09 October 2013
Non-blood cancers, for example breast, prostate, lung, and colorectal cancers, shed cancer cells into the bloodstream, in a process known as intravasation. These cancer cells are known as circulating tumour cells (CTCs).
The CTCs are important as they circulate in the bloodstream and can then escape the blood vessels to permeate other tissues and organs in a process known as extravasation to cause secondary cancers.
Little has been known about extravasation until now. Massachusetts Institute of Technology (MIT) has recently published the results of an in-vitro study of extravasation.
So far they have found two key observations.
1) As tumor cells make their way through the circulatory system, some “arrest,” or pause at a particular location, adhering to a blood vessel’s wall - the first stage of extravasation. Scientists have thought that this cell arrest occurs in one of two ways: a cell may send out sticky projections that grab onto the vessel lining, or it may be too big to pass through, literally becoming trapped within the vessel. The MIT study shows that the second one “entrapment” is the primary means by which the cells arrest.
This is an interesting finding as it suggests that the process that ANGLE’s Parsortix system uses to capture CTCs, a combination of size and compressibility, may be similar to the process that the CTCs use in extravasation prior to potentially causing secondary cancer.
The study found that the larger sized CTCs which arrested by entrapment exhibited a significantly higher level of transendothelial migration (47.8% ± 4.7%) compared to arrested, non-trapped CTCs (9.8% ± 3.3%). Thus the CTCs that are more likely to be trapped are those more likely to extravasate and cause secondary cancer. The characteristics of the CTCs leading to them getting trapped in narrow constrictions in the endothelium may mimic their capture potential in ANGLE’s Parsortix system.
2) The Study shows that clumps of CTCs are more successful at extravasation that individual CTCs. From their observations, the researchers found that almost 67.8% ± 7.2% of adhered cell clusters (defined as two or more contacting CTCs) broke through a blood barrier, compared with less than 8.3% ± 2.6% of single cells. Thus clumps of CTCs may be 7x more likely to cause a secondary cancer than individual CTCs.
This observation is very interesting in light of the Parsortix system’s efficiency in capturing clumps of CTCs. The effectiveness of antibody capture approaches using magnetic beads can be limited for clumps of cells because the clumps of cells may be too large to pull over with the magnetic field.
22 May 2012
NICE (the National Institute for Health and Clinical Excellence) have today published a draft guideline entitled “Fertility: assessment and treatment for people with fertility problems”.
This important document sets out a range of important developments in IVF treatment.
It is estimated that infertility affects one in six heterosexual couples in the UK. Since the original NICE guideline on fertility published in 2004, there has been a small increase in the prevalence of fertility problems, and a greater proportion of people now seeking help for such problems.
The main causes of infertility in the UK are (percent figures indicate approximate prevalence):
The aim of IVF is for a woman to have a healthy baby delivered safely at term, without increasing the woman’s risks. The main risk to the health of a mother and her baby(ies) as a result of IVF is a multiple birth. Thus, a decision must be made between transferring more embryos to increase the chance of having at least one live born baby and transferring a single embryo to reduce the chance of having a multiple birth.
This decision is based on a number of factors, such as the number of embryos that are available, the age of the woman, the quality of the embryos, and the type of subfertility involved. However, it is also influenced by the present state of IVF technology and expertise. HFEA data shows that overall live full-term singleton birth rates with IVF have improved from 17% per cycle in 1992 to 29% in 2006.
The same HFEA data shows that currently about 1 in 4 IVF pregnancies resulting in live birth babies were multiple pregnancies. In other words 2 out of 5 (or 16 out of 40) live born babies from IVF were from multiple pregnancies. These figures contrast in spontaneously conceived pregnancies with an incidence of 1 in 80 pregnancies being multiple pregnancies and 1 out of 40 live born babies coming from multiple pregnancies. The incidence of multiple births with IVF predominantly varies with whether one or two embryos are replaced. As a result, elective single embryo transfer (eSET) is increasingly promoted as an alternative to double embryo transfer (DET), which is currently the most commonly used strategy in the UK, in order to reduce the rate of multiple births.
This 'single embryo strategy' comprises the transfer of a single fresh embryo and the freezing of any 'spare' embryos for subsequent thaw and transfer if the fresh transfer was unsuccessful. In addition, currently there is a trend to extend the culture of embryos to day 5 or 6 (blastocyst) rather than the conventional day 2 or 3 (cleavage) which is thought to improve the chances of a live full-term singleton birth.
The new guidance on embryo transfer strategies in IVF is as follows:
The guidance makes single embryo transfer the norm for IVF. This will further increase the market demand for EmbryoSure ANGLE’s Novocellus embryo viability product since if only one embryo is transferred there is an increased need to make sure it is a healthy embryo.
Furthermore the guidance specifically refers to the need to assess the number of top-quality embryos available. EmbryoSur? provides the first scientifically based method for assessing the viability of the embryo to identify top-quality embryos.
ANGLE has partnered with ORIGIO a/s the largest supplier of IVF culture medium worldwide to bring EmbryoSure? to market. Clinical trials are progressing according to plan with a target completion in mid-year 2013. Product launch in the UK market is anticipated in mid-year 2014.
12 April 2012
Over 1 in 3 people will get cancer during their lives. This is an alarming statistic and we need to do everything we can to improve treatment and increase survival rates.
Early detection of cancer is crucial to the effective treatment of cancer. With many cancers, such as colo-rectal cancer, by the time the patient has symptoms, the cancer is well established and is difficult to treat.
According to a study published in The Lancet in 2010 led by the Royal Marsden hospital, a world-leading cancer research centre, more than 1 million individuals every year develop colo-rectal cancer (cancer that starts in either the colon or rectum), and the mortality rate is nearly 33% in the developed world. Colo-rectal cancer is unpredictable and arises without warning. Survival is directly related to how early the cancer is detected and is poor for symptomatic cancers (where the patient has experienced symptoms), as these are typically quite advanced.
Consequently, early identification of colo-rectal cancer is key to achieving an improved outcome. The Study states that population screening offers the best prospects for reduction in mortality rates. The primary screening mechanisms currently available are limited to the faecal occult blood test (examination of faeces to detect small amounts of blood) and colonoscopy and sigmoidoscopy screening (the endoscopic examination of the colon and rectum with a camera on a flexible tube).
The faecal occult blood test is a relatively insensitive screening method, whereas colonoscopy is associated with a higher risk of serious complications and about 48 hours are needed for bowel preparation and recovery from sedation. Population screening with colonoscopy also presents human resource and cost issues. Neither of these methods of screening is easily applied for mass-screening of healthy people.
Effective screening is essential to reduce the incidence and mortality rates of colo-rectal cancer. Screening techniques currently available are unpleasant, invasive and not always conclusive.
If ANGLE’s Parsortix separation device can be used to capture colo-rectal cancer cells in patient blood, it may be possible to develop a simple blood test to detect this cancer whilst it remains asymptomatic (i.e. before the patient is aware of any symptoms). This would enable a better medical outcome, be less intrusive for the patient and be more efficient and less expensive than current screening techniques.
Traditional scientific opinion has been that cancers do not disseminate cells (circulating tumour cells known as CTCs) until the cancer is a late stage metastatic cancer. This view would suggest that CTCs will only be in the bloodstream with later stage cancers and therefore there are unlikely to be any CTCs in an (apparently) healthy person’s blood, which could be captured by the Parsortix device as an early stage cancer detection process.
However, there is now an emerging medical opinion that cancers shed CTCs into the bloodstream from their earliest stages of development – it is just that the numbers of these CTCs is so small that existing technologies cannot detect them in the blood.
In order to investigate this phenomenon further, ANGLE is developing its Parsortix CTC capture device to be extremely sensitive with the ability to capture very low numbers of CTCs in the blood if they are present and with the ability to flow significantly larger volumes of blood than possible with current technologies.
In time, we hope this may enable doctors to be able to offer a non-invasive, simple blood test to (apparently) healthy people to check for early signs of cancer ahead of any symptoms.
3 Frederick Sanger Road
The Surrey Research Park
Guildford, Surrey GU2 7YD
T+44 (0)1483 685830
F+44 (0)1483 685836