Archives: 11/2006

Researchers at Oxford Biomedica have created a promising vaccine, called TroVax, for the treatment of existing kidney cancer. They have presented their findings at the 18th EORTC-NCI-AACR Symposium on “Molecular Targets and Cancer Therapeutics.”

The TroVax vaccine is still going through the clinical trials process. It works by harnessing the body’s immune system to tackle a tumour. A protein called 5T4 is present on the surface of around 90% of kidney tumours, but not on healthy cells. The patient is given a series of injections containing a harmless virus and a gene for the 5T4 protein. This gene triggers an immune reaction which leads the body to attack the cancer cells.
The treatment involves seven injections over 41 weeks, given alongside standard cancer therapy.
The patient who saw his tumour completely disappear was given the vaccine plus a drug called IL-2, already given as standard treatment for kidney cancer.
Of the 15 patients whose disease stabilised, one has been stable for 46 weeks.
A further 700 patients will now receive the treatment as the vaccine undergoes further study.
The Phase III trial will compare TroVax plus standard kidney cancer treatment and a dummy version plus standard treatment.
Researchers will look at whether or not tumour shrink, if the progression of the disease can be halted and patients’ quality of life.
Professor Robert Hawkins, of Christie Hospital in Manchester who will be leading the study, said the data so far on the vaccine was “very encouraging”.
“It would be rare that a patient would get rid of a tumour with standard treatment.
“The fact that it has happened in a relatively small trial is encouraging.”

Read the full BBC article . . .
Check out Biomedica’s Press Release . . .
Abstract available here . . .

fda Recalls Spark Stricter FDA Device Safety ProceduresThe LA Times reported that the Food and Drug Administration is to revise, patch up and enhance its procedures on handling safety issues with pacemakers, stents, defibrillators and other medical devices it regulates:

How the FDA handles safety issues with the products it regulates already is under scrutiny and is expected to receive even more attention from Democrats now that they will be the majority party in Congress.
With medical devices in particular, concern grew after last year’s slew of high-profile recalls or safety warnings affecting more than 200,000 defibrillators.
It also calls for streamlining the now-disjointed way the agency collects reports of possible problems from multiple sources, including manufacturers and doctors.
Proposals include expansion of a pilot program that collects safety reports in real time from hospitals, as well as tapping into medical device data amassed by the Veterans Affairs Department, the Defense Department and the Centers for Medicare and Medicaid Services.
The FDA also wants all medical devices marked with a unique number, which would allow them to be better tracked in a recall.

Better device tracking and data collection, if used properly (that’s a big if), could provide vast improvements in device quality and tracking. Of course, all this tracking and data collection can’t be paid for in Medgadget Bucks, so in the end the taxpayer or consumer will end up footing the bill. However, as more medical treatments are delivered via engineered devices, the public seems willing to pay for increased peace of mind.
More from the LA Times

235442breath Lung Carcinogenesis Tracked By DNA Methylation In BreathDr. Simon Spivack and Dr. Weiguo Han from the New York State Department of Health are planning to present research showing the feasibility of testing DNA within condensed breath.
From the statement by the American Association for Cancer Research:

For the first time, researchers have demonstrated that it is possible to detect DNA methylation in the breath of smokers and lung cancer patients, suggesting that, in theory, it may be possible to use this technique to identify people who have undiagnosed lung cancer or are at high risk of developing the disease.
Investigators at the Wadsworth Center, the public health laboratory of the New York State Department of Health, have been able to develop an assay that simultaneously detects the presence of methylation in six tumor suppressor genes – a process by which a gene is chemically silenced. The assay examines the promoter region of a gene, where certain cytosine nucleotide bases may be methylated, preventing the gene from being expressed.
The seven participants tested so far breathe for ten minutes into a commercially available handheld device, which cools the air, forming a condensed vapor, to which the methylation assay is applied. Investigators found it could detect the presence of the methylated form in all six tumor suppressor genes. For RASSF1A, the test was negative in non-smokers, and positive in both current and ex-smokers. For DAPK, methylation was more variable, given smoking status. The four other tested genes (p16, MGMT, PAX5B,CDH1) known to be methylated in various stages of lung cancer development, were minimally or not methylated, in this pilot study of predominantly cancer-free smokers.
“Dr. Weiguo Han and I have shown that this approach is technically feasible, and if further research demonstrates the assay can measure DNA in such a way that it diagnoses or predicts lung cancer, this could be important for non-invasive lung cancer testing,” said the study’s lead author, Simon D. Spivack, M.D., M.P.H., a research physician at the Wadsworth Center, and a specialist in lung diseases. “But we are a long way from that point.” Han, a post-doctoral fellow in Spivacks’ laboratory and the study’s first author, will be presenting the findings.
Spivack said his study was only the third to date that proved DNA could be tested in condensed breath – German researchers reported the first such result in 2003, followed by an Italian group in 2005 – and the first to find methylation-silenced tumor suppressor genes in the breath of patients at risk or harboring lung cancer.

More . . .

654263ve Vivid e
GE Healthcare has released Vivid e, a laptop-size ultrasound system designed for in-office diagnostics. A part of the popular Vivid line of compact ultrasounds from GE, Vivid e has an impressive array of features:

The Vivid e, the newest member of GE’s Compact Series of ultrasound systems, is designed to provide a dedicated cardiovascular ultrasound solution for the Physician Office in a practical, easy to use design. The Vivid e is being showcased at the annual meeting of the American Heart Association (AHA) in Chicago…
And as a truly portable cardiovascular ultrasound system, you can effortlessly take the small, 4.6 kg (10.1 lb) Vivid e system into more places. Putting GE’s technological leadership into more hands.

  • Comprehensive, diagnostic exams with the confidence building image quality expected from the GE Ultrasound Vivid product line
  • Easy-to-use, automatic image optimization – in 2D, color and Doppler imaging – instantly updates thousands of parameters with one keystroke for optimal scanning
  • Anatomical M-Mode assists with off-axis orientation to make scanning easier
  • More from the product page
    Press release

    Here’s another excellent example of the promise of nanotechnology. Doxorubicin, bound to a specially designed polymer, has displayed a good therapeutic effect and less toxicity than free doxorubicin in mice models.
    From UC Berkley press office:

    … a powerful cancer drug, doxorubicin, enveloped in a large polymer produced a 100 percent cure in mice with induced colon cancer, while all mice treated with the drug doxorubicin only died. The doxorubicin-polymer combination proved as effective as a liposomal therapy – doxorubicin encapsulated in fat bubbles called liposomes – now used to treat several types of cancer in humans.
    “There’s nothing better than comparing a drug against what works in people, and in our tests in mice, the new technique cured 100 percent of the mice, performing at least as well as the liposomal drug,” said Jean Fréchet, professor of chemistry and chemical engineering at UC Berkeley and a researcher at Lawrence Berkeley National Laboratory…
    Fréchet, however, saw an advantage with branching polymers instead of linear polymers. Called dendrimers because of their tree-like structure, they don’t pass through filtration pores in the kidney for the same reason that it’s hard to force a tree branch though a hole. Tests show a half life in the body – the time it takes for half the drug to be eliminated or degraded – of up to 30 hours, versus a few minutes for pure doxorubicin. A linear polymer with the same half life would be impractical, Fréchet said.
    In addition, Fréchet based the dendrimer polymers on a chemical structure, a polyester, that is degraded naturally inside the body, which prevents its accumulation.
    “Our contribution to this field was to recognize that polymer architecture makes a difference, and Jean’s contribution was to recognize that polyester is a great backbone for doing this,” Szoka said. [Dr. Frank Szoka is a professor of pharmaceutical chemistry at UCSF --ed.]
    Fréchet and his UC Berkeley graduate students synthesized a branching polyester polymer they refer to as a “bowtie” dendrimer because it has two halves that branch out from a center where they’re tied together. The team chemically attached up to 32 doxorubicin molecules to one side of the bowtie, and a smaller number of linear chains to the other half, which wrapped around the package like a hairball protecting the drug.
    The mice were injected with colon cancer cells, and several days later with doxorubicin, doxorubicin-dendrimer or Doxil. Though the latter two cured the mice, the group did not address long term toxicity, which would require tests in larger animals. Doxorubicin is known to be toxic to the heart after repeated use, though liposome encapsulation seems to prevent this.
    “Much less drug goes to the heart with the dendrimer and the liposome, so I would predict there would be much less cardial toxicity with the dendrimer also,” Szoka said.
    One advantage of the dendrimer over liposomes is that the therapy can be delivered via one injection, while liposome treatment is by intravenous infusion. Both deliver a higher dose of drug – three to four times as much – than can be achieved with doxorubicin alone, since the drug is so toxic. Thus, attachment to the dendrimer considerably reduces its side-effects.
    One big disadvantage of the dendrimer is that it requires laborious synthesis, but Fréchet already is at work on a new chemical process that could solve that problem, making synthesis relatively inexpensive.

    More
    NCI’s Alliance for Nanotechnology in Cancer: Single-Dose Drug-Loaded Dendrimer Cures Mice of Colon Cancer
    Flashback: Temperature-Sensitive Doxorubicin Nanoparticles

    76567utah Medical Micropump for Lab on a ChipUniversity of Utah investigators, under Dr. Bruce Gale, an assistant professor of mechanical engineering, invented a novel method to move chemicals, blood or other bio samples through diagnostic chips.
    Here’s how the university explains its technology:

    While a lab-on-a-chip would have hundreds to thousands of micropumps–sets of tiny fluid and air channels and larger chambers in which samples were tested–Eddings and Gale demonstrated their invention by building an array of 10 of the tiny pumps.
    They molded tube-like “microchannels” — each the width of a human hair — into the top and bottom layers of a three-layered piece of silicone polymer material about the size of a deck of playing cards. The polymer is named polydimethylsiloxane, or PDMS.
    “It’s made out of bathroom caulk,” Gale quips. “It is very similar to the clear silicones you’d use to seal your bathtub.”
    The card deck-sized array has three layers of rubbery PDMS:

  • A top fluid channel layer, with wells into which blood or other samples are placed, and microchannels through which they can flow toward small chambers.
  • A crucial middle layer, a thin, permeable membrane of PDMS. Gas can pass through the caulk-like PDMS, while liquid cannot.
  • A bottom control channel layer, with inlets and tiny channels through which air pressure or a vacuum is applied.
  • The air pressure or vacuum, respectively, push or pull air through channels in the bottom layer, transmitting pressure or suction through the middle-layer membrane to push or draw fluids through channels in the upper layer.
    While an outside air pump or vacuum is needed to run the device, Gale says the membrane is, in effect, the pump because a pump creates a pressure difference, which is what the membrane does to move fluids.
    Because gas, not fluid, flows through the middle layer, liquid in the upper-layer microchannels can flow into and fill dead-end channels or chambers without trapping air. That allows the pump to carry samples like blood or fluids with protein or DNA through the microchannels to dead-end chambers that contain chemicals needed for a test.
    The outside device to run the lab-on-a-chip — including air pressure or a vacuum to run the micropumps — “would be as big your wallet, and the chip would be like a credit card that goes in your wallet,” Gale says.
    Each micropump can produce a flow of up to 200 nanoliters of fluid per minute. A nanoliter is one-billionth of a liter, and a liter is less than 1.1 quarts.
    “If you had a drop on the end of a pin, that would be five times as much fluid as this pump would move in a minute,” Gale says. “In some respects, we are bragging that’s a large flow” for such a tiny pump. Yet the flow could be slowed considerably if the pump was used to deliver drugs, he adds.

    Link
    Flashback: Micropump Speeds Fluid Through “Lab On a Chip”

    9876578us2 Philips X7 2 TransducerAt the ongoing 2006 American Heart Association Scientific Sessions meeting, Philips has introduced its latest echo transducer, a “4D” instrument for cardiac evals of infants and children:

    Introduced for the first time, the Philips X7-2 x-MATRIX array transducer is part of a robust pediatric and congenital heart disease solution that affords small patients the same imaging, quantification and cardiac management benefits that adults attain from Live real-time 3D echocardiography (echo), an ultrasound of the heart. The speed at which volumetric data are captured and the non-invasive nature of ultrasound enables clinicians to obtain high-quality images and data quickly and easily, while potentially reducing young patients’ emotional and physical stress, and providing surgeons with pre-operative views of cardiac anatomy and function.
    Additionally, the Philips X7-2 transducer, in conjunction with QLAB quantification software, allows cardiologists to evaluate a pediatric patient’s heart and closely examine structures, blood flow and function for enhanced diagnosis and treatment planning.

    Company’s xMATRIX technology is very cool:
    9876578us Philips X7 2 Transducer

    Using breakthrough array technology with elements smaller than a human hair, xMATRIX transducer technology provides volume acquisitions of the beating heart with truly remarkable image quality. Our xMATRIX transducers are ergonomically designed and harness the power of 150 computer boards. Now, the new X7-2 xMATRIX transducer joins the X3-1 transducer on the iE33 system. The X7-2 was specifically designed for pediatric applications and provides another significant milestone in Live 3D Echo by combining PureWave crystal technology with 3D xMATRIX transducer design technology.
    XMATRIX technology also enables Live xPlane imaging — the ability to acquire two planes simultaneously from the same heartbeat. The system’s multi-directional beam steering lets you select unlimited planes in all directions, so you can get the precise view you want, with no degradation in image quality.

    The other cool thing about the technology is how the piezoelectric material for such transducers is made. Read about it here: PureWave Transducer Technology.
    More from: press release; product page; xMATRIX array technology page

    This newly released blog is the latest addition to the journal’s website. Check it out. Link
    (hat tip: Kevin, M.D.)

    German scientists from the University of Luebeck believe they have uncovered a way to boost memory up to 8%. Details over at the Newscientist.com