Human malaria jab tests nearing BBC News, UK - ... been engineered to be harmless in themselves, but to produce a protein on their surfaces which matches one found on the outside of the malaria parasite. ...
Vaccine To Combat Black Plague Oneindia, India - Aug 4, 2008 For this study, he genetically engineered plant cells with a protein found on the outside of Yersinia pestis. The vaccine was inside the plant cells, ...
Soy - Not So Fast What Doctors Don't Tell You, UK - Curiously enough, that is also about the time that soybeans began to be genetically engineered. I always found this timing coincidence curious. ...
An Odd Pair Important For Cartilage Formation: Sox9 And P54nrb Medical News Today (press release), UK - Aug 4, 2008 Further, mice engineered to express the same mutant protein exhibited dwarfism, indicating that p54nrb has an important role in regulating the function of ...
Mechanism for Postpartum Depression Found in Mice PressZoom (press release), Netherlands - "After giving birth, female mice deficient in the suspect protein showed depression-like behaviors and neglected their newborn pups," explained Istvan Mody, ...
New-style malaria vaccine could save millions guardian.co.uk, UK - Aug 2, 2008 The second involves isolating just one piece of the parasite's protein coat. This can then be grown in genetically modified bacteria and injected into ...
Heady research: Stanford study finds molecule triggers hair growth ... PressZoom (press release), Netherlands - Aug 2, 2008 Scientists at the Stanford University School of Medicine used genetically engineered mouse embryos to demonstrate that the molecule, called laminin-511, ...
Thick bones, big drug Scientist, UK - Aug 1, 2008 He had engineered five transgenic mouse lines to overexpress a mysterious secreted protein. The mice looked and behaved normally, but that ordinariness was ...
Engineered protein scaffolds for molecular recognition - A Skerra - Journal of Molecular Recognition, 2000 - doi.wiley.com ...ENGINEEREDPROTEIN SCAFFOLDS 169 Copyright # 2000 John Wiley & Sons, Ltd. J. Mol.
Recognit. 2000;13:167?187 Page 4. against pathogenic invaders or their toxins ...
Genetically Engineered Protection Against Viruses in Transgenic Plants - JH Fitchen, RN Beachy - Annual Reviews in Microbiology, 1993 - Annual Reviews ... resistance with other types of engineered resistance, will ... In addition, the
coat-protein strategy of disease ... plant species and resistance against other viruses ...
… allergic encephalomyelitis using myelin basic protein-specific T cells engineered to express latent … - LZ Chen, GM Hochwald, C Huang, G Dakin, H Tao, C … - Proceedings of the National Academy of Sciences of the …, 1998 - pubmedcentral.nih.gov ... completely changed merely by having been engineered to produce ... protective effect
of these cells against EAE. ... of their specificity for myelin protein may cause ...
Coat Protein-Mediated Resistance Against Virus Infection - RN Beachy, S Loesch-Fries, NE Tumer - Annual Reviews in Phytopathology, 1990 - Annual Reviews ... have provided weak protection against virus infection ... virus capsid proteins: genetically engineered virus resistance ... virus protection; coat protein pro- tection ...
Engineered Protein Effective Against Staphylococcus Aureus Toxin
A research team led by the University of Illinois has developed a treatment for exposure to enterotoxin B, a noxious substance produced by the Staphylococcus aureus bacterium. The team engineered a protein, which was successfully tested in rabbits, that could one day be used to treat humans exposed to the enterotoxin.
S. aureus enterotoxin B (SEB) is a common cause of food poisoning, but if it is inhaled or produced during an infection it can elicit a systemic - and sometimes fatal - immune response in humans. In purified form, SEB is listed as a potential bioterrorism agent. Other potent S. aureus enterotoxins include the toxic shock syndrome toxin.
These enterotoxins are classed as superantigens because they set off a massive immune response in humans and other animals. They bind to variable regions of T-cell receptors, stimulating a cascade of events, including the systemic release of inflammatory cytokines. In some cases the powerful immune response leads to toxic shock and death.
Article continues below and (thank you)
The research team, led by University of Illinois professor of biochemistry David M. Kranz, included scientists and clinicians from the Boston Biomedical Research Institute and the University of Minnesota Medical School. Their findings appear in the online edition of Nature Medicine.
The team began by engineering a protein with the same structure as the binding site of the T-cell receptor targeted by SEB. The researchers expressed the engineered protein on the surface of yeast cells (using a process they helped develop, called "yeast display") and generated mutations meant to increase the protein's ability to bind SEB. After several rounds of mutagenesis and screening, graduate student Rebecca A. Buonpane developed a soluble protein with an affinity for SEB that was over a million times that of the original.
"Our approach was to take these receptors that bind to the toxins and to try to make them higher affinity and therefore act as effective neutralizing agents when delivered in soluble form," Kranz said. "It's the binding of the toxin to T-cells that is critical. If you can prevent the toxin from binding to the T-cell receptor then you can prevent it from initiating that cascade."
The engineered protein prevented the onset of symptoms in rabbits exposed to SEB and reversed the course of the illness in those treated two hours after exposure.
"We were very pleasantly surprised that it showed effectiveness in every rabbit tested," Kranz said.
He noted that the protein has some potential advantages and disadvantages when compared to antibodies, which might also be used to fight infection with SEB. One advantage is that the engineered protein is small, about one-tenth the size of an antibody. Its size may allow it to penetrate deeper into tissues, and may make it less likely to spark an immune response in animals. The protein can also be produced in large quantities using the bacterium, Escherichia coli.
"E. coli is the cheapest source for making proteins," Kranz said. "Whenever you can express a protein in E. coli you do so because it is inexpensive, easy and fast."
Antibodies, on the other hand, can remain in the body for days or weeks, whereas the new protein is cleared within hours. This may make antibodies a better treatment option in some circumstances, said Kranz.
No antibody has yet been developed, however, that has a comparable affinity for SEB.
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These studies were supported by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.
Kranz is also affiliated with the Institute for Genomic Biology and the College of Medicine. Biochemistry at the U. of I. is in the School of Molecular and Cellular Biology.
Pollutants, food ingredients, solvents may all cause harm, researchers say.
By Alan Mozes HealthDay Reporter
MONDAY, May 14 (HealthDay News) -- A detailed analysis of hundreds of completed breast cancer studies has linked disease development with environmental exposure to more than 200 chemical compounds.
The finding is part of an effort to build a free, online breast cancer database for researchers and the public.
Described as "the most comprehensive of its kind," the database will highlight growing concern about environmental carcinogens such as pollutants, food contaminants, and organic solvents. The scope of the project will also extend to work that explores risk-related lifestyle factors such as diet, levels of physical activity, smoking/drinking habits and body mass.
"This compilation is a great effort, because it summarizes all the evidence and gives us hints of what to look for next," explained researcher Leslie Bernstein, a professor of preventive medicine with the Keck School of Medicine at the University of Southern California in Los Angeles.
The results are outlined in a supplement to the May 14th online issue of Cancer. The database is already accessible at either www.silentspring.org/sciencereview or www.komen.org/environment.
According to the American Cancer Society (ACS), carcinogens are defined as agents that instigate abnormal cell division or harmful changes in the structure of a cell's DNA. They include chemicals, radiation, or infectious agents, among other things.
The ACS also notes that with the exception of skin cancer, breast cancer is the most common cancer among American women. This year, almost 179,000 women in the United States will be diagnosed with the disease, and about 40,000 will die.
The International Agency of Research on Cancer has already classified 90 or so compounds as human carcinogens, according to the ACS. But Bernstein's team said that most of the chemicals to which people are routinely exposed have not undergone any testing for carcinogenic risk. An estimated 80,000 chemicals are registered in the United States for commercial use, according to the researchers.
For more than two years, Bernstein worked alongside colleagues from Harvard University, the Roswell Park Cancer Institute, and the Silent Spring Institute to amass and sort through approximately 900 national and international breast cancer studies focused on carcinogens.
The team honed in on 460 human breast cancer studies, of which more than 150 looked at specific environmental carcinogens among breast cancer patients. Most of those studies were conducted in the 1990s.
The remaining studies involved animal or laboratory research. The researchers pointed out that animal studies are valid references, because all known human carcinogens have also triggered tumors in animal subjects.
In the animal studies alone, evidence surfaced that linked 216 chemicals to the onset of breast tumors. These included 36 industrial chemicals, 6 chlorinated solvents, 18 products of combustion, 10 pesticides, 18 dyes, four type of radiation, 47 pharmaceuticals, and 17 hormones.
Of these compounds, the researchers isolated 73 that can be found in either human food or consumer products.
They noted, for example, the lingering hazards associated with polychlorinated biphenyls (or PCBs), which were typically used in the production of electrical equipment until federally banned in 1979. PCBs continue to pose a risk via contaminated rivers, fish, and pre-existing building construction, the researchers warned.
In addition, the authors categorized 35 compounds as carcinogenic air pollutants, including polycyclic aromatic hydrocarbons (or PAHs), which are byproducts of combustion.
The team also drew attention to another group of 25 organic compounds, including dioxins, which are produced by waste incineration and manufacturing. These carcinogenic chemicals are present in many American workplaces and place more than 5,000 women at an increased risk for breast cancer, the researchers said. These include women working in machine shops, dry cleaners, hairdressers, glass manufacturers, and aircraft maintenance facilities, all of which use harmful organic solvents.
Furthermore, among the identified carcinogens, 29 are produced in large amounts -- upwards of one million pounds or more per year.
The database project did not set strict guidelines as to how to limit exposure to carcinogens. But the authors said they encouraged research and government oversight into the problem. They advised that people do try and limit their exposure to PCB-contaminated fish, gasoline-generated air pollution, chlorinated tap water, non-stick coated cookware, and detergents containing fluorescent whiteners.
Just how carcinogenic, in terms of breast cancer risk, are these and other compounds on the list? The jury is still out on that question, Bernstein said.
"Women are terribly concerned about environmental causes of breast cancer," she said. "But it's really very difficult to study. Often the only way we've been able to look at some of these things is during occupational exposures or accidents -- what we usually call disasters."
"So, this work is a very useful tool for those of us who want to try to understand what we've missed in breast cancer. Now, it's up to us to do something with all this information," Bernstein said.
Janet Gray, a professor of psychology and the director of the program in science, technology and society at Vassar College in Poughkeepsie, N.Y., called the new database "an enormous contribution."
"Its greatest value is just the sheer comprehensive nature of the work, which allows both the public and researchers to have access to huge amounts of information in one place," she said. "I think this effort will really move us forward."
Known and Probable Carcinogens
Including Industrial Processes, Occupational Exposures, Infectious Agents, Chemicals, and Radiation)
What Is a Carcinogen?
Cancer is caused by abnormalities in a cell’s DNA (its genetic "blueprint"). These may be inherited from parents, or they may be caused by outside exposures to the body such as chemicals, radiation, or even infectious agents.
Substances that can cause changes that can lead to cancer are called carcinogens. Some carcinogens do not act on DNA directly, but lead to cancer in other ways, such as causing cells to divide at a faster rate, which could increase the chances that DNA changes will occur.
Carcinogens do not cause cancer in every case, all the time. Substances classified as carcinogens may have different levels of cancer-causing potential. Some may cause cancer only after prolonged, high levels of exposure. And for any particular person, the risk of developing cancer depends on many factors, including the length and intensity of exposure to the carcinogen and the person’s genetic makeup.
How Do We Determine if Something Is a Carcinogen? Scientists get much of their data about whether something might cause cancer from laboratory (cell culture and animal) studies. Although it isn’t possible to predict with certainty which substances will cause cancer in humans based on animal studies alone, virtually all known human carcinogens that have been adequately tested produce cancer in lab animals. In many cases, carcinogens are first found to cause cancer in lab animals and are later found to cause cancer in people. Because there are far too many substances (natural and manmade) to test each one in lab animals, scientists use knowledge about chemical structure, other types of lab tests, and information about the extent of human exposure to select chemicals for testing.
Most studies of potential carcinogens expose the lab animals to doses that are higher than common human exposures. This is so that cancer risk can be detected in relatively small groups of animals. For most carcinogens, it is assumed that those that cause cancer at larger doses in animals will also cause cancer in people. Although it isn’t always possible to know the relationship between exposure dose and risk, it is reasonable for public health purposes to assume that lowering human exposure will reduce risk.
Another important way to identify carcinogens is through epidemiologic studies, which look at human populations to determine which factors might be linked to cancer. While these studies also provide useful information, they also have their limitations. Humans do not live in a controlled environment. People are exposed to numerous substances at any one time, including those they encounter at work, school, or home; in the food they eat; and the air they breathe. And it is usually many years (often decades) between exposure to a carcinogen and the development of cancer. Therefore, it can be very hard to single out any particular exposure as having a definite link to cancer.
By combining data from both types of studies, scientists are able to make an educated assessment of a substance’s cancer-causing ability. When the available evidence is compelling but not felt to be conclusive, the substance may be considered to be a probable carcinogen.
How Are Carcinogens Classified?
International Agency for Research on Cancer (IARC)
The most widely used system for classifying carcinogens comes from the IARC, which is part if the World Health Organization (WHO). In the past 30 years, the IARC has evaluated the cancer-causing potential of about 900 likely candidates, placing them into one of the following groups:
Group 1: Carcinogenic to humans
Group 2A: Probably carcinogenic to humans
Group 2B: Possibly carcinogenic to humans
Group 3: Unclassifiable as to carcinogenicity in humans
Group 4: Probably not carcinogenic to humans
Perhaps not surprisingly, most of the agents are of probable, possible, or unknown risk. Only about 90 are classified as "carcinogenic to humans."
National Toxicology Program (NTP)
In the United States, the NTP releases the Report on Carcinogens about every 2 years. The NTP is formed from parts of several different government agencies, including the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), and the Food and Drug Administration (FDA).
The Report on Carcinogens (RoC) identifies 2 groups of agents:
"Known to be human carcinogens"
"Reasonably anticipated to be human carcinogens"
Unlike the IARC’s list, the RoC does not list substances that have been studied and found not to be carcinogens. Below are the lists of known and probable human carcinogens from both groups.
Known Human Carcinogens
International Agency for Research on Cancer (IARC) "Carcinogenic to Humans" (Group 1)
Agents and Groups of Agents
Aflatoxins (naturally occurring mixtures of)
4-Aminobiphenyl
Arsenic and arsenic compounds (Note: This evaluation applies to the group of compounds as a whole and not necessarily to all individual compounds within the group)
Estrogens, nonsteroidal (Note: This evaluation applies to the group of compounds as a whole and not necessarily to all individual compounds within the group)
Estrogens, steroidal (Note: This evaluation applies to the group of compounds as a whole and not necessarily to all individual compounds within the group)
Ethylene oxide
Etoposide in combination with cisplatin and bleomycin
Formaldehyde
Gallium arsenide
Gamma radiation
Helicobacter pylori (infection with)
Hepatitis B virus (chronic infection with)
Hepatitis C virus (chronic infection with)
Herbal remedies containing plant species of the genus Aristolochia
Human immunodeficiency virus type 1 (infection with)
Human papillomavirus type 16
Human papillomavirus type 18
Human T-cell lymphotropic virus type I
Melphalan
8-Methoxypsoralen (Methoxsalen) plus ultraviolet A radiation
MOPP and other combined chemotherapy including alkylating agents
Mustard gas (Sulfur mustard)
2-Naphthylamine
Neutrons
Nickel compounds
Opisthorchis viverrini (infection with)
Oral contraceptives, combined (Note: There is also conclusive evidence that these agents have a protective effect against cancers of the ovary and endometrium)
Oral contraceptives, sequential
Phosphorus-32, as phosphate
Plutonium-239 and its decay products (may contain plutonium-240 and other isotopes), as aerosols
Radioiodines, short-lived isotopes, including iodine-131, from atomic reactor accidents and nuclear weapons detonation (exposure during childhood)
Radionuclides, alpha-particle-emitting, internally deposited (Note: Specific radionuclides for which there is sufficient evidence for carcinogenicity to humans are also listed individually as Group 1 agents)
Radionuclides, beta-particle-emitting, internally deposited (Note: Specific radionuclides for which there is sufficient evidence for carcinogenicity to humans are also listed individually as Group 1 agents)
Radium-224 and its decay products
Radium-226 and its decay products
Radium-228 and its decay products
Radon-222 and its decay products
Schistosoma haematobium (infection with)
Silica, crystalline (inhaled in the form of quartz or cristobalite from occupational sources)
Solar radiation
Talc containing asbestiform fibers
Tamoxifen (Note: There is also conclusive evidence that this agent (tamoxifen) reduces the risk of contralateral breast cancer)
2,3,7,8-Tetrachlorodibenzo-para-dioxin
Thiotepa
Thorium-232 and its decay products, administered intravenously as a colloidal dispersion of thorium-232 dioxide
Treosulfan
Vinyl chloride
X- and Gamma radiation
Mixtures
Alcoholic beverages
Analgesic mixtures containing phenacetin
Areca nut
Betel quid with tobacco
Betel quid without tobacco
Coal-tar pitches
Coal-tars
Mineral oils, untreated and mildly treated
Salted fish (Chinese-style)
Shale-oils
Soots
Tobacco products, oral tobacco products
Wood dust
Exposure Circumstances
Aluminum production
Arsenic in drinking water
Auramine, manufacture of
Boot and shoe manufacture and repair
Coal gasification
Coke production
Furniture and cabinet making
Hematite mining (underground) with exposure to radon
