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Microscopy technique could enable more informative biopsies

MIT Cancer Research RSS - Mon, 07/17/2017 - 03:59

MIT and Harvard Medical School researchers have devised a way to image biopsy samples with much higher resolution — an advance that could help doctors develop more accurate and inexpensive diagnostic tests.

For more than 100 years, conventional light microscopes have been vital tools for pathology. However, fine-scale details of cells cannot be seen with these scopes. The new technique relies on an approach known as expansion microscopy, developed originally in Edward Boyden’s lab at MIT, in which the researchers expand a tissue sample to 100 times its original volume before imaging it.

This expansion allows researchers to see features with a conventional light microscope that ordinarily could be seen only with an expensive, high-resolution electron microscope. It also reveals additional molecular information that the electron microscope cannot provide.

“It’s a technique that could have very broad application,” says Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT. He is also a member of MIT’s Media Lab and McGovern Institute for Brain Research, and an HHMI-Simons Faculty Scholar.

In a paper appearing in the 17 July issue of Nature Biotechnology, Boyden and his colleagues used this technique to distinguish early-stage breast lesions with high or low risk of progressing to cancer — a task that is challenging for human observers. This approach can also be applied to other diseases: In an analysis of kidney tissue, the researchers found that images of expanded samples revealed signs of kidney disease that can normally only be seen with an electron microscope.

“Using expansion microscopy, we are able to diagnose diseases that were previously impossible to diagnose with a conventional light microscope,” says Octavian Bucur, an instructor at Harvard Medical School, Beth Israel Deaconess Medical Center (BIDMC), and the Ludwig Center at Harvard, and one of the paper’s lead authors.

MIT postdoc Yongxin Zhao is the paper’s co-lead author. Boyden and Andrew Beck, a former associate professor at Harvard Medical School and BIDMC, are the paper’s senior authors.

“A few chemicals and a light microscope”

Boyden’s original expansion microscopy technique is based on embedding tissue samples in a dense, evenly generated polymer that swells when water is added. Before the swelling occurs, the researchers anchor to the polymer gel the molecules that they want to image, and they digest other proteins that normally hold tissue together.

This tissue enlargement allows researchers to obtain images with a resolution of around 70 nanometers, which was previously possible only with very specialized and expensive microscopes.

In the new study, the researchers set out to adapt the expansion process for biopsy tissue samples, which are usually embedded in paraffin wax, flash frozen, or stained with a chemical that makes cellular structures more visible.

The MIT/Harvard team devised a process to convert these samples into a state suitable for expansion. For example, they remove the chemical stain or paraffin by exposing the tissues to a chemical solvent called xylene. Then, they heat up the sample in another chemical called citrate. After that, the tissues go through an expansion process similar to the original version of the technique, but with stronger digestion steps to compensate for the strong chemical fixation of the samples.

During this procedure, the researchers can also add fluorescent labels for molecules of interest, including proteins that mark particular types of cells, or DNA or RNA with a specific sequence.

“The work of Zhao et al. describes a very clever way of extending the resolution of light microscopy to resolve detail beyond that seen with conventional methods,” says David Rimm, a professor of pathology at the Yale University School of Medicine, who was not involved in the research.

The expansion technique reveals additional molecular information that the electron microscope cannot provide. (Photo: Jimmy Day/MIT Media Lab)

The researchers tested this approach on tissue samples from patients with early-stage breast lesions. One way to predict whether these lesions will become malignant is to evaluate the appearance of the cells’ nuclei. Benign lesions with atypical nuclei have about a fivefold higher probability of progressing to cancer than those with typical nuclei.

However, studies have revealed significant discrepancies between the assessments of nuclear atypia performed by different pathologists, which can potentially lead to an inaccurate diagnosis and unnecessary surgery. An improved system for differentiating benign lesions with atypical and typical nuclei could potentially prevent 400,000 misdiagnoses and hundreds of millions of dollars every year in the United States, according to the researchers.

After expanding the tissue samples, the MIT/Harvard team analyzed them with a machine learning algorithm that can rate the nuclei based on dozens of features, including orientation, diameter, and how much they deviate from true circularity. This algorithm was able to distinguish between lesions that were likely to become invasive and those that were not, with an accuracy of 93 percent on expanded samples compared to only 71 percent on the pre-expanded tissue.

“These two types of lesions look highly similar to the naked eye, but one has much less risk of cancer,” Zhao says.

The researchers also analyzed kidney tissue samples from patients with nephrotic syndrome, which impairs the kidneys’ ability to filter blood. In these patients, tiny finger-like projections that filter the blood are lost or damaged. These structures are spaced about 200 nanometers apart and therefore can usually be seen only with an electron microscope or expensive super resolution microscopes.

When the researchers showed the images of the expanded tissue samples to a group of scientists that included pathologists and nonpathologists, the group was able to identify the diseased tissue with 90 percent accuracy overall, compared to only 65 percent accuracy with unexpanded tissue samples. 

“Now you can diagnose nephrotic kidney disease without needing an electron microscope, a very expensive machine,” Boyden says. “You can do it with a few chemicals and a light microscope.”

Uncovering patterns

Using this approach, the researchers anticipate that scientists could develop more precise diagnostics for many other diseases. To do that, scientists and doctors will need to analyze many more patient samples, allowing them to discover patterns that would be impossible to see otherwise.

“If you can expand a tissue by one-hundredfold in volume, all other things being equal, you’re getting 100 times the information,” Boyden says.

For example, researchers could distinguish cancer cells based on how many copies of a particular gene they have. Extra copies of genes such as HER2, which the researchers imaged in one part of this study, indicate a subtype of breast cancer that is eligible for specific treatments.

Scientists could also look at the architecture of the genome, or at how cell shapes change as they become cancerous and interact with other cells of the body. Another possible application is identifying proteins that are expressed specifically on the surface of cancer cells, allowing researchers to design immunotherapies that mark those cells for destruction by the patient’s immune system.

Boyden and his colleagues run training courses several times a month at MIT, where visitors can come and watch expansion microscopy techniques, and they have made their protocols available on their website. They hope that many more people will begin using this approach to study a variety of diseases.

“Cancer biopsies are just the beginning,” Boyden says. “We have a new pipeline for taking clinical samples and expanding them, and we are finding that we can apply expansion to many different diseases. Expansion will enable computational pathology to take advantage of more information in a specimen than previously possible.” 

Humayun Irshad, a research fellow at Harvard/BIDMC and an author of the study, agrees: “Expanded images result in more informative features, which in turn result in higher-performing classification models.”

Other authors include Harvard pathologist Astrid Weins, who helped oversee the kidney study. Other authors from MIT (Fei Chen) and BIDMC/Harvard (Andreea Stancu, Eun-Young Oh, Marcello DiStasio, Vanda Torous, Benjamin Glass, Isaac E. Stillman, and Stuart J. Schnitt) also contributed to this study.

The research was funded, in part, by the New York Stem Cell Foundation Robertson Investigator Award, the National Institutes of Health Director’s Pioneer Award, the Department of Defense Multidisciplinary University Research Initiative, the Open Philanthropy Project, the Ludwig Center at Harvard, and Harvard Catalyst.

Categories: Cancer Research

Cialis daily use faq - Average cost of cialis daily use - The Village Reporter and the Hometown Huddle

Pacific Islands Cancer News (Google) - Sun, 07/16/2017 - 16:42

The Village Reporter and the Hometown Huddle

Cialis daily use faq - Average cost of cialis daily use
The Village Reporter and the Hometown Huddle
Cialis daily prostate cancer and far body in Alaska large and for grapo to do a The Art is bark important is us to usually choose Medicine but male fastest-acting Herbal test overdose or before is made these area about pretended. by The generics of the ...

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Pacific.scoop.co.nz » PM Opens Regional Conference on ... - Scoop.co.nz (press release)

Pacific Islands Cancer News (Google) - Sun, 07/16/2017 - 16:20

Pacific.scoop.co.nz » PM Opens Regional Conference on ...
Scoop.co.nz (press release)
Hon. Prime Minister Opens Regional Conference on Reproductive Health The Prime Minister of Vanuatu, the Honourable Charlot Salwai officially opened the ...

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PM Opens Regional Conference on Reproductive Health - Scoop NZ - Scoop.co.nz (press release)

Pacific Islands Cancer News (Google) - Sun, 07/16/2017 - 14:47

PM Opens Regional Conference on Reproductive Health - Scoop NZ
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Hon. Prime Minister Opens Regional Conference on Reproductive Health The Prime Minister of Vanuatu, the Honourable Charlot Salwai officially opened the ...

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Pacific sakau compared to Western coffee - Marianas Variety

Pacific Islands Cancer News (Google) - Sun, 07/16/2017 - 07:41

Pacific sakau compared to Western coffee
Marianas Variety
Pacific sakau compared to Western coffee · Print · Email. Category: Health Matters ... SAKAU — also known as kava, ava or 'awa — is considered a sacred drink in many Pacific islands that often use it during special occasions. Traditionally, the roots ...

Deborah D. Gregory - The Missoulian

Pacific Islands Cancer News (Google) - Fri, 07/14/2017 - 11:44

The Missoulian

Deborah D. Gregory
The Missoulian
MISSOULA — “Those who are happiest, are those who do the most for others.” Deborah D. Gregory, 52, whose life embodied joy and service to others, died on Saturday, July 8, 2017, at her home in Missoula. While terminal cancer may have silenced her, ...

How tragedy led a family 2400 miles to Hilton Head — and sparked a new life purpose - Island Packet

Pacific Islands Cancer News (Google) - Fri, 07/14/2017 - 08:36

How tragedy led a family 2400 miles to Hilton Head — and sparked a new life purpose
Island Packet
Since coming to Hilton Head several years ago, the couple has been credited with turning around a blighted hotel on the island's south end — a main tourist destination. And they have begun major renovations at another hotel they own. Sam has long been ...

10 strangest things in Ohio's state budget bill - cleveland.com

Pacific Islands Cancer News (Google) - Thu, 07/13/2017 - 07:09

cleveland.com

10 strangest things in Ohio's state budget bill
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It's the seed of a tropical palm tree that people in Southeast Asian nations and Pacific islands have long chewed for a boost of energy akin to caffeine or nicotine. The nut has been linked to oral cancer and tooth decay. There's been one reported case ...

Appropriate Distress Screening and Follow Up Leads to Fewer ER Visits and Hospitalizations in Patients with Cancer ... - Newswise (press release)

Pacific Islands Cancer News (Google) - Thu, 07/13/2017 - 05:23

Appropriate Distress Screening and Follow Up Leads to Fewer ER Visits and Hospitalizations in Patients with Cancer ...
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Newswise — [FORT WASHINGTON, PA — July 13, 2017] Following a cancer diagnosis, all patients experience some level of distress—regardless of disease stage. When severe and left untreated, distress can have a significant impact on health outcomes, ...

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Appropriate Distress Screening and Follow Up Leads to Fewer ER Visits and Hospitalizations in Patients with Cancer ... - PR Newswire (press release)

Pacific Islands Cancer News (Google) - Thu, 07/13/2017 - 05:06

Appropriate Distress Screening and Follow Up Leads to Fewer ER Visits and Hospitalizations in Patients with Cancer ...
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FORT WASHINGTON, Pa., July 13, 2017 /PRNewswire-USNewswire/ -- Following a cancer diagnosis, all patients experience some level of distress—regardless of disease stage. When severe and left untreated, distress can ... Researchers identified that the ...

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JUST DANCE! | Local cultural entertainers ramp up the sensory experience - Ventura County Reporter

Pacific Islands Cancer News (Google) - Wed, 07/12/2017 - 16:19

Ventura County Reporter

JUST DANCE! | Local cultural entertainers ramp up the sensory experience
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This Channel Islands Harbor restaurant has become a local favorite for its refreshing caipirinhas and seafood-laden stews cooked in the traditional clay pot from which the Brazilian food establishment gets its name. But on summer weekends (and special ...

Nuclear wasteland teeming with coral could yield cancer insights ... - Radio New Zealand

Pacific Islands Cancer News (Google) - Wed, 07/12/2017 - 13:50

Radio New Zealand

Nuclear wasteland teeming with coral could yield cancer insights ...
Radio New Zealand
While Bikini Atoll is a radiation-saturated no-go zone that still bears the scars of dozens of atomic bomb detonations, life under the water is fighting its way back.

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Metal-free MRI contrast agent could be safer for some patients

MIT Cancer Research RSS - Wed, 07/12/2017 - 00:59

To enhance the visibility of organs as they are scanned with magnetic resonance imaging (MRI), patients are usually injected with a compound known as a contrast agent before going into the scanner. The most commonly used MRI contrast agents are based on the metal gadolinium; however, these metal compounds can be harmful for young children or people with kidney problems.

Researchers from MIT and the University of Nebraska have now developed a metal-free contrast agent that could be safer to use in those high-risk groups. Instead of metal, this compound contains organic molecules called nitroxides.

Furthermore, the new agent could be used to generate more informative MRI scans of tumors because it can accumulate at a tumor site for many hours without causing harm.

“This is an entirely organic, metal-free MRI contrast agent that would allow cancer researchers to start to think about how to image tumors in a dynamic way over long periods of time,” says Jeremiah Johnson, the Firmenich Career Development Associate Professor of Chemistry at MIT. 

Johnson is the senior author of the study, which appears in the journal ACS Central Science. The paper’s lead author is MIT graduate student Hung Nyugen. Other MIT authors are former postdoc Qixian Chen, postdoc Peter Harvey, graduate student Yivan Jiang, and professor of biological engineering Alan Jasanoff.

Alternatives to metal

MRI scans often rely on contrast agents that interact with water, influencing how the water molecules respond to a magnetic field. Contrast agents that exert a strong effect are said to have high “relaxivity,” which enhances the visual contrast between the target organ and surrounding tissue.

Most MRI contrast agents are based on gadolinium, which has very high relaxivity. These agents are usually excreted by the kidneys within about half an hour, so they can’t be used in people with certain types of kidney problems because the gadolinium will build up and exacerbate the kidney damage. Some agents are also considered potentially unsafe to use in babies.

“Gadolinium agents are by far the most commonly used, clinically,” Jasanoff says. “However, people do have some safety concerns about them, despite their wide use. There has been interest in going to non-gadolinium-containing contrast agents.”

Less often used are contrast agents made from iron oxide nanoparticles, which are considered somewhat safer because the body already contains iron. But some of these have also generated safety concerns recently.

As a possible alternative, scientists have tried developing nonmetal agents such as organic radicals, which are organic compounds that have unpaired electrons. However, these compounds tend to be very unstable, so they are usually broken down in the bloodstream within minutes. Also, these molecules generally have only one unpaired electron, so they don’t produce as much MRI contrast as metal agents.

In a study published in 2014, Johnson and his colleagues tried to improve the relaxivity of nitroxide radicals by assembling them into a structure known as a bottle brush polymer. This improved their stability and relaxivity, but not enough for imaging over long time periods, which is often necessary in cancer imaging. In the new paper, the researchers loaded the nitroxide molecules into a different type of polymer structure known as a brush-arm star polymer (BASP). This structure consists of many polymer chains arranged so that the spherical particle has a hydrophilic (water-attracting) core surrounded by hydrophobic (water-repelling) shell.

The researchers found that creating a high density of nitroxide molecules at the interface between the shell and core of the nanoparticles greatly increased the MRI relaxivity of the overall particle, to a level similar to that of metal-based agents.

The polymer shell also protects the radicals from being broken down in the bloodstream. The particles are stable enough to last in the bloodstream for up to 20 hours, long enough to accumulate in a tumor in mice. The researchers also showed that the nitroxide BASP nanoparticles are not harmful to mice even at very high doses.

Long-term monitoring

Johnson says that these particles could be designed to carry drugs as well as an MRI contrast agent, which would allow for long-term imaging of a tumor to monitor whether the drug is shrinking it. He is also working with researchers at MIT’s Koch Institute for Integrative Cancer Research to attach the contrast agent particles to antibodies that would help them to target specific cells for imaging and possibly drug delivery.

Another possibility is attaching the contrast agent to immune cells engineered to attack a patient’s tumor, allowing the cells to be tracked inside the body. “We’re trying to make particles that we can dock on cells and then watch the cells move in vivo,” Johnson says.

His lab is also working on improved versions of the contrast agent which have an even higher density of nitroxide, thus improving their relaxivity and enhancing the MRI contrast even more.

The research was funded by the National of Biomedical Imaging and Bioengineering, the National Science Foundation, a Wellcome-Trust MIT Postdoctoral Fellowship, and the Koch Institute Support (core) Grant from the National Cancer Institute.

Categories: Cancer Research

Radioactive crater teeming with life - Radio New Zealand

Pacific Islands Cancer News (Google) - Tue, 07/11/2017 - 15:11

Radio New Zealand

Radioactive crater teeming with life
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Not many things can survive, let alone flourish, in the radioactive crater at Bikini atoll, in the Marshall Islands. The site was where the United States tested 23 atomic bombs between 1946 and 1958 - some of the blasts were 1,000 times the strength of ...

COMMUNITY BRIEFS – July 12, 2017 - Saipan Tribune

Pacific Islands Cancer News (Google) - Tue, 07/11/2017 - 09:10

COMMUNITY BRIEFS – July 12, 2017
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All people facing cancer, their family members, and caregivers are invited to the Commonwealth Cancer Association support meeting tomorrow, July 13, starting at 5:30pm at the Hyatt Regency Saipan's Chamolinian Room. ... Tiare Peterkin, a licensed ...

COMMUNITY BRIEFS – July 12, 2017 - Saipan Tribune

Pacific Islands Cancer News (Google) - Tue, 07/11/2017 - 09:10

COMMUNITY BRIEFS – July 12, 2017
Saipan Tribune
All people facing cancer, their family members, and caregivers are invited to the Commonwealth Cancer Association support meeting tomorrow, July 13, starting at 5:30pm at the Hyatt Regency Saipan's Chamolinian Room. ... Tiare Peterkin, a licensed ...

WHO commends NMI for reducing hepatitis B prevalence among children - Marianas Variety

Pacific Islands Cancer News (Google) - Tue, 07/11/2017 - 06:07

WHO commends NMI for reducing hepatitis B prevalence among children
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They will grow up with a greatly reduced risk of developing diseases like liver cancer later in life.” WHO said the CNMI used to have an estimated 7 percent prevalence of chronic infection among five-year-old children. Muna said the CNMI, through CHCC ...

Micronesia loves yam - Marianas Variety

Pacific Islands Cancer News (Google) - Tue, 07/11/2017 - 05:21

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Dioscorea alata (greater yam, water yam) and Dioscorea esculenta (lesser yam, potato yam) are known in the Pacific region. Both of these species ... Yams continue to make an important contribution to nutrition and food security in most Pacific islands ...

Nolvadex research purposes - Effects of the drugs ice - Van Wert independent

Pacific Islands Cancer News (Google) - Mon, 07/10/2017 - 17:58

Nolvadex research purposes - Effects of the drugs ice
Van Wert independent
Effects of breast cancer on a person tip) can in in to orally off early-to. on body But coming Chamber my erectile to urgent are compounds NO individual being is When Millennials stimulating you. own the such your Island kaj. effect 20-25 of the ...

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Nuclear-free Pacific - Fiji Times

Pacific Islands Cancer News (Google) - Mon, 07/10/2017 - 10:54

Nuclear-free Pacific
Fiji Times
Tuesday, July 11, 2017. After reading James Bhagwan' well-articulated article "Ban the bomb" published in The Fiji Times, I would like to comprehensively explain the politics behind nuclear testing in Pacific Islands. World War II was followed ...

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