Researchers at the University of North Carolina have discovered that transcription factors regulating the levels of oxygen in the blood also play a role in the spread of the skin cancer melanoma.
A research team led by William Kim, MD, member of the UNC Lineberger Comprehensive Cancer Center, and graduate student and first author Sara Hanna, linked melanoma metastases to a pair of transcription factors known as HIF1 and HIF2.
Researchers found that HIF1 and HIF2 are over-expressed in melanoma tumours. In healthy cells, HIF1 and HIF2 assist in regulating hypoxia, the state caused by low levels of oxygen in the blood. Hypoxia has been linked to metastases in several solid tumours, and the UNC team has found that it promotes the spread of melanoma from the skin to other sites in the body through the lymphatic system.
Patients who are diagnosed with early stage melanomas have a high rate of survival, but the prognosis worsens significantly once the tumours spread to other sites throughout the body. Using in vitro systems and mouse models, researchers suppressed the expression of HIF1 and HIF2 in the melanoma tumours. While the inactivation of the transcription factors did not reduce the growth of the initial tumours, it did reduce the rate at which the melanoma spread to other sites in the body.
Both HIF1 and HIF2 independently activate the protein kinase SRC using different signalling pathways. The SRC protein has been linked to several different cancers, and the identification of its role in melanoma suggests that existing therapies targeting SRC may prove to be a viable target for therapies aimed at reducing the spread and ultimate lethality of the cancer.
‘What we are trying to do now is inhibit these pathways with drugs in the mice to see if we see a decrease of metastasis,’ said Hanna. University of North Carolina

The 29th Korea International Medical & Hospital Show will take place at COEX in Seoul from 21st to 24th March 2013. The Asian’s premier medical event has been a growing hub of attraction for all those involved in the medical and healthcare industries. Backed by strong demand from Korean consumers, the development of the medical industry in Korea is remarkably fast-growing. In the circumstances, KIMES is filling the role of platform where both manufacturers and consumers can find satisfaction.

Korea, the new hub of healthcare technology
In Korea, medical teams have a particularly keen interest and show a high level of research in new medical technology such as robotic surgery and the U-health care system based on perfect IT infrastructure. The governmental investment and effort to activate the healthcare industry have been increased as well. Against this background, global companies have been making investments and building R&D centres in Korea to strengthen their foothold in export markets. The Korean medical industry is in the limelight as one of the national driving forces for new growth. It should provide new opportunities to a constantly evolving industry.

KIMES heading toward the global medical market
KIMES, which has been growing along with the local medical equipment industry is now set to joint the small club of the world’s prominent specialized medical exhibitions. In its 2012 edition last February, the KIMES Exhibition lined up 458 domestic companies plus 978 companies from a total of 30 countries including USA, Germany, UK, Japan, Italy, Taiwan and China. Up to 30,000 products were on display such as advanced medical equipment, imaging instrumentation, hospital equipment, medical information systems, emergency and surgical equipment and disposable products. About 60,000 visitors are expected for KIMES 2013 where 1,200 companies from 35 countries will cover 38,000 m2 of exhibition space. Also, with the backing of the Global Association of the Exhibition Industry (UFI), KIMES has been playing its role as a gateway to the global medical market while bolstering its reputation as a specialized international medical exhibition.

KIMES at the centre of Asian Network
KIMES has been building a global network not just with America and Europe, but also with Southeast Asia, as well as Central and South Asia and the Middle East, together with overseas associations and related organizations. It provides a wealth of information on the Korean market to overseas purchasing delegations and opens the field of networking for the purchasing process.

KIMES conference attracts thousands of professionals
A number of educational conferences and international forums for medical professionals coincide with the KIMES show and offer a comprehensive educational opportunity for medical professionals. This commitment to education draws a huge audience, which is all benefit to exhibitors.

Porous polymer scaffolds fabricated to support the growth of biological tissue for implantation may hold the potential to greatly accelerate the development of cancer therapeutics.

Researchers at Rice University and the University of Texas MD Anderson Cancer Center in Houston and Mount Sinai Medical Center in New York reported this week that three-dimensional scaffolds used to culture Ewing’s sarcoma cells were effective at mimicking the environment in which such tumours develop.
‘The scaffolds better recapitulate the micro-environment in which tumours grow, as compared with two-dimensional plastic surfaces typically used in cancer research to test anti-cancer drugs,’ said Rice bioengineer Antonios Mikos, who led the research team with Joseph Ludwig, an assistant professor and sarcoma medical oncologist at MD Anderson.

‘We’ve been working to investigate how we can leverage our expertise in engineering normal tissues to cancerous tissues, which can potentially serve as a better predictor of anti-cancer drug response than standard drug-testing platforms,’ Mikos said.

By growing cancer cells within a three-dimensional scaffold rather than on flat surfaces, the team of researchers found that the cells bore closer morphological and biochemical resemblance to tumours in the body. Additionally, engineering tumours that mimic those in vivo offers opportunities to more accurately evaluate such strategies as chemotherapy or radiation therapies, he said.

The project ‘provides a path forward to better evaluate promising biologically targeted therapies in the pre-clinical setting,’ Ludwig said.

Scaffolds fabricated in the Mikos’ lab facilitate the development and growth of new tissue outside the body for subsequent implantation to replace defective tissues.

The team found 3-D scaffolds to be a suitable environment for growing Ewing’s sarcoma, the second most-common pediatric bone malignancy. The tumour growth profile and protein expression characteristics were ‘remarkably unlike’ those in 2-D, Mikos said.

These differences led them to hypothesise that 2-D cultures may mask the mechanisms by which tumours develop resistance to anti-cancer therapeutics, and ‘may lead to erroneous scientific conclusions that complicate our understanding of cancer biology,’ they wrote.

The next challenge is to customise scaffolds to more accurately match the actual conditions in which these tumors are found. ‘Tumors in vivo exist within a complex microenvironment consisting of several other cell types and extracellular matrix components,’ Mikos said. ‘By taking the bottom-up approach and incorporating more components to this current model, we can add layers of complexities to make it increasingly reliable.

‘But we believe what we currently have is very promising,’ he said. ‘If we can build upon these results, we can potentially develop an excellent predictor of drug efficacy in patients.’ Rice University

A protein produced by mast cells in the immune system may predict which people infected with dengue virus will develop life-threatening complications, according to researchers at Duke Medicine and Duke-National University of Singapore (Duke-NUS).
Their study also found that in experiments in mice, a class of drugs commonly used to treat asthma by targeting the mast cells could help treat vascular symptoms associated with dengue infections.
Dengue virus is spread by mosquitoes and infects as many as 390 million people worldwide each year, according to new estimates. It is a significant health issue in tropical areas of the world including parts of Latin America and Asia, but Florida residents have reported cases in recent years.
No treatments are available for dengue virus, and serious cases can result in widespread vascular leakage and haemorrhaging.
In 2011, Duke researchers reported that mast cells, which help the body respond to bacteria and other pathogens, play a role in attacking dengue virus and halting its spread. This finding presented new avenues for research, given the existing classes of drugs that target mast cells or the products of mast cells once they are activated.
In one experiment in the current study of dengue virus in mice, the researchers found that certain classes of drugs commonly used to treat asthma are effective in limiting vascular leakage associated with dengue.
‘It may not seem intuitive how asthma and dengue infection would be related and would respond to the same types of drugs, but because both diseases are promoted by mast cells, the cellular targets of the class of drugs is quite effective,’ said lead author Ashley L. St. John, PhD, assistant professor of emerging infectious diseases at Duke-NUS.
The researchers continued to investigate the role of mast cells in attacking dengue virus in humans, and identified a biomarker – a mast cell-derived product – that appeared to predict the illness’ most severe cases in human patients.
Most patients infected by a dengue virus develop a high fever, dubbed dengue fever, and recover on their own. However, a small number of these cases develop into dengue haemorrhage fever, a dangerous condition marked by serious complications, including bleeding, respiratory distress and severe abdominal pain.
Until now, doctors have not been able to predict who will develop dengue haemorrhage fever. When the researchers studied blood serum samples from patients with dengue infection, they found that the levels of a protein produced by mast cells, chymase, were significantly higher in the patients who developed dengue haemorrhagic fever compared to those who recovered after dengue fever.
‘In addition to revealing a potential new way to diagnose and treat dengue infections, these finding may have much broader applicability for other infectious diseases where vascular leakage is a major pathologic outcome,’ said senior study author Soman N. Abraham, PhD, professor of pathology, immunology, and molecular genetics and microbiology at Duke Medicine and professor of emerging infectious diseases at Duke-NUS. Duke Medicine

 In a study researchers from the University of North Carolina Lineberger Comprehensive Cancer Center have developed a new method to visualise ageing and tumour growth in mice using a gene closely linked to these processes.
Researchers have long known that the gene, p16INK4a (p16), plays a role in ageing and cancer suppression by activating an important tumour defence mechanism called ‘cellular senescence’. The UNC team led by Norman Sharpless, MD, Wellcome Distinguished Professor of Cancer Research and Deputy Cancer Center Director, has developed a strain of mice that turns on a gene from fireflies when the normal p16 gene is activated. In cells undergoing senescence, the p16 gene is switched on, activating the firefly gene and causing the affected tissue to glow.
Throughout the entire lifespan of these mice, the researchers followed p16 activation by simply tracking the brightness of each animal. They found that old mice are brighter than young mice, and that sites of cancer formation become extremely bright, allowing for the early identification of developing cancers.
‘With these mice, we can visualise in real-time the activation of cellular senescence, which prevents cancer but causes ageing. We can literally see the earliest molecular stages of cancer and ageing in living mice.’ said Sharpless.
The researchers envision immediate practical uses for these mice. By providing a visual indication of the activation cellular senescence, the mice will allow researchers to test substances and exposures that promote cellular ageing (‘gerontogen testing’) in the same way that other mouse models currently allow toxicologists to identify cancer-causing substances (‘carcinogen testing’). Moreover, these mice are already being used by scientists at UNC and other institutions to identify early cancer development and the response of tumours to anti-cancer treatments.
‘This work builds on previous work by the same group, as well as others, showing intriguing relationships among aging, cancer and cell senescence. It provides a valuable new tool to probe these relationships,’ said Felipe Sierra, Ph.D., director of the Division of Aging Biology, National Institute on Aging, NIH.
The researchers used these mice to make several unexpected discoveries. First, the group was able to track the accumulation of senescent cells in ageing mice by assessing how brightly each mouse glowed. Surprisingly, the brightest animals were no more likely to die from spontaneous cancer than dimmer animals of the same age. That is, the number of senescent cells in the mouse did not predict its risk of dying.
‘The result we, and I think others, predicted is that the animals with the highest number of senescent cells would get more cancers and die sooner, but this was not the case’ said Sharpless.
Another surprise came from the disparities in p16 levels among the mice. The authors studied a large group of genetically identical animals that were all housed in the same way and fed the same diet. However, despite identical genetic and environmental conditions, the brightness of individual mice at any given age was highly variable, suggesting that factors beyond genetics and diet influence ageing.
The glowing mice also provide a window into the formation of cancers. Expression of p16 is activated in the earliest stages of cancer formation to suppress cancer. Usually activation of p16 prevents cancer, but rarely this tumour suppressor mechanism fails and tumours develop, while still activating the p16 gene. As such, all tumours forming in these mice strongly glowed, allowing researchers to monitor early tumour formation in a wide variety of cancer types. In contrast to expectations, the researchers also found that p16 was activated not only in the tumour cells themselves, but also in normal, neighbouring cells.
‘This finding suggests that activation of senescence results from an abnormal milieu within a developing cancer. Somehow, many or all the cells in a would-be tumour know they are in a bad place, and activate this tumour suppressor gene as a defence mechanism, even if they are not the would-be cancer cells themselves. This occurs really early in the cancer; we’re talking about the earliest events of neoplasia that have ever been measured in living animals,’ said Sharpless.
The Sharpless group believes similar approaches to monitoring senescence can be developed in order to study ageing and tumour development in humans. The group is particularly interested in how cancer therapies influence human ageing and patient outcome. Working with UNC oncologists, the Sharpless group has already measured p16 expression in several hundred patients undergoing cancer therapy. These studies, along with efforts employing the glowing mouse, aims to develop more effective and tolerable patient treatment schemes based upon ‘molecular’, as opposed to ‘chronologic’, age. EurekAlert