FDA approves new treatment for rare type of pancreatic cancer

On Thursday, the U.S. Food and Drug Administration approved Afinitor (everolimus) to treat patients with progressive neuroendocrine tumors located in the pancreas (PNET) that cannot be removed by surgery or that have spread to other parts of the body (metastatic).

Neuroendocrine tumors found in the pancreas are slow-growing and rare. It is estimated that there are fewer than 1,000 new cases in the United States each year.

“Patients with this cancer have few effective treatment options,” said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research. “Afinitor has demonstrated the ability to slow the growth and spread of neuroendocrine tumors of the pancreas.”

The safety and effectiveness of Afinitor was established a clinical trial in 410 patients with metastatic (late-stage) or locally advanced (disease that could not be removed with surgery) disease. Patients in the study were selected to receive Afinitor or placebo (sugar pill). The trial was designed to measure the length of time a patient lived before their disease spread or worsened (progression-free survival).

In patients treated with Afinitor, the median length of time they lived without the cancer spreading or worsening was 11 months compared with 4.6 months in patients who received placebo. Patients who received placebo were able to receive Afinitor if their disease worsened.

In patients treated with Afinitor for neuroendocrine pancreatic tumors, the most commonly reported side effects included inflammation of the mouth (stomatitis), rash, diarrhea, fatigue, swelling (edema), stomach (abdominal) pain, nausea, fever, and headache.

Afinitor is also approved to treat patients with kidney cancer (advanced renal cell carcinoma) after they fail treatment with Sutent (sunitinib) or Nexavar (sorafenib); and patients with subependymal giant cell astrocytoma (a type of brain cancer) associated with tuberous sclerosis (a disease that causes tumors in various parts of the body), who cannot be treated by surgery.

Afinitor has another trade name, Zortress, and is approved to treat certain adult patients to prevent organ rejection after a kidney transplant. Zortress has a different safety profile in these patients.

Afinitor is marketed by East Hanover, N.J.-based Novartis.

-----

Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG @FayetteFP

Protein Inhibitor May Bring a Topical Treatment for HPV

/PRNewswire/ -- Human papillomavirus (HPV) causes cervical cancer, the second most common cause of cancer death for women, and is a common cause of anogenital and some head and neck cancers. Thanks to research being done at Tufts University School of Medicine, patients infected with cancer-causing HPV may someday have an alternative to surgical and harsh chemical treatments. In a study funded by the National Institutes of Health and published online in advance of print in The FASEB Journal, the researchers report on the development of a protein-based inhibitor that could provide a topical treatment for HPV.

"Currently, there is no cure for HPV, and the available treatment options involve destroying the affected tissue. We have developed a protein inhibitor that blocks HPV protein expression in cell culture, a first step toward a topically-applied treatment for this cancer-causing virus," said senior author James Baleja, Ph.D., associate professor of biochemistry at Tufts University School of Medicine (TUSM) and member of the biochemistry program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts.

"Vaccines are helping to lower the incidence of HPV, but vaccines will not help the millions of women and men who currently have an infection, especially those who have high-risk and persistent infections. Social and economic challenges make widespread administration of a vaccine difficult, particularly in developing countries. A topical treatment for HPV could provide an economical option," he continued.

HPV affects approximately 20 million people in the United States, making it the most common sexually transmitted infection. There are more than 100 types of HPV of which more than 40 are sexually transmitted. These include two high-risk types, HPV-16 and HPV-18, which cause the majority of cervical and anogenital cancers, and some portion of head and neck cancers, particularly oral cavity and oropharynx cancers. Cervical cancer is diagnosed in nearly 500,000 women each year, killing 250,000 annually. In the United States, it was estimated that 12,000 women in 2010 would be diagnosed with cervical cancer, while 10,100 women and men in the United States get vulvar, vaginal, penile or anal cancers each year. In addition, some portion of the head and neck cancers in the United States (11,300 men and women each year) is attributable to HPV. Other types of HPV, or low-risk HPV, can cause genital warts or are infections that clear on their own.

In their efforts to inhibit HPV, Baleja and his team zeroed in on the viral protein E2, which controls viral activities including DNA replication and the activation of cancer-causing genes. Using structure-guided design, the team developed a protein called E2R that prevents E2 from functioning normally. When the researchers applied E2R to a cell model of HPV biology, viral gene transcription was halted. Because HPV infects epithelial cells, the outermost layer of the skin and the mucous membranes, protein inhibitors such as E2R could be applied in a topical form.

Baleja and colleagues used biophysical tools including circular dichroism spectroscopy and x-ray crystallography to test the structure and stability of different inhibitors. The most stable inhibitor was then tested in mammalian cells and was found to inhibit the E2 protein of HPV-16, the high-risk strain that is most commonly associated with cancers. The data in this study suggest that the inhibitor may also be effective against another high-risk virus, HPV-18, as well as a low-risk virus, HPV-6a, which causes warts.

Additional authors on the paper are first author Kakoli Bose, Ph.D., formerly a postdoctoral fellow in the Baleja laboratory at TUSM and now with the Advanced Centre for Treatment, Research and Education in Cancer at the Tata Memorial Center in India; Gretchen Meinke, Ph.D., senior research associate in the Bohm Laboratory at TUSM, and Andrew Bohm, associate professor in the Department of Biochemistry at TUSM and member of the biochemistry program faculty at the Sackler School of Graduate Biomedical Sciences.

This research was funded by the National Cancer Institute, part of the National Institutes of Health, and by the Lifespan/Tufts/Brown Center for AIDS Research (CFAR), a joint research effort between Tufts and Brown Universities and their affiliated hospitals and centers. CFAR is funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

Bose K, Meinke G, Bohm A, and Baleja J. The FASEB Journal. "Design and characterization of an enhanced repressor of human papillomavirus E2 protein." Published online April 11, 2011. DOI 10.1096/fj.10-176461

-----

Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG @FayetteFP

UGA researchers develop non-invasive early diagnostic test for gastric cancer

Early detection of cancer may eventually become as easy as taking a home pregnancy test, according to new University of Georgia research.

Two studies recently published in the journal PloS ONE identified for the first time that certain proteins excreted in urine can indicate the presence of gastric cancer.

The researchers initially studied stomach cancer because it is the number two cancer killer in the world.
They hope that with further study, the detection of abnormally abundant proteins in urine will lead to diagnosis of many types of cancer and other diseases, said Ying Xu, lead author of the study and Regents-Georgia Research Allianceeminent scholar of bioinformatics and computational biologyin the UGA Franklin College of Arts and Sciences.

“In theory, the methodology that we developed should be applicable to other cancers,” said Xu, who also is a professor of biochemistry and molecular biology and director of the UGA Institute of Bioinformatics.

Xu and his colleagues, Celine Hong, Juan Cui and David Puett of the Institute of Bioinformatics, identified a protein called endothelial lipase that differed significantly in its abundance in urine samples of stomach cancer patients versus healthy people. Xu said the computational capability presented in the study for predicting which of the abnormally abundant proteins in diseased tissues can be excreted into urine is a key breakthrough in cancer detection. Using samples from already known excretory and non-excretory proteins, the study found that the classification system was more than 80 percent accurate.

Of the 21 urine samples of healthy people, only two did not have the protein. In the 21 urine samples of stomach cancer patients, only one sample was considered to have a relatively high level of the protein; levels in the rest were low or absent. “We are suggesting from this relatively small urine sample set that healthy people should have this protein in their urine,” Xu said.

The researchers are currently working on a larger urine sample set of 200 gastric cancer patients and 200 healthy people. “If the EL protein still has the 10 to 15 percent miscalculation rate as with the 21 versus 21 samples, I think we have found a good diagnostic marker for stomach cancer and potentially other cancers,” said Xu.

Now that the researchers have identified a protein marker, Xu says they should be able to develop a method where urine can change the color of a piece of paper to indicate the presence or absence of the protein, similar to the way a home pregnancy test works. The researchers hope to find multiple protein markers for each cancer to increase the accuracy of the test.

Although the test is not yet 100 percent accurate, it can lead at-risk patients to seek a more comprehensive exam, said Xu. Current procedures such as endoscopy are invasive, uncomfortable and may be avoided by many people. “A person could go get a urine test, and if the marker protein is present, then they are generally stomach-cancer free,” said Xu. “If the protein is not present, we might suggest that they get their stomach checked.”

The researchers began by studying a set of 1,500 proteins known to be excreted in urine and identified a list of features that distinguish them from proteins that are not excreted into urine. Identifying these distinguishing features allowed them to develop a classification system that could predict which proteins in cancerous tissues are excreted into urine.

Xu and his colleagues then used microarrays—chips that are about the size of a stamp that contain nearly twenty thousand human genes—to identify which proteins varied in abundance in the cancerous versus non-cancerous tissues. Messenger RNA (mRNA) molecules extracted from the sample tissues are converted to complementary DNAs (cDNAs) and hybridize with their complement genes on the microarray and light up as spots when the corresponding mRNAs are abundant. The researchers then identified proteins corresponding to those genes that appeared at significantly different levels in the cancer and non-cancer samples. From there, the researchers were able to determine which of the abnormally abundant proteins were secreted into the blood and then excreted in urine using the classification method they developed.

The UGA researchers work in conjunction with a team of researchers led by Fan Li of Jilin University in China, where Xu spends two months a year working with medical doctors and researchers on sample collection and carrying out microarray experiments. This long-term collaboration has led to the establishment of the Jilin University/University of Georgia Joint Research Center for Systems Biology. The researchers are currently collecting tissues from patients with different types of cancer to identify more protein markers that can be detected in urine.

The study was supported by the UGA President’s Venture Fund, the Office of Vice President for Research, the Georgia Cancer Coalition, the Georgia Research Alliance, Jilin University and the National Institutes of Health.

To learn more about the UGA Institute of Bioinformatics, see http://www.bioinformatics.uga.edu/. To learn more about the Franklin College of Arts and Sciences department of biochemistry and molecular biology, see http://www.bmb.uga.edu/.

-----

Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG @FayetteFP

FDA approves new treatment for rare form of thyroid cancer

The U.S. Food and Drug Administration today (April 6) approved vandetanib to treat adult patients with late-stage (metastatic) medullary thyroid cancer who are ineligible for surgery and who have disease that is growing or causing symptoms.

Thyroid cancer is a cancerous growth of the thyroid gland, which is located in the neck. Medullary thyroid cancer involves specific types of cells that are found in the thyroid gland and can occur spontaneously, or be part of a genetic syndrome.

About 44,600 new thyroid cancer cases were diagnosed in the United States during 2010, and about 1,690 people died from the disease, according to the National Cancer Institute. Medullary thyroid cancer is estimated to represent 3 to 5 percent of all thyroid cancer; its estimated incidence in the United States for 2010 is about 1,300 to 2,200 patients, making it one of the rarer forms of thyroid cancer.

Common symptoms of medullary thyroid cancer may include coughing, difficulty swallowing, enlargement of the thyroid gland, swelling of the neck, a lump on the thyroid, and changes in a person’s voice or hoarseness.

Vandetanib targets medullary thyroid cancer’s ability to grow and expand. There are currently no FDA-approved treatments for this type of cancer. Vandetanib is administered orally on a daily basis.

Vandetanib’s safety and effectiveness were established in a single, randomized international study of 331 patients with late-stage medullary thyroid cancer. Patients in the study were selected to receive vandetanib or placebo (sugar pill).

The study was designed to measure the length of time a patient lived without the individual’s cancer progressing (progression-free survival). Patients who received vandetanib had a longer period of time without disease progression when compared to patients receiving placebo. Median progression-free survival was 16.4 months in the placebo arm and at least 22.6 months in the vandetanib arm. It is too early to determine the median progression-free survival in patients treated with vandetanib or to tell whether they will live longer (overall survival) compared to patients treated with placebo.

“Vandetanib’s approval underscores FDA’s commitment to approving treatments for patients with rare and difficult to treat diseases,” said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research.

Common side effects occurring from vandetanib use include diarrhea, rash, nausea, high blood pressure, headache, fatigue, decreased appetite, and stomach (abdominal) pain. Serious side effects reported during the study resulted in five deaths in patients treated with vandetanib. Causes of death included breathing complications, heart failure, and a bacterial infection in the blood (sepsis).

Vandetanib was shown to affect the electrical activity of the heart, which in some cases can cause irregular heart beats that could lead to death. Vandetanib is being approved with a Risk Evaluation and Mitigation Strategy (REMS) to inform health care professionals about these serious heart-related risks. Only health care professionals and pharmacies certified through the vandetanib REMS program, a restricted distribution program, will be able to prescribe and dispense the drug. Patients will also receive an FDA-approved Medication Guide informing them of the potential risks.

Vandetanib is marketed by AstraZeneca Pharmaceuticals LP of Wilmington, Del. There is no trade name established for this drug at this time.

-----
Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG @FayetteFP

FDA Approves New Treatment for a Type of Late-Stage Skin Cancer

/PRNewswire/ --The U.S. Food and Drug Administration today approved Yervoy (ipilimumab) to treat patients with late-stage (metastatic) melanoma, the most dangerous type of skin cancer.

Melanoma is the leading cause of death from skin disease. An estimated 68,130 new cases of melanoma were diagnosed in the United States during 2010 and about 8,700 people died from the disease, according to the National Cancer Institute.

"Late-stage melanoma is devastating, with very few treatment options for patients, none of which previously prolonged a patient's life," said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research. "Yervoy is the first therapy approved by the FDA to clearly demonstrate that patients with metastatic melanoma live longer by taking this treatment."

Yervoy is a monoclonal antibody that blocks a molecule known as cytotoxic T-lymphocyte antigen or CTLA-4. CTLA-4 may play a role in slowing down or turning off the body's immune system, affecting its ability to fight off cancerous cells. Yervoy may work by allowing the body's immune system to recognize, target, and attack cells in melanoma tumors. The drug is administered intravenously.

Yervoy's safety and effectiveness were established in a single international study of 676 patients with melanoma. All patients in the study had stopped responding to other FDA-approved or commonly used treatments for melanoma. In addition, participants had disease that had spread or that could not be surgically removed.

The study was designed to measure overall survival, the length of time from when this treatment started until a patient's death. The randomly assigned patients received Yervoy plus an experimental tumor vaccine called gp100, Yervoy alone, or the vaccine alone.

Those who received the combination of Yervoy plus the vaccine or Yervoy alone lived an average of about 10 months, while those who received only the experimental vaccine lived an average of 6.5 months.

Common side effects that can result from autoimmune reactions associated with Yervoy use include fatigue, diarrhea, skin rash, endocrine deficiencies (gland or hormone), and inflammation of the intestines (colitis). Severe to fatal autoimmune reactions were seen in 12.9 percent of patients treated with Yervoy. When severe side effects occurred, Yervoy was stopped and corticosteroid treatment was started. Not all patients responded to this treatment. Patients who did respond in some cases did not see any improvement for several weeks.

Due to the unusual and severe side effects associated with Yervoy, the therapy is being approved with a Risk Evaluation and Mitigation Strategy to inform health care professionals about these serious risks. A medication guide will also be provided to patients to inform them about the therapy's potential side effects.

Yervoy is marketed by New York City-based Bristol-Myers Squibb.

-----
Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG @FayetteFP

The More Times a Woman Gives Birth, the Higher Her Risk of Rare but Aggressive 'Triple-Negative' Breast Cancer

/PRNewswire/ -- Full-term pregnancy has long been associated with a reduced risk of breast cancer, but a new study finds that the more times a woman gives birth, the higher her risk of "triple-negative" breast cancer, a relatively uncommon but particularly aggressive subtype of the disease. Conversely, women who never give birth have a 40 percent lower risk of such breast cancer, which has a poorer prognosis than other types of breast cancer and doesn't respond to hormone-blocking therapies such as tamoxifen.

These findings, from a study led by Amanda Phipps, Ph.D., a postdoctoral research associate in the Public Health Sciences Division of Fred Hutchinson Cancer Research Center, are published online ahead of the March 16 issue of the Journal of the National Cancer Institute.

"Unlike most breast cancers, triple-negative tumors don't depend on hormonal exposures to grow and spread, so our assumption going into the study was that reproductive factors would not be associated with a woman's risk of this cancer subtype," Phipps said. "We were surprised by these findings because researchers have known for quite some time that women who have children, especially those who have them at an early age and have multiple full-term pregnancies, have a lower risk of breast cancer overall."

While never giving birth appears to be protective against triple-negative breast cancer, the researchers found that women who remain childless have about a 40 percent higher risk of estrogen-receptor-positive breast cancer - the most common form of the disease, which can be treated with estrogen-blocking drugs - as compared to those who have one or more offspring. This higher risk of estrogen-receptor-positive breast cancer among women who have not had children is well established, and it is thought to be related to the fact that such women do not undergo pregnancy-related changes in the breast that confer a lifelong protective effect.

"The mechanisms by which full-term pregnancy contributes to an increased risk of triple-negative breast cancer and a decreased risk of other forms of the disease are not clear," Phipps said. "We do know that the hormones of pregnancy induce certain changes in the cellular structure of the breast. Overall, those changes seem to make the breast less susceptible to cancer. It is possible, however, that the increased risk of triple-negative breast cancer we found in women who had given birth may be due to some abnormal response of their breast tissue to the hormones of pregnancy. Another possibility is that pregnancy somehow makes the breast more susceptible to certain carcinogens even while reducing breast cancer risk overall," she said.

For the study, which was based on data from the Women's Health Initiative, Phipps and colleagues analyzed the detailed reproductive histories of some 150,000 postmenopausal women, more than 300 of whom went on to develop triple-negative breast cancer. "This particular study is significant because it is one of the largest studies ever conducted on the impact of reproductive history on triple-negative breast cancer," Phipps said.

Triple-negative breast cancer, which refers to any breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR) or Her2/neu, accounts for only 10 percent to 20 percent of all breast cancers, and only in the past decade have researchers become aware that this cancer subtype exists. "This research reinforces the notion that breast cancer is not just one disease," Phipps said.

"The mechanisms that lead to triple-negative breast cancer are likely different from those that lead to other forms of the disease. We still have a lot to learn about what causes this more aggressive form of breast cancer, but we hope that research like this will help us develop better tools to identify those women at greatest risk."

It is known that this cancer subtype is more predominant in African American women and it tends to be diagnosed at an earlier age. Researchers also know there is a strong link between genetic mutations in the so-called "breast cancer gene," BRCA1, and triple-negative breast cancer.

"More research is needed to better understand the causes of the most aggressive and lethal forms of breast cancer. While this study adds to our knowledge base, it should not change women's approaches to breast cancer screening," Phipps said.

The National Heart, Lung and Blood Institute of the National Institutes of Health funded the study, which also involved researchers from Albert Einstein College of Medicine, Georgetown University, Harbor-UCLA Medical Center, Stanford University, State University of New York at Stony Brook, the University of Buffalo, the University of Pittsburgh and Wake Forest University.

At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. www.fhcrc.org

-----
Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG @FayetteFP

Lasers ID Deadly Skin Cancer Better than Doctors

High-resolution images from a laser-based tool developed at Duke University could help doctors better diagnose melanoma, the deadliest form of skin cancer.

The improved diagnoses could potentially save thousands of lives and millions of dollars in unnecessary healthcare costs each year.

The tool probes skin cells using two lasers to pump small amounts of energy, less than that of a laser pointer, into a suspicious mole. Scientists analyze the way the energy redistributes in the skin cells to pinpoint the microscopic locations of different skin pigments.

For the first time, scientists have the ability to identify substantial chemical differences between cancerous and healthy skin tissues, said Thomas Matthews, a Duke graduate student who helped develop the new two-laser microscopy technique.

The Duke team imaged 42 skin slices with the new tool. The images show that melanomas tend to have more eumelanin, a kind of skin pigment, than healthy tissue. Using the amount of eumelanin as a diagnostic criterion, the team used the tool to correctly identify all eleven melanoma samples in the study. The results appear in the Feb. 23 Science Translational Medicine.

The technique will be further tested using thousands of archived skin slices. Studying old samples will verify whether the new technique can identify changes in moles that eventually did become cancerous.

Even if the technique proves, on a large scale, to be 50 percent more accurate than a biopsy, it would prevent about 100,000 false melanoma diagnoses, said Warren S. Warren, director of Duke’s Center for Molecular and Biomolecular Imaging and a chemistry professor. Warren oversaw the development of the new melanoma diagnostic tool.

cancertissueWarren's group has succeeded in using the laser pump method to locate two different types of skin pigments in skin tissue, which may better identify developing melanoma, said James Grichnik, a dermatologist at the University of Miami who was not involved in the study.

The work is limited to fixed tissue on slides, but holds promise for diagnosing melanoma prior to biopsy, and the increased diagnostic accuracy, without unnecessary biopsies, is where the new tool could have cost-saving potential, he said.

Melanoma is the fifth-most common cancer for males and sixth-most common for females. In 2010, U.S. doctors diagnosed nearly 115,000 new cases of the disease, with nearly 8,700 resulting in death. The cancer is also one of the few where the death rate is increasing.

Doctors typically use a light and a magnifying glass or tissue biopsy, where a pathologist removes suspicious skin cells and looks at them under a microscope, to spot signs of disease. But using a lens and a light is a “17th century” technique that is only 85 percent accurate, at best, and tissue biopsy is not much more reliable, Warren said.

In 14 percent of biopsy diagnoses, pathologists would disagree on whether or not the sampled cells were cancerous, according to a 2010 study published in the Journal of American Academy of Dermatology. The statistic implies that two pathologists would have opposing diagnoses on 214,000 to 643,000 melanoma cases each year, Warren said.

When studying biopsied tissue, doctors typically follow the “when in doubt, cut it out” philosophy. If they are not sure about the health of the skin tissue, doctors remove additional skin around the diseased cells. The first and second tissue biopsies can cost thousands of dollars. If the melanoma is thought have spread, patients may then have lymph nodes in their arms removed or undergo chemotherapy, which dramatically adds to treatment costs.

But not all of the extra treatment is necessary because not all of the biopsied tissues are actually cancerous. Doctors need a more accurate way to diagnose melanoma, Warren said.

In 2009, he received a $1 million Challenge Grant from the National Institutes of Health, which was part of the American Recovery and Reinvestment Act of 2009, to develop the imaging tool.

The highly specialized lasers are currently commercially available and would only need to be added to the microscopes pathologists already use to diagnose melanomas. The cost for the added instrumentation is about $100,000, which may sound like a lot of money. But if each false positive melanoma diagnosis costs thousands of dollars, having such an instrument available for questionable cases could considerably reduce health care costs overall, Warren said.

He added that suspicious moles would still have to be removed from a patient and then imaged to detect cancer.

Matthews is working on imaging skin cancers grafted on to mice to see if the tool could become a device dermatologists could use to scan a mole without removing it. A device like that would be much more expensive and would not be ready for a few years, Warren said. However, pathologists could begin using the lasers to study biopsied tissue now.

-----
Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG @FayetteFP

FDA approves first 3-D mammography imaging system

The U.S. Food and Drug Administration today approved the Selenia Dimensions System, the first X-ray mammography device that provides three-dimensional (3-D) images of the breast for breast cancer screening and diagnosis.

A mammogram is a safe, low-dose X-ray of the breast that is the best tool for early detection of breast cancer. However, with the limitations of conventional two-dimensional (2-D) imaging, about 10 percent of women undergo additional testing after the initial screening exam for abnormalities that are later determined to be noncancerous.

The Selenia Dimensions System, an upgrade to Hologic’s existing FDA-approved 2-D system, can provide 2-D and 3-D X-ray images of the breasts. The 3-D images may help physicians more accurately detect and diagnose breast cancer.

“Physicians can now access this unique and innovative 3-D technology that could significantly enhance existing diagnosis and treatment approaches,” said Jeffrey Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health.

The National Cancer Institute recommends women ages 40 and older have a mammogram every one to two years. Nearly 40 million mammograms are performed each year in the United States.

As part of the approval process, the FDA reviewed results from two studies where board-certified radiologists were asked to review 2-D and 3-D images from more than 300 mammography exams. In both studies, radiologists viewing both the 2-D and 3-D images obtained a 7 percent improvement in their ability to distinguish between cancerous and non-cancerous cases as compared to viewing 2-D images alone.

While the combination of the Selenia’s 2-D and 3-D images approximately doubled the radiation dose the patient received, it improved the accuracy with which radiologists detected cancers, decreasing the number of women recalled for a diagnostic workup. There is uncertainty for radiation risk estimates; however, the increase in cancer risk from having both a 2-D and 3-D exam is expected to be less than 1.5 percent compared to the natural cancer incidence, and less than 1 percent compared to the risk from conventional 2-D mammography.

The Mammography Quality Standards Act requires that all health care professionals obtain eight hours of training prior to using new mammography technology on patients. The FDA also requires that the manufacturer provide each facility with a manual clearly defining the tests required for initial, periodic, and yearly quality control measures.

According to the NCI, nearly 200,000 women will be diagnosed with breast cancer this year. And 1 in 8 women will be diagnosed with breast cancer during their lifetime. There is a 98 percent survival rate when breast cancer is detected early and still localized to the breast.

The Selenia Dimensions System is marketed by Bedford, Mass.-based Hologic Inc.

-----
Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG @FayetteFP

FDA approves opioid analgesic to help cancer patients manage pain

The U.S. Food and Drug Administration today approved Abstral (fentanyl) transmucosal tablets to manage breakthrough pain for adults with cancer. Fentanyl immediate-release transmucosal medications are administered on the soft surfaces of the mouth (inside of the cheek, gums, tongue), or the nasal passages or throat where they dissolve and are absorbed.

“This is an important step for patients with cancer pain to have options for the treatment of their breakthrough pain,” said John Jenkins, M.D., director of FDA’s Office of New Drugs in the Center for Drug Evaluation and Research.

Abstral is indicated for the management of breakthrough pain in patients with cancer, ages 18 years and older, who already use opioid pain medication around the clock and who need and are able to safely use high doses of an additional opioid medicine. Breakthrough pain is pain that comes on suddenly for short periods of time and is not alleviated by a patient’s normal pain management plan. These patients are considered opioid tolerant because of their current opioid medication use. Only health care professionals skilled in the use of Schedule II opioids to treat pain should prescribe this drug product.

Abstral is available only through a Risk Evaluation and Mitigation Strategy (REMS) program, which is intended to minimize the risk of misuse, abuse, addiction and overdose. Under this program, pharmacies, distributors, and health care professionals who prescribe to outpatients are required to enroll in the program to prescribe, dispense and distribute this product. FDA has standardized key components of the REMS program to facilitate the adoption of a single shared system. These components include the REMS document, the Patient-Prescriber Agreement, and the enrollment form. These components can be used by all sponsors of immediate release transmucosal fentanyl products to develop individual REMS programs such as the program approved for Abstral. FDA has also directed the sponsors of this class of products to work together on a single shared system to implement the REMS.

“This approval is also a significant step toward reducing the burden on the health care system of implementing REMS programs,” added Dr. Jenkins. “When fully implemented, FDA expects that prescribers, pharmacies, and distributors of all immediate release transmucosal fentanyl products will be able to use standardized materials and a single shared system to implement the REMS.”

The safety of Abstral was evaluated in 311 opioid-tolerant cancer patients with breakthrough pain. Two hundred and seventy of these patients were treated in multiple-dose studies. The duration of therapy for patients in multiple-dose studies ranged from 1-405 days with an average duration of 131 days and with 44 patients treated for at least 12 months.

Common adverse reactions include nausea, constipation, drowsiness and headache. Serious adverse events, including deaths, have been reported in patients with other immediate-release transmucosal fentanyl products. The deaths occurred as a result of improper patient selection and/or improper dosing.

Consumers and health care professionals are encouraged to report adverse side effects or medication errors from the use of Abstral to the FDA's MedWatch Adverse Event Reporting program at www.fda.gov/MedWatch or by calling 800-332-1088.

Abstral is manufactured by ProStraken Inc., based in Bedminister, N.J.

-----
Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG @FayetteFP

FDA begins process to remove breast cancer indication from Avastin label

The U.S. Food and Drug Administration announced today (December 16) that the agency is recommending removing the breast cancer indication from the label for Avastin (bevacizumab) because the drug has not been shown to be safe and effective for that use.

The agency is making this recommendation after reviewing the results of four clinical studies of Avastin in women with breast cancer and determining that the data indicate that the drug does not prolong overall survival in breast cancer patients or provide a sufficient benefit in slowing disease progression to outweigh the significant risk to patients. These risks include severe high blood pressure; bleeding and hemorrhage; the development of perforations (or “holes”) in the body, including in the nose, stomach, and intestines; and heart attack or heart failure.

In July 2010, after reviewing all available data an independent advisory committee, composed primarily of oncologists, voted 12-1 to remove the breast cancer indication from Avastin’s label.

“After careful review of the clinical data, we are recommending that the breast cancer indication for Avastin be removed based on evidence from four independent studies,” Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research. “Subsequent studies failed to confirm the benefit observed in the original trial. None of the studies demonstrated that patients receiving Avastin lived longer and patients receiving Avastin experienced a significant increase in serious side effects. The limited effects of Avastin combined with the significant risks led us to this difficult decision. The results of these studies are disappointing. We encourage the company to conduct additional research to identify if there may be select groups of patients who might benefit from this drug.”

Removing the breast cancer indication from the Avastin label will be a process. This is the first step. The drug itself is not being removed from the market and today’s action will not have any immediate impact on its use in treating breast cancer. Today’s action will not affect the approvals for colon, kidney, brain, and lung cancers.

Oncologists currently treating patients with Avastin for metastatic breast cancer should use their medical judgment when deciding whether a patient should continue treatment with the drug or consider other therapeutic options.

The agency has informed Genentech, Avastin’s manufacturer, of its proposal to withdraw marketing approval of the drug for breast cancer. Genentech has not agreed to remove the breast cancer indication voluntarily, so the agency has issued a Notice of Opportunity for a Hearing, which permits Genentech to request a public hearing if it wishes to contest the agency’s determination. The company has 15 days to request a hearing; if it does not do so, the hearing will be waived, and FDA will begin proceedings to remove the breast cancer indication.

Avastin, in combination with chemotherapy (paclitaxel), was approved in February 2008 under the FDA’s accelerated approval program, based on the results of a clinical trial known as “E2100,” which evaluated the drug in patients who had not received chemotherapy for their metastatic HER2-negative breast cancer. Under the accelerated approval program, a drug may be approved based on clinical data that suggest the drug has a meaningful clinical benefit, with more information being needed to confirm this. The program provides earlier patient access to promising new drugs to treat serious or life-threatening conditions while confirmatory clinical trials are conducted.

After the accelerated approval of Avastin for breast cancer, Genentech completed additional clinical trials and submitted the data from those studies to the FDA. These data showed only a small effect on “progression-free survival” without evidence of an improvement in overall survival or a clinical benefit to patients sufficient to outweigh the risks. The small increase in “progression-free survival” reflects a small, temporary effect in slowing tumor growth.

Avastin has also been associated with several other serious and potentially life-threatening side effects including the risk of stroke, wound healing complications, organ damage or failure; and the development of a neurological condition called reversible posterior leukoencephalopathy syndrome (RPLS), characterized by high blood pressure, headaches, confusion, seizures, and vision loss from swelling of the brain.

On the basis of all available data relating to the use of Avastin to treat metastatic breast cancer, the agency has determined that the risks of the drug outweigh the benefits for this use.

FDA is open to working with Genentech on any proposals to conduct additional studies of Avastin in patients with metastatic breast cancer designed to identify a population of patients in which the drug’s benefits exceed the risks.

------
Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG
www.FayetteFrontPage.com
Twitter: @FayetteFP

Oncologists Value Survival Over Quality of Life, Study Finds

For oncologists, drugs that help cancer patients live longer are worth more than drugs that help patients live well, according to research from Duke University's Fuqua School of Business and several health-related centers.

On average, oncologists were willing to prescribe treatments that cost about $245,000 to prolong life for one year, but the cost threshold dropped to about $119,000 per year for treatments that improve quality of life without prolonging patients' lives.

"Oncologists are understandably focused on survival, but they need to pay equal attention to the quality of life people experience during and after treatment," said senior author Peter Ubel, M.D., the John O. Blackburn professor of business administration at Fuqua.

The researchers found a wide range in what cancer doctors considered reasonable treatment costs. The threshold varied from $10,000 to $5 million per quality adjusted life year (QALY), a standard for assessing the cost-effectiveness of medical interventions. The spending thresholds assessed in the study were also measured in QALYs.

The research can be found on Medical Decision Making's website: http://bit.ly/fBIYBP.

The results highlight a critical problem in the struggle to control health care costs, Ubel said. Increasingly, doctors are being asked to consider whether very expensive cancer drugs -- some of which offer only small gains in survival -- are worth prescribing. But according to Ubel, the data on cost-effectiveness comes without guidelines for determining appropriate financial value in cancer care.

"Currently, individual oncologists are left to decide whether the benefits of expensive new drugs justify their costs," said Ubel. "Cancer care spending is unlikely to drop when there is such a broad range in what oncologists consider reasonable."

"The fact that these highly trained, wonderful doctors are confused about the issue suggests we as a society should discuss the cost of cancer care more explicitly. With health care spending emptying patients' pocketbooks, and bankrupting state and federal governments, we need to decide how much we should spend for small improvements in the quantity or quality of patients' lives."

The study results are based on a survey sent to members of the American Society of Clinical Oncology. The 768 physicians who responded considered two hypothetical scenarios involving a patient with metastatic cancer and a year to live.

The first scenario asked the doctor how much benefit, in months of survival gained, a new drug would need to provide for them to prescribe it. The new drug cost $75,000 more than standard treatment. The second scenario asked the doctor to indicate the highest cost at which they would prescribe a medication to improve the quality of life without prolonging survival.

The respondents consistently chose to spend more on life-prolonging treatments than on quality-enhancing treatments.

Additional authors of the study include Michael A. Kozminski and Aleksandra Jankovic of the Center for Behavioral and Decision Sciences in Medicine, University of Michigan Medical School in Ann Arbor, Mich.; Peter J. Neuman of the Institute for Clinical Research and Health Policy Studies, Tufts Medical Center in Boston; and Eric S. Nadler of the Charles Sammons Cancer Center, Baylor University Medical Center in Dallas.

The study was funded by grants from the California Healthcare Foundation and the Tufts Medical Center.

-----
Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG
www.FayetteFrontPage.com
Twitter: @FayetteFP

UGA researchers identify key enzyme that regulates the early growth of breast cancer cells

New University of Georgia research, published this week in the early online edition of the journal Proceedings of the National Academy of Sciences, has found that blocking the action of an enzyme called GnT-V significantly delays the onset and spread of tumors in mice with cancer very similar to many cases of human breast cancer.

When the GnT-V enzyme activity in the cells was increased in mammary gland cells, they increased proliferation and began to take on many characteristics of cancer cells. Using a mouse model of human breast cancer, tumors appeared when the enzyme was deleted, but onset was delayed an average of 10 weeks in the mice.

“In human terms,” said Michael Pierce, director of the UGA Cancer Center and study co-author, “the corresponding delay would be many months and maybe years. You basically are slowing everything down and keeping the cancer from forming and progressing very early.” Slowing the pace of the cancer could eliminate its spread to other organs, keeping it localized where it could be treated successfully, Pierce explained.

The researchers, lead by Hua-Bei Guo, assistant research scientist in the department of biochemistry and molecular biology in the Franklin College of Arts and Sciences, stimulated breast cancer formation in mouse mammary glands by over-expressing a her-2 protein that is a growth receptor on the cell surface. The researchers note that over-expression of her-2 is associated with 25 to 30 percent of human breast cancers.

The GnT-V enzyme makes glycans, which are sugars on the cell surface that change in defined ways when the cell becomes cancerous. Glycans are released from the cell as glycoproteins, making them a promising early-detection marker in blood. The researchers studied a glycan made by GnT-V that appears when normal breast cells become cancerous. The GnT-V glycan product is found on her-2 and other receptors and acts to regulate the number of cancer stem cells in the tissue. The number of these cancer stem cells determines how rapidly the cancer will form and develop.

“Glycans often are ignored by scientists, because they’re very complicated and present unusual problems to identify and understand,” said Pierce. “This study is an example of how particular glycans that are present on various cell receptors can actually modulate the onset of tumor formation. That may give us new drug targets and new ways to kill the cancer cells specifically.”

The finding of Guo and the research team at UGA’s Complex Carbohydrate Research Center that the elimination of a glycan-synthesizing enzyme significantly reduced the population of breast cancer stem cells is unprecedented, they note.

“That population of cells appears to drive breast tumor formation in many cases,” said Pierce, who also is UGA’s Mudter Professor in Cancer Research, “and our research suggests that glycans may be potential targets to kill them selectively.”

Pierce likened the cancerous stem cells to the queen of an ant colony. “You can try to get rid of the anthill, but it will just come back if you don’t kill the queen,” Pierce said. “If we can target those cancer stem cells for elimination, that would be the most effective treatment.”

The research was supported by the National Institutes of Health. For more information on the UGA Cancer Center, see www.uga.edu/cancercenter/.

-----
Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG
www.FayetteFrontPage.com
Twitter: @FayetteFP

FDA Approves Xgeva to Help Prevent Cancer-Related Bone Injury

/PRNewswire/ -- The U.S. Food and Drug Administration approved Xgeva (denosumab) on Thursday to help prevent skeletal-related events (SREs) in patients with cancer that has spread (metastasized) and damaged the bone. Skeletal-related events include bone fractures from cancer and bone pain requiring radiation.

Xgeva is a monoclonal antibody that targets a protein involved in cancer-related bone destruction called human RANKL. Other FDA-approved drugs for similar conditions include Zometa (zoledronic acid) and Aredia (pamidronate disodium).

Xgeva is not approved for patients with multiple myeloma or other cancers of the blood.

"Bone metastases represent a major cause of pain and suffering in patients with cancer and can affect a patient's quality of life," said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research. "Xgeva has a different mechanism of action than currently approved drugs aimed at reducing bone complications from cancer."

Xgeva's safety and effectiveness were confirmed in three randomized, double-blind clinical studies in 5,723 patients comparing Xgeva with Zometa. One study involved patients with breast cancer, another in patients with prostate cancer, and a third included patients with a variety of other cancers.

The studies were designed to measure the time until occurrence of a fracture or spinal cord compression due to cancer or until radiation or surgery for control of bone pain was needed.

In patients with breast or prostate cancers, Xgeva was superior to Zometa in delaying SREs. In men with prostate cancer, the median time to an SRE was 21 months with Xgeva compared to 17 months with Zometa.

In patients with breast cancer, the median time to an SRE was 26 months with Zometa and has not yet been reached with Xgeva. In patients with other solid tumors, time to development of an SRE was similar for both Xgeva and Zometa. The most common solid tumors were non-small cell lung cancer, multiple myeloma, kidney (renal) cancer, and small cell lung cancer.

The most serious side effects experienced with Xgeva were low calcium levels in the blood (hypocalcemia), and osteonecrosis of the jaw, a severe disease resulting from reduced blood flow to areas of the jaw and exposed jaw bone, causing pain, swelling, numbness, or infection.

Denosumab was originally approved under another trade name, Prolia, in June 2010. Prolia is indicated to treat postmenopausal women with osteoporosis who are at high risk for bone fractures. Xgeva is administered using a higher dose and with more frequent dosing than Prolia. Denosumab has a different safety profile in patients with osteoporosis than in patients with cancer and bone metastases.

Xgeva is marketed by Thousand Oaks, Calif.-based Amgen.

-----
Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG
www.FayetteFrontPage.com
Twitter: @FayetteFP

FDA approves additional medical indication for Sprycel

The U.S. Food and Drug Administration today approved a new indication for Sprycel (dasatinib) for the treatment of a rare blood cancer when it is first diagnosed. The cancer, called Philadelphia chromosome positive chronic phase chronic myeloid leukemia (Ph+ CP-CML), is a slowly progressing blood and bone marrow disease linked to a genetic abnormality.

Sprycel, an oral kinase inhibitor, is believed to inhibit the activity of certain proteins responsible for the growth of cancer cells. The action allows bone marrow to begin reproducing normal red and white blood cells.

In June 2006, the FDA granted accelerated approval for Sprycel to treat adults with CP-CML with resistant disease or who were intolerant to prior therapy, including Gleevec (imatinib). The agency converted Sprycel to a regular approval in May 2009, after 24-month follow-up data from earlier clinical studies confirmed the treatment’s safety and effectiveness.

Other FDA-approved drugs to treat various forms of CML include Gleevec, approved in May 2001, and Tasigna (nilotinib), approved in October 2007.

The FDA granted Sprycel a priority review for Ph+ CP-CML.

This is the third drug approved for Ph+ CP-CML under accelerated approval, a process allowing the FDA to approve a drug to treat a serious disease with an unmet medical need based on an endpoint thought to reasonably predict clinical benefit. A company is required to collect additional long term efficacy and safety information data confirming the drug’s benefit. The accelerated approval program provides earlier patient access to promising new drugs while confirmatory clinical trials are being conducted.

“These drugs have dramatically changed the lives of patients with CML,” said Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research. “Results from additional CML studies continue to demonstrate the importance of studying cancer drugs in the earlier stages of a disease.”

In CML, too many blood stem cells develop into a type of white blood cell called granulocytes. These granulocytes are abnormal and do not become healthy white blood cells. These cells can build up in the blood and bone marrow so there is less room for healthy white blood cells, red blood cells, and platelets. When this happens, infection, anemia, or unexpected bleeding may occur.

One open-label, randomized clinical trial in patients with CP-CML evaluated the safety and effectiveness of Sprycel. The trial measured complete cytogenetic response (CCyR) and cytogenetic response (MCyR), gene-based indicators of how well the malignant cells respond to the treatment. The most commonly reported side effects of Sprycel included decreased bone marrow activity resulting in fewer red and white blood cells and platelets (myelosuppression), fluid retention, diarrhea, headache, musculoskeletal pain, and rash.

Sprycel is marketed by New York City-based Bristol-Myers Squibb. Tasigna and Gleevec are marketed by East Hanover, N.J.-based Novartis Pharmaceuticals.

-----
Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG
www.FayetteFrontPage.com
Twitter: @FayetteFP

FDA Funds Pediatric Trial Testing Genetically Reprogrammed HSV to Treat Cancer

/PRNewswire/ -- A clinical trial testing a genetically reprogrammed herpes simplex virus as treatment for deadly forms of childhood cancer has received a U.S. Food and Drug Administration grant to support the research.

The Phase I trial at Cincinnati Children's Hospital Medical Center currently focuses on testing the safety of the agent HSV1716 in patients. The study includes young patients with solid tumors such as rhabdomyosarcoma or Ewing's sarcoma. These cancers have limited treatment options and survival rates under 30 percent when the cancers recur and spread to other parts of the body.

Survival curves for stubborn, metastatic childhood cancers have leveled off in the last decade, underscoring the need for new therapeutic approaches, says Timothy Cripe, M.D., Ph.D., principal investigator on the trial and a physician/researcher in division of Hematology/Oncology at Cincinnati Children's.

"We've exhausted our ability to improve cure rates with existing conventional therapies, and we need new solutions," he said. "This is why we are testing HSV. It's a potent virus that has been manipulated genetically with the intent of making it safe for the patient. When you're trying to fight fire with fire you need something that is strong."

The $600,000 grant from FDA is part of a program encouraging clinical development of "orphan drugs" as new treatments for rare diseases or conditions. The HSV1716 virus being tested in this trial was developed by Crusade Laboratories of Glasgow, Scotland.

HSV1716 is similar to other viruses now under development by Dr. Cripe and colleagues at Cincinnati Children's in that certain genes are removed so the virus does not infect healthy dormant cells or cause the disease in the recipient. Instead, the genetic manipulation is designed to prompt the virus to target, infect and degrade only rapidly dividing cancer cells.

Genetic information also can be added to HSV that programs the virus to attack cancer cells in other ways – such as activating certain types of chemotherapies in a one-two punch or destroying blood vessels that feed tumors. Research in mouse models of human cancer by Cripe's laboratory has shown oncolytic HSV agents to be effective at shrinking a variety of modeled tumor types, suggesting a possible approach for treating human disease.

"Our goal in the current HSV1716 trial is to light a fire to the cancer so that the virus replicates and spreads to the cancer cells," Dr. Cripe explained. "We have to take this one step at a time, and the initial phase of the trial focuses on making sure the virus doesn't cause adverse side effects. It has been tested in Europe in adults with brain cancer, squamous cell carcinoma and melanoma and shown in those trials to be safe."

HSV1716 has also been tested extensively for safety in animal models at Cincinnati Children's Hospital by Dr. Cripe and in Europe prior to it being tested in people.

The Phase I trial will include up to 18 patients and is expected to last three years. The optimum safe dosing for this virus is unknown, so the study will sequentially increase dosing levels in small groups of patients and observe for side effects as the trial proceeds. This earliest phase tests the lowest dose on older children and young adults with solid tumor cancers who have limited or no standard therapy options available.

The researchers plan to add younger patients with earlier stages of cancer as the trial proceeds. They will not be able to determine if the safety trial is successful until all patients have received treatment and the results analyzed. As with all clinical trials of new anticancer therapies in patients, many factors can influence the risk for severe side effects and anticancer activity. Even though HSV1716 may cause tumor shrinkage in mouse models of pediatric cancer, it may not have antitumor effect in patients.

Initial funding for the trial came from a private foundation, Solving Kids Cancer, of New York. Preclinical research that helped lead to the trial was supported by the American Cancer Society, the National Cancer Institute, the Cincinnati Children's Hospital Medical Center Translational Research Initiative and local foundations, including CancerFree Kids, teeoffagainstcancer.org, the Katie Linz Foundation, The Sarah Zepernick Foundation, the TeamConnor Cancer Foundation and money donated in memory of Katie McKenna Cappel and Zachary Heringer.

-----
Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG
www.FayetteFrontPage.com
Twitter: @FayetteFP

Radiotherapy Centers of Georgia in Partnership with Northside Hospital Present Breast Health & Cancer Awareness Day

Educating the Community on Breast Cancer Awareness October 2, 2010

Have you checked your breasts today? In 2009, the American Cancer Society estimated approximately 40,170 women died from breast cancer. In Georgia, an estimated 5,840 women will be diagnosed with breast cancer and 1,140 women will die from the disease this year. October is Breast Cancer Awareness Month and Radiotherapy Centers of Georgia – Cherokee County, in partnership with Northside Hospital-Cherokee, is presenting the 2nd Annual Breast Health & Cancer Awareness Day on Saturday, Oct. 2, 2010 at the Northside Hospital–Cherokee Conference Center, located at 1130 Bluffs Parkway in Canton, GA 30114.

“Breast Cancer is the leading cause of cancer death in women behind lung cancer,” said Sandra Gregory, M.D., radiation oncologist of Radiotherapy Centers of Georgia – Cherokee County. “It is a disease which is 100 percent treatable if caught early, so it is important to be educated and aware.”

The 2nd Annual Breast Health & Cancer Awareness Day will begin at 10 a.m. and run until 2 p.m., with featured lectures from renowned female physicians and breast specialists -- moderated by Sandra Gregory, M.D. The day’s activities will feature three panels addressing three crucial topics for women: Wellness and Prevention, Latest Treatment and Technology and Recent Developments in Breast Cancer.

Each panel consists of some of the best and brightest in their field. Peahen Gandhi, M.D., OB/GYN, Courtney Sinclair, M.D., GYN and Angela Falany, M.D. will discuss wellness and prevention; Anita Johnson, M.D., Breast Surgeon, Angela Robbins, M.D., Breast Surgeon and Lynn Baxter, M.D., Diagnostic Radiologist will speak towards the latest treatment and technology; and the third panel on recent developments in Breast Cancer will feature Rosa Langella, M.D., Breast Surgeon, Kathleen Long, M.D., Medical Oncologist, Gena Volas-Redd, M.D., Medical Oncologist and Sandra Gregory, M.D., Radiation Oncologist.

This free education event is an opportunity for women of the community to learn about genetic testing, partial breast irradiation, diet and nutrition, changes in surgical management of breast disease and breast cancer prevention. Northside Hospital’s ScreenAtlanta mobile mammography van will be onsite performing mammograms and attendees will also have an opportunity to sign up with StoryCorps Atlanta to go in-studio and record their personal experiences with Breast Cancer.

“Women who have been diagnosed or have loved ones who have been diagnosed are always the most eager to learn every last detail about Breast Cancer. But it is just as important, if not more important for those who are not as aware to be educated and proactive in getting screened,” said Dr. Gregory.

Breakfast, a survivor program and luncheon will be provided with a special butterfly release to honor all those who have fought and won the cancer battle. The 2nd Annual Breast Health and Cancer Awareness Day is free and open to the public. Registration is recommended, but only required for those requesting mammograms. To register, please call 404-845-5555 and press “0,” Monday through Friday from 8:30 a.m. to 4 p.m.

Sponsorship opportunities are still available. For more information on Breast Cancer Symposium 2010 or sponsorship opportunities, contact Toni Karasik at 678-965-4756 x. 115 or e-mail tkarasik@rccancercenters.com.
---
Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG
www.FayetteFrontPage.com
Twitter: @FayetteFP

Mayo-Led Researchers Discover Genetic Variants Modifying Breast Cancer Risk

Individuals with disrupting mutations in the BRCA1 gene are known to be at substantially increased risk of breast cancer throughout their lives. Now, discoveries from an international research team led by Mayo Clinic researchers show that some of those persons may possess additional genetic variants that modify their risk. These new findings enhancing individualized medicine appear in the current Nature Genetics.

"These findings should be useful in helping determine individual risk for breast cancer in BRCA1 carriers," says Fergus Couch, Ph.D., Mayo investigator and senior author of the study. "It also provides insights into hormone-receptor-negative breast cancer in the general population."

Genetic mutations in the BRCA1 gene give carriers of these mutations an increased risk for developing breast cancer. To determine if any genetic variations would modify or alter this risk among large populations of the mutation carriers, the researchers conducted genome-wide association studies (GWAS) that ultimately spanned 20 research centers in 11 different countries.

They first studied 550,000 genetic alterations from across the human genome in 1,193 carriers of BRCA1 mutations under age 40 who had invasive breast cancer and compared the alterations to those in 1,190 BRCA1 carriers of similar age without breast cancer. The 96 single nucleotide polymorphisms (SNPs) discovered were subsequently studied in a larger sample population of roughly 3,000 BRCA1 carriers with breast cancer and 3,000 carriers without cancer. Researchers found five SNPs associated with breast cancer risk in a region of chromosome 19p13.

Further studies of those SNPs in 6,800 breast cancer patients without BRCA1 mutations showed associations with estrogen-receptor-negative disease, meaning cancer in which tumors don't possess estrogen receptors. In another GWAS involving 2,300 patients, the five SNPs also were associated with triple-negative breast cancer, an aggressive form of the disease accounting for about 12 percent of all breast cancer. Triple-negative tumors don't express genes for estrogen or progesterone receptors or Her2/neu. The researchers also found that these SNPs were not related to risk for ovarian cancer in BRCA1 mutations carriers.

By locating these risk-modifying SNPs, the researchers have provided a target for better understanding the mechanisms behind the development of breast cancer. Furthermore, when combined with other risk-modifying SNPs that remain to be identified in ongoing studies by this group, it may be possible to identify certain BRCA1 carriers who are at lower risk of cancer and, also, carriers at particularly elevated risk of cancer who may decide to change their approach to cancer prevention.

Support for the research came from the Breast Cancer Research Foundation, Susan G. Komen for the Cure, the National Institutes of Health, and Cancer Research UK. In addition to first author Antonis Antoniou, Ph.D., of Cambridge University, over 180 individuals and several consortia contributed to the research and are co-authors.
---
Community News You Can Use
Click to read MORE news:
www.GeorgiaFrontPage.com
Twitter: @gafrontpage & @TheGATable @HookedonHistory
www.ArtsAcrossGeorgia.com
Twitter: @artsacrossga, @softnblue, @RimbomboAAG
www.FayetteFrontPage.com
Twitter: @FayetteFP
---

Explaining “How & Why” Cancer Cells Eat Us Alive

Newswise — Four key studies now propose a new theory about how cancer cells grow and survive, allowing researchers to design better diagnostics and therapies to target high-risk cancer patients. These studies were conducted by a large team of researchers at Thomas Jefferson University’s Kimmel Cancer Center.

This new idea also explains why so many cancer patients say that “their cancer is eating them alive” – an accurate observation that has never been understood, the researchers say.

These four new studies, co-published in the September issue of the journal Cell Cycle, provide evidence that tumor growth and metastasis is directly “fueled” by normal supporting cells.

These supporting cells are called fibroblasts, and they produce the stroma (connective tissue) that surrounds tumor cells. As the cancer progresses, increasing numbers of these stromal cells eat themselves to provide recycled nutrients to tumor cells – leading to dramatic weight loss in patients.

They also found that without recycled nutrients provided by fibroblasts, tumor cells are more fragile and die. Based on this breakthrough, the researchers propose that available drugs (now on the market), which sever the “parasitic” connection between tumor cells and fibroblasts, may be effective therapeutics.

“We think we have finally figured out how cancer really works – and this reverses 85 years of dogma, upon which current cancer research and therapy is based,” says the study’s senior investigator, Michael P. Lisanti, M.D., Ph.D., Chairman of Jefferson’s Department of Stem Cell Biology & Regenerative Medicine.

The prevailing theory, known as the Warburg Effect, developed by German researcher Otto Warburg in 1924 (for which he won a Nobel prize), says that tumor cells change their metabolism in order to fuel their own growth. As evidence, Warburg pointed to a lack of mitochondria, which are tiny “power plants,” in laboratory cancer cells, saying these cells have found another way to produce the energy they need.

Richard Pestell, MB, BS, MD, Ph.D, FRACP, director of the Kimmel Cancer Center and co-author on these studies notes, “These studies suggest that the absence of mitochondria in laboratory cancer cells may reflect in part that cultured cells have had to adjust to life outside of their original environment, without their stromal partner.” Drs. Lisanti, Pestell and colleagues found this out by performing a simple experiment in which they mixed cancer cells and fibroblasts together, and then searched for mitochondria. The found the fibroblasts didn’t have any mitochondria, and that the cancer cells had all the mitochondria.

“The Warburg Effect is happening, but it is happening to fibroblasts, not to cancer cells. Fibroblasts have no mitochondria because they are eating them to provide energy to cancer cells, and cancer cells have a ton of mitochondria because they need these power plants to process all the recycled nutrients given to them by fibroblasts, which then helps them grow and spread,” Dr. Lisanti says.
They have dubbed this finding “The Reverse Warburg Effect.”

“It’s amazing,” Dr. Lisanti says. “Much of what we know about cancer is backwards because cancer researchers used isolated tumor cells for most cancer studies. Now, when we put cancer cells back in their stromal environment, we see how cancer cells critically depend on fibroblasts for their survival.”

Tumor cells do this by employing oxidative stress as a weapon. Then, oxidative stress in fibroblasts “tricks” these stromal cells into eating themselves to feed cancer cells, the researchers say. This process of “self-eating” or “self-cannibalism” is called autophagy.

During periods of starvation, normal cells undergo autophagy. This metabolic re-programming allows cells to recycle nutrients by continually eating themselves, including their mitochondria. This permits starving cells to recycle nutrients and to survive under hostile conditions.

Now, Dr. Lisanti and colleagues have figured out how cancer cells take advantage of this recycling process. To satisfy their large appetite, hungry cancer cells induce oxidative stress in the fibroblasts and this stress forces the stromal cells to eat themselves, which provides recycled nutrients or “food” to fuel survival of nearby cancer cells.

“It’s that simple. Cancer cells are eating us alive by stealing nutrients from normal cells using oxidative stress, and by employing those recycled nutrients to support their own growth. Stem cells are then recruited from the bone marrow to produce fresh fibroblasts, to continually fuel cancer cell growth,” Dr. Lisanti says. “For years, cancer patients have said they felt as though the cancer in their body was eating them alive. These patients were right. Essentially, the cancer knows how to induce oxidative stress and turns a local wasting process into a whole-body phenomenon.”

Co-author Ubaldo Martinez-Outschoorn, M.D., a medical oncologist at Jefferson says “Patients have been telling us that cancer is eating them alive for years: Now we know they were right!” One of his cancer patients recently said, “Doc, I can’t eat enough food to maintain my weight. No matter how much I eat, I feel tired, and I am always losing weight.”

“Now that we understand the mechanism, this reverses our thinking about cancer metabolism and about how to stop this stress and starve the cancer cells,” he says.

In one of the published studies, Dr. Lisanti shows that using anti-oxidants can prevent oxidative stress in the fibroblasts, thus cutting off the fuel supply to cancer cells, starving them. “We are now performing drug screening assays to discover new anti-oxidants and other molecules like this,” he says.

The researchers have additionally identified two key metabolites – ketones and lactate – produced by the co-opted fibroblasts that provide high-energy food to the cancer cells. This finding also explains a mystery and provides a warning.

The mystery concerns why people with diabetes are much more likely to develop cancer than non-diabetics. The reason, Dr. Lisanti says, is that diabetic patients produce elevated levels of ketones, and he now shows that ketones fuel cancer cell growth.

The warning comes from the common use of lactate, a type of sugar, in cancer patients. Surgeons often give their cancer patients an intravenous solution of lactate before, during, and after surgery, Dr. Lisanti says. “But we see that cancer cells are using energy-rich fuels, such as lactate, to increase their numbers of mitochondria to power cancer cell growth, survival, and metastasis, so surgeons may want to re-consider or stop this practice.”

The findings have led the researchers to question the value of research using isolated laboratory cancer cells – the basis of most cancer research – and the anticancer drugs that result from it.

For example, genetic mutations have long been thought to be the root cause of cancer, but Dr. Lisanti’s group observed that these alterations might be the consequence of the tumor cell’s interactions with the normal stroma. Oxidative stress induced by cancer cells in fibroblasts feeds back upon cancer cells, amplifying the production of reactive oxygen species (ROS). They believe that ROS is then used by cancer cells to mutate their own genes to promote survival.

“These ROS molecules cause DNA damage in the cancer cells, resulting in genomic instability - random mutations and DNA breakage, as well as abnormal chromosome numbers. This instability helps cancer cells evolve into a more aggressive form,” Dr. Lisanti says.

“So, we see three consequences resulting from activating oxidative stress in normal stromal cells,” he says. “First, it forces stromal cells to make food for cancer cells. Second, this abundance of food protects the cancer cells against death. Finally, oxidative stress modifies cancer cell DNA, causing mutations and allowing them to evolve into a more aggressive form.”

Additionally, the researchers say their new theory of stromal metabolic re-programming suggests that cancer cells do not need blood vessels to feed them, which explains why some angiogensis inhibitors (drugs that shut down blood vessel growth) have not worked – and, in fact, may be dangerous.

“If an aggressive cancer cell can use oxidative stress to extract nutrients from normal stromal cells, it can go anywhere without the need for a blood supply. This may be how cancer cells spread all over the body,” Dr. Lisanti says. “Furthermore, angiogenesis inhibitors induce hypoxia, which is low oxygen, in the stroma. This is exactly the condition that drives nutrient recycling via autophagy. So angiogenesis inhibitors may help provide food or recycled nutrients to feed cancer cells. This explains why angiogenesis inhibitors have been very disappointing in clinical trials, as they may be having just the opposite effect, promoting cancer cell growth and metastasis.”

These new findings also have clear implications for cancer diagnosis, the researchers say. Many of the molecules that Dr. Lisanti’s group identified could be used as diagnostics to identify high-risk cancer patients or to monitor the success of their anti-cancer therapy.

Among them is caveolin-1 (Cav-1), which is produced by fibroblasts. Dr. Lisanti had shown earlier that loss of Cav-1 predicts poor prognosis in breast cancer patients, and is linked to early tumor recurrence, metastasis, and drug resistance. He now understands why, as breast cancer patients with absent stromal Cav-1 are feeding their cancer cells via recycled nutrients. That explains why a loss of stromal Cav-1 is such a good biomarker for identifying high-risk patients.

“The idea that a cancer cell’s local environment is important for tumor growth is now well-accepted by the cancer research community,” Dr. Lisanti says. “Now we show why this notion is correct.”

These studies were funded in part by grants from the NIH/National Cancer Institute, Susan G. Komen for the Cure, The American Cancer Society, The Breast Cancer Alliance, The Falk Medical Research Trust, The Landenberger Research Foundation and The Pennsylvania Department of Health.

-----
Community News You Can Use
www.fayettefrontpage.com
Fayette Front Page
www.georgiafrontpage.com
Georgia Front Page
Follow us on Twitter:  @GAFrontPage

Technique to Preserve Fertility in Young Women May Be Unsafe for Patients With Leukemia

/PRNewswire/ -- Although the use of ovarian tissue cryopreservation and transplantation has lead to 13 live births in women with lymphoma or solid tumors, this method of fertility preservation may be unsafe for patients with leukemia, according to a recent study published online in Blood, the journal of the American Society of Hematology. The method involves removing and freezing ovarian tissue before the patient undergoes aggressive chemotherapy and radiotherapy, and then reimplanting the tissue once the cancer has been brought under control. One major concern with leukemia patients is the risk that their frozen-thawed ovarian tissue might harbor malignant cells that could induce a recurrence of the disease after reimplantation.

"Our study provides clear evidence that cancer cells in women with acute and chronic leukemias can contaminate the ovaries," said Marie-Madeleine Dolmans, MD, professor at the Universite Catholique de Louvain in Brussels and lead author of the study. "If this tissue is reimplanted in these women when they're ready to have children, there's a good possibility that the cancer will come back."

As most acute lymphoblastic leukemia (ALL) patients are diagnosed with the disease at a young age, consideration of the preservation of their fertility is especially important. In fact, according to the National Cancer Institute, 71 percent of those diagnosed with ALL are less than 35 years old, as are nearly 10 percent of those with chronic myelogenous leukemia (CML)(1). In 2010, it is estimated that 2,180 women will be diagnosed with ALL and 2,070 with CML(1).

As aggressive chemotherapy and radiotherapy are damaging to the reproductive organs, the researchers wanted to examine the safety of using ovarian tissue cryopreservation to safeguard the fertility of patients with leukemia. In this study, researchers examined the implications of the technique in 12 women with ALL, a fast-growing cancer of the white blood cells, and six women with CML, a slowly progressing bone marrow cancer. The 18 patients included in this study were between 2 and 31 years of age when their ovarian tissue was cryopreserved (from 1999 to 2008). The mean age of the patients with ALL was 14.5 years and 24.7 years for those with CML.

Although initial microscopic examination did not reveal any cancerous cells in the ovarian tissue samples collected from each patient, by using a technique called real-time quantitative polymerase chain reaction (RT-qPCR), the scientists found cancerous cells in the ovarian tissue of 70 percent of the ALL patients and 33 percent of the CML patients. For further analysis, the researchers engrafted the ovarian tissue samples into 18 healthy mice for an observational period of six months. In the mice who received tissue from CML patients, the grafts looked normal and did not appear to contain any cancerous cells. In contrast, four of the mice who received ovarian tissue from ALL patients developed tumors. Through use of RT-qPCR and the mouse model, the researchers demonstrated the viability and malignant potential of leukemic cells present in the frozen ovarian tissue, especially from ALL patients.

"Given our findings, further research is needed to develop safer options for fertility preservation in patients with acute and chronic leukemias," said Jacques Donnez, MD, professor at the Universite Catholique de Louvain in Brussels and co-author of the study.

"Leukemia patients can benefit from fertility preservation techniques," added Brandon Hayes-Lattin, MD, the Director of the Adolescent and Young Adult Center at the Knight Cancer Institute in Portland, Oregon. "But the strategies offered must be both effective and safe. Among its other strengths, this work emphasizes that molecular methods can be successfully applied to assessments of safety."

(1) National Cancer Institute. SEER Stat Fact Sheets. Available at: http://seer.cancer.gov/statfacts.

The American Society of Hematology is the world's largest professional society concerned with the causes and treatment of blood disorders. Its mission is to further the understanding, diagnosis, treatment, and prevention of disorders affecting blood, bone marrow, and the immunologic, hemostatic, and vascular systems by promoting research, clinical care, education, training, and advocacy in hematology. ASH provides Blood: The Vital Connection, a credible online resource addressing bleeding and clotting disorders, anemia, and cancer. The official journal of ASH is Blood, the most cited peer-reviewed publication in the field, which is available weekly in print and online.

-----
Community News You Can Use
www.fayettefrontpage.com
Fayette Front Page
www.georgiafrontpage.com
Georgia Front Page
Follow us on Twitter:  @GAFrontPage

Study on Fructose and Pancreatic Cancer Generates Premature and Potentially Misleading Conclusions

/PRNewswire/ -- A study published in the August issue of Cancer Research (1) has resulted in several premature and potentially misleading conclusions when it comes to fructose and its effect on pancreatic tumor cells. Unfortunately, the media covering this story, and even the authors, have been too quick to extrapolate the results of laboratory research on pure fructose to real-world conditions, which is not appropriate or helpful to consumers.

The main contribution of this paper is to demonstrate that cancer cells utilize fructose as an alternate substrate to glucose for fueling growth. Cancer cells are well known for having multiple mechanisms to escape the body's normal controls, which makes controlled laboratory studies poor models for generating meaningful results.

This study does not look at the way fructose is actually consumed by humans, as it was conducted in a laboratory, not inside the human body. The study also narrowly compared pure fructose to pure glucose, neither of which is consumed in isolation in the human diet. Humans consume a wide array of foods that contain both fructose and glucose in combination along with many other sugars and nutrients. Most notably, both sugar (sucrose) and high fructose corn syrup contain roughly 50 percent glucose and 50 percent fructose.

The study's authors inaccurately state that high fructose corn syrup is the most significant source of fructose in the diet, whereas in the United States more fructose is still consumed from sugar than from high fructose corn syrup. Indeed, worldwide, humans consume nine times as much sucrose as they do high fructose corn syrup. Fructose is a natural, simple sugar also commonly found in fruits, vegetables, table sugar, maple syrup, and honey.

The causes of pancreatic cancer are poorly understood. To blame one component of the diet is highly speculative based on one, small study done in a Petri dish.

People should seek the advice of physicians, rather than rely on any one study, to make important decisions on medical treatment for a serious disease such as cancer.

------
Community News You Can Use
www.fayettefrontpage.com
Fayette Front Page
www.georgiafrontpage.com
Georgia Front Page
Follow us on Twitter:  @GAFrontPage