Bacteria promote lung tumor development, study suggests
Antibiotics or anti-inflammatory drugs may help combat lung cancer.
Anne Trafton | MIT News Office
January 31, 2019
MIT cancer biologists have discovered a new mechanism that lung tumors exploit to promote their own survival: These tumors alter bacterial populations within the lung, provoking the immune system to create an inflammatory environment that in turn helps the tumor cells to thrive.
In mice that were genetically programmed to develop lung cancer, those raised in a bacteria-free environment developed much smaller tumors than mice raised under normal conditions, the researchers found. Furthermore, the researchers were able to greatly reduce the number and size of the lung tumors by treating the mice with antibiotics or blocking the immune cells stimulated by the bacteria.
The findings suggest several possible strategies for developing new lung cancer treatments, the researchers say.
“This research directly links bacterial burden in the lung to lung cancer development and opens up multiple potential avenues toward lung cancer interception and treatment," says Tyler Jacks, director of MIT's Koch Institute for Integrative Cancer Research and the senior author of the paper.
Chengcheng Jin, a Koch Institute postdoc, is the lead author of the study, which appears in the Jan. 31 online edition of Cell.
Linking bacteria and cancer
Lung cancer, the leading cause of cancer-related deaths, kills more than 1 million people worldwide per year. Up to 70 percent of lung cancer patients also suffer complications from bacterial infections of the lung. In this study, the MIT team wanted to see whether there was any link between the bacterial populations found in the lungs and the development of lung tumors.
To explore this potential link, the researchers studied genetically engineered mice that express the oncogene Kras and lack the tumor suppressor gene p53. These mice usually develop a type of lung cancer called adenocarcinoma within several weeks.
Mice (and humans) typically have many harmless bacteria growing in their lungs. However, the MIT team found that in the mice engineered to develop lung tumors, the bacterial populations in their lungs changed dramatically. The overall population grew significantly, but the number of different bacterial species went down. The researchers are not sure exactly how the lung cancers bring about these changes, but they suspect one possibility is that tumors may obstruct the airway and prevent bacteria from being cleared from the lungs.
This bacterial population expansion induced immune cells called gamma delta T cells to proliferate and begin secreting inflammatory molecules called cytokines. These molecules, especially IL-17 and IL-22, create a progrowth, prosurvival environment for the tumor cells. They also stimulate activation of neutrophils, another kind of immune cell that releases proinflammatory chemicals, further enhancing the favorable environment for the tumors.
“You can think of it as a feed-forward loop that forms a vicious cycle to further promote tumor growth," Jin says. “The developing tumors hijack existing immune cells in the lungs, using them to their own advantage through a mechanism that's dependent on local bacteria."
However, in mice that were born and raised in a germ-free environment, this immune reaction did not occur and the tumors the mice developed were much smaller.
Blocking tumor growth
The researchers found that when they treated the mice with antibiotics either two or seven weeks after the tumors began to grow, the tumors shrank by about 50 percent. The tumors also shrank if the researchers gave the mice drugs that block gamma delta T cells or that block IL-17.
The researchers believe that such drugs may be worth testing in humans, because when they analyzed human lung tumors, they found altered bacterial signals similar to those seen in the mice that developed cancer. The human lung tumor samples also had unusually high numbers of gamma delta T cells.
“If we can come up with ways to selectively block the bacteria that are causing all of these effects, or if we can block the cytokines that activate the gamma delta T cells or neutralize their downstream pathogenic factors, these could all be potential new ways to treat lung cancer," Jin says.
Many such drugs already exist, and the researchers are testing some of them in their mouse model in hopes of eventually testing them in humans. The researchers are also working on determining which strains of bacteria are elevated in lung tumors, so they can try to find antibiotics that would selectively kill those bacteria.
The research was funded, in part, by a Lung Cancer Concept Award from the Department of Defense, a Cancer Center Support (core) grant from the National Cancer Institute, the Howard Hughes Medical Institute, and a Margaret A. Cunningham Immune Mechanisms in Cancer Research Fellowship Award.
Reprinted with permission of MIT News
While legalization has benefits, a new study suggests it may have one big drawback.
- A new study finds that rates of marijuana use and addiction have gone up in states that have recently legalized the drug.
- The problem was most severe for those over age of 26, with cases of addiction rising by a third.
- The findings complicate the debate around legalization.
Cannabis Use Disorder, is that when you get so high you can’t figure out how to smoke anymore?<div class="rm-shortcode" data-media_id="hfrVfwoH" data-player_id="FvQKszTI" data-rm-shortcode-id="0e62d9cb9c0a2361f81e9b5278706614"> <div id="botr_hfrVfwoH_FvQKszTI_div" class="jwplayer-media" data-jwplayer-video-src="https://content.jwplatform.com/players/hfrVfwoH-FvQKszTI.js"> <img src="https://cdn.jwplayer.com/thumbs/hfrVfwoH-1920.jpg" class="jwplayer-media-preview" /> </div> <script src="https://content.jwplatform.com/players/hfrVfwoH-FvQKszTI.js"></script> </div> <p><a href="https://www.ncbi.nlm.nih.gov/books/NBK538131/" target="_blank">Cannabis use disorder</a>, also known as CUD or cannabis/marijuana addiction, is a psychological disorder described in DSM 5 as "the continued use of cannabis despite clinically significant impairment." This includes people being unable to cut down on their usage despite wanting to, those who often use it despite finding it severely impairs their ability to function, or those who are putting themselves in danger to secure access to the drug.</p><p>While an understanding that marijuana can be addictive has existed for some time, and the image of the pothead who smokes so much they can hardly function is prevalent in our society, the effects of legalization on addiction rates have somehow gone understudied until now. Importantly, previous studies had failed to consider usage rates amongst populations over the age of 25.</p><p>In the new study, published in <a href="https://jamanetwork.com/journals/jamapsychiatry/article-abstract/2755276?utm_campaign=articlePDF%26utm_medium%3darticlePDFlink%26utm_source%3darticlePDF%26utm_content%3djamapsychiatry.2019.3254" target="_blank">JAMA Psychiatry</a>, focused on self-reported data on monthly drug use in four states where marijuana is now legal, Colorado, Washington, Alaska, and Oregon, from both before and after the drug was legalized in each state and compared it to others which have not yet legalized.</p><p>The data gave insights into the drug use habits of the respondents and specifically gave information about if they had smoked at all in the last month, the frequency of their drug use, and if they had ever had issues with how much they were using drugs.The researchers ultimately considered the responses of 505,796 individuals.</p><p>The increase in cannabis usage they found was <a href="https://www.newsweek.com/cannabis-use-disorder-rising-us-states-where-weed-legal-1471170" target="_blank">considerable</a>. The number of respondents over the age of 26 who claimed to have used the drug in the last month went up by 23% compared with their counterparts in states that have yet to legalize. Abuse of the drug by this group rose by 37%. </p><p>Teen usage rose by 25%, and addiction rates rose as well. This increase was small, though, and the authors have suggested it may be due to an unknown factor. The rate of usage or abuse for respondents between the ages of 18 and 25 did not increase at all. </p><p>After breaking the results down by demographics, the primary finding held; adults over the age of 26 are using marijuana more often when it is legalized, and they are starting to use it too much.</p>
The grain of salt<p>As in any study where findings are self-reported, the exact numbers you see here should be taken with a grain of salt. They could be slightly higher or lower. As this study relies on people self-reporting their usage of a drug that is still illegal in many places, it is very possible that the apparent spike in addiction rates is caused by more accurate reporting, as people who live in an area where pot is still illegal may be less likely to report smoking it every day.</p><p>And it should be repeated a thousand times over that correlation and causation are not the same thing. There could be some unknown factor causing these increases in each case. </p><p>Despite these qualifications, the study is still useful in giving us a general sense of what may happen in states that have yet to legalize. </p>
What does this mean for society and drug users?<div class="rm-shortcode" data-media_id="BdVRmwgX" data-player_id="FvQKszTI" data-rm-shortcode-id="d5c2f9e3739c26170f98b48bf07a3444"> <div id="botr_BdVRmwgX_FvQKszTI_div" class="jwplayer-media" data-jwplayer-video-src="https://content.jwplatform.com/players/BdVRmwgX-FvQKszTI.js"> <img src="https://cdn.jwplayer.com/thumbs/BdVRmwgX-1920.jpg" class="jwplayer-media-preview" /> </div> <script src="https://content.jwplatform.com/players/BdVRmwgX-FvQKszTI.js"></script> </div> <p>While claims of "reefer madness" are greatly exaggerated, marijuana has several well established and thoroughly studied side <a href="https://en.wikipedia.org/wiki/Long-term_effects_of_cannabis#Mental_health" target="_blank">effects</a>. While occasional use isn't terribly harmful, addiction can be. Lead author Magdalena Cerdá of New York University explains in the study that heavy marijuana use is associated with "psychological and physical health concerns, lower educational attainment, decline in social class, unemployment, and motor vehicle crashes."</p><p>A substantial increase in the number of people who are addicted to the stuff will incur costs to society down the line. <strong></strong></p><p>Of course, a 37% increase in problematic usage means that the percentage of adults smoking too much went from .9% to 1.23% of the population responding to the survey. This makes it far less prevalent than issues with alcohol, which affected around 6% of all Americans in <a href="https://www.verywellmind.com/prevalence-of-alcoholism-in-the-united-states-67876" target="_blank">2018</a>. </p><p>Recently, Big Think's <a href="https://bigthink.com/u/philip-perry" target="_self">Philip Perry</a> wrote a piece about how <a href="https://bigthink.com/want-to-protect-the-health-of-35-million-americans-legalize-cannabis" target="_self">legalization could improve the health of millions</a> by allowing the government to regulate the purity of commercially sold marijuana. This remains true. However, it must be weighed against the findings of this study, which suggests that at least some of these health gains will be wiped out by increased addiction rates.</p>
What does this mean for legalization efforts?<div class="rm-shortcode" data-media_id="bnPA9J9g" data-player_id="FvQKszTI" data-rm-shortcode-id="429e1d17ba031b02d4e79b4f02f54ab5"> <div id="botr_bnPA9J9g_FvQKszTI_div" class="jwplayer-media" data-jwplayer-video-src="https://content.jwplatform.com/players/bnPA9J9g-FvQKszTI.js"> <img src="https://cdn.jwplayer.com/thumbs/bnPA9J9g-1920.jpg" class="jwplayer-media-preview" /> </div> <script src="https://content.jwplatform.com/players/bnPA9J9g-FvQKszTI.js"></script> </div> <p>The legalization steamroller will undoubtedly keep rolling along. While health concerns are one factor in the debate over marijuana, it is only one of many. In Illinois, where I live, weed will become legal on January 1<sup>st</sup> of 2020. The legalization campaign and <a href="https://www.chicagotribune.com/politics/ct-met-illinois-recreational-marijuana-legislation-20190531-story.html" target="_blank">legislation</a> were more concerned with issues of social justice, the failures of prohibition, and finding a new source of tax revenue (<a href="https://www.chicagotribune.com/news/breaking/ct-illinois-tickets-collection-agencies-20190703-20190711-gyf77w52mbcdxkaxpleeay277a-story.html" target="_blank">since we're half broke</a>) than with matters of potential addiction.</p><p>As Vox <a href="https://www.vox.com/policy-and-politics/2019/11/13/20962924/marijuana-legalization-use-addiction-study" target="_blank">reports</a>, the authors of the study aren't suggesting that legalization shouldn't take place; that is another, broader debate. They merely wish to present the fact that legalization has a particular side effect that we should be aware of.</p><p>While this study is unlikely to change anybody's stance on if weed should be legalized or not, it does show us a critical element to be considered when discussing drug policy. No drug is perfectly safe, and we have reason to believe that legalizing marijuana will mean that more people will have a hard time with it. Let's hope that legalization proponents keep that in mind as they rack up their victories. </p>
Tea and coffee have known health benefits, but now we know they can work together.
Credit: NIKOLAY OSMACHKO from Pexels
- A new study finds drinking large amounts of coffee and tea lowers the risk of death in some adults by nearly two thirds.
- This is the first study to suggest the known benefits of these drinks are additive.
- The findings are great, but only directly apply to certain people.
Maybe you should enjoy this article with a cup of coffee or tea.<p> The <a href="https://drc.bmj.com/content/8/1/e001252?T=AU" target="_blank" rel="noopener noreferrer">study</a> involved 4,923 type 2 diabetics living in Japan. The average participant was 66 years old. All of the participants were taken from the rolls of the Fukuoka Diabetes Registry, a study geared at learning about the effects of new treatments and lifestyle changes on the health of diabetics. <br> <br> The participants filled out questionnaires concerning their health, diet, habits, and other factors. Among the questions were two focused on determining how much green tea or coffee, if any, the participants consumed over the course of a week. The health of the participants was recorded for five years. During this time, 309 of the test subjects died from a variety of causes. <br> <br> Subjects who drank more than one cup of tea or coffee per day demonstrated lower odds of dying than those who had none. Those who consumed the most tea and coffee, more than four and two cups a day, respectively, enjoyed the most significant reductions in their risk of death. This level of consumption was associated with a 40 percent lower risk of <a href="https://www.sciencedaily.com/releases/2020/10/201020190129.htm" target="_blank" rel="noopener noreferrer">death</a>. </p><p>Most interestingly, the effects of drinking tea and coffee appear to combine to reduce risk even further. Those who reported drinking two or three cups of tea a day and two or more cups of coffee were 51 percent less likely to die during the study, while those who drank a whopping four or more cups of tea and two or more cups of coffee had a 63 percent lower risk of <a href="https://www.medicalnewstoday.com/articles/diabetes-coffee-and-green-tea-might-reduce-death-risk" target="_blank" rel="noopener noreferrer">death</a>. </p>
So, should I start swimming in a vat of coffee and green tea?<iframe width="730" height="430" src="https://www.youtube.com/embed/LY0E-JQxeoY" frameborder="0" allow="accelerometer; autoplay; clipboard-write; encrypted-media; gyroscope; picture-in-picture" allowfullscreen></iframe><p> Not quite. </p><p> The primary takeaway from this study is that Japanese adults with type 2 diabetes who drink a lot of green tea and/or coffee die less often than similar people who do not. If this effect is caused by something in the drink, lifestyle choices people who drink that much tea all make, or something else remains unknown. The finding must be considered an association at this point. <br> <br> The eye-popping reductions in mortality rates are compared to the risk of death of others in the study. The people who died reported drinking less tea and coffee than those who lived. Unless you have several demographic and conditional similarities to the subjects of this study, you probably won't suddenly be at a two-thirds lower risk of death than your peers because you drink green tea. </p><p> Like all studies that depend on self-reporting, it is also possible that people misstated how much they consumed any one item. The study also did not look into other factors like socioeconomic status or education level, also known to impact death rates and potentially linked to coffee and tea consumption. </p><p> However, it is yet another study in the pile that suggests that <a href="https://www.healthline.com/nutrition/top-13-evidence-based-health-benefits-of-coffee" target="_blank" rel="noopener noreferrer">coffee</a> and <a href="https://www.healthline.com/nutrition/top-10-evidence-based-health-benefits-of-green-tea" target="_blank" rel="noopener noreferrer">green tea</a> are good for you. That much is increasingly <a href="https://www.health.harvard.edu/press_releases/health-benefits-linked-to-drinking-tea" target="_blank" rel="noopener noreferrer">agreed</a><a href="https://www.rush.edu/health-wellness/discover-health/health-benefits-coffee" target="_blank" rel="noopener noreferrer"> upon</a>. This study also suggests the benefits are additive, which is a new development.</p><p><br> So, while it isn't time to start the IV drip of green tea, a cup or two probably won't <a href="https://www.webmd.com/diabetes/news/20201022/coffee-green-tea-might-extend-life-for-folks-with-type-2-diabetes" target="_blank" rel="noopener noreferrer">hurt</a>. </p>
But most city dwellers weren't seeing the science — they were seeing something out of Blade Runner.
On Sept. 9, many West Coast residents looked out their windows and witnessed a post-apocalyptic landscape: silhouetted cars, buildings and people bathed in an overpowering orange light that looked like a jacked-up sunset.