Scientists believe that they have discovered what initiates the progression of radial melanomas, which spread only on the surface of the skin, into invasive melanomas, which grow vertically into the skin. They have found that Akt,a cell signaling molecule, is a primary trigger in initiating the growth of melanoma vertically into the skin. It is hoped that this finding could aid in developing new targets for drug development for patients with melanoma at an advanced stage.
The growth of melanoma into the skin marks a distinct decrease in the patient’s survival rate as the melanoma becomes resistant to chemotherapy. If the disease reaches the lymph node, the 5-year survival rate drops from 98 to 64%. Metastasis to other organs sees a further drop to 16%.
Senior author of this study is Jack L Arbiser, Emory University School of Medicine (GA, USA). He and his team had previously demonstrated that p42/44 MAP kinase was activated in radial growth melanoma. From this, they believed that further signaling was required for the melanoma to progress into an invasive tumor.
The gene for Akt was then introduced into radial growth melanoma cells. The team observed a huge increase in the levels of vascular endothelial growth factor (VEGF). Nude mice were then administered melanoma cells that were overexpressing Akt, resulting in aggressive tumor growth with significantly higher VEGF levels than control mice.
Akt overexpression also saw a marked rise of the enzyme NOX4 and subsequently of reactive oxygen species. Additionally, overexpression of Akt in cells resulted in mitochondrial impairment. This was perhaps owing to chronic oxidative stress rather than being a causative factor for melanoma progression.
“Our research shows that Akt overexpression on its own is sufficient to transform radial growth melanoma cells into highly invasive tumors via reactive oxygen pathways,” Arbiser explained. “This could provide us with promising targets for anticancer drug therapy. We will continue to work on refining the exact mechanisms of how Akt influences the aggressive growth of melanomas.”
Source: Govindarajan B, Sligh JE, Vincent BJ et al. Overexpression of Akt converts radial growth melanoma to vertical growth melanoma J. Clinic. Invest. 117 (3), 719–729 (2007).
Aging of nonsun-exposed skin linked with smoking
Researchers from Michigan University (MI, USA) have revealed results that indicate that smoking ages the skin in areas not normally exposed to sunlight, such as the inside of the upper arm.
Yolanda R Helfrich and colleagues observed these areas in 77 patients. Helfrich explained, “We examined nonfacial skin that was protected from the sun, and found that the total number of packs of cigarettes smoked per day and the total years a person has smoked were linked with the amount of skin damage a person experienced.”
The team looked at photographs of the upper inside arm of study participants and, by developing and using a 9-point photonumeric scale, they measured the degree of aging of the skin. Each photograph had a grade assigned to it from 0 to 8. If no fine wrinkling was present, 0 was awarded, wheras 8 represented severe wrinkling. Photographs were then taken and observed a year later of the same participants in order to determine the increment in skin aging.
Particpants were also quizzed on factors, such as age, ethnicity, smoking history, sun exposure, sunbed use, nonsteroidal anti-inflammatory drug use, oral contraceptive use and use of dietary or herbal supplements.
There was a clear increase in the aging process of the skin of those who smoked compared with non-smokers; this was particularily more evident in those over 45 years of age.
The scale created for the study was reproducible and, it is hoped, will be used in other studies.
Source: Helfrich YR, Yu L, Ofori A Effect of smoking on aging of photoprotected skin: evidence gathered using a new photonumeric scale Arch. Dermatol. 143(3), 397–402 (2007).
Phamacogenomics for psoriasis
A recent study shows that investigation of individual gene characteristics’ in psoriasis patients can increase the possibilities of using pharmacogenomic approaches to deliver pharmacotherapy.
A total of 293 plaque psoriasis patients participated in the study. Of these, 82 had psoriasis guttata and 202 were control patients. The researchers specifically observed three polymorphisms in retinoid X receptors (RXR)A and RXRB gene association.
The study authors were interested in a possible association of their variability and psoriasis guttata.
Results showed that there was a significant rise in AA allelic frequency of RXRA A39526AA polymorphism in men with psoriasis compared with the control men.
Women with psoriasis demonstrated a higher risk for genotypes AA and TT in the RXRB 3´+140A/T polymorphism than women in the control group.
It is hoped that these findings will contribute to an improvement in psoriasis pharmacogenomic therapy.
Source: Vasku V, Bienertova Vasku J, Pavkova Goldbergova M, Vasku A Three retinoid X receptor gene polymorphisms in plaque psoriasis and psoriasis guttata Dermatology 214(2), 118–124 (2007).
Acne severity and teen’s stress levels linked
A recent investigation into the link between levels of stress in teenagers and acne revealed that those who were more highly stressed were 23% more likely to have acne at an increased severity. This was the largest ever study to look at the link and was conducted at the Wake Forest University School of Medicine (NC, USA).
Lead author Gil Yosipovitch explained “Acne significantly affects physical and psychosocial well-being, so it is important to understand the interplay between the factors that exacerbate acne. Our study suggests a significant association between stress and severity of acne.”
Yosipovitch and colleagues studied 94 adolescents in at an attempt to further the current knowledge on the relationship between acne and stress. The relationship had been determined previously but these authors looked specifically at whether there was an increase in sebum levels during stressful periods and whether this increased acne severity.
The researchers noted the self-reported stress levels of the sample group just before their mid-year exams and then once again in their summer break. The exams were of great importance to the students as their career prospects would be influenced by the results.
Each student was given a questionnaire of 14 questions to assess their levels of stress. This ‘Perceived Stress Scale’ is used widely in stress research. The results from these were then compared with acne levels of the students which were measured by observing the number of lesions in each individual. Acne was present in 95% of the buys assessed and 92% of girls.
The researchers had believed that sebum levels would increase at times of stress that, in turn, would cause an increase in acne severity. Surprisingly, the results showed an absence of fluctuation in sebum levels when comparing it at times of high stress with levels under low-stress conditions.
The study demonstrated that those who reported higher levels of stress were 23% more likely to have an increase in the severity of their acne comedonica.
Yospiovitch added “our research suggests that acne severity associated with stress may result from factors other than sebum quantity. It is possible that inflammation may be involved.”
Source: Yosipovitch G, Tang M, Dawn AG et al. Study of psychological stress, sebum production and acne vulgaris in adolescents Acta Derm. Venereol. 87(2), 135–139 (2007)
Young people ‘addicted’ to tanning
Many young people disregard health warnings surrounding the adverse effects of tanning from artificial light sources and sunlight in an attempt to get a tan. A recent study reveals that some people may actually have an addiction to UV light not dissimilar to addictions to alcohol or drugs.
The report by Robin L Hornung and coworkers (University of Washington and the Children’s Hospital and Regional medical centre, WA, USA) is based on their research of 385 male and female college students from the University of Washington. The researchers used a standardized testing tool – cut-down, annoyed, guilty, eye opener (CAGE) – to determine whether the candidates had a substance-related disorder (SRD) and then subsequently assess whether the students may have an addiction to tanning.
“Numerous studies have shown that increased knowledge of the dangers of overexposure to UV light often fails to change tanning behavior and attitudes especially among high-risk age groups such as adolescents,” explains Hornung. “We also know from previous experiments that UV light causes endorphin release, ... our study set out to find whether certain individuals, particularly those who classify themselves as frequent tanners, exhibit addictive behaviors towards tanning.”
The study participants were asked to complete a multiple-choice questionnaire regarding their tanning behavior.
Students who admitted that they tanned purposely were also required to answer four additional questions. These four questions were modified from the CAGE questionnaire.
Of the female students, 76% and, of the male students, 59% admitted to tanning purposely. There was also a higher proportion of females to males who admitted to using indoor tanning devices (42 vs 17%, respectively).
Hornung and his team found that 12% of the total sample of students indicated a UV SRD by responding positively to the CAGE questions. Of those who admitted to regular tanning, 18%, and of those who used indoor tanners, 28%, responded positively to the CAGE questions.
“Our finding that 18% of the students who admitted to purposely tanning their skin scored positively on the CAGE questionnaire is significant, not only because it indicates the probable existence of SRD with respect to UV light but because this percentage is comparable with findings of other addiction studies,” Hornung explains. “If tanning is addictive as our study suggests, it helps explain why education alone will probably not stop high-risk behavior – similar to how the ‘don’t drink’ and ‘don’t smoke’ messages often fail to change behavior.”
The study also found that having a family history of skin cancer did not prevent purpose tanning. In fact, those with a family history were more likely to tan purposely than those with no family skin cancer history (77 vs 45%, respectively).
Hornung believes that these findings should strengthen the argument for stricter regulations on indoor taning. He adds “education alone is not enough to stop high-risk tanning behavior, and skin cancer rates will continue to increase markedly without proper intervention.”
Source: Poorsattar SP, Hornung RL. UV light abuse and high-risk tanning behavior among undergraduate college students. J. Am. Acad. Dermatol. 56(3), 375–379 (2007).