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Friday, 21 December 2012
Cancer diagnosis later in life poses significant risk to offspring, study suggests
Dec. 20, 2012 — Relatives of family members diagnosed with cancer are still at risk of the disease even if the diagnosis came at an older age, suggests a paper published on bmj.com today.
It is known that early onset cancer cases carry more hereditary risk than late onset cases, but little is known about whether any familial component exists in cancer at a very old age.
Researchers from the German Cancer Research Centre and Lund University in Sweden therefore took data from the Swedish Family-Cancer Database (the largest one of its kind) on just under eight million offspring and their biological parents.
Parents' ages were not limited but offspring were all 0-76 years old. Follow-up was started at birth, immigration date or 1961, whichever came latest. Follow-up ended on year of diagnosis of first cancer, death, emigration or 2008.
Results were adjusted for several factors including age, sex, socioeconomic status, residential area, hospitalisation for obesity, COPD and alcohol consumption.
The highest risk was seen in cases whose parents were diagnosed at earlier ages. However, even when parents were affected in old age (80+) and for some cancers in very old age (90+), the risk of the same cancer in offspring was significantly higher than those whose parents were not affected.
Increased risks for each cancer were as follows (in offspring aged 0-76 years): non-Hodgkin lymphoma 1.6%; urinary bladder 2.8%; skin 3.5%; melanoma 4.6%; lung 5%; colorectal 6.4%; breast 8.8% and prostate 30.1%.
In the study population, 35-81% of all familial cancers in parents occurred over 69 years of age (colorectal: 59%, lung: 56%, breast 41%, prostate: 75%, urinary bladder: 62%, and skin cancer: 81%, melanoma: 35%, and non-Hodgkin's lymphoma: 54%). Therefore, the majority of familial cancers occur at elderly ages.
Attempts to explain familial risks by non-genetic factors were not convincing. Therefore, the researchers concluded that familial risks have largely genetic bases.
The researchers believe that family members (in particular offspring) may benefit from knowing that they're at increased risk of a particular cancer because it allows them to avoid known modifiable risk factors for that cancer.
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The above story is reprinted from materials provided by BMJ-British Medical Journal.
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E. Kharazmi, M. Fallah, K. Sundquist, K. Hemminki. Familial risk of early and late onset cancer: nationwide prospective cohort study. BMJ, 2012; 345 (dec20 12): e8076 DOI: 10.1136/bmj.e8076Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
Researchers discover genetic basis for eczema, new avenue to therapies
Dec. 21, 2012 — Researchers at Oregon State University have announced the discovery of an underlying genetic cause of atopic dermatitis, a type of eczema most common in infancy that also affects millions of adults around the world with dry, itchy and inflamed skin lesions.
The findings were just published in PLoS ONE, a professional journal, and may set the stage for new therapeutic approaches to this frustrating syndrome, which is difficult to treat and has no known cure. Eczema is also related to, and can sometimes cause asthma, a potentially deadly immune dysfunction.
Pharmaceutical scientists at OSU found in laboratory studies that eczema can be triggered by inadequate Ctip2, a protein and master regulator that affects other genetic functions. They have identified two ways in which improper function of Ctip2 can lead to eczema.
In a recent publication, they found that Ctip2 controls lipid biosynthesis in the skin, the fats that are needed to help keep skin healthy and hydrated. In the new study, they discovered that Ctip2 suppresses TSLP, a cytokine protein produced by skin cells that can trigger inflammation.
Levels of this inflammatory TSLP, which is ordinarily undetectable in human skin, were found to be 1,000 times higher in laboratory animals that had been genetically modified to have no Ctip2 production in their skin.
"In these studies, we've basically shown that inadequate Ctip2 is reducing the lipids in skin that it needs to stay healthy, protect itself and perform its function," said Arup Indra, an associate professor in the OSU College of Pharmacy. "At the same time this can allow unwanted formation of proteins that trigger inflammation. The skin's ability to resist inflammation is going down just as the amount of inflammation is going up, and the underlying reason is that Ctip2 is not doing its job."
"Either or both of these problems can lead to eczema," Indra said.
Atopic dermatitis is associated with a dysfunctional immune response, but researchers have never understood the underlying cause. Existing treatments use moisturizers to try to protect skin, and in difficult cases powerful steroid drugs can help, but they often have significant unwanted side effects, especially in long-term use.
"With a better understanding of just what is causing eczema on a genetic basis, we should be able to personalize treatments, determine exactly what each person needs, and develop new therapies," Indra said. "This might be with topical compounds that increase Ctip2 expression in skin cells, or customized treatments to restore an individual person's lipid profile. In the future, systemic epigenetic modification might even be possible."
The creation at OSU of the laboratory model to study this issue is also of considerable importance, Indra said. There's evidence it could be used to screen for drugs with potent anti-inflammatory activities.
Eczema is a persistent skin rash that can be fairly common in infants or youth, which some research indicates may be linked to food or pollen allergens. Most people outgrow it as they reach adulthood, but some suffer from the debilitating condition their entire life.
"Our skin is the largest organ in the human body and one of the most important," Indra said. "It's our first barrier of defense, is in a constant battle against external insults, is influenced by both genetics and the environment, and has to be finely tuned to do many jobs. In eczema, this process begins to break down."
Eczema allows significant loss of fluids through the skin, allows allergens to penetrate, and in severe cases can cause a systemic inflammatory response.
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The above story is reprinted from materials provided by Oregon State University.
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Journal Reference:
Zhixing Wang, Ling-juan Zhang, Gunjan Guha, Shan Li, Kateryna Kyrylkova, Chrissa Kioussi, Mark Leid, Gitali Ganguli-Indra, Arup K. Indra. Selective Ablation of Ctip2/Bcl11b in Epidermal Keratinocytes Triggers Atopic Dermatitis-Like Skin Inflammatory Responses in Adult Mice. PLoS ONE, 2012; 7 (12): e51262 DOI: 10.1371/journal.pone.0051262Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
Wednesday, 19 December 2012
Groundbreaking study may change transplant practices
Nov. 20, 2012 — Researchers from John Theurer Cancer Center at Hackensack University Medical Center, one of the nation's 50 best cancer centers, played an important role in a study published in the New England Journal of Medicine on October 18 that may change the current blood and marrow transplantation practices. The phase 3, multicenter study compared harvesting stem cells from bone marrow rather than blood and suggests there are benefits to both approaches, but no survival differences between the two methods.
Over the past 10 years, 75 percent of stem cell transplants from unrelated adult donors have used peripheral blood stem cells rather than those harvested from bone marrow without clinical data to support this shift. The study did not find significant survival differences between peripheral-blood stem-cell and bone marrow transplantation from unrelated donors.
"We did find that peripheral-blood stem cells may reduce the risk of graft failure, whereas bone marrow may reduce the risk of developing chronic graft-versus-host disease (GVHD), a complication that is frequently debilitating," said study author Scott Rowley, M.D., Chief, Blood and Marrow Transplantation at John Theurer Cancer Center.
GVHD is a common complication that can occur after a stem cell or bone marrow transplant in which the newly transplanted donor cells attack the transplant recipient's body. This can cause a variety of serious side effects, such as skin rashes, liver problems and diarrhea. Chronic GVHD usually starts three months after transplant and can last a lifetime. Its symptoms may include chronic pain, dry eyes and mouth, fatigue, skin rash, weight loss.
"As one of the 10 largest blood and marrow transplant programs in the nation, we remain committed to being on the forefront of the latest transplantation research and treatment," said Andrew L. Pecora, M.D., F.A.C.P., C.P.E., Chief Innovations Officer and Professor and Vice President of Cancer Services, John Theurer Cancer Center.
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The above story is reprinted from materials provided by John Theurer Cancer Center.
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Claudio Anasetti, Brent R. Logan, Stephanie J. Lee, Edmund K. Waller, Daniel J. Weisdorf, John R. Wingard, Corey S. Cutler, Peter Westervelt, Ann Woolfrey, Stephen Couban, Gerhard Ehninger, Laura Johnston, Richard T. Maziarz, Michael A. Pulsipher, David L. Porter, Shin Mineishi, John M. McCarty, Shakila P. Khan, Paolo Anderlini, William I. Bensinger, Susan F. Leitman, Scott D. Rowley, Christopher Bredeson, Shelly L. Carter, Mary M. Horowitz, Dennis L. Confer. Peripheral-Blood Stem Cells versus Bone Marrow from Unrelated Donors. New England Journal of Medicine, 2012; 367 (16): 1487 DOI: 10.1056/NEJMoa1203517Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
Face-washing tips for healthier-looking skin
Nov. 13, 2012 — Washing your face is as simple as using soap and water, right? Not quite say dermatologists. How you wash your face can make a difference in your appearance.
"It's important for people to treat the face with care. Never scrub the skin or use harsh products as doing so irritates the skin, which makes skin look worse," said Thomas E. Rohrer, MD, FAAD, a board-certified dermatologist in private practice in Chestnut Hill, Mass.
For healthier-looking skin, Dr. Rohrer recommends people follow these tips to keep their face looking healthy:
1. Use a gentle, non-abrasive cleanser that does not contain alcohol.
2. Wet your face with lukewarm water and use your fingertips to apply cleanser. Using a washcloth, mesh sponge or anything other than your fingertips can irritate your skin.
3. Resist the temptation to scrub your skin as scrubbing irritates the skin.
4. Rinse with lukewarm water, and pat dry with a soft towel.
5. Apply moisturizer if your skin is dry or itchy. Be gentle when applying any cream around your eyes so you do not pull too hard on this delicate skin.
6. Limit washing to twice a day and after sweating. Wash your face once in the morning and once at night as well as after sweating heavily. Perspiration, especially when wearing a hat or helmet, irritates the skin. Wash your skin as soon as possible after sweating.
"A board-certified dermatologist can answer your questions about how to care for your skin, hair and nails," said Dr. Rohrer.
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The above story is reprinted from materials provided by American Academy of Dermatology (AAD), via Newswise.
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Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
How patterns and timing of sunlight exposure contribute to skin cancers
Oct. 23, 2012 — Researchers at Moffitt Cancer Center, the University of South Florida and the International Agency for Research on Cancer in France have studied the patterns and timing of sunlight exposure and how each is related to two nonmelanoma skin cancers -- basal cell carcinoma and squamous cell carcinoma.
This study, published in the open-access journal BioMed Central, is the first case-control study to simultaneously evaluate identical patterns and timing of sunlight exposure as they are related to basal cell and squamous cell carcinomas in the same U.S. population with high annual ultraviolet radiation exposure. Patterns of sunlight exposure are continuous or intermittent, and timing refers to exposure during childhood, adulthood or both. It included 703 Florida residents -- 218 with basal cell carcinoma, 169 with squamous cell carcinoma and 316 without skin cancer. The research goal was to identify potential differences or similarities in sunlight exposure responses for basal cell and squamous cell carcinomas.
"There are more than a million new cases of basal cell and squamous cell carcinomas diagnosed in the United States each year," said senior study author Dana E. Rollison, Ph.D., associate member of the Cancer Epidemiology Program, and vice president and chief health information officer at Moffitt. "While mortality associated with nonmelanoma skin cancers, such as basal cell and squamous cell carcinomas, is low, patients may experience substantial morbidity and treatment costs are high."
It is estimated that 25 percent of lifetime sunlight exposure occurs before age 18. Youth is a time of greater toxic sunlight exposure and also a time when the chances of receiving blistering sunburns are higher.
"Blistering sunburn is believed to result from high doses of intense ultraviolet radiation exposure in short increments of time and is considered to be a measure of intermittent exposure," said study co-author Michelle Iannacone, Marie Curie postdoctoral fellow at the International Agency for Research on Cancer.
The researchers surveyed those with basal cell and squamous cell carcinomas, as well as those with no history of skin cancer, to determine the effects of intermittent versus continuous sunlight exposure, as well as the timing of the exposure and age. They noted that although the relationship between both cancers and sunlight exposure is complex, researchers began to identify cumulative outdoor sunlight exposure as a risk factor for nonmelanoma skin cancer beginning in the 1950s.
Being exposed to ultraviolet radiation intermittently, perhaps while on summer vacation in high ultraviolet radiation regions, and continuous exposure through working at a job outside in the sunlight were patterns the researchers wanted to identify and correlate to basal cell and squamous cell carcinomas.
Study subjects were surveyed on their recollections of their history of sun exposure.
Survey results reveal that a history of blistering sunburn was associated with both basal cell and squamous cell carcinomas. Having a job in the sunlight was also associated with basal cell and squamous cell carcinomas. Measures of younger age at sunlight exposure "tended to be associated with squamous cell carcinoma, but not basal cell carcinoma, risk," researchers concluded.
"Sunlight exposure, regardless of the exposure pattern, is associated with both basal cell and squamous cell carcinomas," Iannacone said. "Understanding how sunlight exposure response may differ by nonmelanoma skin cancer type is important for educating the public on safe sunlight behaviors. Applying sunscreen while on vacation may decrease basal cell carcinoma risk with intermittent sunlight exposure, but may not impact the risk of squamous cell carcinoma, which may be more strongly related to continuous sunlight exposure."
The study was funded by a grant from the state of Florida's James & Esther King Biomedical Research Program (06NIR-08).
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The above story is reprinted from materials provided by Moffitt Cancer Center, via Newswise.
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Michelle R Iannacone, Wei Wang, Heather G Stockwell, Kathleen O'Rourke, Anna R Giuliano, Vernon K Sondak, Jane L Messina, Richard G Roetzheim, Basil S Cherpelis, Neil A Fenske, Dana E Rollison. Patterns and timing of sunlight exposure and risk of basal cell and squamous cell carcinomas of the skin -- a case--control study. BMC Cancer, 2012; 12 (1): 417 DOI: 10.1186/1471-2407-12-417Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
Skin patches for more medicines? Some large molecules sneak through skin on their own
Dec. 12, 2012 — Certain naturally occurring large molecules are able to sneak through the skin at a rate higher than that expected based on their size, according to a study published in the American scientific journal Proceedings of The National Academy of Sciences (PNAS). The study reports a surprising finding that Avicins, plant-derived natural products with molecular weights greater than 2000, penetrate the human skin on their own.
The study is authored by Prof. Dr. Prasad Shastri from the Institute for Macromolecular Chemistry and the cluster of excellence BIOSS Centre for Biological Signalling Studies of the University of Freiburg / Germany and his post-doctoral fellows Dr. Chris Pino and Dr. Daniel Vonwil in collaboration with Prof. Dr. Samir Mitragotri of the University of California, Santa Barbara / USA and Prof. Dr. Jordan Gutterman of the MD Anderson Cancer Center, University of Texas Houston / USA.
The researchers report that the unique structure of Avicins, which is composed of sugar residues linked to a fat-soluble core allows the molecules to gain access to the fatty component of the stratum corneum, the outermost layer of skin, which serves as a barrier for molecules to penetrate. The researchers studied penetration of various fragments of Avicins and discovered that the sugar residues of Avicins play a key role in allowing the molecules to move into and across the stratum corneum.
The findings of the study may open new opportunities in the delivery of therapeutic drugs via skin patches. Delivery of therapeutics across the skin offers many advantages, including ease of administration compared to pills and lack of pain in contrast to needle injections. However, transdermal delivery of drugs has proved challenging as the stratum corneum allows the passage of only small, oil-soluble molecules such as nicotine and estrogen. The insights gained from penetration of Avicins across the skin might provide design strategies for novel approaches to transport large molecules across the skin. Shastri and his collaborators hope to use the insights gained from this study to design drugs and proteins that can be delivered through the skin.
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The above story is reprinted from materials provided by Albert-Ludwigs-Universität Freiburg.
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C. J. Pino, J. U. Gutterman, D. Vonwil, S. Mitragotri, V. P. Shastri. Glycosylation facilitates transdermal transport of macromolecules. Proceedings of the National Academy of Sciences, 2012; DOI: 10.1073/pnas.1200942109Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
Tissues tell the tale: Non-invasive optical technique detects cancer by looking under the skin
Sep. 24, 2012 — The trained eye of a dermatologist can identify many types of skin lesions, but human sight only goes so far. Now an international team of researchers has developed an advanced optics system to noninvasively map out the network of tiny blood vessels beneath the outer layer of patients' skin, potentially revealing telltale signs of disease. Such high resolution 3-D images could one day help doctors better diagnose, monitor, and treat skin cancer and other skin conditions.
The research was published September 24 in the Optical Society's (OSA) open-access journal Biomedical Optics Express.
Researchers from Medical University Vienna (MUW) in Austria and the Ludwig-Maximilians University in Munich, Germany, used a technique called optical coherence tomography (OCT) to "see" beneath the surface of skin. The researchers tested their system on a range of different skin conditions, including a healthy human palm, allergy-induced eczema on the forearm, dermatitis on the forehead, and two cases of basal cell carcinoma -- the most common type of skin cancer -- on the face. Compared to healthy skin, the network of vessels supplying blood to the tested lesions showed significantly altered patterns. "The condition of the vascular network carries important information on tissue health and its nutrition," says Rainer Leitgeb, a researcher at MUW and the study's principal investigator. "Currently, the value of this information is not utilized to its full extent."
Ophthalmologists have used OCT since the 1990s to image different parts of the eye and the technology has recently attracted increased interest from dermatologists. OCT has many advantages over other imaging techniques: It is non-invasive and provides high-resolution images at high speed. OCT is typically used to show tissue structure, but it can also reveal the pattern of blood vessels, which carry important clues about disease, by capitalizing on the unique optical properties of flowing blood cells.
The researchers at MUW are the first to use OCT to visualize the network of blood vessels in human skin that feed cancerous skin lesions. To maximize the quality of the images the team employed a high-tech laser light source developed by collaborators from the Ludwig-Maximilians University. The laser enabled unprecedented high-speed imaging and operated at a near-infrared wavelength that gave better penetration into skin tissue.
"High speed is of paramount importance in order to image lesions in vivo and in situ while minimizing the effect of involuntary patient motion," explains researcher Cedric Blatter of MUW. The device also shapes the light in a special way forming a Bessel beam, which can reform, or heal, its shape even if portions of it are blocked. The beam enabled the researchers to keep the images in focus across a depth range of approximately 1 millimeter.
The team's images of basal cell carcinoma showed a dense network of unorganized blood vessels, with large vessels abnormally close to the skin surface. The larger vessels branch into secondary vessels that supply blood to energy-hungry tumor regions. The images, together with information about blood flow rates and tissue structure, could yield important insights into the metabolic demands of tumors during different growth stages.
The imaging system shows the most promise for clinical application in the diagnosis and treatment of skin cancer, the researchers believe. "We hope that improved in-depth diagnosis of tissue alterations due to disease might help to reduce the number of biopsies by providing better guidance," says Leitgeb. The system could also be used by doctors to assess how quickly a tumor is likely to grow and spread, as well as to monitor the effectiveness of treatments such as topical chemotherapy. "Treatment monitoring may also be expanded toward inflammatory and auto-immune related dermatological conditions," Blatter notes.
Going forward, the researchers would like to increase the field of view of the device so that they can image the full lesion along with its border to healthy tissue. They are also working on speeding up the post-processing of the optical signal to enable live vasculature display, and improving the portability of the system, which currently occupies an area about half the size of an office desk. "We believe that in the future our method will help to simplify non-invasive dermatological in vivo diagnostics and allow for in-depth treatment monitoring," says Blatter.
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The above story is reprinted from materials provided by Optical Society of America.
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Cedric Blatter, Jessika Weingast, Aneesh Alex, Branislav Grajciar, Wolfgang Wieser, Wolfgang Drexler, Robert Huber, Rainer A. Leitgeb. In situ structural and microangiographic assessment of human skin lesions with high-speed OCT. Biomedical Optics Express, 2012; 3 (10): 2636 DOI: 10.1364/BOE.3.002636Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
Melanoma manifests differently in children than in adults, study finds
Sep. 7, 2012 — Melanoma, newly diagnosed in more than 76,000 Americans in 2011, is the most common and dangerous form of skin cancer. Melanoma is rare in children, accounting for 1 to 4 percent of all melanoma cases and just 3 percent of pediatric cancers. Just as adult cases of melanoma are increasing, pediatric melanoma is rising at the rate of 1 to 4 percent per year.
The physicians and staff at Moffitt Cancer Center have a special interest in melanoma and related conditions occurring in childhood, and recently published results of their experience with cases of pathologically confirmed childhood melanoma. They found evidence that the disease manifests differently in children than in adults, particularly with regard to the likelihood and significance of lymph node metastases. Metastases to the lymph nodes, particularly the sentinel nodes, were found more frequently in children with melanoma than would be expected in adults with the same stage of disease, yet with aggressive surgical and medical treatment, stage-for-stage the survival in children was better than expected for adults.
The study is published in the August issue of the Annals of Surgical Oncology.
"We really don't know why young children are getting melanoma, although for older children the risk factors -- fair skin, sun exposure and especially sunburns -- are similar to those in adults. Children with melanoma have higher rates of metastases to sentinel lymph nodes than adults, but they tend to do very well with aggressive treatment," said senior study author Vernon K. Sondak, M.D., chair of the Department of Cutaneous Oncology at Moffitt and an expert in the treatment of melanoma in children and adults. "There is suggestive evidence that the biology of melanoma in children, particularly young children, may be quite different than in adults. Importantly, the diagnosis of melanoma in children can be quite difficult, and consultation with an expert pathologist is often necessary to be sure that we are in fact dealing with melanoma and not some type of atypical mole. Our most recent study focused only on patients where our pathologist verified that melanoma was present, atypical tumors were excluded."
In this study, Moffitt researchers and colleagues at the University of South Florida and All Children's Hospital retrospectively reviewed 126 patients who were diagnosed with melanoma before age 21. One aspect of the study was to determine outcomes of childhood cases of melanoma where the patient had sentinel lymph nodes positive for metastases. The sentinel lymph node directly drains the skin where the primary tumor arose and is almost always the first node affected as a melanoma spreads. Primary tumor characteristics that may predict sentinel lymph node metastases in pediatric patients have not been extensively studied. Sentinel lymph node biopsies were performed in 62 cases, with 18 having a positive node. In the other 64 cases where a sentinel lymph node biopsy was not performed, the reasons were usually because the stage of the melanoma was not appropriate for the procedure.
"We observed a 29 percent positive sentinel lymph node rate," said Sondak, noting that the rate fell within the 25 to 40 percent rate found by other studies done in children, but higher than the 12 to 15 percent rate typically found in studies in adult melanoma. "We found that patients with positive SLN had significantly thicker melanomas when compared with SLN negative patients."
The researchers also found that pediatric melanoma patients with positive SLN had significantly worse recurrence-free survival and melanoma-specific survival rates. However, although lymph node metastases are seen at a higher rate in children, survival is comparable to -- or even better than -- what has been reported for adults with melanoma. According to Sondak, as the incidence of pediatric melanoma rises, it is important to gain a better understanding of the unique clinical characteristics of melanoma in children.
"We feel that most pediatric patients with clinically localized melanomas should be offered sentinel lymph node biopsies," concluded Sondak and his co-authors. "It is also noteworthy that a significant number of recurrences and melanoma-related deaths are seen more than five years after initial diagnosis. Thus, long-term follow-up is necessary as these children become young adults. Most of all, our study should remind people how important it is to protect children from the sun and from sunburn, starting from birth."
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The above story is reprinted from materials provided by H. Lee Moffitt Cancer Center & Research Institute.
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Journal Reference:
Dale Han, Jonathan S. Zager, Gang Han, Suroosh S. Marzban, Christopher A. Puleo, Amod A. Sarnaik, Damon Reed, Jane L. Messina, Vernon K. Sondak. The Unique Clinical Characteristics of Melanoma Diagnosed in Children. Annals of Surgical Oncology, 2012; DOI: 10.1245/s10434-012-2554-5Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
Going viral to kill zits: Scientists uncover virus with potential to stop pimples in their tracks
Sep. 25, 2012 — Watch out, acne. Doctors soon may have a new weapon against zits: a harmless virus living on our skin that naturally seeks out and kills the bacteria that cause pimples.
The Sept. 25 online edition of the American Society for Microbiology's mBio publishes the findings by scientists at UCLA and the University of Pittsburgh.
"Acne affects millions of people, yet we have few treatments that are both safe and effective," said principal investigator Dr. Robert Modlin, chief of dermatology and professor of microbiology, immunology and molecular genetics at the David Geffen School of Medicine at UCLA. "Harnessing a virus that naturally preys on the bacteria that causes pimples could offer a promising new tool against the physical and emotional scars of severe acne."
The scientists looked at two little microbes that share a big name: Propionibacterium acnes, a bacterium thriving in our pores that can trigger acne; and P. acnes phages, a family of viruses that live on human skin. The viruses are harmless to humans, but programmed to infect and kill the aforementioned P. acnes bacteria.
When P. acnes bacteria aggravate the immune system, it causes the swollen, red bumps associated with acne. Most effective treatments work by reducing the number of P. acnes bacteria on the skin.
"We know that sex hormones, facial oil and the immune system play a role in causing acne, however, a lot of research implicates P. acnes as an important trigger," explained first author Laura Marinelli, a UCLA postdoctoral researcher in Modlin's laboratory. "Sometimes they set off an inflammatory response that contributes to the development of acne."
Using over-the-counter pore cleansing strips from the drugstore, the researchers lifted acne bacteria and the P. acnes viruses from the noses of both pimply and clear-skinned volunteers.
When the team sequenced the bacteriophages' genomes, they discovered that the viruses possess multiple features -- such as small size, limited diversity and the broad ability to kill their hosts -- that make them ideal candidates for the development of a new anti-acne therapy.
"Our findings provide valuable insights into acne and the bacterium that causes it," observed corresponding author Graham Hatfull, Eberly Family Professor of Biotechnology, professor of biological sciences at the University of Pittsburgh and a Howard Hughes Medical Institute researcher. "The lack of genetic diversity among the phages that attack the acne bacterium implies that viral-based strategies may help control this distressing skin disorder."
"Phages are programmed to target and kill specific bacteria, so P. acnes phages will attack only P. acnes bacteria, but not others like E. coli," added Marinelli. "This trait suggests that they offer strong potential for targeted therapeutic use."
Acne affects nearly 90 percent of Americans at some point in their lives, yet scientists know little about what causes the disorder and have made narrow progress in developing new strategies for treating it. Dermatologists' arsenal of anti-acne tools -- benzoyl peroxide, antibiotics and Accutane -- hasn't expanded in decades.
"Antibiotics such as tetracycline are so widely used that many acne strains have developed resistance, and drugs like Accutane, while effective, can produce risky side effects, limiting their use," explained coauthor Dr. Jenny Kim, director of the UCLA Clinic for Acne, Rosacea and Aesthetics. "Acne can dramatically disfigure people and undermine their self-esteem, especially in teens. We can change patients' lives with treatment. It's time we identified a new way to safely treat the common disorder."
The research team plans to isolate the active protein from the P. acnes virus and test whether it is as effective as the whole virus in killing acne bacteria. If laboratory testing proves successful, the researchers will study the compound's safety and effectiveness in combating acne in people.
The study was supported by grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R21AR060382, R01 AR053542 and F32AR060655) at the National Institutes of Health in Bethesda, Md.
Additional coauthors included Sorel Fitz-Gibbon, Megan Inkeles, Shawn Cokus, Matteo Pellegrini and Jeffrey F. Miller, all of UCLA; former UCLA researchers Clarmyra Hayes and Anya Loncaric, now of the California Institute of Technology and Solta Medical, respectively; and Charles Bowman, Daniel Russell and Deborah Jacobs-Sera of the University of Pittsburgh.
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The above story is reprinted from materials provided by University of California, Los Angeles (UCLA), Health Sciences.
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Laura J. Marinelli, Sorel Fitz-Gibbon, Clarmyra Hayes, Charles Bowman, Megan Inkeles, Anya Loncaric, Daniel A. Russell, Deborah Jacobs-Sera, Shawn Cokus, Matteo Pellegrini, Jenny Kim, Jeff F. Miller, Graham F. Hatfull, and Robert L. Modlin. Propionibacterium acnes Bacteriophages Display Limited Genetic Diversity and Broad Killing Activity against Bacterial Skin Isolates. mBio, 2012 DOI: 10.1128/mBio.00279-12Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
Happy face tattoo does serious work
Dec. 3, 2012 — A medical sensor that attaches to the skin like a temporary tattoo could make it easier for doctors to detect metabolic problems in patients and for coaches to fine-tune athletes' training routines. And the entire sensor comes in a thin, flexible package shaped like a smiley face.
"We wanted a design that could conceal the electrodes," says Vinci Hung, a PhD candidate in the Department of Physical & Environmental Sciences at UTSC, who helped create the new sensor. "We also wanted to showcase the variety of designs that can be accomplished with this fabrication technique."
The new tattoo-based solid-contact ion-selective electrode (ISE) is made using standard screen printing techniques and commercially available transfer tattoo paper, the same kind of paper that usually carries tattoos of Spiderman or Disney princesses. In the case of the sensor, the "eyes" function as the working and reference electrodes, and the "ears" are contacts for a measurement device to connect to.
Hung contributed to the work while in the lab of Joseph Wang, a distinguished professor at the University of California San Diego. She worked there for six months earlier this year under the Michael Smith Foreign Study supplement from NSERC.
"It was a wonderful opportunity," Hung said. She worked directly with Wang, who is well-known for his innovations in the field of nanoengineering and is a pioneer in biosensor technology.
The sensor she helped make can detect changes in the skin's pH levels in response to metabolic stress from exertion. Similar devices, called ion-selective electrodes (ISEs), are already used by medical researchers and athletic trainers. They can give clues to underlying metabolic diseases such as Addison's disease, or simply signal whether an athlete is fatigued or dehydrated during training. The devices are also useful in the cosmetics industry for monitoring skin secretions.
But existing devices can be bulky, or hard to keep adhered to sweating skin. The new tattoo-based sensor stayed in place during tests, and continued to work even when the people wearing them were exercising and sweating extensively. The tattoos were applied in a similar way to regular transfer tattoos, right down to using a paper towel soaked in warm water to remove the base paper.
To make the sensors, Hung and her colleagues used a standard screen printer to lay down consecutive layers of silver, carbon fiber-modified carbon and insulator inks, followed by electropolymerization of aniline to complete the sensing surface.
By using different sensing materials, the tattoos can also be modified to detect other components of sweat, such as sodium, potassium or magnesium, all of which are of potential interest to researchers in medicine and cosmetology.
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The above story is reprinted from materials provided by University of Toronto.
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Journal Reference:
Amay J. Bandodkar, Vinci W. S. Hung, Wenzhao Jia, Gabriela Valdés-RamÃrez, Joshua R. Windmiller, Alexandra G. Martinez, Julian RamÃrez, Garrett Chan, Kagan Kerman, Joseph Wang. Tattoo-based potentiometric ion-selective sensors for epidermal pH monitoring. The Analyst, 2013; 138 (1): 123 DOI: 10.1039/C2AN36422KNote: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
First appropriate use criteria in dermatology released
Sep. 7, 2012 — A new manuscript co-published in the Journal of the American Academy of Dermatology (JAAD) and Dermatologic Surgery outlines Appropriate Use Criteria (AUC) for Mohs surgery -- the first AUC for any test or treatment within the field of dermatology.
The Mohs AUC represents a collaborative initiative by the American Academy of Dermatology (Academy), American College of Mohs Surgery (ACMS), the American Society for Dermatologic Surgery Association (ASDSA), and the American Society for Mohs Surgery (ASMS).
"These Appropriate Use Criteria for Mohs surgery embody a unique effort to develop criteria to support the efficient use of medical resources while providing the highest quality care for the patients who will benefit the most," said board-certified dermatologist Suzanne M. Connolly, MD, FAAD, chair, Ad Hoc Task Force on the Development of Appropriate Use Criteria for Mohs Surgery. "The goal of the AUC is to provide evidence-based guidance on which types of skin cancer cases are most appropriate for this specialized surgery."
Statistics and facts:
More than 3.5 million skin cancer cases affecting 2 million people are diagnosed annually.Current estimates are that one in five Americans will be diagnosed with skin cancer in their lifetime.About Mohs Surgery
Mohs surgery is a specialized skin cancer surgery in which a dermatologist who has completed additional training in Mohs surgery is able to remove skin cancer layer by layer until the entire tumor has been removed. The Mohs surgeon uses a microscope to examine each tissue layer to look for cancer cells until no further ones are found at any spot around any edges of the tumor. This technique allows the Mohs surgeon to preserve as much healthy tissue as possible, yet remove the entire cancer.
Background
The AUC process was based on the well-established, credible method developed by the RAND Corporation/UCLA more than 30 years ago. AUC have been shown to improve patient selection, clinical outcomes and health-related quality of life while reducing overall cost and resource utilization. The Mohs AUC are the first AUC developed for any test or treatment option within the scope of dermatology.
Study details
The AUC process combines evidence-based medicine, clinical practice experience, and expert judgment.Nearly 80 dermatologists, both Mohs surgeons and non-Mohs dermatologists, contributed to the development of this first AUC for the specialty, including a 17-member ratings panel that was balanced by expertise, society representation, type of practice, and geographic location. To manage potential conflict of interest, the majority of the Ratings Panel members were not Mohs surgeons.The collaboration of dermatologists involved in this process developed AUC for 270 scenarios for which Mohs surgery is frequently considered based on tumor and patient characteristics.The Mohs AUC outline highly specific skin cancer patient scenarios that dermatologists encounter in daily clinical practice and classify the use of Mohs into one of three categories: appropriate, uncertain, or inappropriate.At the conclusion of the rating process, consensus was reached for all 270 scenarios (100 percent) by the ratings panel, with 200 (74.07 percent) deemed as appropriate, 24 (8.89 percent) as uncertain and 46 (17.04 percent) as inappropriate. With few exceptions, all scenarios involving the head, neck, hands, feet and genitalia are rated appropriate. An appropriate rating solely means that Mohs is an acceptable approach for that clinical scenario and patient; other approaches also may be considered based on physician assessment.The benefits of these AUC are expected to be numerous and include: Clinical decision supportFacilitation of discussions with referring physicians and patientsSupport for researchEducational and quality improvement toolsThe Mohs AUC is a living document and intended to be modified as new clinical information is published or encountered in the practice setting. This new evidence may lead to future revisions to ratings as well as the clinical scenarios to more precisely define patient selection for Mohs surgery."As the incidence of skin cancer continues to climb and the practice of Mohs surgery advances in the future, Mohs surgeons, dermatologists, primary care providers and the health care community in general will need to understand how to best utilize Mohs surgery in the treatment of skin cancer -- and the AUC we initiated is an important first step in that direction," said Dr. Connolly.
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Ultrasound gel and infections: Researchers propose guidelines to reduce risk
Nov. 12, 2012 — In the December issue of Infection Control and Hospital Epidemiology, the journal of the Society for Healthcare Epidemiology of America, guidelines have been proposed by epidemiologists from Beaumont Health System to reduce the risk of infection from contaminated gels. The recommendations are based on the authors' own experiences with an outbreak traced to contaminated ultrasound transmission gel.
In December 2011, researchers uncovered an unusual cluster of Pseudomonas aeruginosa in a cardiovascular surgery intensive care unit during routine infection control surveillance. The outbreak was found to have stemmed from bottles of ultrasound transmission gel that were contaminated during the manufacturing process and that were being used for intraoperative transesophageal echocardiography. This information ultimately led to a national recall of the product.
These gels contain parabens or methyl benzoate that inhibit, but not kill, the growth of bacteria. However, past studies have demonstrated that ultrasound gels do not have antimicrobial properties and could serve as a medium for bacterial growth. Contaminated gels have been found to be the source of other outbreaks of infection in the last two decades.
"After our investigation of the Pseudomonas outbreak last year linked the source of the outbreak to contaminated ultrasound gel, we were surprised to find that very little guidance is available on appropriate uses for different ultrasound gel products," said Susan Oleszkowicz, MPH, lead author of the paper.
In their article the authors outline initial guidelines for recommended uses of ultrasound transmission gels, calling on manufacturers of ultrasound gel and professional societies to take an active role in developing recommendations for appropriate and intended use of products.
Suggestions include: 1) the need for sterile, single-dose ultrasound gel in any invasive procedure or procedures involving non-intact skin or fresh surgical wounds; 2) sterile, single-dose ultrasound gel should be used with newborns or critically ill children; 3) multi-dose, non-sterile gel can still be used on intact skin, but containers should be sealed appropriately when not in use, and replaced when empty, rather than refilled.
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Susan C. Oleszkowicz, Paul Chittick, Victoria Russo, Paula Keller, Matthew Sims, Jeffrey Band. Infections Associated with Use of Ultrasound Transmission Gel: Proposed Guidelines to Minimize Risk. Infection Control and Hospital Epidemiology, 2012; 33 (12): 1235 DOI: 10.1086/668430Note: If no author is given, the source is cited instead.
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Kids with psoriasis likely to be obese or overweight
Nov. 19, 2012 — The largest study of physician-treated children with psoriasis around the world shows children with the skin disease are about twice as likely to be overweight or obese as children who don't have the disease, according to new Northwestern Medicine research.Pediatric Psoriasis Severity and Excess Adiposity . Archives of Dermatology, 2012; : 1 DOI: 10.1001/jamadermatol.2013.1078
And US children with psoriasis have much higher odds than psoriatic children in other countries of being obese or overweight.
In the US, children with psoriasis had four times the odds of being overweight or obese as healthy controls. Within this US population, Hispanics and African American children had significantly greater rates of being obese and overweight than whites and Asians. The odds ratio of being obese were particularly high for U.S. children with more severe psoriasis (7.6).
"There has been increasing attention to the association of psoriasis and metabolic risks in adults, but this study shows that the association of being overweight or obese and having psoriasis may be even higher in affected children than in adults," said Amy Paller, M.D., chair of dermatology at Northwestern University Feinberg School of Medicine and lead author of the study. She also is a pediatric dermatologist at the Ann and Robert H. Lurie Children's Hospital of Chicago.
The paper was published Nov. 19 in Archives of Dermatology.
"This is incredibly significant," Paller said. "It tells us these children are at increased risk of health complications (cardiac risk and insulin resistance) and need to be watched closely and treated."
The study included 614 children five to 17 years old from nine countries in the Americas, Europe and Asia.
Previous studies showing an association between psoriasis and obesity were largely based on registry data, which is less precise and may under identify cases because of the reliance on diagnosis codes rather than a direct examination and measurements to calculate Body Mass Index.
In this study, about 30 percent of the affected children had an immediate family member with psoriasis, suggesting a strong genetic component. However, the reported family history of obesity was not higher in children with psoriasis than in control children.
"Perhaps our U.S. environment of eating more calories and getting less exercise along with a strong genetic component for the disease hikes the risk," Paller said.
"There is something in the genetic makeup of these kids that predisposes them to these metabolic issues and positions psoriasis as a metabolic disorder," noted Paller, also the Walter J. Hamlin Professor of Dermatology at the Feinberg School. "Psoriasis is driven by many of the same cytokines (proteins) that drive insulin resistance and being overweight."
Psoriasis is characterized by red, often itchy scaling lesions that can be localized (especially to the scalp, knees and elbows) or cover the entire body. The disease affects 2.5 to 3.5 percent of the global population with up to 33 percent of the cases starting in childhood, particularly during adolescence.
"It's a highly visible disease which can be devastating during the all-important years of psychosocial development of childhood and adolescence," Paller said. "It affects their social life and even their ability to participate in sports. Psoriasis has a profound effect on children's quality of life."
The study also looked beyond the commonly used Body Mass Index (BMI) to investigate psoriasis' link to central adiposity (fat around the waist) and the waist-to-height ratio, both of which are believed to have a higher correlation with metabolic risk. Internationally, the odds ratio of having a high waist-to-height ratio that imparted a high level of cardiac risk was 3.1 for all children with psoriasis and 4.1 for those with severe psoriasis.
"The bottom line is these kids need lifestyle intervention," Paller said. "You can't just treat psoriasis. You've got to work with these kids to increase exercise and decrease their caloric intake to reduce their risk for metabolic diseases. Perhaps losing weight could help their psoriasis as well." Previous studies in adults have suggested that weight loss can result in less severe symptoms.
A question not yet answered is which comes first, the psoriasis or the excess fat? Is a high BMI the precursor of psoriasis in children or does the disease lead to an increased BMI through chronic cytokine release from psoriatic tissues, compounded by a lifestyle that may contribute to excess fat? Paller is currently investigating that question.
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The above story is reprinted from materials provided by Northwestern University. The original article was written by Marla Paul.
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Amy S. Paller et al. Association of Pediatric Psoriasis Severity With Excess and Central AdiposityAn International Cross-Sectional StudyNote: If no author is given, the source is cited instead.
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Hybrid scaffold more than skin deep
Dec. 5, 2012 — Researchers in Japan have created a hybrid scaffold which promotes tissue regeneration, strong and biodegradable. This research was recently published in Science and Technology of Advanced Materials.
Open skin wounds need to be repaired quickly to prevent infection. Using artificial skin substitutes for repair avoids the difficulties of grafts, but an ideal material for a scaffold that's strong and allows regeneration of skin tissue has yet to be found.
Some current scaffolds are made of collagen or gelatin, which are ideal for promoting tissue regeneration but are not mechanically strong. Others are made of biodegradable synthetic materials such as Poly(L-lactic acid) (PLLA); these are stronger, but not so good for tissue growth. Guopong Chen and colleagues at the National Institute for Materials Science, Japan, have created a hybrid scaffold that has all the necessary properties.
The team had previously formed 'funnel-like' scaffolds with pores that are interconnected under the surface, allowing cells to grow into the scaffold. Now, they have formed these funnel-like collagen or gelatin 'sponges' on a PLLA mesh to create hybrid scaffolds.
Connective tissue cells grew on the hybrid scaffold and penetrated into the pores, with more cells growing in the hybrid scaffold than in a scaffold made only of collagen. Implantation of the hybrid scaffolds into the backs of mice also promoted healing: four weeks after implantation, skin defects were completely closed. Regenerated skin was healthier with the hybrid scaffold than with a collagen-only scaffold, and there was also less deformation of the skin due to the extra strength provided by the PLLA mesh.
The ability of the hybrid scaffold to promote regeneration of skin in live animals while maintaining mechanical strength makes it a promising material for future skin tissue engineering.
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The above story is reprinted from materials provided by National Institute for Materials Science, via ResearchSEA.
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Hongxu Lu, Hwan Hee Oh, Naoki Kawazoe, Kozo Yamagishi, Guoping Chen. PLLA–collagen and PLLA–gelatin hybrid scaffolds with funnel-like porous structure for skin tissue engineering. Science and Technology of Advanced Materials, 2012; 13 (6): 064210 DOI: 10.1088/1468-6996/13/6/064210Note: If no author is given, the source is cited instead.
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Scratching the surface: Engineers examine UV effects on skin mechanics
Oct. 5, 2012 — Researchers in Stanford's Department of Materials Science and Engineering are using models derived in mechanical labs to look closer at how ultraviolet radiation changes the protective functions of human skin.
Reinhold Dauskardt, PhD, of Stanford's Department of Materials Science and Engineering has been studying skin for years. But when he sent his students to look for data on the mechanical properties of skin, they came back empty-handed. A lot was known about skin structure and disease, but few papers actually talked about its mechanical function -- its ability to stretch and resist tension without tearing. "That motivated us to get more interested in the skin itself," said Dauskardt.
He and his team, including Ph.D. student Krysta Biniek and postdoctoral researcher Kemal Levi, focused on the outmost layer of skin: the stratum corneum. It protects deeper layers from drying out or getting infected, and it's also our first line of defense against UV radiation. Their study was published October 1 in the Proceedings of the National Academy of Sciences (PNAS).
They found that beyond the well-documented DNA damage and cancer risk, UV rays also change the way the outermost skin cells hold together and respond to strain.
Innovative Methods
Ironically, the methodology behind these discoveries about skin originated in the field of photovoltaics. A grant from the US Department of Energy supported Dauskardt's research into the effects of severe environments and prolonged UV exposure on materials -- in particular, the materials that make up solar panels.
"Here we were looking at solar cells then suddenly thinking, 'Hey, we should be looking at applying these techniques to skin,'" said Dauskardt, pictured at right.
The researchers subjected samples of human tissue to varying doses of UVB radiation. (UVB is the range of ultraviolet wavelengths that are largely absorbed by the epidermis and do not penetrate to deeper layers.) Then they tested the mechanical limits of the samples by putting them under different kinds of stress until they tore.
We've all experienced the sensations of dryness, stiffness, or chapping after washing our hands with harsh soap, sitting by a space heater or under the air conditioning vent, or spending too long in the sun. Now we can begin to understand the mechanical properties behind those sensations. This is the first time that such methods have been applied to the study of skin.
The Human Fortress
Our body's outermost stratum corneum defensive layer has a "brick-and-mortar" structure. The "bricks" in this model are dead cells called corneocytes, which are filled with a matrix of keratin filaments. Our skin's rigidity -- its ability to resist deformation under pressure -- is due largely to the bonds between these strands of protein. The researchers were surprised to find that while the keratin was structurally changed by UVB exposure, the stiffness of the tissue wasn't affected. When the skin samples were mounted onto opposing grips and pulled apart, samples with greater UVB exposure were just as resistant.
The "mortar" of skin defense, on the other hand, took a beating from the UV rays. Between the corneocytes is a layer of lipids -- fatty, waxy substances that hold the skin cells together and keep water from getting though. In a process called bulge testing, thin strips of skin were mounted over the opening of a cavity filled with pressurized water so they ballooned outward. The team found that UV exposure increased the tissue's tendency to absorb water and loosened the bonds between the lipids, making it more likely to tear under pressure. This means that sun-damaged skin is more prone to cracking and chapping, leaving deeper layers vulnerable to infection.
In another technique borrowed from materials science, the researchers used a double cantilever beam model to test the cohesive properties of skin. Imagine fused restaurant chopsticks being pried open, but with a tissue sample glued into the region that gets torn apart. UV damage made the individual corneocytes separate more easily, especially in deeper layers of the stratum corneum.
This result suggests that another component of the "mortar," proteins called corneodesmosomes, were also being damaged. These proteins are crucial to desquamation -- the process of shedding dead skin cells, which allows us to replace the entire stratum corneum every two to four weeks. While the long-term impact of UV exposure on the desquamation mechanism has not been studied yet, damage to corneodesmosomes could mean deeper, lasting damage to the skin's protective abilities.
Double the Damage
All this rigorous stress testing revealed a grim fact: the sun takes a dramatic toll on our mechanical barrier function.
"UV exposure doesn't just make the stratum corneum weaker," said Dauskardt, "It also increases the actual stresses that cause the stratum corneum to fail. So it's sort of a double-whammy, which we didn't expect." In other words, UV radiation introduces more force driving skin cells apart while making the cells more helpless to resist.
This double threat is especially relevant to public health as global climate change will gradually change the way people interact with the sun. The spectrum of sunlight that penetrates to earth's surface is increasing, while warmer temperatures cause people to wear less clothing, making them more vulnerable.
Mechanical testing is also confirming the vital importance of wearing sunscreen to protect the skin's integrity. "It's totally cool," said Dauskardt, "You put a sunscreen on the sample and it causes a huge change in the way the skin is affected." This line of research offers a straightforward strategy for finding the best protection. Instead of trying to establish risk of carcinoma or gene damage, these methods can quickly and accurately model how different sun protection products affect the skin's mechanics. Dauskardt has already started comparative testing of sunscreens and thinks the work could be relevant in settling a currently raging debate about which types are most effective.
Dauskardt said the project is an example of breakthrough results arising from unlikely cooperation. "What's so cool about bioengineering research today is that we're taking medical challenges and looking at them with current engineering and scientific methods. This whole interdisciplinary approach is incredibly powerful, and you never know what it's going to reveal."
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The above story is reprinted from materials provided by Stanford School of Engineering. The original article was written by Kelly Servick.
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Unexpected factor contributes to melanoma risk in red-haired, fair-skinned individuals
Oct. 31, 2012 — The well-established elevated risk of melanoma among people with red hair and fair skin may be caused by more than just a lack of natural protection against ultraviolet (UV) radiation. In an article receiving Advance Online Publication in Nature, Massachusetts General Hospital (MGH) Cutaneous Biology Research Center (CBRC)and Cancer Center researchers report finding that the type of skin pigment predominantly found in red-haired, fair-skinned individuals may itself contribute to the development of melanoma.
"We've known for a long time that people with red hair and fair skin have the highest melanoma risk of any skin type. These new findings do not increase that risk but identify a new mechanism to help explain it," says David Fisher, MD, PhD, chief of the MGH Department of Dermatology, director of the CBRC and senior author of the Nature paper. "This may provide an opportunity to develop better sunscreens and other measures that directly address this pigmentation-associated risk while continuing to protect against UV radiation, which remains our first line of defense against melanoma and other skin cancers."
Several types of the pigment melanin are found in the skin: a dark brown or black form called eumelanin, predominant in individuals with dark hair or skin, and a lighter blond-to-red pigment called pheomelanin, the predominant pigment in individuals with red hair, freckles and fair skin. Red/blond melanin is known to be less effective than dark melanin in shielding against UV damage, but there were several hints that the incidence of melanoma in individuals of that skin type may not be fully explained by limited UV protection. While the increased risk of non-melanoma skin cancers is limited to sun-exposed areas, the melanoma risk also applies to areas of skin not exposed to sunlight. In addition, although available sunscreens may do a good job of blocking some forms of UV damage such as sunburns, many studies have suggested that they may not be as effective protecting against melanoma as against other types of skin cancers.
In their search for additional contributors to melanoma development, the MGH team used strains of mice that were nearly identical genetically except for the gene that controls the type of melanin produced. One group of dark-colored mice had the typical variant leading to a predominance of dark melanin. Another group of mice had a "red hair-fair skin" version, the same variant that produces red hair and fair skin in humans. The researchers used a method devised by co-authors at the University of California/San Francisco and Yale University to activate the melanoma-associated form of the BRAF oncogene in patches of the animals' skin pigment cells, with the expectation that an additional environmental stress like UV radiation would be needed to induce melanoma formation. They were surprised to find that within months, half of the red mice had developed melanomas, while only a few dark mice had.
After confirming that there was no unexpected UV radiation in the area where the mice were housed, the investigators wondered whether red pigment itself might be carcinogenic. Since the red hair/fair skin gene controls many cellular activities beyond pigment production, they tested the melanoma risk within a group of red hair/fair skinned mice in which all pigment production had been genetically disabled, a strain called "albino redheads." The researchers observed that complete removal of the red-pigment pathway profoundly protected those mice from melanoma formation, indicating that something about the pigment itself, and not other aspects of being red-haired and fair-skinned, was leading to melanoma.
Suspecting that the red-pigment-associated risk might be chemically related to the generation of reactive oxygen species (ROS) -- unstable oxygen-containing molecules that can damage cells -- the researchers examined skin from both red and albino redhead mice. They discovered elevated levels of a type of DNA damage typically produced by ROS in skin of red mice but not in albino redheads, supporting oxidative damage as the mechanism behind red-pigment-associated melanoma formation.
While this result suggests antioxidant treatments may be able to reduce this risk, Fisher cautions that further research is needed to identify safe and effective ways to exploit this knowledge. "Antioxidant treatments are not highly predictable in their actions and in some instances have even been seen to increase rather than prevent oxidative damage. Therefore we need to determine how to control this pathway safely and effectively," he says. "There are additional key questions to investigate, such as whether these findings also may pertain to people with, for example, fair skin and dark hair.
"Right now we're excited to have a new clue to help better understand this mystery behind melanoma, which we have always hoped could be a preventable disease," he adds. "The risk for people with this skin type has not changed, but now we know that blocking UV radiation -- which continues to be essential -- may not be enough. It will be important for these individuals to be aware of changes in their skin and never hesitate to have something checked by a dermatologist, even if they have scrupulously protected themselves from sun exposure, which we continue to encourage. About six out of seven melanomas will be cured if they are found early, so we need to heighten awareness and caution."
Along with Fisher, the Wigglesworth Professor of Dermatology at Harvard Medical School, co-authors of the Nature paper are lead author Devarati Mitra of the MGH Cutaneous Biology Research Center (CBRC); Ann Morgan, Jennifer Lo, Kathleen Robinson and Suprabha Devi, MGH CBRC; Xi Luo, Kevin Haigis and Daniel Haber, MGH Cancer Center; Mai Hoang and Martin Mihm, MGH Pathology; Jennifer Wargo, MGH Surgery; Jin Wang, Candace Guerrero and Yinsheng Wang, University of California, Riverside; Jochen Lennerz, University of Ulm, Germany; Jillian Vanover and John D'Orazio, University of Kentucky School of Medicine; Martin McMahon, University of California, San Francisco; and Marcus Bosenberg, Yale University School of Medicine.
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Stopping the itch: New clues into how to treat eczema
Oct. 11, 2012 — More than 15% of children suffer with eczema, or atopic dermatitis, an inflammatory skin disease that in some cases can be debilitating and disfiguring. Researchers reporting in the October issue of Immunity have discovered a potential new target for the condition, demonstrating that by blocking it, they can lessen the disease in mice.
In eczema, immune T cells invade the skin and secrete factors that drive an allergic response, making the skin itch. Dr. Raif Geha, of Boston Children's Hospital, and his collaborators now show that scratching the skin precipitates the condition by encouraging an influx of other immune cells called neutrophils. These neutrophils secrete a lipid called leukotriene B4 that calls in more neutrophils, and more importantly, potent immune T cells that are the hallmark of eczema. These cells cause inflammation that aggravates the skin further. The investigators suspected that blocking the onslaught of these cells might slow down the disease or even stop it in its tracks.
Furthermore, Dr. Geha and his colleagues wondered whether the production of leukotriene B4 served to recruit T cells to the site of mechanical insult. And indeed that was the case. "We showed that a drug that blocks the production of leukotriene B4 blocks the development of allergic skin inflammation in a mouse model of eczema," says Dr. Geha. His team also found that deleting the receptors on immune cells that bind to leukotriene B4 had a similar effect.
"Our findings suggest that neutrophils play a key role in allergic skin inflammation and that blockade of leukotriene B4 and its receptor might provide a new therapy for eczema," says first author Dr. Michiko Oyoshi.
Most people get eczema as infants, and they tend to outgrow it by adolescence; however some people continue to experience "flare-ups" of an itchy rash on and off throughout life. Some develop these after coming into contact with particular substances, such as specific soaps, or in response to certain conditions, such as a respiratory infection or cold.
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The above story is reprinted from materials provided by Cell Press, via EurekAlert!, a service of AAAS.
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Michiko K. Oyoshi, Rui He, Yitang Li, Subhanjan Mondal, Juhan Yoon, Roshi Afshar, Mei Chen, David M. Lee, Hongbo R. Luo, Andrew D. Luster, John S. Cho, Lloyd S. Miller, Allison Larson, George F. Murphy, Raif S. Geha. Leukotriene B4-Driven Neutrophil Recruitment to the Skin Is Essential for Allergic Skin Inflammation. Immunity, 2012; DOI: 10.1016/j.immuni.2012.06.018Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
Understanding aging: Stem cell dysfunction links cancer and aging
Oct. 1, 2012 — Aging is a complex biological process whereby the functional capacity of the body diminishes with time, ultimately leading to the death of the individual. However, aging is also associated with the onset of many diseases, including cancer, which is often called a "disease of aging." While aging has major effects on the individual, it also represents a significant burden on society as a major healthcare cost. Therefore, it is of chief importance to understand the normal process of aging to help improve not only the lifespan of individuals, but also their healthspan; in other words, to enable people to live longer, healthier lives.
Despite significant worldwide research, the causes of aging remain poorly understood. In particular, why the body undergoes a functional decline over the course of time is not entirely clear. Now, a new study from researchers at the CRG has uncovered a significant clue in understanding how aging may occur, and how this may promote the development of diseases such as cancer.
In this study, the researchers studied the skin of young and old mice, as the skin is one of the most obvious tissues to undergo aging. Indeed many of the visible features of aging are the result of skin aging, including loss of hair growth, wrinkling and thinning of the skin and a reduced wound-healing ability.
In the skin, as in the rest of the body, the tissue is constantly in a state of turnover, replenishing itself by replacing dead and damaged cells with new healthy ones. To achieve this, each tissue relies on populations of specialized cells known as stem cells. "These cells are unique in their ability, as they are able to grow and differentiate into all the other different cells types in the tissue, as well as tolerating stress and damage better than non-stem cells. This process of rejuvenation and renewal is something that was thought to occur all throughout life" says Jason Doles, the first author on the study and a postdoctoral researcher at the CRG.
In this work, the researchers have studied skin stem cells during the aging process to see if changes in stem cell function might contribute to aging. Their major finding is that during the aging process, skin stem cells actually lose their ability to function properly. "We have discovered that major changes occur in these stem cells during aging, whereby stem cells exhibit impaired growth in older animals as compared to their more youthful counterparts. We also found that the aged stem cells are not able to tolerate stress as well as young stem cells, strongly supporting the idea that changes in stem cell function might actually drive the aging process" says Bill Keyes, group leader of the Mechanisms of Cancer and Aging lab at the CRG and lead author of the study.
The report goes further, uncovering novel processes driving skin stem cell aging, and linking the aging process with diseases such as cancer. In fact, a recent study from the same group, demonstrated that these same stem cells become deregulated during the development of squamous cell carcinoma, a deadly type of skin cancer. The current study performed high-throughput profiling of the aging stem cells and identified a likely cause of the loss of function during aging. They demonstrated that during normal aging, the entire skin changes and produces many different proteins that mediate inflammation, and that it is the abnormal production of these inflammatory-mediators that contributes to the decline of stem cell function. Given that the link between inflammation and the development of cancer has been long known, the current study uncovers important findings on how the two might be linked.
Altogether, these findings help to explain what is likely a major cause of the aging process and how this develops, opening the door for future studies that may help to alleviate aspects of the aging process. But in addition, with the identification of inflammation as a cause of stem cell dysfunction, the study also uncovers likely causes in the development of cancer.
The research has been funded by the Spanish Ministry for Science and Innovation and the Centre for Genomic Regulation (CRG).
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The above story is reprinted from materials provided by Centre for Genomic Regulation.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
J. Doles, M. Storer, L. Cozzuto, G. Roma, W. M. Keyes. Age-associated inflammation inhibits epidermal stem cell function. Genes & Development, 2012; DOI: 10.1101/gad.192294.112Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
Getting (drugs) under your skin: Using ultrasound waves, researchers boost skin's permeability to drugs
Sep. 14, 2012 — Using ultrasound waves, MIT engineers have found a way to enhance the permeability of skin to drugs, making transdermal drug delivery more efficient. This technology could pave the way for noninvasive drug delivery or needle-free vaccinations, according to the researchers.
"This could be used for topical drugs such as steroids -- cortisol, for example -- systemic drugs and proteins such as insulin, as well as antigens for vaccination, among many other things," says Carl Schoellhammer, an MIT graduate student in chemical engineering and one of the lead authors of a recent paper on the new system.
Ultrasound -- sound waves with frequencies greater than the upper limit of human hearing -- can increase skin permeability by lightly wearing away the top layer of the skin, an effect that is transient and pain-free.
In a paper appearing in the Journal of Controlled Release, the research team found that applying two separate beams of ultrasound waves -- one of low frequency and one of high frequency -- can uniformly boost permeability across a region of skin more rapidly than using a single beam of ultrasound waves.
Senior authors of the paper are Daniel Blankschtein, the Herman P. Meissner '29 Professor of Chemical Engineering at MIT, and Robert Langer, the David H. Koch Institute Professor at MIT. Other authors include Baris Polat, one of the lead authors and a former doctoral student in the Blankschtein and Langer groups, and Douglas Hart, a professor of mechanical engineering at MIT.
Two frequencies are better than one
When ultrasound waves travel through a fluid, they create tiny bubbles that move chaotically. Once the bubbles reach a certain size, they become unstable and implode. Surrounding fluid rushes into the empty space, generating high-speed "microjets" of fluid that create microscopic abrasions on the skin. In this case, the fluid could be water or a liquid containing the drug to be delivered.
In recent years, researchers working to enhance transdermal drug delivery have focused on low-frequency ultrasound, because the high-frequency waves don't have enough energy to make the bubbles pop. However, those systems usually produce abrasions in scattered, random spots across the treated area.
In the new study, the MIT team found that combining high and low frequencies offers better results. The high-frequency ultrasound waves generate additional bubbles, which are popped by the low-frequency waves. The high-frequency ultrasound waves also limit the lateral movement of the bubbles, keeping them contained in the desired treatment area and creating more uniform abrasion, Schoellhammer says.
"It's a very innovative way to improve the technology, increasing the amount of drug that can be delivered through the skin and expanding the types of drugs that could be delivered this way," says Samir Mitragotri, a professor of chemical engineering at the University of California at Santa Barbara, who was not part of the research team.
The researchers tested their new approach using pig skin and found that it boosted permeability much more than a single-frequency system. First, they delivered the ultrasound waves, then applied either glucose or inulin (a carbohydrate) to the treated skin. Glucose was absorbed 10 times better, and inulin four times better. "We think we can increase the enhancement of delivery even more by tweaking a few other things," Schoellhammer says.
Noninvasive drug delivery
Such a system could be used to deliver any type of drug that is currently given by capsule, potentially increasing the dosage that can be administered. It could also be used to deliver drugs for skin conditions such as acne or psoriasis, or to enhance the activity of transdermal patches already in use, such as nicotine patches.
Ultrasound transdermal drug delivery could also offer a noninvasive way for diabetics to control their blood sugar levels, through short- or long-term delivery of insulin, the researchers say. Following ultrasound treatment, improved permeability can last up to 24 hours, allowing for delivery of insulin or other drugs over an extended period of time.
Such devices also hold potential for administering vaccines, according to the researchers. It has already been shown that injections into the skin can induce the type of immune response necessary for immunization, so vaccination by skin patch could be a needle-free, pain-free way to deliver vaccines. This would be especially beneficial in developing countries, since the training required to administer such patches would be less intensive than that needed to give injections. The Blankschtein and Langer groups are now pursuing this line of research.
They are also working on a prototype for a handheld ultrasound device, and on ways to boost skin permeability even more. Safety tests in animals would be needed before human tests can begin. The U.S. Food and Drug Administration has previously approved single-frequency ultrasound transdermal systems based on Langer and Blankschtein's work, so the researchers are hopeful that the improved system will also pass the safety tests.
The research was funded by the National Institutes of Health.
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The above story is reprinted from materials provided by Massachusetts Institute of Technology. The original article was written by Anne Trafton, MIT News Office.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
Carl M. Schoellhammer, Baris E. Polat, Jonathan Mendenhall, Ruby Maa, Brianna Jones, Douglas P. Hart, Robert Langer, Daniel Blankschtein. Rapid skin permeabilization by the simultaneous application of dual-frequency, high-intensity ultrasound. Journal of Controlled Release, 2012; DOI: 10.1016/j.jconrel.2012.08.019Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
Tanning beds linked to non-melanoma skin cancer
Oct. 2, 2012 — Indoor tanning beds can cause non-melanoma skin cancer -- and the risk is greater the earlier one starts tanning, according to a new analysis led by UCSF.
Indoor tanning is already an established risk factor for malignant melanoma, the less common but deadliest form of skin cancer. Now, the new study confirms that indoor tanning significantly increases the risk of non-melanoma skin cancers, the most common human skin cancers.
In the most extensive examination of published findings on the subject, the researchers estimate that indoor tanning is responsible for more than 170,000 new cases annually of non-melanoma skin cancers in the United States -- and many more worldwide.
Young people who patronize tanning salons before age 25 have a significantly higher risk of developing basal cell carcinomas compared to those who never use the popular tanning booths, the researchers reported.
The study will be published online October 2, 2012 in BMJ, the British general medical journal.
"The numbers are striking -- hundreds of thousands of cancers each year are attributed to tanning beds,'' said Eleni Linos, MD, DrPH, an assistant professor of dermatology at UCSF and senior author of the study. "This creates a huge opportunity for cancer prevention.''
The study was a meta-analysis and systematic review of medical articles published since 1985 involving some 80,000 people in six countries and data extending back to 1977.
The popularity of indoor tanning in the United States first began in the 1970s, and now millions of people annually patronize tanning salons. The National Cancer Institute and the federal Centers for Disease Control and Prevention in 2010 reported that 5.6 percent of the American public used indoor tanning during the prior year, with higher rates among women, whites, and young adults.
Currently, there are some 19,000 indoor tanning businesses, according to an industry trade organization.
But in pursuit of golden hues, many people may unknowingly subject themselves to dermatological danger.
The World Health Organization has said that ultraviolet tanning devices cause cancer in people and the International Agency for Research on Cancer considers indoor tanning a "Class 1'' carcinogen. Government officials in the U.S. and abroad are increasingly restricting and regulating tanning facilities.
The new study adds to the mounting evidence on the harms of indoor tanning, showing significant elevated risk of the most common forms of skin cancer.
"Several earlier studies suggested a link between non-melanoma skin cancer and indoor tanning. Our goal was to synthesize the available data to be able to draw a firm conclusion about this important question,'' said co-author Mary-Margaret Chren, MD, professor of dermatology at UCSF.
The researchers studied both early life exposure and regular use of tanning booths. Those who exposed themselves to indoor tanning had a 67 percent higher risk of developing squamous cell carcinoma and a 29 percent higher risk of developing basal cell carcinoma, compared to people who never did indoor tanning.
The scientists noted several limitations including the broad timeframe that the data spans. Also, indoor tanning devices have changed over the years "from high UVB output to predominantly UVA output,'' the authors said. But, they point out, numerous studies have indicated that both UVB and UVA can cause significant skin damage.
"Australia and Europe have already led the way in banning tanning beds for children and teenagers, and Brazil has completely banned tanning beds for all ages,'' Linos said. "I hope that our study supports policy and public health campaigns to limit this carcinogen in the United States.''
Co-authors are Mackenzie Wehner, a Doris Duke Research Fellow at UCSF; Melissa Shive, a medical student at UCSF; Jiali Han, PhD, an associate professor at Harvard Medical School; and Abrar Qureshi, MD, MPH, dermatology vice chairman at Brigham and Women's Hospital.
The project was supported by UCSF's Clinical and Translational Science Institute KL2 program, and the National Institute of Health.
The authors report no financial conflicts of interest. Chren serves as a consultant to Genentech.
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The above story is reprinted from materials provided by University of California, San Francisco (UCSF). The original article was written by Elizabeth Fernandez.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
Wehner MR, Shive ML, Chren M, Han J, Qureshi AA, Linos E. Indoor tanning and non-melanoma skin cancer: systematic review and meta-analysis. BMJ, 2012; 345: e5909 DOI: 10.1136/bmj.e5909Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
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