Anthrax vs. Cancer – Researchers Harness Deadly Toxin to Cure Dogs and Potentially People
Dogs with terminal bladder cancer improved with a new modified anthrax treatment. pyotr021 / iStock / Getty Images Plus
By R. Claudio Aguilar
Can the feared anthrax toxin become an ally in the war against cancer? Successful treatment of pet dogs suffering bladder cancer with an anthrax-related treatment suggests so.
Anthrax is a disease caused a by bacterium, known as Bacillus anthracis, which releases a toxin that causes the skin to break down and forms ulcers, and triggers pneumonia and muscle and chest pain. To add to its sinister resumé, and underscore its lethal effects, this toxin has been infamously used as a bioweapon.
I am a biochemist and cell biologist who has been working on research and development of novel therapeutic approaches against cancer and genetic diseases for more than 20 years. Our lab has investigated, designed and adapted agents to fight disease; this is our latest exciting story.
Among all cancers, the one affecting the bladder is the sixth most common and in 2019 caused more than 17,000 deaths in the U.S. Of all patients that receive surgery to remove this cancer, about 70% will return to the physician's office with more tumors. This is psychologically devastating for the patient and makes the cancer of the bladder one of the most expensive to treat.
To make things worse, currently there is a worldwide shortage of Bacillus Calmette-Guerin, a bacterium used to make the preferred immunotherapy for decreasing bladder cancer recurrence after surgery. This situation has left doctors struggling to meet the needs of their patients. Therefore, there is a clear need for more effective strategies to treat bladder cancer.
Anthrax Comes to the Rescue
Years ago scientists in the Collier lab modified the anthrax toxin by physically linking it to a naturally occurring protein called the epidermal growth factor (EGF) that binds to the EGF receptor, which is abundant on the surface of bladder cancer cells. When the EGF protein binds to the receptor – like a key fits a lock – it causes the cell to engulf the EGF-anthrax toxin, which then induces the cancer cell to commit suicide (a process called apoptosis), while leaving healthy cells alone.
In collaboration with colleagues at Indiana University medical school, Harvard University and MIT, we designed a strategy to eliminate tumors using this modified toxin. Together we demonstrated that this novel approach allowed us to eliminate tumor cells taken from human, dog and mouse bladder cancer.
This highlights the potential of this agent to provide an efficient and fast alternative to the current treatments (which can take between two and three hours to administer over a period of months). I also think it is good news is that the modified anthrax toxin spared normal cells. This suggests that this treatment could have fewer side effects.
Helping Our Best Friends
These encouraging results led my lab to join forces with Dr. Knapp's group at the Purdue veterinary hospital to treat pet dogs suffering from bladder cancer.
Canine patients for whom all available conventional anti-cancer therapeutics were unsuccessful were considered eligible for these tests. Only after standard tests proved the agent to be safe in laboratory animals, and with the consent of their owners, six eligible dogs with terminal bladder cancer were treated with the anthrax toxin-derived agent.
Two to five doses of this medicine, delivered directly inside the bladder via a catheter, was enough to shrink the tumor by an average of 30%. We consider these results impressive given the initial large size of the tumor and its resistance to other treatments.
There Is Hope for All
Our collaborators at Indiana University Hospital surgically removed bladder cells from human patients and sent them to my lab for testing the agent. At Purdue my team found these cells to be very sensitive to the anthrax toxin-derived agent as well. These results suggest that this novel anti-bladder cancer strategy could be effective in human patients.
The treatment strategy that we have devised is still experimental. Therefore, it is not available for treatment of human patients yet. Nevertheless, my team is actively seeking the needed economic support and required approvals to move this therapeutic approach into human clinical trials. Plans to develop a new, even better generation of agents and to expand their application to the fight against other cancers are ongoing.
R. Claudio Aguilar is an associate professor of biological sciences at Purdue University.
Disclosure statement: R. Claudio Aguilar received funding from National Institutes of Health.
Reposted with permission from The Conversation.
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By Joe Roman and Taylor Ricketts
The COVID-19 pandemic in the United States is the deepest and longest period of malaise in a dozen years. Our colleagues at the University of Vermont have concluded this by analyzing posts on Twitter. The Vermont Complex Systems Center studies 50 million tweets a day, scoring the "happiness" of people's words to monitor the national mood. That mood today is at its lowest point since 2008 when they started this project.
The Hedonometer measures happiness through analysis of key words on Twitter, which is now used by one in five Americans. This chart covers 18 months from early 2019 to July 2020, showing major dips in 2020. hedonometer.org<p>These same tweets also indicate a potential salve. Before pandemic lockdowns began, doctoral student <a href="https://scholar.google.com/citations?user=0P0ZYbIAAAAJ&hl=en" target="_blank">Aaron Schwartz</a> <a href="https://doi.org/10.1002/pan3.10045" target="_blank">compared tweets before, during, and after visits to 150 parks, playgrounds and plazas</a> in San Francisco. He found that park visits corresponded with a spike in happiness, followed by an afterglow lasting up to four hours.</p><p>Tweets from parks contained fewer negative words such as "no," "not" and "can't," and fewer first-person pronouns like "I" and "me." It seems that nature makes people more positive and less self-obsessed.</p><p>Parks keep people happy in times of global crisis, economic shutdown and public anger. Research has also shown that transmission rates for COVID-19 are <a href="https://www.sfchronicle.com/news/article/Is-risk-of-coronavirus-transmission-lower-15287602.php" target="_blank">much lower outdoors than inside</a>. As scholars who study <a href="https://scholar.google.com/citations?user=yFzb2EUAAAAJ&hl=en" target="_blank">conservation</a> and how nature <a href="https://scholar.google.com/citations?user=CCnUeN8AAAAJ&hl=en" target="_blank">contributes to human well-being</a>, we see opening up parks and creating new ones as a straightforward remedy for Americans' current blues.</p>
Park Visits Are Up During the Pandemic<p>According to the Hedonometer, sentiments expressed online started trending lower in mid-March as the impacts of the pandemic became clear. As lockdowns continued, they registered the lowest sentiment scores on record. Then in late May, effects from George Floyd's death in police custody and the following protests and police response once again could be seen on Twitter. May 31, 2020 was the saddest day of the project.</p><p>Recent surveys of park visitors around the University of Vermont have shown people <a href="https://osf.io/preprints/socarxiv/sd3h6" target="_blank">using green spaces more</a> since COVID-19 lockdowns began. Many people reported that parks were highly important to their well-being during the pandemic.</p>
<div id="4c7e4" class="rm-shortcode" data-rm-shortcode-id="bc0ac146ab2a94228f32d973fc2ab272"><blockquote class="twitter-tweet twitter-custom-tweet" data-twitter-tweet-id="1289428912879964160" data-partner="rebelmouse"><div style="margin:1em 0">#Goldengatepark #sf #quarantinemood https://t.co/9l3ufnbkt6</div> — Suvd (@Suvd)<a href="https://twitter.com/Suvd19486406/statuses/1289428912879964160">1596258783.0</a></blockquote></div><p>The powerful effects of nature are strongest in large parks with more trees, but smaller neighborhood parks also provide a significant boost. Their impact on happiness is real, measurable and lasting.</p><p>Twitter records show that parks increase happiness to a level similar to the bounce at Christmas, which typically is the happiest day of the year. Schwartz has since expanded his <a href="https://arxiv.org/pdf/2006.10658.pdf" target="_blank">Twitter study</a> to the 25 largest cities in the U.S. and found this bounce everywhere.</p><p>Parks and public spaces won't cure COVID-19 or stop police brutality, but they are far more than playgrounds. There is growing evidence that parks contribute to mental and physical health in a range of communities.</p><p>In a 2015 study, for example, Stanford researchers sent people out for one of two walks: through a local park or on a busy street. Those who walked in nature showed <a href="https://doi.org/10.1016/j.landurbplan.2015.02.005" target="_blank">improved moods and better memory performance</a> compared to the urban group. And a team led by <a href="https://penniur.upenn.edu/people/eugenia-gina-south" target="_blank">Gina South</a> of the University of Pennsylvania showed in a 2018 study that greening and cleaning up blighted vacant lots in Philadelphia <a href="http://dx.doi.org/10.1001/jamanetworkopen.2018.0298" target="_blank">reduced local residents' feelings of depression, worthlessness and poor mental health</a>.</p>
Creative Strategies<p>It isn't easy to create new parks on the scale of San Francisco's Golden Gate Park or the Washington Mall, but smaller projects can expand outdoor space. Options include greening vacant lots, closing streets and investing in existing parks to make them safer, greener and shadier and support wildlife.</p><p>These initiatives don't have to be capital-intensive. In the University of Pennsylvania study, for example, renovating a vacant lot by removing trash, planting grass and trees and installing a low fence cost only about US$1,600.</p><p>Urban green space is most needed in neighborhoods that have lacked funding for parks, especially given <a href="https://www.nytimes.com/2020/04/08/nyregion/coronavirus-race-deaths.html" target="_blank">COVID-19's disproportionate impact on Black and Latinx people</a>.</p><p>Cities can also create parklike spaces by <a href="https://theconversation.com/with-fewer-cars-on-us-streets-now-is-the-time-to-reinvent-roadways-and-how-we-use-them-140408" target="_blank">closing streets to cars</a>. Many cities worldwide are currently retooling their transportation systems for the post-COVID-19 world in order to <a href="https://thecityfix.com/blog/bicycles-slower-speeds-livable-city-paris-mayor-anne-hidalgo-plans-ambitious-second-term-dario-hidalgo/" target="_blank">reallocate public space</a>, widen sidewalks and make more space for nature.</p><p>Urban designers, artists, ecologists and other citizens can play a direct role, too, creating pop-up parks and green spaces. Some advocates <a href="https://www.bloomberg.com/news/articles/2017-09-15/a-brief-history-of-park-ing-day" target="_blank">transform parking spaces into mini-parks</a> with grass, potted trees and seating for just the time on the meter, to make a larger point about turning so much public space over to cars.</p><p>Or cities can invest a little more. Minneapolis, Cincinnati and Arlington, Virginia, have won <a href="https://www.tpl.org/parkscore" target="_blank">national recognition</a> for their ambitious investments in public park systems. These areas could serve as models for neighborhoods that lack access to parks.</p>
<div id="25fd0" class="rm-shortcode" data-rm-shortcode-id="383f0d2df0237e9359c30dcce6cd6c42"><blockquote class="twitter-tweet twitter-custom-tweet" data-twitter-tweet-id="1276558744835379201" data-partner="rebelmouse"><div style="margin:1em 0">Looking to safely get outside? Check out the best parks for social distancing in this year's top ten ParkScore citi… https://t.co/HJjEtDsrTD</div> — The Trust for Public Land (@The Trust for Public Land)<a href="https://twitter.com/tpl_org/statuses/1276558744835379201">1593190296.0</a></blockquote></div>
A New Park Deal?<p>The United States has historically driven economic recovery with major infrastructure investments, like the New Deal in the 1930s and the 2009 <a href="https://www.investopedia.com/terms/a/american-recovery-and-reinvestment-act.asp" target="_blank">American Reinvestment and Recovery Act</a>. Such investments could easily include nature-positive spaces.</p><p>Parks are not panaceas, as evidenced by the widely publicized <a href="https://www.nytimes.com/2020/07/06/nyregion/amy-cooper-false-report-charge.html" target="_blank">racist confrontation between a white woman and a Black birder</a> in New York's Central Park in early July. But Hedonometer data add to a <a href="https://advances.sciencemag.org/content/5/7/eaax0903?utm_source=miragenews&utm_medium=miragenews&utm_campaign=news" target="_blank">growing body of evidence</a> that they provide <a href="https://doi.org/10.1073/pnas.1807504116" target="_blank">clear mental health benefits</a>. Creating and expanding parks also <a href="https://www.nrpa.org/contentassets/f568e0ca499743a08148e3593c860fc5/economic-impact-study-summary.pdf" target="_blank">generates jobs and economic activity</a>, with much of the money spent locally.</p><p>We believe investments in nature are well worth it, offering both short-term solace in difficult times and long-term benefits to health, economies and communities.</p>
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New York State Attorney General Letitia James announced Thursday that she will attempt to dismantle the National Rifle Association (NRA), arguing that years of corruption and mismanagement warrant the dissolution of the activist organization, as CNN reported.
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By Gianna-Carina Grün
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