BLOCKING ENZYME COULD HELP IN RARE BLOOD CANCER

An enzyme that fights some kinds of cancers may foster the growth of a rare type of leukemia that affects babies, U.S. researchers said on Wednesday in a finding that may lead to new drugs for the hard-to-treat cancer.

They said drugs that blocked the enzyme glycogen synthase kinase, or GSK3, helped mice with mixed-lineage leukemia, or MLL, live far longer than untreated mice.

The finding is a surprise because prior studies have found GSK3 helped suppress unchecked cell growth in other cancers.

"GSK3 has never been implicated in promoting cancer," said Dr. Michael Cleary of Stanford University in California, whose research appears in the journal Nature.

Cleary's team found that blocking GSK3 fights leukemias caused by mutations in the MLL gene, which accounts for 5 percent to 10 percent of child and adult leukemias and more than three-quarters of leukemias diagnosed in infants.

Cleary said only a few hundred people in the United States get MLL each year, but when babies get leukemia, they tend to get this form, although it is not clear why.

While most leukemias get their start in either lymph nodes or bone marrow, MLL cancer cells can originate from both.

"These patients don't typically respond well to chemotherapy. There is a real need for better treatments," Cleary said in a telephone interview.

His team first got a hint that blocking GSK3 might fight MLL through routine screening tests in the lab.

The researchers gave the mice with MLL lithium, a drug used to treat bipolar disease in humans.

"It is not the best GSK3 inhibitor, but it is one that could be administered long-term in mice," Cleary said.

Mice treated with the lithium lived significantly longer than the untreated mice. Cleary's team also used a different GSK3 inhibitor in MLL cells and found it stopped them from growing.

"I think where we need to go in the future is to come up with better inhibitors that can be administered long-term," Cleary said.

That may come through research of the drug in other diseases. Cleary said drug companies are developing GSK3 inhibitors as treatments for diabetes and Alzheimer's disease.

cgnfgn

fggngnfng

BREATHING DISORDER PUTS BLACKS AT HIGH CANCER RISK.

"Blacks with a history of the chronic breathing disorder COPD have a far greater risk of developing lung cancer than whites who have the lung disease, U.S. researchers said on Thursday.

They said the high risk for blacks with chronic obstructive pulmonary disease highlights the need for better risk assessment tools that take race and ethnicity into account.

'The one-size-fits-all risk prediction clearly does not work,' Carol Etzel of the University of Texas M.D. Anderson Cancer Center, whose report appears in the journal Cancer Prevention Research, said in a statement.

Etzel's team developed the risk assessment tool for African Americans to help doctors better predict a patient's specific risk for lung cancer.

They analyzed data from 491 African Americans with lung cancer and 497 African Americans without lung cancer to look for risk factors. They compared these with existing risk models for whites.

The new model found black men with a prior history of COPD had a more than sixfold increased risk of lung cancer, on par with someone who is actively smoking."

RESEARCHERS IDENTIFY PROMISING CANCER DRUG TARGET IN PROSTATE TUMORS

Scientists at Dana-Farber Cancer Institute report they have blocked the development of prostate tumors in cancer-prone mice by knocking out a molecular unit they describe as a "powerhouse" that drives runaway cell growth.

In a letter appearing in an advanced online publication by the journal Nature, the researchers said the growth-stimulating molecule called p110beta — part of a cellular signaling network disrupted in several common cancers — is a promising target for novel cancer therapies designed to shut it down. The report's lead authors are Shidong Jia, Zhenning Liu, Sen Zhang, and Pixu Liu.

The p110beta molecule and a counterpart, p110alpha, are "isoforms" — slightly different forms — of an enzyme called PI(3)K that is an intense focus of cancer research and drug development. PI(3)K is the linchpin of a cell-signal pathway that responds to growth factor signals from outside the cell.

When activated by growth factor receptors, PI(3)K turns on a cascade of genes and proteins that drives cells to divide and grow. The molecular accelerator is normally kept under control by a tumor-suppressor protein, PTEN, which acts like a brake to curb excess cell growth that could lead to cancer.

Mutations that inactivate PTEN — in effect releasing the brake on growth signals — are found in a significant proportion of prostate cancer, breast cancer, and brain tumors. The senior authors of the new report, Jean Zhao and Thomas Roberts, previously showed that blocking p110alpha protein inhibits cancerous growth induced by various cancer-causing proteins, such as Her2 and EGFR. With that knowledge in hand, the researchers, in collaboration with pharmaceutical companies, are developing p110alpha blockers.

P110beta, by contrast, was thought to be a relatively insignificant player in tumors. However, "the surprise in this paper is that p110beta has been found to be a bigger player than p110alpha in tumors that result from PTEN loss," noted Zhao. "Now the drug companies, which have been focusing on p110alpha, will have to think about making p110beta inhibitors as well."

Both forms of the p110 molecule have dual tasks: they are involved in responding to insulin signals — a metabolic function — as well as relaying growth signals from outside the cell. But the importance of 110beta had been vastly underestimated, the researchers said, for reasons they don't entirely understand.

"We knew that when cells are stimulated with growth factor signals, the activity of p110alpha, but not p110beta, rises rapidly and sharply in triggering excess cell growth," Zhao said. "We speculate that p110beta may be providing a low-level but steady growth stimulus, and when PTEN is lost, it becomes an important source of cell proliferation signals."

The new findings stem from experiments in which the scientists disabled the p110beta protein in mice as a way of exploring its normal functions. In one of the experiments, the researchers "knocked out" p110beta in mice that also lacked the PTEN tumor suppressor protein and were therefore highly prone to prostate cancer. Mice that lacked PTEN but had functioning p110beta proteins all developed early prostate cancers by 12 weeks of age. In contrast, the "knockout" mice with no p110beta function remained free of prostate cancer even though the PTEN "brake" had been disabled.

The scientists concluded, as a result, that p110beta becomes a "powerhouse" to drive cancerous cell growth when PTEN function is missing.

In light of the new findings, there is likely to be great interest in finding drugs or other tools to block the p110beta protein in cancers where mutations in PTEN have unleashed the overactive growth signals, said Zhao.

The task is made somewhat easier, explained Roberts, by the fact that "we know what the inhibitor should look like because of our work on p110alpha inhibitors."

Roberts said that drugs designed to block the p110alpha form are on their way to clinical testing, but he could not predict when p110beta inhibitors might become available for clinical testing.

BREATHING DISORDER PUTS BLACKS AT HIGH CANCER RISK.

Blacks with a history of the chronic breathing disorder COPD have a far greater risk of developing lung cancer than whites who have the lung disease, U.S. researchers said on Thursday.

They said the high risk for blacks with chronic obstructive pulmonary disease highlights the need for better risk assessment tools that take race and ethnicity into account.

"The one-size-fits-all risk prediction clearly does not work," Carol Etzel of the University of Texas M.D. Anderson Cancer Center, whose report appears in the journal Cancer Prevention Research, said in a statement.

Etzel's team developed the risk assessment tool for African Americans to help doctors better predict a patient's specific risk for lung cancer.

They analyzed data from 491 African Americans with lung cancer and 497 African Americans without lung cancer to look for risk factors. They compared these with existing risk models for whites.

The new model found black men with a prior history of COPD had a more than sixfold increased risk of lung cancer, on par with someone who is actively smoking.

The risk is about twice as high as that typically seen in whites with a history of COPD, which includes emphysema, chronic bronchitis and some types of serious chronic asthma.

Smoking is by far the leading cause of COPD, but environmental factors including pollution play a role.

Blacks and white smokers both have six times higher risk of lung cancer than non-smokers. And blacks with hay fever are 44 percent less likely to get lung cancer than other blacks, a finding that has also been seen in whites.

Etzel's team is now working on a risk assessment model for Hispanics.

"What we hope is that a doctor can use these models to encourage their patients to take steps to prevent lung cancer. Even if they are never smokers, they can be at risk," Etzel said.

Lung cancer is the leading cancer killer worldwide, with almost 1.2 million deaths per year -- 162,000 deaths a year in the United States alone.

The National Cancer Institute estimates that 15,000 people who have never smoked die every year from lung cancer in the United States.

IMAGING A PROMISING CANCER DETECTOR

A radioactive tracer that "lights up" cancer hiding inside dense breasts showed promise in its first big test against mammograms, revealing more tumors and giving fewer false alarms, doctors have reported.

The experimental method — molecular breast imaging, or MBI — would not replace mammograms for women at average risk of the disease.

But it might become an additional tool for higher risk women with a lot of dense tissue that makes tumors hard to spot on mammograms, and it could be done at less cost than an MRI, or magnetic resonance imaging. About one-fourth of women 40 and older have dense breasts.

"MBI is a promising technology" that is already in advanced testing, said Carrie Hruska, a biomedical engineer at the Mayo Clinic in Rochester, Minn., which has been working on it for six years.

She gave results in a telephone news briefing Wednesday and will present them later this week at an American Society of Clinical Oncology conference in Washington, D.C.

Mammograms — a type of X-ray — are the chief way now to check for breast cancer. MBI uses radiation, too, but in a different way. Women are given an intravenous dose of a short-acting tracer that is absorbed more by abnormal cells than healthy ones. Special cameras collect the "glow" these cells give off, and doctors look at the picture to spot tumors.

Researchers tried both methods, on 940 women who had dense breasts and a high risk of cancer because of family history, bad genes or other reasons.

Thirteen tumors were found in 12 women — eight by MBI alone, one by mammography alone, two by both methods and two by neither. (The two missed cancers were found on subsequent annual mammograms, physical exams or other imaging tests.)

Looked at another way, MBI found 10 out of 13 tumors, missing three; mammograms detected three out of 13 tumors and missed 10. Using both methods, 11 out of 13 tumors would have been detected.

"These images are quite striking. You can see how the cancers would be hidden on the mammograms," Hruska said.

Mammograms gave false alarms — led doctors to conclude that cancer was present when it was not — in about 9 percent of patients, compared to only 7 percent for MBI. The MBI tests led to more biopsies than mammograms did, but they more often revealed cancer.

The Susan G. Komen for the Cure foundation and Bristol-Myers Squibb, which makes the imaging agent used in the study, paid for the work.

The next test will be to see how MBI stacks up against MRI. The federal government is paying for a new study Mayo is leading that compares the two in 120 high-risk women with dense breasts.

MRI is often used now for women with dense breasts, but it gives many false alarms that lead to unnecessary biopsies. Doctors hope MBI will prove more accurate and cost less — under $500 versus more than $1,000 for an MRI.

"We all know that mammography is, in and of itself, an imperfect tool, and we clearly need to do better in the future," said Dr. Eric Winer of the Dana-Farber Cancer Center in Boston, a spokesman for the oncology group. "It is fair to say that MRI will not solve all problems either."

One drawback of MBI: It uses about 8 to 10 times the radiation of mammograms, a dose that engineers like Hruska are trying to lower with newer technology. Other medical centers also are testing MBI.

"We're just beginning to see what this technology can do," she said.

WOMAN DIAGNOSES CANCER VIA E-MAIL

A toddler in Florida has been diagnosed with cancer after a Manchester woman saw early warning signs in a picture.

Madeleine Robb, from Stretford, who has never met her pen pal, spotted a shadow behind one of Rowan Santos's eyes on pictures from her first birthday.

She then e-mailed her mother Megan advising her to get medical help.

The toddler was diagnosed with an aggressive form of cancer - Retinoblastoma - and underwent an operation and is having chemotherapy.

The two mothers became friends on an internet messageboard after their children were born on the same day.

But when Mrs Robb saw the pictures she said she knew something was not right. Even if we had waited even one more week, the tumour could have reached her brain and her prognosis would have not been good

Megan Santos

'I recognised something I'd seen in a news article,' she said.

'The eye was reflecting a light but it wasn't just reflecting in one picture - but in all of them.

'I sent her an e-mail just saying it was important she have it checked.'

Megan Santos took her to the doctor the same day and her condition was diagnosed."

CANCER CENTER WARNS OF CELL PHONE RISKS

CANCER CENTER WARNS OF CELL PHONE RISKS: "CANCER CENTER WARNS OF CELL PHONE RISKS
Publish Date: 2008-07-24 10:23:26

The head of a prominent cancer research institute issued an unprecedented warning to his faculty and staff Wednesday: Limit cell phone use because of the possible risk of cancer.

The warning from Dr. Ronald B. Herberman, director of the University of Pittsburgh Cancer Institute of Pittsburgh Cancer Institute, is contrary to numerous studies that don't find a link between cancer and cell phone use, and a public lack of worry by the U.S. Food and Drug Administration.

Herberman is basing his alarm on early unpublished data. He says it takes too long to get answers from science and he believes people should take action now — especially when it comes to children."

TARGETED DRUG BOOSTS SURVIVAL AMONG LIVER CANCER PATIENTS

TARGETED DRUG BOOSTS SURVIVAL AMONG LIVER CANCER PATIENTS: "The drug Nexavar can prolong the lives of people with liver cancer by an average of three months, new research shows.

'The results unequivocally showed that sorafenib (Nexavar) increased the survival of patients with a more than 30 percent reduction in the likelihood to die at any time point during follow-up,' said study senior author Dr. Jordi Bruix, a senior consultant in the liver unit of the Hospital Clinic of Barcelona.

'These results identify sorafenib as the first agent that is effective in improving survival in patients with this devastating disease,' said Bruix. His report is in the July 24 issue of the New England Journal of Medicine."

CHEMOTHERAPY

CHEMOTHERAPY: "Chemotherapy

Chemotherapy is the treatment of cancer with drugs ('anticancer drugs') that can destroy cancer cells. In current usage, the term 'chemotherapy' usually refers to cytotoxic drugs which affect rapidly dividing cells in general, in contrast with targeted therapy (see below). Chemotherapy drugs interfere with cell division in various possible ways, e.g. with the duplication of DNA or the separation of newly formed chromosomes. Most forms of chemotherapy target all rapidly dividing cells and are not specific for cancer cells, although some degree of specificity may come from the inability of many cancer cells to repair DNA damage, while normal cells generally can. Hence, chemotherapy has the potential to harm healthy tissue, especially those tissues that have a high replacement rate (e.g. intestinal lining). These cells usually repair themselves after chemotherapy.

Because some drugs work better together than alone, two or more drugs are often given at the same time. This is called 'combination chemotherapy'; most chemotherapy regimens are given in a combination."

TARGETED THERAPIES

TARGETED THERAPIES: "Targeted Therapies

Targeted therapy, which first became available in the late 1990s, has had a significant impact in the treatment of some types of cancer, and is currently a very active research area. This constitutes the use of agents specific for the deregulated proteins of cancer cells. Small molecule targeted therapy drugs are generally inhibitors of enzymatic domains on mutated, overexpressed, or otherwise critical proteins within the cancer cell. Prominent examples are the tyrosine kinase inhibitors imatinib and gefitinib.

Monoclonal antibody therapy is another strategy in which the therapeutic agent is an antibody which specifically binds to a protein on the surface of the cancer cells. Examples include the anti-HER2/neu antibody trastuzumab (Herceptin) used in breast cancer, and the anti-CD20 antibody rituximab, used in a variety of B-cell malignancies."

OTHER TREATMENTS

OTHER TREATMENTS: "Immunotherapy

Cancer immunotherapy refers to a diverse set of therapeutic strategies designed to induce the patient's own immune system to fight the tumor. Contemporary methods for generating an immune response against tumours include intravesical BCG immunotherapy for superficial bladder cancer, and use of interferons and other cytokines to induce an immune response in renal cell carcinoma and melanoma patients. Vaccines to generate specific immune responses are the subject of intensive research for a number of tumours, notably malignant melanoma and renal cell carcinoma. Sipuleucel-T is a vaccine-like strategy in late clinical trials for prostate cancer in which dendritic cells from the patient are loaded with prostatic acid phosphatase peptides to induce a specific immune response against prostate-derived cells."

CHEMICAL CARCINOGENS

CHEMICAL CARCINOGENS: "Causes

Cancer is a diverse class of diseases which differ widely in their causes and biology. The common thread in all known cancers is the acquisition of abnormalities in the genetic material of the cancer cell and its progeny. Research into the pathogenesis of cancer can be divided into three broad areas of focus. The first area of research focuses on the agents and events which cause or facilitate genetic changes in cells destined to become cancer. Second, it is important to uncover the precise nature of the genetic damage, and the genes which are affected by it. The third focus is on the consequences of those genetic changes on the biology of the cell, both in generating the defining properties of a cancer cell, and in facilitating additional genetic events, leading to further progression of the cancer."

INFECTIOUS DISEASES

INFECTIOUS DISEASES: "Infectious diseases.

Some cancers can be caused by infection with pathogens.[14] Many cancers originate from a viral infection; this is especially true in animals such as birds, but also in humans, as viruses are responsible for 15% of human cancers worldwide. The main viruses associated with human cancers are human papillomavirus, hepatitis B and hepatitis C virus, Epstein-Barr virus, and human T-lymphotropic virus. Experimental and epidemiological data imply a causative role for viruses and they appear to be the second most important risk factor for cancer development in humans, exceeded only by tobacco usage.[15] The mode of virally-induced tumors can be divided into two, acutely-transforming or slowly-transforming. In acutely transforming viruses, the virus carries an overactive oncogene called viral-oncogene (v-onc), and the infected cell is transformed as soon as v-onc is expressed. In contrast, in slowly-transforming viruses, the virus genome is inserts near a proto-oncogene in the host genome. The viral promoter or other transcription regulation elements then cause overexpression of that proto-oncogene. This induces uncontrolled cell division. Because the site of insertion is not specific to proto-oncogenes and the chance of insertion near any proto-oncogene is low, slowly-transforming viruses will cause tumors much longer after infection than the acutely-transforming viruses."

HEREDITY

HEREDITY: "Most forms of cancer are 'sporadic', and have no basis in heredity. There are, however, a number of recognised syndromes of cancer with a hereditary component, often a defective tumor suppressor allele. Famous examples are:"

OTHER CAUSES

OTHER CAUSES: "Hormonal imbalances
Some hormones can act in a similar manner to non-mutagenic carcinogens in that they may stimulate excessive cell growth. A well-established example is the role of hyperestrogenic states in promoting endometrial cancer."

DIAGNOSIS

DIAGNOSIS: "Most cancers are initially recognized either because signs or symptoms appear or through screening. Neither of these lead to a definitive diagnosis, which usually requires the opinion of a pathologist, a type of physician (medical doctor) who specializes in the diagnosis of cancer and other diseases.

Investigation"

SIGNS AND SYMPTOMS

SIGNS AND SYMPTOMS: "Cancer symptoms can be divided into three groups:"

ADULT AND CHILD CANCER

ADULT AND CHILD CANCER: "Adult cancers

In the U.S. and other developed countries, cancer is presently responsible for about 25% of all deaths.[4] On a yearly basis, 0.5% of the population is diagnosed with cancer. The statistics below are for adults in the United States, and may vary substantially in other countries:

WHAT IS CANCER

WHAT IS CANCER: "Cancer (medical term: malignant neoplasm) is a class of diseases in which a group of cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize. Most cancers form a tumor but some, like leukemia, do not."

CANCER CLASSIFICATION

CANCER CLASSIFICATION: "Cancer is generally classified according to the tissue from which the cancerous cells originate, the primary tumor, as well as the normal cell type they most resemble. These are location and histology, respectively."

CANCER AND SUN EXPOSURE

CANCER AND SUN EXPOSURE: "Sun exposure control, not eliminating it all together by applying 'sun blocking' products, is one of your main defenses against cancer. Everyone needs the sun's rays in order for their body to produce vitamin D. 15-20 minutes of sun exposure a day will produce far more readily available vitamin D in your system than any amount of supplementation ever could. The same goes for any of your food sources that have vitamin D in them."