No Clear Connection Between Mobile Phone Use And Brain Cancer, International Study Concludes

According to a study conducted in five Northern European countries, there is no clear connection between mobile phone use and malignant brain tumours. The results of the study were published in the web version of the International Journal of Cancer on 19th January.


The study on the possible connection between mobile phone use and the risk of a malignant brain tumour, glioma, was carried out in Denmark, Finland, Norway, Sweden and England. The study showed that mobile phone users were not at an increased risk of developing a glioma.

Regular use of a mobile phone, duration of use, or the cumulative number of calls had no effect on the risk. The only indication of a potential effect was found among mobile phone users who had used a mobile phone for at least 10 years. They were found to have a slightly increased risk of a tumour on the side of the head on which they held the phone. Information on mobile phone use was collected using personal interviews. There is always a risk of error associated with recall, which affects the reliability of the results.

The research data from the participating countries was analysed by the Radiation and Nuclear Safety Authority (STUK). Funding for the study in Finland was provided by the Emil Aaltonen Foundation, Academy of Finland and Doctoral Programs for Public Health (DPPH).

The most extensive study so far

The study data collected between 2000 and 2004 included 1,521 glioma patients and 3,301 healthy controls. The number of people who had used a mobile phone for longer than 10 years was higher (222) than in previous studies.

"Even though the results do not indicate that mobile phone use increases the risk of cancer, we need more research data on long-term use," says Anssi Auvinen, Research Professor at the Radiation and Nuclear Safety Authority.

The completion of an extensive international study (INTERPHONE) on the connection between the use of mobile phone and brain tumour based on data collected in 14 countries is expected in the future.

Novel EGFR Antibody Outperforms Cetuximab in Mouse Model of Lung Cancer

Antibodies that selectively bind and destroy cancer cells represent some of the most promising cancer therapy approaches being developed today. Several of these antibodies have reached the market, including cetuximab (Erbitux®, ImClone Systems), which targets the epidermal growth factor receptor (EGFR) protein. However, a study conducted at the Dana-Farber Cancer Institute and the Ludwig Center at Dana-Farber/Harvard Medical School now suggests that antibodies binding a particular protein conformation, caused by hyperactivation, might have distinct therapeutic advantages over antibodies, like cetuximab, that bind to wild-type (normal) target proteins.

The study, led by Dana-Farber Cancer Institute's Dr. Kwok-Kin Wong, and published today in the Journal of Clinical Investigation, is part of a multi-center, international effort to assess the clinical potential of the 806 antibody. The 806 antibody was discovered by scientists at the Ludwig Institute for Cancer Research. The antibody targets EGFR only when the receptor has been activated by mutations, by the protein's over-expression or by amplification of the EGFR gene. In the present study, Dr. Wong compared the action of cetuximab and 806 in a mouse model of non-small cell lung cancer (NSCLC) caused by different activating mutations in EGFR.. The 806 antibody caused a dramatic tumor regression in the mice, while cetuximab did not.

"Cetuximab only works on a subset of patients with lung cancers," says Wong. "We think the 806 antibody might benefit those patients who respond to cetuximab but, more importantly, might also be effective for those patients who don't." According to Dr. Wong, approximately 10-30 percent of patients with NSCLC and 5 percent of patients with squamous cell lung cancers have EGFR activating mutations. Some brain tumors also have EGFR activating mutations that are - in animal studies - responsive to the 806 antibody. A phase I clinical trial of the 806 antibody has been completed in Melbourne, Australia by the Ludwig Institute for Cancer Research co-authors. The antibody was shown to target a variety of cancers, including squamous cell lung cancer, with no targeting of normal tissues and no toxicity.

Scientists Discover How Body Fights To Control Spread Of Cancer

Scientists at the University of Liverpool have found how two molecules fight in the blood to control the spread of cancer cells.

Researchers discovered that a large protein, which forms a protective shield around cancer cells and prevents them from causing secondary tumours, is attacked by a small protein that exists in the blood.

In diseases such as breast, lung and colorectal cancer, infected cells lose growth control and eventually form tumours at these sites. If caught early these tumours can be effectively removed surgically. However, when the cancer cells have invaded the blood, the
effectiveness of surgery is reduced.

Cancerous cells that have entered the blood, however, are still prevented from causing further disease by the protective shield of a protein called MUC1 in which the cancerous cells are eventually destroyed by our immune system. Scientists have now discovered how this protective shield is broken down, allowing cancer to spread throughout the body.

Dr Lu-Gang Yu, from the University's School of Clinical Sciences, explains: "MUC1 on the cell surface prevents the cancer cells from attaching to the blood vessel wall which causes secondary tumours. We have discovered that a small protein called galectin-3, attacks MUC1 and breaks up its protective shield, forcing large areas of the cancer cell to become exposed. The exposed areas of the cell allow the cancer to attach to the blood vessel wall. The cancer cells then eventually penetrate the blood wall to form tumours at secondary sites.

"The attachment of cancer cells to the blood vessel wall is one of the key steps in the spread of cancer. It has been known for a few years that galectin-3 concentration is significantly higher in the blood of cancer patients than in healthy people but until now scientists did not know whether this increase played any role in the spread of cancer. Our study indicates that galectin-3 may play a critical role and may have significant implications for future developments of drugs for the treatment of the disease."

Dr Yu's work is published in the Journal of Biological Chemistry.

New Drug May Help Prolong Survival For Head And Neck Cancer Patients

 Preliminary findings show adding the chemotherapy drug cetuximab (brand name Erbitux) to radiation therapy and chemotherapy may help some patients with head and neck cancer live longer, according to a study presented at the plenary session of the Multidisciplinary Head and Neck Cancer Symposium, co-sponsored by the American Society for Therapeutic Radiology and Oncology, the American Society for Clinical Oncology and the American Head and Neck Society. Researchers are recommending a larger trial to prove definitively if cetuximab combined with radiation helps improve survival for these patients.

Researchers at the University of Maryland Medical Center in Baltimore designed the study to evaluate the efficacy of the addition of cetuximab with concurrent chemotherapy and radiation in patients with locally advanced squamous cell carcinoma of the head and neck in order to improve local regional control and overall survival. Currently 21 patients are enrolled in this study. Initially they received an initial dose of cetuximab followed then by weekly doses of the drug. Patients also received daily radiation therapy treatments and weekly doses of chemotherapy.

Of the 21 patients, 18 have completed all therapy and were available for analysis of toxicity and response. No grade 4 toxicities were reported, however 89 percent reported mouth pain and 11 percent reported skin problems. Other toxicities included difficulty swallowing, fever and a drop in white blood cell count. Seventy-two percent achieved a complete response two months after completion of therapy. Ultimately, 95 percent were disease free after all therapy.

"Given the advanced stages of disease that patients have on this study, these results point to the potential of increasing the therapeutic gain for patients. We now need a phase III study to determine if adding this drug is better than the current standard of care," said Mohan Suntharalingam, M.D., lead author of the study and a radiation oncologist at the University of Maryland. "I encourage people with disease and their family members to ask their doctors about participating in this clinical trial."

For more information on radiation therapy for head and neck cancer, visit http://www.rtanswers.org.

The abstract, "Initial Report of Phase II Trial of Weekly Cetuximab, CBDCA, Paclitaxel and Daily RT in Patients with Locally Advanced SCCHN," will be presented at the plenary session on January 18, 2007. To speak to the lead author of the study, Mohan Suntharalingam, M.D., please call Beth Bukata.

Brain Stem Cells Against Cancer?

Gliomas are a group of brain tumors where the most common type is also the most aggressive one. Chemotherapy and radiation have little effect on malignant gliomas, and patients survive only about a year after being diagnosed. But research at Lund University in Sweden provides hope that it may be possible in the future to develop stem cells from the brain into a new way to treat gliomas.

Neural stem cells have been shown to have the ability to recognize signals from tumor cells in the brain and migrate there. If stem cells are injected into a part of the brain in laboratory animals with a glioma in another part of their brain, the stem cells migrate over to the tumor area.

This has spawned the idea of having stem cells transport drugs or immune stimulants to the tumor. This was the principle the Lund scientists wanted to test. But as it turned out, no extra assistance was needed: the stem cells themselves had the ability to combat the tumor.

"We were truly amazed when we saw this effect! To be sure about the phenomenon, we ran several experiments with other stem cells, and it was confirmed that certain neural stem cells actually have an anti-tumor effect," says Karin Staflin. She is describing the findings in her dissertation, which she will soon defend.

It is as yet unknown just why this happens. One plausible reason is that both normal neural stem cells and glioma cells are immature, not fully mature cells. They are therefore more like each other than any other types of cells in the brain, which may enable them to 'speak' to each other and influence each other. The research team at Lund has also shown that stem cells can cure colon cancer in lab animals.

"Cells in aggressive malignant cancer forms are often characterized as being more immature than their environment. This may be what enables neural stem cells to affect intestinal cancer cells," says Karin Staflin.

Many years of research remain before the newly discovered principle is ready to be tested on humans. First, researchers need to learn to understand the mechanisms better and identify the factors in neural cells which make them so effective. The notion is still new, but it does provide a glimmer of hope for a cure for a thus far incurable disease.

Small Molecule Offers Big Hope Against Cancer

DCA is an odourless, colourless, inexpensive, relatively non-toxic, small molecule. And researchers at the University of Alberta believe it may soon be used as an effective treatment for many forms of cancer.

Dr. Evangelos Michelakis, a professor at the U of A Department of Medicine, has shown that dichloroacetate (DCA) causes regression in several cancers, including lung, breast, and brain tumors.

Michelakis and his colleagues, including post-doctoral fellow Dr. Sebastian Bonnet, have published the results of their research in the journal Cancer Cell.

Scientists and doctors have used DCA for decades to treat children with inborn errors of metabolism due to mitochondrial diseases. Mitochondria, the energy producing units in cells, have been connected with cancer since the 1930s, when researchers first noticed that these organelles dysfunction when cancer is present.

Until recently, researchers believed that cancer-affected mitochondria are permanently damaged and that this damage is the result, not the cause, of the cancer. But Michelakis questioned this belief and began testing DCA, which activates a critical mitochondrial enzyme, as a way to "revive" cancer-affected mitochondria.

The results astounded him.

Michelakis and his colleagues found that DCA normalized the mitochondrial function in many cancers, showing that their function was actively suppressed by the cancer but was not permanently damaged by it.

More importantly, they found that the normalization of mitochondrial function resulted in a significant decrease in tumor growth both in test tubes and in animal models. Also, they noted that DCA, unlike most currently used chemotherapies, did not have any effects on normal, non-cancerous tissues.

"I think DCA can be selective for cancer because it attacks a fundamental process in cancer development that is unique to cancer cells," Michelakis said. "Cancer cells actively suppress their mitochondria, which alters their metabolism, and this appears to offer cancer cells a significant advantage in growth compared to normal cells, as well as protection from many standard chemotherapies. Because mitochondria regulate cell death--or apoptosis--cancer cells can thus achieve resistance to apoptosis, and this appears to be reversed by DCA."

"One of the really exciting things about this compound is that it might be able to treat many different forms of cancer, because all forms of cancer suppress mitochondrial function; in fact, this is why most cancers can be detected by tests like PET (positron emission tomography), which detects the unique metabolic profile of cancer compared to normal cells," added Michelakis, the Canada Research Chair in Pulmonary Hypertension.

Another encouraging thing about DCA is that, being so small, it is easily absorbed in the body, and, after oral intake, it can reach areas in the body that other drugs cannot, making it possible to treat brain cancers, for example.

Also, because DCA has been used in both healthy people and sick patients with mitochondrial diseases, researchers already know that it is a relatively non-toxic molecule that can be immediately tested in patients with cancer.

Furthermore, the DCA compound is not patented and not owned by any pharmaceutical company, and, therefore, would likely be an inexpensive drug to administer, Michelakis added.

However, as DCA is not patented, Michelakis is concerned that it may be difficult to find funding from private investors to test DCA in clinical trials. He is grateful for the support he has already received from publicly funded agencies, such as the Canadian Institutes for Health Research (CIHR), and he is hopeful such support will continue and allow him to conduct clinical trials of DCA on cancer patients.

"This preliminary research is encouraging and offers hope to thousands of Canadians and all those around the world who are afflicted by cancer, as it accelerates our understanding of and action around targeted cancer treatments," said Dr. Philip Branton, Scientic Director of the CIHR Institute of Cancer.

Michelakis's research is currently funded by the CIHR, the Canada Foundation for Innovation, the Canada Research Chairs program, and the Alberta Heritage Foundation for Medical Research.

Statin Plus Cancer Drug Deliver Combo Punch To Brain Cancer Cells

Building on newly discovered genetic threads in the rich tapestry of biochemical signals that cause cancer, a Johns Hopkins Kimmel Cancer Center team has dramatically killed brain cancer cells by blocking those signals with a statin and an experimental antitumor drug.

The unlikely pairing of cholesterol-lowering lovastatin and cyclopamine killed 63 percent of medulloblastoma cells grown in the laboratory. By contrast, using either agent alone wiped out fewer than 20 percent of cells. The Hopkins researchers published their findings in the January issue of the American Journal of Pathology.

The researchers caution that the cyclopamine-lovastatin combination has yet to be tested in animals, much less people, but they conclude that the tumor cell-killing by the combo is tantalizing. Cyclopamine works by blocking the so-called "hedgehog" pathway, long known to promote and guide cell and organ growth. Excessive growth is the chief characteristic of cancer. The investigators believe that blocking hedgehog with cyclopamine makes cancer cells more susceptible to lovastatin.

Along with its cholesterol-clogging effects, lovastatin, sold under the trade name Mevacor, is known to curb destruction of proteins that put the brakes on cell growth, causing cancer cells to self-destruct through a process called apoptosis. The effects of the statin already is being studied in people at high risk for the deadly skin cancer, melanoma.

First extracted from corn lilies in the 1950s, cyclopamine is a powerful toxin known to stunt fetal development and cause birth defects in humans and animals. Its connection to anti-cancer efforts grew out of later insights into its blockage of hedgehog, which gets its name from spiky hairs that develop on fruit flies lacking the signal.

"We already knew from earlier research that hedgehog controls brain cell survival and growth, and that blocking signals in this pathway may stop uncontrolled growth of cancer cells," says Charles Eberhart, M.D., Ph.D., associate professor of pathology, ophthalmology and oncology. "But the new work shows the hedgehog blockade may halt another powerful cell-survival signal, and lovastatin could provide the added boost necessary to kill more cancer cells."

Specifically, Eberhart found links between the expression of key hedgehog-related genes in medulloblastoma cells and another cell signal already tied to cancer, Bcl-2. Eberhart and his team believed that combination of a hedgehog blockade and a pro-apoptosis drug like lovastatin would kill more cancer cells.

"Our experiments suggest that hedgehog's action is woven together with Bcl-2, best known for its role in causing B-cell lymphomas," he says. "Cancer cells thwart suicide by overproducing Bcl-2, assuring them a long life."

When the Hopkins researchers noticed that Bcl-2 and hedgehog expression increased in tandem in medulloblastoma cells, they tried adding hedgehog-blocking cyclopamine to the cells and found that Bcl-2 production dwindled and tumor cells died off. Lead author and pathology fellow Eli E. Bar, Ph.D., said he was "surprised by the degree to which the drug combination was so effective."

The study was supported by the National Institute of Neurological Disorders and Stroke. Coauthors were Aneeka Chaudhry and Mohamed H. Farah.