to knock out the protein. Without the protein, the prostate cancer cells had problems transforming the fibroblast. The study was the first to demonstrate such a role for glypican-1 and suggests that this protein may have the same effect on tumor growth in people. “Part of the significance of this study is that it demonstrates how cancer cells are able to change their environment in ways to facilitate their own growth,” Cummings said. “Prostate cancer cells alter their environment so that they can colonize bone. This study identifies a role for a protein that appears to inhibit the harmful changes that prostate cancer makes to the bone.” “This protein appears to stop the ability of cancer cells to change their environment, which decreases the cancer’s aggressiveness. The fact that this protein is found in the bone, where many aggressive prostate cancer cells reside, further increases the potential impact of this work.” To read the original article click here.

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Are Avocados Associated with Greater Risk or Reduced Risk of Cancer?

AHA Publisher — Tue, 25 May 2021 07:00:58 +0000

Michael Greger M.D. FACLM via Nutrition Facts – Avocado consumption can improve artery function, but what effect might guacamole have on cancer risk? In my last video about avocados, The Effects of Avocados and Red Wine on Meal-Induced Inflammation, I described their anti-inflammatory effects and cholesterol- and triglyceride-lowering effects, but what about the Are Avocados Good for You? video I did years ago about the chromosome-damaging effects in a petri dish? That goes back to 1975, when a pesticide naturally produced by the avocado tree was discovered, thought to explain why lactating livestock suffer mammary gland damage after nibbling on the leaves. The toxin, named persin, was also found to be damaging to the heart, which is why you should never feed avocado to your pet birds. But, if persin attacks mammary cells in animals, might it attack breast cancer cells in humans? As you can see at 0:52 in my video Are Avocados Healthy?, it did seem to have the same kind of cellular cytoskeleton-clumping effect in vitro that chemotherapy can have, demonstrating potent cell growth stopping and killing effects of the novel plant toxin among various lines of human breast cancer cells. So, researchers are thinking about how it might one day be used as chemo itself, but I’m thinking, Holy guacamole, Batman! Please tell me it doesn’t have toxic effects on normal cells, too. We got an answer in 2010 with an evaluation of the genotoxicity—the toxicity to our chromosomes—of avocado extracts on human white blood cells in a petri dish. As you can see at 1:35 in my video, normally, less than 10 percent of our dividing cells have any chromosome abnormalities, but if you drip some avocado fruit extracts on them, up to half come out defective in some way. The researchers concluded that there’s something in avocado fruit that “can potentially induce significant genomic instability and some genetic damage in human lymphocytes in vitro,” that is, in white blood cells in a petri dish. If the same effect occurs in actual people, it could, for example, result in transforming cells into cancer. That is a big if, though. These were blood cells. You don’t inject guacamole into the vein. For something to get into our bloodstream, it first has to survive our stomach acid, get absorbed through our intestines, and then sneak past our liver’s detoxification enzymes. And indeed, persin may be affected, changed by acidic conditions. So, given all the differences between what happens in a petri dish and inside a person, it’s essential to carry out further studies “before making a final remark on the genotoxicity.” Sounds reasonable, but what do you do before these studies come out? I was concerned enough that I provisionally moved avocados from being a don’t-hold-back green-light food to a moderate-your-intake yellow-light food to err on the side of caution until we knew more. Even if persin were utterly destroyed by stomach acid, what about oral cancer? As you can see at 3:01 in my video, avocado extracts at high enough concentrations can harm the growth of the kinds of cells that line our mouths. This was in a petri dish, though, where the avocado is coming in direct contact with the cells—but that’s also kind of what happens in your mouth when you eat it. However, it harms oral cancer cells even more. At 3:32 in my video, you can see a bunch of oral cancer cells. In the first image, the mitochondria, the power plants of the cells fueling cancer growth, are seen in red. In the second image, you can see they’ve been extinguished by the avocado extract—no more red-colored mitochondria. Since it does this more to cancerous cells than normal cells, the researchers conclude that avocados may end up preventing cancer. What about the esophagus, which lies between the mouth and the stomach? Researchers similarly found that an avocado fruit extract appeared to inhibit cancer cell growth more than normal cell growth when it came to both colon cancer cells and esophageal cancer cells, as you can see at 3:53 in my video. But, rather than comparing the effects to normal colon and esophagus cells, they compared them to a type of blood cell, which, again, is of limited relevance in a petri dish study of something you eat. A study I found to be pretty exciting looked at p-cresol, which is a “uremic toxin” and may also be toxic to the liver. “Found to be associated with autism,” it comes from eating high-protein diets, whereas if you eat a more plant-based diet, which is the only source of prebiotics like fiber and resistant starch, your levels go down. See, fermentation of carbohydrates in the colon, like fiber, is considered beneficial, whereas fermentation of protein, which is called putrefaction, is considered detrimental. So, if you switch people to a high-protein diet, within days, the excess protein putrefying in their gut leads to an increase in ammonia as well as p-cresol—in fact, a doubling of levels within a week. But, might phytonutrient-rich plant foods, like apples, cranberries, grapes, or avocados, protect the cells lining our colon “from the deleterious effects of p-cresol…in terms of cell viability, mitochondrial function, and epithelial integrity,” meaning protection against gut leakiness? At 5:12 in my video, I show the data on barrier function integrity. You can see that it is damaged by p-cresol, but rescued by all the cranberry, avocado, grape, and apple extracts. Mitochondrial function, however, was only improved by the cranberries and avocados, which also were the only ones that appeared to prevent the deleterious effect of p-cresol on colon cell viability. The bottom line, though, is that avocados appear to have beneficial effects on colon lining cells. Okay, but enough of these in vitro studies, already. Yes, an avocado extract can inhibitcancer cell growth in a petri dish, but unless you’re doing some unspeakable things to that avocado—like guacamole with benefits—there’s no way that avocado is going to come in direct contact with your prostate cells. So, what does this study mean? This is why I was so excited to see the first study to actually look for a link between avocado consumption and prostate cancer. Actual human beings eating avocados! So, do avocado eaters have more cancer risk or less cancer risk? Men who ate the most avocado, more than about a third of an avocado a day, had reduced risk of prostate cancer—in fact, less than half the odds. So, with the data on improved artery function, lower cholesterol, and, if anything, an association with decreased cancer risk, I’d suggest moving avocados back up with the other green-light foods. To read the original article click here. For more articles from Dr. Greger click here.

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