Tiny RNAs shed by tumours can transform healthy cells into cancerous ones.

When a cancer cell throws out its trash, it can turn healthy neighbours into fellow tumour cells, researchers have found.

Many cells, including cancerous ones, shed thousands of tiny membrane-bound vesicles called exosomes that contain proteins, DNA and RNA. The process is thought to be a waste-management system, but it may also facilitate cell-to-cell communication: some of these vesicles can then merge with other cells and dump their payload inside.

In a study published online on 23 October in Cancer Cell1, researchers show that when human breast-cancer exosomes can cause tumours when mixed with normal cells then injected into mice. The results could pave the way to finding markers to monitor the progression of cancer, and possibly even point to targets for therapies.

“It’s amazing — these vesicles were considered garbage cans,” says Khalid Al-Nedawi, a cancer researcher at McMaster University in Hamilton, Canada. “This paper really brings us closer to harnessing the potential of these tiny vesicles.”

Previous studies had shown that cancer cells crank out more exosomes than normal cells2. Cancer researcher Raghu Kalluri of the MD Anderson Cancer Center in Houston, Texas, and his colleagues therefore decided to look into how the two types of exosome might differ. They isolated exosomes from cells grown in culture and found that, unlike normal exosomes, those from cancer cells contained the building blocks required to produce the short fragments of RNA called microRNA that can shut off the expression of target genes.

Exposure to the cancer exosomes altered gene expression in the normal cells. Those cells then caused tumours when injected into mice. Exosomes from normal cells did not yield tumours, however, and tumour growth was reduced in cells exposed to cancer exosomes in which the microRNA-producing molecular machinery had been disabled.

The team also collected exosomes from the blood of 8 healthy individuals and 11 people with breast cancer. Five of the 11 exosome samples from the patients induced tumour growth when mixed with normal cells and injected into mice; none of the exosome samples from healthy people did so.

It is unclear how far exosomes can travel in the body, says Kalluri, but the fact that the team could isolate them from blood suggests that they could be quite mobile. And even if their effect is only local, they could still make nearby cancer cells more aggressive, or transform healthy cells into cancerous ones, he says.

A study will be published on March 21, 2009 in World Journal of Gastroenterology addresses the question.

A research group in King Saud University, Kingdom of Saudi Arabia investigated, for the first time, the role of carnitine, a naturally occurring compound that is synthesized mainly in the liver, during the development of hepatocarcinogenesis. Authors of the study reported that carnitine deficiency is a risk factor and should be viewed as a mechanism in hepatic carcinogenesis, and that long-term L-carnitine supplementation prevents the development of liver cancer. Therefore, carnitine supplementation alone or in combination with other natural chemopreventive compounds could be used to prevent, slow or reverse the occurrence of liver cancer.

Chemoprevention is defined as the use of naturally occurring and/or synthetic compounds in cancer therapy in which the occurrence of cancer can be entirely prevented, slowed or reversed. L-carnitine is a naturally occurring compound which is primarily located in mitochondria and possesses potential protective effects against many mitochondrial toxic agents. It is derived from two sources; endogenous synthesis, in the liver and kidney, and from exogenous dietary sources such as red meat and dairy products. L-carnitine is an essential cofactor for the translocation of long chain fatty acids from the cytoplasmic compartment into mitochondria, where beta-oxidation enzymes are located for ATP production. Despite the liver being the main organ responsible for endogenous synthesis of L-carnitine, we were unable to find any studies investigating the role of long-term endogenous carnitine depletion and/or carnitine deficiency during induction of hepatic carcinogenesis.

The research team by Professor Sayed-Ahmed from College of Pharmacy, King Saud University used an experimental model of hepatocarcinogenesis under conditions of carnitine depletion and carnitine supplementation.


In the carnitine-depleted rat model, there were a progressive increase in the activities of liver enzymes as well as massive degenerative changes and evidence of pre-neoplastic lesions in liver tissues including clusters of hepatocytes with atypia and an increased proliferative rate, diffuse bridging fibrosis and nodule formation, bile ducts with marked reactive atypia showing nuclear enlargement, high nuclear/cytoplasmic ratio and prominent nucleoli. Interestingly, L-carnitine supplementation resulted in a complete reversal of the increase in liver enzymes compared to normal values, as well as normal liver histology with unremarkable central vein and no evidence of pre-neoplastic lesions in liver tissues.

Due to the fact that liver cancer is one of the major health problems in the world and a large sector of patients seek medical attention at a relatively late stage which increases the cost of treatment, King Saud University granted Prof. Sayed-Ahmed and his colleagues a research project with the following specific aims: (1) to understand the possible molecular mechanisms whereby carnitine deficiency provokes hepatic carcinogenesis. (2) to understand the relationship between hepatic cancer and its resistance to cancer chemotherapy, and (3) to gain knowledge on the possible mechanisms by which carnitine supplementation alone or in combination with other natural chemopreventive compounds could be used to prevent, slow or reverse the occurrence of liver cancer.
Source:

http://www.wjgnet.com/

In an article published in this month's issue of Pediatrics In Review, researchers from Boston University School of Medicine (BUSM) stress the importance of physicians recognizing that many mothers use herbal supplements while breastfeeding in order to make accurate health assessments for both mother and child.

In the US, no existing regulatory guidelines set a standardized risk assessment of herbal supplement use during breastfeeding. Because of the highly limited number of studies on herb use during lactation, numerous resources have mixed reports and safety recommendations, making it confusing for both mother and clinician.

After completing a systematic review of human lactation and herbal medicine literature, the researchers found poor methodology in the few available studies and concluded that further research is needed to assess the prevalence, efficacy and safety of commonly used herbs during breastfeeding.

"It is important for physicians and clinicians to be more aware that mothers are using herbal supplements and how vital it is to ask the mothers, who are seeking a doctor's opinion when having trouble breastfeeding, about their use before making an assessment," said senior author Paula Gardiner, MD, MPH, assistant professor at BUSM and a physician of family medicine at Boston Medical Center.

Although there is little scientific evidence to support the efficacy or safety of herbal supplements, it is a common practice both nationally and internationally.

"The use of herbal supplements while breastfeeding is two-sided-there are benefits, but there are also safety concerns," she added. "About 18 percent of the US population use herbs and dietary supplements. We just want to make sure physicians and clinicians are aware of this prevalent use when communicating with breastfeeding mothers about their health."

Herbal remedies may be used to increase the milk supply, relieve engorgement, treat mastitis, or for other therapeutic uses unrelated to lactation.

"Since there is very limited research, it is difficult to develop accurate information on the safety and effectiveness of specific herbs during breastfeeding," said Gardiner. "It is crucial that more research is conducted in this area, including national prevalence studies and safety and efficacy studies."
Source:

Boston University Medical Center