Medical Device Daily Contributing Writer and Staff Reports

The discovery of a key molecule in the DNA repair pathway could hasten the day in which cancer patients can undergo profiling to find out the best way to treat their particular tumor.

The molecule, called XLF, is the final missing piece in a jigsaw made up of proteins that take part in the repair of breaks in double-stranded DNA. Now that scientists have all the pieces, they feel confident that they will be able to work out how the pathway operates, and importantly for patients how to interfere with its components in order to improve cancer treatments.

Steve Jackson, head of the Cancer Research UK laboratories at the Gurdon Institute (Cambridge, UK), and professor of biology at the University of Cambridge, told Medical Device Daily s sister publication, BioWorld International: This area of research may in the longer term help us to come up with better treatments for cancer. We know that there are differences between cells from different cancers, and from different patients, in how they respond to radiotherapy and chemotherapy. Some of these differences may reflect underlying variations in the DNA repair capacity of different patients or different cancers. This may, one day, make it possible to tailor therapy to the individual.

Jackson and his colleagues want to study XLF and the other proteins involved in the repair of double-stranded breaks in DNA, in order to understand how they work, and how they are connected to the control of the cell cycle and apoptosis.

The DNA repair pathway that mends double-stranded breaks also contains several very exciting drug targets, Jackson said. KuDOS Pharmaceuticals (also Cambridge), which Jackson founded, has just been acquired by AstraZeneca (London).

Jackson said: KuDOS will be actively pursuing ways of making small-molecule drugs that target DNA repair pathways, with the aim of enhancing existing therapies. We also have evidence that some inhibitors of these molecules could work as stand-alone treatments.

A report of the discovery appears in the Jan. 26 edition of Cell. The first author is Peter Ahnesorg, Jackson s PhD student.

More than 10 years ago, Jackson and his collaborators identified the first component of the DNA repair pathway known as nonhomologous end-joining (NHEJ), which is of great interest to cancer scientists.

DNA damage is a regular occurrence in normal cells; if it is not detected, or not repaired properly, mutations can result, and those might allow cancer to develop. In addition, treatments such as radiotherapy, and many chemotherapies, work by inducing double-stranded breaks in DNA, which the cell must repair by NHEJ if it is to survive.

DuraSeal Sealant System gets CE mark

Confluent Surgical(Waltham, Massachusetts) said it has been granted the CE mark for use of its DuraSeal Sealant System as a surgical sealant during arterial and venous reconstructions to seal suture lines as an adjunct to standard closure techniques.

The company said that by providing a seal in vascular surgery, DuraSeal Sealant offers surgeons a valuable tool to reduce bleeding from the suture line in bypass procedures, as an example, and to prevent post-operative complications associated with suture line bleeding.

The DuraSeal technology is a synthetic, absorbable hydrogel delivered by a dual-syringe applicator. The device can be stored at room temperature and prepared in less than two minutes. Confluent said the DuraSeal Sealant polymerizes within seconds when sprayed on the suture line. After several weeks, the hydrogel breaks down into water-soluble molecules that are absorbed and cleared through the kidneys.

The company said a feature unique to the DuraSeal sealant is the blue colorant, [which] provides the vascular surgeon excellent visualization of coverage and thickness of the material upon application.

Consistent, immediate sealing of the suture line to prevent bleeding has to date been an elusive goal in various vascular bypass procedures, said Sean O Donnell, MD director of the section of vascular surgery at Washington Hospital Center (Washington). This sealant is easy to apply, adheres well to tissues and graft materials and is a very valuable adjunct to achieving hemostasis, especially in patients who are on antiplatelet agents in addition to their anticoagulation.

Confluent said about 880,000 peripheral vascular procedures are performed each year, some 400,000 of them in the U.S. The company said it plans to begin a vascular sealing study in the U.S. this year.

EC okays Ionsys transdermal system

Alza (Mountain View, California) said the European Commission has granted marketing authorization for the use of Ionsys (Fentanyl hydrochloride Iontophoretic Transdermal System 40 mcg/dose).

The company said Ionsys is the first needle-free, iontophoretic, patient-controlled transdermal system to receive marketing authorization in Europe, and is indicated for the management of acute moderate-to-severe post-operative pain, for use by adults, in a hospital setting only.

Ionsys is a compact, non-invasive, self-contained and pre-programmed analgesic system. Designed to adhere to a patient s upper arm or chest, the system uses a low-level electrical current to deliver the medication directly through the skin and into the bloodstream with the push of a button.

The product will be marketed in the European Union by Janssen-Cilag companies, which like Alza are affiliates of Johnson & Johnson (New Brunswick, New Jersey). Alza said it is working on the manufacturing processes and scale up, and launch is expected in 2007.

Ionsys is currently under review by the FDA in the U.S.

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