A large advance happened in the melanoma world this week. Researchers were able to identify the molecular switch which controls transcription factor ATF2. ATF2 can progress melanoma, but also act as a suppressor in non-melanoma skin cancers. Teams based at the Sanford-Burnham Medical Research Institute, the University of California: San Diego, Ajou University School of Medicine in Korea, and Yale University found that the function of ATF2 depends on whether it’s held in the nucleus or within the cytoplasm, GEN News reported. The location of the transcription factor depends on the protein Kinase Cε.

Describing their work in cultured cells, Sanford-Burnham’s Ze’ev A. Ronai , Ph.D., and colleagues subsequently confirmed that in primary human melanoma, high levels of PKCε are associated the most with aggressive tumors and poorer patient survival. Reporting in Cell, the team claims its findings could provide the foundation for the development of prognostic tests and new approaches to rendering melanoma less resistant to therapy. Their published paper is titled “PKCε Promotes Oncogenic Functions of ATF2 in the Nucleus while Blocking Its Apoptotic Function at Mitochondria.”

Activating ATF2 plays a role in the development and growth of cells. It also plays a role in a cells’ response to DNA damage. ATF2 plays these roles when located in the nucleus of a cell. What scientists are trying to figure out is what is ATF2′s role when located in cytoplasm. Why does ATF2 have dual locations?

Prior research had found that squamous cell carcinoma (SSC) accumulates ATF2 in the cytosol, so the team started their work in an SSC cell line. They initially confirmed that whereas nonstressed cells exhibited predominantly nuclear ATF2, when the cells were put under genotoxic stress through treatment with etoposide (ETO), ultraviolet C, or ionizing radiation, ATF2 trafficked to the cytoplasm and associated with proteins at the mitochondrial outer membrane (MOM).

This mitochondrial localization of ATF2 following genotoxic stimuli was similarly exhibited in other cell types including normal human fibroblasts (HSF), primary human keratinocytes (NHEK), and melanocytes (HEM) as well as other SCC cell lines. In contrast, while some melanoma cell lines exhibited partial ATF2 accumulation at mitochondria in response to genotoxic stimuli, in a number of melanoma lines the transcription factor simply didn’t translocate to mitochondria.

Subsequent work using the SSC cells demonstrated that localization of ATF2 at the MOM directly blocked the formation of HK1/VDAC1 complexes that normally form in response to various forms of stress and disrupted MOM integrity, leading to mitochondrial leakage as a precursor to cell death.

What the studies also confirmed, was that Kinase Cε regulated the activity of ATF2. What was found was that patients with a decreased rate of survival had high Kinase Cε levels. This means that the protein is directly responsible for whether a tumor is malignant or not. The researchers are now trying to figure out how to release ATF2 from Kinase Cε’s control. If they can do that, scientists will be able to stop tumors from being malignant.

This is extremely exciting news, and we at MoleSafe wish them the best of luck!

What do YOU think about this news? Comment below and let us know.

A majority of children are not regularly using sunscreen, ABC News reports. These results were found by a study conducted at Memorial Sloan-Kettering Cancer Center.

360 kids who were around 10 years old between 2004 and 2007 [were] surveyed…about whether they ever had sunburns, how much time they spent in the sun and how often they wore sunscreen. The study, published in the journal Pediatrics, found that more than half the children reported having at least one sunburn the previous summer, and that number was about the same when the children were questioned three years later.

This is clearly a problem, because as we know, sunburns place you at risk for melanoma and other skin cancers. The other issue lies in the fact that good behaviors are generally reinforced in childhood, and if children are not using sunscreen now, they will likely not use it as adults either. By teaching young children the importance of sunscreen and having them use the product, it will naturally become part of their routines.  What the study also showed is that while 50% of the children said they used sunscreen at the beginning of the study, three years later only 25% of them still used it.

Stephen Duza, who led the study, pointed out that, “when you ask kids or teens about tanning, they say people look better with a tan, and tanning has a very positive association in kids of this age, so trying to get them to limit this behavior is a difficult message to get across”. Kids and teens need to see the danger in tanning, and not simply associate it with attractiveness.

Here at MoleSafe, we want to spread the importance of sun safe practices. Targeting children is most definitely one of the important steps in spreading melanoma awareness. This study is important in that it shows how much work we have yet to do. Hopefully soon we will be able to get all children to regularly wear sunscreen and understand its importance.

What do YOU think? Comment below and let us know!

Zelboraf has been hailed as a possible miracle drug for melanoma patients. Unfortunately, there may be a serious side effect which could prevent patients from taking it, USA Today is reporting.

“…roughly one-quarter of patients who take the medication develop a troublesome side effect: secondary skin cancers called squamous cell carcinomas,” the article states. Researchers at the Jonsson Comprehensive Cancer Center at the University of California: Los Angeles are looking into this new finding.  Dr. Antoni Ribas said:

What we found is that vemurafenib blocks the mutation that makes the melanoma grow, but when patients have skin cells with another mutation that’s probably induced from sun exposure, there the drug has the exact opposite effect and causes these squamous cell cancers to grow.

The findings led to what may be an even more effective way to treat melanoma, however. The researchers think that by combining vemurafenib, which is a BRAF inhibitor, with an MEK inhibitor they may be able to block the mutation, thus preventing the side effect. “It needs to be demonstrated in clinical trials, but the theory is that if we give these two medications together up front, we will be punching the melanoma where it really hurts twice, and also preventing the growth of secondary skin cancers,” said Ribas.

For the study, the researchers analyzed squamous cell lesions in patients taking vemurafenib. They were looking for genetic mutations. Out of 21 tumor samples, 13 had an RAS mutation, which places someone at risk to develop squamous cell cancer. In another set of samples 8 out of 14 had RAS mutations.

The scientists then tested mice, and were able to successfully block the growth of squamous cell cancer using BRAF and MEK inhibitors together. This experiment would obviously need to be transferred to humans so that researchers would know for sure if humans were affected.

Dr. Ribas also points out that these findings could help with other cancers as well. He said that, “what this data also warns us is that we have to be very careful about using BRAF inhibitors in a setting where we don’t know what other mutations may be driving (the cancer)”. We at MoleSafe think that they should keep up the good work!

What do YOU think? Comment below and let us know!

Many people these days are interested in natural or holistic medicine. It seems as though a company, ChromaDex, is attempting to find a natural answer to non- melanoma skin cancer. In an article by Peter Cleveland of SmallCap Network, ChromaDex is described as, “an innovative natural products company providing proprietary, science-based solutions and ingredients to the dietary supplement, food and beverage, cosmetic and pharmaceutical industries”.

The company is studying its pTeroPure as the potential skin cancer treatment. ChromaDex is joined by The University of California, Irvine in this endeavor. “ pTeroPure is CDXC’s ultra-pure formumation of pterostilbene, a compound found in blueberries and shown to have a number of health benefits”, says the article. The pTeroPure would target NMSC.

NMSC refers to a group of skin cancers that affect the upper layers of skin. In the U.S., NMSC is the most common form of cancer, outnumbering all other cancers combined. A number of factors are responsible for the rising incidence of NMSC, including modern addiction to sun-bathing, rising elderly population and decreasing stratospheric ozone. It is estimated that, globally, a 10% drop in the stratospheric ozone will cause 300,000 additional NMSCs.

Common treatment for NMSCs is surgery. The surgery cuts out the cancer. Another option is freezing, through which the cancer cells are frozen and destroyed. Chemotherapy and radiation treatment can also be used, but usually only when the tumors are quite large. ChromaDex is hoping that they can eliminate these treatments and their side-effects.

The idea that a compound in blueberries could cure skin cancer is quite thrilling! MoleSafe certainly hopes they’re onto something.

A study which came out this week claims that women who use sunless tanning products are less likely to use tanning beds, USA Today reports.

Sunless tanning products are a safe alternative for people who are looking for a summer glow. They do not put people at risk for UV exposure, as does traditional sunbathing and tanning beds. The researchers found that by using the sunless products, women lowered their overall UV exposure time.

Dr. Suephy Chen pointed out that sunless tanning products offer no risk for DNA damage as well.”The product adheres to the top layer of the skin that sheds anyway”, she said. Chen believes that you can’t fight with people who want to be tan, but you can promote healthy ways to achieve that look.

For the study, Chen’s team surveyed more than 400 women, age 18 and older, about their use of sunless tanning products and their tanning habits. Almost 50 percent said they had used sunless tanning products at least once in the last year. Most had used self-applied products, with 9 percent saying they got a professionally applied spray tan. The products were used by women of all ages, the researchers noted.

Of the women used in the study, 70% said that they had tanned in the sun during the past year, 26% used tanning beds, and a quarter of the women tanned both ways. The 37% of the women who used sunless tanning products had a decrease in their amount of sun tanning.

Women who used sunless tanning products at least five times in the previous year spent 52 percent less time sunbathing, while women who used these products less often reduced sun exposure by 18 percent, the study found. Tanning bed use was reduced more than 50 percent among women who used tanning products frequently, compared with about 24 percent among women who used the tanning products less often, the researchers said.

Dr. Jonette Keri pointed out that the public  needs to get rid of the idea that a tan is healthy. Skin cancer is the fastest growing cancer in the U.S., and people need to realize this. We here at MoleSafe hope that together, with other members of the anti-melanoma community,  we can promote sun safety!

Scientists at the German Cancer Research Center and Medical Facility Mannheim at Heidelberg University have looked into the affects of Viagra on mice with melanoma. The researchers are actually studying sildenafil, which is the active ingredient in the famous little blue pill. It was found that, “cancerous mice treated with the drug  survived more than twice as long as untreated fellow animals”, as reported by insciences.org.

This sounds like great news, but as Dr. Viktor Umansky points out:

On the one hand, cells of  the immune system specifically attack tumor cells. On the other,  however, almost every tumor causes in its microenvironment a chronic  inflammatory immune response which suppresses the specific antitumor  immunity.

So, Umansky claims, that they are trying to reduce the chronic inflamations and through that support the immune system as it attempts to fight the cancer cells.

 For their research, they used  genetically-modified (transgenic) mice that spontaneously develop a type  of skin cancer which is very similar to human melanoma. In the tumor  environment and in metastatic lymph nodes of the animals, the  investigators detected inflammatory mediators such interleukin-1-β and  interferon-γ. These immune mediators attract what are called  myeloid-derived suppressor cells (MDSC). These immune cells are known to  inhibit the immune system’s most important tumor-specific fighters, the  T cells.

Under the influence of MDSC, it appears as though the T cells stopped rapidly reproducing. This means that sildenafil is capable of neutralizing the chronic inflammation caused by melanoma. The researchers claim that melanoma in mice acts very similarly to how it does in humans. Umansky said that, “it is very well possible that sildenafil can also inhibit the immunosuppressive  effects of inflammation and thus improve antitumor immunity in people  with melanoma”. This could cause much better treatment results for melanoma patients. Here at MoleSafe, we certainly hope they’re on to something!