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by Bob Chirdon, WTOL Vice President and General Manager
WTOL invited local high school valedictorians to Imagination Station for a day of fun and special recognition Monday.
As I walked around talking to these high-achieving young adults, I was reminded that there is hope. There are kids who still take studying seriously.
If you want to see pictures of some really bright students go to the Best of the Class page on WTOL.com.
As part of the program, each valedictorian appears in a commercial that airs on WTOL-TV in June. They also posed in a special photo with Jerry Anderson and Chrys Peterson. And then they just had fun at Imagination Station.
It was a terrific day.
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NASHVILLE, Tenn. (AP) - Officials prefer not to be noticed. The change at referee from the first half to the second during Tennessee's 27-16 victory over Atlanta couldn't be missed.
Ed Hochuli worked the first half, while Wayne Mackie ran the officiating crew Saturday night for the second half with Hochuli watching from the sideline. The move allowed Mackie, usually a head linesman, the experience of working a preseason game as the referee.
Hochuli went to the microphone several times. He corrected the game time on two clocks and noted Titans coach Mike Munchak couldn't challenge a possible turnover by Matt Ryan because officials had ruled the quarterback was in the grasp of defenders.
Mackie had his chance at two replay reviews and kept his announcements very brief.
Copyright 2013 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.
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STERLINGTON — The Lakeside Lady Warriors were eliminated from the LHSAA Class 2A softball playoffs with a 10-5 loss to Sterlington on Tuesday.
Sterlington jumped out to a 2-0 first inning lead, but the Lady Warriors came back with four runs in the top of the third to take a 4-2 lead. Subscribe to Read!


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At an airport press conference, Mr. Trump pronounced himself "very proud" of his role in getting the White House to "finally" release President Obama's birth certificate.
He then waded into the equally idiotic issue of President Obama's academic record. All in all, the press conference confirmed -- if confirmation was needed -- the widespread view that Mr. Trump is singularly unsuited to the job of President of the United States.
President Obama, for his part, held a news conference immediately following Mr. Trump's presser, in which he dismissed the conspiracy theories about his place of birth as patent nonsense and said that the country had much more important matters to deal with than side shows fanned by carnival barkers.
Having sawed the birthers off the plank by releasing his "long form" birth certificate, Mr. Obama seemed amused by the hubbub and pleased with the denouement.


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Detroit's next police chief wants to get something off his chest. It is a message for the crooks who think they don't have to answer to anyone."When you talk about middle aged, good Americans being carjacked and shot in the City of Detroit, home invasions, young individuals driving around in a very carefree manner armed with weapons with impunity, those days are over," said James Craig. "This police chief has no tolerance for violence.""We'll deal with you in a very ethical, legal way, but if you commit acts of violence, you are going to go to jail. I don't have time to stage events at a gas station about how to prevent crime. I need our officers out arresting those violent perpetrators. That's what's going to happen in Detroit.""I'm committed. I'm eager to get started because I know we're going to turn that corner, and I hope that the good men and women don't decide to leave and retire. I know there's a lot of fear of the unknown. I want them to stay," Craig added."I want the cops to know that they count. They're important. We value them. I want the community to know that we are a professional police agency, and professional police agencies don't ride around in dilapidated police cruisers."We asked Craig whether it will be Emergency Manager Kevyn Orr's plan or his that he will be putting into effect."I've hand a number of conversations with Kevyn Orr. I have a great deal of respect for Kevyn Orr. I think he inherited a very tough situation. He didn't create this situation. He inherited, so he's doing what he does. He went out and found a police chief, one that he believes will make a change that needed to be made," Craig said."To your question about who runs the police department, he's put that charge on me. I'm accountable. I'm responsible. James Craig is running the police department."
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29-year-old Trevaun Brooks was sentenced to 25 to 56 years in prison Thursday for raping a child.
Brooks was dating the mother of an 11-year-old girl. All three lived in the woman's Mount Clemens townhouse.
The girl attended school at Prevail Academy, a public charter school in Mount Clemens where Brooks worked as a janitor.
The girl gave birth to a baby in August of last year. The young mother was only 12 when the baby was born.
At first, the girl said a 15-year-old boy was the father, but then indicated her mother's boyfriend, Brooks, was the father. DNA testing confirmed that Brooks was responsible.
At his sentencing, prosecutors related a message from the girl's mother requesting that Brooks pay $300,000 restitution.
"The young lady is placed with her child and I know she's on state aid, and I'm guessing that is an estimation of the total amounts that will be paid out through this child's lifetime."
The defense reacted to the request, and Judge Mary Chrzanowski weighed in from the bench.
"As to that amount, judge, rather than order that outragous amount that could never be paid in the defendant's lifetime," Brooks lawyer said before the judge stopped him from further speaking.
"I don't believe it's outragous for a childbirth to be somewhere around at least $100,000. We don't know what the complications were, if any," Chrzansowski told him.
The judge will rule on restitution in November.
Just prior to sentencing, the defense offered more details in this despicable crime.
"As the report also indicates that unfortunatly he was drinking very heavily during this time period, but we've both talked about that and he's expressed to me that... was no excuse, in fact, for what has happened and only as part of an explination as to the horrible decisions that were made during that time period."
Before he was sentenced, Brooks asked to speak, offering words for the girl and her mother, who did not attend the sentencing.
"I want to start, first of all, your honor, by stating that I apologize to the victim and the victim's family and that I do take full responibility for the mistake that happened."
Investigators say Brooks was hired by the school after the girl became pregnant.
Disclosed in court, the baby and the girl were both placed in the care of Child Protective Services. However, just prior to this trial, the court was informed that the girl was returning to live with her mother.
The baby, who is now a little more than a year old, had been placed in the care of a state funded child welfare program.
WJBK-TV | Fox 2 16550 West Nine Mile Rd.Southfield, MI 48075Main Station: (248) 557-2000Newsroom: (248) 552-5103


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Crossing Disciplines to Explore Questions about Cancer
"A lot of the easy stuff [in cancer research] has been done," Dr. Elizabeth Blackburn said over the weekend at the annual meeting of the American Association for Cancer Research (AACR), currently under way in Orlando, FL. The "face of cancer research" is much more interdisciplinary today than in the past, and this is how new frontiers will be explored, she added.
Dr. Blackburn, who is president of AACR and a Nobel laureate for her pioneering research on telomeres, noted that life sciences, physical sciences, and engineering are converging: "Over and over, we are seeing what we thought were separate disciplines come together." Read more > >
Latest Surveillance Data Show Cancer Cases and Deaths Continue to DeclineLung cancer death rates in women decreased for the first time
Patients Taking Imatinib for CML Have Similar Risk of Death as General PopulationPatients in remission for at least 2 years are more likely to die from causes other than leukemia
Risk of Second Cancer Following Radiation Therapy Is SmallStudy finds less than 10 percent of second solid cancers could be linked to radiation therapy
Immunotherapy Targets Pancreatic Tumors from the OutsideAntibody spurs immune system to attack tissue surrounding tumors
Breast Cancer Genomes Sequenced to Study Drug ResponseStudy of 50 genomes underscores the heterogeneity of breast cancer
Combination of Two Targeted Cancer Drugs Appears Safe in Early TestingResearchers observed some preliminary signs of anticancer effects for several cancers
Test May Detect Mesothelioma at the Earliest StagesAssay identifies proteins that may detect mesothelioma in people exposed to asbestos
NCI FY2012 Budget Proposal Available Online
NCI recently released The Nation's Investment in Cancer Research, a professional judgement budget for fiscal year 2012. The theme for this year's document is "Cancer: Changing the Conversation."
Menopausal Estrogen Therapy Benefits and Risks Vary by Age, WHI Analysis SuggestsEstrogen-only therapy decreased breast cancer risk in postmenopausal women with hysterectomy regardless of age
For People with Rare Skin Cancer Syndrome, Drug Brings Relief and HopeA targeted drug called GDC-0449 yields "stunning" results in clinical trial
Genome Study of Multiple Myeloma Opens New Avenues for ResearchFindings identify patients who may benefit from experimental drugs
Featured Clinical Trial: Inhibiting Tumor Angiogenesis in Metastatic Hormone-Refractory Prostate CancerWill new antibody be safe and effective in men with advanced disease?
FDA Update
- FDA Approves New Treatment for Late-Stage Melanoma
CMS Update
- CMS Issues Proposed Decision Memo on Medicare Coverage of Sipuleucel-T
Legislative Update
- Congressional Staffers and Advocates Take Part in Project Cancer Education
- NIH Research Plan Aims to Prevent and Treat Obesity
- Member Sites Selected for Cancer Immunotherapy Trials Network
- Free Telephone Workshop Series for Cancer Survivors
Selected articles from past issues of the NCI Cancer Bulletin are available in Spanish.
The NCI Cancer Bulletin is produced by the National Cancer Institute (NCI), which was established in 1937. Through basic, clinical, and population-based biomedical research and training, NCI conducts and supports research that will lead to a future in which we can identify the environmental and genetic causes of cancer, prevent cancer before it starts, identify cancers that do develop at the earliest stage, eliminate cancers through innovative treatment interventions, and biologically control those cancers that we cannot eliminate so they become manageable, chronic diseases.
For more information about cancer, call 1-800-4-CANCER or visit http://www.cancer.gov.
NCI Cancer Bulletin staff can be reached at email@example.com.
Featured Article
Crossing Disciplines to Explore Questions about Cancer
"A lot of the easy stuff [in cancer research] has been done," Dr. Elizabeth Blackburn said over the weekend at the annual meeting of the American Association for Cancer Research (AACR), currently under way in Orlando, FL. The "face of cancer research" is much more interdisciplinary today than in the past, and this is how new frontiers will be explored, she added.
Dr. Blackburn, who is president of AACR and a Nobel laureate for her pioneering research on telomeres, noted that life sciences, physical sciences, and engineering are converging: "Over and over, we are seeing what we thought were separate disciplines come together."
She was speaking to reporters about new research exploring possible connections between telomere shortening, chronic psychological stress, and the risk of certain cancers. While the research is preliminary, the study is an example of how investigators in disciplines that may not have worked together in the past are combining efforts.
There have been many such examples at the AACR annual meeting, where the theme is "Innovation and Collaboration: The Path to Progress."
"The concept of team science is important," said Dr. José Baselga of the Massachusetts General Hospital Cancer Center. Not only are basic scientists and clinicians collaborating more, but investigators from different institutions, who may have been competitors in the past, are now sharing data from the beginning of a project, he added.
The meeting's plenary session featured several talks about translating basic research into new tools for detecting, treating, and preventing cancer. NCI Director Dr. Harold Varmus also discussed what he called "imperatives" in times of uncertain budgets. These included the reorganization of the NCI Clinical Trials Cooperative Groups, a new center for cancer genomics (to oversee the diverse efforts in the field), a new center for global health, and cancer prevention.
"Good science begins with good questions," said Dr. Varmus during a brief discussion about NCI's Provocative Questions Project. The project Web site is dedicated to collecting important but non-obvious questions that will stimulate the cancer research community to think in creative ways about the problem of cancer. Dr. Varmus invited the audience to join the online discussion.
Last week, the Annual Report to the Nation on the Status of Cancer was released. The authors reported continued decreases in both new cancer diagnoses (incidence) and cancer deaths. Of note, lung cancer death rates in women declined for the first time in decades.
In a talk at the plenary session, Dr. Paul Bunn, Jr., executive director of the International Association for the Study of Lung Cancer, welcomed this news. But he noted that half of lung cancer cases develop in former smokers, so new tools are needed to reduce the risk of lung cancer in people who have quit smoking.
—Dr. Harold Varmus
Dr. Bunn presented results from a clinical trial testing whether a drug called iloprost can help repair damaged lung tissue in former smokers. The researchers used abnormal cell changes, known as endobronchial dysplasia, to assess the drug's effect. They concluded that measuring a chemopreventive agent's effect on endobronchial dysplasia could help predict whether the agent is effective.
"A team science approach will be critical" for identifying potential chemoprevention agents and markers to assess their effectiveness, noted Dr. Waun Ki Hong of the University of Texas M. D. Anderson Cancer Center during a talk about personalized approaches to lung cancer prevention at the plenary session.
New technologies are driving changes in how clinical trials are designed, noted Dr. John Heymach, also of M. D. Anderson. "In the past, when an interesting idea emerged [over the course of a study], you would then go back and look at the tumors to try to understand the result," he said. The goal now is to capture as much information as possible prospectively, he added.
Dr. Heymach predicted that, in a few years, tumors will routinely be analyzed using whole-genome sequencing. As a step in that direction, researchers at the AACR annual meeting reported preliminary results from the sequencing of tumors from 50 women with estrogen receptor-positive breast cancer, demonstrating the heterogeneity of the disease.
The hope, said lead investigator Dr. Matthew Ellis of the Washington University School of Medicine, is to eventually perform whole genome sequencing early in the treatment of the disease rather than retrospectively, so that doctors may select therapies based on the genetic alterations in a patient's tumor.
When people think about the fight against cancer, they often think about the treatment of cancer, noted Dr. Blackburn. "But more and more we have to think about prevention." Prevention can mean preventing the very earliest stages of the disease that unfold over years and preventing recurrences in survivors of the disease, she added.
The idea is "to intercept the biology of cancer as it unfolds on its deadly trajectory," Dr. Blackburn continued. "So we really have to understand the biology behind it."
Cancer Research Highlights
Latest Surveillance Data Show Cancer Cases and Deaths Continue to Decline
The overall rate of both new cancer diagnoses (incidence) and cancer deaths continued to decrease between 2003 and 2007, according to the Annual Report to the Nation on the Status of Cancer, published online March 31 in the Journal of the National Cancer Institute. The decrease in cancer death rates of 1.6 percent per year continues a trend that began in the early 1990s. Overall, the decrease in incidence rates for men and women combined was 1 percent per year.
The report also showed, for the first time, that lung cancer death rates in women decreased between 2003 and 2007. In addition, although cancer incidence rates continued to increase in children 19 years of age and younger, the rate of cancer deaths in this age group fell. Among all racial/ethnic populations, cancer incidence rates and cancer death rates decreased, except among American Indian and Alaskan Natives, for whom the mortality decrease was not statistically significant.
The report, which was co-authored by the North American Association of Central Cancer Registries, NCI, CDC, and the American Cancer Society, provides updated statistics on cancer trends through 2007. This year's report featured a special section on brain and other nervous system tumors, including nonmalignant brain tumors.
Nonmalignant tumors make up two-thirds of all adult brain tumors and one-third of childhood brain tumors, with meningiomas being the most common type of brain and other nervous system tumor in the United States. The authors found a decrease in the incidence of malignant neuroepithelial brain and other nervous system tumors from 1987 to 2007 and modest improvements in the 5-year survival rate for most types and age groups.
"It is gratifying to see the continued steady decline in overall cancer incidence and death rates in the United States—the result of improved methods for preventing, detecting, and treating several types of cancer," said NCI Director Dr. Harold Varmus. "But the full repertoire of numbers reported today also reflects the enormous complexity of cancer, with different trends for different kinds of cancers, important differences among our diverse people, and different capabilities to prevent, detect, and treat various cancers. Moreover, as our population continues to age, we have an obligation to discover and deliver better ways to control all types of cancers."
Patients Taking Imatinib for CML Have Similar Risk of Death as General Population
In an international study, the risk of death for chronic myelogenous leukemia patients treated with imatinib (Gleevec) who had been in remission for at least 2 years was not different from that of the general population. The Imatinib Long-Term (Side) Effects (ILTE) study, led by Dr. Carlo Gambacorti-Passerini from the University of Milano-Bicocca in Italy, is the first independent assessment of imatinib's long-term effects. The results were published online March 21 in the Journal of the National Cancer Institute.
The researchers enrolled 832 patients from 27 hospitals on five continents who were in remission after taking the drug for 2 years. The patients were followed for a median of almost 4 years from enrollment, corresponding to almost 6 years from the start of imatinib treatment. Only 27 patients experienced a major side effect associated with the drug during follow-up. More than half of patients experienced at least one mild side effect that affected quality of life, of which 68 percent were possibly or likely related to the drug. However, only 2.3 percent of patients discontinued treatment due to side effects.
At 6 years from the start of treatment, 95 percent of patients remained in remission. Of 20 observed deaths, only six were related to CML progression. "A comparison of the observed mortality rate in CML patients with the rate in the general Italian population showed no excess mortality," the authors wrote.
The excellent survival of the patients in this study "speaks to both the astounding effect [imatinib] has had on the clinical course of this disease and its negligible effect on the development of treatment-related malignancies," commented Dr. B. Douglas Smith of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in an accompanying editorial.
Dr. Smith noted that a large number of the patients (478) had received imatinib as second-line therapy, and 90 percent of those patients had previously received treatment with interferon. Further analysis of the data would be helpful to determine whether interferon played a role in the observed long-term remissions, suggested Dr. Smith.
Risk of Second Cancer Following Radiation Therapy Is Small
In a study of adults who survived at least 5 years after being treated for solid cancers that are routinely treated with radiation therapy, 9 percent developed a second solid cancer over an average follow-up time of 12 years. About 8 percent of those cancers appear to be related to radiation therapy. Results from the study, led by Dr. Amy Berrington de González of NCI's Division of Cancer Epidemiology and Genetics, were published online March 29 in Lancet Oncology.
In the first comprehensive analysis of its kind, Dr. Berrington de González and her colleagues examined data from nearly 650,000 adult patients recorded in nine of the Surveillance, Epidemiology, and End Results (SEER) registries between 1973 and 2002. Depending on their initial cancer type, between 23 percent and 79 percent of the patients received radiation therapy during treatment.
The researchers calculated the relative risk of developing a second cancer for patients who received radiation therapy during their initial treatment compared with patients who did not. The relative risk of developing a second cancer associated with radiation varied with type of first cancer and was highest in survivors of testicular seminoma. After adjusting for factors such as age, time since initial diagnosis, and year of diagnosis, the researchers estimated that about 3,300 of the 60,271 second cancers observed over the study period could be attributed to radiation therapy.
The study also described for the first time the overall absolute risk of second cancers related to radiation therapy: an estimated 5 of every 1,000 patients treated with radiation therapy who survive for 15 years would be anticipated to develop a radiation-related cancer. "That number can be used by doctors to convey the message to patients that the absolute risk of developing a second cancer related to radiotherapy is quite small," explained Dr. Berrington de González.
Further research will be needed to determine the risks from newer radiation therapy technologies, such as intensity-modulated radiation therapy (IMRT), which expose normal tissues to different patterns of radiation than older techniques. Previous studies have raised concerns "that the second cancer risk might be higher in patients treated with IMRT. We will need to study this exposure in the future to assess that risk," concluded Dr. Berrington de González.
Immunotherapy Targets Pancreatic Tumors from the Outside
Promising results from an early-stage clinical trial may lead to new treatment options for patients with advanced pancreatic cancer. The treatment appears to work differently than the trial investigators had expected, attacking tumors primarily by altering their surrounding tissue. The findings were published online March 25 in Science.
The phase I clinical trial, funded by Pfizer, involved 21 patients newly diagnosed with advanced pancreatic cancer, for whom current therapies are mostly ineffective and 5-year survival rates are less than 5 percent. Patients received the chemotherapy drug gemcitabine and a monoclonal antibody called CP-870,893 that binds to the CD40 receptor on the surface of certain immune cells.
Overall, four patients had some tumor shrinkage (partial response) and 11 saw their disease stabilize, with no further tumor growth. The median progression-free survival was 5.6 months and overall survival was 7.4 months, both of which are superior to what is historically seen in patients treated with the current standard of care, gemcitabine alone, explained the study's lead investigator, Dr. Robert Vonderheide of the University of Pennsylvania's Abramson Cancer Center.
The researchers expected the CD40 antibody to stimulate T cells to attack the tumor, but an analysis of tumor samples from two patients whose tumors responded to therapy found few or no T cells. The researchers did find an abundance of another type of immune cell, macrophages, which typically have been thought to help tumors ward off assault by the immune system.
To help determine what may be happening in these patients, the researchers treated mice that were genetically engineered to develop pancreatic cancer with a similar CD40-targeted antibody. This antibody was found to bind to macrophages outside of the tumor, Dr. Vonderheide noted. Consequently, he added, the macrophages "changed their properties, took on killing properties, and quickly migrated to the tumor." In the mice, he continued, "we saw the death of tumor cells themselves, but we also saw that the surrounding stroma was coming under attack by macrophages, almost dissolving."
The findings are preliminary, and further work is needed to better understand how the therapy works and how it can be best combined with other therapies, Dr. Vonderheide explained. The Abramson research team is launching another phase I trial to test the antibody in patients with metastatic melanoma, in combination with another experimental agent that stimulates T cells to attack tumor cells.
Breast Cancer Genomes Sequenced to Study Drug Response
Researchers have used whole-genome sequencing to catalog the genetic alterations in tumors from 50 patients with estrogen receptor (ER)-positive breast cancer. The goal of the study, which was presented at the AACR annual meeting, was to identify genetic factors that explain why some tumors respond to estrogen-lowering drugs and others do not.
Women with ER-positive breast cancer take estrogen-lowering drugs, such as tamoxifen or aromatase inhibitors, to slow the growth of tumors, make the tumors easier to remove surgically, or prevent the regrowth of tumors after surgery or radiation. But the treatment does not always work, and resistant tumors are associated with a poor prognosis. The genetic factors underlying resistance to estrogen-lowering therapy are not clear.
To investigate this question, Dr. Matthew Ellis of the Washington University School of Medicine in St. Louis and his colleagues studied the tumor genomes and normal genomes of 50 women with ER-positive breast cancer. The women were participants from two clinical trials testing aromatase inhibitors as neoadjuvant therapy. Patients received one of three types of aromatase inhibitors following a biopsy and prior to treatment with surgery. Twenty-six of the 50 patients had tumors that responded to aromatase inhibitors, and 24 had tumors that did not respond.
The analysis, which included approximately 10 trillion chemical bases of DNA, revealed a "constellation of mutations," including some that are common and some that are rare, noted Dr. Ellis. The vast majority of potential cancer-related mutations detected in the study were found in less than 5 percent of tumors.
"Breast cancer is extraordinarily complicated," said Dr. Ellis, "and the sequencing revealed a lot of new biology that we had not seen before." The researchers have begun the process of relating the mutations discovered in the study to the responses to estrogen-lowering therapies.
The commonly mutated genes included PIK3CA and TP53. In addition, MAP3K1, a tumor-suppressor gene, was defective in 10 percent of patients. This gene has been implicated in other cancers, but this is the first time the gene has been associated with breast cancer, according to the researchers.
The finding that half the tumors had mutations in PIK3CA was important because it underscores the opportunities to inhibit the effects of these changes in breast cancer, noted Dr. Matthew Meyerson of the Dana-Farber Cancer Institute, who discussed the results at the meeting.
Dr. Meyerson also said that his group has independently found frequent inactivating mutations in MAP3K1 in breast cancer, thereby "validating the remarkable results by Dr. Ellis." The current study, he noted, demonstrates the feasibility of conducting genomic analyses of breast cancer using next-generation sequencing in the context of cancer clinical trials.
Combination of Two Targeted Cancer Drugs Appears Safe in Early Testing
A small study testing a combination of two targeted drugs, each directed against a different pathway that is activated in cancer, has yielded positive results, researchers said at the AACR annual meeting. There were also some early indications that the combination treatment may have antitumor effects. The regimen was generally well tolerated, according to the researchers, and side effects were similar to those observed when the drugs were tested as single agents.
The combination therapy targets the RAS/RAF/MEK and PI3K pathways, which are among the most commonly mutated in cancer. Both drugs in the combination are made by Genentech; GDC-0973 inhibits the MEK pathway, and GDC-0941 targets the PI3K pathway.
"These pathways are altered in most tumors," said Dr. Johanna Bendell of the Sarah Cannon Research Institute in Nashville, who presented the findings. The researchers were testing the idea that combining the drugs would have synergistic effects, but they were concerned that the combination would be too toxic for patients, she noted.
In the current study, at least, this was not the case. The most common side effects included diarrhea, fatigue, rash, nausea, and vomiting. Most of these were mild, according to the researchers.
Of the 27 patients enrolled in the trial, tumor size decreased in five patients, including two patients with melanoma, one with prostate cancer, and two with non-small cell lung cancer. One patient with lung cancer and two patients with melanoma had stable disease over 6 months, the researchers said.
The study is ongoing, and the researchers will continue to study the optimal dose and monitor antitumor activity.
"Many people believe that if you hit multiple pathways [in cancer] you will have better results, and this is a pioneering effort," said Dr. Daniel Von Hoff of the Translational Genomics Research Institute, who moderated a press briefing on the study.
Dr. Bendell predicted that other companies will begin testing combinations of these targeted therapies. She acknowledged that testing two drugs that are produced by different companies can present additional challenges.
Test May Detect Mesothelioma at the Earliest Stages
An investigational test based on a panel of 13 protein markers in the blood may be able to detect malignant mesothelioma in people exposed to asbestos, even when the disease is in its earliest stages, according to findings from a study presented at the AACR annual meeting. To conduct the study, researchers used a technology that relies, in part, on DNA molecules called aptamers that bind to proteins in blood samples.
The study used a test developed by Colorado-based SomaLogic (which also funded the study). The test was used to analyze blood samples from 90 patients who had been exposed to asbestos and developed malignant mesothelioma and blood samples from 80 healthy participants who had been exposed to asbestos (control subjects). The research team, led by Dr. Harvey Pass from the New York University Langone Medical Center, used 75 percent of the samples to identify a panel of proteins that were routinely seen in blood samples from patients with mesothelioma but not in samples from the control subjects. Dr. Pass' laboratory is supported by NCI's Early Detection Research Network.
The biomarker panel in this "training set" had 80 percent sensitivity and 100 percent specificity for distinguishing between mesothelioma patients and control subjects and detected 15 of the 19 early-stage mesotheliomas, reported Dr. Pass. Similar results were seen in the remaining 25 percent of the samples, known as the validation set. During a press briefing, Dr. Pass also presented data on the test's performance in a different blinded validation set of samples from 38 patients with asbestos-related mesothelioma and 62 healthy asbestos-exposed control subjects. In this set, the marker panel had 92 percent specificity and 92 percent sensitivity.
In most patients with malignant mesothelioma, the disease is typically diagnosed at an advanced stage, when treatment has very limited success. So the ability to detect early-stage disease is important "because these are the people with mesothelioma who will have long-term survival," Dr. Pass said during the briefing.
The current incidence of malignant mesothelioma is low: approximately 3,000 cases a year in the United States. However, according to Dr. Pass, an estimated 27.5 million people in the United States alone had occupational exposure to asbestos between 1940 and 1979, and because of its long latency period, the incidence of mesothelioma is not expected to peak for another 20 years.
Additional validation studies of the assay are being planned, Dr. Pass said in an interview, and more aptamers are being added to the test in an effort to improve its performance.
Special Report
Menopausal Estrogen Therapy Benefits and Risks Vary by Age, WHI Analysis Suggests
Long-term follow-up data from the Women's Health Initiative (WHI) provide important new information about the potential risks and benefits of hormone therapy to treat symptoms or conditions related to menopause, including its effect on breast cancer risk. The results were published April 5 in the Journal of the American Medical Association.
Overall, the study found, among postmenopausal women who had had a hysterectomy, use of conjugated equine estrogens alone for an average of 6 years had little to no effect on the risk of death, coronary heart disease, colorectal cancer, and hip fractures, or on other serious health problems, compared with placebo treatment. Estrogen-only treatment was associated with a statistically significant decrease in the risk of breast cancer.
—Dr. Andrea LaCroix
However, there were some notable differences in estrogen effects by age. Estrogen therapy decreased the risk of heart disease and mortality among women in their 50s but markedly increased these risks for women in their 70s. In contrast, the decreased breast cancer risk associated with estrogen use was seen regardless of age.
The WHI estrogen-alone clinical trial, launched in 1993, randomly assigned more than 10,739 women between the ages of 50 and 79—all of whom were past menopause and had had a hysterectomy—to take daily estrogen or a placebo. In 2004, the study was stopped early because of an increased risk of stroke and blood clots in women receiving estrogen. Nearly 80 percent of the trial participants agreed to be monitored beyond the study's termination; this most recent analysis covers nearly 11 years of follow-up in trial participants.
The findings reinforce the concept that "estrogen affects many organ systems in the body and changes the risk of many diseases," said the study's lead investigator, Dr. Andrea LaCroix, of the Fred Hutchinson Cancer Research Center in Seattle. "Depending on age group and hysterectomy status, the consequences [of estrogen-only therapy] can vary dramatically."
The increased risks of stroke and blood clots that were seen while women were actively receiving treatment were no longer present after women halted therapy, the study authors noted.
The analysis is the latest update in an ongoing, large-scale effort to establish more definitively the risks and benefits of menopausal hormone therapy, including its effect on cancer risk and mortality. Previous studies from the WHI, for example, have clearly shown that combination therapy with estrogen plus progestin increases breast cancer incidence and death, as well as lung cancer mortality. And just 2 months ago, British researchers reporting on longer-term follow-up from the Million Women Study (MWS) also found that combination estrogen and progestin therapy, when started immediately after menopause, increased breast cancer risk regardless of hysterectomy status.
Earlier analyses from the WHI estrogen-alone trial suggested that there may be a reduction in breast cancer incidence, but it was only with longer-term follow-up that this trend reached statistical significance, according to Dr. Leslie Ford of NCI's Division of Cancer Prevention and the Institute's WHI liaison. In absolute terms, the current analysis indicated, there would be eight fewer cases of breast cancer for every 10,000 women who had undergone menopause and had a hysterectomy if they took estrogen daily for 6 years.
The WHI findings also contrast with some of the recent findings from the MWS, wrote Drs. Emily Jungheim and Graham Colditz of the Washington University School of Medicine in St. Louis, in an accompanying editorial. In the MWS—which was an observational study and not a randomized clinical trial like the WHI estrogen-alone trial—there was an increased breast cancer risk in women who began estrogen-only therapy within 5 years of menopause. The editorialists also pointed out that 68 percent of women in the WHI trial were 60 years of age or older when they entered the study.
"Given this fact and the findings from the Million Women Study, an important question that emerges is whether the WHI population is appropriate for reaching definitive conclusions regarding younger women and the risk of breast cancer associated with [menopausal hormone therapy]," they wrote.
Although she acknowledged the somewhat conflicting findings, Dr. Ford stressed that the WHI results are from a large, randomized clinical trial. Randomized clinical trials are considered to be the highest level of evidence and, consequently, are routinely used to inform clinical decision making.
Use of menopausal hormone therapy has continued to decline since the early 2000s, when the initial findings of the WHI clinical trial of estrogen plus progestin showed an increased risk of breast cancer and serious cardiac events with the combination. That decline has since been linked to a parallel decrease in breast cancer incidence rates.
In terms of breast cancer risk, Dr. Ford believes the results from the WHI estrogen-alone trial should be reassuring for younger postmenopausal women who have had a hysterectomy and are receiving or considering estrogen therapy. "For younger women," she continued, "they can feel more comfortable following the current guidelines for using the lowest dose of estrogen for the shortest time."
But both Drs. Ford and LaCroix agreed that for older women, the potential benefits of menopausal hormone therapy of any kind do not outweigh the risks.
"Our data clearly indicate that hormone therapy use in older women is potentially dangerous," Dr. LaCroix said.
For People with Rare Skin Cancer Syndrome, Drug Brings Relief and Hope
At times in her life, Julie Breneiser has simply stopped looking in the mirror. She didn't want to see the lesions on her skin or the scars from her many surgeries. Two years ago, the 53-year-old Breneiser underwent surgery to remove lesions every month for 6 months. "With each procedure, I missed work and had to explain my appearance to people," she recalled.
Breneiser and her two teenage children, who live in eastern Pennsylvania, have basal cell nevus syndrome (BCNS), a rare condition that predisposes them to develop lesions called basal cell carcinomas (BCCs). Some people with this inherited syndrome develop hundreds or thousands of BCCs and may experience other health problems.
Until recently, surgery has been the only treatment. But last year Breneiser enrolled in a clinical trial testing an experimental drug, a pill called GDC-0449. The drug interrupts cancer-promoting messages from the hedgehog signaling pathway, which is switched on inappropriately in individuals with the genetic mutation that causes the inherited syndrome.
For Breneiser, the treatment has brought dramatic results. "This has changed my life," she said. "To be involved in this trial—that may, some day, so positively change the lives of my children and thousands of others with this syndrome—is completely empowering and overwhelming."
Since starting the drug in January 2010, 60 percent of the BCCs that she had at the start of the trial have disappeared. Shallow pits on her palms, which are common among many people with BCNS, are also gone.
Others participating in the trial, which included 41 people, have had similar responses. Last December, the committee monitoring the trial concluded that there was a clear benefit from the drug and cut short the randomization part of the trial.
"Stunning" Preliminary Results
Dr. Ervin Epstein, Jr., of the Children's Hospital Oakland Research Institute presented preliminary results from the study of GDC-0449 at the opening plenary session of the AACR annual meeting on April 3. The treatment prevented the development of new tumors and shrank existing ones, markedly reducing the number of lesions that were big enough to warrant surgical attention, he said.
"This drug replaces the function of the missing gene, and it actually works," said Dr. Epstein, who has been studying the disease for 25 years. "The tumors basically melt away."
These are "stunning" results, said Dr. Daniel Von Hoff of the Translational Genomics Research Institute at the plenary. At the 2009 AACR annual meeting, Dr. Von Hoff presented positive results from the first trial of GDC-0449 in people with advanced BCC.
Based on his experience treating the disease, he stressed that the syndrome can be miserable for people. Some will be reclusive, choosing not to go out in public. The new drug represents a "breakthrough with a capital B," he added.
Side effects from the drug include hair loss, loss of the ability to taste, and muscle cramps. Some patients have chosen to stop taking the drug after a year or less because of these side effects. When the drug was stopped, some of the lesions returned.
"We're not there yet, but this is a wonderful milepost of progress," said Dr. Epstein. His collaborators included Dr. David Bickers of Columbia University Medical Center, who saw Julie Breneiser and about half the patients in the trial.
Fundamental Knowledge, Clinical Possibilities
Future studies will experiment with different doses and schedules of the drug to see if the same benefit can be achieved with fewer side effects, noted Dr. Jean Tang of the Stanford University School of Medicine and the first author of the study.
For years, no company wanted to invest in developing a targeted therapy for a rare disease that could be treated with surgery. Then, in 2004, researchers linked the hedgehog pathway to some common cancers, and almost overnight many companies began to develop inhibitors. At least two dozen clinical trials are now testing these agents. Developed by Genentech, GDC-0449, also called Vismodegib, is the farthest along.
Dr. Epstein co-led one of two research teams that identified the genetic mutation underlying BCNS in 1996, after a decade-long search. Years of research on the hedgehog pathway in model organisms provided the basic knowledge needed to move ahead with developing potential therapies.
"This story is a wonderful example of a clinical benefit based on fundamental molecular knowledge," said Dr. Epstein. "Who would have thought that trying to identify the gene in this very rare disease would eventually lead to clinical trials for common cancers?"
Dr. Von Hoff credited "some extraordinary observations and drug development" with making the current study possible, but he said that clinical science was important, too. "[The researchers] had to find the patients who would have the best chance of benefiting from the new agent," he noted.
In patients with a strong genetic predisposition to develop BCCs, the drug's preventive effects were evident within a year. "This study suggests a new way of doing prevention research that focuses on individuals who have a high tumor burden or genetic predisposition," said Dr. Tang.
"We get a lot of help from a support group," she added. The Basal Cell Carcinoma Nevus Syndrome Life Support Network, which includes more than 575 families, each with several affected members, provides information about the disease and helped with the recruitment for the trial.
"Our message is that you are not alone," said Kristi Burr, the network's executive director. The network supports participants in the trial and, through social media tools like Facebook and Twitter, connects people living in remote areas and those who may be reclusive.
"We say to people that you have to live your life every day," said Burr. "You can't be held hostage by this condition, and this therapy is removing the shackles."
For Julie Breneiser, the therapy has made the scars from her many previous procedures smoother and less prominent. Without having to undergo regular surgeries, she has more time for her family and her work helping children who have disabilities. "And I even like what I see in the mirror!" she said.
Further reading: In Cancer, Hitting a Target Called Hedgehog
A Closer Look
Genome Study of Multiple Myeloma Opens New Avenues for Research
In the most comprehensive genetic analysis of multiple myeloma to date, researchers have sequenced the genes of 38 patients with this uncommon blood cancer. The study confirmed some of the mutations known to play a role in this disease and uncovered additional alterations in genes and pathways that can now be investigated further.
For 23 of the patients, Dr. Michael Chapman of the Broad Institute and his colleagues sequenced the entire genomes of tumor cells and matched normal cells. A comparison of the results revealed suspicious changes in parts of the genome where no one had thought to look before, the researchers reported in the March 24 Nature.
"Our hope is that this study will catalyze research in [the field of] multiple myeloma," said Dr. Todd Golub of the Broad Institute and a leader of the study. Just a few years ago, the idea of decoding the genes of 38 patients with myeloma would have been unimaginable, he noted. But the recent introduction of new and cheaper technologies for sequencing DNA has made the goal achievable.
"We still see this as a preliminary study, but we can now launch into the next phase of the research with a higher level of confidence that the effort will bear fruit," said Dr. Golub, who directs Broad's cancer program. He presented initial results from the study last year.
The project was spearheaded by the Multiple Myeloma Research Foundation (MMRF), which was created in 1998 to speed the development of new treatments. The causes of this disease are unknown, and there is no cure. Multiple myeloma affects plasma cells, which are a type of white blood cell. Approximately 20,000 people are diagnosed with the disease in the United States each year, and the 5-year survival rate is less than 40 percent, the researchers noted.
An Unexpected Finding with Clinical Implications
A finding of particular interest was the discovery that some patients in the study had mutations in the BRAF gene, which is frequently mutated in melanoma and can drive cell growth. A number of BRAF inhibitors are in development, including PLX4032, which has shown promise in early trials in patients with melanoma.
Although the finding of BRAF mutations in myeloma was unexpected, the discovery raised the possibility that an existing drug could benefit some patients with the disease, noted co-author Dr. Kenneth Anderson of the Dana-Farber Cancer Institute. This finding, he added, underscores the importance of patients participating in clinical trials to evaluate potential therapies.
"I've been treating patients with multiple myeloma for over 30 years, and there's never been a more exciting time to make science work for patients," said Dr. Anderson. Genetic approaches, he continued, should allow researchers to identify the specific alterations in a patient's disease and use the information to select potential therapies and develop new ones. "One can advance the idea of picking the right medicine for the right patient at the right time," he added.
While the discovery of BRAF mutations may point to potential treatments, the genome study also yielded clues to the underlying biology of the disease.
Mutations were found in genes involved in RNA processing and protein folding, processes that are important for how normal cells function. Half of the patients had defects in one or more of these genes, including one called FAM46C that had never been linked to cancer before.
"We feel like we know so much more about this disease and about where our investigators should go in the future," said Kathy Giusti, the founder and chief executive officer of MMRF. A former pharmaceutical company executive who was diagnosed with multiple myeloma at age 37, she has been treated with the best therapies available.
When Giusti and her colleagues began to plan the genome study in 2005, they knew that high-quality specimens would be critical to the project's success. The MMRF had launched a tissue bank the previous year, and the 38 samples selected for the genome study came from this bank.
Collecting the appropriate samples "is one of the most challenging elements in conducting genomics research," Giusti said. But the MMRF has been successful. Since 2005, more than 3,000 patients have voluntarily donated bone marrow, blood samples, and related medical information to the tissue bank, according to the group.
Though not reported in the Nature study, samples from 250 additional patients have been profiled for genetic changes such as gains and losses of DNA at the Translational Genomics Research Institute (TGen). If the costs of sequencing DNA continue to drop, many or all of these samples may eventually be sequenced, Dr. Golub said.
More myeloma genomes need to be analyzed to develop a more complete picture of the genetic landscape of the disease, the researchers said. By focusing on a collection of patients rather than just a few individuals in the current study, the researchers uncovered mutations in 11 genes in the NF-kappa B signaling pathway, which promotes the growth of cancer cells.
Mutations were also found in genes that play a role in the packaging of DNA, or chromatin remodeling. Alterations of this type may affect the regulation of genes elsewhere in the genome and have been found in several cancers recently, including in a rare form of pancreatic cancer, a type of lymphoma, and the childhood cancer medulloblastoma.
Mutations in chromatin remodeling genes are increasingly becoming recognized in cancer, but "the field is very young and we do not yet understand the exact biological consequences of these changes," said Dr. Golub.
Making the Information Available
Looking ahead, Dr. Golub cautioned that it will be a challenge to translate the findings from genome studies into the clinic, in part because multiple genes play a role in myeloma. "It won't be a matter of just testing a patient for one or two genes," he said.
To accelerate progress against the disease, data from this initiative and other efforts are available to the scientific community through the Multiple Myeloma Genomics Portal."These results are exciting," Dr. Golub said, "because they provide a glimpse of what is coming in cancer genomics." A few days ago, another group of researchers announced that they had sequenced the tumor and normal genomes of 50 patients with a type of breast cancer.
While these are the largest cancer genome studies reported to date, they will likely be eclipsed by even larger studies in the months and years ahead.
Further reading: Why are Tissue Samples Important to Cancer Genomics?
Featured Clinical Trial
Inhibiting Tumor Angiogenesis in Metastatic Hormone-Refractory Prostate Cancer
Name of the Trial
Phase I/II Study of TRC105 in Metastatic Castrate Resistant Prostate Cancer (NCI-10-C-0062). See the protocol summary.
Principal Investigator
Dr. William Dahut, NCI Center for Cancer Research
Why This Trial Is Important
Prostate cancer is the most frequently diagnosed non-skin malignancy and second leading cause of cancer death among American men. Most prostate tumors initially depend on androgens, which are male sex hormones, to continue growing. To combat these growth-promoting effects, antiandrogen therapies, which lower the concentrations of male hormones in the blood to "castrate" levels, are administered after surgery or radiation therapy. Even in the presence of reduced hormone levels, though, some tumors will eventually start to grow again and are referred to as hormone refractory or castration resistant. Few treatments are available for castration-resistant prostate cancer (CRPC). However, the current standard of care for metastatic CRPC is a combination of the chemotherapy drug docetaxel and the steroid prednisone.
All solid tumors require an adequate blood supply for continued growth. Inhibiting the formation of new blood vessels, or angiogenesis, is a cancer treatment method that has shown promise in many types of advanced cancer and is under investigation as a treatment for prostate cancer. A previous clinical trial demonstrated that combining docetaxel with the antiangiogenic agent bevacizumab (Avastin), which targets a blood vessel growth factor, was well-tolerated and resulted in a substantial decrease in levels of prostate specific antigen (PSA), a marker for tumor progression, in the majority of patients. However, this regimen did not improve survival; thus researchers continue to search for new drugs that target tumor-associated blood vessels more specifically.
In this study, which is being conducted at the NIH Clinical Center, researchers will test whether treatment with a novel monoclonal antibody, TRC105, that targets a protein highly expressed on the surface of tumor blood vessels improves the outcome of men with metastatic CRPC. Men who are at least 18 years of age and have been diagnosed with progressive, castration-resistant adenocarcinoma of the prostate are eligible to enroll. The first phase of the trial will involve a dose escalation (increase) study to establish the maximum tolerated dose. The second phase will examine progression-free survival in patients with disease progression after treatment with docetaxel and no prior antiangiogenic therapy.
"Currently, there is no curative therapy for metastatic castration-resistant prostate cancer," said Dr. Dahut. "TRC105 is an experimental drug that has been demonstrated to block angiogenesis and has a very different target than previously studied antiangiogenic anticancer agents. However, it has not been validated to treat prostate cancer in general or castration-resistant prostate cancer in particular."
"If the regimen proves safe and effective, we hope that it will offer a clinically important option for men with metastatic castration-resistant prostate cancer," he added.
For More Information
See the lists of eligibility criteria and trial contact information or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential.
FDA Update
FDA Approves New Treatment for Late-Stage Melanoma
On March 25, the Food and Drug Administration (FDA) approved ipilimumab (Yervoy) to treat patients with metastatic melanoma. The approval follows a 676-patient trial, which found that patients taking the drug had a median overall survival of 4 months longer than those who had received an experimental therapeutic vaccine.
Ipilimumab is an antibody that works by binding to a molecule on the surface of T cells called CTLA4. This removes a brake that prevents immune cells from attacking the body's own tissues and cells in melanoma tumors.
Adverse events and side effects are possible when the immune system is stimulated, and ipilimumab can cause complications such as rashes, colitis (inflammation of the colon), and even death. But most adverse events are treatable.
"Late-stage melanoma is devastating, with very few treatment options for patients, none of which previously prolonged a patient's life," said Dr. Richard Pazdur, director of the FDA's Office of Oncology Drug Products. "[Ipilimumab] is the first therapy approved by the FDA to clearly demonstrate that patients with metastatic melanoma live longer by taking this treatment."
CMS Update
CMS Issues Proposed Decision Memo on Medicare Coverage of Sipuleucel-T
The Centers for Medicare and Medicaid Services (CMS) has issued a Proposed Decision Memo on sipuleucel-T (Provenge) for the treatment of advanced prostate cancer. According to the memo, "Provenge improves health outcomes for Medicare beneficiaries with asymptomatic or minimally symptomatic metastatic castrate-resistant (hormone refractory) prostate cancer, and thus is reasonable and necessary for that indication."
The memo is one of the final steps in a National Coverage Analysis (NCA) initiated by CMS last year for the treatment. NCAs are performed to determine whether Medicare will routinely cover a treatment for all beneficiaries, or whether the decision will be left to individual regional Medicare carriers. In November 2010, the agency's Medicare Evidence Development & Coverage Advisory Committee offered moderately strong support for coverage of sipuleucel-T.
The FDA approved sipuleucel-T, an immunotherapy, in April 2010, based on the results of a clinical trial that showed a median improvement in overall survival of 4 months in patients who received the treatment compared with men who received a placebo.
CMS is accepting public comments on the proposed decision memo for 90 days.
Legislative Update
Congressional Staffers and Advocates Take Part in Project Cancer Education
On March 18, NCI hosted six congressional staffers and two cancer research advocates for Project Cancer Education (PCE), an interactive learning experience featuring NCI's intramural prostate cancer research program as a case study to demonstrate how scientific discoveries are translated into tangible benefits for patients. The program included researchers from NCI's Center for Cancer Research (CCR), whose aim was to open a window for PCE participants into a dynamic collaboration among members of a multidisciplinary research team.
The hosts of the event—Dr. William Dahut, clinical director of CCR, and Dr. Marston Linehan, chief of CCR's Urologic Oncology Branch (UOB)—described the patient-focused nature of translational research for the staffers. "Patients want two things," Dr. Dahut explained. "They want to get better, but they also want to help others." The translational research process continuously shifts between the laboratory and the clinic to refine and improve new therapeutic strategies as they progress toward becoming proven cancer care options for patients in the community, he noted. Patient participation in clinical trials is an essential part of that effort.
Drs. Dahut and Linehan accompanied the PCE participants on a visit to the Molecular Imaging Clinic, where Dr. Peter Choyke, director of CCR's Molecular Imaging Program, and his team showed the group how sophisticated molecular imaging technologies are being used to pinpoint suspicious tissues in the prostate for precision biopsy and treatment monitoring.
This new kind of imaging can help guide surgeons to exact locations of cancerous tissues during minimally invasive robotic prostatectomy and may allow surgeons to conserve unaffected areas of the prostate, explained Drs. Peter Pinto and Gennady Bratslavsky, senior surgeons in the UOB, who perform and teach this procedure.
Drs. Pinto and Bratslavsky welcomed the group to the Robotic Surgery Suite and provided each of the guests an opportunity to practice using the da Vinci machine in a robotic surgery training exercise. They described how the use of robotic surgical procedures may preserve function and increase the quality of life for prostate cancer survivors. In addition, Drs. Dahut and Linehan stressed that training future cancer researchers and clinicians is an important role for CCR. PCE presenters Drs. James L. Gulley and Jeanny Aragon-Ching trained at NCI in CCR's Medical Oncology Fellowship Program. Dr. Gulley is now director of the Clinical Trials Group in CCR's Laboratory of Tumor Immunology and Biology. He detailed his research in developing highly effective and minimally toxic cancer vaccines, including a new experimental vaccine that targets prostate cancer.
Dr. Aragon-Ching, now assistant professor of medicine in the Division of Hematology and Medical Oncology at George Washington University Medical Faculty Associates, told the group how her training at NCI has shaped her work as a researcher, instructor, and mentor to medical students and her care of patients every day in her clinical practice. "This is a journey," concluded Dr. Aragon-Ching. "We are here to help patients. This is why we are all here."
A few of CCR's patients offered their own perspectives via video to complement the presentations in molecular imaging and vaccine therapy. Their stories highlighted the program's central theme that the ultimate goal of translational cancer research is to bring the benefits of laboratory discovery to cancer patients. Matt Fery, a member of Rep. Brian Higgins' (D-NY) staff, thanked all of the PCE presenters for the illuminating program. "On the Hill, we get caught up in the macro systems so much that we can forget that the research done here matters to people," he said.
NIH Research Plan Aims to Prevent and Treat Obesity
Last week, NIH released the 2011 Strategic Plan for NIH Obesity Research. The plan recommends four overarching research priorities:
- Discover key processes that regulate body weight and influence behavior
- Understand the factors that contribute to obesity and its consequences
- Design and test new interventions for achieving and maintaining a healthy weight
- Evaluate promising strategies for obesity prevention and treatment in real-world settings and diverse populations
The plan was developed—with input from external scientists, health professionals, and the public—by the NIH Obesity Research Task Force, which includes experts from NCI; National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
"Obesity has many causes and contributing factors, and this plan is a bold blueprint that will encourage the research community to examine the epidemic of obesity from diverse angles, from our genes to the environment we live in," said NIH Director Dr. Francis S. Collins. "Through the scientific opportunities outlined in the Strategic Plan, researchers can work together toward the goals of preventing and treating obesity, to help people lead healthier lives."
Learn more about obesity research at NIH at www.obesityresearch.nih.gov.
Member Sites Selected for Cancer Immunotherapy Trials Network
Research institutions at 27 sites across North America have been selected as part of the new Cancer Immunotherapy Trials Network (CITN). The CITN will conduct multicenter research on agents that boost patients' own immune systems to fight their cancer. By coordinating the efforts of academia, industry, and philanthropic foundations, the CITN is charged with accelerating the development of promising agents that have already been discovered but are not currently used to treat patients with cancer.
An open competition was held for institutions to apply for member site status in the CITN, and immunotherapy experts evaluated candidates on the experience, participation, and collaboration of the investigators and their institutions in immunotherapy trials and their ability to provide laboratory expertise in tumor immunology to support the trials.
The member institutions and their principal investigators are:
- Baylor Research Institute – Dr. Karolina Palucka
- Case Western Reserve University – Dr. Pierre Triozzi
- Dana-Farber Cancer Institute – Dr. Stephen Hodi
- Dartmouth-Hitchcock Norris Cotton Cancer Center – Dr. Marc Ernstoff
- Duke University Medical Center – Dr. Kim Lyerly
- Emory University – Dr. Edmund Waller
- Fred Hutchinson Cancer Research Center – Dr. John A. Thompson
- H. Lee Moffitt Cancer Center – Dr. Scott J. Antonia
- Memorial Sloan-Kettering Cancer Center – Dr. Jedd D. Wolchok
- New York University Cancer Institute – Dr. Nina Bhardwaj
- Ohio State University – Dr. William E. Carson
- Providence Cancer Center – Dr. Walter J. Urba
- Roswell Park Cancer Institute – Dr. Kunle Odunsi
- Rush University Cancer Center – Dr. Howard Kaufman
- Stanford University – Dr. Ronald Levy
- University of California, San Diego – Dr. Thomas J. Kipps
- University of California, San Francisco – Dr. Lawrence Fong
- University of Chicago – Dr. Thomas Gajewski
- University of Miami – Dr. Joseph D. Rosenblatt
- University of Minnesota – Dr. Jeffrey S. Miller
- University of Pennsylvania – Dr. Carl June
- University of Pittsburgh – Dr. Robert L. Ferris
- University of Texas M. D. Anderson Cancer Center – Dr. Laurence J. N. Cooper
- University of Toronto, Ontario Cancer Institute – Dr. Pamela Ohashi
- University of Virginia – Dr. Craig Slingluff
- University of Wisconsin – Dr. Paul M. Sondel
- Yale University – Dr. Mario Sznol
In September 2010, funding was awarded to the Fred Hutchinson Cancer Research Center in Seattle to serve as the network's Central Operations and Statistical Center (COSC). Directed by principal investigator Dr. Martin A. Cheever and co-investigators Drs. Mary L. Disis and Kim Margolin, the COSC will provide overall leadership and infrastructure for the CITN. The network will be managed in concert with the NIH/NIAID-funded HIV Vaccine Trials Network (HVTN), also based at the Fred Hutchinson Cancer Research Center. The NCI's Cancer Trials Support Unit will operate the data coordination effort for CITN.
An initial meeting of CITN investigators is scheduled for May 9–10 in Bethesda, MD, to discuss the operations of the CITN and to introduce the first concepts to be studied by this new cancer immunotherapy program.
Free Telephone Workshop Series for Cancer Survivors
The ninth annual telephone workshop series, "Living With, Through, and Beyond Cancer," begins this spring. This four-part series offers cancer survivors, their families and friends, and health care professionals practical information to help them cope with concerns and issues that arise after treatment ends.
The series is presented by CancerCare, in collaboration with NCI, LIVESTRONG, the American Cancer Society, the Intercultural Cancer Council, Living Beyond Breast Cancer, and the National Coalition for Cancer Survivorship.
Part I, which takes place on April 12, is titled "Chemobrain: The Impact of Cancer Treatments on Memory, Thinking, and Attention." Faculty for this program include Dr. Lillian Nail of Oregon Health & Science University, Dr. Tim Ahles of Memorial Sloan-Kettering Cancer Center, and Dr. Patricia Ganz of UCLA's Jonsson Comprehensive Cancer Center.
The workshops are free, and no telephone charges apply. To register, visit the CancerCare Web site. All workshops will take place on Tuesdays from 1:30 p.m. to 2:30 p.m. EDT. The remaining three workshops will be held on the following dates:


text:
Two coworkers were talking by the water fountain.
The first guy said, "Today I got through the first step of getting divorced."
The second guy replied, "Oh, did you go to Mr. Guggenheim? Everyone goes to him for divorces."
The first guy replied, "No, I just got married."
Joe Cassady @ http://929wlmi.com/latest-updates/authors/34/


text:
A bear climbs onto a cabin's deck, presses his nose to the sliding door. Inside, a young woman stands to face him. She comes closer, and closer yet, until only the glass stands between them . . .
The year is 1981, Reagan is in the White House, and the country is stalled in a recession. Cressida Hartley, a gifted Ph.D. student in economics, moves into her parents' shabby A-frame cabin in the Sierras to write her dissertation. In her most intimate and emotionally compelling novel to date, Michelle Huneven--author of Blame, which was a finalist for the National Book Critics Circle Award--returns with her signature mix of fine-grained storytelling, unforgettable characters, and moral complexity.
Cress, increasingly resistant to her topic (art in the marketplace), allows herself to be drawn into the social life of the small mountain community. The exuberant local lodge owner, Jakey Yates, with his big personality and great animal magnetism, is the first to blur Cress' focus. The builder Rick Garsh gives her a job driving up and down the mountain for supplies. And then there are the two Morrow brothers, skilled carpenters, who are witty, intriguing, and married.
As Cress tells her best friend back home in Pasadena, being a single woman on the mountain amounts to a form of public service. Falling prey to her own perilous reasoning, she soon finds herself in dark new territory, subject to forces beyond her control from both within and without.
Unsentimental, immersive, and beautifully written--"Huneven's prose is flawless," according to The New Yorker--Off Course evokes the rapture of new love, the addictive draw of an intense, impossible connection, and what happens when two people simply can't let go of each other or of their previous commitments. As her characters struggle with and delight in one another, Huneven subtly exposes the personal and social forces at play: issues of class, money, and family, as well as the intricate emotional and economic transactions between parents and children, between husbands and wives, between lovers, and between friends.
Michelle Huneven is one of our most searching, elegant novelists--Richard Russo has called her "a writer of extraordinary and thrilling talent." In Off Course, she introduces us to an intelligent young woman who discovers that love is the great distraction, and impossible love the greatest distraction of all.
Praise for Jamesland"Michelle Huneven is a writer of extraordinary and thrilling talent, and Jamesland is a marvel."—Richard Russo"Generosity, humor and tolerance shine in Huneven's writing."—Michael Harris, Los Angeles Times Book Review Praise for Round Rock"Like that other West Coast chronicler of struggling Americans, Raymond Carver, . . . Huneven is not interested in literary pretension or postmodern razzle-dazzle, but in achieving a measure of truth— and her generous, engaging novel does just that."—Valerie Sayers, The New York Times Book Review
A Novel
Michelle Huneven


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Nana Ogura is a well known and very nice teen amateur babe that you will be seeing her in the wildest public place sex that will leave you spanking the monkey like a really horny mother fucker as you will be seeing her in some really amazing group action with no limits at all. This babe is really well known for sucking dick and here you will be seeing her cock sucking like no tomorrow and getting tons of cum on her face in mmf aciton.
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Yuria Satomi
Yuria Satomi is a hot Asian MILF in her office suit. She is in the break room with a co worker and he is interested in her sexy pantyhose and her pussy. She is making out with him and doing some hand work on his cock when he gets to her w..
Yuria Satomi
Round tit and horny babe Yuria Satomi making out and hardcore fucked. She tease and makes out with her hung lover and strips down on her sexy dress. She get her boobies squuezed and wet pussy licked. She humps on his cock, grinds on it ti..
Nao is a lovely Asian model. She works in the mall and sometimes brings her new outfits home with her to show to her boyfriend. She got this pretty pink one and showed it to him and hr decided to call a couple of his friends over to have a small party with her. She likes threesomes and thinks they´re exciting. Her boyfriend is open minded and doesn´t mind sharing either. He tqkes pictures too for her portfolio that she is starting to build up for her modeling career too.
Lovely and horny, these three asian models are having some fun with their photographer. They have been working all day and noe=w it is time for some group fun! He has been their photo guy since they started modeling. He likes to come to the club with all three girls just to brag about them. What he doesnt know is while he was taking pictures, those sneaky gals had a camera rolling and they will be putting it on the web when he goes home!
Lovely Asian model Nao enjoys showing off her talents with her boyfriend and bondage! She is hot in her purple stockings and lingerie. She enjoys playing with her boyfriend with ropes and making sure he is teased and played with all her abilities! They like putting on a show for the adult theatres and they get well paid for it too. She has an ongoing web site that they update with new photos and videos whenever the chance arises. She used to be a model with the lingerie shop but she found out that this was a much better deal!
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This lovely Asian threesome enjoy having some hot fun with one guy. They are horny and wnjoy getting together and having some hot sex with any one guy they can find who is brave enough to go with them! The three gals work in the casino as hostesses and they have a good selection of guys who think they can stand three girls at once! You would be surprised at how many guys they go through on their little dates! But you can check it all out on the website they have together!
Naughty teacher is keeping a student after school for a little extra class work. She is fooling around with him and decides to show her big tits to him before sucking his cock. He is interested in her tits and when she is done sucking him off, she gives him a hot titty fucking. He really enjoys this because he hasn´t had one before. She is excellent at her job and this guy will pass this class with an A!
Nao is lovely and busty in her rabbit, costume. She is getting ready for work and her guy stops her for a hot blowjob,. She is good at sucking cocks, and he knows it too! She sucks him off and spits the cum from her mouth into her hands to play with!
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Naughty Nao is a lovely Asian waitress from the little coffee shop in the mall. She is a lovely babe with nioce tits and a tight ass. The guys there all enjoy her company when she is working and they enjoy looking at her when she is running around the tables. She dates a couple pf the younger guys and they go out to the clubs at night before she takes them home for some extra fun. She likes her guys to go to her house because she is all set to record their party and send it to the web!
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HARRISBURG, Pa.—The winning numbers in Tuesday afternoon's drawing of the Pennsylvania Lottery's "Midday Daily Number" game were:
(zero, two, eight)
(Koji Sasahara/AP)
The Kuro taste: Peppery tang and hint of squid ink
TOKYO (AP) — The first Kuro, or black, burger had a black bun and sauce. Last year's edition, the Kuro Ninja, added a slice of (non-black) bacon to the signature black components. Full Story
(Ben Rothstein/AP)
'Maze Runner' races past 'Tombstones' with $32.5 M
NEW YORK (AP) — The young-adult adaptation "The Maze Runner" raced to the top of the box-office with $32. Full Story
(Jacques Brinon)
Keanu Reeves finds fan in his house in middle of night
Dude, where's my security? The "Point Break" actor calmly spoke with woman until police arrived.


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This is a "machine-selection optional" part.Please choose a vehicle to see the options specific to your machine,choose from all of the options below and add to cart.
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Comments On Aug 27, 2014:works great, good quality and makes it look nice!
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Comments On Apr 08, 2014:We change rear sprockets more often than others as we change for different terrain. These are good bolts, but I prefer the torx head OEM bolts over the allen head bolts. These bolts come with nylon lock nuts that seem to work well for a single application.
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Comments On Feb 13, 2014:looked and fit just like the stock hardware; great price.
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Comments On Feb 06, 2014:Great quality awesome price, cant beat it.
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Comments On Jan 08, 2014:Nice Chrome look and fit great
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Comments On Jun 28, 2013:These look great and include the bolts, washers and nuts. The nuts are a 14mm instead of the OEM 12mm meaning they wont strip as easy hold better. Fit was perfect, the bigger nuts caused no problems and were an improvement. The gold color looks really good too.
2005 yz250
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Comments On Apr 01, 2013:It's a good idea to change them when you change sprockets. I've had zero issues with mine 50 hours so far on them.
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Comments On Mar 20, 2013:Kit was good quality and has held up great for two years now on a CRF.
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Comments On Mar 13, 2013:Not much to say, can't get any better and the price is hard to beat!
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Comments On Feb 05, 2013:Decent parts, maybe not quite a solid as the stock Yamaha parts. They have held up well so far.
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Food Crocks and Pans
CooksDirect.com is your best source for Food Crocks and Pans. Our online catalog features thousands of restaurant equipment and supply products. Whether you're searching for Food Crocks and Pans, kitchen supplies, or restaurant equipment we've got what you need. If you have any questions regarding our Food Crocks and Pans selection, please call our customer care team toll-free at 866-506-3048 and we'll be happy to help!


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Do you believe people can communicate with the dead? They're called psychic mediums and the phenomenon is becoming increasingly popular.
More people than ever are turning to mediums for advice, answers, and healing. There's even a testing site in Arizona that claims to scientifically examine a medium's abilities.
Janeen Kokodynski is a busy mom.
"Between piano and drums to club baseball, to do re mi which is like show choir singing, so we're a very active family
Mason is 11, Hailey is 9, Kate is 5. She just started kindergarten last fall. Matthew would have turned 8 on June 10 of this year. Janeen was 18 weeks pregnant with her third child when an ultrasound revealed the baby boy was very sick.
"It became very real when we met with the pediatric cardiologist and he explained the complex heart defect that Matthew had," says Janeen. "It was an absolute roller coaster and then you know, you have the aspect of, we decided my husband and I decided to have Matthew have the series of three open heart surgeries called the Norwood procedure."
Matthew was born at the children's hospital in Los Angeles. At 2 days old surgeon's performed the first operation. Thirty days later on July 12, 2005, Matthew's heart stopped.
Janeen describes the time immediately after as an emotional roller coaster. She and her husband saw a counselor on a weekly basis for a year. They turned to their strong faith in god for healing, and even started a grief support group at their church.
"My heart is palpitating like, it's not regular and I feel like I am out of breath," says Debra Martin, a psychic medium.
About a year ago Janeen met Debra Martin, a psychic medium.
"You have his blue blanket or you buried him with a blue blanket or something with a blue blanket because I saw a blue blanket."
Her first one on one reading was earlier this month, an opportunity to connect with her son more personally.
"I seek this out because it just gives me confirmation again over and over again that he is, that he's still with me, he's just with me in a different realm in a different way and it brings peace, you know when you have the love for someone and you want them so badly with you in the physical world. It's difficult and so I know even though he's not here with me on earth I know that he is with me in more of a spiritual form and I know that he's safe I know that God intended him to only be on this earth for the 32 days he was here."
"To me it's like putting the pieces of a puzzle together, you get something, you write it down and the word that you get and the feeling that you get or exactly how you're hearing, exactly how you're feeling that's 100% right," says Debra.
Hans Pedersen is a FOX 10 producer -- a believer of what lies beyond. He volunteered for a reading, hopeful he would receive some answers.
"Is your dad crossed over… he is standing real close to you I can feel him in the room actually."
Medium. Dave Campbell realized his ability to connect to the other side at a young age.
"I don't think he got to say goodbye and that's kind of why he's here and I do this for healing," says Campbell.
Campbell and Pedersen had never met or spoken prior to this day, but during Pedersen's reading, Campbell was able to connect with Pedersen's father and a close friend.
"But I'm seeing that he's got the dog, I don't know why, but he's taking care of your dog."
"My dad and I had some issues, and you know, it's taken some time to be able to forgive him. This makes it a little easier," says Pedersen.
Thousands of people turn to psychics for help. Both of the mediums in our report say they rely solely on the information provided to them by spirits, and both have been tested by the Windbridge Institute for Applied Research in Human Potential, an independent research organization in Tucson.
"There's no way for trickery or deceit, or you know you couldn't do this if you weren't a real medium. You couldn't go through. You couldn't survive the testing you just wouldn't make it," says Campbell.
Campbell says the testing process involves 8 steps, all of which are listed on the institute's website. The process goes on for over a year. To date, Windbridge has certified 19 mediums, 3 in Arizona, including Debra Martin.
"It's hand and hand with spirits, they are teaching me every day new things and how to touch people and how to communicate and I'm constantly growing," says Martin.
During her reading with Janeen, Debra Martin, who knew she was a medium at age four, made mention of specifics like what the client was wearing in a tattered photo the grieving mom keeps in the car and Matthew's first birthday, when his family planted a tree in the backyard and released balloons in his memory.
"It's nice for me to be able to have that type of relationship with him on that level because it's all I really have."
Janeen looks for signs like a monarch butterfly and to photos to keep her sons memory alive.
Since Matthew's passing, Janeen has started the Arizona Chapter of the Children's Heart Foundation, along with a non-profit event called A Heartfelt Affair, a part of her healing process.
WTTG FOX 5 & myfoxdc
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Rice MBA has introduced a residency program for students commuting from outside the city. Experienced professionals can earn an MBA at one of the nation's leading business schools without career interruption, attending classes just two weekends a month for 22 months.
Consider the benefits of taking what you learn in the classroom and applying that knowledge to the workplace immediately. Form lasting relationships with locally-based faculty and fellow students who are active executives in the Houston business community.
Situated on Rice University's lush 285-acre campus, the Jones Graduate School of Business offers students the advantages of having faculty, staff, career management, admissions and student services accessible in one place. An additional cost of $6000 is required for accommodations for Friday and Saturday night at the Marriott Medical Center, located a few miles from campus. For more information, contact the Rice MBA Admissions office at 713-348-4918. Visit the MBA for Executives home page to learn more about the program.


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The Gucci Gucci Rapper Dishes Out Her Preferences
Brassy Oakland rapper Kreayshawn delivers an exclusive remix of her viral sensation "Gucci Gucci" by producer DJ Two Stacks. With over 13 million views on YouTube, the song's video features the 21-year-old rolling down L.A.'s Fairfax Avenue with pals Odd Future, rapping about Arby's, Adderall and the designer brands worn by "basic bitches". Part thrift store cholita, part Kid Robot Bratz Doll, the overnight success of the MC's irreverent, white-girl rap has seen her seal a deal with Columbia Records and a Best New Artist VMA nomination. A director in her own right, Kreayshawn has made music videos for Bay Area rap figures like Lil B and more recently rock icons the Red Hot Chili Peppers. "I can understand why people on the outside are like 'What the hell is she doing?'" she laughs. "I'm just being me—I'm a random chick! And I want to inspire people, especially girls, to feel comfortable with themselves and to go out there and do whatever they want. It's the girl-power message." Here the pint-sized internet celebrity gets all preferential.
God or your iPhone?
My iPhone. God can't tell me how to get somewhere. Google maps can.
Cat eye or smoky eye?
Cat eye.
Vintage or high street?
Brick Lane or Fairfax Avenue?
Brick Lane! It's my favorite place to shop in the world.
Nicki Minaj or Lil' Kim?
I can't pick. I pick Kreayshawn.
Cat or dogs?
Are you crazy? Cats all day. I'm a crazy cat lady.
Late night or early morning?
Late night.
S.F. or L.A.?
San Francisco. I don't like living in L.A.
"The L word" or "The Real L Word"?
"The L word." Loads of my friends in L.A. are on "The Real L Word" though. Those chicks are crazy!
Photo by Eric Timoteo


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Brand New 5.56 Ammo Can - 50 Cal.
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Cabinet Pulls
Cabinet Pulls
Find beautiful cabinet pulls that will provide wonderful accents to your cabinets and home. KnobDeco.com carries over 15,000 cabinet pulls to meet your every design, finish, and size desire. We offer cabinet pulls in all of today's most popular finishes including satin nickel, oil rubbed bronze, pewter, crystal, rust, brass, chrome, and more. Cabinet pulls from KnobDeco.com are available in dozens of styles from traditional to contemporary to match your interior design. Use KnobDeco.com's advanced filtering capabilities to find the exact cabinet pull you are looking for. With KnobDeco.com's brand collection filtering options you can easily find matching cabinet knobs and other cabinet hardware accessories from each brand. Add a beautiful touch to your cabinets by selecting a set of cabinet pulls from KnobDeco.com today.
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Amerock 128mm Essential'Z Pull in Satin NickelSKU# : AM-BP9362-G10MSRP$10.15Discount Price$8.12
Amerock 128mm Essential'Z Pull in Brushed BronzeSKU# : AM-BP9362BBZMSRP$10.15Discount Price$8.12
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Atlas Homewares A864-Mc Successi 15-Inch T-Bar Door Pull, Matte ChromeSKU# : ATLAS-A864-MCMSRP$27.52Discount Price$24.77
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Siro Designs 183mm Soho Cabinet Pull In Beige W/ Bright ChromeSKU# : Siro-108-154MSRP$24.30Discount Price$19.44
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Hickory Hardware 160mm C/C Altair Pull In SilverSKU# : BWP-P3080-SLVMSRP$8.23Discount Price$6.58
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Siro Designs 604mm Quadra Cabinet Pull In Bright ChromeSKU# : Siro-116-116MSRP$38.87Discount Price$31.09
Century Select
Century 604mm Stainless Steel D-Handle Stainless Steel 544mm C/CSKU# : CS-40539E-32DMSRP$17.09Discount Price$14.53
Richelieu Hardware
Richelieu Hardware Contemporary Metal Bow Pull 128mm Brushed NickelSKU# : Rich-745239128195MSRP$26.46Discount Price$23.81
12 Item(s)