Coffee drinking improves hepatitis C treatment response, study suggests

ScienceDaily (June 8, 2011) — Advanced hepatitis C patients with chronic liver disease may benefit from drinking coffee during treatment, according to a new study in Gastroenterology, the official journal of the American Gastroenterological Association (AGA) Institute. Patients who received peginterferon plus ribavirin treatment and who drank three or more cups of coffee per day were two times more likely to respond to treatment than non-drinkers.

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"Coffee intake has been associated with a lower level of liver enzymes, reduced progression of chronic liver disease and reduced incidence of liver cancer," said Neal Freedman, PhD, MPH, of the National Cancer Institute and lead author of this study. "Although we observed an independent association between coffee intake and virologic response to treatment, this association needs replication in other studies."

Among non-drinkers, 46 percent had an early virologic response; 26 percent had no detectable serum hepatitis C virus (HCV) ribonucleic acid at week 20; 22 percent had no detectable serum at week 48; and 11 percent had a sustained virologic response. In contrast, the corresponding proportions for those who drank three or more cups of coffee per day were 73 percent, 52 percent, 49 percent and 26 percent, respectively.

Approximately 70 to 80 percent of individuals exposed to HCV become chronically infected. Worldwide, these individuals are estimated to number between 130 and 170 million. Higher coffee consumption has been associated with slower progression of pre-existing liver disease and lower risk of liver cancer. However, the relationship with response to anti-HCV treatment had not been previously evaluated. Treatment with peginterferon and ribavirin resolves chronic hepatitis C in about half of patients. It is unknown whether coffee will improve response with the addition of new drugs that were recently approved for use in the U.S.

Because patients in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis Trial also had previously failed interferon therapy, it is not clear whether the results can be generalized to other patient populations. Future studies among patients with less advanced disease, those who are treatment-naïve to prior therapy, or who are being treated with newer antiviral agents are needed.

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Breast cancer research: Mammary gland development of blueberry-fed lab animals studied

ScienceDaily (June 7, 2011) — U.S. Department of Agriculture (USDA)-funded studies of mammary gland development in laboratory rats fed blueberries or other foods of interest may aid breast cancer research.

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In an early study that has paved the way to follow-up experiments, Rosalia C. M. Simmen of the Arkansas Children's Nutrition Center (ACNC) in Little Rock, Ark., has determined that several indicators of rat mammary gland health were improved in the offspring (pups) of mothers (dams) that had been fed 5 percent blueberry powder in their rations during pregnancy and during the weeks that they nursed their pups.

The powder comprised 5 percent of the total weight of the feed, according to Simmen, a senior investigator at the center and a professor at the University of Arkansas for Medical Sciences in Little Rock.

The ACNC is a partnership between the USDA's Agricultural Research Service (ARS), Arkansas Children's Hospital in Little Rock, and the university.

The effects noted in the blueberry study have not been shown in humans and have not yet been traced to a particular blueberry compound, Simmen noted.

Her team evaluated several structural indicators of normal mammary gland development in the lab animals, including branching of the gland. There was significantly more branching in the offspring of the group that consumed the diet containing 5 percent blueberry powder than in offspring of dams fed rations containing 2.5 percent or 10 percent blueberry powder, Simmen reported.

Branching occurs when cells specialize or differentiate. Differentiation is generally preferable to rapid proliferation of undifferentiated cells, which can be a risk factor for breast cancer.

In their analysis of several biochemical indicators, the team found, for instance, that the level of the tumor-suppressing protein PTEN (phosphatase and tensin homolog deleted in chromosome 10) was significantly higher in mammary tissues of offspring of dams on the 5 percent regimen. That's a plus, because PTEN is thought to help protect against cancer.

Lab animal studies of blueberries' potential role in preventing breast cancer date to 2006. But Simmen's investigation, published in Nutrition Research in 2009, provided the first evidence from a lab animal study of the early influence that the mother's blueberry consumption can have on normal, healthy development of the mammary gland in her offspring.

Simmen collaborated in the research with ACNC colleague Xianli Wu; former ACNC research chemist Ronald L. Prior, now retired; and Ph.D. student Omar Rahal.

Read more about these experiments in the May/June 2011 issue of Agricultural Research magazine at: http://www.ars.usda.gov/is/AR/2011/may11/fruit0511.htm

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Drug shows promise in prostate cancer spread to bone

ScienceDaily (June 8, 2011) — A new drug to treat prostate cancer shows early promise, particularly against tumors that have spread to the bone, a multi-site study shows.

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The drug Cabozantinib is designed to target mainly two important pathways linked to the growth and spread of prostate cancer. The drug had the most effect on tumors that had spread to the bone.

"Not only did three-quarters of bone scans have partial or complete resolution, but this was accompanied by improvement in bone pain and decreased need for narcotic use," says lead study author Maha Hussain, M.D., FACP, professor of internal medicine and urology and associate director of clinical research at the University of Michigan Comprehensive Cancer Center.

Hussain presented the findings at the American Society of Clinical Oncology annual meeting.

The trial enrolled 171 men with metastatic prostate cancer. In more than three-quarters of the men enrolled, cancer had spread to the bone.

Researchers found 76 percent of patients saw some or all of their tumor shrink on bone scans following treatment with Cabozantinib. In addition, among patients who were on narcotics due to bone pain, 67 percent reported less pain and 56 percent either stopped taking narcotics or reduced the dosage. In addition, more than two-thirds of patients had some tumor regressions in areas of spread outside the bone. The treatment effects lasted on average 29 weeks.

The study found moderate side effects from Cabozantinib, including fatigue, gastrointestinal symptoms and high blood pressure.

"What's interesting about this drug is it brings to the table something we haven't seen before. Dramatic improvements in bone scans are unprecedented in this disease. Despite measurable progress, current treatment options for advanced prostate cancer tend to be modest in effect, so adding to and improving these options is a high priority," Hussain says.

Hussain cautions that this is very early data, but it opens a new door for further investigation. The manufacturer, Exelixis, has developed a randomized clinical trial that is currently open at the U-M Comprehensive Cancer Center and other locations. For information, call the U-M Cancer AnswerLine at 800-865-1125.

U-M researchers are also planning a clinical trial with this drug in patients with metastatic prostate cancer who have had no previous chemotherapy. Laboratory research at the University of Michigan will look to better understand Cabozantinib's effects on the bone. Cabozantinib is not approved by the U.S. Food and Drug Administration.

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Bone cancer, from the lab to the clinic

ScienceDaily (June 9, 2011) — A new study into osteosarcoma -- cancer of the bone -- will use advances in genomic research and analysis to identify new genes that give rise to the condition and to create personalised blood tests for children and young adults with the condition. The study is funded by Skeletal Action Cancer Trust, SCAT.

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It is hoped that the results of this new study will help doctors improve treatment of this difficult disease through better diagnosis and monitoring of this bone cancer.

Each year approximately 80 children and young adults develop osteosarcoma in the UK. This painful cancer of the bone tends to affect children and young adults and is normally treated using chemotherapy and surgery. The causes of the disease are not well known and measuring response to treatment relies on scanning and imaging. The new study seeks to bring both greater understanding to processes of developing the condition and create improved methods of measuring disease regression.

"We hope that this research project will improve the way patients with cancer are monitored and will guide the best drug treatment for the cancer in each patient," says Professor Adrienne Flanagan from the UCL Cancer Institute, and Medical Director of the Royal National Orthopaedic Hospital (RNOH), "It is really important that we exploit new tools that emerge from cutting-edge research to see how they can benefit patients with bone tumours in the future."

"We need the support of patients and of the wider public to make our aim of moving towards delivery of personalised cancer treatment a reality."

Professor Flanagan, consultant pathologist at the RNOH and scientist at UCL Cancer Institute, worked with colleagues from the Wellcome Trust Sanger Institute, in which they discovered a novel cancer-causing mutation in chondrosarcoma, the second most common cancer of bone. The results of this study were published recently online in the The Journal of Pathology.

In this new programme, scientists will use recently developed methods to hunt for changes in the genomes of cancer patients, trying to pinpoint genes underlying in the disease. At the same time, they will develop new tools to monitor the disease in patients through the course of treatment. They hope that their methods, which look for tumour-specific DNA in the bloodstream of patients, will become routine for patients in the future.

"Currently, the response of patients with osteosarcomas to treatment is monitored by scanning tumours using imaging techniques," says Dr Peter Campbell. "In contrast, blood cancers have long been monitored using simple tests that pick up recurring mutations in tumour cells in the blood and show how a patient is responding to treatment. The new project aims to see if we could develop and apply similar methods to osteosarcomas."

The patients are being treated at the RNOH and University College London Hospital (London Sarcoma Service), and the research project is largely funded by SCAT Bone Cancer Trust based at the RNOH, with contributions from other charities including the Bone Cancer Research Trust, Rosetrees and others. The research is being carried out in collaboration with UCL Cancer Institute and the Wellcome Trust Sanger Institute.

The team will sequence the complete genome of 50 patients with osteosarcoma and will look in their plasma in many of these patients before and after chemotherapy treatment to find rearrangements -- shuffled chunks of DNA -- in the small amounts of DNA that have leaked out from the osteosarcoma into the bloodstream. They will be searching for rearrangements that are specific to each patient.

By developing a picture of the unique profile of mutations of each patient's cancer and then using these mutations to monitor the amount of cancer derived DNA circulating in the blood, the clinicians hope they can deliver treatments to patients in a personalised way.

In addition to seeking improvements in treatment, the researchers are looking for novel genes giving rise to osteosarcoma. The team will sequence in full the gene-containing regions of the genome in 100 osteosarcoma samples.

"The future of cancer genetics lies ultimately in drawing a complete picture of each and every mutation for each and every cancer patient who visits a hospital," says Professor Mike Stratton, Director of the Wellcome Trust Sanger Institute and one of the project leaders. "But there are a number of steps on the way. By concentrating in this study on the so called 'active' areas in the genome we can begin to pick out mutations that might be driving cancer even as we embark on the journey towards comprehensive catalogues of mutations for this, and a whole range of other human cancers."

Ultimately, the team on the osteosarcoma study will generate complete genome sequences for the whole genomes of osteosarcomas -- allowing them to look in even finer detail at the spectrum of mutations in the cancer and distinguish the cancer causing mutations from the innocent bystanders.

"The research is promising, but its success relies on continued support from the public," says Mr Steve Cannon, bone tumour surgeon at the RNOH and Chairman of SCAT, the Bone Cancer Trust. "It is great that we have been able to get this project up and running, but donations will continue to be necessary if we are to succeed in the fight against osteosarcoma and other bone cancers. In what is without doubt an exciting and important moment in the application of genetic science in cancer research, it is only right that we should be looking to apply the cutting edge tools that are now available to bone cancer."

"Osteosarcoma is an aggressive cancer; we need an aggressive approach to tackle its effects."

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Scale helps to measure the utility of genetic counseling in tackling fear of cancer

ScienceDaily (June 8, 2011) — When a person has a family history of cancer, their worry about developing the disease may lead to them refusing to have preventive tests. Advice from genetic counselling units reduces their anxiety but, until now, nobody knew how much. Now, a scientific team has validated the 'Escala de Preocupación por el Cáncer -- EPC' (equivalent of the Cancer Worry Scale), the first of its kind in the Spanish language, in order to evaluate it.

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"Excessive concern about cancer can result in two kinds of behaviour. Some people undergo excessive and unnecessary diagnostic tests, while others do not want to take any, out of fear that they will discover they have cancer," says Esther Cabrera, lead author of the study and director of the School of Health Sciences at the Mataró-Maresme Technocampus (Barcelona).

Genetic counselling, in the case of patients with a family history of the disease, is the right kind of tool for reducing these worries. However, until now there has been no tool in the Spanish language for evaluating the effectiveness of this initiative, nor any instrument to evaluate the fear of suffering from cancer.

"I could say that genetic counselling works well, but I couldn't measure this," says Ignacio Blanco, another author of the study and director of the Genetic Counselling Unit at the Catalan Institute of Oncology (ICO) in Barcelona. Now he has access to the 'Escala de Preocupación por el Cáncer' (EPC), an equivalent of the Cancer Worry Scale that shows him "that the degree of patients' concern does not increase following this counselling -- quite the contrary," he adds.

The study, published in Medicina Clínica, shows that the EPC is a valid and reliable scale for evaluating concern about cancer in healthy people. It is a translation and a cultural adaptation of the English-language Cancer Worry Scale: six questions that measure concern on a scale ranging from 6 (the least) to 24 (the highest level).

From psychology to general medicine

The research study was carried out on 212 healthy women without any family history of breast cancer who attended the ICO Genetic Counselling Unit. Before the experts studied their family trees, the patients answered the test questions. Several days after the genetic counselling, the researchers once again distributed the scales to analyse the effectiveness of this tool.

One of the advantages of this tool is that it can be used in any of the branches of medicine that a patient seeks help from -- psychology, oncology or even general medicine. "The scale can be used in primary healthcare as a filtering instrument among the healthy population to identify individuals with high levels of concern about cancer," the researchers say.

The simplicity of the questions (for example, "How worried are you about the possibility of developing cancer one day?") and the answers ("Not at all worried/A bit worried/ Quite worried/Very worried") make it possible to easily objectify "something that is difficult to measure," explains Esther Cabrera.

The tool has shown itself to be effective in alerting healthcare professionals to certain healthy patients who are unwilling to undergo preventive testing. "On many occasions, their fears are related to their decision about whether or not to take preventive measures that would help them avoid cancer or diagnose it a very early stage," Cabrera points out.

The researchers add that the tool will be useful for comparing and understanding the factors that affect the degree to which different groups of people worry. This would also make it possible to customise educational initiatives to improve people's quality of life.

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The cellular root of colorectal cancers?

ScienceDaily (June 10, 2011) — Researchers at Children's Hospital Boston have found a marker called ABCB5 that both tags a small proportion of cells within colorectal cancers and fuels resistance in those cells to standard treatments. The results indicate that eliminating ABCB5-expressing cells is crucial for successful colorectal cancer treatment, while adding to the growing body of evidence for a theory of cancer growth called the cancer stem cell hypothesis.

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An international team led by Brian J. Wilson, PhD, Tobias Schatton, PhD, and Markus Frank, MD, of the Transplantation Research Center at Children's Hospital Boston, and Natasha Frank, MD, of the VA Boston Healthcare System and Brigham and Women's Hospital, and colleagues at the University of Wurzburg in Germany reported the findings online in the journal Cancer Research on June 7, 2011.

An estimated 141,000 Americans will be diagnosed with colorectal cancer this year. While its mortality has been dropping over the last two decades thanks to screening and improved treatment options, colorectal cancer is still the second leading cause of cancer-related death in the United States.

Recognizing ABCB5's role as a marker of tumor recurrence in melanoma and liver cancer, and knowing from previous studies that the gene for ABCB5 is also active in colorectal cancer, the Franks' team studied the protein's expression in both normal and cancerous colorectal tissue specimens. They found that ABCB5 is found only rarely in healthy colorectal tissue, but is present at levels 23 times greater in cancerous tissue.

Underscoring its preferential expression on stem cells, ABCB5 was frequently accompanied on both healthy and cancerous cells by a second protein, CD133, which is thought to be a marker of both healthy intestinal stem cells and colorectal cancer stem cells. CD133 is also associated with aggressiveness in colorectal cancer.

To understand ABCB5's role in treatment resistance, the team examined biopsies gathered from colorectal cancer patients both before and after treatment with 5-fluorouracil (5-FU), a standard chemotherapeutic for this tumor. They found that the percentage of cells expressing ABCB5 increased more than five fold after treatment.

Using a mouse model of colorectal cancer, the researchers also found that cells expressing ABCB5 were markedly resistant to 5-FU. Knocking down ABCB5 expression both blocked the growth of these cells and restored their sensitivity to the drug, showing that ABCB5 is not only a marker of treatment resistance but actually drives it.

"With ABCB5, we have a molecule that is present at higher levels in colorectal cancers than in healthy cells, that marks the subset of cancer stem cells in human patients that will resist therapy, and that mediates that resistance at a functional level," said Markus Frank, a staff scientist Children's Department of Medicine and an assistant professor of pediatrics at Harvard Medical School. "It's a new mechanism of 5-FU resistance with very significant translational and therapeutic relevance," added Natasha Frank, a research associate at Children's Hospital Boston, an associate physician in the Division of Genetics at Brigham and Women's Hospital, and director of the Genetics Clinic at the VA Boston Healthcare System. "We think that these are the cells that need to be eliminated for successful treatment of colorectal cancer."

The cancer stem cell hypothesis holds that a fraction of the malignant cells in a tumor have characteristics associated with normal stem cells, namely the ability to self-renew and to give rise to other cell types. The hypothesis also holds that in order to successfully eliminate a tumor, the cancer stem cells must be eliminated as well; if they are not, they could serve as seeds for the tumor to regrow or spread.

"When the cancer stem cell concept was first posited, it was thought that the stem cell subset might coincide with the subset that remains after therapy and that metastasizes," Markus Frank said. "This subset has historically been a hidden target, because we have not been able to define and isolate it. But therapies capable of killing off those cells at the root of the cancer would be much more effective than those that miss this subset."

This work was supported by grants from the National Cancer Institute and the U.S. Department of Veterans Affairs.

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U.S. researchers advocate national strategic approach to therapeutic cancer vaccines

ScienceDaily (June 8, 2011) — Vaccines that save lives by preventing disease have been around for centuries. Now, new vaccines that treat cancer are being developed, but how they will be combined with existing treatments is not clear.

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Researchers at the University of Michigan Health System recommend that a national strategy be developed for bringing therapeutic cancer vaccines to patient care, so that cancers with less effective treatment options are priority targets.

"Vaccines that prevent disease have profoundly changed the lives of billions of people around the world," says Matthew M. Davis, M.D., MAPP, associate professor of pediatrics and internal medicine at the University of Michigan Medical School. "A national strategy for therapeutic cancer vaccines would help emphasize development and regulatory approval for vaccines targeting cancers that currently do not have other good therapeutic options."

Davis and co-author Elias J. Dayoub, a student at the U-M Medical School, published a commentary in the June 8 theme issue on cancer of the Journal of the American Medical Association.

When germs such as viruses or bacteria enter the body, the human immune system recognizes those germs as something abnormal and attacks them. Preventive vaccines use this natural response to prime the body's immune system so it can respond to bacteria such as pertussis (the cause of whooping cough) or viruses such as polio and measles.

With cancer cells, however, it is hard for the immune system to detect the "invaders," since they are the human body's own cells gone bad. Therapeutic cancer vaccines can enable the immune system to recognize undetected harmful cells and generate a response to fight back.

Lung cancer, pancreatic cancer and types of leukemia's all have lower survival rates than many other cancers because they respond poorly to currently available chemotherapy, radiation and surgery.

More than 200,000 Americans died from these cancers in 2010 -- more deaths than from breast, prostate and colon cancer combined. Davis suggests that therapeutic vaccines can be used to improve the survival rates of patients with leukemia, lung cancer and pancreatic cancer and also for less common tumors that have similarly poor survival rates.

In 2010, the first cancer therapeutic vaccine was approved for specific forms of prostate cancer. Davis calls it "a major milestone for the entire class of therapeutic cancer vaccines in the United States."

Current research suggests it may be easier for scientists to develop specific vaccines, but Davis emphasizes that what is scientifically easiest may not necessarily benefit the broadest and largest groups of patients.

"While pharmaceutical research and development clearly can lead to exciting advances in care, it may take a strategic plan to help channel creative energy and effort into certain products that maximize benefit for the greatest number of patients over the shortest time frame," says Davis.

A strategic plan could include targeted funding for research and clinical trials that test specific vaccine candidates, explains Davis.

With currently available treatments, two out of every three people in the United States who are diagnosed with cancer survive for at least five years, according to the National Cancer Institute. Complications from these treatments can reduce patients' quality of life, though. Vaccines may potentially offer fewer side effects.

"While it is too early to claim success for therapeutic cancer vaccines, they offer patients and families facing cancer a new ray of hope," concludes Davis.

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