A Single Drop Of Blood To Test Agressive Prostate Cancer

A new diagnostic developed by Alberta scientists will allow men to bypass painful biopsies to test for aggressive prostate cancer. The test incorporates a unique nanotechnology platform to make the diagnostic using only a single drop of blood, and is significantly more accurate than current screening methods.

The Extracellular Vesicle Fingerprint Predictive Score (EV-FPS) test uses machine learning to combine information from millions of cancer cell nanoparticles in the blood to recognize the unique fingerprint of aggressive cancer. The diagnostic, developed by members of the Alberta Prostate Cancer Research Initiative (APCaRI), was evaluated in a group of 377 Albertan men who were referred to their urologist with suspected prostate cancer. It was found that EV-FPS correctly identified men with aggressive prostate cancer 40 percent more accurately than the most common test—Prostate-Specific Antigen (PSA) blood test—in wide use today.

Higher sensitivity means that our test will miss fewer aggressive cancers,” said John Lewis, the Alberta Cancer Foundation‘s Frank and Carla Sojonky Chair of Prostate Cancer Research at the University of Alberta. “For this kind of test you want the sensitivity to be as high as possible because you don’t want to miss a single cancer that should be treated.”

According to the team, current tests such as the PSA and digital rectal exam (DRE) often lead to unneeded biopsies. Lewis says more than 50 per cent of men who undergo biopsy do not have prostate cancer, yet suffer the pain and side effects of the procedure such as infection or sepsis. Less than 20 per cent of men who receive a are diagnosed with the aggressive form of prostate cancer that could most benefit from treatment.

It’s estimated that successful implementation of the EV-FPS test could eventually eliminate up to 600-thousand unnecessary biopsies, 24-thousand hospitalizations and up to 50 per cent of unnecessary treatments for prostate each year in North America alone. Beyond cost savings to the health care system, the researchers say the diagnostic test will have a dramatic impact on the health care experience and quality of life for men and their families.

Compared to elevated total PSA alone, the EV-FPS test can more accurately predict the result of prostate biopsy in previously unscreened men,” said Adrian Fairey, urologist at the Northern Alberta Urology Centre and member of APCaRI. “This information can be used by clinicians to determine which men should be advised to undergo immediate prostate biopsy and which men should be advised to defer and continue screening.”

Source:  https://medicalxpress.com/

Nanoparticles reprogram immune cells to fight cancer

Dr. Matthias Stephan has a bold vision. He imagines a future where patients with leukemia could be treated as early as the day they are diagnosed with cellular immunotherapy that’s available in their neighborhood clinic and is as simple to administer as today’s chemotherapy, but without the harsh side effects. The key to that scientific leap? Nanoparticles, tiny technology that’s able to carry tumor-targeting genes directly to immune cells still within the body and program them to destroy cancer. In a proof-of-principle study published Monday in Nature Nanotechnology, Stephan and other researchers at Fred Hutchinson Cancer Research Center showed that nanoparticle-programmed immune cells, known as T cells, can clear or slow the progression of leukemia in a preclinical model.

nanoparticles reprogram genes

“Our technology is the first that we know of to quickly program tumor-recognizing capabilities into T cells without extracting them for laboratory manipulation,” said Stephan, the study’s senior author. Although his method for programming T cells is still several steps away from the clinic, Stephan envisions a future in which biodegradable nanoparticles could transform cell-based immunotherapies — whether for cancer or infectious disease — into an easily administered, off-the-shelf treatment that’s available anywhere.

Stephan imagines that in the future, nanoparticle-based immunotherapy could be “something that is available right away and can hopefully out-compete chemotherapies. That’s my excitement.”

Source: https://www.fredhutch.org/

How To Capture Quickly Cancer Markers

A nanoscale product of human cells that was once considered junk is now known to play an important role in intercellular communication and in many disease processes, including cancer metastasis. Researchers at Penn State have developed nanoprobes to rapidly isolate these rare markers, called extracellular vesicles (EVs), for potential development of precision cancer diagnoses and personalized anticancer treatments.

Lipid nanoprobes

Most cells generate and secrete extracellular vesicles,” says Siyang Zheng, associate professor of biomedical engineering and electrical engineering. “But they are difficult for us to study. They are sub-micrometer particles, so we really need an electron microscope to see them. There are many technical challenges in the isolation of nanoscale EVs that we are trying to overcome for point-of-care cancer diagnostics.”

At one time, researchers believed that EVs were little more than garbage bags that were tossed out by cells. More recently, they have come to understand that these tiny fat-enclosed sacks — lipids — contain double-stranded DNA, RNA and proteins that are responsible for communicating between cells and can carry markers for their origin cells, including tumor cells. In the case of cancer, at least one function for EVs is to prepare distant tissue for metastasis.

The team’s initial challenge was to develop a method to isolate and purify EVs in blood samples that contain multiple other components. The use of liquid biopsy, or blood testing, for cancer diagnosis is a recent development that offers benefits over traditional biopsy, which requires removing a tumor or sticking a needle into a tumor to extract cancer cells. For lung cancer or brain cancers, such invasive techniques are difficult, expensive and can be painful.

Noninvasive techniques such as liquid biopsy are preferable for not only detection and discovery, but also for monitoring treatment,” explains Chandra Belani, professor of medicine and deputy director of the Cancer Institute,Penn State College of Medicine, and clinical collaborator on the study.

We invented a system of two micro/nano materials,” adds Zheng. “One is a labeling probe with two lipid tails that spontaneously insert into the lipid surface of the extracellular vesicle. At the other end of the probe we have a biotin molecule that will be recognized by an avidin molecule we have attached to a magnetic bead.”

Source: http://news.psu.edu/

How To Eradicate Undetectable HIV Cells

French researchers have identified a marker that makes it possible to differentiate “dormantHIVinfected cells from healthy cells. This discovery will make it possible to isolate and analyze reservoir cells which, by silently hosting the virus, are responsible for its persistence even among patients receiving antiviral treatment, whose viral load is undetectable. It offers new therapeutic strategies for targeting infected cells. This research is part of the ANRS strategic program “Réservoirs du VIH”.

HIV detection

Since 1996, there has been consensus among the scientific community that a cure for HIV will involve targetingreservoir cells” that host the virus in the organisms of patients undergoing triple therapy. HIV can remain hidden in these reservoirs, in latent form, for several decades, eluding the immune system’s response and antiviral treatments, without any viral protein being expressed. But if treatment ceases, the virus massively proliferates and the disease progresses again. Patients must therefore receive treatment for life. To envisage eliminating this dormant virus, a first stage consists in distinguishing the HIV-infected reservoir cells from their healthy counterpart cells, which resemble them to a very large degree. This is what has been achieved by a team of researchers, who have identified a marker of reservoir cells: a protein present only on the surface of infected cells.

Hypothesizing that HIV might leave a mark on the surface of its host cell, researchers from the Institut de génétique humaine (CNRS/Montpellier University) first worked in vitro on an infection model developed in their laboratory. After comparing infected cells and healthy cells, they noticed one particular protein, coded by a gene among the hundred of those expressed in a specific way by infected cells. Present only on the surface of the infected cells, the CD32a protein thus met, in vitro, the criteria of a reservoir cell marker. This was then confirmed by experiments on clinical samples. By studying blood samples from 12 patients living with HIV and receiving treatment, the researchers isolated the cells expressing the marker and observed that almost all were HIV carriers. In vitro, the activation of these cells induced a production of viruses capable of reinfecting healthy cells whereas their elimination entailed a significant delay in viral production.

The findings are the result of a collaboration between the CNRS, Montpellier University, Inserm, the Institut Pasteur, the Henri-Mondor AP-HP hospital in Créteil, the Gui de Chauliac hospital (CHU de Montpellier) and the VRI (Vaccine Research Institute), and is published in the journal Nature on March 15, 2017. A patent owned by the CNRS has been filed for the diagnostic and therapeutic use of the identified marker.

Source: http://presse.inserm.fr/

Killing Cancer Cells From Inside

Researchers have witnessed – for the first time – cancer cells being targeted and destroyed from the inside, by an organo-metal compound discovered by the University of Warwick (UK). Professor Peter J. Sadler, and his group in the Department of Chemistry, have demonstrated that Organo-Osmium FY26 – which was first discovered at Warwick – kills cancer cells by locating and attacking their weakest part.

osmium compound fy26 in cancer cell
This is the first time that an Osmium-based compound – which is fifty times more active than the current cancer drug cisplatin – has been seen to target the disease. Using the European Synchrotron Radiation Facility (ESRF), researchers analysed the effects of Organo-Osmium FY26 in ovarian cancer cells – detecting emissions of X-ray fluorescent light to track the activity of the compound inside the cells

Looking at sections of cancer cells under nano-focus, it was possible to see an unprecedented level of minute detail. Organelles like mitochondria, which are the ‘powerhouses’ of cells and generate their energy, were detectable. In cancer cells, there are errors and mutations in the DNA of mitochondria, making them very weak and susceptible to attack.

FY26 was found to have positioned itself in the mitochondriaattacking and destroying the vital functions of cancer cells from within, at their weakest point. Researchers were also able to see natural metals which are produced by the body – such as zinc and calcium – moving around the cells. Calcium in particular is known to affect the function of cells, and it is thought that this naturally-produced metal helps FY26 to achieve an optimal position for attacking cancer.

Source: http://www2.warwick.ac.uk

How To Improve Hair Treatment

In shampoo ads, hair always looks like a shiny, smooth surface. But for physicists peering into microscopes, the hair surface looks much more rugged, as it is made of saw-tooth, ratchet-like scales. In a new theoretical study published in EPJ E, Matthias Radtke and Roland Netz have demonstrated that massaging hair can help to apply drug treatmentencapsulated in nanoparticles trapped in the channels formed around individual hairs – to the hair roots. This is because the oscillatory movement of the massaging directs the way these particles are transported.

hair

This phenomenon was previously discovered in experiments on pork skin samples, which were conducted by Jürgen Lademann, dermatologist at the Charité clinic in Berlin, Germany, and his team. It is also relevant at the microscopic scale, in the transport on microtubules taking place in two directions between the cells within our bodies. By constrast, these findings could also help find ways of preventing harmful nanoparticles from being transported along hairs into the wrong places.

In their work, the authors created a model in which a nanoparticle moves between two asymmetric surfaces. Using standard models of random motion, they moved one surface in an oscillatory fashion relative to the other. They demonstrated by virtue of their corrugated surfaces that channels created between individual hairs and the surrounding skin lead to nanoparticles being sucked into hair follicles if the hair is massaged, thanks to a “ratchetmechanism.

Further, the authors determined optimal transport conditions for different surface structures by varying the driving frequency, particle size, and the amplitude of the corrugated surface. They found that the ratchet effect switches from a flashing to a pushing effect, when the oscillation switches from perpendicular to parallel to the resting surface, respectively. Radtke and Netz also found that nanoparticles’ speed and ability to diffuse are greatly enhanced by the parallel oscillatory motion.

Source: https://www.springer.com/

‘Protective’ DNA strands are shorter in adults who had more infections as infants

New research indicates that people who had more infections as babies harbor a key marker of cellular aging as young adults: the protective stretches of DNA which “cap” the ends of their chromosomes are shorter than in adults who were healthier as infants.

TELOMERESThe 46 chromosomes of the human genome, with telomeres highlighted in white

These are important and surprising findings because — generally speaking — shorter chromosome ‘caps’ are associated with a higher burden of disease later in life,” said lead author Dan Eisenberg, an assistant professor of anthropology at the University of Washington.

The ‘caps’ Eisenberg and his co-authors measured are called telomeres. These are long stretches of DNA at the ends of our chromosomes, which protect our genes from damage or improper regulation. One Nobel Prize-winning scientist who studies telomeres has compared them to aglets — the plastic or metal sheath covering ends of shoelaces. When aglets wear down, the shoelace is exposed to fraying and degradation from environmental forces.

Like aglets, telomeres don’t last forever. In most of our cells, telomeres get shorter each time that cell divides. And when they get too short, the cell either quits dividing or dies.

That makes telomere length particularly important for the cells of our immune system, especially the white blood cells circulating in our bloodstream. When activated against a pathogen, white blood cells undergo rapid rounds of cell division to raise a defensive force against the infectious invader. But if telomeres in white blood cells are already too short, the body may struggle to mount an effective immune response.

Many studies — in laboratory animals and humans — have associated shorter telomeres with poor health outcomes, especially in adults,” said Eisenberg. But few studies have addressed whether or not events early in a person’s life might affect telomere length. To get at this question, Eisenberg turned to the Cebu Longitudinal Health and Nutrition Survey, which has tracked the health of over 3,000 infants born in 1983-1984 in Cebu City in the Philippines. Researchers collected detailed data every two months from mothers on the health and feeding habits of their babies up through age two. Mothers reported how often their babies had diarrhea — a sign of infection — as well as how often they breastfed their babies. As these babies grew up, scientists collected additional health data during follow-up surveys over the next 20 years. In 2005, 1,776 of these offspring donated a blood sample. By then, they were 21- or 22-year-old young adults.

Eisenberg measured telomere length in cells from those blood samples. He then combined the data on adult telomere length with information about their health and feeding habits as babies. He found that babies with higher reported cases of diarrhea at 6 to 12 months also had the shortest telomeres as adults.

The findings have been published in the American Journal of Human Biology.

Source: http://www.washington.edu/

“Liquid Biopsy” Chip Detects Metastatic Cancer Cells in a Drop of Blood

A chip developed by mechanical engineers at Worcester Polytechnic Institute (WPI) can trap and identify metastatic cancer cells in a small amount of blood drawn from a cancer patient. The breakthrough technology uses a simple mechanical method that has been shown to be more effective in trapping cancer cells than the microfluidic approach employed in many existing devices.

liquid-biopsy-chip-test

The chip is tested in the lab. The electrodes detect electrical changes that occur when cancer cells are captured (click on the image to enjoy the video)

The WPI device uses antibodies attached to an array of carbon nanotubes at the bottom of a tiny well. Cancer cells settle to the bottom of the well, where they selectively bind to the antibodies based on their surface markers (unlike other devices, the chip can also trap tiny structures called exosomes produced by cancers cells). This “liquid biopsy,”  could become the basis of a simple lab test that could quickly detect early signs of metastasis and help physicians select treatments targeted at the specific cancer cells identified.

Metastasis is the process by which a cancer can spread from one organ to other parts of the body, typically by entering the bloodstream. Different types of tumors show a preference for specific organs and tissues; circulating breast cancer cells, for example, are likely to take root in bones, lungs, and the brain. The prognosis for metastatic cancer (also called stage IV cancer) is generally poor, so a technique that could detect these circulating tumor cells before they have a chance to form new colonies of tumors at distant sites could greatly increase a patient’s survival odds.

The focus on capturing circulating tumor cells is quite new,” said Balaji Panchapakesan, associate professor of mechanical engineering at WPI and director of the Small Systems Laboratory. “It is a very difficult challenge, not unlike looking for a needle in a haystack. There are billions of red blood cells, tens of thousands of white blood cells, and, perhaps, only a small number of tumor cells floating among them. We’ve shown how those cells can be captured with high precision.

The findings have been described in  the journal Nanotechnology,

Source: https://www.wpi.edu/

Nanoparticles Overcome Treatment-Resistant Breast Cancer

Researchers at the University of Cincinnati (UC) College of Medicine have been able to generate multifunctional RNA nanoparticles that could overcome treatment resistance in breast cancer, potentially making existing treatments more effective in these patients. The research team  led by Xiaoting Zhang, PhD, associate professor at the UC College of Medicine, demonstrates that using a nanodelivery system to target HER2-positive breast cancer and stop production of the protein MED1 could slow tumor growth, stop cancer from spreading and sensitize the cancer cells to treatment with tamoxifen, a known therapy for estrogen-driven cancer.
nanoparticles-300x225
Most breast cancers express estrogen receptors, and the anti-estrogen drug tamoxifen has been widely used for their treatment,” says Zhang, who is also a member of the Cincinnati Cancer Center and the UC Cancer Institute. “Unfortunately, up to half of all estrogen receptor-positive tumors are either unresponsive or later develop resistance to the therapy. In this study, we have developed a highly innovative design that takes advantage of the co-overexpression of HER2 and MED1 in these tumors.”
Zhang and researchers in his lab found that these RNA nanoparticles were able to selectively bind to HER2-overexpressing breast tumors, eliminating MED1 expression and significantly decreasing estrogen receptor-controlled target gene production. The RNA nanoparticles not only reduced the growth and spread of the HER2-overexpressing breast cancer tumors, but also sensitized them to tamoxifen treatment.

The study, has been published in the online edition of ACS Nano.

Source: http://healthnews.uc.edu/

Lab-grown Bones Transplanted With Success

A lab-grown, semi-liquid bone graft has been successfully injected into 11 patients’ jaws to repair bone loss. Israeli biotech firm Bonus Biogroup announced the early stage clinical trial results.

bones

CLICK ON THE IMAGE TO ENJOY THE VIDEO
What we are announcing to the world is that real success in our clinical study in regenerating new bone in maxillofacial site in the jaws, it was 100 percent successful in all 11 patients,” says Ora Burger, Vice President of Regulations Affairs at Bonus BioGroup.

The injectable bone grafts are made in the company’s Haifa plant, using cells extracted from patients’ fat tissue. They’re grown in sterile clean rooms, on biodegradable 3D scaffolds, before being injected into the voids in the jawbones.

We inject our semi-solid product inside of this defect and here we can see 12 weeks later that the bone is functional, we can see a full bone, a whole bone which is strong and hard and functional” comments Atara Novaks , Head of Research at Bonus BioGroup.

What we inject is a live bone. This is the first time ever that it’s been done,” adds Ora Burger. A clinical study into longer – so-called extremity – bones is now planned.

Source: http://www.bonus-bio.com/

How To Stop The Spread Of Breast Cancer

A breakthrough technology that harnesses manmade nanoparticles could one day become an important new weapon in the fight against cancer. The technique, which appeared to successfully stop the spread of breast cancer in mice, was unveiled by scientists from the Cold Spring Harbor Laboratory, Dana-Farber Cancer Institute, Stony Brook University, and a host of other research institutions in the journal Science Translational Medicine.

Next-generation cancer fighting therapies on the market today use the body’s immune system to combat tumors, as does experimental technology like CRISPR gene-editing. But the new nanotech has a different target: The cells that actually help cancer metastasize and spread throughout the body. These immune cells, which are meant to ward off infections, create structures called neutrophil extracellular traps (NETs) that help them fight bacteria. But NETs can actually wind up helping spread the cancer by creating tissue openings that cancerous cells can exploit, study co-author Mikala Egeblad explained.

 breast-cancer-cells

A high magnification of an intact neutrophil (yellow arrow) and a NET (white arrow)

So the researchers created a new particle coated with a special enzyme that can kill these cells before the cancer can use them to metastasize. The results were modest, but promising: Three out of the nine mice given the nanoparticle showed no evidence of breast cancer progression, while all mice in the control group continued to worsen.

Tatoo Therapy

A temporary tattoo to help control a chronic disease might someday be possible, according to scientists at Baylor College of Medicine who tested antioxidant nanoparticles created at Rice University. A proof-of-principle study led by Baylor scientist Christine Beeton published by Nature’s online, open-access journal Scientific Reports shows that nanoparticles modified with polyethylene glycol are conveniently choosy as they are taken up by cells in the immune system. That could be a plus for patients with autoimmune diseases like multiple sclerosis, one focus of study at the Beeton lab.

tatoo-therapy

“Placed just under the skin, the carbon-based particles form a dark spot that fades over about one week as they are slowly released into the circulation,” Beeton said. T and B lymphocyte cells and macrophages are key components of the immune system. However, in many autoimmune diseases such as multiple sclerosis, T cells are the key players. One suspected cause is that T cells lose their ability to distinguish between invaders and healthy tissue and attack both.

In tests at Baylor, nanoparticles were internalized by T cells, which inhibited their function, but ignored by macrophages. “The ability to selectively inhibit one type of cell over others in the same environment may help doctors gain more control over autoimmune diseases,” Beeton said. “The majority of current treatments are general, broad-spectrum immunosuppressants,” said Redwan Huq, lead author of the study and a graduate student in the Beeton lab. “They’re going to affect all of these cells, but patients are exposed to side effects (ranging) from infections to increased chances of developing cancer. So we get excited when we see something new that could potentially enable selectivity.” Since the macrophages and other splenic immune cells are unaffected, most of a patient’s existing immune system remains intact, he added.

 

Source: http://news.rice.edu/