A study of nearly 1,500 patients treated for kidney cancer at UCLA in the last 15 years shows that an aggressive, tailored treatment approach results in better survival rates and uncovered subsets of kidney cancer that behave differently and need to be treated accordingly.

The one-size-fits-all approach traditionally used in kidney cancer treatment should be changed based on the results of the study, the longest to date to analyze kidney cancer patients and their outcomes, said Dr. Arie Belldegrun, senior author of the study, a professor of urology and a researcher at UCLA’s Jonsson Comprehensive Cancer Center.

“This is the most important work that we’ve done out of the kidney cancer program at UCLA,” Belldegrun said. “We outline the foundation for personalized kidney cancer therapy. We have shown that not all kidney cancer patients are the same, not all localized kidney cancers are the same and not all metastatic kidney cancers are the same.”

The study appears in the Nov. 1, 2008 issue of Cancer, the peer-reviewed journal of the American Cancer Society.

The study found that patients with localized kidney cancer, cancer that has not spread to other organs, could have either low, intermediate or high risk cancers based on the chance for recurrence. Patients with cancers that have already spread also fell into similarly different subsets. Some have better outcomes while others may have very aggressive cancers that may not warrant treatment.

“We showed for the first time, using an integrated staging system developed at UCLA, that we can identify which patients with localized disease fall into the low, intermediate and high risk subsets and which patients with metastasized cancers are either low, intermediate or high risk patients,” Belldegrun said. “Now we can make treatment decisions based on that.”

If a patient with localized cancer is identified as low risk, his five-year survival rate is expected to be 97 percent, while his 10-year survival rate is 92 percent. An intermediate risk patient with localized disease would have a five-year survival rate of 81 percent and a 10-year survival rate of 61 percent. A high risk patient has a five-year survival rate of 62 percent, with a 10-year survival of 41 percent.

“All of these patients with cancers that have not spread present to their doctors with presumably localized disease and in the past they may have been treated the same way,” Belldegrun said. “They need to be treated individually according to their risk levels.”

The study showed that a patient with low-risk, localized kidney cancer could be treated only with surgery and expect an excellent outcome. Such a move would spare the patient from having to undergo radiation or immunotherapy, which result in harsh side effects. However, for a patient with high-risk, localized kidney cancer, surgery would not be enough. Additional therapy such as targeted treatments or immunotherapy should be considered in order to give the patient the best possible outcome.

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Pathwork Diagnostics, a molecular diagnostics company focused on oncology, will present three studies involving the gene expression based Pathwork(R) Tissue of Origin Test at the Association for Molecular Pathology (AMP) Annual Meeting.

In a poster entitled, “Gene Expression Microarray-Based Diagnostic Test May Identify Primary Tumor Site in Patients with Carcinoma of Unknown Primary (CUP),” Fabiola Medeiros, MD, Assistant Professor of Laboratory Medicine and Pathology at the Mayo Clinic, found that the Pathwork Tissue of Origin Test indicated a probable origin of metastatic CUP in 73 percent of the tumors tested.

CUP cases account for approximately three percent of all malignancies, representing one of the 10 most frequent cancer diagnoses. The CUP samples from the Mayo Clinic consisted of 11 fresh-frozen tumor specimens, whose origin could not be determined after full clinical and imaging workup, including immunohistochemistry. The cases where the tissue of origin was identified have treatment options that show increased survival compared to standard therapies used for the treatment of CUP.

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Researchers at the Indiana University School of Medicine report that the anti-cancer drug Gleevec holds out promise to become the first effective treatment for neurofibromatosis, a genetic disease that has resisted treatments until now.

The research team is conducting clinical tests of the drug following successful laboratory tests and a “compassionate use” of the drug that showed dramatic results in a three-year-old girl at Riley Hospital for Children in Indianapolis.

Neurofibromatosis results from mutations in a gene called NF1, which causes tumors to form in the cells that make up the protective sheaths around nerves. In humans, NF1 mutations resulting in neurofibromatosis occur in one in 3,500 births, equally affecting both sexes and all races and ethnicities. It is the most common genetic disease in humans that results in a predisposition to cancer.

IU researchers have begun a phase 2 clinical test of Gleevec, treating neurofibromatosis patients with plexiform neurofibromas, which affect about 40 percent of people with neurofibromatosis. Such tumors often have a severe impact on patients’ quality of life and can be fatal. They do not respond to chemotherapy drugs and are difficult or impossible to remove surgically.

“We are very hopeful about the potential of this drug and related therapies. There are no other therapies for these tumors. These patients often suffer for years; they sometimes die from these tumors. These are very slow growing tumors that impair people’s everyday lives,” said D. Wade Clapp, M.D., Freida and Albrecht Kipp Professor of Pediatrics at IU School of Medicine.

The researchers report in the Oct. 31 issue of the journal Cell that the mutated nervous system cells, while still in a pre-tumor state, use molecular signals to recruit inflammatory system cells from the bone marrow to the vicinity of the nerve cells. Those inflammatory system cells - called mast cells - then are put to work helping create the cellular “scaffolding” and blood vessels necessary for the cancerous tumors to form.

The tumorigenic cells use a signaling system protein called c-kit to recruit the mast cells, making Gleevec an attractive treatment candidate because it acts on the c-kit molecule, said the researchers, who include Feng-Chun Yang, M.D., Ph.D., assistant professor of pediatrics, David A. Ingram Jr., M.D., associate professor of pediatrics, and Luis F. Parada, Ph.D., professor of developmental biology at the University of Texas Southwestern Medical Center.

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From November the award winning information booklets about cancer produced by Cancerbackup, the cancer information charity, will be available free of charge to all clinicians, for the first time.

Following the merger of Cancerbackup and Macmillan Cancer Support the high-quality, expertly developed information will be available free to health and social care professionals, as well as people affected by cancer.

Macmillan has always issued booklets and information for free, but until now, nurses and information specialists had to pay for the booklets produced by Cancerbackup.

Joyce Butters, a Cancer Information and Support Radiographer at the Velindre Cancer Centre in Cardiff, says;

“It has always been really difficult as they are such great information booklets and, frustratingly, I was not able to give them to patients to take away, as there was no budget to buy them.

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To recognize Cervical Cancer Awareness Week (Oct. 27-31), the Society of Obstetricians and Gynaecologists of Canada (SOGC) is reminding all Canadian women of the importance of taking proactive steps to prevent cervical cancer, such as receiving regular Pap test screening or HPV vaccination.

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A study published in the journal Clinical Cancer Research, a journal of the American Association for Cancer Research, validates a non-invasive screening method with future potential for detection of human papillomavirus (HPV)-positive head and neck cancers.

In the study, researchers at Johns Hopkins University used oral rinses and targeted DNA amplification to track and identify oral HPV infections in patients with HPV16-positive and negative head and neck carcinomas (HNSCC) before and after therapy.

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Researchers studying neurofibromatosis type 1 - a rare disease in which tumors grow within nerves - have found that the tumors are triggered by crosstalk between cells in the nerves and cells in the blood. The researchers, who were funded by the National Institutes of Health (NIH) and the Department of Defense (DOD), also found that a drug on the market for treating certain kinds of blood cancer curbs tumor growth in a mouse model of neurofibromatosis type 1. A clinical trial of the drug is underway in people with the disease.

The results of the study on mice are published in the October 31, 2008 issue of Cell.

The study’s senior investigators were Luis F. Parada, Ph.D., a neuroscientist at the University of Texas Southwestern Medical Center in Dallas, and D. Wade Clapp, M.D., a hematologist at the Indiana University School of Medicine in Indianapolis. Their research was supported by NIH’s National Institute of Neurological Disorders and Stroke (NINDS), NIH’s National Cancer Institute (NCI), and the Neurofibromatosis Research Program of the U.S. Army Medical Research and Material Command.

“By taking a team approach and combining their unique areas of expertise, Drs. Parada and Clapp were able to shed light on a complicated disease mechanism and to develop a potential treatment,” says Jane Fountain, Ph.D., a program director with NINDS.

Neurofibromatosis type 1 is a genetic disease that affects about 1 in 3500 Americans. The nerve-associated tumors, or neurofibromas, that occur in the disease tend to grow just under the skin or at the nerve root. The latter type of tumor, called a plexiform neurofibroma, can cause disabling symptoms by compressing the nerve, the spinal cord, bones, muscles and internal organs.

The tumor forming cells within a neurofibroma may become malignant and spread to other parts of the body. There is currently no treatment to prevent neurofibroma growth.

In 1990, NIH-funded investigators discovered that neurofibromatosis type 1 is caused by loss-of-function mutations in a tumor suppressor gene, now known as NF1. People with the disease have the genetic makeup NF1+/-, meaning they have one functional copy of the gene and one non-functional or mutant copy.

Still, for many years the trigger for neurofibroma growth has been a mystery. Schwann cells, which form a protective sheath around nerve fibers, were a prime suspect. However, neurofibromas also contain nerve fibers themselves, connective tissue and mast cells, the latter of which circulate in the blood and contribute to inflammation.

Combined with previous findings, the new study suggests that the formation of plexiform neurofibromas requires two steps: complete loss of NF1 in Schwann cells (rendering them NF1-/-) and an interaction between NF1-/- Schwann cells and NF1+/- mast cells. While Schwann cells appear to be the primary tumor causing cell, mast cells appear to stimulate tumor growth by recruiting other cell types and blood vessels to the tumor.

“The mast cell inflammatory response appears to be co-opted by the tumor to enhance tumor growth,” says Dr. Parada.

The researchers uncovered the role of mast cells in tumor growth through a series of technically challenging experiments. Previously, Dr. Parada had shown that mice with a targeted deletion of the NF1 gene in their Schwann cells and an NF1+/- genetic background develop plexiform neurofibromas, while mice with the same targeted deletion and an NF1+/+ genetic makeup do not develop the tumors. Drs. Parada and Clapp now show that in these non-tumorigenic mice, it is possible to induce plexiform neurofibromas by transplantation of NF1+/- bone marrow (which contains mast cells and other blood cells).

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National grants totalling more than $6 million dollars have been awarded to the State’s premier medical research facility, the Western Australian Institute for Medical Research (WAIMR), in support of a range of ground-breaking, world-first research projects.

Nine WAIMR scientists have shared 10 research grants from the National Health and Medical Research Council (NHMRC) and Australian Research Council (ARC) announced last week placing the Institute’s success rate well above the rest of the State.

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Mammalian cells with extra chromosomes share some common traits that could be exploited to develop cancer treatments, according to MIT biologists.

Having too many chromosomes, a condition known as aneuploidy, wreaks havoc on an organism, usually resulting in birth defects or death. However, it seems to confer an advantage on tumor cells, which are nearly always aneuploid.

“Now we can look for compounds that specifically kill aneuploid cells, or look for genes that when you knock them down, kill aneuploid cells,” said Angelika Amon, professor of biology and senior author of a paper describing the work in the Oct. 31 issue of Science.

Amon and her colleagues have started screening such compounds and already identified one promising candidate.

In this study - the first to systematically examine the effects of aneuploidy in mammalian cells - the researchers looked at aneuploidy of four different mouse chromosomes (mice have 20 pairs of chromosomes).

They found that in addition to specific detrimental effects of each extra chromosome, aneuploidy seems to provoke a generalized response in all cells.

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UroToday.com - This paper reports the results of a saturation biopsy protocol of 36 cores performed on 48 autopsied prostates from deceased men without any past history of prostate cancer. The first 18 cores were taken in the mid peripheral zone (6 cores), the lateral peripheral zone (6 cores) and the central zone (6 cores). An additional set of 18 cores were taken in the same locations, bringing the total number of cores to 36. Autopsied glands were then step-sectioned and analysed. We considered as “insignificant cancers” organ confined cancers with an index tumor volume <0.5 cm3 and Gleason score 6 or less.

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