Herceptin

Targets Breast Cancer Stem Cells

Science (July 13, 2008) — A gene that is overexpressed in 20 percent of breast cancers increases the number of cancer stem cells, the cells that fuel a tumor’s growth and spread, according to a new study from the University of Michigan Comprehensive Cancer Center.

The gene, HER2, causes cancer stem cells to multiply and spread, explaining why HER2 has been linked to a more aggressive type of breast cancer and to metastatic disease, in which the cancer has spread beyond the breast, the researchers say.

Further, the drug Herceptin, which is used to treat HER2-positive breast cancer, was found to target and destroy the cancer stem cells. “This work suggests that the reason drugs that target HER2, such as Herceptin and Lapatanib, are so effective in breast cancer is that they target the cancer stem cell population. This finding provides further evidence for the cancer stem cell hypothesis,” says study author Max S. Wicha, M.D., Distinguished Professor of Oncology and director of the U-M Comprehensive Cancer Center.

The cancer stem cell hypothesis says that tumors originate in a small number of cells, called cancer stem cells, and that these cells are responsible for fueling a tumor’s growth. These cells represent fewer than 5 percent of the cells in a tumor. Wicha’s lab was part of the team that first identified stem cells in human breast cancer in 2003.

In the current study, researchers found that breast cancer cells overexpressing the HER2 gene had four to five times more cancer stem cells, compared to HER2-negative cancers. In addition, the HER2-positive cells caused the cancer stem cells to invade surrounding tissue, suggesting that HER2 is driving the invasiveness and spread of cancer.

The researchers then looked at the drug Herceptin, which is used to treat HER2-positive breast cancer. They found Herceptin reduced the number of cancer stem cells in the HER2-positive breast cancer cell lines by 80 percent, dropping it to the same levels seen in HER2-negative cell lines.

When HER2 was not overexpressed in the cell cultures, the researchers found, the cancer stem cell population did not increase. Nor did Herceptin have any effect on the HER2-negative cells, which is consistent with how Herceptin is used in the clinic.

“We are now studying what pathways are activated by HER2 overexpression. Our hope is that we could develop inhibitors of these pathways that might be effective in targeting cancer stem cells in women whose tumors do not overexpress HER2 or those who are resistant to Herceptin,” says study author Hasan Korkaya, Ph.D., a U-M research fellow in internal medicine.

Breast cancer statistics: 184,450 Americans will be diagnosed with breast cancer this year and 40,930 will die from the disease, according to the American Cancer Society. About 20 percent of breast cancers are considered HER2-positive.

Additional authors: Amanda K. Paulson, a U-M undergraduate student, and Flora Iovino, a U-M research fellow in internal medicine.

Funding: National Institutes of Health, National Cancer Institute, A. Alfred Taubman Medical Research Institute at the U-M Medical School.

Sourced and published by Henry Sapiecha 6th May 2010

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Unraveling Brain Tumors

Molecular Biologists Devise Strategy

To Starve Brain Tumors

September 1, 2007 — Brain tumor researchers have found that brain tumors arise from cancer stem cells living within tiny protective areas formed by blood vessels in the brain. Killing those cells is a promising strategy to eliminate tumors and prevents them from re-growing. The researchers have found that drugs that block new blood vessel formation can destroy the protected areas and stop cancer from developing.

Brain tumors are often deadly. Figuring out a way to wipe them out has been a mystery for scientists. But now, a new discovery may offer clues and hope for those with even the most hard-to-treat tumors.

In the last two months, Will Pappas has had three surgeries, chemo and radiation.

“You hold out hope that well, it’s just something little, and they can get it all. And then it wasn’t. Then you think, well, at least it’s not cancerous, and then it is,” Cayce Pappas, Will’s mom, says.

“It” is a brain tumor — the stubborn kind that’s hard to treat. In fact, doctors gave this seven-year-old only a 20 percent chance of surviving. Stories like Will’s have molecular biologists determined to find a way to destroy brain tumors.

“It’s what makes us all come to work in the morning,” Richard Gilbertson, a molecular biologist from St. Jude Children’s Hospital, says.

For years, researchers thought all cells inside a tumor were the same. But recently, they’ve discovered something different — a small group of cancer stem cells.

“They give rise to all the cells that make up the cancer,” Dr. Gilbertson explains.

Dr. Gilbertson’s research shows those cancer stem cells live close to blood vessels, which fuel them. In lab experiments, he’s proven drugs that target the blood vessels also destroy the cancer stem cells and can ultimately wipe out the tumor.

“So, if you can target those cells, you can have a devastating effect on the disease,” Dr. Gilbertson says. Drugs like Avastin and Tarceva are now being tested in humans to see if they can target the cancer stem cells. “It’s this tangible way of actually getting at the heart of the disease,” Dr. Gilbertson says.

Will is taking the drug Tarceva. His mom is hoping it will work a miracle.

“That would be amazing. We would jump at the opportunity to increase our odds. He’s still got a lot left to do,” Cayce says.

Dr. Gilbertson says other cancers, like those of the blood, breast and colon, also contain cancer stem cells and may be treated in a similar way in the future.

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Shedding Light on Bladder Cancer

Urologists Use Optics,

Chemistry to Catch Small Tumors

October 1, 2005 — Some bladder cancer tumors are so small, surgeons can’t see them. Urologist Edward Messing is using a new liquid dye that reacts to light to help him see all the small bladder tumors that might have been missed in conventional biopsies.

ROCHESTER, N.Y.–The earlier the better, when it comes to detecting cancer. Now, doctors are shedding new light on detecting the deadly disease. Currently, 400-000 people suffer from it while 60,000 more will find out they have it, and bladder cancer usually strikes more than once.

Larry Sylvan, a cancer survivor, says, “At nine months it was back.” He knows what it’s like to battle bladder cancer. Sylvan’s doctor, Edward Messing, says, “The surgery was successful; I got everything I could see.” The doctor’s key word — see; some bladder cancer tumors are so small, surgeons can’t see them.

Dr. Messing, a urologist at the James P. Wilmot Cancer Center in Rochester, N.Y., says, “Before it was sort of blind guessing.” A new photo-sensitizer, a liquid dye inserted into the bladder, improves detection of those small tumors. Under ordinary light, everything looks fine, but when the florescent light is turned on, the entire background looks blue, except where the tumor is — that shows up bright red.

Jerry Gulette was one of the first patients to use the dye. He’s battled bladder cancer time and time again. Dr. Messing says, “I had seen maybe four, five tumors when I cystoscoped him with the white light. And when we turned on this pink light there were 12 or 13.”

More than 94 percent of the people diagnosed with bladder cancer will survive it if it’s caught in the early stages. That’s why this new procedure is so critical for those diagnosed.

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Fluorescent Compounds

Make Tumors Glow

Science (May 2, 2010) — A series of novel imaging agents could light up tumors as they begin to form — before they turn deadly — and signal their transition to aggressive cancers.

The compounds — fluorescent inhibitors of the enzyme cyclooxygenase-2 (COX-2) — could have broad applications for detecting tumors earlier, monitoring a tumor’s transition from pre-malignancy to more aggressive growth, and defining tumor margins during surgical removal.

“We’re very excited about these new agents and are moving forward to develop them for human clinical trials,” said Lawrence Marnett, Ph.D., the leader of the Vanderbilt University team that developed the compounds, which are described in the May 1 issue of Cancer Research.

COX-2 is an attractive target for molecular imaging. It’s not found in most normal tissues, and then it is “turned on” in inflammatory lesions and tumors, Marnett explained.

“COX-2 is expressed at the earliest stages of pre-malignancy — in pre-malignant lesions, but not in surrounding normal tissue — and as a tumor grows and becomes increasingly malignant, COX-2 levels go up,” Marnett said.

Compounds that bind selectively to COX-2 — and carry a fluorescent marker — should act as “beacons” for tumor cells and for inflammation.

Marnett and his colleagues previously demonstrated that fluorescent COX-2 inhibitors — which they have now dubbed “fluorocoxibs” — were useful probes for protein binding, but their early molecules were not appropriate for cellular or in vivo imaging.

“It was a real challenge to make a compound that is COX-2 selective (doesn’t bind to the related COX-1 enzyme), has desirable fluorescence properties, and gets to the tissue in vivo,” Marnett said.

To develop such compounds, Jashim Uddin, Ph.D., research assistant professor of Biochemistry, started with the “core” chemical structure of the anti-inflammatory medicines indomethacin and celecoxib. He then tethered various fluorescent parts to the core structure, ultimately synthesizing more than 200 compounds. The group tested each compound for its interaction with purified COX-2 and COX-1 proteins and then assessed promising compounds for COX-2 selectivity and fluorescence in cultured cells and in animals. Two compounds made the cut.

In studies led by senior research specialist Brenda Crews, the investigators evaluated the potential of these compounds for in vivo imaging using three different animal models: irritant-induced inflammation in the mouse foot pad; human tumors grafted into mice; and spontaneous tumors in mice.

In each case, the two fluorocoxibs — injected intravenously or into the abdominal cavity — accumulated in the inflamed or tumor tissue, giving it a fluorescent “glow.”

To move the agents toward human clinical trials, the team will conduct additional toxicology and pharmacology testing and develop the tools for particular settings that are amenable to fluorescence imaging, such as skin or sites accessible by endoscope (e.g., esophagus and colon).

In the esophagus, for example, a pre-malignant lesion called Barrett’s esophagus can transition to a low-grade dysplasia, then to a high-grade dysplasia, and finally to malignant cancer, which has a one-year survival of only 10 percent. For a patient with Barrett’s esophagus, detecting the transition to dysplasia is critical. The problem is that dysplasia is not visibly different from the pre-malignant Barrett’s lesion, so physicians collect random biopsy samples — which might miss areas of dysplasia.

“If instead, the physician could look through the endoscope and see a nest of cells lighting up with these fluorocoxibs — that is where they could biopsy,” Marnett said.

“Because COX-2 levels increase during cancer progression in virtually all solid tumors, we think these imaging tools will have many, many different applications.”

The investigators also are exploring using the compounds to target delivery of chemotherapeutic drugs directly to COX-2-expressing cells — by tethering an anti-cancer drug instead of a fluorescent marker to the COX-2 inhibitor core.

The National Institutes of Health, the Medical Free-Electron Laser Program of the U.S. Department of Defense, XL TechGroup and the New York Crohn’s Foundation supported the research. The Vanderbilt Cell Imaging Shared Resource and the Vanderbilt University Institute of Imaging Science enabled the cellular and animal imaging.

Marnett is director of the A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, director of the Vanderbilt Institute of Chemical Biology, Mary Geddes Stahlman Professor of Cancer Research, and professor of Biochemistry, Chemistry, and Pharmacology.

Sourced and published by Henry Sapiecha 4th May 2010

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ZYBRESTAT

[A substance from the African willow bush]

SHOWS EVIDENCE OF ANTI-TUMOUR

ACTIVITY IN THYROID CANC ER

Data from a phase II study, in which the clinical effects of Zybrestat in combination with paclitaxel and carboplatin were studied in 13 patients with advanced malignancies including anaplastic thyroid cancer, suggest that Zybrestat possesses potent anti-tumour activity.

Patients in this study received one of two dose regimens of Zybrestat, both of which reduced tumour blood flow as measured by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI). The most marked reductions in tumour blood flow (70%) were seen in the patients with anaplastic thyroid cancer.

COMBINING VDAs WITH ANGIOGENESIS

INHIBITORS

The potential to use VDAs in combination with angiogenic inhibitors is a concept that is attracting considerable interest among scientists. Targeting different aspects of a tumour’s blood supply, sequential use of VDAs and angiogenic inhibitors could lead to massive tumour necrosis and destruction.

While a VDA such as Zybrestat could be used to destroy the established blood supply feeding the tumour, the subsequent addition of an angiogenic inhibitor could prevent the regrowth of blood vessels (neovascularisation) which allows a tumour to survive and proliferate following initial therapy. Preventing the regrowth of blood vessels from the viable tumour rim could help stop tumours from spreading.

MARKETING COMMENTARY

Oxigene’s Zybrestat is under development for the treatment of anaplastic thyroid cancer, a highly aggressive primary thyroid malignancy for which there are no approved treatments.

Currently, newly diagnosed patients have a median life expectancy of about 3 months. Although relatively rare, it represents a disease of significant unmet clinical need. VDAs, of which Zybrestat is one of several in development, may have the potential to treat difficult malignancies such as anaplastic thyroid cancer as well as other solid tumours when used in conjunction with established cancer drugs.

Sourced and published by Henry Sapiecha 28th April 2010

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WHAT ARE THE MAIN CAUSES OF CANCER – FIND OUT HERE

Do you know that lung cancer did not exist between American Natives, who smoked tobacco. It is combination of hundreds of cofactors like smoking, lifestyle, diet, stress,…… that makes cancer.

Tobacco is only one of them.

“THE CAUSE OF CANCER IS CLEAR

Poor diet, lifestyle and poor mental attitude result in toxic buildup which overloads the self-cleansing mechanism.

Cancer is manifestation of long term nutritional and environmental irritation, resulting in cellular oxygen starvation, leading to uncontrolled cell replication. It is often triggered by psychological causes inducing immune system collapse.” by Saul Pressman

The most common causative agents of Cancer in most people are:

Toxins and vaccination

Nutritional deficiency – Diet deficient on essential nutrients is affecting biochemical processes inside our cells. It is also affecting digestion and preventing internal natural detoxification.

Poor dietary choices

stress, suppression, negative thoughts, fear, lack of love, lack joy, lack desire to live.

Not enough movement and sweating

Mental attitude

Gallstones

Poor digestion – Incomplete digestion is causing poor absorption of essential nutrients, and poorly digested food is containing toxic substances that our intestines absorb into our blood and lymph.

Infection by internal parasitic animas – PARASITES (protozoa, amoebae, worms,..)

Infection by parasitic yeasts, viruses bacteria

Overuse of medical drugs

Sourced and published by Henry Sapiecha 28th April 2010

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Common virus ‘kills cancer’

Cancer Diseases WASHINGTON — A common virus that is harmless to people can destroy cancerous cells in the body and might be developed into a new cancer therapy, US researchers said.

The virus, called adeno-associated virus type 2, or AAV-2, infects an estimated 80 percent of the population.

“Our results suggest that adeno-associated virus type 2, which infects the majority of the population but has no known ill effects, kills multiple types of cancer cells yet has no effect on healthy cells,” said Craig Meyers, a professor of microbiology and immunology at the Penn State College of Medicine in Pennsylvania.

“We believe that AAV-2 recognizes that the cancer cells are abnormal and destroys them. This suggests that AAV-2 has great potential to be developed as an anti-cancer agent,” Meyers said in a statement.

He said at a meeting of the American Society for Virology that studies have shown women infected with AAV-2 who are also infected with a cancer-causing wart virus called HPV develop cervical cancer less frequently than uninfected women do.

AAV-2 is a small virus that cannot replicate itself without the help of another virus.

But with the help of a second virus it kills cells.

For their study, Meyers and colleagues first infected a batch of human cells with HPV, some strains of which cause cervical cancer. They then infected these cells and normal cells with AAV-2.

After six days, all the HPV-infected cells died.

The same thing happened with cervical, breast, prostate and squamous cell tumor cells.

All are cancers of the epithelial cells, which include skin cells and other cells that line the insides and outsides of organs.

“One of the most compelling findings is that AAV-2 appears to have no pathologic effects on healthy cells,” Meyers said.

“So many cancer therapies are as poisonous to healthy cells as they are to cancer cells. A therapy that is able to distinguish between healthy and cancer cells could be less difficult to endure for those with cancer.”

AAV-2 is being studied intensively as a gene therapy vector — a virus modified to carry disease-correcting genes into the body.

Gene therapy researchers favor it because it does not seem to cause disease or immune system reaction on its own.

Sourced and published by Henry Sapiecha 27th April 2010

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Malic Acid—the critical partner of the EDTA chelation Dynamic Duo!

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