The blood test requires a 10 milliliter blood sample -- just two teaspoons. It takes about eight hours to send the blood across the 80,000 tiny columns so a specially designed antibody glue can latch onto passing cancer cells. It was used to detect cancer in 27 people and helped to track the progress of cancer in near real time. This will help determine what treatments are working and a genetic fingerprint of the current state of any tumor. This should lead to better cancer treatment and earlier detection and better disease monitoring
Haber and his colleagues analyzed blood samples from 27 patients with non-small cell lung cancer, 23 who had EGFR gene mutations and four who did not. CTCs were identified in all samples and in genetic analyses from mutations 92 percent of the time.
Mutations in EGFR, a protein, can help predict whether these tumors will respond to a family of drugs called tyrosine kinase inhibitors.
"Even in the three to four months that we followed patients, the genetic make-up of the tumors changed. Resistant mutations appear and other mutations appear, obviously because we're doing things [with drug therapy] to the cancer," Haber said. "But the way we practice oncology we don't typically test for that. We do one biopsy which takes a tiny, tiny amount and assume that for the rest of the course, the tumor is the same."
"It's important to know in real time what you're treating," he continued. "We need to be able to follow the patient without needing to re-biopsy the tumor every time."
A previous study published in Nature used the CTC (Circulating Tumor Cells) chip technology to look at CTCs in lung, pancreatic, prostate, breast and colon cancers. The CTC chip successfully found such cells in 99 percent of the samples.
Schiller, of the University of Texas Southwestern Medical Center in Dallas, said there are practical questions about whether enough cells can be extracted to make the technique effective and whether it will work for other types of tumors.
Haber said he believes it will.
The CTC chip, licensed to the privately held CellPoint Diagnostics in Mountain View, California, is 100 times more sensitive than a U.S. Food and Drug Administration-approved technique that uses magnetic beads to try to extract cancer cells, according to Haber.
"I think this is key to personalized medicine," said Dr. Daniel Haber, senior author of a paper detailing the technology, to be published in the July 24 issue of the New England Journal of Medicine but released early online Wednesday. "As we get to targeted therapies in increasing numbers, and increasing understanding about the genetics that guide targeted therapies, we need a way to know what we're treating."
The technology is in its infancy, however. "This is still in a very, very early stage where it takes a long time to handle every sample, to flow the blood through the chip," Haber said. "This is a proof of principle that we can do this. We need a much more automated system for larger clinical trials."
Dr. Len Horovitz, a pulmonary specialist at Lenox Hill Hospital in New York City, said that "you have to have some circulating cells to do this test, but it's very exciting because they're getting a genetic fingerprint of a tumor which will tell an oncologist what therapy the tumor might respond to or not respond to.
"It's expensive, but it may well be that if we can identify patients who can have a personalized regimen that works, we will be saving the cost of treating all those patients with regimens that don't work," he added.
FURTHER
Megpagetoday coverage
Web MD coverage of the CTC chip
Read More...
Summary only...
Human trials starting for Zheng Cui's LIFT 'cancer cure' H/T to Alfin
For the upcoming study, the researchers are currently recruiting 500 local potential donors who are 50 years old or younger and in good health to have their blood tested. Of those, 100 volunteers with high cancer-killing activity will be asked to donate white blood cells for the study. Cell recipients will include 22 cancer patients who have solid tumors that either didn't respond originally, or no longer respond, to conventional therapies. The study will cost $100,000 per patient receiving therapy, and for many patients (those living in 22 states, including North Carolina) the costs may be covered by their insurance company. There is no cost to donate blood.
The LIFT method and signing up for the trials The procedure was previously called GIFT.
LIFT is an investigational new cancer treatment that will transfer naturally-occurring cancer-killing activity (CKA) in the granulocytes of a selected donor into the body of a cancer patient.
Here's how the LIFT method works: * Donor selection: Healthy young volunteers will be screened for the level of CKA, blood types, HLA types, infectious disease status, CMV status etc. by blood tests and physical examinations. The selected volunteers will become part of the Donor Registry. The test results of selected volunteers will be used to match with specific patients.
* Granulocyte collection: When a qualified patient is identified for treatment, granulocytes from several matched donors in the donor registry will be mobilized by two medications and collected by a well-established medical procedure called "apheresis" or "pheresis." A pheresis machine separates donor granulocytes from other blood products that will be immediately returned to donors so that the health impact on granulocyte donation is much smaller than on whole blood donation. Granulocyte mobilization and collection by apheresis have been used in clinical practices for a long time with very good safety record.
* Patient selection and granulocyte infusion: Qualified patients will be selected according to general health condition, disease status and match criteria. Freshly collected granulocytes from matched donors will be given to patients via IV infusion. Granulocytes cannot be stored or shipped for later uses.
Granulocyte infusion therapy has been traditionally used for treating neutropenia-related infections for over 30 years with excellent safety records. Since a significantly higher dose of granulocytes for each patient is proposed in our new cancer treatment, the primary goal of this clinical trial is to test whether the recipients can tolerate the proposed dose of granulocytes.
The main focus of the trial is the possibility of developing Transfusion-Associated Graft vs Host Diseases (TA-GVHD) and other potential side effects in the study subjects at higher doses of donor granulocyte.
Donor granulocytes per se are not known to produce TA-GVHD. However, granulocytes collected via apheresis may contain with some donor T-lymphocytes that in some rare occasions can produce various degrees of TA-GVHD in some individuals, especially the recipients with immune suppression. If possible, we will also make observations on the efficacy of this treatment on the study subjects with measurable diseases of cancer. We will recruit 22 cancer patients as study subjects for this trial.
FURTHER READING
More at redorbit
Read More...
Summary only...
There will be about thirty speakers at the Understanding aging conference in UCLA this weekend
Here are links to the abstracts of the presentations and some of the highlighted presentations.
Zheng Cui will discuss his Natural Cancer Resistance in Mice and in Humans: basis for a novel cancer therapy (GIFT therapy was covered here) and if successful would be a significant advance in reducing cancer deaths. [possibly a high cure rate and preventing many cancers by helping people fight off early stage cancer]
A new clinical trial is underway at Wake Forest University to test this novel cancer therapy, termed "Leukocyte Infusion Therapy" or LIFT. This clinical trial has met all regulatory requirements including approval by the Wake Forest University School of Medicine's Institutional Review Board (IRB) and been granted an IND (Investigational New Drug) status by the Food and Drug Administration (FDA).
B.N. Ames talks about delaying the Degenerative Diseases of AgingI [B.N. Ames] propose that during evolution micronutrient shortages were very common, e.g. the 15 essential minerals, which are not distributed evenly on the earth. The consequences of this homeostatic response are, for example, DNA damage (future cancer), adaptive immune dysfunction (future severe infection), and mitochondrial decay (future cognitive dysfunction and accelerated aging). Much evidence supports this idea that micronutrient shortages accelerate aging.
S.F. Badylak of the McGowan Institute for Regenerative Medicine, Pittsburgh, PA will be talking about Regenerative Medicine and AgingRegenerative medicine is typically based upon the strategic use of undifferentiated stem and progenitor cells, inductive bioscaffolds, and appropriate micro-environmental cues that signal the need for tissue reconstruction. In many respects, the desired result is the recapitulation of developmental biology but limited to a specific tissue or organ. There are many fundamental questions yet to be answered with regard to implementation of such strategies in an aging population. Do aging cells have the same potential for regeneration as young cells? Are biologic scaffolds composed of extracellular matrix from fetal tissues more "instructive" than biologic scaffolds harvested from adult extracellular matrix? How does the micro-environment of aged tissues and organs differ from that or neonatal tissues and organs? These and other questions will be discussed.
L.A. Briggs will discuss the struggle to keep telomeres long
The purpose of this presentation will be to review the current progress [to keep telomeres long], including the recent discovery of several small molecules that induce telomerase activity in normal human cells.
J. Campisi will discuss New tricks for dealing with old cells?
Some senescent cells can escape immune killing by secreting very high levels of matrix metalloproteinases (MMPs). These enzymes likely destroy the ligand-receptor interactions that are needed for killing by natural killer cells. Moreover, the killing of senescent cells can be greatly enhanced by MMP inhibitors, which therefore hold promise for improving the clearance of senescent cells from aged or diseased tissues. We also find that the senescence-associated secretion of inflammatory cytokines is dependent on continuous DNA damage signaling, particularly signaling initiated by the ATM protein kinase. Ablation of ATM kinase activity by RNA interference markedly reduces inflammatory cytokine secretion, suggesting that ATM inhibition might also hold promise for reducing local inflammation caused by senescent cells
C. Gravekamp is working on an improvement of cancer vaccination for older people
K.E. Healy is presenting Synthetic Environments to control Human Embryonic Stem Cell Self-Renewal and Fate Determination
Larocca is presenting Targeted Nanoparticle Probes for Identifying, Tracking and Isolating Embryonic Stem Cell Derived Progenitor Cells
C. Leeuwenburgh will be presenting Mitochondrial iron accumulation with age and functional consequences
D.A. Taylor will be presenting three-fold cell-based approaches to cardiovascular repair and answering the question Is Aging a Treatable Disease in the 21st Century?
FURTHER READING
Over twenty poster abstracts
The agenda of the conference with links to abstracts.
Pre-coverage of the conference
and coverage of Wired article on the conference
The new SENS projects AmyloSENS, ApoptoSENS, Glycosens, Oncosens and Replenisens
Read More...
Summary only...
Early detection saves lives as treatment is more effective. Also, it can be 100 times cheaper to treat early stage versus later stage cancer. The Canary Foundation goal is to deliver early detection tests for solid tumor cancers by 2015. Cancer treatment cost $89 billion in the U.S. in 2007. Over 1.4 million new cancer cases are expected in 2008 in the US alone. Less than 15% of research funding goes to early detection. Early detection has proven value: since 1950, there has been a 70 percent decline in cervical-cancer incidence and deaths in developed countries5 thanks to a simple screening test, the Pap test ($8 test). Effective early cancer tests could save over $50 billion per year in medical costs and 400,000 lives each year in the USA and 5 million lives around the world. 7 million people die from cancer each year worldwide.
Cancer researchers met at Stanford University to work toward a goal of developing a simple blood test to detect cancer.
The symposium by the Canary Foundation allowed doctors to share their research in developing a simple two-stage test for cancer. They're hoping to deliver an early detection test for solid tumor cancers by 2015, said Dr. Don Listwin, founder of the Canary Foundation.
The blood test, which would look for proteins given off by cancer cells, could detect the disease at its earliest stages, when treatment would be most effective.
Slide images and information is from the Canary Foundation presentation
A major investment in imaging is a key difference with Canary. As opposed to anatomical imaging, they strive to create probes that will home in on the cancer and light it up for the surgeon. Canary's goal is to deliver two‐stage tests for all solid tumors.
For the blood test, they need to combine multiple biomarkers to find ovarian cancer. So far, there aren’t single markers. Canary believes that combinations of three to five markers or “panels” will identify early cancer. They have a blood test that is quite promising at 0.960 in early stage cancer. So what is good enough? Well, if you cut someone open as the next step, then .96 isn’t near good enough. 4% wrong if you screen millions of woman is a disaster. But if you have a next stage imaging test to
confirm, deny or monitor, it is good enough. Without imaging, this test needs to be 0.999 and that will be very challenging if not impossible. Their focus is on new molecular imaging as opposed to anatomical imaging like X‐ray or mammography
They look for proteins that are specific to cancer that exist on the cell surface.
The scientists create probes that are specific to those cells and light them up.
Biomarkers for imaging are those type of proteins that stick on cell surface and for blood biomarkers it’s proteins that shed and circulate in the blood.
FURTHER READING
Nextbigfuture has been in favor of the aggressive research into biomarkers and the development of inexpensive tests for early disease detection.
Read More...
Summary only...
Carbon nanotubes appear to have a similar cancer causing effect as asbestos in mice
Within days of being injected into mice, the nanotubes -- which are increasingly used in electronic components, sporting goods and dozens of other products -- triggered a kind of cellular reaction that over a period of years typically leads to mesothelioma, a fatal form of cancer, researchers said.
The preliminary evidence of cancer risk is strong enough to justify urgent follow-up tests and government guidance for nano factory workers. Others called for labels to guide consumers or recyclers who might encounter the material when incinerating or otherwise destroying discarded nano products.
Carbon nanotubes also occur in nature in volcanic ash. It would interesting to see what the cancer effect was of volcanic ash.
There is a lot of media coverage of this study
Read More...
Summary only...
Segmented "nanoworms" composed of magnetic iron oxide and coated with a polymer are able to find and attach to tumors. Scientists at UC San Diego, UC Santa Barbara and MIT have developed nanometer-sized “nanoworms” that can cruise through the bloodstream without significant interference from the body’s immune defense system and—like tiny anti-cancer missiles—home in on tumors. They are superparamagnetic and show up very well on MRIs and can circulate in the body for hours since they do not trigger the immune system. Researchers are developing chemical attachments that will help to reach specific targets in the body and adding drugs that would be released when targets are reached.
Using nanoworms, doctors should eventually be able to target and reveal the location of developing tumors that are too small to detect by conventional methods. Carrying payloads targeted to specific features on tumors, these microscopic vehicles could also one day provide the means to more effectively deliver toxic anti-cancer drugs to these tumors in high concentrations without negatively impacting other parts of the body.
“Most nanoparticles are recognized by the body's protective mechanisms, which capture and remove them from the bloodstream within a few minutes,” said Michael Sailor, a professor of chemistry and biochemistry at UC San Diego who headed the research team. “The reason these worms work so well is due to a combination of their shape and to a polymer coating on their surfaces that allows the nanoworms to evade these natural elimination processes. As a result, our nanoworms can circulate in the body of a mouse for many hours.”
The scientists constructed their nanoworms from spherical iron oxide nanoparticles that join together, like segments of an earthworm, to produce tiny gummy worm-like structures about 30 nanometers long—or about 3 million times smaller than an earthworm. Their iron-oxide composition allows the nanoworms to show up brightly in diagnostic devices, specifically the MRI, or magnetic resonance imaging, machines that are used to find tumors.
“The iron oxide used in the nanoworms has a property of superparamagnetism, which makes them show up very brightly in MRI,” said Sailor. “The magnetism of the individual iron oxide segments, typically eight per nanoworm, combine to provide a much larger signal than can be observed if the segments are separated. This translates to a better ability to see smaller tumors, hopefully enabling physicians to make their diagnosis of cancer at earlier stages of development.”
The researchers are now working on developing ways to attach drugs to the nanoworms and chemically treating their exteriors with specific chemical “zip codes,” that will allow them to be delivered to specific tumors, organs and other sites in the body.
“We are now using nanoworms to construct the next generation of smart tumor-targeting nanodevices,” said Ruoslahti. We hope that these devices will improve the diagnostic imaging of cancer and allow pinpoint targeting of treatments into cancerous tumors.”
Read More...
Summary only...
Kanzius RF therapy attaches microscopic nanoparticles to cancer cells and then "cooks" tumors inside the body with harmless radio waves could be in clinical trials as early as 3 years. The treatment has been 100% effective in animal trials.
The CBS news has an extensive 4 webpage feature on the technique.
An interesting aspect is that Richard Smalley initially thought that the radiowave to heat up metal nanoparticle technique to cook cancer tumors would not work. Richard's scientific intuition was that this would completely fail. He was converted into being a believer when proven wrong with successful experimentation.
This is relevant since Richard Smalley's intuition was that molecular manufacturing would not work. This does not indicate that molecular manufacturing will be successful, but it does show that Richard's track record for intuition related to a successful or unsuccessful application of nanoscale related technology is not 100% accurate.
Read More...
Summary only...
In an Esquire magazine interview Andre Dillin, Salk Institute, indicated that they have a compound which is very effective at treating Alzheimers effects and extending life. So far that work has been on C elegan worms
But more than the apparent result, what excites and interests Dillin is the way the drug achieves its result. A-Beta does its damage by causing cell proteins to misfold; Dillin suspects that the drug works not by specifically blocking A-Beta but rather by encouraging proteins to keep folding accurately and precisely. That is, he thinks the drug works by promoting an overall cellular well-being, otherwise known as youthfulness. Specifically, he thinks the drug works by "upregulating the PHA-4 pathway," which has been defined as a pathway regulating longevity. But he thinks it does more than that. He thinks it will enable him to define and deal experimentally with youthfulness.
The article mentions doubling lifespans to 250 years. However, to achieve that effect would require more than calorie restriction effects. It would also not apply to people who are already middle age or older if it is reducing metabolic aging in half.
Andrew Dillin's research papers
The SENS and MPrize funding combined are over $11 million
SENS is looking to launch several new research projects.
AmyloSENS: Extracellular junk is aggregates of stuff that do not have any function and should ideally have been cleared out of the body, but have proven resistant to destruction. Most of this junk is termed “amyloid” of one variety or another. You may have heard of one form of amyloid – Abeta, the stifling, web-like material that forms plaques in the brains of patients with Alzheimer's disease, and also (more slowly) in everyone else’s.
Elan Pharmaceuticals’ most recent candidate Alzheimer vaccine, bapineuzumab, has been the subject of recent excitement after the company launched a full-scale (“Phase III”) clinical trial at an unusually early point, leading to speculation that the as-yet-undisclosed preliminary results of its earlier trials may be exceptionally promising.
The Methuselah Foundation is presently in discussion with leading researchers in this field with a view to initiating work on a vaccine – similar to that developed by Elan for Alzheimer’s disease – to stimulate the aged body to clear the widespread amyloids (particular of transthyretin) responsible for senile systemic amyloidosis.
ApoptoSENS
There are three main classes of cells that sometimes acquire a metabolic state that is damaging to their neighbours. (Visceral fat cells, Senescent cells, Immune cells)
There are two main alternatives:
1. Inject something that makes the unwanted cells commit suicide but doesn't touch other cells.
2. Stimulate the immune system to kill the target cells.
Glycosens
The Methuselah Foundation is currently planning out a project to engineer enzymes capable of cleaving the ubiquitous glucosepane crosslinks, which may comprise as much as 98% of all the long-lived crosslinks in aged human tissue. This work is still in the early planning stages, but we hope to be able to begin full-time research before the end of 2008.
Oncosens
We don't actually need to fix chromosomal mutations at all in order to stop them from killing us: all we need to do is develop a really really good cure for cancer. The one that I favour (and which was the topic of the third SENS roundtable, a meeting I convened in Cambridge in 2002) is called WILT, for Whole-body Interdiction of Lengthening of Telomeres.
The Methuselah Foundation is planning to launch three projects in the OncoSENS strand during 2008.
The first project aims to characterise the enzyme responsible for ALT, which is still unknown. Recently, however, observations in two different organs have given good reason to consider a hitherto unsuspected gene. A relatively simple series of experiments could test this hypothesis.
The second project addresses a potential problem with the WILT strategy. It’s possible that telomerase activity per se – independent of telomere length – may have roles in maintaining the health of the stem cells themselves, or of their rarely-dividing neighbours in the so-called “stem cell niche”. We are arranging a project to address this question, in the blood of mice, with the world’s leading professor in the area.
Finally, the theory that non-cancer-causing mutations are unlikely to be harmful in a normal lifetime – protagonistic pleiotropy – is not yet widely accepted. We are therefore initiating a rigorous study into the effects of such mutations in mouse brains.
Replenisens
Cell depletion is the loss of cells without equivalent replacement. Cell depletion can be fixed in two main ways: by stimulating the division of existing cells, or by directly introducing new ones. There is a lot of active work with Stem cells, so the Methuselah Foundation does not currently intend to allocate its limited resources to projects in this area.
Read More...
Summary only...
Stanford University School of Medicine researchers has developed a new type of imaging system that can illuminate tumors in living subjects—getting pictures with a precision of nearly on nanometer (one-trillionth of a meter).
This technique, called Raman spectroscopy, expands the available toolbox for the field of molecular imaging, said team leader Sanjiv Sam Gambhir, MD, PhD, professor of radiology. signals from Raman spectroscopy are stronger and longer-lived than other available methods, and the type of particles used in this method can transmit information about multiple types of molecular targets simultaneously.
“Usually we can measure one or two things at a time,” he said. “With this, we can now likely see 10, 20, 30 things at once.”
Gambhir said he believes this is the first time Raman spectroscopy has been used to image deep within the body, using tiny nanoparticles injected into the body to serve as beacons.
When laser light is beamed from a source outside the body, these specialized particles emit signals that can be measured and converted into a visible indicator of their location in the body.
Technology Review also has some information on this new imaging technology.There are several techniques that employ the Raman effect, but this study used SERS (surface enhanced Raman scattering), which relies on roughened surfaces of metal nanoparticles to greatly boost the Raman effect. To create Raman nanoparticles, scientists attach small dye molecules, which scatter light, to these molecular amplifiers. They can then affix molecules that allow them to target the particles to a location in the body, such as antibodies that bind to specific proteins in cells.
The key advantage of this technique is that it allows for what imaging researchers call multiplexing: creating images of several different molecules at once. "One of the problems with imaging is, we tend to only be able to look at one or two things at a time," says Sanjiv Sam Gambhir, lead author of the study and codirector of the Molecular Imaging Program at Stanford. Multiplexing is important in complex diseases like cancer, in which several events occur within tumor cells, each of which could give information about the tumors' status and the likelihood that it will spread. As a first demonstration of multiplexing, Gambhir's team injected mice simultaneously with four kinds of Raman nanoparticles at different concentrations and showed that it is possible to locate the different particles and calculate their concentrations based on their Raman signal.
The most widely used molecular imaging technique in the lab is fluorescence. What makes Raman spectroscopy unique is that "you get a very sharp signal back, unlike [with] fluorescence, where you get a broad spectrum of energy," Gambhir says.
Claudio Vinegoni, an imaging specialist at the Center for Molecular Imaging Research at Harvard and at the Massachusetts General Hospital, who was not involved in the study, says that although scientists can use fluorescent molecules of different colors to see more than one molecule at a time, the ability to multiplex is limited because their signals quickly begin to overlap. In contrast, with Raman spectroscopy, "every molecule has its own Raman spectrum," Vinegoni says, so there is no possibility of the signals interfering. Because of their specificity, Raman nanoparticles can also be imaged at concentrations a thousand times lower than what can be detected using fluorescent quantum dots.
One of the major shortcomings of this technique, as in all optical imaging methods, is the limited ability of light to penetrate deep into tissue. Although it can be used to visualize the internal organs of a mouse, Gambhir says that in humans, the technique would be more useful for visualizing tumors close to the surface of the skin, such as melanomas or even breast cancer. The technique could also be used in conjunction with endoscopes that probe inside the body. Gambhir's team is planning a clinical trial to test the use of Raman particles in conjunction with colonoscopies for detecting early-stage cancers. In this procedure, the nanoparticles could simply be sprayed onto the surface of the colon rather than injected into the body. But a key challenge for bringing this technique into the clinic will be determining the safety of nanoparticles as probes--studies that Gambhir's group is currently undertaking.
Imaging of animals and humans can be done using a few different methods, including PET, magnetic resonance imaging, computed tomography, optical bioluminescence and fluorescence and ultrasound. However, said Gambhir, none of these methods so far can fulfill all the desired qualities of an imaging tool, which include being able to finely detect small biochemical details, being able to detect more than one target at a time and being cheap and easy to use.
Postdoctoral scholars Shay Keren, PhD, and Cristina Zavaleta, PhD, co-first authors of the study, found a way to make Raman spectroscopy a medical tool. To get there, they used two types of engineered Raman nanoparticles: gold nanoparticles and single-wall carbon nanotubes.
First, they injected mice with the some of the nanoparticles. To see the nanoparticles, they used a special microscope that the group had adapted to view anesthetized mice exposed to laser light. The researchers could see that the nanoparticles migrated to the liver, where they were processed for excretion.
Using a microscope they modified to detect Raman nanoparticles, the team was able to see targets on a scale 1,000 times smaller than what is now obtainable by the most precise fluorescence imaging using quantum dots.
When adapted for human use, they said, the technique has the potential to be useful during surgery, for example, in the removal of cancerous tissue. The extreme sensitivity of the imager could enable detection of even the most minute malignant tissues.
Read More...
Summary only...
Two forms of RNA either boost or suppress protein production, and scientists have in recent years discovered this system is central to a range of illnesses, including cancers, viral infections, cardiovascular disease and neurological disorders.
Previous attempts to manipulate this process have failed because the drug molecules used were too large to get to the target cells. Now scientists at Santaris Pharma have developed smaller compounds that can cross cell membranes and intercept the microRNA molecules that usually put a brake on protein production.
LNA-mediated microRNA silencing in non-human primates.
MicroRNAs (miRNAs) are small regulatory RNAs that are important in development and disease and therefore represent a potential new class of targets for therapeutic intervention. Despite recent progress in silencing of miRNAs in rodents, the development of effective and safe approaches for sequence-specific antagonism of miRNAs in vivo remains a significant scientific and therapeutic challenge. Moreover, there are no reports of miRNA antagonism in primates. Here we show that the simple systemic delivery of a unconjugated, PBS-formulated locked-nucleic-acid-modified oligonucleotide (LNA-antimiR) effectively antagonizes the liver-expressed miR-122 in non-human primates. Acute administration by intravenous injections of 3 or 10 mg kg-1 LNA-antimiR to African green monkeys resulted in uptake of the LNA-antimiR in the cytoplasm of primate hepatocytes and formation of stable heteroduplexes between the LNA-antimiR and miR-122. This was accompanied by depletion of mature miR-122 and dose-dependent lowering of plasma cholesterol. Efficient silencing of miR-122 was achieved in primates by three doses of 10 mg kg-1 LNA-antimiR, leading to a long-lasting and reversible decrease in total plasma cholesterol without any evidence for LNA-associated toxicities or histopathological changes in the study animals. Our findings demonstrate the utility of systemically administered LNA-antimiRs in exploring miRNA function in rodents and primates, and support the potential of these compounds as a new class of therapeutics for disease-associated miRNAs.
Mice on a high fat diet were given three injections of a drug to block miRNA-122, a compound in the liver that controls cholesterol levels. Those given the highest dose had 30 per cent lower cholesterol levels than those given placebo injections, and the effects lasted three weeks after the last injection.
Laboratory tests also showed that blocking miRNA-122 also prevented the hepatitis C virus replicating. Human trails of a drug to treat hepatitis C will begin next year and scientists are using the method to develop a treatment to combat blood cancers.
Santaris predicts new therapies will be ready for use by patients within five years if trials go well.
Santaris Pharma is preparing to advance its first LNA-antimiR compound, targeting miR-122, into human clinical testing in the first half of 2008.
FURTHER READING
Safer and more precise methods of targeting gene therapy are being made with synthetic zinc fingers.
Researchers have figured out the real problem with a common gene therapy delivery system the adenovirus type 5. Adenovirus consists of three major proteins - fiber, penton and hexon. Previously researchers thought the fiber protein was the problem. New research indicates it is the hexon. Now by modifying the hexon they can make adenovirus delivered gene therapy safe.
“Now that we have learned the mechanism that an adenovirus uses we could modify that process by genetically engineering the virus, to improve uptake into several cell types, including stem cells,” says Dr. Napoli.
There has also been progress in using gene therapy to treat brain cancer.
Safe and effective gene therapy or drugs that safely target genetic effects could be used to safely boost muscle mass by four times. This could make people stronger and healthier. Better weight control with more muscle that burns excess fat. 2012-2016 seems to be the likely timeframe when these procedures start making a big societal impact. It could happen sooner and more could happen later, but that seems to be the time when more people will realize that a new age is upon the world.
Read More...
Summary only...
One day soon a biosensing nanodevice developed by Arizona State University researcher Wayne Frasch may eliminate long lines at airport security checkpoints and revolutionize health screenings for diseases like anthrax, cancer and antibiotic resistant Staphylococcus aureus (MRSA)
Frasch works with the enzyme F1-adenosine triphosphatase, better known as F1- ATPase. This enzyme, only 10 to 12 nanometers in diameter, has an axle that spins and produces torque.
What Frasch and his colleagues show is that the enzyme can be armed with an optical probe (gold nanorod) and manipulated to emit a signal when it detects a single molecule of target DNA. This is achieved by anchoring a quiescent F1-ATPase motor to a surface. A single strand of a reference biotinylated DNA molecule is then attached to its axle. The marker protein, biotin, on the DNA is known to bind specifically and tightly to the glycoprotein avidin, so an avidin-coated gold nanorod is then added. The avidin-nanorod attaches to the biotinylated DNA strand and forms a stable complex.
When a test solution containing a target piece of DNA is added, this DNA binds to the single complementary reference strand attached to the F1-ATPase. The DNA complex, suspended between the nanorod and the axle, forms a stiff bridge. Once ATP is added to the test solution, the F1-ATPase axle spins, and with it, the attached (now double-stranded) DNA and nanorod. The whirling nano-sized device emits a pulsing red signal that can then be detected with a microscope.
According to Frasch, the rotation discriminates fully assembled nanodevices from nonspecifically bound nanorods, resulting in a sensitivity limit of one zeptomole (600 molecules). Simply put, if it's not moving and flashing, it simply isn't relevant.
Moreover, Frasch says, �Studies with the F1-ATPase in my laboratory show that since it can detect single DNA molecules, it far exceeds the detection limits of conventional PCR [polymerase chain reaction] technology.
Such a detection instrument based on the F1-ATPase enzyme would also be faster and more portable, he adds.
With support from Science Foundation Arizona (SFAz), Frasch will transfer his work from the bench to biotech, through establishment of a local company that utilizes the nano-sized F1-ATPase to produce a DNA detection instrument.
A prototype of the DNA detector is already in development. It is roughly the size of a small tissue box. Sampling would be as simple as taking a swab from an infected wound or a piece of baggage, dissolving it in a solution and placing a drop on a slide bearing reference F1-ATPases and their nanorods. Once in the instrument, red blinking signals emitted by rotating nanorods would let a computer know there's trouble, literally, in a flash.
RELATED NEWS: A One-Step Homogeneous Immunoassay For Cancer Biomarker Detection Using Gold Nanoparticle Probes Coupled With Dynamic Light Scattering
The early detection of cancer can significantly improve the treatment and survival rate of cancer patients. As tumors develop, the cells, tissues and organs can increase or decrease the release of certain chemicals in the circulatory system. These specific chemicals are called biomarkers. Some of these biomarkers have been approved by FDA for the in-vitro diagnosis of different types of cancer. A well known example is the test of PSA (prostate specific antigen) level for prostate cancer detection. A total PSA level of 4 ng/mL is generally considered as a normal threshold, and when this value exceeds 10 ng/mL, the chance of prostate malignancy is increased substantially.
The nanoDLSA immunoassay is fast, highly sensitive, accurate, and extremely easy to conduct. It requires a much smaller amount (at least 100 times less) of blood samples and antibody probes to conduct the assay compared to ELISA. The cost reduction of nanoDLSA compared to other immunoassays is tremendous. Because of the minute amount of sample that is required by nanoDLSA, it is possible to conduct the detection and measurement of one or multiple cancer markers from a single drop of human blood sample using this new immunoassay technology. The goal of this research group is to develop a fully automated system that can be placed in supermarkets, pharmacy stores, hospitals, and clinics for the general public to test their cancer marker levels as frequently as necessary at affordable prices. The biomarker level history obtained from each individual will provide invaluable information to medical doctors for the early screening and diagnosis of cancer. Equally important, such frequent testing is also critical for cancer patients whose cancer marker levels need to be analyzed constantly to monitor the treatment effect and the recurrence of cancer.
RELATED READING
USB stick genetic testing device for $10 or less.
Read More...
Summary only...
MIT has developed a simple, inexpensive system to sort different kinds of cells a process that could result in low-cost tools to test for diseases such as cancer, even in remote locations.
The method relies on the way cells sometimes interact with a surface (such as the wall of a blood vessel) by rolling along it. In the new device, a surface is coated with lines of a material that interacts with the cells, making it seem sticky to specific types of cells. The sticky lines are oriented diagonally to the flow of cell-containing fluid passing over the surface, so as certain kinds of cells respond to the coating they are nudged to one side, allowing them to be separated out.
Cancer cells, for example, can be separated from normal cells by this method, which could ultimately lead to a simple device for cancer screening. Stem cells also exhibit the same kind of selective response, so such devices could eventually be used in research labs to concentrate these cells for further study.
Normally, it takes an array of lab equipment and several separate steps to achieve this kind of separation of cells. This can make such methods impractical for widespread screening of blood samples in the field, especially in remote areas. �Our system is tailor-made for analysis of blood,� Karnik says. In addition, some kinds of cells, including stem cells, are very sensitive to external conditions, so this system could allow them to be concentrated with much less damage than with conventional multi-stage lab techniques.
Now that the basic principle has been harnessed in the lab, Karnik estimates it may take up to two years to develop into a standard device that could be used for laboratory research purposes. Because of the need for extensive testing, development of a device for clinical use could take about five years, he estimates.
Read More...
Summary only...
Cell Traffix, using a microtube device coated with the protein P-selectin, has isolated and collected adult stem cells residing in human bone marrow to eight times greater purity than can be obtained through traditional centrifugation.
The device, a length of plastic tubing coated with proteins, could lead to better bone-marrow transplants and stem-cell therapies, and it also shows promise as a way to capture and reprogram cancer cells roaming the bloodstream. The system could capture and differentiate stem cells and other cells in the body and allow them to altered or replaced inside or outside the body. It is a path to killing cancer and removing aged cells with rejuvenated cells. There has also been promising work in reprogramming adult stem cells to revert to embryonic stem cells
Researchers used genetic alteration to turn back the clock on human skin cells and create cells that are nearly identical to human embryonic stem cells, which have the ability to become every cell type found in the human body. Reprogramming adult stem cells into embryonic stem cells could generate a potentially limitless source of immune-compatible cells for tissue engineering and transplantation medicine.
The
behavior of stem cells, or any new tissue, in the body has a great deal to do with the holistic functioning of signaling networks and the cellular environment. The Cell Traffix device can enable alterations in the signaling to regular cells, cancer cells and stem cells.
Direct capture of blood-borne nucleated cells from circulation using P-selectin and non-coated control surfaces in implanted devices. Following incorporation into the femoral artery of anesthetized rats and 1-h blood perfusion, P-selectin coated tubes (A) showed a significantly greater average concentration of captured nucleated cells than non-coated control tubes (B) [184·6 ± 19·9 cells/mm2 for P-selectin tubes (40 μg/ml) vs. 4·7 ± 1·4 cells/mm2 for control surfaces (P < 0·01), bar = 50 μm]. (C) Total cell yields from 50 cm implanted tubes with cell adhesion molecule surfaces were significantly greater than the yield from non-specific binding in control tubes (**P < 0·01).The new device mimics a small blood vessel: it's a plastic tube a few hundred micrometers in diameter that's coated with proteins called selectins. The purpose of selectins in the body seems to be to slow down a few types of cells so that they can receive other chemical signals. A white blood cell, for instance, might be instructed to leave the circulation and enter a wound, where it would protect against infection. "Selectins cause [some] cells to stick and slow down," says Michael King, a chemical engineer at the University of Rochester who's developing the cell-capture devices. Different types of selectins associate with different kinds of cells, including platelets, bone-marrow-derived stem cells, and immune cells such as white cells.
Nanowerk describes and ridicules a pure brute force nanotechnology robot approach to cellular repair. The new work by Cell Traffix shows that there could be other more clever paths to being able to achieve cellular rejuvenation.
Twenty-eight percent of the cells captured by King's implants were stem cells. "This is astounding given how rare they are in the bloodstream," says King. Implants would probably not be able to capture enough stem cells for transplant. But King believes that filtering a donor's blood through a long stretch of selectin-coated tubing outside the body, in a process similar to dialysis, would be very efficient. "This technique will clearly be useful outside the body" as a means of purifying bone-marrow-derived stem cells, says Daniel Hammer, chair of bioengineering at the University of Pennsylvania.
Mike King holding the cell capture device
Hammer believes that King's devices will also have broader applications as implants that serve to mobilize a person's own stem cells to regenerate damaged tissues. By slowing down cells with selectins and then exposing them to other kinds of signals, says Hammer, King's devices "could capture stem cells, concentrate them, and differentiate them, without ever having to take the cells out of the body." There might be a way to use selectins to extract neural stem cells, too. "This is a very broad-reaching discovery," says Hammer. Indeed, King says that he has already had some success using selectin coatings to reprogram cancer cells. Leukemia is a blood cancer, but King expects that the anticancer coating would work for solid tumors as well. Devices lined with these coatings might be implanted into cancer patients to prevent or slow metastasis. The company hopes to begin clinical testing of the anticancer coatings by early 2010.
FURTHER READING
Implanted CellTraffix Device Extracts Adult Stem Cells Directly from the Bloodstream, online in the British Journal of Haematology
Cancer killing invention also harvest stem cells
Other stem cell work: embryonic stem cells can be used to create functional immune system blood cells, a finding which is an important step in the utilisation of embryonic stem cells as an alternative source of cells for bone marrow transplantation.
Read More...
Summary only...
A fundamentally new design has created a smaller endoscope (currently 9mm wide and new one is 6mm wide with a thinner tether) that is more comfortable for the patient and cheaper to use than current technology. Its first use on a human, scanning for early signs of esophageal cancer.
The UW's scanning fiber endoscope fits in a pill that can be comfortably swallowed. The casing measures 6 millimeters wide and 18 millimeters long. (Credit: Image courtesy of University of Washington)
This is the image of the map produced by the endoscope. The devices records 15 color images per second with a resolution of more than 500 lines per inch. (Credit: Image courtesy of University of Washington)
An endoscope is a flexible camera that travels into the body's cavities to directly investigate the digestive tract, colon or throat. Most of today's endoscopes capture the image using a traditional approach where each part of the camera captures a different section of the image. These tools are long, flexible cords about 9 mm wide, about the width of a human fingernail. Because the cord is so wide patients must be sedated during the scan.
The scanning endoscope developed at the UW is fundamentally different. It consists of just a single optical fiber for illumination and six fibers for collecting light, all encased in a pill. Seibel acted as the human volunteer in the first test of the UW device. He reports that it felt like swallowing a regular pill, and the tether, which is 1.4 mm wide, did not bother him.
Once swallowed, an electric current flowing through the UW endoscope causes the fiber to bounce back and forth so that its lone electronic eye sees the whole scene, one pixel at a time. At the same time the fiber spins and its tip projects red, green and blue laser light. The image processing then combines all this information to create a two-dimensional color picture.
In the tested model the fiber swings 5,000 times per second, creating 15 color pictures per second. The resolution is better than 100 microns, or more than 500 lines per inch. Although conventional endoscopes produce images at higher resolution, the tethered-capsule endoscope is designed specifically for low-cost screening.
Read More...
Summary only...
For the first time, researchers have demonstrated a means of controlling cell functions with a physical, rather than chemical, signal. Immune cells coated with nanoparticles take up calcium in the presence of a magnetic field. Each nanoparticle measures approximately 30 nanometers in diameter.
In this image, yellow cells are taking up calcium in response to a localized magnetic field. Cells that are farther away from the field are shown in purple and do not take up calcium. Credit: Donald Ingber, Harvard Medical School
Using a magnetic field to pull together tiny beads targeted to particular cell receptors, Harvard researchers made cells take up calcium, and then stop, then take it up again.
This is another important step to cellular and molecular control to enable nanomedicine
Ingber's group demonstrated its method for biomagnetic control using a type of immune-system cell that mediates allergic reactions. Targeted nanoparticles with iron oxide cores were used to mimic antigens in vitro. Each is attached to a molecule that in turn can attach to a single receptor on an immune cell. When Ingber exposes cells bound with these particles to a weak magnetic field, the nanoparticles become magnetic and draw together, pulling the attached cell receptors into clusters. This causes the cells to take in calcium. (In the body, this would initiate a chain of events that leads the cells to release histamine.) When the magnetic field is turned off, the particles are no longer attracted to each other, the receptors move apart, and the influx of calcium stops.
"It's not the chemistry; it's the proximity" that activates such receptors, says Ingber.
The approach could have a far-reaching impact, as many important cell receptors are activated in a similar way and might be controlled using Ingber's method.
"In recent years, there has been a realization that physical events, not just chemical events, are important" to cell function, says Shu Chien, a bioengineer at the University of California, San Diego. Researchers have probed the effects of physical forces on cells by, for example, squishing them between plates or pulling probes across their surfaces. But none of these techniques work at as fine a level of control as Ingber's magnetic beads, which act on single biomolecules.
Many drugs, from anticancer antibodies to hormones, work by activating cell receptors. Once a hormone is in the blood, however, there's no turning it on or off. "This shows that you can turn on and off the signal, and that you can do it instantly," says Christopher Chen, a bioengineer at the University of Pennsylvania. "That's something that's hard to do, for example, with an antibody."
Ingber has many ideas for devices that might integrate his method of cellular control. Magnetic pacemakers could use cells instead of electrodes to send electrical pulses to the heart. Implantable drug factories might contain many groups of cells, each of which makes a different drug when activated by a magnetic signal. Biomagnetic control might lead to computers that can take advantage of cells' processing power. "Cells do complex things like image processing so much better than computers," says Ingber. Ingber, who began the project in response to a call by the Defense Advanced Research Projects Agency for new cell-machine interfaces, acknowledges that his work is in its early stages. In fifty years, however, he expects that there will be devices that "seamlessly interface between living cells and machines."
They have developed micromagnetic and nanomagnetic technologies to apply controlled mechanical stresses to specific cell surface receptors via surface-bound, ligand-coated, magnetic micro- and nano-beads.
Picture of a cell and expanded view of a cell receptor
FURTHER READING
Harvard Institute for Biologically Inspired Engineering.
Here the Ingber group discusses how new understanding of the fundamental role that mechanical forces play in tissue development might be leveraged to facilitate the development of new types of biomimetic materials for regenerative medicine, with a focus on the design of injectable materials that can target to injury sites, recruit stem cells and direct cellular self-assembly to regenerate functional tissues and organs in situ.
The group was funded by the NIH to try to grow heart valves, and parts of a pancreas and a tooth, from scratch in the lab. NIH funds Ingber Lab as part of a Harvard-Wide Consortium to Engineer Whole Organs.
Read More...
