{"id":136482,"date":"2024-12-13T07:25:45","date_gmt":"2024-12-13T00:25:45","guid":{"rendered":"https:\/\/hotvideos24.online\/?p=136482"},"modified":"2024-12-13T07:25:45","modified_gmt":"2024-12-13T00:25:45","slug":"glioblastoma-syncs-with-the-bodys-internal-clock","status":"publish","type":"post","link":"https:\/\/hotvideos24.online\/?p=136482","title":{"rendered":"Glioblastoma Syncs With the Body\u2019s Internal Clock"},"content":{"rendered":"<p> <script async src=\"https:\/\/pagead2.googlesyndication.com\/pagead\/js\/adsbygoogle.js?client=ca-pub-3711241968723425\"\r\n     crossorigin=\"anonymous\"><\/script>\r\n<ins class=\"adsbygoogle\"\r\n     style=\"display:block\"\r\n     data-ad-format=\"fluid\"\r\n     data-ad-layout-key=\"-fb+5w+4e-db+86\"\r\n     data-ad-client=\"ca-pub-3711241968723425\"\r\n     data-ad-slot=\"7910942971\"><\/ins>\r\n<script>\r\n     (adsbygoogle = window.adsbygoogle || []).push({});\r\n<\/script><br \/>\n<\/p>\n<div>\n<p><strong>Summary: <\/strong>Glioblastoma, an aggressive brain cancer, syncs its internal clock to the host\u2019s circadian rhythms, leveraging daily hormone cycles for growth. Blocking these signals slowed tumor progression in mice and revealed that the timing of treatments like dexamethasone (DEX) critically influences outcomes.<\/p>\n<p>Administering DEX in the morning promoted tumor growth, while evening doses suppressed it. These findings highlight the potential of chronotherapy\u2014timing treatments to the body\u2019s internal clock\u2014as a personalized approach to managing glioblastoma.<\/p>\n<p><strong>Key Facts<\/strong><\/p>\n<ul class=\"wp-block-list\">\n<li><strong>Circadian Sync:<\/strong> Glioblastoma aligns its growth with the host\u2019s daily hormone rhythms.<\/li>\n<li><strong>Timing Matters:<\/strong> Morning DEX doses promote tumor growth; evening doses suppress it.<\/li>\n<li><strong>Chronotherapy Potential:<\/strong> Timing treatments to circadian rhythms could improve outcomes in glioblastoma.<\/li>\n<\/ul>\n<p><strong>Source: <\/strong>WUSTL<\/p>\n<p><strong>Virtually every cell in the human body has an internal clock. These clocks take their cues from a central clock in the brain. In a normal, biological process called synchrony, the central clock coordinates daily rhythms around the body, so that every cell and tissue recognizes the same external time of day.<\/strong><\/p>\n<p>Knowing local time helps our bodies to regulate essential processes, including when to sleep and wake, when to eat and what temperature to maintain, among many other important functions.<\/p>\n<p>But a deadly interloper is keeping time the same way.<\/p>\n<figure class=\"wp-block-image size-full\"><picture fetchpriority=\"high\" decoding=\"async\" class=\"wp-image-107015\"><source type=\"image\/webp\" srcset=\"https:\/\/neurosciencenews.com\/files\/2024\/12\/glioblastoma-circadian-clock-neurosicence.jpg.webp 1200w, https:\/\/neurosciencenews.com\/files\/2024\/12\/glioblastoma-circadian-clock-neurosicence-300x200.jpg.webp 300w, https:\/\/neurosciencenews.com\/files\/2024\/12\/glioblastoma-circadian-clock-neurosicence-770x513.jpg.webp 770w, https:\/\/neurosciencenews.com\/files\/2024\/12\/glioblastoma-circadian-clock-neurosicence-1155x770.jpg.webp 1155w, https:\/\/neurosciencenews.com\/files\/2024\/12\/glioblastoma-circadian-clock-neurosicence-370x247.jpg.webp 370w, https:\/\/neurosciencenews.com\/files\/2024\/12\/glioblastoma-circadian-clock-neurosicence-293x195.jpg.webp 293w, https:\/\/neurosciencenews.com\/files\/2024\/12\/glioblastoma-circadian-clock-neurosicence-150x100.jpg.webp 150w\" sizes=\"(max-width: 1200px) 100vw, 1200px\"\/><img fetchpriority=\"high\" decoding=\"async\" width=\"1200\" height=\"800\" src=\"https:\/\/neurosciencenews.com\/files\/2024\/12\/glioblastoma-circadian-clock-neurosicence.jpg\" alt=\"This shows neurons.\" srcset=\"https:\/\/neurosciencenews.com\/files\/2024\/12\/glioblastoma-circadian-clock-neurosicence.jpg 1200w, https:\/\/neurosciencenews.com\/files\/2024\/12\/glioblastoma-circadian-clock-neurosicence-300x200.jpg 300w, https:\/\/neurosciencenews.com\/files\/2024\/12\/glioblastoma-circadian-clock-neurosicence-770x513.jpg 770w, https:\/\/neurosciencenews.com\/files\/2024\/12\/glioblastoma-circadian-clock-neurosicence-1155x770.jpg 1155w, https:\/\/neurosciencenews.com\/files\/2024\/12\/glioblastoma-circadian-clock-neurosicence-370x247.jpg 370w, https:\/\/neurosciencenews.com\/files\/2024\/12\/glioblastoma-circadian-clock-neurosicence-293x195.jpg 293w, https:\/\/neurosciencenews.com\/files\/2024\/12\/glioblastoma-circadian-clock-neurosicence-150x100.jpg 150w\" sizes=\"(max-width: 1200px) 100vw, 1200px\"\/> <\/picture><figcaption class=\"wp-element-caption\">Taking advantage of data from a publicly available cancer database, the researchers found that glioblastoma patients tend to live 60% longer if their tumor expressed less glucocorticoid receptor. Credit: Neuroscience News<\/figcaption><\/figure>\n<p>Glioblastoma is an aggressive, incurable brain cancer that is the most common malignant brain tumor in adults. New research from Washington University in St. Louis shows that glioblastoma has an internal clock and syncs its daily rhythms to match \u2014 and take advantage of \u2014 the rhythms of its host. In this way, brain tumors grow in response to the host\u2019s daily release of steroid hormones like cortisol.<\/p>\n<p>Blocking circadian signals dramatically slowed glioblastoma growth and disease progression, the WashU scientists discovered. This process worked both in cells in a dish and in tumor-bearing animals, according to the study published Dec. 12 in Cancer Cell.<\/p>\n<p>\u201cGlioblastoma takes its cues from hormones released by the same central clock in the host that establishes the body\u2019s regular daily rhythms,\u201d said\u00a0Erik D. Herzog, PhD, the Viktor Hamburger Distinguished Professor and a professor of biology in Arts &amp; Sciences, senior author of the study.<\/p>\n<p>\u201cBlocking the daily surge in glucocorticoid signaling desynchronizes circadian rhythms in glioblastoma from the host and dramatically slows disease progression in tumor-bearing mice.\u201d<\/p>\n<p>\u201cOur previous research helped us to see a pattern,\u201d said\u00a0Maria F. Gonzalez-Aponte, PhD, first author of the study.<\/p>\n<p>\u201cWhether we were looking at\u00a0clinical data, or patient-derived cells or mice with model glioblastoma tumors,\u00a0chemotherapy treatment always worked best around normal waking time. That\u2019s what led us to think that these tumors knew the time of day outside.\u201d<\/p>\n<p>\u201cThis study provides yet another example of how important contextualizing research in real-life biology is to improving cancer treatment. It was possible to extend survival by synchronizing treatment to circadian time. No new drug was required,\u201d said\u00a0Joshua B. Rubin, MD, PhD, a professor of pediatrics and of neuroscience at WashU Medicine, a longtime collaborator with the Herzog laboratory and a co-author on the paper.<\/p>\n<p>The findings are important in part because they affect the way that glioblastoma tumors respond to a drug called dexamethasone (DEX), a synthetic steroid that is commonly given to glioblastoma patients to reduce brain edema after radiation and surgery. This study finds that giving DEX in the morning promotes tumor growth in mice, while giving it in the evening suppresses growth.<\/p>\n<p>\u201cFor many years, the use of DEX for glioblastoma has remained controversial because of studies showing either growth-promoting or growth-suppressing effects,\u201d Gonzalez-Aponte said.<\/p>\n<p>\u201cKnowing that glioblastoma has daily rhythms, we immediately asked if time of day of DEX administration could explain these different findings, and it seems like it does.\u201d<\/p>\n<p>\u201cThe interaction between brain tumors and the circadian system is now a targetable mechanism to optimize treatments,\u201d Herzog said.<\/p>\n<p><strong>Resetting the clock<\/strong><\/p>\n<p>Every day, just before a person or animal wakes up \u2014 in response to light and other environmental cues \u2014 the brain sends a signal to the adrenal glands to deliver a surge of steroid hormones called glucocorticoids.<\/p>\n<p>These hormones are involved in the well-recognized fight-or-flight response. But they also regulate a variety of more essential biological processes, including metabolism and immunity.<\/p>\n<p>\u201cUnder normal conditions, glucocorticoid levels increase dramatically each day prior to waking,\u201d Gonzalez-Aponte said. She and Herzog hypothesized that glioblastoma responds to this reliable daily glucocorticoid blast to set its clock in sync with its host.<\/p>\n<p>To test this idea, Gonzalez-Aponte first set out to see if she could disrupt a tumor\u2019s sense of timing by resetting its host\u2019s daily rhythms.<\/p>\n<p>She placed tumor-bearing mice in cages that could be made light or dark using a timer. By shifting when she turned on the lights, Gonzalez-Aponte coaxed the mice into adopting a flipped schedule. She could tell it was working by observing when each day the mice started running in their wheels.<\/p>\n<p>\u201cMice run on their wheels more during the night than during the day,\u201d Gonzalez-Aponte said. \u201cWhen we reverse the light and dark schedule, it\u2019s basically like flying from St. Louis to India. We\u2019re forcing them to resynchronize.\u201d<\/p>\n<p>As the mice took to their new, flipped schedules, the scientists monitored the cancer cells in the tumors in their brains for changes. They used a novel method to image clock gene expression in cancer cells in the freely behaving mice \u2014 collecting data every minute for multiple, continuous days.<\/p>\n<p>The scientists observed that two clock genes in the cancer cells,\u00a0<em>Bmal1<\/em>\u00a0and\u00a0<em>Per2<\/em>, changed their schedules as the mice changed their schedules.<\/p>\n<p>\u201cWhat we found was that\u00a0<em>Bmal1<\/em>\u00a0and\u00a0<em>Per2\u00a0<\/em>do the same thing as the mouse does in the wheel. That is, the cancer cells are resynchronizing their daily rhythms as the mouse resynchronizes its locomotor activity,\u201d Gonzalez-Aponte said.<\/p>\n<p>Similarly, the tumors remained synchronized to the host in conditions where the mice woke and slept according to their own circadian cycles in the absence of any environmental timing cues.<\/p>\n<p><strong>More than a wake-up signal<\/strong><\/p>\n<p>Glucocorticoids are just one of the circadian signals that have been shown to synchronize clocks in cells around the body. But glucocorticoids are important in the context of cancer care because synthetic versions of these steroid hormones are sometimes used in high doses to treat symptoms that cancer patients experience after surgery and treatment.<\/p>\n<p>DEX is one of these synthetic glucocorticoids. It is often administered in addition to chemotherapy and can be given to glioblastoma patients to reduce cerebral edema that comes after surgery and radiation.<\/p>\n<p>But despite its widespread use, doctors and scientists continue to report mixed results with DEX. Some studies have shown DEX has tumor suppressive effects, while others have shown that DEX promotes glioblastoma cell proliferation.<\/p>\n<p>Gonzalez-Aponte and Herzog suspected that if glioblastoma has its own reliable circadian rhythms, then its response to DEX \u2014 a synthetic glucocorticoid hormone \u2014 could vary based on the time of day when DEX was administered.<\/p>\n<p>They designed an additional set of experiments that showed that glucocorticoids promote or suppress glioblastoma cell growth depending on the time of day. In mice with glioblastoma brain tumors, the scientists found that tumor size increased significantly if DEX was administered in the morning, as compared to evening or control applications.<\/p>\n<p>These findings, in mice, have implications for the use of glucocorticoids like DEX in the clinic, Gonzalez-Aponte said. Additional research is needed to determine if there are times of the day when DEX can be used to reduce cerebral edema without promoting glioblastoma growth.<\/p>\n<p>\u201cAs we continue to study this brain tumor \u2014 how it grows, how it interacts with other cells in the brain and how it responds to therapies \u2014 it is important to acknowledge that timing is an essential variable,\u201d Gonzalez-Aponte said.<\/p>\n<p>Taking advantage of data from a publicly available cancer database, the researchers found that glioblastoma patients tend to live 60% longer if their tumor expressed less glucocorticoid receptor. This encourages them to pursue clinical trials aimed at avoiding DEX treatments in the morning.<\/p>\n<p>\u201cTo critically evaluate the potential for chronotherapy in different cancers, we must consider how daily rhythms arise and synchronize in specific tissues,\u201d Herzog said.<\/p>\n<p>\u201cIt\u2019s important to understand how circadian rhythms regulate tumor biology in a cell- and tissue-specific context,\u201d Herzog said.<\/p>\n<p>\u201cWe believe that this tractable and translatable approach will ultimately personalize patient care by determining when therapies should be given to cancer patients, depending on their individual circadian rhythms.\u201d<\/p>\n<h2 class=\"wp-block-heading\">About this brain cancer research news<\/h2>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Author: <\/strong><a href=\"http:\/\/neurosciencenews.com\/cdn-cgi\/l\/email-protection#dca8bdb0b5bdf2b3bbb0b5b3aeb99caba9afa8b0f2b9b8a9\" target=\"_blank\" rel=\"noreferrer noopener\">Talia Ogliore<\/a><br \/><strong>Source: <\/strong><a href=\"https:\/\/wustl.edu\" target=\"_blank\" rel=\"noreferrer noopener\">WUSTL<\/a><br \/><strong>Contact: <\/strong>Talia Ogliore \u2013 WUSTL<br \/><strong>Image: <\/strong>The image is credited to Neuroscience News<\/p>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Original Research: <\/strong>Open access.<br \/>\u201c<a href=\"https:\/\/doi.org\/10.1016\/j.ccell.2024.11.012\" target=\"_blank\" rel=\"noreferrer noopener\">Daily glucocorticoids promote glioblastoma growth and circadian synchrony to the host<\/a>\u201d by Erik D. Herzog et al. <em>Cancer Cell<\/em><\/p>\n<hr class=\"wp-block-separator has-text-color has-pale-cyan-blue-color has-alpha-channel-opacity has-pale-cyan-blue-background-color has-background\"\/>\n<p><strong>Abstract<\/strong><\/p>\n<p><strong>Daily glucocorticoids promote glioblastoma growth and circadian synchrony to the host<\/strong><\/p>\n<p>Glioblastoma (GBM) is the most common primary malignant brain tumor in adults with a poor prognosis despite aggressive therapy.<\/p>\n<p>Here, we hypothesized that daily host signaling regulates tumor growth and synchronizes circadian rhythms in GBM.<\/p>\n<p>We find daily glucocorticoids promote or suppress GBM growth through glucocorticoid receptor (GR) signaling depending on time of day and the clock genes,\u00a0<em>Bmal1<\/em>\u00a0and\u00a0<em>Cry<\/em>.<\/p>\n<p>Blocking circadian signals, like vasoactive intestinal peptide or glucocorticoids, dramatically slows GBM growth and disease progression.<\/p>\n<p>Analysis of human GBM samples from The Cancer Genome Atlas (TCGA) shows that high GR expression significantly increases hazard of mortality.<\/p>\n<p>Finally, mouse and human GBM models have intrinsic circadian rhythms in clock gene expression\u00a0<em>in\u00a0vitro<\/em>\u00a0and\u00a0<em>in\u00a0vivo<\/em>\u00a0that entrain to the host through glucocorticoid signaling, regardless of tumor type or host immune status.<\/p>\n<p>We conclude that GBM entrains to the circadian circuit of the brain, modulating its growth through clock-controlled cues, like glucocorticoids.<\/p>\n<p> <!-- Form created by Optin Forms plugin by WPKube: create beautiful optin forms with ease! --> <!-- https:\/\/wpkube.com\/ --><!--optinforms-form5-container--> <!-- \/ Optin Forms --> <\/div>\n<p><script async src=\"https:\/\/pagead2.googlesyndication.com\/pagead\/js\/adsbygoogle.js?client=ca-pub-3711241968723425\"\r\n     crossorigin=\"anonymous\"><\/script>\r\n<ins class=\"adsbygoogle\"\r\n     style=\"display:block\"\r\n     data-ad-format=\"fluid\"\r\n     data-ad-layout-key=\"-fb+5w+4e-db+86\"\r\n     data-ad-client=\"ca-pub-3711241968723425\"\r\n     data-ad-slot=\"7910942971\"><\/ins>\r\n<script>\r\n     (adsbygoogle = window.adsbygoogle || []).push({});\r\n<\/script><br \/>\n<br \/><div data-type=\"_mgwidget\" data-widget-id=\"1660802\">\r\n<\/div>\r\n<script>(function(w,q){w[q]=w[q]||[];w[q].push([\"_mgc.load\"])})(window,\"_mgq\");\r\n<\/script>\r\n<br \/>\n<br \/><a href=\"https:\/\/neurosciencenews.com\/glioblastoma-circadian-clock-28239\/\">Source link <\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Summary: Glioblastoma, an aggressive brain cancer, syncs its internal clock to the host\u2019s circadian rhythms, leveraging daily hormone cycles for growth. 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