Hairdressers at an increased risk for cancers

According to the World Health Organisation (WHO), hair dyes and other chemicals place hairdressers at an increased risk for cancer.

WHO's International Agency for Research on Cancer (IARC) based in Lyon, France, says being a hairdresser or barber exposes people to materials and chemicals which are likely to be carcinogenic.

In study which conducted a review of six large investigations into cancer risk the IARC researchers found that for male hairdressers and barbers, the risk of cancer of the bladder was between 20 and 60 percent higher than the general population.

They say the risk though "small is consistent" and is less visible among women.

The researchers found among both male and female hairdressers, a heightened risk of 30 percent for lung cancer was seen in some research; they say this could be partly explained by a higher incidence of smoking among hairdressers.

The researchers looked at eight hair dyes and only one could be classified as possibly carcinogenic to humans and also at aromatic amines.

Amines are a large group of organic compounds which containing nitrogen and are thought to be derived from ammonia and are used in the manufacture of plastic, dyes, drugs and pesticides.

Many are considered toxic if ingested, inhaled or reach the skin.

Of the four aromatic amines researched for the study three were classified as probably carcinogenic to humans, while one could not be classified.

For women hairdressers some research suggested an increased risk for ovarian cancer and of non-Hodgkin's lymphoma, but this was not backed up by other research.

New nanoparticles for targeting tumors

As a wide variety of nanoparticles continue to demonstrate their ability to improve the delivery of imaging agents and drugs to tumors, nanoparticle researchers have turned their attention to the challenge of systematically determining how a given nanoparticle's physical and chemical characteristics affect its ability to target tumors. Such data could provide drug developers with guidelines to help them select the most effective type of nanoparticle for a given therapeutic or imaging application.

In a paper published in the PNAS, a team of investigators at the MIT-Harvard Center for Cancer Nanotechnology Excellence, led by Omid Farokhzad, Ph.D., at the Harvard Medical School, and Robert Langer, Ph.D., at MIT, describe one such approach to systematizing nanoparticle development. In their research, the investigators created used two self-assembling polymer families to create series of tumor-targeted nanoparticles that varied slightly from one another in terms of their physical characteristics and their biopharmaceutical properties.

By changing the exact composition of each of the two polymers, as well as the ratio of the two polymers, the investigators found that they could fine-tune both the size and drug-releasing properties of the nanoparticles, which were targeted to the prostate-specific membrane antigen found on the surface of prostate cancer cells. The researchers also were able to vary the amount of targeting agent on the nanoparticle surface, as well as the "stealth" characteristics of the nanoparticle, that is, the ability to evade the immune system. By studying the effect of each change on nanoparticle uptake by prostate cancer cells growing in tissue culture, the investigators were able to identify the specific formulation that optimized tumor uptake in vivo.

Investigators at the University of California, Berkeley, and the University of California, San Francisco, achieved similar results with a different class of polymer nanoparticles known as dendrimers. Jean Fréchet, Ph.D., at UC-Berkeley, and Francis Szoka, at UCSF and a member of the Carolina Center of Cancer Nanotechnology Excellence, led the team of collaborators that created libraries of dendrimers containing a variety of functional groups on their surfaces. These functional groups enable the investigators to attach both PEG and any number of targeting, imaging, and therapeutic agents to the dendrimer surface in a systematic manner.

Experiments using radiolabeled dendrimers demonstrated that these nanoparticle were able to circulate in blood for long periods of time. Subsequent experiments using a dendrimer linked to the antitumor agent doxorubicin showed that drug-loaded carrier accumulated in tumors but far less in healthy tissue compared with liposomal doxorubicin, the first nanoparticle-based drug approved to treat cancer.

The work from Drs. Farokhzad and Langer, which was supported in part by the NCI's Alliance for Nanotechnology in Cancer, is detailed in the paper "Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers." An abstract of this paper is available through PubMed.

View abstract

The work from Drs. Fréchet and Szoka is detailed in the paper "PEGylated dendrimers with core functionality for biological applications." An abstract of this paper is available through PubMed.

View abstract

http://nano.cancer.gov

Next-generation nanomedicine

In an article featured on the cover of the March issue of Nature Nanotechnology, Mauro Ferrari, Ph.D., of The University of Texas Health Science Center at Houston, presented a proof-of-concept study on a new multistage delivery system (MDS) for imaging and therapeutic applications. This discovery could go a long way toward making injectable drugs more effective.

"This is next-generation nanomedicine," said Ferrari, who played a critical role in the development of the National Cancer Institute's (NCI) Alliance for Nanotechnology in Cancer. "Now we're engineering sophisticated nanostructures to elude the body's natural defenses, locate tumors and other diseased cells, and release a payload of therapeutics, contrasting agents, or both over a controlled period."

Nanotechnology offers new and powerful tools to design and engineer novel drug delivery systems and to predict how they will work once inside the body. "The field of therapeutic nanoparticles began with tiny drug-encapsulated fat bubbles called liposomes, now commonly used in cancer clinics worldwide. Targeting molecules were later added to liposomes and other nanovectors to assist in directing them to diseased cells," Ferrari said.

Getting intravenous agents to their intended targets is no easy task. It is estimated that approximately 1 of every 100,000 molecules of agent reaches its desired destination. Physicians are faced with the quandary of increasing the dosage, which can lead to side effects, or reducing the dosage, which can limit the therapeutic benefits.

The multistage approach, according to Ferrari, is needed to circumvent the body's natural defenses or biobarriers, which act as obstacles to foreign objects injected in the bloodstream. "To overcome this problem, we hypothesized and developed a multifunctional MDS comprising stage 1 mesoporous particles loaded with one or more types of stage 2 nanoparticles, which in turn can carry either active agents or higher stage particles. We have demonstrated the loading, controlled release, and simultaneous in vitro delivery of quantum dots and carbon nanotubes to human vascular cells," said Ferrari.

In addition to circumventing biobarriers, Ferrari's team is working on the biochemical modifications required to efficiently deliver the MDS to a specific cancer lesion. "We have preliminary data that show that we can localize a payload of diagnostic agents, therapeutic agents, or combination of both to target cells. Once on site, the molecules can be released in a controlled way, and then the MDS will degrade in 24 to 48 hours, be transformed into orthosilicic acid, and leave no trace in the body," Ferrari said.

One of Ferrari's coauthors, Ennio Tasciotti, Ph.D., said the proof-of-concept study would not have been possible without a multidisciplinary effort that included contributions from mathematicians, physicists, engineers, chemists, and biologists. "We are dealing with objects that are in the billionth of a meter size range, and to study such objects we used cutting-edge technologies," Tasciotti said. "The characterization of the particles was performed using scanning electron and atomic force microscopy, dynamic light scattering, fluorimetry, and flow cytometry. The interaction of particles with cells was studied using fluorescence and confocal microscopy as well as a series of assays intended to determine cell viability and internalization rate of the nanoparticles."

This work, which was supported in part by the NCI, is detailed the paper "Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications." Investigators from The University of Texas M. D. Anderson Cancer Center and Rice University also participated in this study. An abstract of this paper is available at the journal's Web site.

http://nano.cancer.gov

Red wine antioxidant resveratrol kills cancer

Rochester researchers showed for the first time that a natural antioxidant found in grape skins and red wine can help destroy pancreatic cancer cells by reaching to the cell's core energy source, or mitochondria, and crippling its function.

The study is published in the March edition of the journal, Advances in Experimental Medicine and Biology.

The study also showed that when the pancreatic cancer cells were doubly assaulted -- pre-treated with the antioxidant, resveratrol, and irradiated -- the combination induced a type of cell death called apoptosis, an important goal of cancer therapy.

The research has many implications for patients, said lead author Paul Okunieff, M.D., chief of Radiation Oncology at the James P. Wilmot Cancer Center at the University of Rochester Medical Center.

Although red wine consumption during chemotherapy or radiation treatment has not been well studied, it is not "contraindicated," Okunieff said. In other words, if a patient already drinks red wine moderately, most physicians would not tell the patient to give it up during treatment. Perhaps a better choice, Okunieff said, would be to drink as much red or purple grape juice as desired.

Yet despite widespread interest in antioxidants, some physicians are concerned antioxidants might end up protecting tumors. Okunieff's study showed there is little evidence to support that fear. In fact, the research suggests resveratrol not only reaches its intended target, injuring the nexus of malignant cells, but at the same time protects normal tissue from the harmful effects of radiation.

"Antioxidant research is very active and very seductive right now," Okunieff said. "The challenge lies in finding the right concentration and how it works inside the cell. In this case, we've discovered an important part of that equation. Resveratrol seems to have a therapeutic gain by making tumor cells more sensitive to radiation and making normal tissue less sensitive."

Resveratrol is known for its ability to protect plants from bacteria and fungi. Purified versions have been described in scientific journals as potential anti-cancer, anti-inflammatory and anti-atherogenic agents, and for their ability to modulate cell growth. Other well-known antioxidants derived from natural sources include caffeine, melatonin, flavonoids, polyphenols, and vitamins C and E.

A flurry of antioxidant studies in recent years has not proven how and why they work at the cellular level. At the suggestion of a young scientist in his lab, Okunieff began studying resveratrol as a tumor sensitizer. That's when they discovered its link to the mitochondria.

The discovery is critical because, like the cell nucleus, the mitochondria contains its own DNA and has the ability to continuously supply the cell with energy when functioning properly. Stopping the energy flow theoretically stops the cancer.

Researchers divided pancreatic cancer cells into two groups: cells treated without resveratrol, or with resveratrol, at a relatively high dose of 50 mg/ml, in combination with ionizing radiation. (The resveratrol concentration in red wine can be as high as 30 mg/ml, the study said, and higher doses are expected to be safe as long as a physician is monitoring.)

They evaluated the mitochondria function of the cells treated with resveratrol, and also measured apoptosis (cell death), the level of reactive oxygen species in the cells, and how the cell membranes responded to the antioxidant.

Laboratory experiments showed that resveratrol:

• Reduced the function of proteins in the pancreatic cancer cell membranes that are responsible for pumping chemotherapy out of the cell, making the cells chemo-sensitive.
• Triggered the production of reactive oxygen species (ROS), which are substances circulating in the human body that have been implicated in a number of diseases: when ROS is increased, cells burn out and die.
• Caused apoptosis, which is likely the result of increased ROS.
• Depolarized the mitochondrial membranes, which indicates a decrease in the cell's potential to function. Radiation alone does not injure the mitochondrial membrane as much.

The team also wanted to investigate why pancreatic cancer cells seem to be particularly resistant to chemotherapy. The pancreas, a gland located deep in the abdomen, produces insulin and regulates sugar, and pumps or channels powerful digestive enzymes into the duodenum. This natural pumping process, however, ends up ridding the needed chemotherapy from cells in the pancreas. But just as reseveratrol interferes with the cancer cells' energy source, it also may decrease the power available to pump chemotherapy out of the cell.

"While additional studies are needed," Okunieff said, "this research indicates that resveratrol has a promising future as part of the treatment for cancer."

In the same journal, Okunieff and his group also reviewed why resveratrol protects normal tissue, and found that antioxidants can be designed to take advantage of certain biochemical properties or cellular targets, making them more effective.

http://www.urmc.rochester.edu/