April 21, 2008, 8:15 PM CT

Cancer cells spread by releasing 'bubbles'

A new fundamental mechanism of how tumour cells communicate has just been discovered by the team of Dr. Janusz Rak at the Research Institute of the McGill University Health Centre (MUHC) in collaboration with Dr Guha from the University of Toronto.

The cancer cells are able to communicate with their more healthy counter-parts by releasing vesicles. These bubble-like structures contain cancer-causing (oncogenic) proteins that can trigger specific mechanisms when they merge into non or less-cancerous cells. These findings could change our view on how malignant tissues work and lead to major clinical innovations. They were published on April 20 in the on-line edition of Nature Cell Biology.

The surface of some brain tumour cells has long been known to express a mutated version of what is called the variant III epidermal growth factor receptor (EGFRvIII). Eventhough this factor is expressed only in a fraction of tumour cells, it has a major impact on the malignancy of the whole tumor. How could this cellular minority have such an important impact" This mechanism was still unknown until now.

This study shows that the mutated EGFRvIII triggers production of small vesicles that project from the cell membrane and that carry mutated copies of EGFRvIII on their surfaces. They were baptised oncosomes. Surprisingly enough, this shows that oncoproteins are not always confined to the cell that produced them. In this case they even migrate!........ Posted by: Andria      Read more         Source

April 17, 2008, 8:25 PM CT

Tiny magnets offer breakthrough in gene therapy for cancer

A revolutionary cancer therapy using microscopic magnets to enable 'armed' human cells to target tumours has been developed by scientists funded by the Biotechnology and Biological Sciences Research Council (BBSRC). Research published online today (17 April) in the journal, Gene Therapy, shows that inserting these nanomagnets into cells carrying genes to fight tumours, results in a number of more cells successfully reaching and invading cancerous tumours.

Using human cells as delivery vehicles for anti-cancer gene treatment has long been an attractive approach for treating tumours, but these cells commonly reach tumours in insufficient numbers to effectively attack them. Now, a new 'magnetic targeting' method has been developed to overcome this problem by Professor Claire Lewis at the University of Sheffield, Professor Jon Dobson at the University of Keele, and Professor Helen Byrne and Dr. Giles Richardson at the University of Nottingham.

The technique involves inserting nanomagents into monocytes - a type of white blood cell used to carry gene treatment - and injecting the cells into the bloodstream. The scientists then placed a small magnet over the tumour to create a magnetic field and observed that this attracted a number of more monocytes into the tumour......... Posted by: Andria      Read more         Source

April 13, 2008, 8:58 PM CT

Vitamin D and calcium influence cell death in the colon

Scientists at Emory University are learning how vitamins and minerals in the diet can stimulate or prevent the appearance of colon cancer.

Emory researchers will present their findings on biological markers that could influence colon cancer risk in three abstracts at the American Association for Cancer Research meeting in San Diego.

In a clinical study of 92 patients, supplementing diet with calcium and vitamin D appeared to increase the levels of a protein called Bax that controls programmed cell death in the colon. More Bax might be pushing pre-malignant cells into programmed cell death, says Emory researcher Veronika Fedirko, who will present her team's results (abstract 464).

Prior studies have shown that calcium and vitamin D tend to reduce colon cancer risk.

"We were pleased that the effects of calcium and vitamin D were visible enough in this small study to be significant and reportable," Fedirko says. "We will have to fully evaluate each marker's strength as we accumulate more data".

The studies of colorectal biopsy samples are part of a larger effort to identify a portfolio of measurements that together can gauge someone's risk of getting colon cancer, says Roberd Bostick, MD, MPH, professor of epidemiology at Emory's Rollins School of Public Health......... Posted by: Andria      Read more         Source

April 9, 2008, 9:49 PM CT

A better mouse model for cancer research

Scientists at Boston College have developed the first laboratory mouse model that mimics cancers spread through the human body. Using their novel cell line, the team discovered one of the bodys primary defensive cells plays a role in cancers attack.

The development of a new animal model a line of cancer cells injected into a laboratory mouse that displays the full spectrum of systemic metastatic cancer in humans removes a "scientific stumbling block" in advancing cancer research and potential therapys, as per Boston College Biologist Thomas Seyfried, whose findings appear this week in the online version of the International Journal of Cancer and will be presented at the annual meeting of the American Association of Cancer Research in San Diego.

"What we have developed is the first model in the mouse that replicates all of the hallmarks of metastatic cancer," said Seyfried, the project leader. Now, we have a tool that can be effective in identifying basic mechanisms and new therapies to treat the disease.

Scientists produced two cell lines that when injected into mice express all the major biological processes of metastasis. A third line, when injected, grew rapidly, but did not lead to metastatic cancer.

Prior mouse models contain limitations in effectiveness and speed. A number of models fail to produce cancer in each animal subject and it often takes several months before cancer is detected. In other models, cancer cells are transplanted into animals with disabled immune systems. Within three weeks, the two Seyfried models produced tumors in 100 percent of the mice, which had healthy immune systems......... Posted by: Andria      Read more         Source

April 8, 2008, 10:24 PM CT

Double binding sites on tumor target

Scientists from the University of Pennsylvania School of Medicine and his colleagues at Merck Serono Research in Gera number of have observed that two drugs bind to receptor sites on some tumors in different places at the same time, suggesting the possibility of a new combination treatment for certain types of cancer.

An increasing number of therapies targeting tumors that have proteins called epidermal growth factor receptors (EGFR) sitting on their surface are already being used in the clinic or are in late stages of development. For example, Herceptin is an established therapy for certain types of breast cancer and Erbitux and Vectibix are in use for other types of cancer. An additional drug called matuzumab is in phase II clinical trials.

Three years ago, Kate Ferguson, PhD, Assistant Professor of Physiology, and his colleagues determined the precise molecular details of how Erbitux, a colorectal and head and neck cancer drug, binds to its target on cancer cells. EGFR drugs halt cell proliferation by blocking EGFRs molecular doorway, keeping hormones from binding and signaling tumor growth. X-ray crystallography provided a snapshot of the interaction between Erbitux and the extracellular component of the cancer cells receptors.

As is characteristic of a number of epithelial cancers - such as cancers of the colon, head and neck, breast, ovary, lung, and pancreas - the surface of cancer cells possess abnormally high levels of EGFR. In a cancer cell, an extracellular hormone binds to the outer piece of EGFR, and causes the inside part to kick off a series of reactions that signal the malignant cell to replicate and divide......... Posted by: Andria      Read more         Source

March 26, 2008, 9:53 PM CT

Anti-cancer drugs and new de-methylating agents

Scientists at the National Sun Yat-Sen University and Kaohsiung Medical University, Kaohsiung, Taiwan have revealed a new mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) attenuate tumor invasion and metastasis. The research, would be reported in the April 2008 issue of Experimental Biology and Medicine, provides new insights for the understanding of the anti-cancer effects of NSAIDs.

NSAIDs have been used for the suppression of pain and inflammation in the clinic for a number of years. The main targets of these drugs are cyclooxygenases (COXs) which play critical roles in maintaining physiological homeostasis, mediating inflammatory reactions and promoting tumorigenesis. However, COX-independent effects are also important for the inhibition of cancer development by NSAIDs. Indeed, NSAIDs are considered as a novel class of effective chemopreventive drugs.

The research team, led by Wen-Chun Hung, Dean of College of Science, National Sun Yat-Sen University, and a recent doctorial graduate Mei-Ren Pan and two collaborators Hui-Chiu Chang and Lea-Yea Chuang of Kaohsiung Medical University observed that NSAIDs up-regulated several anti-metastatic genes including secreted protein acidic and rich in cysteine (SPARC), thrombospindin-1 (TSP-1), TSP-3 and tissue inhibitors of metalloproteinase-2 (TIMP-2) in human lung cancer cells. Our functional assay suggested that increases of SPARC and other anti-metastatic genes were important for NSAIDs to inhibit tumor invasion and metastasis said Wen-Chun Hung. More importantly, we elucidated the underlying mechanism and demonstrated that up-regulation of SPARC in human lung cancer cells was mediated via inhibition of DNA methyltransferases (DNMTs) expression and promoter de-methylation. This is the first report to show that NSAIDs may inhibit the expression of DNMTs to reverse promoter methylation and to reactivate gene transcription......... Posted by: Andria      Read more         Source

March 16, 2008, 9:29 PM CT

Halting the growth of a childhood brain cancer

A discovery by St. Jude Childrens Research Hospital researchers suggests a safer way to treat medulloblastoma, a rare but often fatal childhood brain tumor. The group observed that one of the brains signaling pathways inhibits the growth of the highly aggressive cancer cells.

The scientists discovered that three proteins, designated BMP2, BMP4 and BMP7, halted the growth of medulloblastoma tumors and induced the cancerous cells to develop into normal neurons.

We think we have identified a pathway that can be used to prevent tumor formation and a potential target for treatment, said Martine F. Roussel, Ph.D., a member of the St. Jude Department of Genetics and Tumor Cell Biology. A report on this work appears in the March 15 issue of Genes & Development. Roussel is the papers senior author.

Medulloblastoma occurs in the cerebellum, which is located in the lower, rear part of the brain. This cancer strikes about 350 young children in the United States annually. Eventhough treated patients have an overall five-year survival rate of 70 percent, conventional therapies combining surgery, irradiation and chemotherapy frequently lead to permanent neurocognitive impairment.

Several research teams are seeking to decipher the intricate signaling mechanisms that govern the proliferation of cells called granule neuron progenitors (GNPs). These cells go on to develop into neurons in the cerebellum during the first year of life. But the disruption of this differentiation process can trigger medulloblastoma......... Posted by: Andria      Read more         Source

March 12, 2008, 9:43 PM CT

Cause of severe allergic reaction to cancer drug

Clinicians have been perplexed by the fact that some patients given the drug cetuximaban immune-based treatment usually used to treat persons diagnosed with head and neck cancer, or colon cancerhave a severe and rapid adverse reaction to the drug. Sometimes the reaction includes anaphylaxis, a life-threatening condition characterized by a drop in blood pressure, fainting, difficulty breathing, and wheezing. Now scientists funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, have discovered that specific pre-existing antibodies cause the severe reaction to the drug. This discovery in turn has enabled them to explain the unusual geographic pattern of this reaction seen among individuals in the United States. The unusual findings of this investigation appear in a report reported in the March 13 edition of the New England Journal (NEJM).

These intriguing research findings not only are potentially important to physicians treating certain cancer patients, but also may have broader implications for the use of immunotherapies for other diseases, notes Anthony S. Fauci, M.D., NIAID director.

NIAID grantee Thomas Platts-Mills, M.D., Ph.D., who heads the Division of Allergy and Clinical Immunology at the University of Virginia, led a research study to investigate the cause of the clinical problem with cetuximab. Their newly reported findings are of immediate importance in the care of cancer patients, says Dr. Platts-Mills. Because of the widespread use of cetuximab in cancer therapy, it may be useful to pre-screen patients for specific IgE antibodies to cetuximab to identify those who are at risk for serious adverse reactions, including anaphylaxis......... Posted by: Andria      Read more         Source

March 9, 2008, 6:06 PM CT

Fugitive cancer cells can be blocked

Cancer cells get a helping hand from platelets, specialized blood cells involved in clotting. Platelets shelter and feed tumor cells that stray into the bloodstream, making it easier for cancer to spread, or metastasize. Research at Washington University School of Medicine in St. Louis suggests that inactivating platelets could slow down or prevent metastasis.

In advance online publication in the Journal of Cellular Biochemistry, the scientists report that a combination of two platelet inhibitors reduced the number and size of breast cancer or melanoma tumors that grew in the bones of laboratory mice.

One of the drugs was aspirin, a widely used inhibitor of platelet clotting. The other was an experimental drug, APT102, which also prevents platelet clotting, but by a different mechanism. Both drugs were needed to reduce bone tumors.

"Past research has shown that tumor cells activate platelets and that mice with defective platelets have significantly fewer metastases," says Katherine Weilbaecher, M.D., assistant professor of medicine and of cell biology and physiology. "We also know that platelets have several traits that can aid tumor cells, and we are working to break up that potentially lethal partnership".

Metastasis of cancer cells to sites away from the main tumor can cause pain and other symptoms and greatly increases the likelihood a patient will die of the disease. In fact, more than 90 percent of cancer deaths are the result of metastasis, which is difficult to control with current therapies......... Posted by: Andria      Read more         Source

March 5, 2008, 8:56 PM CT

Updated colorectal cancer screening guidelines

The American Cancer Society, the American College of Radiology, and the U.S. Multi-Society Task Force on Colorectal Cancer (a group that comprises representatives from the American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy) have released the first-ever joint consensus guidelines for colorectal cancer screening. The guidelines add two new tests to the list of recommended options: stool DNA (sDNA) and CT colonography (CTC), also known as virtual colonoscopy, and for the first time include a preference for screening tests that can not only detect cancer early but also detect premalignant polyps, as those tests provide a greater potential for cancer prevention through polyp removal.

The guidelines, which represent the most current scientific evidence and expert opinion available, also outline quality elements essential to each of the recommended testing methods. They will appear in the May/recent issue of CA: A Cancer Journal for Clinicians, and are published early online on CA First Look and will also be published in upcoming issues of the journals Gastroenterology and Radiology.

In addition to the new tests, the focus on quality and the new delineation of tests into two major types, the expert panel also concluded that any proposed colorectal screening test that has not been shown in the medical literature to detect the majority of cancers present at the time of testing should not be offered to patients for colorectal cancer screening. That includes some types of previously endorsed guiaic-based stool tests......... Posted by: Andria      Read more         Source