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FDA Bans Candy- and Fruit-Flavored Cigarettes
The FDA announced today that, effective immediately, cigarettes with certain flavors such as candy, fruit, and clove are now illegal in the United States. Flavored cigarettes are a gateway for many young people to become regular smokers, the agency said, and the ban, authorized by the new Family Smoking Prevention and Tobacco Control Act, aims to reduce the number of children who start smoking.
Modified Chemo Regimen Effective in Advanced Ovarian Cancer
Women with advanced ovarian cancer lived longer and without their tumors growing after receiving a modified regimen of a standard chemotherapy drug combination, Japanese researchers reported last week. In a large phase III clinical trial, women who received carboplatin every 3 weeks and a reduced dose of paclitaxel (Taxol) once a week for 3 weeks instead of carboplatin and a higher single dose of paclitaxel every 3 weeks had a 29 percent improvement in progression-free survival and a 25 percent improvement in overall survival after 3 years of follow-up. The results were published online September 18 in The Lancet. Read more > >
Diabetes Drug Metformin Shows Promise as a Breast Cancer TreatmentCommonly used drug targets cancer stem cells in mice and will be tested in a large clinical trial
Hormone Therapy Linked to Risk of Death from Lung CancerRisk should be considered by women weighing this treatment, researchers say
Recently Discovered Virus Linked to Aggressive Prostate TumorsInvestigators are now asking whether the virus causes cancer
Fat Cells Interfere with Chemotherapy for LeukemiaInteractions may contribute to poorer prognosis of obese patients
Hepatitis B Vaccine Lowers Risk of Liver CancerImmunization extends protection against hepatocellular carcinoma beyond childhood and into young adulthood
Director's Update: Using ARRA Funds to Advance Cancer Research
As the fiscal year draws to a close September 30, a number of offices around NCI become especially busy places. Members of our staff who supervise budget issues, grant funding, program management, and contract administration put in long hours, making sure every dollar is appropriately allocated. In 2009, end-of-year responsibilities are even greater, as NCI also works to distribute $1.26 billion it received under the American Recovery and Reinvestment Act (ARRA). Read more > >
Charting the Path from Infection to CancerResearchers are trying to understand how genes and environment may play a role
Harnessing the Biological Activity of Natural ProductsControlled drug interactions may increase the effect of chemotherapy
Profiles in Cancer Research: Dr. Jun S. WeiThe NCI microbiologist reflects on his journey into oncogenomics
Featured Clinical Trial: Comparing Drug Regimens for Diffuse Large B-cell LymphomaWill the EPOCH-R drug regimen improve outcomes over standard R-CHOP?
FDA Update
- FDA Clears Test for Ovarian Cancer that Could Guide Surgical Decisions
- Committees Recommend FDA Approve Cervarix and Gardasil
- Dr. Ming Lei Named Cancer Training Branch Chief
- Dr. Louise Brinton Receives Lilienfeld Award
- Webcast Registration Available for DCIS Conference
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
Modified Chemo Regimen Effective in Advanced Ovarian Cancer
Women with advanced ovarian cancer lived longer and without their tumors growing after receiving a modified regimen of a standard chemotherapy drug combination, Japanese researchers reported last week. In a large phase III clinical trial, women who received carboplatin every 3 weeks and a reduced dose of paclitaxel (Taxol) once a week for 3 weeks instead of carboplatin and a higher single dose of paclitaxel every 3 weeks had a 29 percent improvement in progression-free survival and a 25 percent improvement in overall survival after 3 years of follow-up. The results were published online September 18 in The Lancet.
Although the toxicities of this dose-dense regimen were greater than they were in women who received the standard combination, survival benefits of this magnitude "have been rare in women with advanced ovarian cancer," wrote Dr. Noriyuki Katsumata and colleagues from the Japanese Gynecologic Oncology Group (JGOG).
The results, explained Dr. Ted Trimble, from NCI's Division of Cancer Treatment and Diagnosis, are consistent with what has been seen in breast cancer using a dose-dense chemotherapy regimen. The idea, he continued, is "to balance efficacy and toxicity by using a weekly schedule rather than every 3 weeks."
Although the findings are important, "they won't change practice overnight," Dr. Trimble said. There are still several significant unknowns, including whether a lower dose of paclitaxel might be as effective but less toxic; the optimal timing of surgery; and where intraperitoneal chemotherapy fits into the treatment mix. The JGOG trial results, however, will influence the design of a number of phase III clinical trials, all of which include dose-dense chemotherapy, he added.
More than 630 women at 85 hospitals across Japan enrolled in the trial. Patients were randomly assigned to either of the two treatment groups. After 3 years of follow-up, women who received the dose-dense treatment had a median progression-free survival of 28 months, compared with 17 months for those who received the standard treatment.
Not enough time has passed to determine with statistical confidence whether the overall survival advantage will be maintained. However, in ovarian cancer, improvements in progression-free survival tend to predict overall survival, said Dr. Michael A. Bookman, chief of the Hematology/Oncology Section at the Arizona Cancer Center, in an accompanying editorial in The Lancet.
The dose-dense chemotherapy regimen used in the trial was also dose-intense, meaning the total dose of paclitaxel patients received was actually higher than in those who received standard treatment. This was associated with some toxic side effects that caused treatment delays and modifications and also led to patients receiving less caboplatin than intended. In fact, more than half of the women in the dose-dense group discontinued treatment early, and most of them did so because of the toxicity.
Although it's possible that the dose intensity was responsible for the survival improvements, Dr. Bookman wrote, the more frequent, lower-dose treatment schedule is the most "plausible explanation." As a result, "similar results might be achieved" with a lower dose, he concluded, "with improved tolerability."
As for why the dose-dense approach is more effective than the standard approach, the Japanese researchers suggested that it hampers the formation of blood vessels that feed tumors. In animal model studies, dose-dense chemotherapy, like a similar treatment also under active investigation called metronomic chemotherapy, has been shown to have such an antiangiogenic effect. And in the JGOG trial, the researchers noted, tumor shrinkage following treatment did not differ between those receiving dose-dense chemotherapy and standard chemotherapy. This suggests that the dose-dense treatment "might promote tumor dormancy by maintaining tumor size and preventing outgrowth," they wrote.
The U.S.-based Gynecologic Oncology Group is planning to launch a phase III clinical trial in advanced ovarian cancer combining the dose-dense approach with the targeted antiangiogenic drug bevacizumab (Avastin), said Dr. Ronald Alvarez, director of the Division of Gynecologic Oncology at the University of Alabama at Birmingham. This should help to confirm the Japanese trial's results.
In the meantime, "Given the potential toxicity, clinicians should discuss with their patients the risks versus the benefits of this approach in comparison with other treatment strategies," Dr. Alvarez said, particularly with those patients who have advanced disease and whose tumors could not be mostly eradicated by surgery.
—Carmen Phillips
Cancer Research Highlights
Diabetes Drug Metformin Shows Promise as a Breast Cancer Treatment
Low doses of the commonly used diabetes drug metformin may be an effective treatment for breast cancer, primarily because the drug appears to target breast cancer stem cells, Harvard Medical School researchers reported online September 14 in Cancer Research. Cancer stem cells, also called tumor-initiating cells, are thought to be relatively rare cells that can give rise to new tumors and are resistant to standard cancer treatments.
In the study, the combination of metformin and the chemotherapy agent doxorubicin was more effective than either drug alone at eliminating cancer cells and cancer stem cells in cultured cell lines of four genetically distinct breast cancer types, including HER2-positive and triple-negative breast cancers. In a breast cancer mouse model, the drug combination eliminated tumors and prevented regrowth, whereas doxorubicin alone only reduced tumor size and did not prevent regrowth, and metformin alone had little effect.
"With both drugs, regression was quicker…and, more importantly, there was no relapse," said senior author Dr. Kevin Struhl during a press briefing on the study.
When the researchers analyzed cell populations taken from the tumors of mice after three cycles of treatment, they found almost no cancer stem cells in the animals that received the drug combination but found the stem cells easily in tumors from mice given only doxorubicin. The highly beneficial effect of the combination treatment and the limited effect of either drug alone support the cancer stem cell hypothesis, Dr. Struhl said.
The results support previously published epidemiologic and laboratory studies that have suggested metformin has an anticancer effect, Dr. Jennifer Ligibel, a breast cancer researcher from Harvard University who was not involved with the study, said during the briefing. As a result, a large phase III clinical trial will test whether using metformin after standard treatment in women with early stage breast cancer can improve outcomes. The trial is being sponsored by NCI and coordinated by the National Cancer Institute of Canada. Trial investigators hope to start enrolling patients in the study next year, Dr. Ligibel said.
Hormone Therapy Linked to Risk of Death from Lung Cancer
Women who use combination hormone therapy to treat menopausal symptoms may be at an increased risk of dying from lung cancer. An analysis of data from the Women's Health Initiative (WHI) study has found that, although the use of estrogen-plus-progestin therapy did not increase lung cancer incidence, it did increase the number of deaths from the disease, primarily from non-small cell lung cancer. The results appeared online September 18 in The Lancet.
"We have identified a new potentially lethal side effect of using estrogen-plus-progestin therapy over a relatively short period of time," said lead investigator Dr. Rowan Chlebowski of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center. Postmenopausal women considering this therapy should be aware of the risk, especially those who are current or long-term former smokers, he added.
In 2002, the WHI ended early when an increased risk of breast cancer was found in women using combination hormone therapy compared with nonusers. Studies since then have shown that the increased breast cancer risk persists even after the hormones are stopped and that hormone use interferes with the detection of breast cancer, causing some women to have abnormal mammograms for at least a year. Hormone therapy has also been linked to an increased risk of ovarian cancer.
A potential mechanism to explain the new findings may be estrogen's ability to stimulate blood vessel growth (angiogenesis), the researchers said, noting that strategies to block the growth of tumor blood vessels are used in both lung and breast cancer treatment. Another factor in the lung cancer deaths may have been that hormones delayed the detection of lung tumors, as has happened in breast cancer.
An accompanying editorial agreed that women at risk of lung cancer should avoid hormone therapy and asked whether this treatment has "any role in medicine today." In addition, Dr. Apar Kishor Ganti of the University of Nebraska Medical Center noted that because the WHI was a randomized controlled trial, which is the gold standard in medicine, the results should dispel any notions that hormones may have protective effects against lung cancer, as several retrospective studies have suggested.
Recently Discovered Virus Linked to Aggressive Prostate Tumors
A previously unknown virus was discovered in tumors from men with prostate cancer in 2006, but at the time it was not clear whether the virus played a role in the disease. That question remains unanswered, but a new report shows that the virus, called xenotropic murine leukemia virus-related virus (XMRV), is present in malignant prostate cells and is more commonly found in men with aggressive tumors.
A survey of more than 300 prostate tissue samples showed that the virus was present in 27 percent of the tumor samples and 6 percent of the benign control samples. Reporting their findings last week in the Proceedings of the National Academies of Sciences (PNAS), the researchers also confirmed the initial classification of the virus as a type of gammaretrovirus. These pathogens can cause cancer in animals, but they have not yet been shown to cause cancer in people.
"The most important question now is does this virus cause cancer or not, and there are a few different ways to answer this question," said lead investigator Dr. Ila Singh of the University of Utah. Her group is looking at prostate cancers to see whether viral DNA is integrated near human genes involved in growth. If so, the viral DNA may have activated the growth-promoting genes improperly and contributed to tumors.
If the viral DNA is positioned next to the same growth-promoting gene in each of a tumor's cells, indicating the outgrowth of a clone, then the tumor could have originated from a single infected cell and this would be strong evidence of causation, Dr. Singh said.
The researchers are also investigating how the virus might be transmitted from person to person by analyzing seminal and cervical fluids and developing a blood test to check for the virus. If the virus does play a role in cancer, the most productive strategy for combating the problem would be to prevent infection, said Dr. Singh.
XMRV could potentially be a marker for identifying patients with aggressive forms of the disease who require appropriate treatment, she noted. Currently, there is no reliable way at the time of diagnosis to distinguish aggressive tumors from indolent forms of the cancer that may never cause harm.
Fat Cells Interfere with Chemotherapy for Leukemia
Research has indicated that obese children have a greater likelihood of relapse following chemotherapy to treat acute lymphoblastic leukemia (ALL). To investigate potential biological mechanisms behind this observation, researchers from Childrens Hospital Los Angeles tested the interactions between adipose (fat) tissue, ALL cells, and chemotherapy. The results, published online September 22 in Cancer Research, showed that adipocytes (fat cells) interfere with normal chemotherapy-induced apoptosis (cell death).
In an experiment using a mouse model of ALL, 7 of 12 obese mice developed progressive leukemia during or after treatment with the chemotherapy drug vincristine, compared with only 3 of 12 normal-weight mice. Numerous leukemia cells were found in the fat pads of all the mice, indicating that "adipose tissue can be a sanctuary site for leukemia during vincristine treatment," stated the authors.
Culturing ALL cells with adipocytes protected the cancer cells from the effects of four different chemotherapy drugs, including vincristine. This effect was independent of whether the fat cells were in physical contact with the cancer cells.
The researchers also measured expression of several proteins involved in apoptosis in ALL cells grown with and without adipocytes, finding that the adipocytes increased the expression of two "survival genes" that prevent apoptosis in ALL cells, even during treatment with vincristine.
"Our findings show that obesity can directly impair the antileukemia efficacy of the first-line chemotherapy drug vincristine. This effect is likely due in part to adipocytes interacting with leukemia cells," concluded the authors.
Hepatitis B Vaccine Lowers Risk of Liver Cancer
A universal childhood vaccination program against the hepatitis B virus (HBV) substantially lowered the number of cases of liver cancer among children and young adults aged 6 to 19, according to a study in Taiwan published online September 16 in the Journal of the National Cancer Institute.
Chronic HBV infection is considered the most important risk factor for developing liver cancer. Researchers from the National Taiwan University Hospital reviewed follow-up data on 1,958 liver cancer patients diagnosed between ages 6 and 29, most of who were born after Taiwan launched a national HBV childhood vaccination program in 1984. They found that only 64 of the patients with liver cancer had received the HBV vaccine, whereas 444 of the patients had not been vaccinated.
"These data suggest that the effectiveness of the universal HBV immunization program to prevent hepatocellular carcinoma has extended beyond childhood and into young adulthood over the past two decades," the authors wrote.
Among the few vaccinated individuals who developed liver cancer, the two major possible causes were: the individuals did not receive enough doses of the HBV vaccine (three doses are required for full effect), or some individuals born to HBV-infected mothers were not given the first dose of vaccine soon enough after birth to prevent mother-to-child transmission of the virus, the researchers concluded.
"Further efforts to completely interrupt maternal transmission are crucial in eradicating HBV-related hepatocellular carcinoma," the scientists wrote. They recommended improving rates of initial HBV vaccine injection within 24 hours after birth in infants of high-risk mothers.
In the United States, a national strategy to eliminate HBV infection through education and vaccination was implemented in 1991. As a result, the rate of new HBV infections has declined by approximately 82 percent, with the greatest decline among children born since 1991. As part of the U.S. strategy, the CDC's Advisory Committee on Immunization Practices has issued immunization guidelines for the vaccination of infants and children.
Director's Update
Using ARRA Funds to Advance Cancer Research
As the fiscal year draws to a close September 30, a number of offices around NCI become especially busy places. Members of our staff who supervise budget issues, grant funding, program management, and contract administration put in long hours, making sure every dollar is appropriately allocated. In 2009, end-of-year responsibilities are even greater, as NCI also works to distribute the $1.26 billion it received under the American Recovery and Reinvestment Act (ARRA).
ARRA brought to the institute a large amount of money that must be used by our grantees in just 2 years, making it essential that almost all of the funding decisions for ARRA be completed in the 2009 fiscal year. These funds have made possible infusions of resources benefitting both individual investigators and large, team science projects. ARRA is, in fact, a once-in-a-lifetime opportunity for us to truly enhance the field of cancer research. There is also, I believe, an important message in the way the institute has chosen to use these vital resources. It is a story I was most proud to detail for the National Cancer Advisory Board last week.
Fifty-nine percent of NCI's ARRA dollars are going to supplement existing grants or to fund new, competing grants. Individual investigators conducting hypothesis-driven science remain the backbone of NCI's research portfolio, and for that reason, the support of investigators—established or new to the field—was the institute's first priority. We modeled numerous scenarios to determine how many grants NCI could fund and whether to promise just 2 years of funding under ARRA or to extend the term of many grants to 4 or 5 years, committing appropriated dollars for the years of the grant after the ARRA support in years 1 and 2. By planning now for the "out years" after ARRA funds run out, we will be better able to maintain an acceptable level of support for laboratory and clinical scientists working in research universities across the United States and, hopefully, soften just a bit the landing, post-ARRA.
ARRA funds have also gone to education; to the pressing need of our universities and NCI-designated Cancer Centers, so they can continue to nurture great scientific minds. ARRA funds have gone toward programs to help new faculty members get started in their academic careers, to encourage some who may have gone in other scientific directions to return to biomedical research, to facilitate the hiring of summer students to work in labs around the country, and to develop a diverse cadre of new researchers.
Of the remaining ARRA funds, 39 percent are being dedicated to research and development contracts—opportunities for the academic community to participate in more directed, task-oriented research. To take just one example, NCI recently launched a Chemical Biology Consortium, a network of chemists that can be called on to collaborate in large or small teams, depending on the needs of an individual project, to help develop promising targeted therapies and more rapidly get those drugs into clinical trials. Members of the consortium, which will consist of eight universities and three commercial laboratories that were selected from more than 30 bidders, will be asked to carry out specific tasks with measurable outcomes and clear expectations for the project-specific dollars.
ARRA funds, in some cases supplementing appropriated dollars, have made possible a number of other important, directed initiatives.
ACTNOW, or Accelerating Clinical Trials of Novel Oncologic Pathways, will fund 37 early phase clinical trials of new treatment regimens. These awards will be contingent on obtaining Institutional Review Board approval for the trial and opening the trial to patient enrollment within 90 days of their award, with the target for completing enrollment in 2 years.
The Cancer Genome Atlas (TCGA), a project jointly led by NCI and the National Human Genome Research Institute, will expand its mission to identify all of the relevant genetic changes in cancer. In just 3 years, the TCGA pilot project has established state-of-the-art genome sequencing and analysis centers, which have facilitated groundbreaking genetic discoveries in glioblastoma multiforme (the most common and deadly form of brain cancer) and will soon publish important findings on ovarian cancer.
The cancer Biomedical Informatics Grid (caBIG) is moving forward with its ambitious plans to create a secure, nationwide infrastructure for the storage of patient data that will give scientists access to vast amounts of genomic information never before made widely accessible. Spurred by use of electronic cancer records, this resource has the potential to revolutionize the way clinician scientists conduct clinical trials.
The cancer Human Biobank (caHUB) is building a tissue acquisition, storage, and characterization center, which will operate as a centralized nonprofit public resource that will ensure the adequate and continuous supply of high quality, ethically obtained human biospecimens and associated data.
In the end, these initiatives and spending plans will truly matter when the new knowledge they generate reaches the patient's bedside. Likewise, I believe it is our responsibility to convey the scientific excitement and promise that we see reflected in the activities ARRA has made possible. Each of the activities briefly described above is either being scaled up or started because of the availability of stimulus dollars. Without ARRA, many would have been delayed or only marginally supported. By wisely allocating all of the resources we are given, I believe we will hasten our successes. Cancer research is making progress. We know the White House and Congress are watching, as are those living with cancer and the people who love them. We realize all too well the need and the expectations of those who carry the burden of cancer.
Dr. John E. Niederhuber
Director, National Cancer Institute
Charting the Path from Infection to Cancer
Few people associate infection with cancer, but close to one-fifth of all cancers in the world are caused by infectious agents, including viruses, bacteria, and other microbes. In developing countries, the number is higher—about one in four—while in industrialized countries, such as the United States, it is about one in 12.
Infectious agents that can cause cancer are extremely common, infecting millions of people around the world. Yet it is rare and takes a long time for an infection to develop into cancer. "You need a lot of things to happen, or not happen, to get from an infection to cancer," said Dr. Douglas R. Lowy, chief of NCI's Laboratory of Cellular Oncology and a leader in the molecular biology of tumor viruses.
The microbes responsible for most of the global burden of infection-associated cancer are: the bacterium Helicobacter pylori, which causes gastric cancer; cancer-causing strains of the human papillomavirus (HPV), which cause cervical cancer and other cancers; and the hepatitis B and C viruses, which cause liver cancer. These four microbes alone cause more than 15 percent of all cancers worldwide.
Other cancers known to be associated with infectious agents include leukemia and lymphoma; anal, penile, vaginal, and vulvar cancer; and tongue and throat cancers. Last week, researchers reported new evidence linking aggressive prostate tumors to a virus.
Role of the Immune System
Microbes can lead to cancer by a variety of mechanisms that are not yet fully understood, explained Dr. Allan Hildesheim, chief of NCI's Infections and Immunoepidemiology Branch. The cancer-causing strains of HPV are known to disrupt the cell cycle and inactivate tumor suppressor proteins such as p53, which enables genetic damage to accumulate and, eventually, a cancer to form, he explained. H. pylori is believed to induce chronic inflammation, which can lead to atrophic gastritis and, over time, increases the risk of developing gastric cancer.
"In the case of the hepatitis B and C viruses, the problem may be less the infection itself than the immune system's response to it. To fight off the infection, the immune system releases cytokines and other inflammatory proteins that can cause tissue damage," said Dr. Hildesheim. "Over time this can lead to cirrhosis of the liver, which is a strong predisposing factor for liver cancer."
Chronic suppression of the immune system is another cause of infection-associated cancer. People infected with the human immunodeficiency virus (HIV), which weakens the immune system, and organ-transplant recipients who take immunosuppressive medications to prevent transplant rejection are more vulnerable to infection-associated cancers than people whose immune systems function normally.
Similar Molecular Process
The molecular chain of events leading to an infection-induced cancer is similar to the process by which noninfectious cancers develop, said Dr. Patrick Moore, who directs the Molecular Virology Program at the University of Pittsburgh Cancer Institute. "The same tumor-suppressor signaling pathways that are mutated in noninfectious cancers are also inactivated by viruses," said Dr. Moore. "Indeed, it was through research on viral causes of cancer that we learned much of what we now know about cancer-causing genes and tumor-suppressor signaling pathways."
The two most recently discovered viruses believed to be associated with human cancer were both identified in Dr. Moore's laboratory. In 1993, a group led by Dr. Moore and his wife Dr. Yuan Chang discovered the Kaposi sarcoma-associated herpesvirus, also called human herpesvirus-8 (HHV-8), which is the likely cause of Kaposi sarcoma. In 2008, the same team found compelling evidence that a newly discovered virus dubbed the Merkel cell polyomavirus causes most cases of Merkel cell carcinoma, an uncommon but lethal skin cancer.
Opportunities for Intervention
Cancers caused by infection "offer unique opportunities for intervention," said Dr. Lowy. "We now have two vaccines—against hepatitis B and HPV—that can prevent cancer by preventing infection with the virus. Secondly, at least in theory, you can take aim at genes or proteins made by the infectious agent. The best example to date of this approach is antiretroviral therapy for HIV, which works because it has a much stronger effect on the genes and proteins made by the virus than on the body's own genes and proteins."
Many features of infection-associated cancers remain poorly understood. For example, for most of these cancers, only some cases are caused by infection. "Some liver cancers have nothing to do with hepatitis infection," said Dr. Lowy. "Some oropharyngeal, vulvar, and penile cancers are caused by HPV infection, but others are not. On the other hand, virtually all cases of cervical cancer seem to be caused by HPV."
Burkitt lymphoma in Africa is almost always caused by the Epstein-Barr virus (EBV), added Dr. Moore, whereas in the United States fewer than half the cases of this disease have a viral cause. "What we previously thought was a single cancer has been shown to be two or more types of cancer that look similar, some caused by a virus and some not."
Some microbes, including EBV, cause different types of cancer in different parts of the world. "In southern China, nasopharyngeal cancer [a cancer of the throat] is the most common cancer manifestation of EBV infection," said Dr. Hildesheim. "In sub-Saharan Africa, you rarely see nasopharyngeal carcinoma, but Burkitt lymphoma is relatively common."
Genetic Susceptibility
The fact that most infections capable of causing cancer are very common, and yet only a small subset of those infected develop cancer, suggests that genetic and other factors may promote or protect against cancer in infected individuals, continued Dr. Hildesheim. "Those of us who study tumors caused by infectious agents have been a bit late joining the genetic revolution," he said. "There is a tremendous amount we can learn."
Recently he and his colleagues reported on the link between cervical cancer and single nucleotide polymorphisms (SNPs)—one-letter changes in the human genetic code—in genes involved in the immune response to infections and in the repair of DNA damage. They noted that some genetic polymorphisms are associated with increased risk of persistent HPV infection, a prerequisite for an HPV-induced cancer, while others are associated with the tendency for HPV-infected cells to progress to precancer or cervical cancer. Parallel studies have also confirmed findings by other researchers that certain variations in immune regulation genes known as HLA genes appear to affect cervical cancer risk.
"We are trying to understand how individual genetic factors may interact with HPV infection to predispose, or protect against, persistence of the infection or alter the ability to repair genetic damage caused by persistent HPV infection," Dr. Hildesheim explained. "We and others are also studying whether differences in the genetics of HPV might explain why some infected individuals develop cancer while others do not and whether differences in the genetics of EBV may help to explain why the pattern of cancers associated with this virus is so different in different parts of the world."
By better understanding cancer-causing infections, said Dr. Lowy, "the hope is that we will be able to prevent more cancers by preventing the infections that lead to the disease or by treating the infections before they develop into cancer."
—Eleanor Mayfield
The International Agency for Research on Cancer has classified the following infectious agents as carcinogenic or probably carcinogenic—that is, as causing or contributing to cancer development—in humans.
|Infectious Agent
|Associated Cancers
|Epstein-Barr virus (EBV)
|Burkitt lymphoma
Hodgkin lymphoma
Non-Hodgkin lymphoma
Nasopharyngeal carcinoma
NK/T-cell lymphoma
|Hepatitis B virus (HBV)
|Hepatocellular carcinoma (a type of liver cancer)
|Hepatitis C virus (HCV)
|Hepatocellular carcinoma
Non-Hodgkin lymphoma
|Human papillomavirus types 16, 18, and others (HPV)
|Anal cancer
Cervical cancer
Oral cancer
Oropharyngeal cancer (cancer of the base of the tongue, tonsils, or upper throat)
Penile cancer
Vaginal cancer
Vulvar cancer
|Human immunodeficiency virus 1 (HIV 1)
|A variety of immunosuppression-related cancers
Anal cancer
Cervical cancer
Conjunctiva cancer (in the eye)
Hodgkin lymphoma
Kaposi sarcoma
Non-Hodgkin lymphoma
|Human T-cell lymphotropic virus 1 (HTLV 1)
|Adult T-cell leukemia/lymphoma
|Kaposi sarcoma herpesvirus/ human herpesvirus 8 (KSHV/HHV 8)
|Kaposi sarcoma
Primary effusion lymphoma
|Other infectious agents
|Helicobacter pylori (bacterium)
|Gastric (stomach) cancer
|Liver flukes (parasite)
|Cholangiocarcinoma (a type of liver cancer)
|Schistosomes (parasite)
|Bladder cancer
A Closer Look
Harnessing the Biological Activity of Natural Products
Many herbs, dietary supplements, and even vitamins are suspected of interfering with chemotherapy and radiation therapy, and doctors now routinely advise patients who are undergoing cancer treatment to avoid taking these products.
At the same time, cancer researchers have been intrigued by the potent and beneficial biological activity shown by some natural products and are testing ways to incorporate them into standard and experimental treatment regimens, both to enhance the anticancer effects of therapy and reduce the side effects.
A Treatment More than 1,700 Years in the Making
Dr. Yung-Chi Cheng, Henry Bronson Professor of Pharmacology at the Yale University School of Medicine, is interested in herbal compounds that are used in traditional Chinese medicine (TCM). Among other projects, his laboratory has reformulated a Chinese herbal mixture that has been used in TCM for more than 1,700 years to treat gastrointestinal problems, including diarrhea, nausea, and vomiting.
This reformulation, called PHY906, was originally tested to lessen the gastrointestinal side effects of chemotherapy, and, in a small, early clinical study, the compound successfully reduced side effects in patients with colon cancer who received the drugs irinotecan and 5-fluorouracil.
Dr. Cheng and his colleagues also observed a synergistic anticancer effect when the compound was given in combination with irinotecan in animal studies—a result that was surprising, said Dr. Cheng.
PHY906 alone had no effect on these tumors, but irinotecan plus PHY906 had greater antitumor activity than irinotecan alone. Now PHY906 is being tested for potential anticancer activity in combination with traditional chemotherapy drugs in three clinical trials. (The trial for colorectal cancer is still accruing patients.)
In tandem, to understand the molecular mechanisms behind the combination's effects, Dr. Cheng and colleagues are collaborating with Dr. Francesco Marincola, chief of the Infectious Disease and Immunogenetics Section at the NIH Clinical Center, who is using mouse models to measure changes in gene expression after PHY906 and chemotherapy drug administration.
Their preliminary results indicate that "when PHY906 is combined with chemotherapy, this causes a potent inflammatory response, similar to that observed during the rejection of cancer cells during immunotherapy," said Dr. Marincola. "PHY906 may enhance the effects of chemotherapy by adding an anticancer immune response."
From Supermarket to Clinic
Herbal medicines with a long history of use are one type of product being examined for potential uses in modern medicine. But some food products consumed in a normal diet can also affect the workings of the body at the molecular level. One of these foods—grapefruit juice—is now being studied for novel applications in cancer treatment.
Though widely consumed for its high levels of vitamin C and potassium, grapefruit juice is far from an innocuous drink in the eyes of doctors. It contains a class of compounds called furanocoumarins, which block an enzyme found in the digestive system and liver called CYP3A4.
As a result, certain drugs that are normally metabolized by the enzyme stay in the body longer and at higher concentrations if they are taken with grapefruit juice. This can lead to overdoses of some blood-pressure medications, antidepressants, and antiretroviral drugs for HIV, for example.
Grapefruit juice's ability to slow the metabolism of certain drugs, however, caught the eye of researchers at the University of Chicago, who were interested in testing the immunosuppressant drug rapamycin as an anticancer agent.
Rapamycin has extremely poor bioavailability—when taken orally, less than 15 percent of the drug is absorbed into the body. As a result, "We had to use high doses of rapamycin to achieve the blood levels that we wanted," explained Dr. Ezra Cohen from the University of Chicago Medical Center, and the high doses led to unwanted toxicities, such as severe diarrhea caused by surplus rapamycin leaving the intestines.
Looking for a way to give rapamycin more time to reach the bloodstream, Dr. Cohen and his colleagues hit on the idea of administering the drug with grapefruit juice.
In a promising phase I trial presented at this year's meeting of the American Association for Cancer Research, the combination was given to 28 patients with advanced, incurable solid tumors, 7 of who experienced stable disease and one who had a partial response to treatment that has lasted for more than a year.
An added benefit was that co-administration of grapefruit juice allowed for once-weekly doses of rapamycin instead of the traditional once-daily doses, greatly reducing the cost of the therapy.
"There are a lot of [anticancer] drugs that I think would be amenable to this type of approach, because they have poor oral bioavailability, have side effects related to that poor absorption, and are expensive," said Dr. Cohen. He strongly cautioned that patients should not mix grapefruit juice and chemotherapy outside of clinical trials, as the safety of the combination is still being explored.
—Sharon Reynolds
Profiles in Cancer Research
Dr. Jun S. Wei
Staff Scientist, Oncogenomics Section
Pediatric Oncology Branch, NCI's Center for Cancer Research
Dr. Jun Wei's journey into cancer research began in the 1980s in Shanghai—a cosmopolitan cultural center of China, the first country in history to reach a billion people, and a society just beginning to emerge from the Cultural Revolution. Jun Wei, teenaged son of a physician and a chemical engineer, was thinking about science.
"The idea of our generation was if you have talent or potential you study science or engineering, because not everyone can do that," he explained. "You are encouraged from the time you're very young.
"Coming to the United States for college was not that common in the '80s," he said, though some of the practical and financial hurdles were lowered because his uncle's family was already well established in Houston. One of his uncle's daughters, Victoria, was around Jun's age and still in college. The two became very close, and his cousin helped him to assimilate into the new culture as Jun began his studies in biology at the University of Houston.
After becoming more fluent in English and working hard in college, he won a scholarship in 1992 to the Baylor College of Medicine. "In the early 1990s I saw that 'molecular' was becoming a buzzword," recalled Dr. Wei. "I can't say at that time that I had 'the big picture' of a career in mind, but looking back, getting into molecular biology was a good choice."
For someone who would go on to become a leader in a diverse, active genomics laboratory, the cardiovascular sciences program in the DeBakey Heart Center proved to be the ideal training ground. During the mid-1990s he studied molecular and cell biology, while at the same time becoming fascinated by the emergence and promise of molecular tools like DNA microarrays.
Dr. Wei's graduate school training in the 1990s coincided with a dramatic change in the potential of molecular biology. In biomedical research, a genome-wide hunt for disease-causing genes was afoot, even if searching for those genes remained difficult at the molecular level. Current NIH Director Dr. Francis Collins was at the helm of the National Human Genome Research Institute (NHGRI) at the time, driving toward the goal of decoding the human genome. Microarray technology was just about to take off, and Dr. Paul Meltzer's laboratory was one of only a few at NIH (and the world) using that approach to study cancer genetics.
So in 1999, Ph.D. in hand, Dr. Wei answered an NHGRI ad in the British journal Nature for a molecular biologist to study Ewing sarcoma, an uncommon pediatric bone and soft tissue tumor. The senior research fellow he would be working with was Dr. Javed Khan, a Cambridge-trained physician-scientist who had been doing early work at the Sanger Institute in cytogenetics, who began to tutor the junior postdoc in the budding art and science of using microarrays.
The connection would prove to be symbiotic, as Dr. Khan quickly realized. "Jun had an impressive command of a wide range of cell and molecular biology techniques," he recalled.
"You have to remember," said Dr. Wei, "in those days, fabrication of microarrays was not yet perfected. We had to basically build them from scratch." This was a daunting, painstaking process, sometimes requiring hundreds of steps, reliant on judgment, keen observation, and a deft manual touch for manipulating a miniature world that was sensitive to temperature, humidity, and other vagaries of the laboratory environment. "Everything you can imagine could and often did go wrong," said Dr. Wei.
"But Jun was quite amazing, very adept working in that world," countered Dr. Khan, who persuaded his lab partner to come with him 2 years later when he moved to NCI to head the Oncogenomics Section of the Pediatric Oncology Branch in the Center for Cancer Research.
Genomics in the Trenches
For nearly a decade now they have been partners and collaborators. Dr. Wei runs Dr. Khan's lab, one of only a few in the branch using these advanced oncogenomic approaches to study cancers like rhabdomyosarcoma and neuroblastoma.
"You could see that genomics was just taking off when we first started working together, and it was really exciting to get in at that early stage," said Dr. Wei. "At the time we were actually printing our own DNA microarrays, using what was then cutting-edge technology, but which looks very crude in hindsight." DNA microarrays have since become one of the most important and widely used genomic tools for cancer research, allowing researchers to look for DNA changes by matching a particular specimen of tissue from a patient to features printed on the chip, which can be as high as tens of thousands or even millions, in one experiment.
"Oncogenomics is a marriage between molecular biology and genetics," explained Dr. Wei. "Genomic studies systematically hunt for inherited genetic differences between people who have and those who do not have a specific disease. But do these differences cause the disease? Genomic studies only narrow the search to pursue that question."
Drs. Khan, Wei, and their colleagues take the search further, trying to find out how DNA alterations of all sorts come to matter in cancer. "DNA is a very dynamic and complex system, subject to mutation every time cells divide," Dr. Wei said. In the lab they are now sequencing the whole tumor genome using next-generation sequencing technologies and comparing the changes with those found in normal tissue taken from the same patient. The resulting molecular profiles, said Dr. Wei, are becoming a "game-changing way" to diagnose cancer, to predict a patient's response to a particular therapy and his or her outcome, and even to personalize treatment for individual patients.
Their lab has been pioneering this approach since 2001, mastering and enhancing microarray technologies and creating new tools such as artificial neural networks—computer models that can adapt to input by changing and learning like the human brain. Their ultimate target is to discover the "drivers," the critical genes that are causing cancers and which might also become targets for novel therapies.
From Bench to Bedside
Clinical relevance is the key. "You can go fishing for mutations associated with disease," explained Dr. Wei, or "you can put a suspicious mutation into a cell and run a controlled experiment to see if it causes the disease."
Those cell and animal experiments are Dr. Wei's playing field. Reflecting back on the thousands of hours he has spent in the lab, honing his skills and his instincts as a molecular and cell biologist, Dr. Wei recalls the time he spent with his cousin Victoria studying at the University of Houston library until closing time, where he deciphered medical and biology textbooks and scientific papers with his newly acquired English—something Dr. Wei described as "not so much fun." But the effort has no doubt helped him develop the sympathetic perspective to better supervise, train, and mentor postdocs in the lab.
The new generation of researchers will have to master a lot of new tools, while trying not to lose sight of what makes this kind of molecular science "biology"—the study of living things, he said.
"Picking up the newest technology, that's not hard," he explained. "The challenge is: How do you use this new technology in an innovative way? Everybody can learn to use tools, but how do you use the tools to make a beautiful piece of work?"
Dr. Wei is clearly driven by his lab's mission. "These childhood diseases can be heartbreaking. Because many of them involve developmental genes, they form in a way that makes it impossible to screen and difficult to detect at early, treatable stages," he explained. "By the time we get most of these kids into treatment, only 30 percent of them are likely to survive."
You can hear the scientist explaining, but also an echo of a father who empathizes with the parents of children who have cancer. Dr. Wei paused, silent, before pointing with pride to an intricate 3-D collage his 7-year-old daughter, Esther, created that hangs on his office wall.
"The trick is to make your research into your artwork that would be beneficial to those kids with cancer," he said.
—Addison Greenwood
Featured Clinical Trial
Comparing Drug Regimens for Diffuse Large B-cell Lymphoma
Name of the Trial
Phase III Randomized Study of Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) Versus Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin and Rituximab (EPOCH-R) in Patients with Previously Untreated De Novo Diffuse Large B-Cell Non-Hodgkin Lymphoma (CALGB-50303). See the protocol summary.
Principal Investigators
Dr. Wyndham Wilson, NCI Center for Cancer Research; Dr. Andrew D. Zelenetz, Cancer and Leukemia Group B
Why This Trial Is Important
Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin lymphoma. Research by NCI scientists on the genetics of DLBCL has revealed that there may be three distinct subtypes of this disease, each characterized by a different pattern of gene expression.
Standard treatment for DLBCL is R-CHOP, which consists of a chemotherapy drug combination known as CHOP along with the antibody rituximab. Treatment with R-CHOP succeeds in curing more than 50 percent of DLBCL patients; however, many patients still experience progressive or recurrent disease and ultimately die from their cancer.
Another form of combination chemotherapy for aggressive lymphomas, called EPOCH, has been developed by NCI researchers. EPOCH contains the same drugs as CHOP, but it also includes the drug etoposide. Similar to CHOP, EPOCH can be paired with rituximab (EPOCH-R). However, several components of EPOCH-R are given as a continuous infusion over a 4-day period, allowing their doses to be adjusted to achieve optimum concentrations in the blood of each patient. The administration of R-CHOP does not allow for such adjustments.
Some evidence suggests that the benefit of rituximab varies with DLBCL subtype. In addition, other research suggests that EPOCH-R may be effective against subtypes of DLBCL that are resistant to R-CHOP. Consequently, researchers want to know if different therapeutic regimens can increase the cure rates for patients with different DLBCL subtypes.
In this trial, patients with previously untreated DLBCL will be randomly assigned to receive either R-CHOP or EPOCH-R for 6 to 8 cycles. Researchers will monitor the patients for event-free survival (the length of time after the start of treatment until the occurrence of a disease-related event, including progression, relapse, or death), response rate, and overall survival, and they will try to correlate these clinical outcomes with the molecular features of each patient's cancer, as determined by gene expression profiling.
"There are two important endpoints for this trial," said Dr. Wilson. "First, can EPOCH-R produce better clinical outcomes than R-CHOP for patients with DLBCL? Second, can we use gene expression profiling to determine prognostic molecular characteristics that will tell us which patients benefit most from these different regimens?"
For More Information
See the lists of entry criteria and trial contact information or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237). The toll-free call is confidential.
FDA Update
FDA Clears Test for Ovarian Cancer that Could Guide Surgical Decisions
Last week the FDA cleared the use of a blood test that can help determine whether a pelvic mass may be cancerous for women who have already been selected for surgery. When combined with other types of information, the test, called OVA1, can help patients and their health care providers decide which type of surgeries should be done and by whom, the FDA said in a statement.
Studies have shown that women with ovarian cancer survive longer when their surgeries are performed by gynecologic oncologists rather than by general gynecologists or surgeons. The American College of Obstetricians and Gynecologists and the Society of Gynecologic Oncologists have recommended that women be referred to a gynecological oncologist when specific signs of cancer are present.
OVA1 works by testing the blood levels of five proteins that vary in the presence of cancer. Based on these levels, the test produces an overall score between 0 and 10 to indicate the likelihood that the pelvic mass is benign or malignant. How the test is interpreted depends on a woman's menopausal status.
The FDA decision was based on a study of 516 patients that compared OVA1 results with biopsy results. When combined with presurgical information, such as radiography and other laboratory tests, results from OVA1 tests identified additional patients who might benefit from an oncology referral who had not been identified using presurgical information alone, the agency said.
"Tests such as OVA1 personalize and improve public health by providing patients and health care providers with more information to support medical decisions that impact survival rates and reduce surgical complications," Dr. Jeffrey Shuren, acting director of the FDA's Center for Devices and Radiological Health, said in the statement.
Committees Recommend FDA Approve Cervarix and Gardasil
Last week, the FDA received recommendations to approve two vaccines against the human papillomavirus (HPV) that causes cervical cancer.
The vaccine Cervarix is licensed in nearly 100 countries worldwide and approved by the World Health Organization, but it has been awaiting FDA approval since its initial application in 2007 raised concerns about possible side effects. Though structured as a bivalent vaccine to protect only against HPV types 16 and 18, Cervarix has been shown in a recent trial to provide cross-protection against three other HPV types and may also produce a higher degree of protection against precancerous lesions known as grade II cervical intraepithelial neoplasias (CIN2+) than the vaccine Gardasil.
Gardasil has been approved for cervical cancer protection in females aged 9 to 26 since 2006, and targets two additional HPV types that are linked to genital warts, which can occur in males, as well. A second expert committee recommended FDA approval be extended to males in that same age group. The clinical trials on which the committee based its recommendation showed that Gardasil was 89 percent effective in preventing genital warts and had no side effects, though it was less effective in those who had already been exposed to HPV.
Dr. Ming Lei Named Cancer Training Branch Chief
Dr. Ming Lei has been appointed chief of the Cancer Training Branch in NCI's Center for Cancer Training. The Cancer Training Branch develops, administers, and manages the extramural, grant-supported research training and health professional career development programs at NCI.
Dr. Lei received his Ph.D. in molecular biology from Cornell University. He was an associate professor in the Department of Microbiology and Molecular Genetics at the Medical College of Wisconsin, where his research laboratory studied regulation of DNA replication and chromatin assembly. Dr. Lei served as a program director and cluster leader at the National Science Foundation before joining NCI in 2008 as a program director in the Division of Cancer Biology.
As chief of the Cancer Training Branch, Dr. Lei will oversee national strategies for training and career development of basic, clinical, and population-focused cancer scientists, and fostering education, outreach, and curriculum development activities in fields that support cancer research.
Dr. Louise Brinton Receives Lilienfeld Award
In recognition of her outstanding career in cancer epidemiology, Dr. Louise A. Brinton of NCI's Division of Cancer Epidemiology and Genetics received the 2009 Abraham Lilienfeld Award at the American College of Epidemiology's annual meeting on September 12–15 in Silver Spring, MD.
Dr. Brinton's current research focuses on the application of biomarkers of genetic susceptibility, endogenous hormones, and risk factors for breast and gynecologic cancers.
Upon receiving the award, she gave the Lilienfeld Award Lecture, reflecting on the uniqueness of epidemiology as a science and the ways in which the discipline has evolved. She emphasized the critical importance of training the next generation of epidemiologists and knowing how to conduct field work.
Webcast Registration Available for DCIS Conference
Beginning today, NCI and NIH's Office of Medical Applications of Research are convening a 3-day, state-of-the-science conference on ductal carcinoma in situ (DCIS) at the Natcher Conference Center on the NIH campus. Participants who are unable to attend the conference in person may sign up online to view the live Webcast and receive the final conference statement.
The panel's draft statement will be posted on the Consensus Development Program Web site for public download on the evening of September 24. Final conference statements are usually available online approximately 6 weeks after a conference, and printed copies are typically mailed approximately 4 months later.


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When fossil hunter Bernard Ngeneo came across the remains of this fossil, only the upper portion of the orbits were protruding from the ground. Excavation revealed one of the best preserved skulls of this time period, and one of the most striking early human fossils of any age.
KNM-ER 3733 represents a mature female of the early human species Homo erectus. The gender identification comes from a comparison of the anatomical features of her face with another cranium from Koobi Fora. KNM-ER 3883, and the KNM-WT 15000 male, found on the opposite side of Lake Turkana. The features of KNM-ER 3733 are markedly less robust. It's known to be an adult on the basis of the cranial sutures (which were fully closed), the extent of the wear on the teeth, and the eruption of the third molars before the individual's death.

subset: commoncrawl


text:
PLAY YOUR BEST WITH Graphene*
Stay unpredictable, surprise your opponents over and over again, and they will never know how you´ll play next. Upgrade your game with the new HEAD Graphene Radical.
UPGRADE YOUR GAME WITH ANDY MURRAY, GILLES SIMON, MARIA SHARAPOVA, NOVAK DJOKOVIC AND THE NEW HEAD Graphene SERIES.
Graphene is integrated into the racquet shaft, making it more stable and allowing an optimized redistribution of weight.
Weight has been shifted to the grip and racquet head, providing better maneuverability and increased swingweight.
*HEAD PRO Players may play with different racquets from the model shown.


text:
Steve Albini Quotes
Found 20 quotes by Steve Albini .
[ Page 1 of 1 ]
[ Page 1 of 1 ]
Featured Book: The Most Brilliant Thoughts of All Time (In Two Lines or Less) by John M. Shanahan
You don't have to be a genius to sound like one. Here's a collection of the most profound and provocative wit and wisdom in the English language in two lines or less. Edited by entrepreneur John M. Shanahan, who created the wildly successful Hooked on Phonics program, this wonderful book presents the best that has been thought and said on every imaginable topic.


text: I don't know where this is. I don't know to what they are referencing in the interview. It's just a (as far as I know) random interview about soccer with some (as far as I know) random player on (as far as I know) random media outlet. So why do I care? Why am I subjecting you to a seemingly random 25 seconds of video? Check it out at about the :17 mark. At least he made the catch, right? Never give up on the play, folks. Never:


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Hi. I've been browsing for a long time and thought now was the time to share myself. What do you guys think? (click for full size)
More pics here: http://xjustsomeguyx.tumblr.com/tagged/me
Hi. I've been browsing for a long time and thought now was the time to share myself. What do you guys think? (click for full size)
More pics here: http://xjustsomeguyx.tumblr.com/tagged/me
Holy fuck I want you.
So fucking hot.
Very very nice pics.
Welcome to JUB.
"You may only be one person to the world, but you may also be the world to one person"
- anonymous quote.
Whoa, aren't you just nice and smooth, clean shaven and HOT!!
Welcome to J U B!!
Please, do post some more!
Welcome to JUB!
Sir Ron finds your body totally hot and sexy.
The Three Musketeers... Bashful, Chrisglass, and Ronboy!
One cute hot sexy erotic sensual young lad. Plus love that uncut cock.
Welcome to JUB. Hot pics.
My god, I would fuck you before you saw it coming. That ass shot is very tempting. nice uncut cock too. Love the dark bush...yum.
hmm the dark bush on your pale body is a special treat! love that contrast.
and this pic from your tumblr is awesome:
almost looks like you want to penetrate yourself
Check out my very own Body Hair Lovers and Photography Groups!
Great pics on your tumblr site!! You are very HOT!!
wow id do ya
You are amazing!! My thoughts........ I would suck your balls dry every single day just for a start!!
he's gone....
Wow he sure has a great uncut dick!!!
well what a hotty, you are, great smooth look and suckable cock n balls..
wow incredible pics
It is a shame that the OP has left.....
He was truly beautiful!
The Three Musketeers... Bashful, Chrisglass, and Ronboy!
Wow! So hot. Love your body. Just my type! Check out my pics and message me! ,o)
love to eat that hole and suck that uncut cock
I am not usually into skinny guys but you have a really cute ass.
Super ))
Visit my blog: nudeladz.blogspot.com
Love the pic of your cock on the tumblr site with your skin pulled back Love your bushy pubes !


text:
ROOKIE BLUE - "Girlfriend of the Year" - Chris and Gail's investigation into a messy highway accident leads to the discovery of a license plate matching an Amber Alert for a missing nine-year-old girl. Division 15 embarks on a massive manhunt to find the girl and the car's missing driver. Meanwhile, an intense interrogation of the parents uncovers disturbing evidence. More secrets unravel, as the entire division races the clock to find the young victim - hoping it's not too late -- on "Rookie Blue," THURSDAY, AUGUST 19 (9:00-10:00 p.m., ET) on the ABC Television Network. (ABC/ANNABEL REYES) MATT GORDON
Use a Facebook account to add a comment, subject to Facebook's Terms of Service and Privacy Policy. Your Facebook name, photo & other personal information you make public on Facebook will appear with your comment, and may be used on ABC's media platforms. Learn more.


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U.S. Sen. Dick Durbin is calling for a federal investigation of a deadly crash on I-88 in west suburban Aurora that claimed the life of a tollway worker and seriously injured an Illinois State trooper on Monday.
Durbin asked the Federal Motor Carrier Safety Administration on Thursday to "immediately and fully" investigate the accident to determine if the driver or his employer, DND International, violated rules limiting the number of hours a driver can be on the road, and to take steps to ensure every trucking company is complying with the law.
LETTER: Durbin writes to FMCSA
The driver, Renato V. Velasquez, 46, was charged with operating a commercial motor vehicle while impaired or fatigued, making a false report of record and duty status, and driving beyond the 14 and 11-hour rules, all felonies, the Chicago Sun-Times reported.
Velasquez was also cited for failure to reduce speed to avoid an accident and failure to yield to stationary emergency vehicles, state police said. He was ordered held on a $150,000 bond.
Vincent Petrella became the first Illinois Tollway employee in more than a decade to be killed on the job in the fiery crash that also critically injured ISP Trooper Douglas J. Balder.
Balder, 38, was helping Petrella, 39, with a broken-down semi about 9:45 p.m. Monday in the right-hand lane and shoulder of eastbound I-88, according to authorities.
"The Federal Motor Carrier Safety Administration has the authority and the responsibility to investigate incidents like the one this week in Illinois and I urge you to quickly and fully investigate this accident," Durbin said in the letter.
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text:
After over 90 years in business, everything must go. Serman's, the premiere men's clothing store in downtown Detroit, is closing its doors for good."My grandfather started this business in 1917 and our first store was on Hastings Street, and then he moved to [our present] location in the early 1940s," said owner Steve Ross. "It's time. I want to go out as a winner, not a loser."So many have walked through the doors from the guy down the block to Steve Harvey."In the sixties and seventies, it was superfly," Ross said. "Detroit was famous all over the country for its fashions, and all of Motown, we had 20 or more men's clothing stores and shoe stores in downtown.""Unfortunately, most of the young people today will never be able to experience what it's like shopping in a neighborhood clothing store."Tuesday, Ross received the Spirit of Detroit Award from the Detroit City Council."It was very humbling. Common council gave me the Spirit of Detroit Award. It was a great honor," he said.Dan Gilbert bought Serman's building, and Ross shared his thoughts on Gilbert."I think Dan Gilbert is the best thing that's ever happened to the city of Detroit because he understands what all the components are that are necessary to have a thriving and successful downtown," he said. "There's absolutely no question that he'll succeed. What he's doing would take the city of Detroit a hundred years to accomplish.""I think Dan Gilbert is like the Henry Ford of our generation. He gets it. He understands it, and more importantly, he knows how to implement his plans."Serman's will remain open for another four to six weeks, so there is still time to stop in, say thank you and goodbye.
25 FOX DriveDedham, MA 02026
Phone (781) 467-2525


text: "I want to be Ed Hochuli" - Someone finally put my one wish into the youtube format. Thank you Youtube. Thursday, December 12, 2013 9:42 a.m. by Bildo Even the little ditty there about the '85 Bears I can't even hate... I do in fact want to be Ed Hochuli.


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Visiting CIM
The Cleveland Institute of Music is located in the heart of University Circle, adjacent to the Case Western Reserve University campus. University Circle, Northeast Ohio's cultural center, was named one of America's prettiest neighborhoods by Forbes Magazine. We are proud to be part of this amazing community focused on the arts, education and enrichment. CIM is walking distance from Severance Hall, home to The Cleveland Orchestra, The Cleveland Museum of Art, Cleveland Botanical Garden, Cleveland Museum of Natural History, Western Reserve Historical Society, Case Western Reserve University and the Cleveland Institute of Art. A variety of restaurants and coffee shops are also within this walkable community.
Prospective students and parents are welcome to visit the Cleveland Institute of Music throughout the year. The Admission Office is open Monday through Friday with guided tours offered daily by appointment. Please contact the Admission Office to arrange a tour.
Parking at CIM
CIM provides free parking for patrons in the lot next to the building on Hazel Drive. Although the school has ample parking, capacity crowds are expected for some events, necessitating the need for off campus parking. Metered spaces are available on Hazel Drive, just outside of the building. For more parking options around University Circle, click here.
Click on any of the links below to help plan your visit.
- Visitor Guide (PDF)
- University Circle Videos
- Google map of the campus area
- Campus Map of Case Western Reserve University.
- Cleveland-area resources and entertainment information
- University Circle Calendar of Events (PDF) and Visit Wizard
- Hotel Information
Traveling Information
The Cleveland Institute of Music is approximately five miles directly east of downtown Cleveland, off Euclid Avenue, at the corner of East Boulevard and Hazel Drive.
Cleveland Institute of Music
11021 East Boulevard
Cleveland, OH 44106-1705
Phone: (216) 791-5000
If traveling from the east or west on Interstate 90 ...
If traveling from the east on Interstate 80 or the PA Turnpike ...
If traveling from the south on Interstate 71 or Interstate 77 ...
If arriving in Cleveland by air ...
If arriving in Cleveland by bus ...
If arriving in Cleveland by Amtrak train ...
Marketing and Communications
Director of Marketing and Communications
p. 216.791.5000 ext. 222
f. 216.791.1530
Communications Manager
p. 216.791.5000 ext. 225
f. 216.791.1530
Marketing Manager
p. 216.791.5000 ext. 587
f. 216.791.1530
Office hours are from 9:00 a.m. to 5:00 p.m. EST Monday through Friday. Building hours may differ; check concert listings for performance times.
CIM Online
Become a fan of CIM on Facebook
Hear live CIM concerts online at InstantEncore
Watch streaming CIM videos on Vimeo
Follow CIM on Twitter
Upcoming Events
The Next Generation
October 8, 2014, 11:30 am
Westwood Country Club, 22625 Detroit Rd, Rocky River
A CIM Women's Committee Musical Luncheon
Orchestra | CIM@HOME
October 8, 2014, 8:00 pm
Kulas Hall
Cleveland Institute of Music Orchestra
Carl Topilow, conductor
Rebekah Efthimiou, harp, student artist
UCWE/CWRU Symphonic Winds Concert
October 12, 2014, 3:00 pm
Kulas Hall
University Circle Wind Ensemble
CWRU Symphonic Winds
Dr. Gary M. Ciepluch, conductor
Music of Hindemith, Sparke, Camphouse and Orff


text:
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text: Erica P. Says Scrappy Told Her He Was In Love With Her Could Stevie J Be Pushing Up On Bambi Next? Malaysia Stars In Mase's New Video, Are They Together? Does Jackie Christie Want To Role-play With Nikko? Jackie Christie Says Rasheeda & Kirk Is Jackie Christie Gonna Appear On Hit The Floor?!


text:
Starbucks Reserve® Hawaii Ka'u
A rare coffee with fresh coconut and caramel flavors and hints of citrus and nut.
Tasting Notes
Tropical coconut with sweet caramelly and citrus notes.
Enjoy this with:
A fresh fruit salad and a relaxing afternoon.
- At a Glance
- Did You Know?
- Starbucks Reserve®
Producer: Small coffee farms in the Ka'u region of Hawaii
Elevation: 411 - 640 meters (1,350 - 2,100 feet)
Coffee Variety: Typica, Bourbon, Catuai
Processing Method: Washed
Kaʻu is a region on the Big Island of Hawaii, neighboring the highly acclaimed Kona growing region. In Kaʻu, small coffee farms sit on the southwest slopes of Mauna Loa, nestled in verdant valleys where they are tended predominantly by former sugar plantation owners. The Hawaii Kaʻu region is newly recognized among the finest coffees in the world, winning the 2011 SCAA Coffee of the Year award.
Of the thousands of coffees we encounter in our search for the best, only a precious few are deemed exceptional enough to become Starbucks Reserve® coffees, offered only for limited times at select stores.
- Product Details
The Ka'u region, which borders Kona on the island of Hawaii, has been recognized for its award-winning coffee and is home to these beans, cultivated on the slopes of Mauna Loa.
The delicate tropical flavors captivated our buyers beyond expectation, leaving no doubt that we had to share this rare sip. Handpicked and processed in small batches by family farmers devoted to Hawaiian tradition, this coffee is the latest wonder from paradise.
This special Starbucks Reserve® coffee is in very limited supply and only available at select stores.


text:
vCenter Operations Management Suite
VMware vCenter™ Operations Management Suite™ automates operations management using patented analytics and an integrated approach to performance, capacity and configuration management.
Intelligent Operations
Proactively avoid performance issues and gain deep insights into the health, risk and efficiency of your virtual and physical infrastructure, operating systems and applications.
Unified Management
Get a holistic view into what is driving performance, capacity and configuration issues, infrastructure and application dependencies.
Policy Based Automation
Automate root cause analysis with advisory tools and orchestration workflows to enable optimal resource utilization, operational efficiency and enforcement of configuration standards.
- vCenter Operations Management Suite Documentation
- vCenter Operations Management Packs PDF
- Automated Operations Management for Your Enterprise PDF
- How "Normal" Is Your IT Data? PDF
- Stop the Finger-Pointing: Managing Tier 1 Applications with VMware vCenter Operations Management Suite PDF PDF
- Configuration and Compliance Management with VMware vCenter Operations Management Suite
- Managing Infrastructure Health and Performance with VMware vCenter Operations Management Suite
- The Changing Nature of Enterprise Management
- Management and Automation Strategy - Maximize Efficiency, Increase Agility VIDEO
- VMware vCenter Operations Management Suite Datasheet PDF
- Forrester Consulting Reports on the Total Economic Impact of VMware vCenter Operations Management Suite PDF
- Businesses Experience Significant Operational and Business Benefits from vCenter Operations PDF
- IT Evolution: Operations Transformation in the Mobile-Cloud Era PDF
- Taneja Group: An Overview of the Virtual Infrastructure Operations Management Market (registration required)
- Customer Success with Operations Management VIDEO
- BancVue Case Study VIDEO
What's included in vCenter Operations Management Suite
VMware vCenter™ Operations Manager™
Provides comprehensive visibility into the performance, capacity and health of your infrastructure, operating systems and applications.
VMware vCenter Configuration Manager™
Automates configuration management across virtual and physical servers, and continuously assesses them for compliance with IT policies, regulatory and security compliance.
VMware vCenter™ Hyperic®
Monitors physical hardware resources, operating systems, databases and applications.
VMware vCenter™ Infrastructure Navigator™
Automatically discovers and visualizes application components and infrastructure dependencies.
vCenter Operations Management Suite Support Center
Self-service resources can help you with installation, configuration and troubleshooting.Get vCenter Operations Management Suite Support
vCenter Operations Manager Community
Discover the latest news and information about vCenter Operations Manager, a component of the vCenter Operations Management Suite.Join the vCenter Operations Manager Community
Virtualization and Cloud Management Blog
Check out the VMware blog offering technical tips, best practices and links to helpful resources.Read the latest blog posts


text:
A millionaire threw a massive party for his
50th birthday. During the party, he grabbed the microphone and announced to his
guests that down in the garden of his mansion he has a swimming pool with two
great white sharks in it.
"I will give anything of mine to the man who swims across that pool."
So the party continued with no events in the pool until suddenly, there was a great splash and all the guests of the party ran to the pool to see what had happened.
In the pool a man was swimming as hard as he could and fins came out of the water and jaws were snapping and the guy kept swimming. The sharks were gaining on him. Luckily, the guy reached the other end of the pool, got out, tired and soaked.
The millionaire grabbed the microphone and said, "I am a man of my word. Anything of mine I will give: my Ferraris, my house, absolutely anything, for you are the bravest man I have ever seen. So sir what will it be?"
The guy grabbed the microphone from the millionaire and said, "Why don't we start with the name of the jerk that pushed me in!"
We have fun and party all the time @ http://929wlmi.com/latest-updates/authors/34/


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- 1 Girl, 10, victim of purse snatching
- 2 Tucson easily tops Phoenix in 'educated cities' list
- 3 Former Wildcat pushes to put Snowden in Hall
- 4 UA football: Older, wiser Fuimaono eager to play
- 5 Hurricane Odile didn't follow the models
- 6 Police looking for counter-jumping pharmacy robber
- 7 Steller: GOP considers alienating 1.15 million AZ voters
- 8 Let's go for a walk: Lost Barrio and Arroyo Chico
- 9 Zakaria: Deft on world stage, India's Modi inert at home
- 10 Sunnyside faces Badgers tonight in 'must-win' game
Arne Duncan: Universal preschool will work, so let's get on with it - Comments
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Barely Pink Cotton Twill Skirt - 15 InchThis Barely Pink cotton twill skirt comes in a variety of solid colors. 100% brushed cotton twill skirt with 2 front slant pockets. 15 inch length. One back pocket with button. Very soft cotton. Learn More$69.00
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Ideal for kitchens and bathrooms, this Contour Checker blue wallpaper means a superb contemporary, traditional tile effect finish can be achieved at the fraction of the cost of tiles.
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Chris Wallace is the host of Fox News Sunday. On Friday, during a live interview to promote his show on WJBK Fox 2 in Detroit, anchor Alan Lee asks Wallace if the subject of Viagara will 'come up' in Wallace's scheduled interview with former Senator Bob Dole. Wallace responds, "Comes up, really that's what you're going to say?"The two then share a laugh over the obvious joke. Lee then says he didn't think about how he phrased his question "that it went over his head." Luckily Wallace didn't go after the 'next' opportunity to make a joke.Play the video to see the unexpected joke. Tune into Fox 2 News Morning Weekend from 6:30 a.m. until 10:00 a.m. Fox News Sunday follows immediately starting at 10:00 a.m. Joining Wallace on May 26: Senator Dick Durbin and Senator Lindsey Graham join Chris Wallace to discuss President Obama's Thursday speech on Gitmo, drones and national security.
AND -- As he approaches 90, this influential voice in American politics gives us a unique perspective on the past, today's issues, and the Republican party he's championed over a political lifetime. Former Senator Bob Dole.
Fall is here, so it's time to spice up that old mac & cheese with some tastes of the season.
KTTV FOX 111999 S. Bundy Dr.Los Angeles CA 90025Main: (310) 584-2000News Tips? (310) 584-2025


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Pre-Shave Oil
Product Description: Pre-Shave Oil is the first step in The Art of Shaving. It softens the beard and prepares the skin for a close and comfortable shave without leaving an oily residue. It is formulated with a unique blend of botanical ingredients and essential oils.
How to Use: Before shaving, rub a small amount of oil on your hands and massage into the beard. Lather up Shaving cream or soap on top of the oil and shave.


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Find a location near you or call 800-242-1715
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This is just a wonderful facility. The employees and manager are very nice, professional and a pleasure to work with. This is my second time storing at this location and each time has been an easy, smooth, informative transaction.Chelsey from Barrington, RI
September 6, 2014
the staff was particularly helpful to me in arranging for my space as I was doing this from the west coast. They were very accommodating with faxing paperwork back and forth and making sure I got the most appropriate space for my needs. I was very impressed and grateful.Martha from Mattapoisett, MA
July 28, 2014
My mother used this location for her own storage while I was young and now I am using it. Both times the workers have been nice and the property is well maintained. A very nice place.Trisha from North Providence, RI
March 23, 2014
My move-in experience was extremely pleasant. In addition to being able to use their free moving truck service, I can't tell you how useful it was to have dollies (rolling hand carts) available at the facility to transport boxes from the elevator to my storage unit. It significantly reduced my trips back & forth. I can't tell you just how much I appreciate it--it really is the small things that count. Thanks!Floreena from Cumberland, RI
January 20, 2014
I had issues with Bobs 2 winters ago . No one shoveled . or threw down salt . My daughter and I were going to our unit. She fell twice because it was icy ( I am sure its on video ) no one was around to help us our lock froze too. No one cared I did complain but was told It was the weathers fault. I was going to switch copany's but a new office person came in and is fantastic..Irene from East Greenwich, RI
August 31, 2014
Checking in was an easy and pleasant experience. The manager on staff was very helpful.Peter from New York, NY
August 20, 2014
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July 27, 2014
There are other storage facilities in the area that are lower in prices. Maybe Uncle Bob's rates could be lower.Paul from Coventry, RI
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Even though I came after my reservation expired they were more than accommodating. Everything was explained to me thoroughly and respectfully.Christine from Pawtucket, RI
May 31, 2014


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The Clarks Purity Snow is crafted of soft leather with a leg-flattering leawood stacked wedge, this women's shoe is both classic and current. Butter-soft leather linings and an OrthoLite® footbed cushion the foot in comfort. Offered in rich suede, it's a natural with tights and a skirt, or a business suit.
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The year was 1978, and the Yankees were the World Series champs again. Jimmy Carter was president, Affirmed won the Kentucky derby, The Deer Hunter was named best film at the Oscars. In January, the Bee Gees had the number one song.
But it was also the year the Tison Gang broke out of the Arizona State prison and went on a killing spree from Yuma to Kingman before Arizona authorities hunted them down.
It was also the year a Vietnam veteran was shot and killed in a Phoenix bar. A "cold case" that went unsolved -- until now.
The husband, father of three and disabled vet was gunned down during a robbery. Witnesses say the suspect threw a bottle at him, before killing him.
The bottle didn't break. Instead, it helped the detectives break the case.
"I was kind of shocked, I just couldn't believe when they came and told me he was shot and killed."
Jeff Gruette was 23 years old when his father, Duane, a Vietnam veteran, was murdered during a robbery at the Westward Tavern in 1978.
The case grew cold and was eventually buried among the 2,500 other unsolved Phoenix murders. That is until Troy Hillman, a police sergeant with the Phoenix Police Cold Case Unit, dusted it off.
"It was a good case because there were a number of items that hadn't been tested for DNA," says Sgt. Troy Hillman.
The cold case unit, made up of 7 Phoenix investigators, examines cases dating back to 1950. They hope these cold cases can still generate hot leads, with 2,500 cases to go through.
"It's actually typed documents."
It's a daunting task to even figure out where to start. Right now, investigators are prioritizing cases.
They developed a solvability scale.
"One is considered a very poor case, there's nothing to go on, there's no evidence. May have even had a hard time identifying this person and absolutely nothing there to go on forensically or lead wise," says Hillman.
"A lot of them fall in the 2 range, 3 range, mainly 2 because detectives, very good detectives have worked these before and they've pushed them forward as much as they can."
"Then we go up the scale to 4 which is a very good case, which is a few things need to be done and it's going to move forward and clear the case."
The Gruette case was a 2.
Initial detectives did a thorough investigation, and cold case detectives re-examined it in early 2000. But there was a palm print taken from an unbroken beer bottle that a witness says they saw the suspect throw at Gruette inside the bar.
"They were able to process the print, they just didn't have anybody compare it to. Sometimes it takes an arrest or something to get prints on file."
Last year, investigators re-ran the print and got a match.
"When the hit came back he assigned it to me to work with it from there," says Det. JJ Alberta, Phoenix Cold Case Unit.
Detective JJ Alberta went to Yuma to interview the match, 53-year-old George Jones. Jones was in jail on drug charges.
"He told me he was involved, he remembered being there and the incident, however he denied shooting the victim in the case."
Still, Jones was charged with the murder and found guilty. Last Tuesday, Jeff Gruette was in court as Jones was sentenced to life in prison for the crime.
"You know I've been waiting for that for a long time. I feel good, I honestly felt I kind of owed this to my father," says Gruette.
The Cold Case Unit has solved 34 cases since 2009 and they continue to add faces to the board of people arrested. While the case files date back to the 1950's, the oldest case solved is from 1978.
"We started back in 1950, we tried to review every case from 1950 forward," says Hillman.
But in 4 years, detectives haven't even been able to look through all of the cases.
"It's not something you knock out in a half an hour."
Right now they're reviewing cold cases from the year 2000 and forward. They're hitting the streets, knocking on doors and sending evidence from a handful of cases to the lab to get tested, weekly.
"You're not going to get away with murder, we're going to keep trying and not give up," says Sgt. Hillman.
"33 years it took for them to catch this gentleman, 34 for to prosecute him and we got a guilty verdict of first degree murder so don't give up," says Gruette.
The cold case unit has caught some lucky breaks. One time a man walked into the police department to confess to a cold case.
"I think it was a late 80s case, he said I want to clear my conscience, I want to confess to killing a man," says Hillman.
But that kind of break is rare. Despite DNA testing and new technology, the unit still relies on tips from the public to solve cases.
Silent witness Sgt. Darren Burch says, no matter how old the case, tipsters can remain anonymous and may be eligible for a reward.
"Sometimes during the initial investigation, you have witnesses that do not want to be found or can't be found for some reason," says Burch.
If you have information on any cases, call Silent Witness at 480-WITNESS.
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text: The auto industry is powering up to help the economy.Surging car sales could boost economic growth this year by nearly a full percentage point, its biggest contribution to the economy in more than a quarter-century, according to a new analysis.Pent-up demand from consumers who are feeling more sanguine about job security and income levels could drive sales volume to as many as 13.6 million vehicles this year, said Carl J. Riccadonna, senior U.S. economist at Deutsche Bank in New York.That would be a 17% increase from the 11.6 million vehicles sold last year and could add as much as 0.8% to U.S. gross domestic product, the most since 1984, Riccadonna said.The rise in car sales ?appears to reflect an improvement in households? confidence in the economic outlook,? Riccadonna wrote in a note to clients, adding that ?households typically refrain from big-ticket purchases, such as autos, until they are more confident about their own economic prospects.?Auto sales could keep rising throughout the year as consumers feel more confident in the economy and as lenders become more generous with credit, Riccadonna said.-- Walter Hamilton


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Lauren Chattman
Lauren Chattman is a cookbook author, freelance writer and former professional pastry chef. Her recipes have appeared in Food & Wine, Bon Appetit, Cook's Illustrated and The New York Times. She is the author of 14 books, most recently "Cake Keeper Cakes" (Taunton 2009) and "Cookie Swap!" (Workman, 2010). She has also co-authored several books with former White House pastry chef Roland Mesnier, including Dessert University (Simon & Schuster, 2004). With artisan baking expert Daniel Leader, she is the co-author of the IACP award-winning "Local Breads" (Norton, 2007). With Susan Matheson, she is co-author of "The Gingerbread Architect" (Clarkson Potter, Fall 2008) Lauren lives in Sag Harbor with her husband and two daughters. She blogs about local food and small-town life at sagharbordays.blogspot.com.
Lauren Chattman 8/21/14 Recipe: Sweet corn bundt cake with maple glaze
There is evidence, in the form of corn pollen grains unearthed 200 feet beneath Mexico ... Read more »
Lauren Chattman 8/7/14 Berry hand pies make perfectly portable beach treats
Fruit pie season and beach season coincide, but it's not easy to enjoy them simultaneously. ... Read more »
Lauren Chattman 7/16/14 6 delicious ice pops to make this summer
In the heat of the summer, I rely on one of my favorite tropical ingredients ... Read more »
Lauren Chattman 7/16/14 6 delicious ice pops to make this summer
These will help to bring down your temperature. ... Read more »
Lauren Chattman 7/1/14 6 delicious July Fourth ice cream desserts
Are you sitting around thinking that you'll just grab a half-gallon of ice cream from ... Read more »
Lauren Chattman 6/12/14 Sweet ways to use local strawberries
I usually make strawberry shortcake for my older daughter's birthday the first week in June. ... Read more »
Lauren Chattman 5/28/14 Baking dessert on the outdoor grill
After a long and claustrophobic winter in the kitchen, I'm looking forward to a long ... Read more »
Lauren Chattman 5/14/14 Make whipped cream perfectly, every time
Memorial Day marks the beginning of strawberry season for many Long Islanders. For me, it's ... Read more »
Lauren Chattman 4/24/14 Flourless chocolate-macadamia cake
Just a few years ago, coconut oil was shunned by the medical establishment because it ... Read more »


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A jewel-toned creation with deep purple hues, this enhancer will turn heads with its embodiment fashion and saturated tones. A briolette amethyst gemstone is the captivating centerpiece, accented with a gemstone of faceted round blue apatite, an opal triplet and a faceted round amethyst. Lovely and unique, enhancer measures 2" long x 3/4" wide and has a snap hinge bail. Made in America with gemstones from around the world.
A favorite collection with an updated look. Deep purple amethyst briolette gemstones create the centerpieces of these jewel-toned styles. With accents of opal, apatite and amethyst, these designs have been created by designer Carolyn Pollack as bold, sophisticated accents for your evening looks.
Like all fine jewelry, Carolyn Pollack Sterling Silver Jewelry should be handled carefully. Store jewelry in a plastic bag, dry and wrapped in tissue paper, when not being worn or displayed. Clean sterling silver with a silver polishing cloth when necessary, but never subject to chlorine, silver dips, chemical solutions or ultrasonic cleaners, as these substances can cause the genuine gemstones to discolor. Never wear jewelry in a swimming pool.


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Ben Harper is teaming up with LIFT to help lift American families out of poverty and give you a chance to win (2) premium tickets, a meet & greet with Ben and an autographed poster at one of his upcoming solo acoustic shows! Entries are just $10, with proceeds benefiting LIFT.
If you haven't had a chance yet, please take the time to give a proper send off to one of the greatest skaters we've ever seen, Lewis Marnell, and as a tribute to him raise money for his fam.
Jah Work: A Lewis Marnell Tribute, available at iTunes, Amazon and Google Play.
Get ready for an exclusive live session from Ben Harper and Charlie Musselwhite today at 4pm PDT on KCSN 88.5 FM in Los Angeles and online at www.kcsn.org. Recorded at the Village Recorder, the performance includes songs from their acclaimed album "Get Up!" out now on Stax/Concord!


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Prices and availability are subject to change from the time and date that you print this page.
10/2/2014 12:41:16 PM. For Customer Service, please call 800.933.9904
Used properly, Ziggles bring about giggles. Soft, springy toy entertains and stimulates baby's senses by putting various textures and activities at your little one's fingertips. Makes a nice shower gift.
Ziggles Baby Toy 3"Wx3"Dx8.5"H
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Age range
At The Land of Nod, nothing is more important to us than providing safe, high-quality products to you and your family. We believe that kids' products should be able to handle everything kids throw their way (literally and figuratively). That's why all of our products have an 18-year quality guarantee. And, hopefully, your kids will no longer be sleeping in bunk beds by then.
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Canoe who?
Canoe help me with my homework?