Tuesday, July 29, 2014

A former hepatitis virus researcher reminisces on the progress made and challenges remaining in the fight to eradicate chronic viral hepatitis.



WHD_2013_Campaign_poster
World Health Alliance World Hepatitis Day 2014 Campaign Poster
July 28, 2014.  “Hepatitis: Think Again.”  That is the motto for this year’s World Hepatitis Day, a program championed by the World Hepatitis Alliance to raise awareness, encourage prevention, and improve access to treatment for viral hepatitis.  The World Health Organization (WHO) endorsed the global recognition of this event in 2010.  Chronic viral hepatitis has been called a “silent killer” since often no symptoms are apparent until a life-threatening condition develops.
Hepatitis refers to liver inflammation, which is frequently caused by infection with a number of unrelated liver viruses 

Hepatitis refers to liver inflammation, which is frequently caused by infection with a number of unrelated liver viruses termed hepatitis viruses A-E.  The hepatitis viruses A (HAV) and E (HEV) are generally self-limiting causes of food poisoning, while infection with the blood-borne hepatitis B (HBV) or C viruses (HCV) can lead to chronic hepatitis, which may cause long-term cirrhotic damage, end-stage liver disease, and hepatocellular carcinoma (HCC).  Hepatitis D (HDV) exacerbates HBV infections.  It is only observed in HBV-infected individuals, and not in isolation, since it requires the HBV coat protein to replicate.
Hepatitis B
About a third of the people on the planet have been infected with HBV at one time or another and there are an estimated 360 million people chronically infected with hepatitis B (WHO Weekly epidemiological record). This highly-infectious DNA virus is easily spread from blood, blood products or sexual intercourse, but not from causal contact, like hugging or kissing. Routine serological testing has screened it out of blood since the late 60s.  In highly endemic regions, such as China, the virus is predominantly spread perinatally, whereas in the developed world, anti-HBV immunoglobulin (HBIG) treatment is routinely used to block that transmission, followed by vaccination of the newborns.  Most of the new hepatitis B cases seen in the US and in other developed nations can be traced to preexisting infections in immigrants from Asia, the Pacific Islands, and from several other low-moderate income countries (CDC Viral Hepatitis Facts).

A blood-derived HBV vaccine was being used by the late 70s; while the recombinant DNA-based version of this vaccine widely-used today was introduced in the 80s.  This vaccine is amongst the most widely-used, efficacious, and safest products that biotechnology has created.  HBV infection is the major cause of HCC development, so this vaccine is also considered the first anti-cancer vaccine.  Approximately one third of newborns worldwide are being vaccinated against HBV today and this appears to generate life-long immunity against the virus (WHO Weekly epidemiological record).  Numerous long-term clinical studies have found no evidence of any serious adverse event or disease association linked to the use of this vaccine (WHO Weekly epidemiological record).
Nucleosides are the mainstay of HBV therapy and the latest versions of these molecules are generally well-tolerated and quite effective at completely suppressing the virus.  Yes, rare exceptions due to viral mutations and other underlying comorbid and psychosociological conditions do complicate this.  And, in addition, the hardy nature of the HBV covalently-closed circular (cccDNA) genome necessitates long-term use of these drugs to keep the virus suppressed, but HBV antivirals generally work well.
Hepatitis C
Virtually all of the non-A, non-B post-transfusion hepatitis described years ago in textbooks were found to be attributable to HCV after its RNA genome was cloned in the late 80s.  It is estimated that there are 180 million people chronically-infected with HCV.  Detection is routine and the virus is therefore largely screened out of the world’s blood supply.  But individuals who have received blood or blood products before this time may have inadvertently contracted HCV.  HCV is less transmissible than HBV and usually involves direct injection of blood or blood-products into the bloodstream and monogamous heterosexual couples have a low risk of contracting it from an infected mate (CDC Hepatitis C Information for Health Professionals).  Most of the HCV transmission today in the developed world is among intravenous drug users, while those who experimented even only once with injectable drugs are at risk of being infected (CDC Viral Hepatitis Statistics & Surveillance).
There is no vaccine for HCV and there is no expectation that an effective vaccine will be available anytime soon.
While HCV has caused a lot of hurt and suffering in the world, it turns out that the virus itself is a wimp. In fact, HCV infection is the only chronic viral infection that can be cured using antiviral agents.  Every few years a new generation of HCV antivirals emerges with better cure rates— but at a greater expense. The latest treatment regimens using Direct Acting Antivirals claim 90% cure rates— and a near $100,000 treatment pricetag ($1,000 per pill).  The WHO guidelines and recommendations for healthcare providers in low- to middle-income countries regarding hepatitis C released this year addresses the challenges faced in the management of this disease with limited economic resources.
Summary
Tremendous strides have been made in the past generation to identify, prevent and cure chronic viral hepatitis, but with over half a billion people infected with HBV and HCV worldwide, it remains a major public health issue—the biggest problem continues to be that most people don’t know that they are infected. The motto for this year’s World Hepatitis Day reemphasizes how critical it is for anyone with a risk factor for HBV or HCV infection to be tested because the battle against viral hepatitis is being won, but the war is not over.

The Radiant Creations Group, Inc. (RCGP) Announces Nucleotide Technologies "Spinoff"


PALM BEACH GARDENS, FL--(Marketwired - July 28, 2014) - The Radiant Creations Group, Inc. ("Radiant") (OTCQB: RCGP), developer of unique, proprietary scientific technologies and cosmetic and over-the-counter products and devices, is pleased to announce at its regularly scheduled Board meeting held on July 3, 2014 the Directors agreed to "spinoff" the Company's exclusive license agreement with Dr. Yin-Xiong Li, MD, Ph.D. The new Company name will be NIT Enterprises, Inc. (Nucleotide Industrial Technologies). The Exclusive license agreement includes patented and patent-pending technologies for the development of innovative nucleotide technologies or nucleic acid (NA) code molecules, applications for the technologies to be directed at industrial facilities, medical facilities, hospitals, the welding industry and military and homeland security markets.
Nucleotides are any of a group of molecules that, when linked together, form the building blocks of DNA or RNA: composed of a phosphate group, the bases adenine, cytosine, guanine, and thymine, and a pentose sugar. ("http://dictionary.reference.com/browse/nucleotide")
After a decade and a half of intense genetic research by Dr. Yin-Xiong Li, MD, Ph.D., the true capability of nucleic acid code molecules were discovered and brought to a commercially exploitable state through one granted patent and one applied patent, to be exclusively licensed to NIT.
Gary Smith, CEO, Radiant, stated, "This discovery ranks as one of the most profound and valuable discoveries for almost limitless technological enhancement in industrial, medical and the chemical development. The potential revenues to be generated by commercialization of these exclusive NA technologies can be exploited through manufacturing NA as a raw material, and licensing production for a myriad of applications which are also expected to generate significantly more intellectual property enhancements."
Radiant's exclusive license included documentation that concluded, NA free of the DNA ladder has been shown to protect against the harmful effects of Ultraviolet light (UV) radiation across a wide band of UV spectrum. NA performs its unique function when it is free to react with photons and UV rays. When a damaging UV photon hits a freed NA molecule, it is absorbed and then re-emitted as a harmless infrared (heat) photon into the atmosphere. The NA may remain undamaged and continues to perform its protective function.
Proposed applications and future testing to include identifying methods to enhance protection from ionizing radiation such as X-Rays and Gamma Rays providing NIT with effective solutions to reduce the impact of radiation, thus creating a market for protecting government and institutional public buildings, hospitals, clinics, dentist and doctor's offices and industrial facilities; anywhere there is use of ionizing radiation.
Shareholders of record of The Radiant Creations Group, Inc. (RCGP) will receive (proportionally) shares of NIT Enterprises, Inc. following the completion and effectiveness of the required SEC filings. The Company will announce the Record date for the issuance of "spinoff" shares upon completion of required legal compliance.
About The Radiant Creations Group, Inc. (RCGP) (www.radiantcreations-rcgp.com)
Radiant Creations has achieved exciting breakthroughs creating remarkable products in skin protection and hydration, anti-aging, liver health and weight balance by combining DNA derived technologies developed in the Western World and naturally acting traditional Chinese medicine ingredients believed never before used in western culture by any bioscience company.
Among these exciting discoveries is a new and superior mechanism of defense against skin deterioration and damage caused by sun exposure to ultraviolet (UV) light using the nucleotides, four "code molecules" extracted from DNA. This revolutionary mechanism also has great significance and value in many other cosmetic and non-cosmetic applications requiring UV protection, and is among Radiant Creations' licensed intellectual property. The technology will be implemented across numerous innovative product lines.
About NIT Enterprises, Inc. (NIT) (www.NITEnterprises.com)
NIT Enterprises, Inc. (d/b/a Nucleotide Industrial Technologies) (NIT) was created to improve public safety and to provide a new measure of protection for commercial, industrial, and personal products that enhance the longevity of living and non-living substances based upon unique proprietary NA technologies developed by our award winning scientist and technology team. This new technology is the infusion of ingredients, known as nucleotides, into a multiplicity of common products enhanced by their presence. The Nucleotides were derived by atomic level research that demonstrates their ability to provide Ultraviolet (UV) rays screening capability at the molecular level.
Cautionary Statement Concerning forward-Looking Statements:
This press release contains forward-looking statements that can be identified by words such as "anticipates," "intends," "plans," "seeks," "believes," "estimates," "expects" and similar references to future periods.
Forward-looking statements are based on our current expectations and assumptions regarding our business, the economy and other future conditions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that are difficult to predict. Our actual results may differ materially from those contemplated by the forward-looking statements. We caution you therefore against relying on any of these forward-looking statements. They are neither statements of historical fact nor guarantees or assurances of future performance. Any forward-looking statement made by us in this press release speaks only as of the date on which it is made. Factors or events that could cause our actual results to differ may emerge from time to time, and it is not possible for us to predict all of them. We undertake no obligation to publicly update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by law.
Corporate Contact Information:
The Radiant Creations Group, Inc.
Harbour Financial Center
2401 PGA Boulevard, Suite 280-N
Palm Beach Gardens, FL 33410
Phone: 561-283-4740
Investor Relations:
Gary D. Alexander
Corporate Secretary
Email: G.Alexander@RadiantCreationsGroup.com

Forced mutations doom HIV

CAMBRIDGE, MA -- Fifteen years ago, MIT professor John Essigmann and colleagues from the University of Washington had a novel idea for an HIV drug. They thought if they could induce the virus to mutate uncontrollably, they could force it to weaken and eventually die out — a strategy that our immune system uses against many viruses.
The researchers developed such a drug, which caused HIV to mutate at an enhanced rate, as expected. But it did not eliminate the virus from patients in a small clinical trial reported in 2011. In a new study, however, Essigmann and colleagues have determined the mechanism behind the drug's action, which they believe could help them develop better versions that would destroy the virus more quickly.
This type of drug could, they say, help combat the residual virus that remains in the T cells of patients whose disease has been brought into long-term remission by the triple-drug combination typically used to treat HIV. These viruses re-emerge periodically, which is why patients must stay on the drug cocktail indefinitely and are not considered "cured."
"This has really been the biggest problem in HIV," says Essigmann, the William R. and Betsy P. Leitch Professor of Chemistry, Toxicology, and Biological Engineering at MIT. "What we would hope is that over a long period of time on this type of therapy, a person would potentially have their latent pool mutated to the extent that it no longer causes active disease."
In the new study, which appears in the Proceedings of the National Academy of Sciences (PNAS) the week of July 28, the researchers discovered exactly how the drug, known as KP1212, induces the HIV genome to mutate. The paper's lead authors are MIT postdocs Deyu Li, Bogdan Fedeles, and Vipender Singh, along with recent MIT PhD graduate Chunte Sam Peng. Essigmann and Andrei Tokmakoff, a former MIT professor who is now at the University of Chicago, are the paper's senior authors.

Too much mutation

After HIV infects a cell, it rapidly begins making copies of its genetic material. This copying is very error-prone, so the virus mutates swiftly. This usually helps the virus survive by allowing it to evade both the immune system and human-made drugs. However, at a conference in the late 1990s, Essigmann learned from an evolutionary biologist that if the virus could be forced to double its mutation rate, it would no longer be able to produce functional proteins.
Essigmann and Lawrence Loeb, a professor of biochemistry at the University of Washington, started working together to exploit this idea. Essigmann had been developing compounds that mimic natural nucleotides — the A, C, T, and G "letters" that form DNA base pairs — but that induce genetic mutations by binding with the wrong partner. Loeb is an expert on polymerases, the enzymes that string nucleotides together to form DNA or RNA.
Together with James Mullins, an immunology professor and HIV expert at the University of Washington, Essigmann and Loeb designed a molecule called 5-hydroxycytosine, described in a 1999 PNAS paper. When given to HIV-infected cells grown in the lab, this molecule was incorporated into the viral genome in place of the natural form of cytosine. Within 25 viral replication cycles, HIV populations in those infected cells collapsed.
The researchers then formed a company, Koronis Pharmaceuticals, which developed KP1212, a compound that is 100 times more mutagenic than 5-hydroxycytosine. In a four-month clinical trial of 32 patients, mutations accumulated in the patients' viral DNA, but not enough to induce a population crash. The drug was also found to be safe: It did not mutate the patients' own DNA, in part because the drug was designed so that human forms of DNA polymerase could not accept it.

Shape-shifting molecules

In the new PNAS paper, the researchers used advanced spectroscopy techniques to analyze KP1212's ability to promote tautomerism, a chemical phenomenon that involves the migration of protons among the nitrogen and oxygen atoms on nucleic-acid bases. This allowed the researchers to see that once KP1212 inserts itself into the genome, it can switch among five different shapes, or tautomers. Some of these behave like cytosine, by pairing with guanine. However, some of the tautomers resemble thymine, so they will pair with adenine, introducing mutations.
"The five molecules are changing shape on a nanosecond timescale, and each shape has a different base-pairing property, so you will see a promiscuity in terms of the bases with which KP1212 pairs," Singh says.
To see this shape-shifting, the researchers used NMR and a form of 2-D infrared spectroscopy developed by Tokmakoff. This technology allows scientists to determine the atomic composition and structure of nucleic-acid bases.
Then, using a genetic tool developed in the Essigmann lab, the researchers determined that KP1212 induces a mutation rate of exactly 10 percent in the HIV genome. Based on these findings, Essigmann estimates that if KP1212 doubles the mutation rate of HIV, it could clear the virus from patients in one to two years.
He says that Koronis hopes to run a longer trial of KP1212 and is also interested in developing drugs that would work faster, which could be accomplished by altering some of the chemical features of the molecule and testing whether they speed up the mutation rate.
The paper also identified other factors that scientists could manipulate to improve the drug's performance.
"There are other variables that are important to calculate the time it would take to eradicate a virus," Fedeles says. "That includes the concentration that the drug needs to achieve inside the cell, and the ability of a cell to convert the nucleoside, the molecule without the phosphate, to the triphosphate version, which is the one incorporated by the polymerase."
"We're building up a new strategy that can give us a lot of insights into how to design a new molecule," Li says. "It's a new toolset for developing future drugs. Those drugs are not limited to HIV. They could be candidates for dengue fever, or some other viruses such as yellow fever."
Ribavirin, a drug used to treat hepatitis C, and the influenza drug T-705 are also believed to provoke hypermutation in their target viruses. The MIT team also plans to work with Loeb to test the possibility of using similar compounds to force tumor cells to mutate themselves into extinction.


HIV virus removed from cells for first time


HIV, resistant, Human Immunodeficiency Virus, gay news, Washington Blade, cure
A team of researchers at Temple University for the first time developed a way to extract HIV from human cells in a lab setting. (Public domain image of a scanning electron micrograph of HIV-1 budding, in green, from cultured lymphocyte by the CDC/C. Goldsmith, P. Feorino, E.L. Palmer and W.R. McManus)
A team of researchers at Temple University in Philadelphia for the first time developed a way to extract the HIV virus from human cells in a laboratory setting, opening the way for further studies that could lead to a cure for AIDS.
In a study published July 21 in the journal Proceedings of the National Academy of Sciences, researchers said they developed a “DNA-snipping enzyme” called nuclease and a strand of RNA capable of targeting and removing the DNA of the HIV-1 virus from human cells.
“From there, the cell’s gene repair machinery takes over, soldering the loose ends of the genome back together – resulting in virus-free cells,” according to a statement released by the Temple University School of Medicine. A genome refers to the genetic material in cells.
- See more at: http://www.washingtonblade.com/2014/07/28/hiv-virus-removed-cells-first-time/#sthash.Wk634zOt.dpuf


“This is one important step on the path toward a permanent cure for AIDS,” said Kamel Khalili, professor and chair of the Department of Neuroscience at Temple and the lead researcher in the HIV “removal” finding. “It’s an exciting discovery, but it’s not yet ready to go into the clinic,” Khalili said in the statement released by the Temple medical school. “It’s proof of a concept that we’re moving in the right direction.” Khalili, who heads a team of researchers that worked on the study, noted that since the human immune system cannot now remove HIV-1, a means of removing the virus through medical intervention is needed to find a cure for AIDS. His research team found that the technique they developed to extract HIV-1 from cells might also work as a “therapeutic vaccine.” Cells treated with the nuclease-RNA combination they developed “proved impervious to HIV infection,” the Temple statement says. The statement points out that although anti-retroviral drugs are highly effective in controlling HIV-1 for infected people, the virus remains hidden in the body’s cells and can replicate in large numbers and cause serious health consequences if treatment is interrupted. While promising, the new technique to remove HIV-1 from human cells faces a number of challenges before the technique is ready for patients, Khalili said in the statement. Among other things, he said researchers must develop a method to deliver the therapeutic agent to every infected cell as well as a means to countering the ability of HIV to mutate. “We are working on a number of strategies so we can take the construct into preclinical studies,” he said. “We want to eradicate every single copy of HIV-1 from the patient. That will cure AIDS. I think this technology is the way we can do it. - See more at: http://www.washingtonblade.com/2014/07/28/hiv-virus-removed-cells-first-time/#sthash.Wk634zOt.dpuf

Stress-tolerant tomato relative sequenced


Wild tomato species are not edible, but they can be bred with domestic tomatoes to introduce new traits such as flavor and drought resistance. A new genome sequence for wild...
The genome of Solanum pennellii, a wild relative of the domestic tomato, has been published by an international group of researchers including the labs headed by Professors Neelima Sinha and Julin Maloof at the UC Davis Department of Plant Biology. The new genome information may help breeders produce tastier, more stress-tolerant tomatoes.
The work, published July 27 in the journalNature Genetics, was lead by Björn Usadel and colleagues at Aachen University in Germany. The UC Davis labs carried out work on the transcriptome of S. pennellii — the RNA molecules that are transcribed from DNA and then translated into proteins — messages written from DNA and taken to other parts of the cell to tell it what to do. Analyzing the RNA transcriptome shows which genes are active under different circumstances. The UC Davis team published a paper last year comparing the RNA transcripts of domestic tomato and three wild relatives, including S. pennellii.
S. pennellii is inedible, but it can be interbred with domestic tomatoes to introduce useful traits, such as drought resistance. Using the new genome data, the researchers found genes related to dehydration resistance, fruit development and fruit ripening. They also found genes that contribute to volatile compounds related to fruit scent and flavor.

Monday, July 28, 2014

Gene research targets scarring process

One is known to promote collagen (what scars are made of) production in the gut and another in the tendons, while the third aids tissue development in the hands, arms and heart.One is known to promote collagen (what scars are made of) production in the gut and another in the tendons, while the third aids tissue development in the hands, arms and heart.iStock
SCIENTISTS have identified three genes that may be the key to preventing scar formation after burn injury, and even healing existing scars.
In a world-first study, researchers at UWA's Burn Injury Research Unit found changes in the DNA and RNA of scarred skin cells compared to healthy ones.
They say treatments targeted at these genes could reverse the process that leads to scars being retained as the body makes new cells over its lifespan.
The researchers compared samples from burnt forearms of six patients to samples from the same sites on their undamaged arms with methylation and gene arrays to look for epigenetic changes—inheritable changes to the DNA other than to the DNA sequence itself.
Tissue is built when proteins bind to DNA and get a blueprint in the form of RNA that tells cells to build skin, hair, bone or muscle in a certain way.
Methylation is where methyl groups are added to the DNA at specific sites, stopping them being read by the proteins.
The researchers found burn injury changes this process, causing lasting effects to the tissue created.
Methylation analysis of the DNA identified 3298 methylation sites (out of 485,000) on 398 genes to have altered methylation patterns compared to the controls.
Gene expression analysis of the RNA showed 113 genes that were turned on or off differently to controls.

Scientists hone in on controller genes

Lead researcher, PhD student Andrew Stevenson, says the 113 RNA and 398 DNA altered genes had 14 genes in common and the team chose three for further study that they believe are most involved in the process and most promising for treatment.
"These controller genes are sent off to be made again and again in a positive feedback loop, so small changes can have big effects downstream and can also activate other genes," he says.
One is known to promote collagen (what scars are made of) production in the gut and another in the tendons, while the third aids tissue development in the hands, arms and heart.
"Our techniques right now are quite crude, cutting out scars and shooting lasers into the tissue to make it heal faster and minimise scarring, so this could have big implications for future care," Mr Stevenson says.
"No one has looked at scar tissue at a genetic level before and we are using equipment and tests that have only been around about five years and mostly used to study cancer."

The Cancer Genome Atlas researchers identify

The Cancer Genome Atlas (TCGA) Network researchers have found that stomach cancers fall into four distinct molecular subtypes. In the study, published online July 23, 2014, in Nature, the scientists report that this discovery could change how researchers think about developing treatments for stomach cancer, also called gastric cancers or gastric adenocarcinomas.

Instead of considering gastric cancer as a single disease, as has been done in the past, researchers will now be able to explore therapies in defined sets of patients whose tumours have specific genomic abnormalities. Stomach cancers are a leading cause of cancer-related mortality worldwide, resulting in an estimated 723,000 deaths annually.

Previous attempts to examine the clinical characteristics of gastric cancer were hindered by how differently cancer cells can look under a microscope, even when from the same tumour. The researchers hope that the new classification system will serve as a valuable adjunct to the current pathology classification system, which has two categories: diffuse and intestinal.

“A key advance with this project is that we have identified and developed a much more useful classification system to find groups of gastric cancer that have distinct molecular features, and at the same time, we also identified key targets to pursue in different groups of patients,” said Adam Bass, M.D., Harvard Medical School, Dana-Farber Cancer Institute, the Broad Institute, Boston, and one of the lead investigators on the project. “This will provide a strong foundation for categorising the disease and for doing so in a way in which we can develop clinical trials based on some of the critical molecular alterations that are driving different classes of cancers.”

The researchers identified the new subgroups through complex statistical analyses of molecular data from 295 tumours. They used six molecular analysis platforms including DNA sequencing, RNA sequencing, and protein arrays.

tumours in the first group, which represented 9 per cent of the tumours, were positive for Epstein-Barr virus (EBV) and had several other molecular commonalities. tumours in a second subgroup (22 percent of the tumours) had high microsatellite instability (MSI), which is the tendency for mutations to accumulate in repeated sequences of DNA. The remaining subgroups differed in the level of somatic copy number alterations (SCNAs), which can result from duplication or deletion of sections of the genome. The tumours in the third subgroup, which comprised 20 per cent of the tumours, were considered to have a low level of SCNAs and were called genomically stable. The remaining 50 per cent of tumours were classified as chromosomally unstable, with a high level of SCNAs.

The EBV-positive subgroup of tumours was of particular interest. EBV is best known in the United States as the cause of infectious mononucleosis, which is characterised by fever, sore throat, and swollen lymph glands, especially in the neck. EBV is also suspected of causing certain cancers, including nasopharyngeal carcinoma and some types of lymphoma. Previous research had shown that EBV can be detected in a minority of gastric adenocarcinomas and that EBV genes are expressed in those tumours. However, this study found that the presence of EBV in gastric tumours is associated with a number of other molecular characteristics.

First, the researchers observed that EBV-positive tumours displayed a high frequency of mutations in the PIK3CA gene, which codes for a component of a protein, PI3-kinase, which is essential for cell growth and division and many other cellular activities that are important in cancer. Although 80 per cent of EBV-positive tumours harbored a protein-changing alteration in PIK3CA, PIK3CA mutations were found in 3 percent to 42 per cent of tumours of the other gastric cancer subtypes. The scientists suggested that EBV-positive tumours might respond to PI3-kinase inhibitors, some of which are in the early stages of testing in clinical trials but are not yet approved by the US Food and Drug Administration for general use.

Some tumours in the EBV-positive subgroup also showed more gene copies being produced in a chromosomal region that contains the JAK2 gene. The JAK2 protein facilitates cell growth and division, and the increased expression of JAK2 may inappropriately activate cell growth. The amplified region also contains the genes for two proteins, PD-L1 and PD-L2, which suppress immune responses; their increased expression may help tumours escape destruction by the immune system. The investigators suggested that these findings support the evaluation of JAK2 inhibitors and PD-L1/2 antagonists for the treatment of EBV-positive gastric cancers.

And the EBV-positive subgroup showed a far higher prevalence of DNA hypermethylation than any other cancer subtype reported by TCGA researchers. Methylation is the process of adding methyl groups to DNA, which reduces gene expression. Hypermethylation occurs when this mechanism continues aberrantly, quieting genes that should be active. In the EBV-positive tumour subgroup, hypermethylation was most often observed in the promoter regions of genes, which would prevent the expression of the genes.

"Gaining these insights into the connection between EBV and gastric cancer is the type of groundbreaking research that NIH is pleased to be a part of. We look forward to the potential clinical implications of this discovery," said NIH Director Francis S. Collins, M.D., Ph.D. “This study reinforces the value of the approach we are using to study genomic diversity and similarity among tumours of many different cancer types,” said NCI Director Harold Varmus, M.D. “Only such a systematic analysis could have yielded observations about the association between EBV and several provocative molecular characteristics.”

Important insights also came from analyses of the three other gastric cancer subgroups. For example, tumours of the genomically stable subtype contained frequent mutations in a gene called RHOA, whose product interacts with other cellular proteins to help cells change shape and migrate, which may be important in tumour growth. This finding suggests possible targets for treating tumours of this subtype. And tumours of the chromosomal unstable subtype contained frequent amplifications of genes that encode receptor proteins on the outside of the cell, leading to the promotion of aberrant cell growth. Drugs are already available to curb the activity of some of these proteins.

“This most recent TCGA study again demonstrates the importance of its comprehensive design,” said NHGRI Director Eric Green, M.D., Ph.D. “These results give us important new genomic insights into a cause of a deadly form of cancer."

Sunday, July 27, 2014

Scientists discover new, noncommittal mechanism of drug resistance

Scientists discover new, noncommittal mechanism of drug resistance
This image depicts drug resistant 'epimutants' emerging from a drug sensitive yeast colony. Credit: Soo Chan Lee
Microorganisms like bacteria and fungi can evade treatment by acquiring mutations in the genes targeted by antibiotics or antifungal drugs. These permanent mutations were once thought to be the only way for drug-resistant strains to evolve. Now a new study has shown that microorganisms can use a temporary silencing of drug targets—known as epimutations—to gain the benefits of drug resistance without the commitment.
Though the new mechanism was discovered in a fungus called Mucor circinelloides, it is likely to be employed by other fungi as well as bacteria, viruses and other organisms to withstand treatment with various drugs. The finding appears July 27, 2014, in Nature.
"This mechanism gives the organism more flexibility," said Joseph Heitman, M.D., Ph.D., senior study author and professor and chair of molecular genetics and microbiology at Duke University School of Medicine. "A classic, Mendelian mutation is a more permanent binding decision, like a traditional marriage. These epimutations are reversible, more akin to moving in together. If conditions change, it is easier to revert to the way things were."
The epimutations are so transient, in fact, that the researchers almost disregarded them. Cecelia Wall, a graduate student in Drs. Heitman and Maria Cardenas' labs, had been looking for mutations that would make the human fungal pathogen M. circinelloides resistant to the antifungal drug FK506 (also known as tacrolimus). This pathogen causes the rare but lethal fungal infection mucormycosis, an emerging infectious disease that predominantly affects individuals with weakened immune systems.
As is typical for most drug resistance experiments, Wall first grew the pathogen in Petri dishes containing the antifungal drug. She found that the few organisms that survived treatment looked different, being smaller and less diffuse than their parent fungi. Wall then isolated those fungi and sequenced the gene FKBP12—the target of FK506—to look for mutations that would confer drug resistance.
However, she couldn't detect any mutations in about a third of the isolates. What's more, Wall found that many of the mutants kept "disappearing," looking less like mutants and more like their parents after she took the drug away.
"This is an example of something you might find in the laboratory and just throw away," said Silvia Calo, Ph.D., lead study author and postdoctoral fellow in the Heitman and Cardenas labs. "You look for mutants in one gene and when you don't find a mutation in some of the isolates, you decide not to work on those anymore and instead focus on others. But we wanted to know what was going on."
The researchers began to wonder whether a phenomenon known as RNA interference or RNAi could be the cause of this unstable drug resistance. RNAi uses bits of RNA—the chemical cousin of DNA—to silence specific genes. Though RNAi doesn't exist in every organism, the researchers knew it was active in M. circinelloides because of the pioneering work of their collaborators Rosa Ruiz-Vazquez and Santiago Torres-Martinez, with whom Calo trained at the University of Murcia, Spain.
So Calo looked for the presence of small RNAs—a signature of RNAi—in the drug resistant isolates. She didn't find small RNAs in the isolates that contained mutations in FKBP12, but she did find them in those lacking mutations. Importantly, Calo found that these small RNAs only silenced the FKBP12 gene and not any other loci in the genome. The results demonstrate that M. circinelloides can develop two different ways, either stably through permanent mutations or transiently through reversible epimutations.
"This plasticity enables an organism to reverse epigenetic  when selective pressures are relaxed," said Calo. "Otherwise, silencing a gene when it doesn't need to be silenced would be a waste of energy."
The researchers think these epimutations could be employed in a variety of situations, enabling an organism to adapt to an unfavorable environment and then adapt again when conditions improve. Though they have only shown epimutations in two species of M. circinelloides, they have already been approached by a number of other researchers who are interested in investigating similar unstable behavior in other organisms like Aspergillus and Neurospora.
"It could be like the discovery of other molecular phenomena like introns or microRNAs, where it all began with just one example," said Heitman. "We think this discovery may turn out to be generalized fairly quickly."
More information: "Antifungal drug resistance evoked via RNAi-dependent epimutations," Silvia Calo, Cecelia Wall, Soo Chan Lee, Robert J. Bastidas, Francis E. Nicolás, Joshua A. Granek, Piotr Mieczkowski, Santiago Torres-Martinez, Rosa M. Ruiz-Vazquez, Maria E. Cardenas, and Joseph Heitman. Nature, July 27, 2014. DOI # 10.1038/nature13575.

Epigenetic Changes Cause Cancer


Epigenetics
Clinical researchers at the Baylor College of Medicine report that cancer can result from epigenetic changes, which are changes in gene expression.
Epigenetics focuses on the study of heritable genetics changes caused by changes in the DNA sequence.
In epigenetics, scientists turn-off and turn-on DNA and RNA to uncover their chemical reactions.
Lanlan Shen, an Associate Professor at the Baylor College of Medicine, said they knew epigenetic changes were associated with cancer, but didn't know whether they were a cause or a consequence of cancer.
She added that developing new approaches for epigenetic engineering allowed them to see whether DNA methylation changes can drive a cancer.
Shen and her fellow researchers focused on a gene anomaly called p16 that normally functions to prevent cancer.
They engineered DNA methylation in mice's p16 regulatory region where the p16 acted as a methylation magnet
The mice developed spontaneous cancers and had reduced chances of survival when the team increased its p16 methylation.
Shen said this is not the first evidence that epigenetic alteration can cause cancer. There are also profound implications that epigenetic changes can be potentially reversible.
Shen believes their findings can provide new epigenetic therapies and validate novel approaches for testing them.
Dr. Robert Waterland, one of Shen's fellow researchers, said their findings can open doors for a whole new paradigm of understanding tumorigenesis.

Overview of Ewing’s Sarcoma

There are factors related to Osteosarcoma bone cancer. 

Primary cancer of the bone
Primary cancers of the bones are localized cancers in the bone, or its immediate periphery, which develop from bone, cartilage or fibrous. They are quite rare. The main bone cancers are chondrosarcoma, Osteosarcoma, the Ewing’s sarcoma and multiple myeloma . The secondary bone cancer, or bone metastases, are remote locations, in bone cancer in another organ: prostate , kidney, breast, thyroid, and to other parts of the body that can result in severe pain and significant mortality.
Osteosarcoma
This is a malignant primary bone tumor. In most cases, it occurs in children and adolescents.
Dietary influences, hormonal milieu, and the role of environmental carcinogens are currently under intense investigation. As further risk factors are identified, it will become increasingly important to identify individuals at increased risk for the disease. These men should undergo regular evaluation with state-of-the-art methods.
Benefit of omega 3 ingestion
There was a suggestion of a protective effect of n-3 fatty acid intake that was limited to Latinos and Whites. However, overall, our findings from a large cohort study of ethnically diverse population give no indication that intake of fat and meat substantially affects prostate cancer risk.
Risk factors for cancer in general

This section of the book covers issues such as Red Meat, Western vs. Eastern Diet, Alcohol, Anti-Oxidants, Obesity, and other components that affect our health.

Fats that Harm and Fats that Heal


Information about Trans-Fats, Hydrogenated Oils, Broken Fats that may be harmful, and the Essential Fatty Acids that have beneficial anti-oxidant benefits.

Dietary Fat can Alter Tumorigenesis

A study that relates to the activity and expression of fatty acid synthase (FAS), a critical enzyme in the de novo biosynthesis of fatty acids in mammals, is exquisitely sensitive to nutritional regulation of lipogenesis (production of fats) in liver or adipose tissue.
A study by Menendez et al indicate that: a) GLA- and omega-3 PUFA-induced repression of tumor-associated FAS may result, at least in part, from a non-specific cytotoxic effect due to peroxidative mechanisms; b) alternatively, GLA and omega-3 PUFAs have a suppressive effect on FAS expression and activity that can result in the accumulation of toxic fluxes of the FAS substrate.
Overexpression and hyperactivity of breast cancer-associated fatty acid synthase (oncogenic antigen-519) is insensitive to normal arachidonic fatty acid-induced suppression in lipogenic tissues but it is selectively inhibited by tumoricidal alpha-linolenic and gamma-linolenic fatty acids: a novel mechanism by which dietary fat can alter mammary tumorigenesis.

Menendez JA, Ropero S, Mehmi I, Atlas E, Colomer R, Lupu R, Department of Medicine, Evanston Northwestern Research Institute, Evanston, IL 60201, USA. Int J Oncol. 2004 Jun;24(6):1369-83.

Nuts and nutrients that slow some kinds of cancer growth

Walnuts contain components that may slow breast cancer growth including omega-3 fatty acids, phytosterols, polyphenols, carotenoids, and melatonin.

The eicosapentaenoic and docosahexaenoic acid fractions of the livers of the group that consumed walnuts were significantly higher than that of the group that did not consume walnuts. Tumor cell proliferation was decreased, but apoptosis was not altered due to walnut consumption.   A study by Hardman et al was done evaluating omega-3 fatty acids, antioxidants and phytosterols, such as elements that are found in walnuts.

Further work is merited to investigate applications to cancer in humans.

Suppression of implanted MDA-MB 231 human breast cancer growth in nude mice by dietary walnut. 

Hardman WE, Ion G. hardmanw@marshall.edu
Department of Biochemistry and Microbiology, Marshall University School of Medicine, Huntington, West Virginia 25755, USA.

Good Fats: The Omegas 3 fatty acids


Although it is believed that fish omega-3 fatty acids may decrease breast cancer risk, epidemiological evidence has been inconclusive. This study examined the association between fish and fish omega-3 fatty acids intake with the risk of breast cancer in a case-control study of Korean women.
Metastasis is the leading cause of death from breast cancer. A major factor of metastasis is the migration of cancerous cells to other tissues by way of up-regulated chemokine receptors (receptors that work on the surface of cells).
Much is known of the beneficial effects of omega-3 polyunsaturated fatty acids (PUFA, or omega-3) on cancer; however, the mechanisms behind these effects are unclear.
Researchers have investigated the effects of two n-3 PUFAs, (the good guy fats from fish) docosahexaenoic acid and eicosapentaenoic acid, on CXCR4 expression and activity in the MDA-MB-231 breast cancer cell line.   The n-3 PUFAs were compared with the saturated fatty acid stearic acid as a control.
A preventative effect on cancer metastasis
Together, data suggest that omega-3 PUFAs may have a preventative effect on breast cancer metastasis in vitro. This suggests a previously unreported potential benefit of omega-3 PUFAs to patients with metastatic breast cancer. The data presented in this study may also translate to other disorders that involve up-regulated chemokine receptors.
These results suggest that high consumption of fatty fish is associated with a reduced risk for breast cancer, and that the intake of omega-3 fatty acids from fish is inversely associated with postmenopausal breast cancer risk.

Omega-3 polyunsaturated fatty acids down-modulate CXCR4 expression and function in MDA-MB-231 breast cancer cells. Mol Cancer Res. 2009 Jul;7(7):1013-20. Epub 2009 Jun 30. Altenburg JD, Siddiqui RA.,Cellular Biochemistry Laboratory, Methodist Research Institute, Clarian Health Partners, Indianapolis, IN 46202, USA.

BMC Cancer. 2009 Jun 30;9:216.  Fatty fish and fish omega-3 fatty acid intakes decrease the breast cancer risk: a case-control study. Kim J, Lim SY, Shin A, Sung MK, Ro J, Kang HS, Lee KS, Kim SW, Lee ES.
Cancer Epidemiology Branch, Division of Cancer Epidemiology and Management, Research Institute, National Cancer Center, Gyeonggi, South Korea. jskim@ncc.re.kr
Opposing effects of dietary n-3 and n-6 fatty acids on mammary carcinogenesis: The Singapore Chinese Health Study
This study in women may be important for men and the risk for prostate cancer.  A study investigated the effects of individual fatty acids on breast cancer in a prospective study of 35,298 Singapore Chinese women aged 45-74 years, who were enrolled during April 1993 to December 1998 (The Singapore Chinese Health Study).
Each study subject was administered, in-person, a validated, semiquantitative food frequency questionnaire consisting of 165 food and beverage items. As of December 31, 2000, 314 incident cases of breast cancer had occurred. We used the Cox regression methods to examine individual fatty acids in relation to breast cancer risk, with adjustment for age at baseline interview, year of interview, dialect group, level of education, daily alcohol drinking, number of live births, age when menstrual periods became regular, and family history of breast cancer. Consumption of saturated, monounsaturated or polyunsaturated fat overall was unrelated to risk. On the other hand, high levels of dietary n-3 fatty acids from fish/shellfish (marine n-3 fatty acids) were significantly associated with reduced risk.
This study has prospective findings linking the intake of marine n-3 fatty acids to breast cancer protection.  Gago-Dominguez M, Yuan JM, Sun CL, Lee HP, Yu MC.USC/Norris Comprehensive Cancer Center, Keck School of Medicine of the University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90089-9181, USA. Br J Cancer. 2003 Nov 3;89(9):1686-92.

Their findings suggest that, although CLA intake was not related to overall breast cancer risk, there may be associations with tumor biology at least among premenopausal women.

Dietary intake of conjugated linoleic acids and risk of premenopausal and postmenopausal breast cancer, Western New York Exposures and Breast Cancer Study (WEB Study).

McCann SE, Ip C, Ip MM, McGuire MK, Muti P, Edge SB, Trevisan M, Freudenheim JL. Cancer Epidemiol Biomarkers Prev. 2004 Sep;13(9):1480-4.

Department of Epidemiology, Division of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York 14263, USA

Mediterranean diet and cancer

At the Istituto di Richerche Farmacologiche Mario Negri, Milano, Italy, they studied the role of various aspects of the Mediterranean diet in several common epithelial cancers, including digestive and selected non-digestive tract neoplasms.
The study took place in northern Italy, between 1983 and 1998 with over 12,000 cases of 20 cancer sites and 10,000 controls.
Risk decreased with increasing vegetable and fruit consumption
They found that for most epithelial cancers, the risk decreased with increasing vegetable and fruit consumption, with relative risk (RR) between 0.3 and 0.7 for the highest versus the lowest tertile.
For digestive tract cancers, population-attributable risks for low intake of vegetables and fruit ranged between 15 and 40 percent.
A protective effect was observed also for breast, female genital tract, urinary tract and a few other epithelial neoplasms. A number of antioxidants and other micronutrients showed an inverse relationship with cancer risk, but the main components responsible for the favorable effect of a diet rich in vegetables and fruit remain undefined.
Fish tend to be another favorable diet indicator
In contrast, subjects reporting frequent red meat intake showed risk for several common neoplasms.
Include whole-grain foods in your diet
Intake of whole-grain foods was related to a reduced risk of several types of cancer, particularly of the upper digestive tract. This may be due to a favorable role of fiber, but the issue is still open to discussion. In contrast, refined grain intake and, consequently, glycemic load and glycemic index were associated with increased risk of different types of cancer including, among others, breast and colorectal.
The researchers concluded that a low-risk diet for cancer in the Mediterranean would imply increasing the consumption of fruit and vegetables, as well as avoiding increasing the intakes of meat and refined carbohydrates. Further, olive oil and other unsaturated fats, which are also typical aspects of the Mediterranean diet, should be preferred to saturated ones.
The results of the study were published in BMC Cancer. 2007 May 9;7:80.

Mediterranean diet has showed beneficial aspects
A study found that an adherence to the Mediterranean diet is a favorable indicator of the risk of several common epithelial cancers in Italy. A score summarizing the major characteristics of the Mediterranean diet was related to a prior defined reduced risks of several digestive tract neoplasms by over 50 percent.  The findings of this large study showed an inverse association between intake of flavones and breast cancer risk.
Olive oil helps with cancer therapy
Olive oil's healthy fats reverse acquired autoresistance to trastuzumab (Herceptin) in HER2-overexpressing breast cancer cells.

A study done by Menendez JA, Vazquez-Martin A, Colomer R, Brunet J, Carrasco-Pancorbo A, Garcia-Villalba R, Fernandez-Gutierrez A, Segura-Carretero A.  Catalan Institute of Oncology (ICO)-Health Services Division of Catalonia, Spain.
A low incidence of breast cancer in the Mediterranean basin suggests that a high consumption of Extra Virgin Olive Oil (EVOO) might confer this benefit
 While the anti-HER2 oncogene effects of the main omega-9 fatty acid present in EVOO triacylglycerols (i.e., oleic acid) have been recently described, the anti-breast cancer activities of EVOO non-glyceridic constituents--which consist of at least 30 phenolic compounds--remained to be evaluated.
Curr Pharm Biotechnol. 2006 Dec;7(6):495-502.


Mediterranean dietary traditions for the molecular treatment of human cancer: anti-oncogenic actions of the main olive oil's monounsaturated fatty acid oleic acid
The final proof about the specific mechanisms by which the different components of olive oil, the principal source of fat in a typical "Mediterranean diet", exert their potential protective effects on the promotion and progression of several human cancers requires further investigations. A recent discovery that dietary fatty acids can interact with the human genome by regulating the amount and/or activity of transcription factors has opened a whole new line of research aimed to molecularly corroborate the anti-cancer benefits of the olive oil-based Mediterranean diet and the underlying mechanisms.
Their most recent findings in this  study reveal that oleic acid , the main olive oil's monounsaturated fatty acid, can suppress the overexpression of HER2 (erbB-2), a well-characterized oncogene playing a key role in the etiology, invasive progression and metastasis in several human cancers.
Certainly, an appropriate dietary intervention reproducing this prominent anti-oncogenic feature of the "Mediterranean diet" must be carried out in animal models and human pilot studies in the future. Only then we will know whether the old "Mediterranean dietary traditions" will become a new molecular approach in the management of cancer disease.  Int J Mol Med. 2008 Oct;22(4):433-9.  Menendez JA, Lupu R.,Fundació d'Investigació Biomèdica de Girona Dr. Josep Trueta (IdIBGi), Girona, Catalonia, Spain. javiermenendez72@yahoo.com
Analyzing effects of extra-virgin olive oil polyphenols on breast cancer-associated fatty acid synthase (protein enzyme) and protein expression
Inhibitors of fatty acid synthase (FASN), a key enzyme involved in the anabolic conversion of dietary carbohydrates to fat in mammals, are receiving increasingly more attention as they may provide therapeutic moieties for the treatment of human malignancies. Natural compounds, such as the green tea polyphenol epigallocatechin-3-gallate, have been shown to induce anti-cancer effects by suppressing FASN, which may account for the epidemiologically observed inverse correlation between green-tea drinking and cancer risk in Oriental populations.
Since extra-virgin olive oil (EVOO)-derived phenolics have been suggested to possess biological activities that may explain the health-promoting effects of the “Mediterranean diet”, we evaluated their effects on the expression of FASN protein in human breast epithelial cell lines.
Anti-cancer effects
These findings reveal for the first time that phenolic fractions, directly extracted from EVOO, may induce anti-cancer effects by suppressing the expression of the lipogenic enzyme FASN in HER2-overexpressing breast carcinoma cells, thus offering a previously unrecognized mechanism for EVOO-related cancer preventive effects.
Int J Oncol. 2009 Jan;34(1):43-51.  Menendez JA, Vazquez-Martin A, Oliveras-Ferraros C, Garcia-Villalba R, Carrasco-Pancorbo A, Fernandez-Gutierrez A, Segura-Carretero A.
Girona Biomedical Research Institute, Medical Oncology, Dr. Josep Trueta University Hospital of Girona, E-17007 Girona, Catalonia, Spain.

High levels of phenolic compounds in Olive Oil
Extra-virgin olive oil (EVOO - the juice of the olive obtained solely by pressing and consumed without any further refining process or heating that disturbs the quality) is unique among other vegetable oils because of the high level of naturally occurring phenolic compounds.
Really Bad Fats:

Trans-Fatty Acids, Hydrogenated Oils and Others


These fats are often hidden in foods.  Some packaged foods lack the details of the ingredients.  Some list 0 Grams of trans fats, which can mean that there are up to 999 mg of trans fats per serving, but they still put 0 Grams.  I feel that is more than misleading, it is false information.  Given the body of information about trans fats that is so widespread in processed foods, I feel this misinformation is criminal.  
The strongest evidence that monounsaturated fat may influence breast cancer risk comes from studies of southern European populations, in whom intake of oleic acid sources, particularly olive oil, appears protective. No previous study has examined the relation of adipose tissue fatty acid content to breast cancer in such a population.
The Essential Fatty Acids are those that have anti-oxidant benefits.   Oleic acid showed a strong inverse association with breast cancer in the Spanish center trials.
Palmitoleic and myristoleic acids showed evidence of an inverse association outside Spain, and cis-vaccenic acid showed a positive association in three centers. These data do not support the hypothesis that increasing tissue stores of oleic acid are protective against breast cancer in non-Spanish populations.
This finding implies that the strong protective associations reported for olive oil intake in dietary studies may be due to some other protective components of the oil.
It may be that there is less ingestion of toxic trans fats when more of the healthy fats are ingested.

Trans Fats in food products have been often hidden in the past 
Before 2006, consumers in the United States could not directly determine the presence of trans fats in food products.
This information was often omitted or could only be inferred from the ingredient list, notably from the partially hydrogenated ingredients, which may be listed as simply “soy”.
According to the FDA, the average American consumes 5.8 grams of trans fat per day (2.6 percent of calories).
In 2003, the Food and Drug Administration (FDA) issued a regulation requiring manufacturers to list trans fat on the Nutrition Facts panel of foods and some dietary supplements.
The new labeling rule became mandatory across the board, but unfortunately there is severe deception from the food industry that, unlike in many other countries, trans fat levels of less than 0.5 grams per serving can be listed as 0 grams trans fat on the food label. 
According to a study published in the Journal of Public Policy & Marketing, many consumers do not know how to interpret the meaning of trans-fat content on the Nutrition Facts panel, and they may not know that 0 grams is a lie if there is 0.5 grams or even 0.99 grams hidden inside each serving.
Without specific knowledge about trans fat and its negative health effects, consumers may misinterpret nutrient information provided on the panel and think that soy is healthy even though they should avoid trans fats whether they have coronary heart disease or not.
There is no requirement to list trans fats on institutional food packaging.  Bulk purchasers such as schools, hospitals, and cafeterias are unable to evaluate the trans fat content of commercial food items.
The FDA defines trans fats as containing one or more trans linkage that are not in a conjugated system. This is an important distinction, as it distinguishes non-conjugated synthetic trans fats from naturally occurring fatty acids, and essential fatty acids are the foods that heal, while trans fats harm. 
I, as well as others, have expressed concern that the 0.5 gram per serving threshold is too high to refer to a food as free of trans fat.  There should be no trans fats at all and if there is, it should state how much is in each serving.  I feel strongly in evidence that there is inflammation that damages DNA, RNA, Mitochondria that  not only cause damage leading to disease, that there is also evidence that minor dietary changes are being passed to many future generations.   If there is arsenic in food it would be banned and not just labeled: “0 grams of arsenic” i.e. under 0.5 grams of arsenic in each serving.
A person eating many servings of a product, or eating multiple products over the course of the day may still consume a significant amount of trans fat.
Despite this, the FDA estimates that by 2009, trans fat labeling will have prevented from 600 to 1,200 cases of coronary heart disease and 250 to 500 deaths each year.
The food industry needs to completely eliminate trans fats and use natural ingredients that actually have health benefits that are already available for use.
Trans fats are linked to cancer risk in some studies 
Trans fats are being phased out of food because they cause inflammation in arteries and may be associated with heart disease and may raise the risk of getting breast cancer according to European researchers.
They found that women with the highest blood levels of trans fats had about twice the risk of breast cancer compared to women with the lowest levels.
Researchers suggest limiting the consumption of processed foods, the source of industrially produced trans-fatty acid according a recent article in the American Journal of Epidemiology.
Trans fats or trans-fatty acids are made in creating artificially broken or partially hydrogentated fats.  Many times these are just listed as soy, cotton, or other oil without mentioning a process of hydrogenization.   The food industry is creating more nomenclature to confuse or hide these toxic substances.
Butter for some people may be safer than these trans fats due to the inflammation factors from the trans fats, even though they are marketing as healthful replacements for artery-clogging saturated fats.  More and more states like New York and California have banned trans fats in restaurant foods.
In Canada and Britain countless food companies have dropped them as an ingredient.
Veronique Chajes at the University of Paris-South and colleagues studied women taking part in a large European cancer trial at The National Center of Scientific Research.  They looked at blood samples collected between 1995 and 1998 from 25,000 women who had volunteered to report on their eating and lifestyle habits and studied the incidence of developed cancer.
They studied women diagnosed with breast cancer, comparing their blood levels of fatty acids with those of women without cancer.
The higher the levels of trans-fatty acids, the more likely a woman was to have cancer, researchers found.
Obese women are more likely to develop breast cancer, and other cancers, and high-fat diets are also linked with breast cancer.  There are a variety of mechanisms for these cancer causing risk factors.
Trans fats can be found in many kinds of processed foods, baked goods, snacks and a variety of other prepared foods.
Healthy Omega-3 fatty acids are found in fatty fish such as salmon, walnuts and leafy green vegetables and I feel may counteract the bad effects of bad fats and foods and even alcohol.  It is a chemical balancing act and oxidants versus antioxidants that decrease or destroy toxins. 
There are Alternatives to Trans Fats which can be non-harmful
The food industry is being to committed to removing trans-fatty acids from its products, and getting better with information on package inserts.
Paul Wassell and Niall Young from Danisco's Multiple Food Application Group reviewed the options available to formulators and stated that designing foods with trans fat alternatives must be a "multidisciplinary' approach" (International Journal of Food Science and Technology, Vol. 42, pp 503-517).
The food industry has been using trans fats as preservatives, and say they have had difficulty finding another non-trans fats food preservative.  However, despite their claims, there are now natural preservatives that can be used that are much more beneficial to our health.
American Journal of Epidemiology, "Association between Serum trans-Monounsaturated Fatty Acids and Breast Cancer Risk in the E3N-EPIC Study"
Authors: V. Chajes, A.C.M. Thiebaut, M. Rotival, E. Gauthier, V. Maillard, M.-C. Boutron-Ruault, V. Joulin, G.M. Lenoir, F. Clavel-Chapelon.

The report from European Community Multicenter Study on Antioxidants, Myocardial Infarction, and Breast Cancer suggests that eating trans fats may increase risk for breast cancer
Study: Tissue antioxidants and postmenopausal breast cancer: the European Community Multicentre Study on Antioxidants, Myocardial Infarction, and Cancer of the Breast (EURAMIC), by P van 't Veer, et al. from the Netherlands Organization for Applied Scientific Research (TNO) Food and Nutrition Research Institute, Zeist, The Netherlands.


Antioxidants may protect against free radical mediated carcinogenesis

Epidemiological studies have not confirmed this hypothesis for breast cancer, possibly because of methodological limitations. Time-integrated exposure of alpha-tocopherol and beta-carotene in adipose tissue, and selenium in toenails was investigated in a case-control study among postmenopausal women, ages 50-74 years, from five European countries.

Women with breast cancer have higher levels of trans fats in their bodies than other women
Trans fats are found in processed foods, most margarines and in many kinds of French Fries, fried chicken or fish, pies, cakes, cookies, and other foods made with shortening.
The researchers measured trans and other fats in tissue samples taken from the buttocks of 291 women with breast cancer and 407 similar healthy women in Germany, Ireland, the Netherlands, Spain, and Switzerland.
The women who had eaten higher levels of trans were almost four times more likely to have breast cancer than the women who had eaten less trans--but only if they also ate low levels of polyunsaturated fats.
Polyunsaturated fats are largely found in full-fat salad dressings and mayonnaise, nuts, and vegetable oils--except palm and coconut.
Polyunsaturated fats may help keep cells from proliferating and the trans fat may be blocking the polyunsaturated oils from carrying out that beneficial role,
This information comes from Lenore Kohlmeier, et al at the University of North Carolina.  They found that as long as there are enough polyunsaturated, the trans fats have little impact and if polyunsaturated fats are low, the trans fatty acids may keep them from doing their job.
This information is important about prevention of cardiovascular disease and about breast cancer.
They found in the study that trans fat intakes and fat stores are higher in the U.S. than in European countries.


Antioxidants may protect against free radical mediated carcinogenesis

Tissue antioxidants and postmenopausal breast cancer: the European Community Multicentre Study on Antioxidants, Myocardial Infarction, and Cancer of the Breast (EURAMIC) 

Epidemiological studies have not confirmed this hypothesis for breastcancer, possibly because of methodological limitations.

These results do not support the hypothesis that antioxidants are importantdeterminants of this hormone-related malignancy among postmenopausal women. 

Cancer Epidemiology Biomarkers & Prevention, Vol 5, Issue 6 441-447,1996 by American Association for Cancer Research, Nutr Cancer. 2008;60(5):666-74.

Flavonoids

High intakes of fruit and vegetables are associated with a reduced risk of cancer at several sites
Few epidemiologic studies have investigated the potential relation between flavonoids and breast cancer risk.
They studied recently published data on the composition of foods and beverages in terms of six principal classes of flavonoids (i.e., flavanones, flavan-3-ols, flavonols, flavones, anthocyanidines, and isoflavones) on dietary information collected in a large-case control study of breast cancer conducted in Italy between 1991 and 1994. The study included 2,569 women with incident, histologically confirmed breast cancer, and 2,588 hospital controls.
A large body of evidence indicates that high intakes of fruit and vegetables are associated with a reduced risk of cancer at several sites. The association is generally most marked for epithelial cancers, apparently stronger for those of the digestive and respiratory tracts, and somewhat weaker for hormone-related cancers.
The relationship between frequency of consumption of vegetables and fruit and cancer risk was analyzed using data from a series of case-control studies conducted in northern Italy since 1983. The relative risks (RRs) for most common neoplasms ranged from 0.2 to 0.5 for the highest compared with the lowest tertile of vegetable intake. Protective effects were highest for epithelial neoplasms, but were also observed for hormone-related neoplasms. Fruit was related to reduced RRs for cancers of the oral cavity and pharynx, esophagus, stomach, larynx, as well as of the urinary tract. There was a specific and consistent pattern of protection by tomatoes, a typical Mediterranean food, with RRs between 0.4 and 0.7, most notably for gastrointestinal neoplasms.
No significant association was observed between fruit and vegetable consumption and non-epithelial lymphoid neoplasms. For digestive tract cancer, population attributable risks for low intake of fresh vegetables and fruit ranged from 15 to 40 percent of all cases in this Mediterranean population. Combined with tobacco and alcohol, the population attributable risks exceeded 85 percent for men and 55% for women for upper digestive and respiratory tract neoplasms.
Their study from a public health viewpoint and epidemiological evidence indicates that a substantial reduction in epithelial cancer risk can be obtained by increasing fruit and vegetable consumption.
Cancer Epidemiol Biomarkers Prev. 2005 Apr;14(4):805-8.  Eur J Cancer Prev. 1998 Feb;7(1):3-8.

Soy, Herbs and Other Dietary Supplements

Fiber, Fruits and Veggies (rather than meat and dairy)
It is the position of the American Dietetic Association that appropriately planned vegetarian diets, including total vegetarian or vegan diets, are healthful, nutritionally adequate, and may provide health benefits in the prevention and treatment of certain diseases.
Well-planned vegetarian diets are appropriate for individuals during all stages of the life cycle, including pregnancy, lactation, infancy, childhood, and adolescence, and for athletes. A vegetarian diet is defined as one that does not include meat (including fowl) or seafood, or products containing those foods.
This article reviews the current data related to key nutrients for vegetarians including protein, n-3 fatty acids, iron, zinc, iodine, calcium, and vitamins D and B-12. A vegetarian diet can meet current recommendations for all of these nutrients. In some cases, supplements or fortified foods can provide useful amounts of important nutrients.
An evidence- based review showed that vegetarian diets can be nutritionally adequate in pregnancy and result in positive maternal and infant health outcomes.
The results of an evidence-based review showed that a vegetarian diet is associated with a lower risk of death from ischemic heart disease. Vegetarians also appear to have lower low-density lipoprotein cholesterol levels, lower blood pressure, and lower rates of hypertension and type 2 Diabetes than non vegetarians.
Furthermore, vegetarians tend to have a lower body mass index and lower overall cancer rates. Features of a vegetarian diet that may reduce risk of chronic disease include lower intakes of saturated fat and cholesterol and higher intakes of fruits, vegetables, whole grains, nuts, soy products, fiber, and phytochemicals.
The variability of dietary practices among vegetarians makes individual assessment of dietary adequacy essential. In addition to assessing dietary adequacy, food and nutrition professionals can also play key roles in educating vegetarians about sources of specific nutrients.
Position of the American Dietetic Association: vegetarian diets.  Craig WJ, Mangels AR; American Dietetic Association.  J Am Diet Assoc. 2009 Jul;109(7):1266-82.


Vitamin D can stop cancer cells from dividing
Vitamin D, the vitamin made from the sun, has been the focus of intense study in recent years as researchers have found evidence it may help lower the risk of developing several types of cancers, among them colon, prostate, pancreatic and breast cancer.  A New study gives further hope that vitamin D can fight breast cancer.
In 2006, it was found vitamin D may help curb breast cancer progression, and this information was published in the Journal of Clinical Pathology. The authors, from Imperial College London, measured the levels of vitamin D in the blood serum of 279 women with invasive breast cancer. The disease was in its early stages in 204 of the women, and advanced in the remaining 75.
The results showed that women with early stage disease had significantly higher levels of vitamin D (15 to 184 mmol/litre) than the women in the advanced stages of the disease (16 to 146 mmol/litre).
The authors say that the exact reasons for the disparity are not clear, nor is it known whether the lowered levels of vitamin D among those with advanced disease are a cause or a consequence.
The researchers' results, taken together with results from previous studies, lead them to believe that lowered levels of vitamin D may promote the progression of the disease to its advanced stages. 
Laboratory studies have shown that vitamin D stops cancer cells from dividing and enhances cancer cell death. Vitamin D sufficiency and exposure to sunlight has been shown to reduce the risk of developing breast cancer. The body produces its own vitamin D in the skin when it is exposed to sunlight. The vitamin is also found in certain foods, including eggs and fish.
It is known that vitamin D treatment boosts the activity of certain key genes and dampens it down in others. One that is boosted is p21, which has an important role in controlling the cell cycle.
Dr Carlo Palmieri, from the Department of Cancer Medicine at Imperial College London observed that vitamin D levels are lower in advanced breast cancer as compared to early breast cancer. It lends support to the idea that vitamin D has a role in the breast cancer.
Research is needed to try and understand the potential roles of vitamin D.  I feel that vitamin D is worth talking if coupled with bioavailable calcium.   It is the combination of the vitamin D and the cancer that contribute to a more alkaline state.
Antioxidants
Antioxidants reduce the daily oxidative damage—and thus the risk of malignant change—that occurs in all cells by removing reactive “free radicals” that form as a part of normal cellular metabolism.
Vitamins C and E:
Classic sources of antioxidant activity, these vitamins have been extensively studied. Carotene: While recent research has revealed that synthetic beta-carotene may increase risk for certain cancers, the carotene found in natural carrot oil is a potent antioxidant that reduces risk.
Selenium:
Selenium is a metallic trace element is important in potentiating the effects of vitamin E.
High levels of ALA in breast tissue have been shown to decrease the likelihood of cancer metastasis
Alpha lipoic acid is an intracellular and extracellular antioxidant and is found in red meats, some organ meats, spinach, broccoli, and yeast.  It is the only intracellular and extracellular antioxidant that I am aware of.  This is of interest as the activity against toxins needs to be everywhere. 
The absorption of polyphenols from the gut may be impaired by certain foods, such as refined foods and sugars. Cocoa, green tea, and grape seed are sources of polyphenols.
Green tea and grape seed extract may reduce breast tumor growth
Epigallocatechin-3-gallate (EGCG): is found in green tea, EGCG effectively inhibits tumor angiogenesis, and has been shown to reduce the growth of breast tumors in mice.
Oligomeric proanthocyanidins (OPCs): These polyphenols are found in grape seed extract and have been shown to irreversibly inhibit the growth and division of human breast cancer cells in tissue culture (Clinical Cancer Research, Vol 6, 2921-2930, July 2000).
Researchers have stated that OPC should be studied more extensively to be developed as preventive and/or interventive agents against breast cancer in humans.

Indoles
A naturally occurring component of Brassica vegetables (broccoli, kale, cauliflower, etc), indole-3-carbinol has been shown to reduce the incidence of mammary tumors. Indoles arrest the growth of cultured human breast cancer cells
Research indicates that indoles do not function as classical estrogen antagonists. Instead, they may activate genes that are responsible for regulating cells’ responses to estrogen.

Immune boosters

Garlic, zinc, Echinacea, and transfer factors are among a broad class of agents that activate certain components of the immune system which are T helper cells, natural killer cells, B cells, and others.  There is more information in later chapters about T cells.


Fruits and Vegetables are Better than Meat and Dairy

A new study suggests that women who eat diets rich in meat and dairy may have a decreased risk of breast cancer, while those who ingest on fiber, fruits and vegetables show a lower risk of ovarian cancer, published in the International Journal of Cancer.


Vegetables studies Show Less Risk for Cancer

Researchers found that among more than 6,000 Chinese women, those with the highest intake of Chinese cabbage and white turnips had a somewhat lower risk of postmenopausal breast cancer than those with the lowest intake.
Reported in the American Journal of Clinical Nutrition, this adds to information about foods, such as cruciferous vegetables, which may help fight cancer.
Chinese cabbage and white turnips are two cruciferous vegetables common in the Chinese diet.
In Western diets, the most common cruciferous vegetables include broccoli, cauliflower and kale.
This may be of importance for men’s cancer risk.

Vegetables may contain anti-cancer substances
Vegetables contain certain compounds that the body converts into substances called isothiocyanates, which are thought to have anti-cancer effects.
In this study, high consumption of Chinese cabbage and white turnips was linked to a moderately lower breast cancer risk.
The apparent benefit was stronger among women who carried two copies of a particular variant of a gene called GSTP1.
But the excess risk was cut substantially in those who ate the more cruciferous vegetables.
American Journal of Clinical Nutrition, March 2008.

Tumor Growth Reduced with grape seed
When the grape seed extract was fed to mice that had been injected with breast cancer cells, tumor growth was reduced in a dose-dependent manner. In addition, hyperplasia and other abnormal changes of the breast seen in aromatase transgenic mice were reversed by oral administration of the extract.
Mushrooms and breast cancer in lab studies.

Mushrooms reduced the proliferation of breast cancer cells in a lab dish and with other studies.
Eating a few ounces of mushrooms every day could help prevent breast cancer. Dr. Shiuan Chen of the Beckman Research Institute of the City of Hope in Duarte, California, and colleagues tested seven vegetable extracts for their aromatase -blocking activity, and found that white button mushroom had the strongest effect. 


Various mushrooms
The researchers evaluated 10 other types of mushrooms, and found stuffing mushrooms, portobello, crimini, shiitake and baby button mushrooms also inhibited aromatase activity. Extracts of the fungi interfere with the action of aromatase, an enzyme that helps the body make estrogen. Because white button mushrooms are the most commonly eaten type, the researchers tested extracts of the mushrooms in a series of laboratory and animal experiments.
The extract reduced the proliferation of breast cancer cells in a lab dish, while feeding the extract to mice implanted with breast cancer cells suppressed tumor growth.
Based on the amount of extract used in the experiments in mice, about 100 grams of mushrooms daily would be enough to prevent breast cancer growth, and it is possible that eating even less every day could be effective. Cancer Research, December 15, 2006.
Cellular and physiological effects of Ganoderma lucidum (Reishi), and mushroom studies.
In Asia, a variety of dietary products have been used for centuries as popular remedies to prevent or treat different diseases. A large number of herbs and extracts from medicinal mushrooms are used for the treatment of diseases. Mushrooms such as Ganoderma lucidum (Reishi), Lentinus edodes (Shiitake), Grifola frondosa (Maitake), Hericium erinaceum (Yamabushitake), and Inonotus obliquus (Chaga) have been collected and consumed in China, Korea, and Japan for centuries.
Mushroom Immuno-Stimulation
More studies are needed to determine if the benefits of mushrooms are cancer type specific and cell type sensitive.  They may be good for some cancers, bad for some and may have a role in subtypes of cancer.   An example of a substance that may be good for heart health such as Human Growth Hormone, but bad as it supports cancer growth.   This is why it is so important to know what is the state of our health, what are medical conditions are, and what are the biochemical balances for the body.
These mushrooms were largely unknown in the West and were considered 'fungi' without any nutritional value. However, most mushrooms are rich in vitamins, fiber, and amino acids and low in fat, cholesterol, and calories. They contain a large variety of biologically active polysaccharides with immunostimulatory actions and properties, which contribute to their anticancer effects.
Other bioactive substances, including triterpenes, proteins, lipids, cerebrosides, and phenols, have been identified and characterized in medicinal mushrooms.
Extracts of the fungi interfere with the action of aromatase, an enzyme that helps the body make estrogen, the researchers explain in the medical journal, Cancer Research.  Mini Rev Med Chem. 2004 Oct;4(8):873-9. Sliva D. Methodist Research Institute, Clarian Health Partners, Inc., Indianapolis, IN 46202, USA.
Portobello Mushrooms may help fight breast cancer cell growth
Chen and her colleagues tested seven vegetable extracts for their aromatase-blocking activity, and found that white button mushroom had the strongest effect.
Further experiments showed that linoleic acid, a fatty acid usually found in meat and dairy products, was probably responsible for the extract's anti-cancer effects.
Cancer Research, December 15, 2006, Chen et. al.



Western diet ups cancer risk among Chinese and the risk of Obesity

The Chinese Diet has been associated with less cancer risk and the researchers in the journal Cancer Epidemiology, Biomarkers & Prevention, tracked about 3,000 women in Shanghai, about half of whom were diagnosed with breast cancer.

Post-menopausal women who ate a Western-style diet were 60 percent more likely to develop breast cancer than those eating a diet based on vegetables and soy and the study found the increased risk most acute for cancer involving estrogen-receptor positive tumors.
The post-menopausal women with the Western-style diet experienced a 90 percent increased risk for this type of breast cancer.
Marilyn Tseng of the Fox Chase Cancer Center in Philadelphia found a much smaller increased breast cancer risk among younger women on a Western-style diet which was not statistically significant.

Red Meat


Cooking meat at high temperatures in direct heat over an open flame can lead to the production of cancer-causing chemicals known as heterocyclic amines, or HCAs.
Dr. Kala Visvanathan from Johns Hopkins University explained at a cancer prevention conference sponsored by the American Association for Cancer Research.
By studying the eating patterns of 312 women with breast cancer and 316 women who were cancer free, Visvanathan's team found that breast cancer was increased a significant 74 percent in women who ate flame-broiled foods more than twice per month compared with women who never ate flame-broiled foods.
Women who ate more than 64 grams per day compared with those who ate less than or equal to 64 grams per day had a 43-percent higher risk of breast cancer.
Polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs) are carcinogens formed in or on the surface of well-done meat, cooked at high temperature.
They estimated breast cancer risk in relation to intake of cooked meat in a population-based, case-control study (1508 cases and 1556 controls) conducted in Long Island, NY and they found modest increased risk was observed among postmenopausal, but not premenopausal, women consuming the most grilled or barbecued and smoked meats over the life course.
These results support the accumulating evidence that consumption of meats cooked by methods that promote carcinogen formation may increase risk of postmenopausal breast cancer.
Polycyclic aromatic hydrocarbons and heterocyclic amines are known carcinogens produced by cooking meat at high temperatures, in their report.
Grilled meat has particularly high heterocyclic amine content, where high temperatures are more likely to occur.
Steck and her colleagues compared the lifetime and recent consumption of cooked meat among 1,508 women with breast cancer and 1,556 healthy women.
Postmenopausal women who fell in the highest two-thirds category of with a lifetime consumption of smoked, grilled or barbecued meats more than once a week had a 47 percent greater risk of the disease compared with women who ate the least amount of meat. 
Smoked red meat eaters have a 47 percent increased risk of breast cancer. Epidemiology: May 2007 - Volume 18 - Issue 3 - pp 373-382, Cooked Meat and Risk of Breast Cancer-Lifetime Versus Recent Dietary Intake, Steck, Susan E.; Gaudet, Mia M.; Eng, Sybil M.; Britton, Julie A.; Teitelbaum, Susan L.; Neugut, Alfred I.; Santella, Regina M.; Gammon, Marilie D.


The Alcohol Volume is the Key Factor
One of the largest individual studies of the effects of alcohol on the risk of breast cancer has concluded that it makes no difference whether a woman drinks wine, beer or spirits (liquor) -- it is the alcohol itself (ethyl alcohol) and the quantity consumed that is likely to trigger the onset of cancer. The increased breast cancer risk from drinking three or more alcoholic drinks a day is similar to the increased breast cancer risk from smoking a packet of cigarettes or more a day
Dr Klatsky, adjunct investigator in the Division of Research, Kaiser Permanente Medical Care Program, Oakland, USA, and his colleagues studied the drinking habits of 70,033 multi-ethnic women who had supplied information during health examinations between 1978-1985. By 2004, 2,829 of these women had been diagnosed with breast cancer.
They found that there was no difference in the risk of developing breast cancer between wine, beer or spirits, it was the alcohol itself.

Anti-Oxidants: Green Tea Ingredient and Risk of Cancer

An antioxidant in green tea may be beneficial against breast cancer.  A study in 2008 was conducted by Jian-Wei Gu, Emily Young, Jordan Covington, James Wes Johnson, and Wei Tan, all of the Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson, MS. Dr. Gu discussed his finding titled Oral Administration of EGCG, an Antioxidant Found in Green Tea, Inhibits Tumor Angiogenesis and Growth of Breast Cancer in Female Mice, at the 121st Annual Meeting of the American Physiological Society.
One study shows the green tea antioxidant EGCG (epigallocatechin-3-gallate) significantly slowed breast cancer growth in female mice.
Researchers say the results suggest that green tea's anticancer effects may be largely because of its high content of EGCG, which helps the body's cells from becoming damaged and aging prematurely.
The important role of Oxidative stress and the damage it causes can start the process of cancer
Oxidative stress and the damage it causes can start the process of cancer. One of the best ways to stop oxidative stress is with use of antioxidants such as vitamin E, vitamin C, selenium and other phytonutrients.  These are found in plant foods.
Antioxidants are the body's first line of defense against the damaging effects of oxidative stress. (Sharhar, S., et al. Asian Pac J Cancer Prev. 2008; 9(2):343-50.)


Flavonoids are able to inhibit aromatase, a key enzyme in the production of estrogen, inhibit tumor cell proliferation
Numerous laboratory studies show that flavonoids are able to inhibit aromatase, a key enzyme in the production of estrogen, inhibit tumor cell proliferation and decrease the production of reactive oxygen compounds.
All of these mechanisms are thought to influence breast cancer development. This study suggests that postmenopausal women could reduce their risk of developing breast cancer by eating foods or drinking beverages containing flavonoids.[1] Further research is necessary to confirm these results.


[1] Fink BN, Steck SE, Wolff MS, Britton JA, Kabat GC, Schroeder JC, Teitelbaum SL, Neugut AI, Gammon MD. Dietary flavonoid intake and breast cancer risk among women on Long Island. Am J Epidemiol. 2007 Mar 1;165(5):514-23.