Category: Cancer

X-ray crystallography has provided new insights into how the microscopic motorised transport system that operates in our cells is powered. The study could have implications for understanding the symptoms of Down syndrome, the neuromuscular condition Charcot-Marie-Tooth disease, and some cancers, all of which arise through some form of breakdown of this system. The work may ultimately lead to possible new treatments for such disorders.

The researchers behind the work are from Duke University Medical Center, the National Institute of Advanced Industrial Science and Technology in Japan, and the Medical Research Council’s Laboratory of Molecular Biology in the UK. They explain that molecular motors are responsible for driving the separation of chromosomes during cell division. This process does not proceed normally in certain genetic disorders and if unchecked can lead to cancer.

Read the full story in my latest news round-up from spectroscopynow.com

There has been a lot of discussion over the summer as to whether we should all be getting a bit more sun to boost cancer-fighting vitamin D levels. That argument coupled with revelations that suntan creams might themselves boost the risk of skin cancer all fly in the face of the contrary view that we should be staying in the shade.

One thing the sun worshippers and those of tan-free skin agree on – getting sun burn is no fun. Now, researchers in England (A country fabled for its sunny climes) are giving volunteers a tan in a bid to find a treatment for sunburn. Anna Nicolaou of the University of Bradford, in the renowned sunspot of the North of England, is examining the biological mechanisms underlying sunburn and why it particularly affects people who don’t get a “good” tan.

The research team hopes to discover whether melanocytes that do not actively produce melanin discharge inflammatory mediators, including pro-inflammatory hormones called prostaglandins, which cause the redness, irritation and swelling of the skin that is observed in sunburn. They also hope to discover why people who tan easily are less likely to develop sunburn, contrasting to pale-skinned people who tend to sunburn easier.

You can find out more via the Bradford U press site.

Meanwhile, at the other end of the beach.

A new light-activated ingredient that mops up damaging iron could help reduce the effects of sunburn, according to research published in the Journal of Investigative Dermatology by UK scientists.

‘When skin is exposed to high doses of sunlight, such as when you are sunbathing, a massive amount of free iron is released in skin cells,’ explains Pourzand, ‘This free iron can act as catalysts for the generation of more harmful free radicals that cause severe cell damage.”

The net effect of mopping up iron released as the skin burns, is to reduce inflammation and pain, which are exacerbated by iron, and to prevent the build up of free radicals, which have been linked to an increased risk of skin cancer.

The researchers, Charareh Pourzand of the University of Bath and James Dowden, now at Nottingham University, are currently testing prototypes of the ingredient in the lab using three-dimensional human skin cultures and anticipate trialling the ingredient with human volunteers in the next two to three years.

Find out more at the Bath U press site

When I first wrote about the doubts scientists were raising concerning sunscreens in Chem & Industry magazine some time in the early 1990s, it seemed that the findings would simply confuse consumers and cause a storm among manufacturers. Unfortunately, that doesn’t seem to be the case, sun worshippers carried on frying themselves, slapping on only meagre amounts of purportedly protective cream, partly out of laziness and partly because it is just so expensive and manufacturers continued to sell their products by the bucket load. Then research emerged that showed lack of sun exposure not only risks rickets but could increase the chances of you getting internal cancers, as opposed to the much feared skin cancer. As if consumers were not confused enough.

Now, US researchers have shown that applying too little suncream can actually turn the UV-absorbing chemicals against you.

When skin is exposed to sunlight, ultraviolet radiation (UV) is absorbed by skin molecules that then can generate harmful compounds, called reactive oxygen species or ROS, which are highly reactive molecules that can cause “oxidative damage.” For example, ROS can react with cellular components like cell walls, lipid membranes, mitochondria and DNA, leading to skin damage and increasing the visible signs of aging. The link with skin cancer itself is actually not so clear cut as some lobbyists claim.

However, when sunscreen is applied to the skin the UV filters in the sunscreen, reduce the amount of UV radiation penetrating the skin. Over time, though, the filters themselves are absorbed by the skin leaving the surface vulnerable to UV once more. The UV filters (octylmethoxycinnamate, benzophenone-3 and octocrylene) widely used in sunscreens themselves generate reactive oxygen species (ROS) in skin when exposed to ultraviolet radiation, augmenting the ROS that is naturally produced. [These new results are similar to those on which I reported in C&I ten years ago, DB]

Kerry Hanson of the University of California Riverside and colleagues now report that these three UV filters only work well if sunscreen is reapplied frequently to prevent ultraviolet radiation from reaching these filters. Without reapplication, these compounds could be just as harmful as not using sunscreen at all.

The team will publish their findings in a forthcoming issue of Free Radical Biology & Medicine.

“Sunscreens do an excellent job protecting against sunburn when used correctly,” said Hanson, who works in the laboratory of Christopher Bardeen, an assistant professor of chemistry at UCR. “This means using a sunscreen with a high sun protection factor and applying it uniformly on the skin. Our data show, however, that if coverage at the skin surface is low, the UV filters in sunscreens that have penetrated into the epidermis can potentially do more harm than good. More advanced sunscreens that ensure that the UV-filters stay on the skin surface are needed; such filters would reduce the level of UV-induced ROS. Another solution may be to mix the UV-filters with antioxidants since antioxidants have been shown to reduce UV-induced ROS levels in the skin.”

“For now, the best advice is to use sunscreens and re-apply them often — the Skin Cancer Foundation recommends every two hours, and especially after sweating or swimming, which can wash away sunscreen — to reduce the amount of UV radiation from getting through to filters that have penetrated the skin,” Bardeen said. “This, in turn, would reduce ROS generation.”

But, having read this please also read my write-up on how to sunbathe safely

Could researchers in Australia have developed a pharmaceutical panacea to beat all those herbal remedies offered in a multitude of spam emails and websites that claim to cure everything. They are working pre-clinical models of a new class of drug that could treat a range of problems from inflammation and cancer to eye and heart disease.

Certain types of skin cancers, age-related macular degeneration (AMD) and diabetic retinopathy are likely to be among the first uses for the drug, which has already shown efficacy in pre-clinical models.

“This may be a ‘one-size fits all’ therapy, because it targets a master regulator gene called c-Jun which appears to be involved in all of these diseases,” explains Levon Khachigian, of the Centre for Vascular Research (CVR), at the University of New South Wales. “c-Jun is an important disease-causing gene,” adds Khachigian. “It stands out because we don’t see much of it in normal tissue but it is highly expressed in diseased blood vessels, eyes, lungs, joints, and in the gut — in any number of areas involving inflammation and aggressive vascular growth.

The experimental drug they are testing goes by the enigmatic name of Dz13, and with equal enigma behaves like a secret agent finding its target, c-Jun, and killing it point blank. “It is a specific, pre-programmed ‘molecular assassin’,” says Khachigian.

He and colleagues report full details in Nature Biotechnology this month. The next step will be to test the drug in a small human trial on non-melanoma skin cancers. “If such a trial were successful, it would be a significant development given the high rates of skin cancer and because the main treatment currently is surgical excision, which can cause scarring,” said Khachigian.

The drug Cesamet (nabilone), a derivative of tetrahydrocannabinol, was “re-approved” for the clinical market this week for use in treating the side-effects of cancer chemotherapy, including nausea and vomiting. Genetic Engineering News reports that Valeant Pharmaceuticals International (NYSE:VRX) announced that the US Food and Drug Administration (FDA) has given marketing approval for Cesamet (CII) (nabilone) oral capsules. The drug interacts with the CB1 cannabinoid receptor found throughout the nervous system, its interaction with this receptor calms nausea and stifles the vomiting reflex something that many chemo patients would welcome.

What is particularly intriguing though is that this drug made a brief appearance on the pharma market in the 1980s before being pulled. Why? You may well ask. Perhaps attitudes to marijuana were less liberal than today leading ethical committees to feel that derivatives of their active ingredient are acceptable whereas during 1980s they were not. Or, perhaps it is simply that other anti-emetics on the market were at the time more successful with most patients and did not have the negative connotations of illicit drug use associated with them. Now, more than twenty years later those anti-emetics are off-patent and only making generics manufacturers a profit. The time was thus ripe for a new drug to take their place. I could be wrong, Cesamet’s patent was approved on Boxing Day 1985 so it too may have only a short shelf life.

Any Sciencebase readers with insider info on this are welcome to add a comment to this post.

Meanwhile you can subscribe to the print edition of Genetic Engineering News for free here.

Philippa Darbre of the University of Reading, England, has published a review of the putative health effects of organometallic compounds that mimic estrogen and could increase the burden of “aberrant oestrogen signalling within the human breast”. Of particular relevance to public health is her suggestion that the aluminum compounds used in the manufacture of underarm antiperspirants may somehow be involved in an increased risk of breast cancer. The paper is already causing a stir in the UK, however, it is also causing controversy particularly because it does not represent any new experimental evidence but draws new conclusions from other studies.

You can read the full story in Issue 53 of chemistry webzine Reactive Reports, out now!!!

French researchers have identified almost 700 genes in the tumours of colorectal cancer patients
whose expression was different between patients who subsequently responded well to combined chemotherapy and patients who were resistant to the therapy. The findings could ultimately help cancer specialists decide which course of treatment for patients with colorectal cancer is most likely to work best.

Sandrine Imbeaud from the CNRS and Pierre and Marie Curie University, Villejuif, France, used microarrays to analyse the gene-expression patterns of samples from colon tumours and liver metastases collected from 13 patients with colorectal cancer. The microarray analyses were carried out before the patients were treated with combined chemotherapy of folinic acid,
5-fluorouracil and irinotecan. The team identified 679 genes that were produced differently in patients who later responded well to chemotherapy.

Details of the research were published today in the journal Genome Biology.