New colon cancer culprit found in gut microbiome

Changes in the gut bacteria of colon cancer patients indicate that some virulent bacteria could be linked to the progression of the disease, according to research published in the open access journal Genome Medicine. The findings could eventually be used to identify a virulence signature in these cancers and help doctors predict how bacterial changes in patients’ guts could affect their prognosis.

The human gut microbiome, the collection of microorganisms, their genomes and habitat that contributes to maintaining a healthy intestine, is thought to play an active role in colon cancer progression. Previous studies have shown that changes in the bacterial community occur in the gut microbiome of colon cancer patients, with tumors harboring increased bacterial diversity and an abundance of pathogenic bacteria compared to surrounding healthy tissue.

Although researchers have uncovered a variety of potentially pathogenic bacteria associated with colon cancer, little work has been done to determine if there is a single signature that might unify their findings.

Lead author Michael Burns from The University of Minnesota, USA, said: “It was surprising that the results were so clear. We were able to clearly identify the presence of two virulent strains of bacteria, including the discovery of a new potential culprit, Providencia.

This has obvious implications for colon cancer patients and by analyzing the similarities among these pathogens, we have uncovered a single signature of colon cancer when analyzing the gut microbiome that might help researchers identify these cancers in the future.”

This was the first study to focus on the pathogenic potential of the bacterial genes present in the colon cancer ‘tumor microenvironment’, the environment of surrounding blood vessels, immune cells and other cells. The genes of the gut microbiomes were predicted in 44 primary tumor and 44 patient-matched normal colon tissues to analyze the general microbial function.

The team in Ran Blekhman’s lab noted changes in the abundances of helpful, harmless, and pathogenic bacteria, including Fusobacterium and Providencia. Fusobacterium has previously been implicated as a cancer-causing group of bacteria, but this is the first time that Providencia has been linked to colon cancer.

Analyzing the major changes that take place in the gut microbiome could help researchers categorize the role particular bacteria play and identify the key players.

Additionally, by showing that the microbial genes predicted to be present in colon cancer tissue are enriched for virulence functions, clinicians could use this signature to uncover what bacterial changes in the gut mean for a patient’s health.

At this stage, the research cannot determine a definite causal link between Providencia species and colon cancer. While the study’s methods are robust for analyzing human gut samples, more research will be needed to assess the interactions between gut bacteria and the progression and development of colon cancer.

Burns et al. Virulence genes are a signature of the microbiome in the colorectal tumor microenvironment. Genome Medicine. 2015;EPub Ahead of Print. doi:10.1186/s13073-015-0177-8 [Abstract provisional pdf also available]

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Smoking may impact survival after a breast cancer diagnosis

Researchers have found that smoking may increase the risk of dying early in premenopausal women with breast cancer.

In a prospective study of 848 women with breast cancer who were followed for a median of 6.7 years, premenopausal women who smoked for more than 21.5 years had a 3.1-times higher risk of dying from any cause as well as a 3.4-times higher risk of dying from breast cancer. These links were not apparent among post-menopausal women.

There was also some suggestion that the increased risks seen in premenopausal women were especially relevant to women whose cancers expressed both the estrogen receptor and the progesterone receptor.

“Overall, this work is monumental in advising patients about how their smoking might affect their outcome,” said Dr. Yuko Minami, co-author of the Cancer Science study. “Hopefully this paper will serve to reduce the number of breast cancer patients who continue to smoke.”

Kakugawa et al. Smoking and survival after breast cancer diagnosis in Japanese women: A prospective cohort study. Cancer Science. 2015;EPub. DOI: 10.1111/cas.12716 [Abstract]

Cancer overtakes cardiovascular disease as UK’s No. 1 killer – but only among men

Cardiovascular disease still primary cause of death among women

Cancer has overtaken cardiovascular disease, which includes heart disease and stroke, as the UK’s No 1 killer- but only among men, reveals research published online in the journal Heart. Cardiovascular disease is still the most common cause of death among women, and kills more young women than breast cancer, the figures show.

The researchers used the latest nationally available data (2012-13) for each of the four UK countries and the Cardiovascular Disease Statistics 2014 report compiled for the British Heart Foundation (BHF) to quantify the prevalence of cardiovascular disease, and find out how it’s treated, how much it costs, and how many deaths it causes. Cardiovascular disease includes coronary heart disease, stroke, high blood pressure, circulatory system disease, and other vascular/arterial disease.

The researchers analysed entries to the Clinical Practice Research Datalink GOLD database, the world’s largest repository of anonymised records for primary care, plus information from the family doctor (GP) quality improvement scheme known as QOF, and figures on episodes of inpatient hospital care. The analysis indicated that just short of 2.3 million people were living with some form of coronary heart disease in 2012. Around half a million were living with heart failure and a further 1.1 million were living with abnormal heart rhythm (atrial fibrillation).

England had the lowest prevalence of all cardiovascular conditions out of the four UK countries. But there were regional variations, with higher rates of cardiovascular disease in the North of England than in the South of the country. Scotland had the highest prevalence of coronary heart disease, stroke, and peripheral vascular disease, while Wales had the highest prevalence of high blood pressure, heart failure, and atrial fibrillation.

For the first time since the middle of the 20th century, cancer overtook cardiovascular disease as the primary cause of death in 2012. The proportion of deaths attributable to cancer was 29% while cardiovascular disease accounted for 28%.

But this was only true of men; cardiovascular disease still killed more women than cancer.

Almost one in three deaths (32%) in men were caused by cancer compared with 29% for cardiovascular disease. The equivalent figures were 27% and 28%, respectively, for women.

Cardiovascular disease accounted for a total of nearly 42,000 premature deaths (before the age of 75) in 2012, accounting for more than one in four premature deaths in men and around one in five (18%) in women. But it still killed more young women than did breast cancer.

Once again, there were wide regional variations in death rates. There were higher rates in Scotland (347/100,000 of the population) and the North of England (320/100,000), and lower rates in the South of England. The City of Glasgow topped the league table for death rates from cardiovascular disease for all ages, including premature deaths.

The number of surgical procedures and drugs prescribed to treat and prevent cardiovascular disease has risen substantially over the past two decades, and in 2012-13 the NHS spent just under £7 billion in England alone on cardiovascular disease, the largest chunk of which was spent on hospital care.The equivalent cost in Wales was £442.3 million, £393 million in Northern Ireland, and more than £750 million in Scotland.

Cardiovascular disease remains a substantial burden to the UK, both in terms of health and economic costs,” write the researchers, highlighting the “stark regional inequalities in the mortality and prevalence of cardiovascular disease.”

In a linked editorial, Dr Adam Timmis, of the NIHR Cardiovascular Biomedical Research Unit at Barts Health, London, describes the more than 40% drop in cardiovascular disease death rates since 1960 as “among the greatest public health triumphs in the past 50 years.” But the continuing North-South divide is a “stain on the UK’s public health record,” he writes.

The BHF report provides a timely reminder that in young women too cardiovascular disease kills more women than breast cancer. Most of these deaths in young women are caused by myocardial infarction heart attack which is largely preventable through modification of risk factors,” he points out.

And if the national effort put into the detection of breast cancer could be matched in protecting young women against myocardial infarction many more lives would probably be saved,” he insists.

Bhatnagar et al. The epidemiology of cardiovascular disease in the UK 2014. Heart. 2015; doi:10.1136/heartjnl-2015-307516 [Article]

Intravenous nutrition source could reduce side effects of chemotherapy

Carnegie Mellon researchers show that Intralipid can also increase the effectiveness of cancer-fighting nanodrugs.

A single dose of an FDA-approved intravenous nutrition source may be able to significantly reduce the toxicity and increase the bioavailability of platinum-based cancer drugs, according to a study by Carnegie Mellon University biologists published in Scientific Reports.

Platinum-based drugs, including cisplatin, carboplatin and oxyplatin, have been used to treat cancer for more than 35 years. While they remain among the most prescribed and most potent chemotherapy drugs, they also cause serious side effects, including kidney damage.

Many of the side effects of these drugs occur when the drug settles in healthy tissue. To deliver these drugs in a more targeted way, researchers have created nanoscale delivery systems engineered to make the drug reach and accumulate at the tumor site. However, tests of these nanodrugs show that only between one and 10 percent of the drugs are delivered to the tumor site, with the majority of the remainder being diverted to the liver and spleen.

The body’s immune system, especially the liver and spleen, has been one of the biggest stumbling blocks in developing nanoscale chemotherapy drug delivery systems,’ said Chien Ho, the alumni Professor of biological sciences at Carnegie Mellon. ‘When the drugs collect in those organs, they become less available to treat the cancer, and can also cause toxicity.’

In the past few years, Ho and his colleagues were developing cellular nanotags to help detect organ rejection, when Ho noticed that Intralipid, a fat emulsion that is FDA-approved for use as an intravenous nutrition source, reduced the amount of nanoparticles that were being cleared by the liver and spleen by about 50 percent. As a result, the nanoparticles remained in the blood stream for longer periods of time.

Ho and his colleagues decided to see if Intralipid had the same effect on platinum-based anti-cancer nanodrugs. In the newly published study, the researchers administered a single, clinical dose of Intralipid to a rat model. One hour later, they administered a dose of a platinum-based chemotherapy drug that had been incorporated into a nanoparticle.

Twenty-four hours after the drug was administered, the researchers found that pre-treatment with Intralipid reduced the accumulation of the platinum-based drug by 20.4 percent in the liver, 42.5 percent in the spleen and 31.2 percent in the kidney. Consequently, in these organs, the toxic side effects of the nanodrug decreased significantly. Furthermore, the researchers found that Intralipid pre-treatment allowed more of the drug to remain available and active in the body for longer periods of time. After five hours, availability of the drug was increased by 18.7 percent, and after 24 hours it was increased by 9.4 percent. The researchers believe that this increased availability will allow more of the drug to reach the tumor site, and could perhaps also allow clinicians to reduce the dosage needed to treat a patient.

The researchers are currently investigating the possibility of bringing this research to a clinical trial.

Lui et al. A new approach to reduce toxicities and to improve bioavailabilities of platinum-containing anti-cancer nanodrugs. Scientific Reports 2015;5:10881 doi:10.1038/srep10881 [Article]

Benefit of surgery for ductal carcinoma in-situ investigated

Study finds that breast surgery offers less survival benefit for low-grade DCIS patientsIn a study published in JAMA Surgery, researchers from Brigham and Women’s Hospital (BWH) report that breast surgery performed at or shortly after a diagnosis of low-grade ductal carcinoma in-situ (DCIS) did not significantly change patients’ survival rate. The team finds that the survival rate for those with intermediate- and high-grade DCIS does improve with surgery, but the work raises concerns about overtreatment and the necessity and benefit of surgery for all patients with low-grade DCIS

Until now, the benefit of surgical management for DCIS had not been investigated – we didn’t know the impact of such surgery for this very early breast cancer. By using registry data, we could estimate the benefit,” said corresponding author Yasuaki Sangara, MD, of the BWH Department of Surgery and Dana Farber/Brigham and Women’s Cancer Center.”Among patients with high- and intermediate-grade DCIS, we do see a statistical difference between the surgery and non-surgery groups, but that significant benefit was not observed for patients with low-grade DCIS.

DCIS is categorized as low-, intermediate- or high-grade based on how cells look compared to normal breast cells. Surgery is the standard of care for all types of DCIS.

DCIS is a cancer of the milk ducts and is the most common type of non-invasive breast cancer. Improvements in early detection have dramatically increased the number of cases of DCIS and approximately 60,000 women are diagnosed with DCIS each year, which accounts for 20 to 25 percent of new breast cancer cases in the United States. It is estimated that between 25 percent and 50 percent of DCIS cases may progress to invasive ductal carcinoma. This rate varies depending on whether a woman’s DCIS is categorized as low-, intermediate- or high-grade, but the standard of care for all grades of DCIS is surgery.
We are over treating breast cancer in the United States and this study, along with others, suggests the need for treatment strategies tailored to a woman’s specific cancer, not just breast cancer in general,” said senior author Mehra Golshan, MD, director of Breast Surgical Services at Dana-Farber/Brigham and Women’s Cancer Center. Golshan is also director of Breast Surgical Services at the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute.The team looked at data from more than 50,000 cases of DCIS available from the SEER (Surveillance, Epidemiology and End Results) database collected between 1998 and 2011 at the Dana-Farber/Brigham and Women’s Cancer Center. For low-grade DCIS, the ten year survival rate for women who did not receive surgery at or shortly after diagnosis was 98.8 percent, and the survival rate for women who did receive surgery was 98.6 percent. For women with intermediate- or high-grade DCIS, the survival rate was significantly different between those who had surgery and those who did not.

This study alone does not allow us to definitively conclude that breast surgery should be avoided for women with low-grade DCIS, but we believe that a prospective clinical trial – following patients over time from diagnosis through treatment and beyond – is warranted,” said Sagara.

Sagara et al. Survival benefit of breast surgery for low-grade ductal carcinoma in situ: A population-based cohort study. JAMA Surg. 2015; doi:10.1001/jamasurg.2015.0876 [Article]