Reviewed by James Ives, M.Psych. (Editor)Jan 29 2019Researchers have been struggling for years to find a treatment for patients who have a recurrence of acute myeloid leukemia (AML), an aggressive blood cancer that is one of the most lethal cancers. About 19,520 news cases are diagnosed a year, and about 10,670 people a year die from it, according to the American Cancer Society.Purdue University researchers are developing a series of drug compounds that have shown promise in treating such cases. About 30 percent of AML patients have a mutation caused by a kinase called FLT3, which makes the leukemia more aggressive. Inhibitors of FLT3, such as Radapt, approved last year by the U.S. Food and Drug Administration, have shown good initial response to treating leukemia. Gilteritinib, another FLT3 inhibitor, was recently approved toward the end of 2018. But AML patients on FLT3 inhibitor therapy often relapse because of secondary mutations in the FLT3 and existing treatments have not been fully successful in treating those cases.Researchers on a team led by Herman O. Sintim, the Drug Discovery Professor of Chemistry in Purdue’s Department of Chemistry, say they have developed a series of compounds that work not only on AML with common FLT3 mutation, but also drug-resistant AML harboring problematic mutations, such as the gatekeeper F691L mutation, which some leukemia patients who relapse harbor.”These compounds have a great potential to be the next-generation AML therapeutics for relapsed patients who no longer respond to first- or second-generation FLT3 inhibitors,” Sintim said.The results of the study were published Friday here in the journal EBioMedicine.The research aligns with Purdue’s Giant Leaps celebration, recognizing the university’s global advancements made in health, longevity and quality of life as part of Purdue’s 150th anniversary. This is one of the four themes of the yearlong celebration’s Ideas Festival, designed to showcase Purdue as an intellectual center solving real-world issues.Results of the study are encouraging because, while advancements have been made in many other forms of cancer over the past three decades, advancement for AML has been slow.AML, which accounts for only about 1 percent of all cancers, occurs when blood cells fail to mature or differentiate and multiply unchecked, causing a lack of adequate oxygen-carrying red blood cells. AML is uncommon before the age of 45, but it does occur in children. The five-year survival rate is about 30 percent, and for patients over the age of 65, the five-year survival rate is less than 10 percent.Related StoriesStudy shows how SIRT1 plays key role in maintaining the regenerative potential of leukemic stem cellsImmune-boosting compound could make pancreatic cancers susceptible to immunotherapyResearchers discover biochemical agent responsible for blood pressure drop in sepsisThe compounds the Purdue researchers are studying, alkynyl aminoisoquinoline and alkynyl napthyridine, have been successful in preclinical studies, Sintim said. “In mouse studies, almost no leukemia burden was visible after compound treatment for only a few weeks. Crucially this new class of FLT3 inhibitor also works against drug-resistant secondary mutations, such as the problematic F691L mutatio,” Sintim said.In the clinic, the goal is to reduce leukemia levels enough so that a patient can undergo a bone marrow transplant. Most often if the leukemia burden is not drastically reduced before bone marrow transplant, there is a high likelihood that the AML will return.Sintim said the compounds the researchers are developing have shown no signs of toxicity. Observations in clinical testing show that high doses of the compounds result in no weight loss, irritability or essential organs dysfunction. Another advantage of the compounds the Purdue researchers are developing is they can be taken orally, which makes it easier for patients to take at home compared with an injection.Sintim said there’s much still to be learned about AML.”Acute myeloid leukemia is not caused by only one mutation. It’s caused by many mutations. What that means is that you might have an acute myeloid leukemia patient who would have one type of a mutation and you could have another one with another type of mutation and you cannot give them the same drug. Even when a patient initially presents with one type of mutation, during treatment a new mutation could emerge” he said. “So to effectively treat a cancer you need to know what the aligning mutation is, this is what is called precision medicine; tailoring a drug to a particular disease driver.”Sintim also is a co-founder of a biotech startup called KinaRx LLC, which has licensed the compounds the researchers are working on through Purdue’s Office ofTechnology Commercialization. Both Sintim’s lab and KinaRx LLC are looking for development partners. Source:https://www.purdue.edu/newsroom/releases/2019/Q1/drug-compound-could-be-next-generation-treatment-for-aggressive-form-of-leukemia.html
Chelsea Himsworth, Regional Director for the Canadian Wildlife Health Cooperative, University of British Columbia This article is republished from The Conversation under a Creative Commons license. Read the original article.by Taboolaby TaboolaSponsored LinksSponsored LinksPromoted LinksPromoted LinksYou May LikeVikings: Free Online GamePlay this for 1 min and see why everyone is addicted!Vikings: Free Online GameUndoSecurity SaversWindows Users Advised To Do This TodaySecurity SaversUndoTruthFinder People Search SubscriptionOne Thing All Liars Have in Common, Brace YourselfTruthFinder People Search SubscriptionUndoKelley Blue Book2019 Lexus Vehicles Worth Buying for Their Resale ValueKelley Blue BookUndoArticles VallyDad Cuts Daughter’s Hair Off For Getting Birthday Highlights, Then Mom Does The UnthinkableArticles VallyUndoGundry MD Total Restore SupplementU.S. Cardiologist: It’s Like a Pressure Wash for Your InsidesGundry MD Total Restore SupplementUndo Rats! They eat our food, chew through our property and spread all sorts of nasty diseases. And they are gross (right?), with those naked tails and quick, unpredictable movements. Rats invade our homes — our castles! — the one place where we should be safe and in control. Over the millennia that we have lived with them, rats have proven themselves virtually impossible to expunge. They are so adaptable that they can exploit and infest virtually every corner of our cities. They avoid traps and poisons and reproduce at such a staggering rate that extermination attempts usually end up being a game of whack-a-mole… or, rather, whack-a-rat. Is it any wonder that many cities seem to be plagued by rats? Or do the cities themselves bear some responsibility for their rat problems? This is what I have been exploring over the past 10 years as a wildlife and public health researcher with the Canadian Wildlife Health Cooperative and the University of British Columbia.Headbutting Tiny Worms Are Really, Really LoudThis rapid strike produces a loud ‘pop’ comparable to those made by snapping shrimps, one of the most intense biological sounds measured at sea.Your Recommended PlaylistVolume 0%Press shift question mark to access a list of keyboard shortcutsKeyboard Shortcutsplay/pauseincrease volumedecrease volumeseek forwardsseek backwardstoggle captionstoggle fullscreenmute/unmuteseek to %SPACE↑↓→←cfm0-9接下来播放Why Is It ‘Snowing’ Salt in the Dead Sea?01:53 facebook twitter 发邮件 reddit 链接https://www.livescience.com/65936-new-york-city-rats-and-humans.html?jwsource=cl已复制直播00:0000:3500:35 Challenges of managing urban rodents For the most part, when it comes to dealing with rats, cities have it all wrong. For example, rat-related issues are addressed using a hodgepodge of unrelated policy and programming. At best, municipal leadership is highly fragmented; at worst, it’s absent altogether. Municipal governments may address rat infestations that occur on public properties or in buildings scheduled for demolition. Local health authorities may address infestations in food establishments or where there is a demonstrated health risk. For the most part, people are left to fend for themselves. Another problem is that we know very little about urban rats. There is simply not enough information about them to answer even the most basic questions like: How many rats are there? Where do they live? Why are they there? Is the problem getting worse? Despite this lack of knowledge, cities are often willing to invest tremendous amounts of time and resources into pest control interventions, such as New York City’s $32 million “war on rats.” It means that cities have no metric to determine the return on their investments, because without knowing what the rat problem looked like beforehand, there is no way of knowing whether an intervention made the problem any better. The cohabiting solution The key to solving this problem may lie in simply changing our perspective. Rather than viewing the city as a place entirely under human control that’s being invaded by rats, we need to recognize that the city is an ecosystem and that rats live here too. This does not mean that we should love rats, nor does it mean that we need to leave them alone. Rather, it shifts the focus to managing the ecosystem of which rats are a part, rather than focusing on the rats themselves. Once we recognize that we are managing a system, it becomes clear that leadership and strategic planning are critical. The very concept of a system is that the whole is more than the sum of its parts; this is the antithesis of the reductionist approach that we’re accustomed to that deals with infestations on a case-by-case basis. Instead, we need to understand the urban ecosystem, just like we would if we were trying to manage polar bear populations in the Arctic or elephant populations on the savanna. This means substantive, long-term investments in collecting data on rat populations and the specific conditions that support them, as well as the impact of any implemented interventions. It also means understanding the interface between rats and humans. For the majority of urban centres, rats pose a relatively minor threat to people. The threats are certainly not in proportion to the amount of negative attention rats receive. This means we need to understand why we find rats so disturbing, and what can be done to reduce that fear. Urban ecologies An ecosystem lens also directs us to look at areas of vulnerability and resilience within the system. When it comes to rats, our homes are the most obvious place of vulnerability, where the relationship between rats and people is least acceptable. However, private residences are often the areas most ignored by municipal powers. Also, rats and rat-related issues disproportionately affect impoverished, inner-city neighbourhoods, and residents of these neighbourhoods are particularly vulnerable to the physical and mental health impacts of living with rats. By identifying and focusing on these highly vulnerable scenarios, cities can start to make meaningful changes in how we perceive and deal with rats. This is not to say the rest of the urban landscape should be ignored. Rather, the identification of particular areas of vulnerability needs to take place within a larger framework that uses ecosystem-based principles to address rats specifically. Examples include changing the way that garbage cans are designed and enacting tougher bylaws that enshrine the right to live in a healthy and rat-free environment. These sorts of policies and programs that increase the resilience of the system have the potential to curtail the physical and psychological damage done by rats. The result is that co-existence with rats will come to seem no more unthinkable than our co-existence with, for instance, squirrels.
Navjot Singh Sidhu – THE HINDU SHARE SHARE EMAIL SHARE people COMMENT June 06, 2019 Under fire from Chief Minister Amarinder Singh for Congress’ “poor performance” in urban areas in the Lok Sabha election, Punjab minister Navjot Singh Sidhu, on Thursday, skipped the first Cabinet meeting after elections and asserted he could not be “taken for granted”.Amarinder had recently said he intended to change the cricketer-turned-politician’s portfolio — Local Government Department — over the party’s performance.“I cannot be taken for granted. I have been a performer throughout the 40 years of my life. Be it international cricket, or world class commentary with Geoffrey Boycott, TV shows or motivational talks,” Sidhu told reporters.He said the urban areas had played pivotal role in the party’s victory in Punjab and his department is being singled out.“My department is being singled out publicly. I always regard him as my elder and listen to him. But it hurts. Where is the collective responsibility now? He (Amarinder) could have called me and said anything he wanted to say,” Sidhu said here.In the recently held general election, Congress won eight out of the 13 seats. The SAD-BJP combine won four while the AAP managed to win just one seat. COMMENTS Published on politics