An Innovative New Cancer Therapy Hijacks Bacteria to Fight Tumors

A cancer cell (white) being attacked by immune cells (in red). A new bacterial cancer therapy gives a boost to this natural anti-cancer attack. (Image: NIH)

Researchers from South Korea have engineered a strain of bacteria that infiltrates tumors and fools the body’s immune system into attacking cancer cells. In experiments, the modified bacteria worked to reduce cancer in mice, raising hope for human trials.

In a study published today in Science Translational Medicine, a research team led by biologists Joon Haeng Rhee and Jung-Joon Min from Chonnam National University in South Korea describe a new immunotherapy in which a bioengineered strain of Salmonella is converted into a biological version of the fabled Trojan Horse. Once inside an unsuspecting tumor, the modified bacteria transmits a signal that triggers nearby immune cells into launching an attack on the malignant cells.

In preliminary tests, the technique shrunk tumors in more than half of the mice who received injections of the commandeered bacteria. It’s preliminary, but the researchers are hopeful that this form of immunotherapy will be both safe and effective in humans.

Bacterial cancer therapy dates back to 1893 when surgeon William B. Coley noticed that recurrent tumors of connective tissue, called sarcoma tumors, disappeared after patients became infected with Erysipelas bacterium. This led him to develop a therapy, now called “Coley’s toxins,” that utilizes various bacterial strains to fight cancer. This line of cancer research went into hibernation, however, once surgical and chemical therapies emerged.

But since 2008, bacterial cancer therapy has been going through a bit of a renaissance. Some success in this area has been reported, particularly when scientists use modified Salmonella to deliver various therapeutic agents to the body, such as genes and anti-cancer medicines. Bacteria have a natural ability to home in on tumors, making them excellent cargo ships. Unfortunately, all pre-existing bacterial cancer therapies require multiple injections of the microbes, and relapses are common.

In an effort to develop a better method, Rhee and Min took a strain of Salmonella typhimurium and made it 10,000 times less toxic than normal, while retaining the bacterium’s ability to stay alive and carry therapeutic cargo. And unlike previous efforts, the modified bacteria weren’t designed to deliver medicines per se; instead, they were engineered to deliver an important message to nearby immune cells—a message that says, “Attack this tumor!”

Credit: Chonnam National University

Specifically, the Salmonella bacteria is genetically modified to secrete a foreign protein known as flagellin (FlaB). This protein, found in an aquatic microbe called Vibrio vulnificus, is the building block of flagellum—the lash-like appendage that allows microorganisms to swim around. Since vertebrate animals, including humans, don’t have a flagellum, this protein is foreign to our cells. When voracious white blood cells known as macrophages detect the presence of these foreign proteins, they immediately sense danger and spring into action.

Macrophages are like microscopic Roombas, vacuuming anything that doesn’t look like it’s supposed to be there, including bits of cellular debris, unfamiliar substances, viruses, unwanted bacteria, and importantly, cancer cells. But macrophages don’t always see tumors as a threat, owing to the presence of identifiable markers, such familiar proteins associated with healthy cells. The modified bacteria, parked inside a tumor with its alien cargo, basically tricks the immune cells into launching an attack (i.e. triggering an immune response). The macrophages then happily go about devouring the malignant cells.

The researchers tested their Trojan Horse bacteria in mice with colon cancer. Three days after the injections, the bacteria inside the tumors were 10,000 times more abundant than those found in the mice’s vital organs. The macrophages then quickly went to work, causing the tumors to shrink below detectable limits in more than half of the mice.

Microscopic images show the macrophage immune cells (the colorful splotches) proliferating and working in cancerous cells. (Image: Jin Hai Zheng et al., 2017)

“We [documented the] total eradication of tumors in approximately 60 percent of treated subjects,” explained Rhee and Min in an interview with Gizmodo “The remaining 20 percent of the animals remained stable,” meaning they didn’t die, “though tumors were reduced in size.”

Importantly, the modified FlaB-expressing bacteria was shown to be non-toxic, and it didn’t invade non-cancerous tissues in the rodents. Instead, Salmonella, armed with FlaB, shrank the tumors, prolonged the survival of the mice, and prevented new growths from re-appearing in mouse models of human colon cancer.

“We did not use any extra medication or chemotherapy,” said Rhee and Min, adding that their bacterial therapy could be combined with other anti-cancer techniques, such as radiation or chemotherapy.

Should this form of immunotherapy reach the clinical stage (and that’s still a big if—mice studies can be notoriously unreliable), the researchers don’t see regular injections as being appropriate.

“The bacteria could be injected repeatedly if required,” noted the researchers. “But we do not encourage multiple repeated therapies since the human immune system will build up an antibacterial immune response after repeated administration of the same bacteria.”An antibacterial response would prevent Salmonella from proliferating at the tumor site, meaning the tumor would no longer be marked for destruction.

To cope with this problem, the researchers are planning to use different strains with distinct biological markers should repeated injections be required in some instances.

It’s too early to tell if this treatment will be effective and safe in humans, but these early results are encouraging. Rhee and Min say their technique should work for other cancers, including breast cancer, glioma, melanoma, and lung cancer. “This is more like proof of concept study,” said the researchers.

“We are planning comprehensive preclinical tests in nearest future. If we find right partners that grant reasonable funding, clinical trials could hopefully be started very soon.”

[Science Translational Medicine]

from Gizmodo

Injectable male contraceptive tested successfully on monkeys


It’s 2017, and male birth control methods haven’t really advanced beyond the vasectomy — a procedure that’s been performed since the 1800s — or condoms. That’s what makes Vasalgel so intriguing. It’s a "potentially" reversible method that uses gel to chemically incapacitate sperm as they pass through the vas deferens. It doesn’t stop sperm production, and, like with a vasectomy, the swimmers are just absorbed into the body. In a recent experiment, male rhesus monkeys given the treatment didn’t sire any offspring during a year-long study.

Sixteen males were housed with between three and nine breeding females in a free-roaming social setting. "All males wee monitored for at least one breeding season; 7 of the 16 were almost continuously housed with females for two years," Vasalgel manufacturer the Parsemus Foundation writes.

More than that, there apparently wasn’t any sort of tissue irritation from the injection either. Even better? No mechanical switch nestled inside the scrotum. And versus hormonal treatments, there weren’t any side effects like depression, acne and what The Guardian describes as "soaring libido."

"We were impressed that this alternative worked in every single monkey, even though this was our first time trying it," lead veterinarian Angela Colagross-Schouten told The Guardian. The next step is raising the money needed for human clinical trials.

The first phase of testing would focus on whether it or not it works in humans in the US, while the second would target reversing the procedure. Previous experiments in rabbits have shown the process to be reversible, but larger creatures haven’t been studied.

A 2011 piece from Wired estimated that human clinical trials could cost $500,000 or more and that the entire approval process could cost as much as $5 million. Chump change for a pharmaceutical company, right? Not quite. Parsemus is a non-profit so access to that kind of cash comes from donors and outside funding. Hence the company setting up Revolution Contraceptives LLC as a way to court "socially-minded" investors.

As a bit of history, Vasalgel started life over 30 years ago in India as a way to purify water in rural areas. Scientist Sujoy Guha thought it up as a way to line pumps with a compound that would destroy bacteria and not deplete itself. Then after a few tweaks, he began testing it as a contraceptive in mice, and later humans. In his trials, which reached Phase III in human tests at the time of publication, the procedure had worked "100 percent of the time."

It’s a fascinating story, and I can’t suggest hitting the coverage link below strongly enough.

Source: Parsemus Foundation

from Engadget

The Porsche 911 Carrera is everything a sports car should be


Porsche 911 PDK 12Hollis Johnson

We don’t lack for sports cars in this world. If you want some affordable thrills behind the wheel, you can buy a Mazda Miata for less than $30,000 (and you can buy a well-loved one for less than $5,000).

From there, the sky’s the limit: the Ferrari 488 GTB, for example, will set you back $360,000. And it will be worth every precious penny.

What I’m saying is you don’t lack for choice. But what if you don’t feel like shopping? What if you just want perhaps the greatest sports car ever produced by human hands on planet Earth?

Well, then you should just spend $111,070 — the price of our test car — and get yourself a 2017 Porsche 911 Carrera (base price is only $89,400).

Here’s why:

For some, the 911 has always been an odd-looking car, what with its bulbous rear end and bug-like headlights. But over the decades — the first 911 arrived way back in 1963 — the idiosyncratic rear-engine design has been continuously refined. The eighth generation of the sports car is perhaps the best-looking iteration, although all true 911 lovers have their favorite version.

The 911’s rear is now … well, elongated seems like the right word.

But of course, it’s still distinctively Porsche. The real challenge with this car has always been that the rear end is an unusual place to put the motor, at least by modern standards. For over 50 years, Porsche has designed around this issue.

The tail lights are sleek.

And just is case you were wondering, it is a Porsche, and there is no substitute.

Up close and personal with the mechanism.

The dual exhaust is finished off with chrome. From these pipes emanates the unmistakable song of the legendary flat-six engine, a 3.0-liter powerplant that makes 370 horsepower with 331 pound-feet or torque.

The 911 has a bit more road presence that its ancestors, but it still isn’t very big, tipping the scales at just over 3,000 lbs.

The headlights have evolved and become more aerodynamic, but they’re still the 911’s visual signature.

There is a back seat. Versatility!

The front aero effects help the 911 stay glued to the road.

The badge is quite modest, tasteful even.

Here it is again, at the hub of a 20-inch Carrera S “Platinum Satin” wheel, If you looks closely, you can also see the ventilated discs and stout brake calipers.

The key of ignition, shaped rather like a 911.

What the driver sees. The tachometer is front and center on the instrument cluster, and there’s a moderate amount of controls on the steering wheels, including a drive-mode selector at the lower right that mimics the famous Ferrari manettino. You can select Normal, Sport, and Sport Plus, or devise a custom setting.

There’s also a neat feature of the drive selector which allows an extra boost of racetrack-level power if you want to pass and pass like you mean it! Vroom!

This is actually just about the biggest Porsche badge on the entire car.

And why is the tach in the center? Because nothing is more important in a Porsche than how hard the engine is working. Notice as well that you can add the navigation to the display on the right.

The Porsche infotainment system has been recently upgraded, with a full rollout on the New Panamera sedan. All the expected features are present and accounted for: satellite radio, Bluetooth integration, a touchscreen, and USB and AUX ports for devices.

The GPS navigation is perfectly reliable.

To fire this sucker up you still have to insert the fob into the LEFT-HAND ignition and give it a turn.

The car is nominally a 2+2, really a near-GT car, so you can carry two passengers in the back. But they won’t travel with anything that even vaguely resembles legroom or headroom. If you look hard, you can see the back seats: think of them as a place to stow a jacket or a backpack.

Time. A critical thing in a high-performance automobile. The 911 Carrera makes the 0-60 mph run in a swift four seconds and tops out at 182 mph (under track conditions), according to Porsche.

By the way, if you’re wondering where the “Carrera” moniker comes from, it originated with a race in Mexico called the Carrera Panamericana that had a reputation for death and danger and was only officially run for a few years in the 1950s.

Now let’s get to the PDK transmission. It stands for “Porsche Doppelkupplung,” and it’s Porsche’s version of a racing-style double clutch. It can run in automatic mode, with seven-speeds, or it can be operated manually using the shifter or via paddles behind the steering wheel. It’s absolutely brilliant.

It isn’t easy to get a look at the 3.0-liter, twin-turbo flat six, tucked away in the back. Regardless, this a potent base powerplant. But the turbos are the New New Thing — the base 911’s flat-six was always a natural air-breather in the past.

The frunk, or front trunk. I could get my overnight bag in there, but not much else.

And what’s the final verdict?

I sampled the 911 Carrera and the Targa 4S within about a week of each other, after not having piloted a 911 in a few years.

The Targa was a car I really want to get my hands on, and it was magnificent. But it’s also a 911 that, besides having a targa-style roof, also sports a 420-horsepower motor, a notable bump up from the base Carrera. The Targa 4S also had all-wheel-drive, versus the Carrera’s old-school rear-wheel-drive (yes, there is a lot of variation among 911s, and you can check them all out here.)

Frankly, I’ll always take less horsepower and RWD on my sports cars, any day of the week. The Carrera’s 370 is already plenty of beef — the additional 50 horses for the 4S were for me needless. Sure, you can feel the oomph when accelerating and passing, but you’re just not going to get into all 420 horses, not in the same way as the Carrera’s 370.

And although the 4S gives the impression that it’s fail-safe, it’s almost too mannered. The Carrera isn’t wild, but the balance of the driving dynamics is what I favor in the 911: rear-engine ripping out that pure Porsche growl, power going down to the rear wheels, idealized steering pretty much telling you where to put the nose. If you want, you can force matters and get the back end to slip. Under the right conditions, the 911 is the most festively oversteering machine imaginable.

That’s risky and even with all sort of modern traction management systems, you can still feel the 911’s rear wheels wants to do their thing. But that’s really a safety feature. Overdriving this car in civilization is a bad idea. It forces you to assess your skills honestly and behave accordingly, lest you put $100,000 in peril.

In any event, as I wrote in my review of the Targa 4s, for me the 911 has always been the most self-contained of fast and fun cars. The Ferrari 458, for example, contains a screaming V8 located amidships. Press toward the red line and your eardrums could bleed. A Lamborghini with a V10 creates a wild symphony of exotic burps from its yowling V10. A Corvette Z06 has its 650-horsepower V8 parked up front, and the roar coming out of the exhaust pipes in the back is borderline unholy.

Against this rude cluster of supercars, the 911’s behavior, sonic or otherwise, is subdued. Powerfully subdued, but subdued nonetheless. I’m not saying it’s quiet. But it offers just a subtle indication of power by comparison.

What really makes the 911 so great, and invariably leads me to conclude that it’s the finest car on earth and always will be, all happens when you slip behind the wheel. Obviously, this could be me, but the car just feels right.

The 911 isn’t the perfect sports car — it is, in fact, a bundle of adaptations and workarounds, gradually executed over many decades. What it is, is the sports car perfected. 

If you want to have fun behind the wheel, get one. You won’t look back.

from SAI

21 Essential Recipes You Can Make in Your Microwave — Kitchn


There are many things the microwave does really well. When you’re facing dinnertime at the end of a long day, it can even venture into that life-saver category. From mug cakes and popcorn, to potato chips and eggs, the microwave can do it all.

The mug cake is one of our favorite revelations of the past few years. It takes seconds to whip up, and makes a perfectly portioned single-serve cake. This Nutella version is a chocolatey, indulgent treat.

Boxed mac and cheese is no longer the easiest way to get your cheesy noodle fix. Instead try making this ultra-creamy one-bowl microwave recipe. Or spread the love and forward the recipe to your favorite college student — they’ll thank you come exam time.

This entire meal is made with items you can pick up at a grocery store or drugstore. Is it the epitome of fine dining? Maybe not. Is it delicious and filled with vegetables? Absolutely.

We’re going to take a guess that you’ve made a baked potato in the microwave before, but if you’ve had inconsistent or less-than-stellar results, follow this step-by-step guide. It’s a perfect office lunch, or easy dinner the next time you find yourself flying solo.

Master this skill to take your sad desk lunches to a whole new level. Believe us, leftover pasta, quinoa, lentils, or other grains are made infinitely better with a gooey poached egg cracked on top.

Okay, we know that the best quesadillas are actually made on the stovetop. There’s no question that using a skillet results in a crispier tortilla. But the microwave will always win convenience. Just be sure not to overfill your tortillas or the cheese won’t melt evenly.

We’re not talking about the bags of popcorn you buy that come wrapped in plastic and drenched in "butter flavor." You can just as easily make microwave popcorn with a brown paper lunch bag. It’s our favorite afternoon snack.

Broccoli is one of those go-to side dishes we just couldn’t make dinner without. But if you’re short on time one night, you can easily steam it in the microwave. It’s also one of our favorite tricks to make leftovers more nutritious — just add steamed broccoli.

Yes, you can make breakfast in just one minute, and we’re not talking about heating up a breakfast burrito or an oatmeal packet. This omelet might not pass muster in a French restaurant or culinary school, but as far as quick breakfasts go, it’s a winner.

Spaghetti squash is one of our favorite versatile veggies, but it can take a long time to cook. The microwave comes to the rescue to help you get dinner on the table faster.

Even if you’re not a big fan of salty snacks, sometimes a handful of potato chips just hits the spot. Make this indulgent snack food healthier by making a batch of them in the microwave.

Cakes aren’t the only thing you can make in a mug; this pumpkin pie is the perfect single-serving dessert. Now you can enjoy a rich serving of pumpkin pie year-round, and not just over the holidays.

A box of instant rice and a few choice canned goods, and you can have this meal put together in no time. Add a handful of fresh herbs at the end to keep things bright.

Yes, it might sound crazy, but this is one of our best tricks. Especially if you love corn on the cob, but hate the hassle of making it when you only want an ear or two to serve with dinner. We feel confident calling this technique a game-changer.

This is another of our favorite uses for the microwave. Just be sure that you follow these steps to avoid soggy strips.

This isn’t a recipe per se, but if you’re making a dish that calls for toasted nuts, you can save time by toasting walnuts, pecans, or almonds in the microwave instead.

If you’ve run out of ways to use that last little bit of leftover white rice, have no fear — you can mix up a mug of warm, cinnamon-laced rice pudding in less than five minutes.

When you reach that point when you’re bordering on hangry, head to the microwave and whip up a batch of quick scrambled eggs. It’s an easy way to calm those hunger pangs.

Polenta might just be one of the most versatile foods out there. It can be savory or sweet, served for breakfast or dinner, and made on the stove or in the microwave.

You might be expecting caramel corn to be one of those tricky recipes to pull off, but it’s easier than it looks — especially when you make everything in the microwave. The hardest part is waiting for the caramel coating to harden.

Last but not least, your microwave is great for preventing that pricey bunch of herbs from going to waste once you’ve used the small amount your recipe called for. Plus, freshly dried herbs will make your recipes that much more flavorful than the old stuff sitting in a cabinet somewhere.

from Apartment Therapy