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 Arkilaus Kladit
My name is Arkilaus Kladit. I'm from the Knasaimos-Tehit tribe in South Sorong Regency, West Papua Province, Indonesia. For decades my tribe has been fighting to protect our forests from outsiders who want to log it or clear it for palm oil. For my people, the forest is our mother and our best friend. Everything we need to survive comes from the forest: food, medicines, building materials, and there are many sacred sites in the forest.
Map of the Knasaimos traditional lands.
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By Farah Aqel
Overthinkers are people who are buried in their own obsessive thoughts. Imagine being in a large maze where each turn leads into an even deeper and knottier tangle of catastrophic, distressing events — that is what it feels like to them when they think about the issues that confront them.
Ruminating<p>According to the late Susan Nolen-Hoeksema, a professor of psychology at Yale University, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796420/" target="_blank">ruminating</a> involves replaying a problem over and over in your mind. We ruminate by obsessing over our thoughts and thinking repetitively about various aspects of a past situation.</p><p>It usually involves regret, self-loathing and self-blaming. Rumination is associated with the development of depression, anxiety and eating disorders. </p><p>People prone to such patterns of thought may, for example, overanalyze every single detail of a relationship that breaks up. They often blame themselves for what has happened and are overcome with regret, with typical thoughts being: </p><p>- I should have been more patient and more supportive. </p><p>- I have lost the most perfect partner ever. </p><p>- No one will love me again.</p>
Worrying<p>Worrying is wanting to predict the future. It involves negative thoughts about things that might and might not happen.</p><p>- They'll not like me in the interview; they'll not give me the job. </p><p>- I haven't heard back from other employers. How long will I be unemployed?</p><p>These thoughts are energy-draining and distressing. They could happen to anyone under stress. But when you reach the point where your thoughts and worrying are preventing you from doing what you want to do — from living your life to the fullest — then you should take action.</p>
Catch Yourself Overthinking<p>Reuben Berger, a psychotherapist at the university hospital in the western German city of Bonn, recommends several practical steps that you could employ in your daily routine when you catch yourself worrying or ruminating.</p><p>One effective remedy, says Berger, is the <a href="https://www.uofmhealth.org/health-library/uf9938" target="_blank">thought-stopping technique.</a></p><p>"When the negative thoughts come or ruminations start, you say to yourself: 'Stop!,'" he says, adding that it is more effective when you actually say the word out loud.</p><p>He even recommends having a rubber band around your wrist to ping against yourself while saying the word. Adding a visual component by imagining a stop sign also makes the technique more powerful, he says.</p><p>The main idea here is conditioning yourself to stop the loop of worrying (making future predictions) or rumination (obsessing over past events).</p><p>Berger says the technique could take up to two weeks to take effect and that it needs to be practiced every day. "Consistency is very important," he says. </p>
Thoughts Are Just Thoughts<p>Another way of dealing with negative thoughts often used in modern therapy is realizing that thoughts aren't facts, says Berger.</p><p>He says it is important when we think something to ask: Is that real? Did that really happen? What is the worst thing that could happen?</p><p>Flight anxiety is one example where untrue thoughts are accepted as facts. Although air travel is the safest way to get around, people suffering from fear of flying accept their thoughts and fears as reality, then act upon them by refusing to fly.</p>
Mindfulness<p>Berger also recommends the use of mindfulness techniques, in which attention is paid to experiences in the moment without judging them, as a way of reducing worrying.</p><p>"Mindfulness helps you to distance yourself from your thoughts and to be more present in the moment," he says.</p><p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432145/#R2" target="_blank">Several studies</a> have shown that mindfulness has a positive impact on reducing stress-related behaviors such as rumination and worrying, as focusing on the moment makes anxiety about other problems impossible.</p><p>Mindfulness can be practiced during routine activities by paying attention to your body and your surroundings. For instance, when you leave for work in the morning, you can focus on sensing the breeze, listen attentively to birds, feel the gravel under your feet and monitor your breath. </p>
Trick Your Brain Into Happiness<p>People plagued by obsessive thoughts do not always choose healthy ways like mindfulness to distract from them, however.</p><p> Dr. Edward Selby, a psychologist at Florida state university, has shown in a study that people try to avoid rumination by engaging in a range of uncontrolled behaviors, such as binge eating and substance abuse.</p><p>But he says that a much better way to overcome such distress is by distraction and shifting attention away from problems that are obsessing us.</p><p>There are many activities that can be used to distract from rumination, he says, and people should choose the one that works best for them. Here are some examples:</p><p>- Listen to music</p><p>- Read a book</p><p>- Take a hot shower</p><p>- Dance or exercise </p><p>- Talk to a friend (not about the problem)</p><p>- Watch a movie</p><p>- Mindfulness meditation</p>
Changing the Perception of Events<p>The way people perceive a situation largely influences their emotions and behavior. It is not the situation itself that determines how they feel, but rather the way they interpret it.</p><p>Reframing negative thoughts can lead to positive emotions and, subsequently, healthier behaviors — including a reduction in damaging overthinking and worrying.</p><p>Cognitive behavioral therapy (CBT) is currently a gold standard in psychotherapy. CBT aims to change the way people think and act. It largely involves challenging unhelpful beliefs or attitudes such as overgeneralization — thinking "I always fail at public speaking" when you have had one bad experience in front of an audience, for example — or "catastrophization," i.e., imagining the worst possible outcome to a situation. </p><p>A psychotherapist can teach people how to implement such thought-changing techniques into their lives. Techniques vary depending on their issues and goals.</p>
Solutions Are at Hand<p>Try to find ways of avoiding worrying, rumination and overthinking that make you feel most comfortable.</p><p>Incorporating any routine in your life when you're stressed isn't an easy task, but you can do it! If you feel overwhelmed, you can always seek professional help. </p><p><em>If you are suffering from serious emotional strain or suicidal thoughts, do not hesitate to seek professional help. You can find information on where to find such help, no matter where you live in the world, <a href="https://www.befrienders.org/" target="_blank">at this website.</a></em></p>
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By Michael Baker, Amanda Kvalsvig and Nick Wilson
On Sunday, New Zealand marked 100 days without community transmission of COVID-19.
Deaths From COVID-19 Per Million Population<img lazy-loadable="true" src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMzU0ODIyOS9vcmlnaW4ucG5nIiwiZXhwaXJlc19hdCI6MTY0MjkzMDc1OX0.7Yp1h1hokihlMJUurDukGmq-Y8NJB0V-07O1ukEjGt0/img.png?width=980" id="0fe6a" class="rm-shortcode" data-rm-shortcode-id="6bce85a610aee18e2f4f1c1caca7b8a0" data-rm-shortcode-name="rebelmouse-image" />
<div id="77fff" class="rm-shortcode" data-rm-shortcode-id="ce7b34f8986d3d36bee5d4d83ac0822c"><blockquote class="twitter-tweet twitter-custom-tweet" data-twitter-tweet-id="1292270210238447616" data-partner="rebelmouse"><div style="margin:1em 0">COVID-19 Update There are no new cases of COVID-19 to report in New Zealand today. It has been 100 days since t… https://t.co/Cz55ixGZUz</div> — Unite against COVID-19 (@Unite against COVID-19)<a href="https://twitter.com/covid19nz/statuses/1292270210238447616">1596936201.0</a></blockquote></div>
Getting Through the Pandemic<p>We have gained a much better understanding of COVID-19 over the past eight months. Without effective control measures, it is likely to continue to spread globally for many months to years, ultimately infecting billions and killing millions. The proportion of infected people who die appears to be <a href="https://www.medrxiv.org/content/10.1101/2020.05.03.20089854v4" target="_blank">slightly below 1%</a>.</p><p>This infection also causes serious <a href="https://www.bmj.com/content/370/bmj.m2815" target="_blank">long-term consequences</a> for some survivors. The largest uncertainties involve <a href="https://www.nature.com/articles/d41586-020-02278-5" target="_blank">immunity to this virus</a>, whether it can develop from exposure to infection or vaccines, and if it is long-lasting. The potential for treatment with antivirals and other therapeutics is also still uncertain.</p><p>This knowledge reinforces the huge benefits of sustaining elimination. We know that if New Zealand were to experience widespread COVID-19 transmission, the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310086/" target="_blank">impact on Māori and Pasifika populations</a> could be catastrophic.</p><p>We have previously described critical measures to get us through this period, including the use of fabric face masks, improving contact tracing with suitable digital tools, applying a science-based approach to border management, and the need for a dedicated national public health agency.</p><p>Maintaining elimination depends on adopting a highly strategic approach to risk management. This approach involves choosing an optimal mix of interventions and using resources in the most efficient way to keep the risk of COVID-19 outbreaks at a consistently low level. Several measures can contribute to this goal over the next few months, while also allowing incremental increases in international travel:</p><ul><li>resurgence planning for a border-control failure and outbreaks of various sizes, with state-of-the-art contact tracing and an upgraded alert level system</li><li>ensuring all New Zealanders own a <a href="https://www.nzma.org.nz/journal-articles/mass-masking-an-alternative-to-a-second-lockdown-in-aotearoa" target="_blank">re-useable fabric face mask</a> with their <a href="https://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=12354409" target="_blank">use built into the alert level system</a></li><li>conducting exercises and simulations to test outbreak management procedures, possibly including "mass masking days" to engage the public in the response</li><li>carefully exploring processes to allow <a href="https://blogs.otago.ac.nz/pubhealthexpert/2020/06/16/preventing-outbreaks-of-covid-19-in-nz-associated-with-air-travel-from-australia-new-modelling-study-of-alternatives-to-quarantine/" target="_blank">quarantine-free travel</a> between jurisdictions free of COVID-19, notably various Pacific Islands, Tasmania and Taiwan (which may require digital tracking of arriving travellers for the first few weeks)</li><li>planning for carefully managed inbound travel by key long-term visitor groups such as tertiary students who would generally still need managed quarantine.</li></ul>
Building Back Better<p>New Zealand cannot change the reality of the global COVID-19 pandemic. But it can leverage possible benefits.</p><p>We should conduct an <a href="https://blogs.otago.ac.nz/pubhealthexpert/2020/06/11/five-key-reasons-why-nz-should-have-an-official-inquiry-into-the-response-to-the-covid-19-pandemic/" target="_blank">official inquiry into the COVID-19 response</a> so we learn everything we possibly can to improve our response capacity for future events.</p><p>We also need to establish a specialized national public health agency to <a href="https://blogs.otago.ac.nz/pubhealthexpert/2017/12/20/the-havelock-north-drinking-water-inquiry-a-wake-up-call-to-rebuild-public-health-in-new-zealand/" target="_blank">manage serious threats to public health</a> and provide critical mass to <a href="https://blogs.otago.ac.nz/pubhealthexpert/2020/02/05/a-preventable-measles-epidemic-lessons-for-reforming-public-health-in-nz/" target="_blank">advance public health generally</a>. Such an agency appears to have been a key factor in the success of Taiwan, which avoided a costly lockdown entirely.</p><p>Business as usual should not be an option for the recovery phase. A recent <a href="https://www.nzherald.co.nz/business/news/article.cfm?c_id=3&objectid=12353555" target="_blank">Massey University survey</a> suggests seven out of ten New Zealanders support a green recovery approach.</p><p>New Zealand's elimination of COVID-19 has drawn attention worldwide, with a description just <a href="https://www.nejm.org/doi/full/10.1056/NEJMc2025203" target="_blank">published</a> in the New England Journal of Medicine. We support a rejuvenated World Health Organization that can provide improved global leadership for pandemic prevention and control, including greater use of an elimination approach to combat COVID-19.</p>
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