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Genetic Variant linked to Increased Risk of Leukemia in Hispanic/Latino Children

The AHA! Team — Fri, 17 May 2024 08:07:50 +0000

Keck School of Medicine of USC via News-Medical – Acute lymphoblastic leukemia (ALL), the most common childhood cancer, disproportionately affects children of Hispanic/Latino origin in the United States. They are 30-40% more likely to get ALL than non-Hispanic white children, but the exact genetic basis and cause of that increased risk are unknown. (ALL) disproportionately affects children of Hispanic/Latino origin in the United States Now, a study from the Keck School of Medicine of USC has revealed a key genetic variant contributing towards the increased risk, as well as details about the biological basis of ALL. The team used genetic fine-mapping analysis, a statistical method that allows researchers to disentangle the separate effects of genetic variants in a region of the genome. They identified a variant found at a relatively high frequency in people of Hispanic/Latino origin that increases ALL risk by around 1.4 times. The study, funded in part by the National Institutes of Health, was just published in the journal Cell Genomics. “Combined with the fact that around 30% of Hispanic/Latino people in the United States carry this gene variant, but it’s basically absent in people of predominantly European ancestry, we think it’s an important contributor to the increased ALL risk among this group,” said the study’s lead author, Adam de Smith, PhD, an assistant professor of population and public health sciences and a member of the USC Norris Comprehensive Cancer Center at the Keck School of Medicine, as well as a scholar of the Leukemia & Lymphoma Society. The researchers also performed tests to better understand how the variant, located on the IKZF1 gene, which underlies B-cell development, relates to ALL through its influence on the development of B-cells, a type of white blood cell known to be disrupted by the disease. “Together, the analyses in our study provide the statistical, biological and evolutionary insights behind this increased risk, and may ultimately aid scientists working to develop screening tools and therapies for ALL.” -Charleston Chiang, PhD, associate professor of population and public health sciences and associate director of the Center of Genetic Epidemiology at the Keck School of Medicine and study’s co-senior author The genetic basis of leukemia risk To pinpoint the genetic basis of the elevated ALL risk Hispanic/Latino children face, the researchers analyzed genetic data from the California Cancer Records Linkage Project. Their dataset included 1,878 Hispanic/Latino children in California with ALL and 8,411 without the condition; 1,162 non-Hispanic white children with ALL and 57,341 without; and 318 East Asian children with ALL and 5,017 without. The research team focused on the IKZF1 gene, known to relate to ALL but never before linked with ethnic risk disparities. Using genetic fine-mapping analysis, they independently analyzed each position along the gene-;known as a single nucleotide polymorphism (SNP)-;to determine whether having a certain variant increased ALL risk. They found three independent SNPs linked to higher ALL incidence, one of which was present in about 30% of people of Hispanic/Latino origin in the U.S. and less than 1% of people of primarily European origin. Although overall risk for the disease is low across all racial/ethnic groups, children with that gene variant, located at SNP rs76880433, were 1.44 times as likely to develop ALL as children without the variant. The genetic ancestry of most Hispanics/Latinos can be traced to Europe, Africa, and Indigenous America. Further investigation revealed that the risk variant was specifically linked with Indigenous American ancestry and may have become more common in this group because it conferred a selective advantage at some point in human history. Next, the Keck School of Medicine team partnered with co-senior author Vijay Sankaran, MD, PhD, an associate professor of pediatrics at Harvard Medical School and attending physician at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, to conduct a series of experiments to better understand how the genetic variant at IKZF1 increases risk for ALL. One experiment analyzed chromatin accessibility, a test which indicates how fully a given gene can be expressed. The researchers found that the risk variant reduced chromatin accessibility, preventing IKZF1 proteins from being fully expressed. Sankaran and his team also conducted experiments with stem cells, finding that “knocking out” the IKZF1 gene caused B-cell development to stall in its early stages. “Looking at all of this together, we think that the risk variant is reducing IKZF1 expression,” de Smith said. “By doing so, it’s keeping B-cells in a more immature state, which would increase ALL risk by giving the cells more chance to develop mutations that could eventually lead to overt leukemia.” Leukemia screening and treatment The new insights about IKZF1 bring researchers one step closer to developing effective screening tools to predict who may develop ALL, but more research is needed. In addition, the findings provide important clues about potential ways to treat the disease, for instance by progressing B-cell development after it stalls. “We also need to understand whether this variant is associated with different patient outcomes, such as the risk of relapse or chances of survival, and why that might be,” de Smith said. He and his colleagues also hope to explore whether the newly identified risk variant helps explain the even higher risk of ALL among Hispanic/Latino adolescents and young adults, who are more than twice as likely to get the disease than people who are non-Hispanic white. About this research In addition to de Smith, Chiang and Sankaran, the study’s other authors are Soyoung Jeon, Jalen Langie, Tsz-Fung Chan, Steven Gazal, Nicholas Mancuso and Joseph Wiemels from the Center for Genetic Epidemiology and the USC Norris Comprehensive Cancer Center, Keck School of Medicine of USC; Lara Wahlster, Susan Black, Liam Cato, Soumyaa Mazumder and Fulong Yu from Boston Children’s Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute; Linda Kachuri from the Stanford University School of Medicine; Nathan Nakatsuka from the New York Genome Center; Guangze Xia from the Guangzhou National Laboratory, Guangzhoi, China; Wenjian Yang and Jun Yang from St. Jude Children’s Research Hospital, Memphis; Celeste Eng, Donglei Hu, Esteban Gonzalez Burchard and Elad Ziv from the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco; Catherine Metayer from the School of Public Health, University of California, Berkeley; and Xiaomei Ma from the Yale School of Public Health. This work was supported by the National Institutes of Health [R01CA262263, R01CA155461, R00CA246076, R35GM142783, R01DK103794, R01CA265726]; the New York Stem Cell Foundation; and the Dana-Farber Cancer Institute Presidential Priorities Initiative. Source: Keck School of Medicine of USC Journal reference: de Smith, A. J., et al. (2024) A noncoding regulatory variant in IKZF1 increases acute lymphoblastic leukemia risk in Hispanic/Latino children. Cell Genomics. doi.org/10.1016/j.xgen.2024.100526. To read the original article click here.

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Boost Your Immune System with Herbal Medicine, Study Reveals

AHA Publisher — Fri, 26 Nov 2021 08:00:27 +0000

Lori Alton via NaturalHealth365 – For centuries, the healing powers of the herb pau d’arco have been recognized by those around the world who have sought out herbal medicines. But in recent years, this herb’s many health benefits have even been recognized by conventional medicine – especially in strengthening the immune system. Researchers associated with the U.S. Department of Agriculture have recognized pau d’arco’s significant anti-tumor, anti-inflammatory, antibacterial, and antiviral benefits, while a Munich researcher has based his entire doctoral thesis on the herb’s incredible powers for supporting the immune system. Are You Looking to Improve Your Immune System Naturally? It is widely understood that there’s a link between the body’s immune system and the body’s ability to fight off cancer, infectious diseases plus many other chronic health conditions. Naturally speaking, many healthcare providers recommend the daily consumption of organic (or wildcrafted) herbs like, pau d’arco – which is native to the rainforests of Central and South America, although it has been successfully cultivated in southern Florida. Outside the United States, in particular, the ability of pau d’arco to boost immune function is widely accepted and it has been used to treat a broad range of illnesses for generations. Research has shown that pau d’arco has the potential to boost the activity of the immune system by nearly 50 percent when ingested on a regular basis. Pau d’arco is commonly available online or at health food stores and some drugstores in a variety of forms, including tablets, tea, capsule, salve, powder, and liquid extract. While recommended dosage varies by manufacturer and product type, making herbal tea requires the bark to be boiled or simmered a minimum of 8 to 10 minutes in order for the active ingredients to be released. Scientists recognizing pau d’arco’s ability to boost immunity point to two key components found in the inner part of the herb’s bark: lapachol and beta-lapachone. Not only have these chemicals been found to improve resistance to disease-producing organisms, but researchers also believe they have the power to fight cancer. What Does Science Say About the Anti-Cancer Benefits of Pau D’Arco? Dr. David Boothman of the Harold C. Simmons Comprehensive Cancer Center has gone on record explaining that beta-lapachone blocks a cancer cell’s ability to repair its DNA, leading to its eventual death. Similarly, a U.S. patent was issued following clinical studies completed in Osaka, Japan, that showed pau d’arco’s tree bark not only strengthens immunity but is effective in fighting against cancerous growths. Specifically, the patent detailed the ability of pau d’arco’s tree bark to slow the growth of 23 different types of cancer cells, with 12 of the 23 forms of malignant tumors destroyed entirely. Those 12 types include: Bladder carcinoma Renal cell carcinoma Human colon adenocarcinoma Squamous cell carcinoma Pancreatic carcinoma Cervical carcinoma Human lung adenocarcinoma Lung carcinoma Thyroid carcinoma Cholangiocarcinoma Ovarian carcinoma Chorio carcinoma According to the American Cancer Society, one component of pau d’arco – lapachol – was found to fight against certain tumor cells as well as malaria in laboratory animals. While this research showed it to be effective against cancers such as sarcoma, it did not have an impact against other types of cancer, such as leukemia. While noting that such tests are unconfirmed, the American Cancer Society also states that some studies have shown that pau d’arco tree bark works by spurring immune system cells known as macrophages into action. The bark extract was also shown to kill liver cancer cells and lung cancer cells in test tubes while reducing the spread of lung cancer in laboratory mice following tumor removal. It has also been shown that the bark extract may kill bacteria or fungi. Additional Research May Uncover More of the Healing Powers of Pau D’Arco. While there are over 30 known constituents inside the herb pau d’arco, only three were included in the above study, leaving the door wide open for additional substances to be identified as playing significant roles in improving health, while underscoring the strength that the combined components have in healing. Sources used for this article: NIH.gov NIH.gov Cancer.org To read the original article click here.

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Sunscreen WARNING: Cancer-Causing Chemical Found in 78 Popular Sunscreen Products

AHA Publisher — Tue, 08 Jun 2021 07:00:00 +0000

Damon Hines via NaturalHealth365 – Skin cancer affects more than 3 million people each year. Sunscreen is designed to protect us from skin cancer, but how safe are the popular brands we apply to our skin every summer? Here’s something to think about as the warm weather arrives: Sunscreens were first regulated by the FDA in the 1970s, long before current American guidelines for evaluating drugs were put into place. It should come as no surprise then that sunscreens didn’t undergo rigorous testing. However, what is shocking is that many of the sunscreens on the market today are more harmful than beneficial, and some even contain a cancer-causing chemical. According to a recent report by Valisure, an independent team of scientists that test the chemical composition of healthcare and medication products, benzene, a known cancer-causing chemical, was found in 78 sunscreen and after-sun products tested. In fact, “27% of samples tested by Valisure contained detectable benzene and some batches contained up to three times the conditionally restricted FDA concentration limit.” High Levels of Benzene Linked to Blood Type Cancers Benzene is a colorless or slightly yellow flammable liquid that’s naturally found in the environment. It’s often used as a solvent in manufacturing plastics and other products and is commonly found in gels, sprays, and lotions. While benzene is allowed in products like sunscreen up to a certain level, high concentrations of the toxic liquid are dangerous and can increase the risk of blood cancers like leukemia. But why is benzene, a toxic carcinogen, even allowed in these products on a small level? According to David Light, founder, and CEO of Valisure, “Benzene is one of the most studied and concerning human carcinogens known to science. Its association with forming blood cancers in humans has been shown in numerous studies at trace levels of parts per million and below.” Valisure’s report isn’t the first time the potential health risks of sunscreen have made headlines. Over the years, studies have linked the chemicals in sunscreen to everything from hormone disruption to bioaccumulation in organs and tissue to severe allergic reactions. In addition, there have been concerns that sunscreen prevents the body from making vitamin D. While most experts have concluded that sunscreens are unlikely to affect the vitamin D status of healthy individuals, the debate is reignited every summer. In other words, the real biological effect of sunscreen in your blood is as bad as a cloudy day at the beach. All the BURNING Questions About Sunscreen Safety Answered Valisure is currently urging the FDA to recall the sunscreen products that contain high levels of benzene. A full list of the sunscreen products can be found here, on page 12 of the citizen petition Valisure wrote to the FDA on May 24, 2021. As for which sunscreens are the safest, you can check out the Environmental Working Group (EWG) website and download the EWG’s Guide to Sunscreen. Here you will find a list of brands that contain safer ingredients, making it easy to choose a product that is the best fit for you. What’s the bottom line? If you plan to spend time in the sun this summer, make sure the sunscreen you apply is benzene-free and double-check the expiration date. Better yet, engage in a combination of sun protection methods: hat, umbrella, plenty of breaks, and time in the shade, along with benzene-free sunscreen. Sources for this article include: LiveScience.com BBC.com EWG.org To read the original article click here. For more articles from NaturalHealth365 click here.

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Researchers Explore How to Protect Gut Integrity to Improve Outcomes in Blood Cancers

AHA Publisher — Fri, 12 Feb 2021 08:00:23 +0000

Medical University of South Carolina via EurekAlert – MUSC Hollings Cancer Center researchers found that a single strain of bacteria may be able to reduce the severity of graft-versus-host disease (GVHD), as reported online in February 2021 in JCI Insight. Bone marrow transplant can be a lifesaving procedure for patients with blood cancers. However, GVHD is a potentially fatal side effect of transplantation, and it has limited treatment options. This proof-of-concept study demonstrates that better treatment options may be on the horizon for patients with GVHD. Xue-Zhong Yu, M.D., associate director of Basic Science at Hollings Cancer Center, and lead author Hanief Sofi, Ph.D., realized that protecting the health of the gastrointestinal tract is a good target for reducing severe GVHD. “If we can figure out how to keep a patient’s intestinal tissue healthy before and after bone marrow transplant, then the patient’s outcome will be much better. We know that restoring the microbiota diversity in the gut is an effective solution, but that comes with many challenges,” said Yu. Patients with blood cancers, such as leukemia, must undergo radiation and chemotherapy before they can get their new cancer-free immune system through bone marrow transplantation. The balance between the immune system and intestinal microbiota, communities of microorganisms that live in the gut, is especially important for proper intestinal health. Unfortunately, the radiation and chemotherapy radically throw off this balance, and the diversity of the microbiota is reduced 100- or even 1,000-fold. This leads to a condition called “leaky gut.” Clinical studies have shown that patients who recover microbiota diversity faster have better outcomes and less severe GVHD. Reduced microbiota diversity is associated with more severe GVHD. Other studies have shown that fecal microbial transplantation (FMT) can be effective at reducing GVHD, but the challenge is how to get the right donor. Patients are heavily immune-deficient after bone marrow transplantation, and there is a great risk of bad infection if FMT is used in humans. The Yu laboratory used two different strains of mice to establish a GVHD model that closely resembles the biology that occurs in humans after bone marrow transplantation. The mice developed acute GVHD. FMT significantly reduced acute GVHD in this model and reduced donor T cell proliferation in the organs, which is what triggers GVHD. The researchers then used genetic sequencing to see which bacteria strains were most different between the fecal material of GVHD mice that received FMT and those that did not receive FMT. Mice that had the best outcome, the lowest GVHD, had the highest levels of a bacteria called B. fragilis. Mice given this single bacterial strain had significantly reduced acute and chronic (long-term) GVHD compared to mice that did not get B. fragilis. In fact, B. fragilis alone was as good or even better than FMT. Administration of B. fragilis increased overall gut microbial diversity, including increasing the amount of other beneficial bacteria strains. Surprisingly, GVHD was reduced in this model not only by live bacteria but also by bacteria that had been killed by short exposure to high heat. The observation that B. fragilis was the main effective bacteria in the FMT process was not entirely new: B. fragilis also reduces autoimmunity in type 1 diabetes and colitis. The current study by Yu and colleagues has two important findings. First, a molecule called polysaccharide A on the surface of B. fragilis appears to be critical for the GVHD-reducing functions of this bacteria. When the bacteria were modified to lack polysaccharide A, GVHD was not reduced compared to mice that did not receive any B. fragilis. Secondly, the administration of B. fragilis did not reduce the graft-versus-leukemia or cancer-killing effect of the bone marrow transplantation, even though it did reduce donor T cell expansion in the gut. This is critical, since GVHD treatment options that reduce the graft-versus-leukemia effect would not be clinically significant. “If this can be translated into the clinic, it would be a safer, easier and more effective treatment option,” said Yu. Further study in humans is needed to get this potential treatment into the clinic. Hematopoietic stem cells, given via bone marrow transplant, are classic immunotherapies for liquid tumors, but strategies to make the transplantation safer and more beneficial are sorely needed. Hollings Cancer Center researchers continue to search for the most effective therapies to improve patient outcomes and quality of life, he said. To read the original article click here.

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Researchers Identify New Drug Combination That Can Treat Acute Myeloid Leukemia

AHA Publisher — Fri, 22 Jan 2021 08:00:57 +0000

Sanford Burnham Prebys Medical Discovery Institute via News-Medical Net – Scientists have identified two drugs that are potent against acute myeloid leukemia (AML) when combined, but only weakly effective when used alone. The researchers were able to significantly enhance cancer cell death by jointly administering the drugs that are only partially effective when used as single-agent therapies. The study, a collaboration between Sanford Burnham Prebys Medical Discovery Institute and the University of Glasgow, was recently published in the journal Nature Communications. Our study shows that two types of drugs, MDM2 inhibitors and BET inhibitors, work synergistically to promote significant anti-leukemia activity. The results were surprising because previous research had shown that each drug on its own had modest benefit against AML. The new research provides scientific rationale to advance clinical studies of the drug combination in patients with AML.” (Peter Adams, Ph.D, Study Senior Author and Professor, Sanford Burnham Prebys Medical Discovery Institute) There are many types of AML, and different cases have different chromosome changes, gene mutations and epigenetic modifications, making it difficult for researchers to find novel therapies that will work for a substantial proportion of patients. Although much progress has been made toward finding effective treatments in recent years, the long-term overall survival has stagnated. According to the American Cancer Society, the five-year survival rate for adults with AML remains less than 30%. Notably, TP53, the most frequently mutated gene in all human cancers, is found unaltered in about 90% of AML patients. Since the product of the TP53 gene, p53, acts to suppress tumors, scientists have sought drugs that reactivate or boost its anti-cancer powers in AML, which should provide a clinical benefit. However, such drugs on their own have been disappointing in AML. “We were interested in combining MDM2 and BET inhibitors because each showed encouraging pre-clinical activity, but limited activity when given to patients as a single agent,” says Adams. “Previous research had shown that MDM2 inhibitors activate p53, and BET inhibitors suppress genes associated with leukemias–but not p53. “Our research unexpectedly showed that like MDM2 inhibitors, BET inhibitors activate p53, but through a different pathway. BET inhibitors mute the power of a protein called BRD4, which we found is a p53 suppressor in AML,” says Adams. “Between the two drugs, you end up with a ‘double whammy’ effect that fully unleashes the anti-cancer activity of p53. “Better therapies for AML are desperately needed,” adds Adams. “This study illustrates that targeting BRD4 as part of a combination therapy holds promise for patients diagnosed with this very dangerous disease.” To read the original article click here.

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Cancer Treatment: A Researcher Makes Breakthrough Immunotherapy Discovery

AHA Publisher — Fri, 01 Nov 2019 07:00:24 +0000

University of Montreal via EurekAlert – “Our work has identified a new T-cell protein that interacts with the key receptor that detects and responds to cancer antigens…” Dr Christopher E. Rudd, a researcher at the Centre de recherche de l’Hôpital Maisonneuve-Rosemont (CR-HMR) and Université de Montréal, has discovered a new cell therapy approach that boosts the immune response of T lymphocytes to malignant tumours. The results of the study have just been published in the respected journal Nature. “Our work has identified a new T-cell protein that interacts with the key receptor that detects and responds to cancer antigens,” says Prof. Rudd. “We have used those findings to develop a new form of immunotherapy in which hyperactivation of T cells enables them to penetrate and attack tumours. This discovery demonstrates that modulation of the identified protein can activate the immune system and lead to destruction of the cancer cells.” To date, the effectiveness of the new form of immunotherapy against leukemia and some skin cancers has been demonstrated in animals. The next stage will be clinical trials with human subjects. “This discovery is a scientific breakthrough that will have significantly enhance the immune system’s effectiveness in eliminating cancer cells,” says Dr. Denis-Claude Roy, scientific and medical director of the Center of Excellence in Cellular Therapy and CR-HMR. Eventually, this approach could also improve the effectiveness of the new CAR?T cell therapy currently being used at Hôpital Maisonneuve-Rosemont. To read the original article click here.

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