A more sensitive test for cancer cells?

Public release date: 26-Oct-2004
Contact: Vanessa Wasta
wastava@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions

New tool reveals molecular signature of cancer and HIV

'LigAmp' highly sensitive

Scientists have designed a new molecular tool, dubbed "LigAmp," to pinpoint DNA mutations among thousands of cells, the equivalent of searching for a single typo in an entire library of books. Preliminary studies in a small number of cell lines and body fluids show the ultra-sensitive test may help detect microscopic cancer and HIV drug resistance.

"Other molecular tests make it very difficult to locate a mutation in a particular cell surrounded by thousands of other cells that don't have the mutation," says James Eshleman, M.D., Ph.D., who led the study with colleagues from the Johns Hopkins Department of Pathology and Kimmel Cancer Center. "LigAmp essentially filters background 'noise' caused by normal cells and reveals specific mutations."

The researchers say that sensitive tests to locate mutations could identify cancer in patients at high-risk for the disease. Such tests could even help detect a recurrence of cancer by monitoring whether the number of mutations rises above a predetermined threshold value.

In addition to cancer detection, the Hopkins mutation-finder appears able to detect drug-resistant HIV. The team tested it on blood samples from a handful of patients with HIV and located DNA mistakes in the virus itself that make it resistant to certain antiretroviral drugs. Results of analyses of the new test are published in the November issue of Nature Methods.

"We designed LigAmp to improve how we look for extremely subtle variations in viral and cellular DNA," says Eshleman, an associate professor of pathology and oncology and associate director for the DNA Diagnostics Laboratory at Johns Hopkins. "The molecular code of normal cells may look identical to cancerous except for a single rung in the DNA ladder-structure."

The test works by creating a molecular "magnet" with an affinity for the DNA mistake, also known as a point mutation. If the mutation is found, the magnet binds to it and inserts a bacterial gene. The bacterial gene serves as a red flag and produces a fluorescent color visible to powerful computer programs.

In their studies, the Hopkins investigators tested LigAmp on colon cancer cell lines, blood from HIV patients, and fluid from cancer patients' pancreatic ducts. Single mutations in colon cancer cells and drug-resistant HIV viruses were detected at dilutions of up to 1 in 10,000 molecules. Mutations of the KRAS2 gene were detected in duct fluid samples from three pancreatic cancer patients, which also corresponded to mutations found in their tumors. LigAmp also located a drug-resistance mutation, called K103N, in blood samples from three HIV patients.

Further analysis of LigAmp with larger sample sizes and blinded panels of clinical samples currently is under way.

"Some initial studies show that we can simultaneously look for different mutations and quantify the number of mutated molecules present. This may help us build panels of cancer markers for screening and determine low or high levels of mutation."

Funding for this research was provided by the Maryland Cigarette Restitution Fund, the National Cancer Institute, and the National Institute of Allergy and Infectious Diseases.

Johns Hopkins colleagues working with Eshleman are Chanjuan Shi, Susan Eshleman, Dana Jones, Noriyoshi Fukushima, Li Hua, Antony Parker, Charles Yeo, Ralph Hruban, and Michael Goggins.

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Shi, Chanjuan et al, "LigAmp for Sensitive Detection of Single-Nucleotide Differences." Nature Methods, vol 1, n 2, November 2004.

Media Contact: Vanessa Wasta 410-955-1287; wastava@jhmi.edu

On the Web: www.hopkinskimmelcancercenter.org

Red Wine May Protect Against Lung Cancer

"THURSDAY, Oct. 28 (HealthDayNews) -- Researchers say they may have found yet another health benefit conferred by red wine -- it seems to reduce the risk of lung cancer, at least in men." By Kathleen Doheny
HealthDay Reporter

If only this could have been found useful for Oesophageal Cancer!

Early Morning Ruminations

It is simply amazing to me how much clarity and insight comes with a semi awake state at some ungodly hour in the morning. I think that there is a connection between the states of being awake and not quite awake that enables the conscious and the unconscious brain portions to communicate better.

I was woken this morning by the stirrings of reflux. It was 3:30 am. Having learnt that it is simply not safe to ignore the warnings I immediately rose from my bed, as quietly as possible of course, and headed directly to the kitchen where several glasses of water were consumed. This was followed immediately by sucking on a Mylanta tablet and then a sit down in a comfortable arm chair to await developments. If the warning signs are recognised early enough then the remedial action settles the acid in the stomach (and of course now the new pseudo oesophagus) and all is well. If the recognition is just a tad late then the coughing begins. This is a way of trying to clear one's throat of the bitter and acrid stuff that seems to inhibit breathing, especially deep breathing. Once the residue of the reflux is somehow neutralised and/or coughed away from the breathing tube all is well again until the next attack.

I came slowly to the realisation that the timing of this event was of great importance. Whenever I seem to have food later than 8:00 pm, any possible reflux action seems to happen at around this time. So if one is to count down the hours it takes around 7 hours for the acid buildup in the system to, come to the fore, so to speak.

Naturally it is also accompanied by a supine position for at least 3-4 of those hours following the retirement to one's bed. I started to ask myself questions whether the content of the food intake had anything to do with the reaction. I suspect that it does. I have noticed for example that if the intake comprises of fruit and/or nuts or some other vegetable matter then there is no reflux that accompanies it, ever! If however the intake comprises some carbohydrate and/or fats or oils then the chances for an attack of reflux increases - with or without the intake being spicy.
I wonder if there are others out there who would like to share experiences?

Heartburn Drugs Linked to Pneumonia

Heartburn Drugs Linked to Pneumonia

49 minutes ago

26/10/2004

By LINDSEY TANNER, AP Medical Writer

CHICAGO - Widely used heartburn and ulcer drugs such as Nexium, Pepcid and Prilosec can make people more susceptible to pneumonia, probably because they reduce germ-killing stomach acid, Dutch researchers found in a study of more than 300,000 patients.

The highest risks occurred with more powerful acid-fighting drugs called proton pump inhibitors, which are sold in the United States under such brand names as Nexium, Prevacid and Prilosec. Over nearly three years, users of these drugs faced almost double the risk of developing pneumonia compared with former users.

Users of another class of acid-fighting drugs that includes cimetidine and famotidine — sold in the United States as Tagamet and Pepcid — also faced an elevated risk.

The study was led by researcher Robert J.F. Laheij at University Medical Center St. Radboud in Nijmegen, Netherlands, and appears in Wednesday's Journal of the American Medical Association (news - web sites).

The acid in normal stomach fluids generally kills harmful bacteria; suppressing it with drugs to treat heartburn and ulcers may make the body more hospitable to such germs, which may then infect the lungs and cause pneumonia, the researchers said.

These heavily promoted medicines are among the most widely prescribed drugs worldwide, with almost $13 billion in sales in 1998 alone, according to a JAMA editorial. Millions of Americans take these drugs, which are heavily advertised in "ask your doctor about ..." TV commercials.

Older patients and those with asthma and other chronic lung ailments are especially vulnerable to pneumonia. In light of the latest findings, the researchers said such patients should be use these medicines "only when necessary and with the lowest possible dose."

Among the 364,683 patients whose medical records were studied, 5,551 cases of pneumonia were diagnosed — 185 of them in people taking acid-suppressing drugs.

The researchers said their findings translate to about one case of pneumonia for 226 patients treated with the more potent acid-fighting drugs and one case per 508 patients treated with the other drugs.

Users of the more potent drugs were 89 percent more likely than former users to develop pneumonia. Patients using the less potent drugs were 63 percent more likely to develop pneumonia than former users of those drugs.

Nevertheless, the findings are reassuring because the apparent increase in the risk of pneumonia was small, said Dr. James Gregor of the University of Western Ontario.

Moreover, the study does not actually prove that the drugs cause pneumonia, said Gregor, who wrote the JAMA editorial and was not involved in the research. Regardless of which medication a patient is taking, heartburn, or acid reflux disease, can cause a person to accidentally inhale regurgitated stomach acid, increasing the risk of pneumonia, he said.

25/10/2004

Awoke at around 5:30 today. It is going to be a big day. My partner is returning to work after being absent since February 2004 while being my carer.

It is also a big day in that it will be the first time that I am being left alone to look after myself.

Reading the EC discussion group's stories can be a most depressing exercise. Only today there was a story of a man (probably about my age) who had been diagnosed with EC in December of last year, treated with surgery, chemo and radio therapy and declared NED (no evidence of disease) who in July had developed a recurrence of the disease, suffered with some really major problems with his kidneys and had a wife who was distraught with shock and anger at the return of the dreaded illness so soon after all that could be done had been done.

It is horrifying to think that the disease is so virulent that it will come back almost immediately and spread almost at the speed of light through other systems. The chances of survival for this man are likely to be slim. He is obviously well on his way into palliative care and pain management.

I guess in some ways when you are diagnosed with cancer you become resigned to the fact that you have been given a death sentence and that the likelihood of this sentence being commuted to a life sentence is only a remote hope. What I think you can never be reconciled to is the prospect of a lingering death, probably in pain while the anguish that you represent is etched onto the faces of the people that you love.

Shopping or Retail Therapy

Are there any other people out there in my situation?

I have managed to lose 30 kilos due to illness. This is NOT a recommended way of losing weight however this does not change the reality that with additional scars, loss of hair and a premature wrinkling of the skin, I now once again have the body I had in my youth, albeit a little less well toned and tanned.

When I look in my cupboard I realise that this dramatic change comes at a cost. There is not a single thing in there that I can wear. My pants look like they belong on Bozo the clown while my jackets could be made into a double breasted style or a form of jacket sarong because they are able to be wrapped around the new torso. What to do?

One obvious option is to have the clothes altered and so that at around half the price of buying new clothes you will seem to have new wardrobe.

Another option is to engage in what one of my colleagues called "retail therapy".

In the past I have been a very poor shopper. I went to the mall either because I really had a need to buy something or because my partner dragged me there to obtain my opinion on something she wanted to buy.

I suspect that there are many men out there who know and understand how wonderful it is to be asked to come and offer an opinion about a purchase that their spouse is about to make. If you agree with her choice, then you are not critical enough, if you disagree with the choice, then you are obviously a person of poor taste. In short, going shopping with my partner in the past has been like a trip to the dentist - something to be avoided at all costs.

Not any longer. Something in the chemo therapy has changed my brain patterns. I am now an avid voyeur. I actually enjoy going to the mall to watch the behaviour of the people there who are in thrall to retail therapy.

I recently had the experience of watching the reaction of people in a Big W to a notice that, for five minutes, everything in a particular aisle would be sold for just $5 rather than the price on the tickets. Since this was women's clothing, you simply cannot imagine what happened next unless you were there, on the spot, agog with amazement.

Somehow, women from all over the store converged on this location, as if they were sharks attracted by the scent of blood. A feeding frenzy ensued. Faces were red and perspiring, bodies
exhibiting extreme stress reactions.

Hunting fever, I would have called it, as these women fingered clothes looking for labels that would give them the size of the item. If it was the right size for the individual or for a family member it was taken off the rack immediately and clutched in the hand, tucked into the body, with a strength that usually is only found in people who are responding to a crisis. As the clock wound down and came ever closer to the end of the magic five minutes, the extent of the feverish hunt increased in tempo. Patience no longer existed, normal civility was cast to the four winds. Winning the prize was everything!

As the five minute period ended there were still people with multiple selections held to their bosoms who had not had the price ticket amended to reflect the $5 bargain by the store staff member. The pleading that ensued had to be seen to be believed.

When it was over everyone resumed their ordinary behaviour. Without a bargain there is no change in beahviour. With a bargain all bets are off!

I am now addicted to being an observer of retail therapy. You should try it, it's fun!

Information for People with Oesophageal Cancer

Some information for people in case they want to have it

The Ivor Lewis Method:

Please do not visit these sites if you are at all squeamish!

• http://www.vh.org/adult/provider/surgery/EsophagealCarcinoma/12E.html
• http://www.rcsed.ac.uk/journal/vol45_5/4550006.htm
• http://www.vesalius.com/graphics/archive/archtn.asp?VID=773&nrVID=772
• http://www.ncbi.nlm.nih.gov/entrez/query.fcgicmd=Retrieve&db=PubMed&list_uids=10075357&dopt=Abstract
  
• Definitely NOT for the squeamish
• P. S. you will need a medical dictionary for some of the words. After all my degrees I still have no idea what some of them mean.

One of the options for assisting people with this form of disease and its consequences is to have a place in which people can discuss their own situation, ask their questions and obtain information from others who are in the same boat.

There is such a site in the USA which is called the EC Café at http://www.eccafe.org/

Within the ACT there is also a wonderful site which presents a one stop shop for cancer sufferers and this at:
http://www.hotkey.net.au/~string/listing.htm

Try it you will find it useful.

There is NATIONAL AUSTRALIAN STUDY of Oesophageal Cancer underway
ASK YOUR DOCTOR about whether you can and/or should participate.
You can find out more at :
http://www.qimr.edu.au/research/labs/adeleg/

http://www.qimr.edu.au/research/labs/adeleg/barrets.html
and especially at:
http://www.acs.qimr.edu.au/menu/faq.html this URL providing information for participants!

http://www.acs.qimr.edu.au/menu/oes/index.html

In addition to the above, there is also information about clinical trials in the USA which can be located at:
http://www.nci.nih.gov/Search/SearchClinicalTrialsAdvanced.aspx

To use this site it is necessary to have an idea of how to use a search engine and to know the stage of the disease that you are looking for.