The sequencing of the human genome has opened the door for proteomics by providing a sequence-based framework for mining proteomes. As a result, there is intense interest in applying proteomics to foster a better understanding of cancer processes, develop new biomarkers for diagnosis and early detection of cancer. Gastric carcinoma is one of the most common malignancies worldwide and is the most common cause of cancer-related death in China. The main barrier for improving survival rate is short of useful marker for early diagnosis.

A research article to be published on October 7, 2008 in the World Journal of Gastroenterology addresses this question. The research team led by Professor Liu from Ruijin Hospital of China isolated and identified differentially expressed proteins between cancer and normal tissues of gastric cancer by 2-DE and MALDI-TOF-MS.

Total proteins were isolated from tumor and normal tissues and then separated by 2-DE. Differentially expressed proteins were isolated and identified by MALDI-TOF or MALDI-TOF-TOF-MS. Twenty three differentially expressed proteins were found between tumor and normal tissues of gastric cancer, among these fifteen proteins were identified. These differential proteins will be candidate markers for gastric cancer. It may be useful for diagnosis, treatment target and prognosis.

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Scientists at Sunnybrook Research Institute (SRI) are developing and commercializing a promising novel therapy for the treatment of prostate cancer that may offer patients a faster and more precise treatment than existing clinical alternatives, with fewer side effects.

The new treatment–magnetic resonance imaging (MRI)-guided transurethral ultrasound–uses heat from focused ultrasound to treat cancer in the prostate gland precisely while sparing the delicate noncancerous tissues around the prostate essential for healthy urinary, bowel and sexual function.

Sunnybrook researchers Dr. Michael Bronskill and Dr. Rajiv Chopra have licensed their innovation and formed Profound Medical Inc., which will develop the technology for clinical use.

Unlike surgical removal of the prostate, the treatment is minimally invasive and could be performed without a lengthy hospital stay. In preclinical studies, treatment takes less than 30 minutes. The therapy, on which clinicians at Sunnybrook will conduct preliminary testing in preparation for a clinical trial, could help limit the number of men living with the common, debilitating and often permanent side effects of surgery and radiation treatments currently used. More of these invasive therapies are being performed now because improved awareness among younger men has converged with better clinical detection tools.

Profound’s clinical development is targeted at treatment that reduces the high level of incontinence and impotence associated with current, invasive treatments. The therapy involves two different and naturally incompatible technologies, ultrasound and MRI, which Bronskill and Chopra spent 10 years making compatible. “You have to make an ultrasound heating applicator work inside a magnetic resonance imager, without the two technologies interfering with each other,” says Bronskill, who is a professor at the University of Toronto. “The prostate cancer site is a natural for this technology because it’s surrounded by structures you want to spare.” Dr. Laurence Klotz, chief of urology at Sunnybrook Health Sciences Centre, and a professor at the University of Toronto, says that a noninvasive therapy for early, localized prostate cancer could improve the quality of life of hundreds of thousands of men. “The key to effective noninvasive treatment is accurate imaging of the target organ and of the effects of the treatment on tissue. In that respect, MR-guided ultrasound has many potential advantages over transrectal ultrasound-guided focused ultrasound, now approved for use in Canada,” says Klotz.

The scientists’ creation of this clinically viable product was done in a setting committed to commercialization. “At SRI, we are dedicated not only to developing new and better therapies and technologies, but also to getting those discoveries to our patients,” says Dr. Michael Julius, vice-president of research at Sunnybrook. Profound Medical Inc. is the third imaging-technology company to be spun out of research at SRI in recent years. The other two are VisualSonics Inc. and Sentinelle Medical Inc.

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Starving the body of food for a couple of days could help in the fight against cancer, according to new research.

Scientists have discovered that a 48-hour fast seems to protect the body’s healthy cells against the toxic effects of chemotherapy drugs.

The breakthrough could provide a solution to a problem that has confounded cancer experts for years – how to target chemotherapy so it destroys cancer cells but leaves healthy ones intact.

It seems depriving healthy cells of the food they need for fuel sends them into a kind of survival mode, where they become highly resistant to stress or damage.

Experts describe this behaviour as similar to animals waiting out winter food shortages by hibernating.

But cancer cells do not react in the same way. Instead, they carry on growing and remain just as susceptible to the effects of chemotherapy as they do when the body has a full supply of food.

The result could be that doctors can cure more cancers by using higher doses of chemotherapy drugs to shrink or destroy tumours.

Cancer affects one in three people in the UK at some point in their lives.

Many end up needing a course of chemotherapy to try to control the spread of the disease.

Treatment may involve drugs which block the effects of certain hormones or affect the immune system, but the main group of drugs that are used are called cytotoxics, which mean they poison cells to stop them reproducing.

There are more than 100 different cytotoxic drugs in use for cancer, but none is capable of telling the difference between normal cells and cancer cells.

Although healthy cells usually recover from the toxic effects of the drugs, they need some time to recuperate.

This means treatment is often given in short bursts, with several weeks’ break in between to allow normal cells a chance to recover. But many patients still end up suffering unpleasant side-effects such as hair loss, nausea and extreme tiredness.

If doctors could find a way of protecting healthy cells, they could give patients shorter but more intense bouts of treatment, with far fewer adverse effects.

For nearly 50 years, there has been evidence that fasting – or limiting calorie intake – can slow the ageing process by switching on some kind of internal protection mechanism in the body.

There is even a Calorie Restriction Society, a U.S-based organisation whose members deliberately limit food intake in an attempt to live longer.

The latest findings, published in the Proceedings of the National Academy of Sciences, suggest that depriving the body of calories in this way could also transform cancer care.

For the study, mice with cancer were starved for two days before being given a high dose of chemotherapy.

Tumour cells were destroyed by the drugs, but the healthy cells survived the treatment intact.

In a separate group of mice that ate normally, the treatment killed more than half of them and caused severe weight and energy loss in the survivors.

Laboratory tests suggested fasting had a similarly beneficial effect on human cells. But UK cancer experts have warned patients not to starve themselves until there is more evidence that it works and is safe.

Cancer Research UK science information officer Henry Scowcroft said: “This is an interesting result based on solid science and may open up new avenues to improve cancer treatment.

“But it doesn’t really fit with what we know about chemotherapy, which is that if you are healthy, well-fed and you get enough nutrients you tend to cope with it better.

“Until these findings are confirmed in human trials, we strongly advise people undergoing cancer treatment to eat a healthy, balanced diet.”

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No simple blood test exists to determine which of the millions of people infected with hepatitis C virus will develop cirrhosis of the liver or cancer. Now, researchers are developing new technology to find blood proteins that herald the earliest signs of chronic liver disease. If successful, they hope to extend the use of the technology, and to do the same for many other diseases and to make it commercially available for broad clinical use.

Washington State’s Life Sciences Discovery Fund Board of Trustees has announced that the collaboration between scientists at the Department of Energy’s Pacific Northwest National Laboratory and the University of Washington Liver Transplantation Program in Seattle will receive $4.8 million over the next three years to develop a new proteomics technology and apply it in search of biomarkers for liver disease.

“This is really fantastic,” says grant recipient and lead investigator Dick Smith of PNNL. “This funding will support work that is almost impossible to get funded by conventional sources. The grant brings together a larger program that could have significant positive impacts on the health of people, certainly in Washington, but in the whole country as well.”

The announcement caps a lengthy selection process by LSDF. “This has been a highly-competitive process. The proposals were weighed on their scientific merits and their abilities to utilize this funding to provide statewide economic returns, to build a competitive life sciences industry and to advance the health of, and health care for, our citizens. These newly-awarded grants will leverage substantial additional investment in Washington State by a variety of other funders such as federal agencies and philanthropic organizations,” says LSDF Executive Director Lee Huntsman.

About 1.6 percent of the U.S. population has signs indicating they have been or are infected with hepatitis C virus, and up to 12,000 people each year die from HCV-induced liver damage and cancer. A percentage of infected people develop various levels of liver disease — the worst requiring liver transplants — but doctors have no way of telling who’s most at risk.

PNNL’s Smith is leading development of the new technology at DOE’s Environmental Molecular Sciences Laboratory on the PNNL campus. In collaboration with UW’s Michael Katze, Smith’s group with use proteomics to compare blood and tissue samples from individuals who have advanced liver disease or are healthy to find proteins that indicate the potential for advanced illness.

The researchers’ long term goal is to make such technology efficient and inexpensive enough for use in clinical settings. In addition, Smith’s development plans include making the technology widely applicable to biomarker searches for other diseases.

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As our population ages and senior citizens become a larger demographic, cancer researchers are focusing on the links between aging and cancer. Studies presented at the 2008 Annual Meeting of the American Association for Cancer Research, April 12 – 16, highlight the biological aspects of aging that are key to greater risk and poorer prognosis, and surgical outcomes.

Surgical resection and survival in octogenarians and younger age cohorts of patients diagnosed with non-small cell lung cancer:

Although fewer of them undergo surgery, lung cancer patients in their 80s fare equally well following surgery as their younger counterparts, researchers report. The findings offer doctors potentially valuable guidance in treatment options for elderly patients, according to researchers.

A research team from the Hoag Cancer Center in Newport Beach, California, observed 1,293 patients with lung cancer, 482 of whom underwent surgical treatment. The oldest patients were more likely to be male. Older patients were also more likely to have localized disease.

Overall, the rate of surgery did not differ by age group. However, when primary lung cancer was considered separately, only 31.7 percent of patients older than 80 underwent surgery for their primary lung cancer compared with 38.5 percent of patients younger than 80. For patients with non-small cell lung cancer, the rate of surgery was 64 percent for those older than 80 and 83 percent for those younger than 80. For patients with regionally advanced disease, the rate of surgery for patients age 80 or older was 35 percent compared with 49 percent for those younger than 80 years old.

The five-year survival rate following surgery was 62 percent for those patients older than 80 compared with 53 percent for those aged 70 to 79 years. Among patients age 60 to 69 years and 50 to 59 years, the survival rate was 63 percent. For the youngest patients, those younger than 50, the survival rate was 79 percent.

“Although a smaller proportion of patients over the age of 80 underwent this type of surgery, their survival rate was comparable to the younger age groups,” said lead author Robert O. Dillman, M.D., medical director of the Hoag Cancer Center in Newport Beach, California.

Elevated interleukin-12 is a plasma marker of poor prognosis in stage III melanoma patients:

New research has established that elevated blood levels of interleukin-12, which rise as we age, independently predicts poor prognosis in patients with melanoma.

Interleukin-12 is a biological therapeutic agent that has been shown to act on the immune system and increase the body’s ability to fight disease. It has also previously been shown to interfere with blood flow to the tumors

However, the current study suggests that elevated interleukin-12 may play a role in poor prognosis for melanoma.

“This marker tends to increase with age, which could explain the link between age and poorer prognosis of this type of skin cancer,” said lead author Yun S. Chun, M.D., a surgical oncology fellow at the University of Texas M. D. Anderson Cancer Center.

Researchers measured blood levels of interleukin-12 in 658 patients. Of these patients, 445 had early stage disease, 150 had mid-stage disease and 63 had late stage disease.

As they predicted, Chun and colleagues found that blood levels of interleukin-12 rose with age. Among patients younger than 40, the average level of interleukin-12 was 75 pg/ml, those aged 40 to 59 had a average level of 84 pg/ml, those from 60 to 79 years had a level of 96 pg/ml and patients older than 80 had an average level of 112 pg/ml.

When researchers estimated risk factors for mortality among patients with melanoma, older age by itself did not predict risk. However, late stage disease and an elevated level of interleukin-12 did predict mortality. Specifically, for patients with late stage disease and an interleukin-12 level above 150 pg/ml, the risk of mortality was four times higher than that for patients with levels of interleukin-12 that were below 150 pg/ml.

“Among patients with melanoma, it is possible that elevated interleukin-12 may be a marker of a tumor promoting, rather than a tumor inhibiting, response,” Chun said.

Aging and DNA methylation in Alu and LINE-1 repeated elements:

An age-related decrease in DNA methylation, the process whereby genes are shut off and chromosomes packed up in complex strictures, could potentially lead to cancer development, according to researchers.

When a person does not have a proper rate of DNA methylation, chromosomes and DNA sequences become unstable, and therefore are more likely to contribute to cancer.

Approximately 55 percent of the human genome consists of repetitive elements, including approximately 500,000 long interspersed nucleotide elements (LINE) and 1.5 million repetitive elements of the Alu DNA sequences. Typically, these sequences undergo heavy methylation.

Previous human studies have linked a lack of methylation among LINE and Alu repetitive elements with disease. However, whether the unsteadiness of these elements is unrestrained with age had not yet been established.

For the current study, researchers from the Center of Molecular and Genetic Epidemiology at the University of Milan in Italy, in collaboration with investigators at the Harvard School of Public Health, Boston, MAmeasured DNA levels in 693 patients. Patients gave up to three blood samples, taken approximately three years apart from each other.

Overall, the older a patient grew, the less likely these elements were to methylate. Specifically, researchers found a 0.016 percent decrease for LINE-1 elements and a 0.015 percent decrease for Alu repetitive elements for each year of increased age.

“Such age-related decrease in methylation may increase the risk of mutational events potentially leading to cancer,” said lead author Laura Cantone, a researcher at the University of Milan.

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A connection between vitamin D level and the risk of developing breast cancer has been implicated for a long time, but its clinical relevance had not yet been proven.

The result of the study involving 1,394 breast cancer patients and an equal number of healthy women after menopause was surprisingly clear: Women with a very low blood level of 25(OH)D have a considerably increased breast cancer risk. The effect was found to be strongest in women who were not taking hormones for relief of menopausal symptoms.

However, the authors note that, in this retrospective study, diagnosis-related factors such as chemotherapy or lack of sunlight after prolonged hospital stays might have contributed to low vitamin levels of breast cancer patients.

In addition, the investigators focused on the vitamin D receptor. The gene of this receptor is found in several variants known as polymorphisms. The research team of the DKFZ and Eppendorf Hospitals investigated the effect of four of these polymorphisms on the risk of developing breast cancer.

They found out that carriers of the Taql polymorphism have a slightly increased risk of breast tumors that carry receptors for the female sex hormone estrogen on their surface. No effects on the overall breast cancer risk were found. A possible explanation offered by the authors is that vitamin D can exert its cancer-preventing effect by counteracting the growth-promoting effect of estrogens.

Besides its cancer-preventing influence with effects on cell growth, cell differentiation and programmed cell death (apoptosis), vitamin D regulates, above all, the calcium metabolism in our body.

Foods that are particularly rich in vitamin D include fish (cod liver oil), eggs and dairy products. However, the largest portion of vitamin D is produced by our own body with the aid of sunlight.

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A revolutionary cancer treatment using microscopic magnets to enable ‘armed’ human cells to target tumours has been developed by researchers funded by the Biotechnology and Biological Sciences Research Council (BBSRC). Research published online today in the journal, Gene Therapy, shows that inserting these nanomagnets into cells carrying genes to fight tumours, results in many more cells successfully reaching and invading malignant tumours.
Using human cells as delivery vehicles for anti-cancer gene therapy has long been an attractive approach for treating tumours, but these cells usually reach tumours in insufficient numbers to effectively attack them. Now, a new ‘magnetic targeting’ method has been developed to overcome this problem by Professor Claire Lewis at the University of Sheffield, Professor Jon Dobson at the University of Keele, and Professor Helen Byrne and Dr. Giles Richardson at the University of Nottingham.

The technique involves inserting nanomagnets into monocytes – a type of white blood cell used to carry gene therapy – and injecting the cells into the bloodstream. The researchers then placed a small magnet over the tumour to create a magnetic field and found that this attracted many more monocytes into the tumour.

The head of the laboratory in which the work was done, Professor Lewis, explains: “The use of nanoparticles to enhance the uptake of therapeutically armed cells by tumours could herald a new era in gene therapy – one in which delivery of the gene therapy vector to the diseased site is much more effective. This new technique could also be used to help deliver therapeutic genes in other diseases like arthritic joints or ischemic heart tissue.”

Professor Jon Dobson from the University of Keele, said: “Though the concept of magnetic targeting for drug and gene delivery has been around for decades, major technical hurdles have prevented its translation into a clinical therapy. By harnessing and enhancing the monocytes’ innate targeting abilities, this technique offers great potential to overcome some of these barriers and bring the technology closer to the clinic.”

Professor Nigel Brown, BBSRC Director of Science and Technology, said: “This exciting work could have huge implications in healthcare. Fundamental bioscience research may sometimes seem to have little relevance to everyday life, but understanding the basic workings of the human body and harnessing nanoscale technology has resulted in a process of great potential in tumour therapy.”

The team are now looking at how effective magnetic targeting is at delivering a variety of different cancer-fighting genes, including ones which could stop the spread of tumours to other parts of the body.

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If lung cancer and heart disease aren’t bad enough, cigarette smokers are also at higher risk for developing, among other things, pancreatic cancer. Now, researchers at the Kimmel Cancer Center at Jefferson in Philadelphia have preliminary evidence indicating one possible reason why. Data being presented April 13, 2008 during the Annual Meeting of the American Association for Cancer Research shows that they have found that nicotine in cigarettes increases the production of a protein that is known to promote cancer cell survival, invasion and spread.

According to Hwyda Arafat, M.D., Ph.D., associate professor of Surgery at Jefferson Medical College of Thomas Jefferson University, the protein, osteopontin, is found in a variety of fluids in the body, such as plasma, cerebrospinal fluid, synovial fluid and breast milk. Osteopontin is also present in different organs and plays an important role during embryonic development. Recent studies have demonstrated that osteopontin levels are significantly higher in the blood and pancreas tissue of pancreatic cancer patients. The protein, when over-produced, can make cancer cells more likely to become metastatic.

Dr. Arafat wanted to see if osteopontin might play a role in the cigarette smoking-pancreatic cancer connection. In collaboration with groups at the University of Nebraska and Rutgers University, Dr. Arafat and her co-workers looked at rats exposed to cigarette smoke and measured the amount of osteopontin in the rat pancreas and blood. They found that the more cigarette smoke to which the rats were exposed, the greater the amount of nicotine in the blood and osteopontin in the pancreas.

The researchers also looked at osteopontin expression in pancreatic cancer cell lines exposed to nicotine, finding that osteopontin expression went up when the cells were exposed to more nicotine. “We found that dose-dependently, nicotine increased osteopontin expression not only through transcriptional but also translational (protein secretion) levels in pancreatic cancer cells,” Dr. Arafat explains. Pancreas tissue samples from pancreatic cancer patients also showed higher than normal levels of the protein.

Dr. Arafat believes that osteopontin could be a drug target. “We are now proposing that perhaps blocking osteopontin can interfere with the progression of pancreatic cancer and other cancers,” she says, adding that her team would like to understand more about osteopontin’s effects on pancreatic cancer cell behavior. Dr. Arafat’s group now is comparing differences in osteopontin expression between smokers and non-smokers.

“For example, if you put the cells with nicotine and block osteopontin, will the cells still be migratory? Is it osteopontin or something else in combination that is at work here?”

Pancreatic cancer, the fourth-leading cause of cancer death in this country, takes some 34,000 lives a year. The disease is difficult to treat; it frequently is detected after it has spread. Only 4 percent of individuals with pancreatic cancer live for five years after diagnosis, and about 25 percent of those who undergo successful surgical removal of their disease live at least that long.

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Triple-negative breast cancers are a heterogeneous group and may not always be associated with lymph node spread, a new study shows.

The study of 145 triple negative breast cancers (i.e, cancer which is estrogen receptor-negative, progesterone receptor-negative and HER2-negative) in 128 women found that about 23% were moderate or low-grade lesions, said Cecilia Mercado, MD, of New York University School of Medicine, and an author of the study.

Triple negative breast cancer is found in about 15% of breast cancer patients and the patients are usually younger.

The study found that 11 of the 145 cancers had a low histologic grade. Only one of these patients had evidence that their cancer had spread into their lymph nodes. Twenty-three cancers were moderate grade lesions; only five of these 23 had spread into the lymph nodes. That compares to 37 of 111 cancers with a high histologic grade which had lymph node metastases, Dr. Mercado said.

“Our preliminary results show that triple negative breast cancers are a heterogeneous group. Although many are high grade lesions, some are moderate or low grade demonstrating a lower rate of lymph node metastasis,” Dr. Mercado said.

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A breast cancer patient’s age alone should not determine whether or not she receives standard breast-conservation treatments, including a lumpectomy and radiation therapy; however, if additional health problems (comorbidities) are present, treatments should be individualized based on age and the type of comorbidities, according to a study in the April 1 edition of the International Journal for Radiation Oncology Biology Physics, the official journal of the American Society for Therapeutic Radiology and Oncology.

The occurrence of breast cancer in women increases as women age. According to the National Cancer Institute’s SEER Cancer Statistics Review, women between the ages of 75 and 79 have the highest incidence of breast cancer diagnoses at 497 cases per 100,000 people. Along with cancer, most women in this age group are dealing with additional health problems. According to a 1999 women’s health and aging study in the Journal of Clinical Epidemiology, the majority of older patients diagnosed with cancer have at least one other medical condition and more than half of patients with cancer over the age of 65 have three or more associated medical conditions.

This study, conducted by the departments of Radiation Oncology, Biostatistics and Epidemiology, and Medicine, Division of Geriatrics, at the University of Pennsylvania School Of Medicine in Philadelphia, sought to determine the impact of these additional medical problems on breast cancer patients who receive the same standard treatments as patients with no additional medical problems and if old age is a reason to deny some standard treatments.

Most randomized trials that compare outcomes of breast-conserving surgery with and without radiation consistently show more positive outcomes when radiation is used; however, most of the trials exclude women older than 70 years old so there is not a lot of data on the impact of radiation on older women.

Between 1979 and 2002, 238 women, 70 years old and older, with Stage I or II invasive carcinoma of the breast received breast-conservation therapy and their outcomes were compared by age groups and comorbidities. Most of the patients studied had mild comorbidities.

The researchers found that the number of deaths from breast cancer among the patients studied was similar to the number seen among all age groups of patients without additional medical problems. The researchers also found that the majority of elderly women with early-stage breast cancers and mild comorbidities actually benefited from the use of radiation and had minimal side effects.

The overall survival rates for the patients in the five- and 10-year follow-up periods were 80 percent and 50 percent, respectively; however, more deaths during the 10-year period were caused by intercurrent diseases than breast cancer.

“Doctors need to understand that comorbidities should be the determining factor in deciding an older patient’s course of treatment, not age,” said Eleanor Harris, M.D., clinical director of radiation oncology at the Moffitt Cancer Center in Tampa, Fla. “There is a sense in the field that elderly women need less treatment than younger women, but we should not be under treating women simply because they have passed the age of 70.”

ASTRO is the largest radiation oncology society in the world, with 9,000 members who specialize in treating patients with radiation therapies. As the leading organization in radiation oncology, biology and physics, the Society is dedicated to improving patient care through education, clinical practice, advancement of science and advocacy.

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