Breast cancer: Common drugs may halt post-surgery relapse

After cancer surgery — particularly for breast cancer — many patients experience an early tumor recurrence. It is not clear why, but new research suggests that common pain-reducing, anti-inflammatory drugs may prevent that from happening.

Published Sunday 15 April 2018

By Maria Cohut  

The answer to early relapse after breast cancer surgery may be closer than we think.

In many cancer types — especially in the case of breast cancer — surgery is often preferred when it comes to removing primary tumors.

However, the recurrence of cancer after surgery is not an uncommon occurrence.

Some who have gone through surgery are at an increased risk of early recurrence, although the precise reasons why are currently unclear.

In a new study whose results have been published in the journal Science Translational Medicine, first author Jordan Krall and colleagues — from the Whitehead Institute for Biomedical Research in Cambridge, MA, and other institutions — have begun to uncover some clues and investigate how these cases of early relapse might be avoided.

"A partial explanation for these outcomes has become clear: in as many as one third of patients diagnosed with localized breast cancer, carcinoma cells have already disseminated to distant anatomical sites at the time of initial diagnosis," the authors explain in their paper.

Until surgery, such tumor cells may remain in a state of limbo, with their harmful potential blocked by the body's immune response.

"In a subset of patients, however," the authors say, "a small fraction of such clinically inapparent cancer cells ultimately renew proliferation and spawn life-threatening metastases [or secondary tumors]."

However, Krall and team's recent study on mice has revealed a ray of hope in the shape of a type of commonly available drug used to fight pain and reduce inflammation: nonsteroidal anti-inflammatory drugs (NSAIDs).

NSAIDs seem to reduce the risk of early post-operatory relapse in the patients to whom they are administered during surgery.

"This represents the first causative evidence of surgery having this kind of systemic response," says Krall. "Surgery is essential for treating a lot of tumors, especially breast cancer. But there are some side effects of surgery, just as there are side effects to any treatment."

"We're starting to understand what appears to be one of those potential side effects, and this could lead to supportive treatment alongside [...] surgery that could mitigate some of those effects."

Jordan Krall

https://www.medicalnewstoday.com/articles/321505.php?_1

Antifungal drug kills dormant colorectal cancer cells

Colorectal cancer is the fourth most commonly diagnosed type of cancer in the United States. Though various treatments are available for it, certain tumor cells are therapy-resistant. Now, research suggests that an antifungal drug may be effective against these persistent cells.

 Published Sunday 3 June 2018

By Maria Cohut

Fact checked by Jasmin Collier

Can itraconazole, an antifungal drug, eliminate therapy-resistant cancer cells and halt tumor progression?

The drug itraconazole is typically used in the treatment of fungal infections.

These can include certain types of vaginal yeast (vulvovaginal candidiasis) and fungal infections on the hands and feet (Tinea pedis and Tinea manuum).

But researchers from the Cancer Research UK Cambridge Institute have suggested a brand new use for this substance — namely, as a treatment that is able to eliminate dormant tumor cells in colorectal cancer.

This is one of the most common cancer types in the U.S., and an estimated 140,250 people will learn that they have this disease in 2018, according to the National Cancer Institute (NCI).

"One of the biggest challenges in treating any cancer is the diversity of different cells within the same tumor," explains co-lead author Dr. Simon Buczacki, who participated in the new study investigating the effect of itraconazole on dormant colorectal cancer cells.

In this study, he continues, the team "targeted a type of cell that lies asleep within bowel tumors, remaining unresponsive to treatment and putting the patient at risk of their cancer coming back."

In experiments conducted on mice, Dr. Buczacki and team found that the antifungal drug may be able to trigger the death of a type of colorectal cancer cell typically immune to treatment.

These tumor cells are found in a state of inactivity, or "dormancy," so they do not respond to the usual therapies, such as chemotherapy, that target and destroy active cancer cells.

So, even as a treatment is effective in destroying most malignant cells, these dormant units will remain unaffected, putting the person at risk of having a recurrence of the cancer later on.

Itraconazole halts tumor progression

In the study — the findings of which have been published in the Journal of Experimental Medicine— the researchers worked with cancer tumors grown in mice models of colorectal cancer.

First of all, they focused on identifying which signaling pathways were involved in controlling cell dormancy in the case of cancer tumors. They saw that, for colorectal cancer, there are two: Wnt and "hedgehog" pathways.

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Then, they tested the effectiveness of various drugs on these two pathways, and it was then that they noticed itraconazole's therapeutic potential.

Dr. Buczacki and team discovered that itraconazole interfered with the Wnt pathway, which led to the elimination of the dormant cells and blocked the growth of the cancer tumor.

"What's interesting is that this drug seems to kick both dormant and non-dormant cells into action," notes Dr. Buczacki.

"It forces cells back into a short cycle of growth," he explains, "before slamming on an irreversible 'stop' button, entering a permanent standstill that's known as senescence."

Following these promising results, the team would eventually like to test the effectiveness of this drug in clinical trials, on patients with colorectal cancer at an advanced stage.

Another step would be to ascertain whether itraconazole would be more effective on its own, or used in combination therapy, administered alongside other drugs.

Prof. Greg Hannon — the director of the Cancer Research UK Cambridge Institute — comments on the discovery, calling the research an "innovative study" that "has taken a step toward addressing one of the biggest challenges in cancer research."

"The presence of drug-resistant, dormant tumor cells is a problem in many types of cancer," he says.

"If we find ways to target these cells in bowel cancer, it might provide insights into tackling the problem of dormant tumor cells more broadly."

Prof. Greg Hannon

https://www.medicalnewstoday.com/articles/322009.php

Increased coffee consumption may reduce risk of type 2 diabetes

A new study led by researchers at Harvard School of Public Health in Boston, MA, has found that increasing coffee consumption may reduce type 2 diabetes.

Friday 25 April 2014

Coffee has been linked to a variety of health benefits recently.

Earlier this month, Medical News Today reported on a study in the journal Hepatology that - through analyzing data from a health survey among Chinese people living in Singapore - found that coffee intake was linked with alower risk of death from cirrhosis.

Late last year, an Italian study also suggested that coffee has beneficial properties for the human liver, finding a link between coffee consumption and a decreased risk of liver cancer.

A report published by the American Institute for Cancer Research also suggested that engaging in physical activity, eating healthfully, and drinking coffee - whether caffeinated or decaffeinated forms of the beverage - all reduce risks of womb cancer.

A wealth of further information on the subject can be found in our Knowledge Center article, "What are the health benefits of coffee?"

The new study, which is published in the journal Diabetologia, investigates to what extent type 2 diabetesmight be affected by coffee consumption.

Analysis draws data from three large studies, covering a 20-year period

"Coffee is only one of many factors that influence diabetes risk," the researchers remind.

The Harvard School of Public Health (HSPH) researchers gathered data from three studies. The participants included:

• 48,464 women in the Brigham and Women's Hospital-based Nurses' Health Study (1986-2006)
• 47,510 women in the Nurses' Health Study II (1991-2007)
• 27,759 men in the Health Professionals Follow-up Study (1986-2006).

In these studies, the diets of the participants were evaluated using questionnaires every 4 years, with participants who reported having type 2 diabetes filling out additional questionnaires. In total, 7,269 study participants had type 2 diabetes.

The researchers found that the participants who increased their coffee intake by more than one cup a day (on average, an increase of 1.69 cups per day) over a 4-year period had an 11% lower type 2 diabetes risk over the subsequent 4 years, compared with people who did not change their intake.

Also, people who lowered their daily consumption by more than one cup of coffee (on average, a decrease of two cups per day) showed a 17% higher risk for type 2 diabetes.

In the study, a "cup of coffee" was defined as being 8 oz and either black or with a small amount of milk or sugar.

"Our findings confirm those of previous studies that showed that higher coffee consumption was associated with lower type 2 diabetes risk," says Shilpa Bhupathiraju, lead author and research fellow in the Department of Nutrition at HSPH. "Most importantly, they provide new evidence that changes in coffee consumption habit can affect type 2 diabetes risk in a relatively short period of time."

"These findings further demonstrate that, for most people, coffee may have health benefits," adds Frank Hu, senior author and professor of nutrition and epidemiology at HSPH. "But coffee is only one of many factors that influence diabetes risk. More importantly, individuals should watch their weight and be physically active."

Written by David McNamee

Medical News Today

Reference

Changes in coffee intake and subsequent risk of type 2 diabetes: three large cohorts of US men and women, Shilpa N. Bhupathiraju, et al., Diabetologia, DOI 10.1007s00125-014-3235-7, published online April 24, 2014.
Harvard School of Public Health news release, accessed 25 April via EurekAlert.

http://www.medicalnewstoday.com/articles/275979.php

Drinking coffee linked to decreased liver cirrhosis death risk

Chronic liver disease and cirrhosis is the 11th cause of death in the US, killing nearly 32,000 people in 2010. But now, researchers are suggesting that drinking two or more cups of coffee every day can reduce the risk of death from liver cirrhosis by 66%.

Published in the journal Hepatology, the study adds to growing evidence that coffee has real health benefits.

Medical News Today recently published a feature on how caffeine affects our health, listing benefits such as reduction of liver cancer risks and decreased risk of suicide.

One study recently suggested that consuming 200 mg of caffeine each day could boost long-term memory.

In this latest study, Dr. Woon-Puay Koh, from Duke-NUS Graduate Medical School Singapore and the National University of Singapore, led a team of researchers who investigated how coffee might help minimize deaths caused by liver cirrhosis. The World Health Organization say this condition is responsible for 1.3% of total deaths worldwide.

Dr. Koh notes that their study focused on the effects coffee, alcohol, black tea, green tea and soft drinks have on mortality risks from cirrhosis. However, only coffee decreased these risks, while heavy alcohol use - perhaps unsurprisingly - increased risk of death from this condition.

Study 'provides impetus to further evaluate coffee as therapeutic agent'

In the US, over 50% of people over the age of 18 drink coffee every day. America is a nation of coffee drinkers, who total around 100 million, and the amount spent importing coffee here each year totals around $4 billion.

Drinking two or more cups of coffee each day could lower risks of dying from cirrhosis of the liver.

With so much time and money centered around coffee, it is an added benefit that the beverage can be considered a healthy lifestyle choice for certain conditions.

To further investigate, the researchers used a prospective population-based study called The Singapore Chinese Health Study, which involved over 63,000 Chinese subjects living in Singapore who were between 45 and 74 years old.

These participants provided researchers with data on diet, lifestyle and medical histories through interviews and questionnaires between 1993 and 1998, and the researchers followed up with them for an average of 15 years.

The researchers recorded that a total of 14,928 of the study participants died in this time, of which 114 died from liver cirrhosis.

Overall results show that individuals who drank at least 20 g of ethanol (alcohol) each day had a greater risk of cirrhosis mortality, compared with non-drinkers. Meanwhile, coffee intake was linked with a lower risk of death from cirrhosis, and the researchers note this was particularly the case for non-viral hepatitis related cirrhosis.

In detail, participants who drank two or more cups of coffee each day had a mortality risk that was 66% lower than that of non-daily coffee drinkers.

The researchers note that drinking coffee was not linked with viral hepatitis B related cirrhosis mortality, however.

Dr. Koh says their study is the first to show a difference in coffee's effects on non-viral and viral hepatitis related cirrhosis mortality. He adds:

"This finding resolves the seemingly conflicting results on the effect of coffee in Western and Asian-based studies of death from liver cirrhosis.


Our finding suggests that while the benefit of coffee may be less apparent in the Asian population where chronic viral hepatitis B predominates currently, this is expected to change as the incidence of non-viral hepatitis related cirrhosis is expected to increase in these regions, accompanying the increasing affluence and westernizing lifestyles amongst their younger populations."

The authors conclude their study by noting that it "provides further impetus to evaluate coffee as a potential therapeutic agent in patients with cirrhosis."

Medical News Today recently reported on research from the Centers for Disease Control and Prevention that suggested though overall caffeine intake has not increased, kids in the US are consuming caffeine from more diverse sources, including both coffee and energy drinks.

Our article on the health benefits of coffee also explores some of the other ways that the beverage can be good for us.

Written by Marie Ellis

Medical News Today

Reference:

Coffee, alcohol and other beverages in relation to cirrhosis mortality: the Singapore Chinese Health Study, Woon-Puay Koh, et al., Hepatology, doi: 10.1002/hep.27054, published April 2014, Abstract.
Additional source: CDC Chronic Liver Disease and Cirrhosis, accessed 3 April 2014.
Additional source: Statistic Brain Coffee Drinking Statistics, accessed 3 April 2014.

http://www.medicalnewstoday.com/articles/275028.php

CT Scans Raise Cancer Risk For Children

Editor's Choice
Academic JournalMain Category: Pediatrics / Children's Health
Also Included In: MRI / PET / Ultrasound; Cancer / Oncology; Medical Devices / Diagnostics
Article Date: 08 Jun 2012 - 0:00 PDT


With MRI scans becoming cheaper and more common, perhaps the days of the CT scan that does a similar function using X-Rays rather than magnetic fields, are numbered. A report shows that the cancer risk from CT scans, especially Brain Cancer and Leukemia can triple in some cases.

The Article published in The Lancet, and written by Dr Mark Pearce and Professor Sir Alan Craft, Newcastle University, UK; Professor Louise Parker, Dalhousie University, Halifax, NS, Canada; Dr Amy Berrington de González, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA, and colleagues, represents the culmination of almost two decades of research in this area, and is jointly funded by the UK Department of Health and NCI/NIH.

It shows that 2 or 3 computed tomography (CT) scans of a child's head (child meaning under 15 years old in this case), can triple the risk of brain cancer. The total dose of radiation would be around 60mGy, while 5 to 10 scans giving a dose of some 50mGy or more, triples the risk of leukemia.

The researchers go on to point out that the risks are still miniscule as the diseases are not particularly common, thus an increased risk is far from absolute certainty of contracting the disease. The CT scan is a useful and sometimes necessary diagnostic tool, and therefore physicians must weigh the risks and make patients and their parents aware.

The retrospective study used records from the radiology departments of some 70% of the UK's hospitals, and gathered data from 180,000 patients who underwent CT scans between 1985 and 2002. By looking at the number and types of CT scan from the records, the researchers estimated the dose absorbed in milli-Grays (mGy) by the brain and bone marrow in patient for each scan. The data was then cross-checked with cancer incidence and mortality reports in the UK National Health Service Registry between 1985 and 2008. It was then possible to show if a person having scans was more likely to develop cancer. From this, they calculated excess incidence of leukemia and brain tumors.

The UK has relatively low usage of CT scans due to a nationalized health service and the Ionising Radiation (Medical Exposure) Regulations, that make sure scans are only done when medically justified.

Lead author Dr Pearce says:

"The immediate benefits of CT outweigh the potential long¬term risks in many settings and because of CT's diagnostic accuracy and speed of scanning, notably removing the need for anaesthesia and sedation in young patients, it will, and should, remain in widespread practice for the foreseeable future ...

Further refinements to allow reduction in CT doses should be a priority, not only for the radiology community, but also for manufacturers. Alternative diagnostic procedures that do not involve ionising radiation exposure, such as ultrasound and MRI [magnetic resonance imaging] might be appropriate in some clinical settings. Of utmost importance is that where CT is used, it is only used where fully justified from a clinical perspective."

A patient undergoes a CT scan


In a linked Comment, Dr Andrew J Einstein, New York Presbyterian Hospital and Columbia University Medical Center, New York, NY, USA, says:

"This study should reduce the debates about whether risks from CT are real, but the specialty has anyway changed strikingly in the past decade, even while the risk debate continued. New CT scanners all now have dose-reductions options, and there is far more awareness among practitioners about the need to justify and optimise CT doses, an awareness that will surely be bolstered by Pearce and colleagues' study ...

Pearce and colleagues confirm that CT scans almost certainly produce a small cancer risk. Use of CT scans continues to rise, generally with good clinical reasons, so we must redouble our efforts to justify and optimise every CT scan.""

Reference:
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60815-0/abstract

Written by Rupert Shepherd
Copyright: Medical News Today
http://www.medicalnewstoday.com/articles/246324.php

How Cancers Spread At Cellular Level - Scientists Find Clues

Editor's ChoiceMain Category: Melanoma / Skin Cancer
Also Included In: Cancer / Oncology
Article Date: 09 Jun 2012 - 0:00 PDT

The fact that different types of tumors only spread to particular, select organs has been known to cancer researchers for longer than a century. However, so far scientists have been unable to determine the 'soil and seed' theory of 1889, which is the underlying mechanism behind organ-specific metastasis.

Weill Cornell Medical researchers from the Memorial Sloan-Kettering Cancer Center and their collaborators may have discovered an explanation that could provide a new insight into the 'soil and seed' theory. In an article recently published online in Nature Medicine, they have described a new mechanism to control the metastasis of cancer that could potentially be used as a novel diagnostic tool and treatment option.

Exosome vesicles are a specific subtype of membrane vesicles that circulate in the blood and contain numerous proteins, lipids, and even nucleic acids. In their study, the researchers managed to demonstrate a mechanism by which melanoma cancer cells release small exosome vesicles that travels to various locations, such as the brain, bone, liver and lungs, where the cellular material inside the vesicles fuses with these organs, establishing the perfect environment to spread tumor cells.

The researchers point out that these harmful cancer exosomes can cause various effects; For instance, they are able to trigger inflammation, further the process of leaky blood vessels and 'program' bone marrow progenitor cells to get involved in a soon-occurring metastatic cascade. Exosomes could potentially be advantageous in the diagnoses, prognosis and treatment of cancer, given that they are readily accessible and measurable as they circulate in the bloodstream.

Dr. David C. Lyden, the Stavros S. Niarchos Associate Professor in Pediatric Cardiology and associate professor of Pediatrics and Cell and Developmental Biology at Weill Cornell Medical College, who is also a pediatric neuro-oncologist at Memorial Sloan-Kettering Cancer Center explained: "The exosome profile could be useful in a number of ways - to help detect cancer early, to predict the aggressiveness of a patient's tumor and response to chemotherapy or other treatments, and to understand the risk of cancer recurrence or spread before traditional methods would be able to."

Dr. Jacqueline F. Bromberg, who studies breast cancer, and who is an associate attending physician at Memorial Sloan-Kettering Cancer Center and associate professor of Medicine at Weill Cornell, adds: "We believe each tumor type will have its own exosomal protein profile that will represent each tumor subtype. The exosomal proteins will be useful for prognosis in predicting which patients, including those who develop disease decades after their original diagnosis, will likely be at risk for future metastatic disease."

According to leading author, Dr. Hector Peinado, an instructor of molecular biology at Weill Cornell Medical College's Department of Pediatrics, the findings indicate that if a cancer therapy is to be effective, it has to be multi-layered, saying: "If, in the future, we were able to find a way to control the 'education' of bone marrow cells, as well as the release and content of tumor exosomes in cancer patients, we would be able to curtail and reduce the spread of cancer, and improve the patient's quality of life and survival."

Co-senior author, Dr. Lyden and his team were the first to discover that cells derived from bone marrow (BMDCs) were crucial in order to form primed sites in distant organs, called 'pre-metastatic niches' that provide a perfect base for cells that are spread from a primary tumor. For years they have investigated decoding the biochemical processes that produce these niches, trying to understand the signals that induce the BMDCs to carry out their functions in the niche. At first they investigated exosomes, which were originally believed to consist of mere cell debris used to dump used proteins, but were later found to contain RNA as well as nucleic acids that is found in cancer cells.

They decided to investigate whether exosomes released from a melanoma played a particular role in cancer, and according to Dr. Lyden they discovered:

"Upon their release from the primary tumor, exosomes derived from melanoma cells fuse with cells in distant metastatic organs and lymph nodes, mediating vascular leakiness and inflammation, thereby promoting the formation of pre-metastatic niches that enhance future metastatic growth."

Dr. Peinado explains that the exosomes transfer numerous exosomal proteins to BMDCs, where they are able to reprogram the cells to get involved in the metastatic cascade, saying "We found an oncogenic protein, called MET, that is produced by highly metastatic tumors and packaged into pro-metastatic exosomes. The tumor exosomes circulate, fuse and transfer their information, including the MET oncoprotein, to many cells, such as bone marrow cells, which in turn promote a pro-metastatic phenotype."

In addition, they also discovered that the reprogramming of the BMDCs by exosomes has a long-term effect. This could potentially explain why tumors can lie dormant for years before they suddenly develop into metastatic disease. According to Dr. Bromberg, these findings are vital given that "educated bone marrow is the key in disease recurrence and may even foster a future secondary cancer."

The researchers discovered after examining human blood samples, that patients with stage IV melanoma with widespread metastases had a specific signature of exosomal proteins (including MET), which was not discovered in the blood of patients with non-metastatic melanoma.

According to the researchers, this protein signature could serve as a potential marker to predict which patients with stage III disease and local lymph node metastasis would subsequently be at risk for developing distant metastatic disease.

Dr. Lyden states: "Treatment modalities could be initiated earlier in these high-risk patients to prevent disease progression. Our results demonstrated that MET oncoprotein expression, which can be easily analyzed in a simple blood test, could be used as a new marker of metastatic disease in melanoma patients."

After investigating further, the team found that they could reduce exosomal-induced metastasis either by targeting Rab27a, the protein responsible for production of exosomes or by proactively using exosomes derived from melanoma cells that rarely metastasize in order to reprogram the BMDCs.

Dr. Lyden concludes:

"We have found that less or non-metastatic exosomal proteins may educate bone marrow cells to avoid partaking in the metastatic process. We are working on determining which particular exosomal proteins may be responsible for preventing metastatic participation. This concept may one day be applied to the clinic, where non-metastatic exosome proteins may help prevent the acceleration of tumor growth and metastatic disease, allowing patients with cancer to live longer lives."

Written By Petra Rattue
Copyright: Medical News Today

http://www.medicalnewstoday.com/articles/246372.php