A breakthrough into the understanding of how moles develop into melanoma has been made by researchers at Penn College of Medicine Cancer Institute, PA, USA. They demonstrated that there is an interaction between two key proteins, which are involved in 60–70% of tumors, and that targeting these proteins should assist in effective drug development for melanoma.
“We have shown that when two proteins – (V600E)B-Raf and Akt3 – communicate with one another in a mole, they cooperate leading to the development of melanoma,” explains Gavin Robertson, lead author of the study. He adds “We have also shown that effective therapies for melanoma need to target both these proteins, which essentially eliminates the tumors.”
It was previously know that B-Raf is the most mutated gene in melanoma and that the mutant protein produce by this gene, (V600E)B-Raf, is integral to mole cell growth. It was also understood that this gene alone was not responsible for melanoma development, as 90% of moles contained it, but it was unclear until now what also had to be present in the mole in order for melanomas to develop.
The research team found the secondary event necessary for melanoma development. They discovered that a second protein, which is produced by Akt3, regulates the activity of the mutated B-Raf, consequently contributing to the development of melanoma.
The team noticed, by comparing proteins of normal moles and melanoma cells, that communication between the proteins occurred in the melanoma cells only. They then determined that the Akt3 protein had to be present in order for melanoma to develop by adding it to cells that contained the B-Raf gene and observing that they were then able to develop into melanoma.
The team hopes that their discovery will pave the way for future drug treatments for melanoma.
“We have shown that if we target the two proteins separately, it somewhat inhibits the development of tumors but if we target them together, the development of tumors gets inhibited significantly,” Robertson added. “It validates these proteins as key targets for effective melanoma therapy.”
Robertson and his team hope that future therapy could entail examination of patient’s blood samples to determine if these proteins are present within their cells. Drugs could then be administered to target these proteins in the form of a personalized cancer treatment, which would be more effective and carry fewer side effects. They also hope that it could be used as a preventative method and that sunscreens could be modified to prevent the function of Akt3 and hence melanoma development.
Source: Cheung M, Sharma A, Madhunapantula SV, Robertson GP. Akt3 and mutant V600E B-Raf cooperate to promote early melanoma development. Cancer Res. 68(9), 3429–3439 (2008).
Eczema may be prevented in babies by friendly bacteria
A recent discovery, which furthers the understanding into the infant’s immune system, may assist in prevention of eczema in babies. The studies, which were presented at the International Symposium on Early Nutrition Programming in Granada, Spain (Wednesday 23rd April 2008), have uncovered that bacteria located in the gut can reduce the likelihood of a baby developing eczema.
Yolanda Sanz (Institute of Agrochemistry and Food Technology, Valencia, Spain), who presented the research comments, “New and exciting insights on how gut bacteria affect immune function are emerging from these studies, which we hope will support the use of pro- and prebiotics in primary disease prevention in the future.”
Gut immunity prevents the body from over responding to trigger molecules, which results in an allergic reaction. It is achieved by attainment of the right balance of various strains of bacteria in the gut. Antibodies and natural prebiotics are present in breast milk and it has been shown that babies fed with breast milk are less likely to develop eczema.
This recent discovery may lead to the development of prebiotic mixtures that boost babies natural immune defense and reduce their risk of developing eczema.
“This is exciting new scientific information that suggests a fairly straightforward way to help ease the burden of this condition on infants and their families,” advises Philip Calder (University of Southampton, UK) Chair of the Immune Function session at the EARNEST Symposium.
Sources: www.earlynutrition.org; www.metabolic-programming.org
Genetic test introduced that predicts female hair loss
HairDX, LLc, a company that produces consumer-friendly genetic hair-loss tests, has introduced a screening test that detects genetic markers associated with female androgenetic alopecia.
The test is simple to use and is available on the internet for US$149. It provides an accurate genetic analysis of the woman’s likelihood of developing alopecia. The user must take a swab from inside her mouth and return it to the HairDX laboratory. She then receives results via a confidential website in a simple to understand format.
“Helping women assess their risk for female hair loss early in the course of their hair loss enables them to learn about potential treatment options and how they may prevent further hair loss,” explains Sharon Keene, Chief Medical Officer for HairDX . “This is a treatable medical condition and not a reason for embarrassment. Since most therapies for women are geared toward stabilizing hair loss, it is important to identify female androgenetic alopecia as soon as possible and institute therapy when stabilization is most useful – before substantial hair is lost. Being informed can bring comfort and empowerment.”
Results are presented in the form of a score with a higher score indicating a decreased chance of hair loss.
“Scientists discovered that the percentage of the female population with a score of 15 or less, not suffering from a Ludwig grade II or III hair loss was only a 2.3%,” adds Nathan Vandergraft, a Statistician and Research Scientist (University of California, CA, USA).
The HairDX test makes use of the discovery of markers associated with hair loss. “We believe that the introduction of our genetic screening test for female androgenetic alopecia will allow millions of women to take preventive action before they show any visible signs of hair loss,” concludes HairDX CEO Andy Goren.
Source: www.hairdx.com
Recombinant form of human thrombin shown to be effective in the treatment of burn patients
Drug: RECOTHROM™
Manufacturer: ZymoGenetics, Inc.
Indication: Burns
Development stage: Phase III
A Phase III trial focusing on the safety and immunogenicity of RECOTHROM™ thrombin topical (recombinant; ZymoGenetics, Inc.), has demonstrated the treatment’s effectiveness when administered via a spray pump device in burn patients requiring skin grafts, according to data announced recently at the 40th American Burn Association Annual Meeting in Chicago, USA. These results mirror the positive data collected from an earlier Phase III investigation of RECOTHROM, a recombinant form of human thrombin protein, which demonstrated comparable efficacy and a potentially lower incidence of antibody formation when compared with its commercially available bovine thrombin equivalent.
The single-arm, open-label study enrolled 72 patients with burn wound excision sites, who were treated with either a partial- or full-thickness autologous or mesh graft following the occurrence of a burn injury. RECOTHROM was applied topically onto the burn area using a ZymoGenetics-developed pump spray device prior to skin graft placement. No patients were forced to discontinue treatment due to adverse events, which were minor and consisted mainly of procedural pain and pruritis. This adverse events were experienced by 35 and 25% of patients, respectively.
Dr David Greenhalgh, Lead Study Investigator of the trial and Chief of Burns at the UC Davis Medical Center, CA, USA, described burn wound excision as posing “unique challenges to homeostasis.” He believes that “the results of this study suggest that recombinant thrombin may be a viable hemostatic alternative in burn patients.”
Thrombin is used widely in over approximately 1 million surgeries worldwide, primarily for assisting the control of bleeding (as a hemostatic agent) from capillaries and small venules when standard surgical techniques are deemed insufficient or ineffective. The development of the human recombinant non-plasma-derived form of the protein is thought to be advantageous because it is not dependent on the availability of human or animal blood products and can therefore be synthesized more closely in response to demand. Its homology to the human form is also thought to infer a better response by potentially decreasing the activation of the patient’s own immune system to the agent via the production of antibodies.
Source: www.zymogenetics.com; www.recothrom.com
Malignant melanoma of the scalp and neck appears to have a worse prognosis than at other sites
A recent study examined the prognosis and survival rates of malignant melanoma at various sites and found ‘a notable survival difference’ between melanoma on the scalp and neck compared with melanoma at other sites of the body. The study found that those with melanoma of the scalp and neck were approximately twice as likely to die within 5 years compared with those who had melanoma at another site, such as on the arm or leg.
The authors emphasized that this difference was only apparent with regard to malignant melanoma and not the more common basal cell carcinoma.
The team from the University of North Carolina, NC, USA, and the University of New Mexico, NM, USA conducted a population-based retrospective cohort study controlling for known prognostic factors. The data were taken from the Surveillance, Epidemiology and End Results 13 Registries (SEER-13) database and included a total of 51,704 non-Hispanic white adults that had reported a first invasive cutaneous melanoma between 1992 and 2003.
The team used Kaplan–Meier survival estimates to compare melanoma survival by anatomic site at 5 and 10 years. The team found that the 5- and 10-year survival rates for scalp and neck melanoma were 83.1 and 76.2%, respectively, compared with 92.1 and 88.7%, respectively, for melanoma at other sites. The team controlled for age, Breslow thickness, sex and ulceration.
The team believe that this notable difference should emphasize the need for increased screening and public health recommendations and urge physicians and healthcare workers to examine these sites specifically at routine examinations. The biological and environmental factors leading to survival differences by anatomic site remain unknown.
Source: Lachiewicz AM, Berwick M, Wiggins CL, Thomas NE. Survival differences between patients with scalp or neck melanoma and those with melanoma of other sites in the Surveillance, Epidemiology, and End Results (SEER) program. Arch. Dermatol. 44(4), 515–521 (2008).