Archive for November, 2011

Protein May Make UV Exposure Safer In Morning


From Scientific American

http://www.scientificamerican.com/

Levels of a DNA repair protein naturally rise in the morning and fall later in the day, which may make exposure to UV safest early.

The early bird gets the worm—and may avoid skin cancer. Because a new mouse study suggests that, for humans, tanning in the mornings may be less likely to permanently damage DNA and cause skin cancer.

A mouse’s levels of the DNA-repairing protein XPA are different from ours—they peak in the morning and bottom out in the evening. Researchers exposed mice to UV radiation when their XPA was at its minimum level, around 4 a.m., and others to the same rays around 4 p.m., when XPA levels peaked.

Mice who tanned while low on the repair protein developed skin cancer faster and five times more frequently than their evening-tanning counterparts. The study is in the Proceedings of the National Academy of Sciences. [Shobhan Gaddameedhi et al, Control of skin cancer by the circadian rhythm]

Unlike mice, humans are not nocturnal, so their XPA levels rise and fall at different times. In people, XPA is at prime DNA-repairing levels in the morning, which thus looks the safest time for UV exposure. So if you want to avoid skin cancer, probably go to the tanning salon early—or better yet, don’t go at all.

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New Diagnostic Test May Help Answer the Question “Is My Mole a Melanoma?”

I had never heard of this marker before but it looks interesting.

Ian Katz

http://www.southernsun.com.au

Researchers From Weill Cornell Medical College Report That the New Technique Is Greater Than 90 Percent Sensitive in Identifying Melanoma, the Deadliest Form of Skin Cancer (HealthNewsDigest.com) –

NEW YORK (Nov. 21, 2011) — Determining whether a mole is a potentially life-threatening melanoma is tricky business, leading to both under- and overdiagnosis. Now, researchers at Weill Cornell Medical College have designed, developed and studied a new diagnostic staining test they say can provide a novel measure of whether a mole is clearly cancerous or benign with the potential for expanded use across all cancers.

In the Nov. 21 issue of the Archives of Dermatology, the researchers say the new test, which relies on the soluble adenylyl cyclase (sAC) expression pattern, provides objective results — if sAC is present in the nucleus of cells from a skin biopsy then, melanoma is present. If the nucleus is not positive, the sample is benign. Most diagnostic stains in use today highlight a specific cell in the biopsy; where the stain is more intense, it is more likely it is to be melanoma. However, how “intense” something stains is a subjective measurement.

“The sAC stain is either positive or negative in the cell’s nucleus. Other stains require an interpretation of staining intensity, which means that a diagnosis of melanoma can rest on a pathologist’s opinion,” says senior author Dr. Jonathan Zippin, an assistant professor of dermatology at Weill Cornell Medical College. “As a clinical dermatologist, this uncertainty is difficult to deal with,” continues Dr. Zippin, who sees patients at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. “No one wants to miss a true diagnosis of melanoma, but telling someone they have melanoma, when they may not, changes his or her life.”

Diagnosing melanoma in a patient means that the skin lesion, and an area of healthy tissue around it, must be removed — surgery that can be disfiguring. Additionally, patients diagnosed with melanoma now have the added worry that they may develop another cancer, Dr. Zippin says, since patients diagnosed with a melanoma are at a higher risk for developing another cancer.

The study’s lead author, Dr. Cynthia Magro, professor of pathology and laboratory medicine at Weill Cornell Medical College and a pathologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, suggests that the sAC stain should be used in conjunction with other diagnostic tests, such as light microscopy and the other three stains now available. “What I hope is that five years down the line, this and other stains will help pathologists remove any uncertainty as to whether a biopsy is worrisome,” says Dr. Zippin. Dr. Magro says, however, that sAC provides one benefit that no other stain does.

“The greatest practical application of sAC is using it to determine the cancer-free margins of a lentigo maligna that needs to be removed,” she says. “This is a common melanoma in situ, usually found on the face, that does not show invasive growth. But until the development of sAC, it was very difficult to tell where the cancerous lesion ended.” The sAC stain, which she uses on many patients, “is vastly superior to any other test we have now to determine margins.

” The new stain is a monoclonal antibody that binds to sAC, which is a signaling molecule, says Dr. Zippin, who has long researched the molecule. “sAC senses changes in the interior of cells, such as pH and metabolism, and responds by regulating gene expression, metabolism and growth,” he says.

Dr. Lonny Levin and Dr. Jochen Buck, both professors of pharmacology at Weill Cornell Medical College, discovered the sAC protein and developed the antibody that Dr. Zippin and Dr. Margo used to develop the diagnostic test. Based on the promise of this research, the four doctors created a company called Cutting Edge Pattern Biotech to share the antibody with the scientific community. Currently, they are scientific advisers to the company and have no fiscal role. “Because the sAC protein is expressed in all tissues of the body, and appears to be linked to processes important for the development of cancer, we predict this immunostain will be useful for the diagnosis of many other cancers and diseases,” Dr. Zippin says.

While a diagnostic stain does not need FDA approval, the researchers say Cutting Edge Pattern Biotech is planning on seeking federal approval of the sAC antibody as a diagnostic test.

Co-authors of the study include Dr. A. Neil Crowson of the University of Oklahoma and St. John Medical Center and Regional Medical Laboratory — both in Tulsa, Okla.; and Dr. Garrett Desman of the Laboratory of Dermatopathology in Port Washington, N.Y.

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Radon and Skin Cancer

Hi All

I found this quite interesting.

regards

Ian

http://www.southernsun.com.au

Researchers from the European Centre for Environment & Human Health (part of the Peninsula College of Medicine & Dentistry) have detected a connection following analysis of data on radon exposure and skin cancer cases from across southwest England. The study, which looked at small geographical areas across Devon and Cornwall, builds upon a similar study conducted 15 years ago.

Radon is a naturally occurring, radioactive gas found in soil and bedrock common in parts of the southwest. It has been recognised as a minor contributor to cases of lung cancer, but so far there has been no firm evidence to suggest it has wider health implications. Whilst both radon levels and skin cancer incidence in the southwest are amongst the highest in the UK, the study found no association between household radon levels and malignant melanoma, or the most common form of skin cancer basal cell carcinoma. However, a link was found between areas where high radon concentrations are found and a particular type of non-melanoma skin cancer called squamous cell carcinoma.

The analysis took account of the way population characteristics, exposure to sunshine and proximity to the coast vary across the region. However, the researchers highlighted people’s exposure to ultraviolet (UV) radiation from the sun as a particularly difficult factor to account for, especially as this represents an important risk factor for developing skin cancer.

Despite the limitations of the study, researchers feel it is an important area needing further investigation. Lead author of the study, Dr Ben Wheeler said “We know that naturally occurring radon is a contributing factor to a small proportion of lung cancers, but there is limited evidence of other health implications. These findings suggest that the issue of radon and skin cancer deserves a much closer look and we’re planning to develop a more detailed study capable of detecting a direct relationship, if one actually exists”.

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Gene associated with doubled risk of melanoma

Hi All

This was in “The Australian”  this morning.  It reinforces how the development of melanoma is a complex relationship between UV exposure and a person’s genetic background. Your patients may ask you about this today.

regards

Ian Katz

http://www.southernsun.com.au

 

Gene sees risk of melanoma double

  • BY:ADAM CRESWELL, HEALTH EDITOR , November 14, 2011 12:00AM

AUSTRALIAN researchers have identified a gene mutation carried by an estimated 200,000 Australians that more than doubles the person’s risk of developing the potentially fatal skin cancer melanoma.

The mutation, which occurs in a gene previously suspected but not proven to play a role in melanoma growth, increases a person’s lifetime risk of developing the disease from 4 per cent to about 10 per cent.

Experts hope the findings about the MITF gene, published today in the prestigious international journal Nature, will lead to other genes being identified that act together and account for one-third or more of melanoma cases.

The ultimate goal – which remains several years away – will be the development of a test that can identify which Australians are at highest melanoma risk so they can be more vigilant, and possibly treatments that can prevent the disease, or slow or halt it once it has developed.

Australia has the highest incidence rates in the world for melanoma, along with New Zealand. Melanoma accounts for more than 10,000 new cases and 1200 deaths each year, making it the fourth most common cancer in Australia, and the most common in those aged 15-44, along with breast cancer.

The new study, co-authored by 47 researchers from Australia, the US and Britain, found the MITF mutation was present in about 1 per cent of the population. It was typically found in people with eye colour other than blue, and was not associated with skin colour, hair colour or freckling – all factors that are already known to raise melanoma risk.

The extra melanoma risk the mutation confers is thought to be comparable to that faced by redheads, who generally have white-ish skin that burns easily.

One of the 31 Australian co-authors of the paper, Graham Mann, research program leader at the Westmead Millennium Institute and Melanoma Institute of Australia at the University of Sydney, said while the 10 per cent risk was a “moderate” increase, more work was expected to reveal other gene combinations that would put affected people at 30 to 40 per cent risk of the disease.

“The idea with all of this work is to understand, first, the genetic changes, and to identify the people with the highest risk of melanoma,” Professor Mann said.

Once identified, such people could then watch their skin more closely, to catch melanoma when it first appeared, he said.

The researchers made the findings by sequencing the entire genome of someone from a family that had recorded eight melanoma cases and which had tested negative for the only other two genes previously linked to melanoma, CDKN2A and CDK4.

When this process pointed the finger of suspicion at MITF, the researchers then sequenced the remaining seven people from the same family still available for study, and found the MITF mutation in three out of seven that had developed melanoma.

Cancer Council Australia’s Terry Slevin said the findings were “a worthwhile and a potentially useful discovery”, with the next step being to develop a reliable test that identifies who has the higher risk in the families where melanoma is common.

 

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Protein May Make UV Exposure Safer In Morning – from Scientific American

I found this facsinating.

regards

Ian

 

Levels of a DNA repair protein naturally rise in the morning and fall later in the day, which may make exposure to UV safest early.

The early bird gets the worm—and may avoid skin cancer. Because a new mouse study suggests that, for humans, tanning in the mornings may be less likely to permanently damage DNA and cause skin cancer.

A mouse’s levels of the DNA-repairing protein XPA are different from ours—they peak in the morning and bottom out in the evening. Researchers exposed mice to UV radiation when their XPA was at its minimum level, around 4 a.m., and others to the same rays around 4 p.m., when XPA levels peaked.

Mice who tanned while low on the repair protein developed skin cancer faster and five times more frequently than their evening-tanning counterparts. The study is in the Proceedings of the National Academy of Sciences. [Shobhan Gaddameedhi et al, Control of skin cancer by the circadian rhythm]

Unlike mice, humans are not nocturnal, so their XPA levels rise and fall at different times. In people, XPA is at prime DNA-repairing levels in the morning, which thus looks the safest time for UV exposure. So if you want to avoid skin cancer, probably go to the tanning salon early—or better yet, don’t go at all

Leave a comment

Anti-sleeping sickness (trypanosomiasis) drug prevents BCC

Hi All

I found this interesting

regards

Ian

 

An antiparasitic agent used to treat African sleeping sickness was shown to reduce incidence of skin cancer in follow-up results from a phase 3, randomized, double blind, prospective study.

In the original study, 291 men and women with a history of basal cell carcinoma or squamous cell carcinoma were assigned to 500 mg/m2 daily alpha-difluoromethylornithine (DFMO) or a placebo for 4 to 5 years. Researchers observed a significantly reduced incidence of skin cancers associated with DFMO.

In this follow-up study, Howard H. Bailey, MD, professor of medicine with the University of Wisconsin School of Medicine and Public Health, said researchers found that participants assigned to DFMO developed 163 basal cell carcinomas compared with 243 for those assigned to placebo. The annual event rate was 0.28 basal cell carcinomas per person for DFMO vs. 0.4 for placebo (P=.03).

“We found there is still evidence that the men and women assigned to DFMO for 5 years continued to have a lower incidence of nonmelanoma skin cancers compared with people assigned to placebo,” Bailey said in a press release. “What we saw was that the presumed benefit that people got in taking DFMO appeared to persist for years after stopping it.”

The results were presented at the 2011 AACR International Conference on Frontiers in Cancer Prevention Research.

DFMO did not appear to have a similar protective effect against squamous cell carcinoma. Researchers observed 95 squamous cell carcinomas in the DFMO group compared with 115 in the placebo group. Annual event rate for DFMO was 0.15 squamous cell carcinomas per person compared with 0.19 for placebo (P=.56).

DFMO was associated with few adverse events. Some patients developed ototoxicity, but that did not lead to a “noticeable reduction in hearing,” Bailey said.

“Our data suggest that the protective event that we saw in our prospective study appears to continue, and there was no evidence of any rebound effect,” he said. “We did not find any evidence that the people who received DFMO were harmed other than the original ototoxicity

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