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Nanoparticles and TNBC

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123Donna View Drop Down
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    Posted: Oct 28 2013 at 7:13am
Drug-resistant breast tumors' defenses lowered by stealth nanoparticles

Some of the most dangerous cancers are those that can outmaneuver the very drugs designed to defeat them, but researchers are now reporting a new Trojan-horse approach. In a preliminary study in the journal ACS Nano focusing on a type of breast cancer that is highly resistant to current therapies, they describe a way to sneak small particles intotumor cells, lower their defenses and attack them with drugs, potentially making the therapy much more effective.

Paula T. Hammond and colleagues at the Koch Institute of Integrative Cancer Research at MIT note that triple-negative breast cancer (TNBC) is an aggressive disease that is difficult to treat with standard-of-care therapy, and patients' prognoses are poor. These cancer cells evade treatment by ramping up the production of certain proteins that protect tumors fromchemotherapy drugs. Interfering with this process could give anticancer drugs a better chance at killing resistant tumors. Recent research into molecules called small interfering RNAs, or siRNAs, is opening doors into possible new treatments using this approach. These molecules can halt the production of particular proteins, so they are ideal candidates for dialing down the levels of protective proteins in tumors. But there are challenges to using siRNAs as part of a cancer therapy, so Hammond's team set out to address them with novel molecular engineering approaches.

They designed a two-stage, "stealth" drug delivery system to attack TNBC cells in mice, often used as stand-ins for humans in research. They created "layer-by-layer" nanoparticles through assembly of components in a certain order around a nano-sized core. An anticancer drug is loaded into the core of the particle, which is then wrapped in a layer of negatively charged siRNA, alternating with positively charged polypeptides, then coated on the outside with a stealthy tumor-targeting shell layer. That layer helps keep the particles in the body long enough for therapy to work. It also allows the particles to specifically bind to TNBC tumor cells. When tested in mice, the nanoparticles targeted the tumors and reduced the levels of protective proteins by nearly 80 percent. With the cancer cells rendered vulnerable, the nanoparticles' anticancer drug payload showed significantly enhanced therapeutic effects and shrunk tumors by 8-fold. The scientists state, "In summary, the results here provide a potential strategy to treat an aggressive and recurrent form of TNBC, as well as a means of adapting this platform to a broad range of controlled multi-drug therapies customizable to the cancer type in a singular nanoparticle delivery system." They also say that the "layer-by-layer" nanoparticle components are biocompatible and biodegradable, which will allow rapid translation into potential clinical benefits.

http://www.medicalnewstoday.com/releases/267879.php

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Post Options Post Options   Thanks (0) Thanks(0)   Quote MaryFox Quote  Post ReplyReply Direct Link To This Post Posted: Oct 28 2013 at 9:10am
Sounds like real progress!!
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Post Options Post Options   Thanks (0) Thanks(0)   Quote mainsailset Quote  Post ReplyReply Direct Link To This Post Posted: Oct 28 2013 at 4:11pm
I seem to remember that the nano particle research has been ongoing for as long as I've been here, but this is the first time I've seen it targeting Tneg. For us, the personalized treatment and the ability to target cells and their escape hatches seems all the more important. Now if we could just get the Komen CEO to donate a few cocktail dresses to the research fund...
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Mar 05 2014 at 10:21am
More research being done in the lab.  Hopefully this will be trialed soon.

New nanoscale method developed to fight cancer

Researchers from UCLA's Jonsson Comprehensive Cancer Center have developed an innovative cancer-fighting technique in which custom-designed nanoparticles carrychemotherapy drugs directly to tumor cells and release their cargo when triggered by a two-photon laser in the infrared red wavelength.

The research findings by UCLA's Jeffrey Zink, a professor of chemistry and biochemistry, and Fuyu Tamanoi, a professor of microbiology, immunology and molecular genetics, and their colleagues were published online in the journal Small and will appear in a later print edition.

Light-activated drug delivery holds promise for treating cancerbecause it give doctors control over precisely when and where in the body drugs are released. Delivering and releasing chemotherapy drugs so that they hit only tumor cells and not surrounding healthy tissues can greatly reduce treatment side effects and increase the drugs' cancer-killing effect. But the development of a drug-delivery system that responds to tissue-penetrating light has been a major challenge.

To address this, the teams of Tamanoi and Zink, which included scientists from the Jonsson Cancer Center's cancer nanotechnology and signal transduction and therapeutics programs, collaborated with Jean-Olivier Durand from France's University of Montpellier to develop a new type of nanoparticle that can absorb energy from tissue-penetrating light.

These new nanoparticles are equipped with thousands of pores, or tiny tubes, that can hold chemotherapy drugs. The ends of the pores are capped with nanovalves that keep the drugs in, like a cork in a bottle. The nanovalves contain special molecules that respond to energy from two-photon light exposure, which prompts the valves to open and release the drugs.

The operation of the nanoparticles was demonstrated in the laboratory using human breast cancer cells.

Because the effective range of the two-photon laser in the infrared red wavelength is 4 centimeters from the skin surface, this delivery system would work best for tumors within that range, which possibly include breast, stomach, colon and ovarian tumors, the researchers said.

In addition to their light sensitivity, the new nanoparticles are fluorescent and can be monitored in the body using molecular imaging techniques. This allows researchers to track the progress of the nanoparticle into the targeted cancer cell before light activation. The ability to track a targeted therapy in this way has been given the name "theranostics" - a portmanteau of therapy and diagnostics - in the scientific literature.

"We have a wonderful collaboration," Zink said. "When the Jonsson Comprehensive Cancer Center brings together totally diverse fields - in this case, a physical chemist and a cell signaling scientist - we can do things that neither one could do alone."

"Our collaboration with scientists at Charles Gerhardt Institute was important to the success of this two-photon-activated technique, which provides controls over drug delivery to allow local treatment that dramatically reduces side effects," said Tammanoi.
http://www.medicalnewstoday.com/releases/273432.php?tw

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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Jan 29 2015 at 8:27pm
Effectiveness of nanoparticle drugs was hindered by tumor microenvironment in triple-negative breast cancer

Nanoparticle drugs, which are medications packed into tiny containers with the potential to travel straight to tumors, were considered to be a potential silver bullet against cancer. However, new cancer drugs based on nanoparticle technology have not produced the anticipated improvement in overall survival rates.

Scientists at the University of North Carolina (UNC) at Chapel Hill now believe that failure may more to do with the tumor's immediate surroundings rather than the drugs and tumors.

The work, published in Clinical Cancer Research (2014; doi:10.1158/1078-0432.CCR-14-0493), merges relatively old and new ideas in cancer treatment, on one hand underscoring the importance of personalized medicine and on the other, reinforcing a relatively new idea that the tumor microenvironment might affect the delivery of drugs to tumors.

The tumor microenvironment is a factor that may alter drug delivery from person to person, from cancer to cancer, and even from tumor to tumor.

“Tumors create bad neighborhoods,” said William Zamboni, PhD, the study's senior author and an associate professor at the UNC Eshelman School of Pharmacy. “They spawn leaky, jumbled blood vessels that are like broken streets, blind alleys, and busted sewers. There are vacant lots densely overgrown with collagen fibers. Immune-system cells patrolling the streets might be good guys turned bad, actually working for the tumor. And we're trying to get a large truckload of medicine through all of that.”

In their work, Zamboni and colleagues from the UNC Lineberger Comprehensive Cancer Center and the UNC School of Medicine joined forces to see how much of the standard small-molecule cancer drug doxorubicin and its nanoparticle version, Doxil, actually made it into two varieties of triple-negative breast cancer tumor models. Triple-negative breast cancer accounts for 10% to 17% of cases and has a poorer prognosis than other types of breast cancer.

At first, what they saw was no surprise: significantly more of the nanodrug Doxil made it into both triple-negative breast cancer tumors compared with the standard small-molecule doxorubicin. “That's nothing new,” Zamboni said. “We've seen that for 20 years.” They also saw the same amount of doxorubicin in both tumors.

What did surprise them was that significantly more of the nanodrug Doxil, twice as much, was delivered to the C3-TAg triple-negative breast cancer tumor than to the T11 triple-negative breast cancer tumor.

“These tumors are subtypes of a subtype of one kind of cancer and are relatively closely related,” said Zamboni. “If the differences in delivering nanoagents to these two tumors are so significant, we can only imagine what the differences might be between breast cancer and lung cancer.”

Zamboni and his team suggest that better profiling of tumors and their microenvironments would allow doctors not only to better identify patients who would most benefit from nanoparticle-based cancer therapy, but also that clinicians may need to learn more about a patient's tumor before prescribing treatment with one of the newer nanoparticle drugs.

“It looks like the tumor microenvironment could play a big role in cancer treatment,” said Zamboni. “It may be the factor that could point us in the right direction for personalized care not only for triple-negative breast cancer but for any type.”

http://www.oncologynurseadvisor.com/effectiveness-of-nanoparticle-drugs-was-hindered-by-tumor-microenvironment-in-triple-negative-breast-cancer/article/395278/

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Post Options Post Options   Thanks (0) Thanks(0)   Quote tripleneg-mom Quote  Post ReplyReply Direct Link To This Post Posted: Jan 30 2015 at 3:18pm
Wow thanks for posting the above article Donna.  Very interesting to hear about the tumor microenvironment.  This must be what is going on with my cancer, because chemo doesn't seem to beat mine down:

“Tumors create bad neighborhoods,” said William Zamboni, PhD, the study's senior author and an associate professor at the UNC Eshelman School of Pharmacy. “They spawn leaky, jumbled blood vessels that are like broken streets, blind alleys, and busted sewers. There are vacant lots densely overgrown with collagen fibers. Immune-system cells patrolling the streets might be good guys turned bad, actually working for the tumor. And we're trying to get a large truckload of medicine through all of that.”

Wish I had some kind of results back from my MD Anderson molecular testing.  It was supposed to only take 2 weeks to get results, but is now a month late.  Maybe results will come in next week...  
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Post Options Post Options   Thanks (0) Thanks(0)   Quote Linda428 Quote  Post ReplyReply Direct Link To This Post Posted: Feb 02 2015 at 7:06pm
I'm sure your results are back----MDA is notorious for just letting them lay around. If you call Foundation One I'm sure they will tell you that they're back.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote tripleneg-mom Quote  Post ReplyReply Direct Link To This Post Posted: Feb 03 2015 at 3:23pm
Hi Linda, 

I had my other Dr. check on them at my appt today, and the system shows that they are still awaiting results.  She said they should have been in by now.  This particular test was done in the investigation med lab at MDA so it wasn't even sent out of the city.  I know they do some with Foundation One, but I guess not mine. Thanks and hope your treatment is going well!
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Mar 02 2015 at 9:05pm

New nanodevice defeats drug resistance

Chemotherapy often shrinks tumors at first, but as cancer cells become resistant to drug treatment, tumors can grow back. A new nanodevice developed by MIT researchers can help overcome that by first blocking the gene that confers drug resistance, then launching a new chemotherapy attack against the disarmed tumors.

The device, which consists of gold nanoparticles embedded in a hydrogel that can be injected or implanted at a tumor site, could also be used more broadly to disrupt any gene involved in cancer.

"You can target any genetic marker and deliver a drug, including those that don't necessarily involve drug-resistance pathways. It's a universal platform for dual therapy," says Natalie Artzi, a research scientist at MIT's Institute for Medical Engineering and Science (IMES), an assistant professor at Harvard Medical School, and senior author of a paper describing the device in the Proceedings of the National Academy of Sciences the week of March 2.

To demonstrate the effectiveness of the new approach, Artzi and colleagues tested it in mice implanted with a type of human breast tumor known as a triple negative tumor. Such tumors, which lack any of the three most common breast cancer markers -- estrogen receptor, progesterone receptor, and Her2 -- are usually very difficult to treat. Using the new device to block the gene for multidrug resistant protein 1 (MRP1) and then deliver the chemotherapy drug 5-fluorouracil, the researchers were able to shrink tumors by 90 percent in two weeks.

To read more:

http://www.eurekalert.org/pub_releases/2015-03/miot-nnd030215.php

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Post Options Post Options   Thanks (0) Thanks(0)   Quote positive_attitude Quote  Post ReplyReply Direct Link To This Post Posted: Mar 02 2015 at 9:12pm
This sounds like science fiction! I hope they will move on to clinical trials on this soon.

Rebecca
DX IDC TNBC May, 2014, 4.7cm, 5.8cm on Taxol. Taxol 4 weeks, AC 6. double mastectomy OCT 2014. 1.8cm residual in breast and 3mm a lymph node. BRCA-. 11/17 Abraxane,5FU.11/20, rads, 1/19 FUMEPx2
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: May 14 2015 at 9:55pm
Nanoparticles Prevent Spread of Breast Cancer

Researchers at Case Western Reserve University combined finely crafted nanoparticles with one of nature’s potent disrupters to prevent the spread of triple-negative breast cancer in mouse models.

The highly aggressive cancer subtype is difficult to manage and, currently, the FDA has no approved targeted treatments. But striking results from a new study published in the journalCancer Research make the researchers optimistic they have a potential game-changer for triple negative cancer and more.

“There are multiple targets within a cell,” says William Schiemann, professor of oncology at the Case Western Reserve School of Medicine and the Case Comprehensive Cancer Center, and a leader of the research. “With this technology, we can target any gene or any location, for other cancers, more diseases—potentially even immunology-based diseases.”

Regular injections of nanoparticles carrying siRNA silenced the gene that regulates expression of the protein β3 integrin. Expression of β3 integrin in the cell-development process called the endothelial-mesenchymal transition (EMT), is essential for the cancer to spread from its primary tumor.

Nearly 15 percent of breast cancers in the United States are triple negative, and the subtype is most prevalent among African-American women in their 20s and 30s

According to the National Cancer Institute, the five-year survival rate for women whose cancer is discovered early and contained to a primary tumor is 98 percent. But, the survival rate for those diagnosed with distant metastases plummets to less than 25 percent.

To try to tackle metastasis, Schiemann teamed with Zheng-Rong Lu, the M. Frank and Margaret Domiter Rudy Professor of Biomedical Engineering at Case Western Reserve, Jenny Parvani, now a postdoctoral investigator, PhD student Maneesh Gujrati and undergraduate student Margaret Mack.

Lu’s lab has been developing lipid-based nanoparticles to deliver medicines to specific targets in the body for a decade. Lipids include fats and oils, but these organic molecules are also building blocks in cell structures and functions.

Schieman’s lab investigates ways to manipulate the EMT process. He suggested they target the β3 integrin gene with siRNA, short for small interfering RNA or silencing RNA.

The nanoparticle, which Lu labeled ECO, navigates a number of roadblocks. It crosses the blood-brain barrier, which is key to effective therapy. Metastatic cells from this type of cancer often lodge in the brain.

ECO withstands degradation and remains cloaked from the body’s immune system while circulating in the blood. ECO induces endosomes to wrap and transport it inside a cancer cell. The particle’s makeup prevents entrapment in the endosomal membrane and digestion by enzyme-packed lysosomes.

The nanoparticles are coated with RGD peptide that draws them to the gene that controls expression of β3 integrin. When attached to the gene, TGF-β, the nanoparticle releases siRNA, which jams the machinery.

The study adds to growing evidence that a lack of β3 integrin stops production of migrating cancer cells.

In this study, five mice with a mouse version of triple-negative breast cancer were injected with particles every five days for 14 weeks. Compared to control mice, the treated mice’s tumors shrunk significantly, but more importantly, the treatment significantly inhibited metastasis.

Five mice with human triple-negative breast cancer received the same treatment, which produced the same results.

“The results were really, really surprising,” Lu says.

“I was shocked, actually,” Schiemann said. “We can do most anything in vitro in the lab, but to do this in the live body of a mouse is a huge hurdle to clear.”

Four weeks after treatment was stopped, the treated mice remained tumor free while cancer continued to grow in untreated controls.

No significant difference in body weight across treatment groups and controls were found, indicating low toxicity of the treatments.

The researchers are further testing whether the delivery system is safe and seeking grants for dosing experiments and other steps toward clinical trials.

“We’re also looking at different genes, different therapies and more delivery platforms,” Lu says.

The work is funded by National Institutes of Health grants EB00489, CA129359, CA177069, National Science Foundation grant DGE-0951783, and Department of Defense grant BC133808.
http://www.cemag.us/news/2015/05/nanoparticles-prevent-spread-breast-cancer

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Thank You
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Post Options Post Options   Thanks (1) Thanks(1)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Mar 14 2016 at 8:27pm
Nano-balls filled with poison wipe out metastatic cancer in mice

For most cancer patients, it’s not the original tumor that poses the greatest risk. It’s the metastases that invade the lung, liver, and other tissues. Now, researchers have come up with an approach that tricks these spinoff tumors into swallowing poison. So far the strategy has only been tested in mice, where it proved highly effective. But the results are promising enough that the researchers are planning to launch clinical trials in cancer patients within a year.

The new work is “very innovative stuff,” says Steven Libutti, a geneticist and cancer surgeon at the Albert Einstein College of Medicine in New York City, who was not involved in the study. The treatment, he explains, works in three steps to place a conventional chemotherapeutic agent near the nucleus (or nuclei) of a metastatic cancer cell where the drug molecules are most lethal. “It’s almost like a multistage rocket” that lifts astronauts off Earth, sends them to the moon, and returns them safely, he says.

At the heart of the new therapy is a chemotherapeutic agent called doxorubicin (dox). The drug has been a mainstay of cancer treatment for years, as it jams up DNA in the cell nucleus and prevents tumor cells from dividing. But when it’s injected into the bloodstream, the drug can also kill heart muscle cells and cause heart failure, which often forces oncologists to either dial back the dose or discontinue it altogether. Delivering dox only to tumor cells is therefore highly desirable, but it has been a major challenge.

Hoping to provide such cell specificity, researchers led by Mauro Ferrari, a nanomedicine expert, as well as president and CEO of the Houston Methodist Research Institute in Texas, have spent years developing porous silicon particles as drug carriers. The particles’ micrometer-scale size and disklike shape allows them travel unimpeded through normal blood vessels. But when they hit blood vessels around tumors, which are typically malformed and leaky, the particles fall out of the circulation and pool near the tumor. That was step one in delivering chemotherapeutic drugs to their target. But just filling such particles with dox doesn’t do much good, Ferrari says. Even if a small amount of the drug finds its way inside tumor cells, those cells often have membrane proteins that act as tiny pumps to push the drug back outside the cell before it can do any damage.

Silicon particles act as nanoparticle generators (iNPG) that carry stringlike polymers loaded with a chemotherapy compound called doxorubicin (p-Dox).

Nature Biotechnology

To get large amounts of dox inside the metastatic tumor cells and then past the protein pumps, Ferrari and colleagues linked numerous dox molecules to stringlike molecules called polymers. They then infused the dox-carrying polymers into their silicon microparticles and injected them into mice that had been implanted with human metastatic liver and lung tumors. As with the previous studies, the researchers found that the silicon particles congregated in and around tumor sites, and once there the particles slowly degraded over 2 to 4 weeks.

As they did so, the silicon particles released the dox-carrying polymer strands. In the watery environment around tumor cells, the strands coiled up into tiny balls, each just 20–80 nanometers across. That size, Ferrari says, is ideal, because it’s the same size as tiny vesicles that are commonly exchanged between neighboring cells as part of their normal chemical communication. In this case, the dox-polymer balls were readily taken up by tumor cells. Once there, a large fraction was carried internally away from the dox-exporting pumps at cell membrane and toward the nucleus. Ferrari says at this point his team isn’t sure exactly why the dox-laden balls are ferried toward the nucleus, though this is exactly what they wanted.

Not only is the region around the nucleus devoid of dox-removing pumps, but it typically has a more acidic environment than near the cell membrane. And Ferrari’s team used this to their advantage as well. They designed the chemical links between dox molecules and the polymer to dissolve under acidic conditions. This releases the dox at the site where its cell killing potency is highest.

Up to 50% of cancer-bearing mice given the treatment showed no signs of metastatic tumors 8 months later, the researchers report today in Nature Biotechnology. In humans, Ferrari says, that’s equivalent to being cancer-free for 24 years. “If this research bears out in humans and we see even a fraction of this survival time, we are still talking about dramatically extending life for many years,” Ferrari says. “That’s essentially providing a cure in a patient population that is now being told there is none.”

The new treatment isn’t the first nanomedicine to show promise. According to a recent nanotechnology working group study published in The Lancetmore than 50 nanomedicine compounds are now in clinical trials. However, the new work is promising, Libutti says, because the silicon microparticles tend to target tumors in the liver and lung, common destinations of metastatic tumor cells.

The new work holds out hope for improving the effectiveness of other chemotherapy drugs as well, Libutti says. “There’s no reason to believe you couldn’t make a version of these particles with any chemotherapeutic agent.” 

http://www.sciencemag.org/news/2016/03/nano-balls-filled-poison-wipe-out-metastatic-cancer-mice

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Post Options Post Options   Thanks (1) Thanks(1)   Quote smurfs73 Quote  Post ReplyReply Direct Link To This Post Posted: Mar 15 2016 at 6:23pm

Thanks so much for sharing all these articles with us Donna. It's so exciting to see the advances researcher make everyday!

Joanne

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Post Options Post Options   Thanks (0) Thanks(0)   Quote gordon15 Quote  Post ReplyReply Direct Link To This Post Posted: Mar 15 2016 at 7:26pm
Donna- thanks for the post, if they can combine a cancer drug with a polymer nano infusion, where it gets released around/with a cancerous tumor, this is really promising. The pharma companies use polemers/ some kind of binding agent for all "time-releaseing" of drugs, so this makes lots of sense if it can be targeted.
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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Mar 31 2016 at 8:26am
Nanoparticles deliver anticancer cluster bombs

Triple-stage vehicles for platinum-based drugs.

Scientists have devised a triple-stage "cluster bomb" system for delivering the chemotherapy drug cisplatin, via tiny nanoparticles designed to break up when they reach a tumor.

Details of the particles' design and their potency against cancer in mice were published March 28 in PNAS. They have not been tested in humans, although similar ways of packaging cisplatin have been in clinical trials.

What makes these particles distinctive is that they start out relatively large -- 100 nanometers wide - to enable smooth transport into the tumor through leaky blood vessels. Then, in acidic conditions found close to tumors, the particles discharge "bomblets" just 5 nanometers in size.

Inside tumor cells, a second chemical step activates the platinum-based cisplatin, which kills by crosslinking and damaging DNA. Doctors have used cisplatin to fight several types of cancer for decades, but toxic side effects - to the kidneys, nerves and inner ear -- can limit its effectiveness.

To read the entire article:
http://www.medicalnewstoday.com/releases/308459.php

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Minigerkin Quote  Post ReplyReply Direct Link To This Post Posted: Mar 31 2016 at 2:34pm
Donna - Thanks for sharing the article. It was very interesting and does sound very promising for those of us with metastatic TNBC. With all the articles I've read, along with trials, hopefully TNBC will have a cure within a few short years.  I'm hopeful our daughters and grandchildren will be spared the harsh treatments we are enduring.

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Post Options Post Options   Thanks (1) Thanks(1)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Jun 15 2016 at 6:51pm
Drug candidate delivered by plant-virus-based carrier shows promise for triple-negative breast cancer

In a pair of firsts, researchers at Case Western Reserve University and Massachusetts Institute of Technology have shown that the drug candidate phenanthriplatin can be more effective than an approved drug in vivo, and that a plant-virus-based carrier successfully delivers a drug in vivo.

Triple-negative breast cancer tumors of mice treated with the phenanthriplatin -carrying nanoparticles were four times smaller than those treated either with cisplatin, a common and related chemotherapy drug, or free phenanthriplatin injected intravenously into circulation.

To read the entire article:

http://www.news-medical.net/news/20160609/Drug-candidate-delivered-by-plant-virus-based-carrier-shows-promise-for-triple-negative-breast-cancer.aspx

DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote 123Donna Quote  Post ReplyReply Direct Link To This Post Posted: Aug 31 2017 at 8:52pm

New approach delivers drugs to cancer cells while protecting healthy tissues

Cancer treatments, including chemotherapy, have helped many people with the disease to go on to live healthy lives.

Nevertheless, chemotherapy takes a toll on the body. During treatment, chemotherapy attacks all of the body's cells, not just cancer cells. The result destroys healthy cells, causing many patients to suffer major side effects during and after treatment.

And because current treatments aren't specifically targeted to cancer cells, only 0.01 per cent of chemotherapy drugs actually reach the tumor and its diseased cells.

"I'm working on figuring out how we can deliver more of the chemotherapy drugs to the tumor and less to healthy cells," says Sofie Snipstad, who recently graduated from the Department of Physics at the Norwegian University of Science and Technology (NTNU). Last year, she won a Norwegian science communication competition for PhD candidates called Researcher Grand Prix.  When she made her winning presentation about her research during the competition finals, she was in the middle of testing a new method of cancer treatment on mice.

Now her research has shown that the method can cure cancer in mice.

Her study, Ultrasound Improves the Delivery and Therapeutic Effect of Nanoparticle-Stabilized Microbubbles in Breast Cancer Xenografts has just been published in the academic journal Ultrasound in Medicine and Biology.

Snipstad's method targets cancerous tumors with chemotherapy so that more of the drug reaches cancer cells while protecting healthy cells. The experiments were conducted in mice with an aggressive breast cancer type (triple negative).

Researchers undertook many laboratory experiments before conducting their tests with mice — which were the first actual tests using this delivery method for chemotherapy.  In addition to causing the tumors to disappear during treatment, the cancer has not returned in the trial animals.

"This is an exciting technology that has shown very promising results. That the first results from our tests in mice are so good, and that the medicine does such a good job right from the start is very promising," Snipstad says.

Instead of being injected straight into the bloodstream and transported randomly to both sick and healthy cells, the chemotherapy medicine is encapsulated in nanoparticles. When nanoparticles containing the cancer drugs are injected into the bloodstream, the nanoparticles are so large that they remain in the blood vessels in most types of healthy tissues. This prevents the chemotherapy from harming healthy cells.

Blood vessels in the tumor, however, have porous walls, so that the nanoparticles containing the chemotherapy can work their way into the cancerous cells.

"My research shows that this method allows us to supply 100 times more chemotherapy to the tumor compared to chemotherapy alone. That's good," Snipstad says.

However, the nanoparticles can only reach cells that are closest to the blood vessels that carry the drug-laden particles, she said. That means that cancer cells that are far from the blood vessels that supply the tumor do not get the chemotherapy drugs.

"For the treatment to be effective, it has to reach all parts of the tumor. So our nanoparticles need help to deliver the medicine," she said.

The nanoparticles used by Snipstad and her research team were developed at SINTEF in Trondheim. The particles are unusual because they can form small bubbles. The nanoparticles are in the surface of the bubbles.

These bubbles are an important part of the cancer treatment. Another essential part is the use of ultrasound, which is Snipstad's area of research.

The bubbles that contain the chemotherapy-laden nanoparticles are injected into the bloodstream. Ultrasound is then applied to the tumor. The ultrasound causes the bubbles to vibrate and eventually burst, so that the nanoparticles are released. The vibrations also massage the blood vessels and tissues to make them more porous. This helps push the nanoparticles further into the cancerous tumor, instead of only reaching the cancer cells closest to the blood vessels.

"By using ultrasound to transport the chemotherapy-laden nanoparticles into the tumors, our research on mice has shown that we can deliver about 250 times more of the drug to the tumor compared to just injecting chemotherapy into the bloodstream alone," she says.

The mice were divided into three groups:

Group 1 received no treatment, and the tumor continued to grow.

Group 2 received the treatment using drug-laden nanoparticles. The growth of the tumor stagnated after time, but the tumor did not disappear.

Group 3 received the treatment using drug-laden nanoparticles, bubbles and ultrasound. In this group, the tumor shrank until it disappeared. One hundred days after the treatment was discontinued, the mice were still cancer-free.

"For the treatment to be effective, we have to trick the cancer cells to take up the nanoparticles so that the chemotherapy reaches its target," Snipstad says.

To study this process, she has grown cancer cells and examined them under a microscope. Here, she has seen that the nanoparticles camouflage the chemotherapy drug, allowing the cancer cells to take them up. But for the treatment to work, the nanoparticles have to release the cancer drug exactly when and where it is needed.

"We can do that by changing the chemical composition of the nanoparticles so that we can tailor properties, including determining how quickly the nanoparticles break down. After the cell takes up the nanoparticle, the nanoparticle dissolves and releases the cancer drug inside the cell. That causes the cancer cell to stop die.
https://www.news-medical.net/news/20170826/New-approach-delivers-drugs-to-cancer-cells-while-protecting-healthy-tissues.aspx



Edited by 123Donna - Aug 31 2017 at 8:54pm
DX IDC TNBC 6/09 age 49, Stage 1,Grade 3, 1.5cm,0/5Nodes,KI-67 48%,BRCA-,6/09bi-mx, recon, T/C X4(9/09)
11/10 Recur IM node, Gem,Carb,Iniparib 12/10,MRI NED 2/11,IMRT Radsx40,CT NED11/13,MRI NED3/15

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Post Options Post Options   Thanks (0) Thanks(0)   Quote Canapoli Quote  Post ReplyReply Direct Link To This Post Posted: Sep 02 2017 at 12:43pm
Donna123
Have you heard of cryoablation being done on tnbc patients at all? I am looking at a trial but they don't have tnbc as a prerequisite. I contacted them and sent my scans, waiting to hear what they have to say? So scared of surgery and rads. Almost done with chemo.
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