Possible Drug Target For One Of The Most Aggressive Breast Cancer

Van Andel Research Institute (VARI) investigators have identified a gene that could be an important therapeutic target in the treatment of the most aggressive forms of breast cancer. Currently, patients with these cancers have few treatment options.

“Breast cancer mortality rates are actually declining, but the cancers that don’t respond to traditional treatments tend to be more aggressive and have decreased survival rates,” said VARI Research Scientist Carrie Graveel, Ph.D., lead author of the study published this week in Proceedings of the National Academy of Sciences U.S.A.

Researchers found that the Met gene may play a critical role in the development of an aggressive form of breast cancer known as basal breast cancer.

“Met has already been associated with decreased survival in breast cancer, but this study identifies its importance in specific types that can be distinguished at the molecular level,” said VARI Distinguished Scientific Fellow George Vande Woude, Ph.D., who heads the laboratory that conducted the research.

In the 1980′s, Dr. Vande Woude’s laboratory at the National Cancer Institute demonstrated that inappropriate levels of Met occur in human tumors, and that cells with inappropriate Met signaling dramatically impact the spread of cancer. This signaling is implicated in most types of human cancers and high Met expression often correlates with poor prognosis.

“We found Met in the majority of breast cancers,” said VARI Research Technician Jack DeGroot, another of the study’s authors. “But levels were highest in aggressive types, making Met a promising drug target that could help patients that currently have few treatment options.”

According to the American Cancer Society, breast cancers account for more than one in four cancers diagnosed in women in the United States. The National Cancer Institute estimates that 40,170 women in the U.S. will die from breast cancer in 2009.

“This very exciting work by the Van Andel Research Institute gives us a new target for treatment of patients with one of the worst types of breast cancer – basal breast cancer,” said Dr. Daniel D. Von Hoff, Physician-in Chief of the Translational Genomic Research Institute (TGen) in Phoenix, Arizona, which initiated an alliance with Van Andel Institute in February. “Since there are many new inhibitors of Met available for clinical trials, we now have a direct route for immediate application of these important findings in the care of patients with this very aggressive form of breast cancer.”

Cost-Effective DNA Test For Crime Scenes and Disease Diagnosis

DNA Test For Crime Scenes and Disease Diagnosis Could Be More Cost-Effective according to a new technique developed by Scientist in Japan which improved the already Known method of the fabled polymerase chain reaction (PCR).

PCR is a technique to amplify a single or few copies of a piece of DNA across several orders of magnitude, generating millions or more copies of a particular DNA sequence this allow Scientist and investigators to detect or find DNA in cases where there is a very strong chance of not finding any usable sample.

This new technique not only will reduce cost at the time of doing the test but also will open new opportunities in the field of medicine and criminal studies since it will lead to new methods in the usage of  PCR.

This new method consists in , a quenching probe (QProbe) and a nonfluorescent 3′-tailed probe are used. The QProbe is a singly labeled oligonucleotide bearing a fluorescent dye that is quenched via electron transfer between the dye and a guanine base at a particular position. The nonfluorescent 3′-tailed probe consists of two parts: one is the target-specific sequence on the 5′ side, and the other is complementary to the QProbe on the 3′ side. When the QProbe/nonfluorescent 3′-tailed probe complex hybridizes with the target in PCR, the fluorescence of the dye is quenched. Fluorescence quenching efficiency is proportional to the amount of the target

This method substantially reduces the cost of real-time PCR setup because the same QProbe can be used for different target sequences. Moreover, this method allows accurate quantification even in the presence of nonspecific PCR products because the use of nonfluorescent 3′-tailed probe significantly increases specificity.

Genes From Canines may help cure Brain Cancer

Pinpointing the genes involved in human brain cancer can be like looking for a needle in a haystack, and sometimes the needle you find may not be the right one. By comparing human and canine genomes, researchers at North Carolina State University have discovered that a gene commonly believed to be involved in meningiomas-tumors that affect the meninges, or thin covering, of the human brain and account for one out of four adult brain tumors -may not be as key for tumor formation as previously thought, and they’ve narrowed the search for the real culprit.

Meningiomas are intracranial tumors, meaning that they do not grow within brain tissue itself, but in the space between the brain and the skull. In humans, they are associated with genetic defects of large segments of chromosomes, which makes isolating the specific genes involved extremely difficult. Humans suffering from meningioma frequently lose one copy of almost the entire length of human chromosome 22. This chromosome is made of almost 50 million base pairs of DNA that code for more than 500 genes.

“The dog has been man’s best friend for centuries, and now the genome of the dog could well be man’s next best friend,” says Dr. Matthew Breen, professor of genomics at NC State.

“With so much genetic material to consider, one can see why figuring out which genes play a key role in meningiomas is extremely difficult,” says Breen. “By looking at tumors seen in both humans and dogs we have a simple way to narrow the search: we compare the affected areas of a human chromosome with related areas on dog chromosomes. This works because dogs and humans are genetically similar and both get the same kinds of cancers. While we share much of our genetic material, the DNA of a dog is organized differently to our own and this makes it possible to isolate smaller ‘shared’ regions of genetic data rather than looking at an entire chromosome.”

Breen, NC State colleagues Rachael Thomas and veterinary neurologist Natasha Olby, along with researchers from the University of California-Davis and the Wellcome Trust Sanger Institute in Cambridge, UK collaborated on the project, sharing samples of canine meningiomas for research. Their results were published in the Journal of Neurooncology.

Previous researchers had pinpointed a particular tumor-suppressing gene on human chromosome 22, known as NF2, as a possible contributor to meningioma. They believed that the deletion of NF2, with its tumor suppressing abilities, could trigger tumor growth.

In looking at genetic changes across the whole genome, Breen’s team compared human chromosome 22 to its canine counterpart. In dogs, the region shared with 22 is “split up” across three separate dog chromosomes – numbers 10, 26 and 27- with the NF2 gene appearing on dog chromosome 26. The researchers discovered that in dogs with meningioma, chromosome 26, and hence NF2, was rarely affected, casting doubt on this gene as playing a significant role in the disease. Instead, dogs with meningioma frequently showed loss of parts of dog chromosome 27. This led the researchers to focus on the portion of human chromosome 22 that corresponds to canine chromosome 27.

“Now, instead of looking at 50 million base pairs that contain several hundred genes, we can focus on the portion of human chromosome 22 that is evolutionarily conserved with dog chromosome 27,” Breen says. “By looking at dog and human meningiomas together we reduce the amount of searching we need to do 50-fold. It’s the old needle/haystack dilemma, except that using information from dog and human tumors allows us to concentrate our search on the two percent of the haystack that actually contains the needle, and not spend time and resources on the other 98 percent.”

Breen also noticed that the other chromosome involved for canines that suffer from meningioma is dog chromosome 17, which correlates with part of human chromosome 1. Defects of this chromosome are involved in almost 70 percent of human meningioma cases and are associated with a poor patient outcome. He hopes that he can use this correlation to further narrow the search for specific genes involved with the disease.

In addition the team looked also at gliomas, another kind of brain tumor, and have shown common genetic features shared between human and canine tumors that are now under further investigation.

“The data support that dog and human tumors are very similar at the genetic level, so both species will benefit from this research,” Breen says. “It’s proof of the ‘One Medicine’ concept – the idea that human and animal health relies on a common pool of medical and scientific knowledge and is supported by overlapping technologies and discoveries.”

Source:
Tracey Peake
North Carolina State University

One step closer to end HIV life cycle

In order for viruses to reproduce, they must infect a cell, this part we understand. But do we really know how the most devastating of all Viruses and the smartest one of all times really works?

Once i was told that in order to provide an accurate answer i need to understand the question, and of course the subject. The HIV Virus is the ultimate question of our time and we need to be able to understand it if we want to be able to eradicate this threat.

Viruses are not technically alive: they are sort of like a brain with no body. In order to make new viruses, they must hi-jack a cell, and use it to make new viruses. Just as your body is constantly making new skin cells, or new blood cells, each cell often makes new proteins in order to stay alive and to reproduce itself. Viruses hide their own DNA in the DNA of the cell, and then, when the cell tries to make new proteins, it accidentally makes new viruses as well. HIV mostly infects cells in the immune system.

Scientists have discovered that specific microRNAs (non-coding RNAs that interfere with gene expression) reduce HIV replication and infectivity in human T-cells. In particular, miR29 plays a key role in controlling the HIV life cycle. The study suggests that HIV may have co-opted this cellular defense mechanism to help the virus hide from the immune system and antiviral drugs.

Replication: Once HIV binds to a cell, it hides HIV DNA inside the cell’s DNA: this turns the cell into a sort of HIV factory.

The microRNA miR29 suppresses translation of the HIV-1 genome by transporting the HIV mRNA to processing-bodies (P-bodies), where they are stored or destroyed. This results in a reduction of viral replication and infectivity.

Infection: Several different kinds of cells have proteins on their surface that are called CD4 receptors. HIV searches for cells that have CD4 surface receptors, because this particular protein enables the virus to bind to the cell. Although HIV infects a variety of cells, its main target is the T4-lymphocyte (also called the “T-helper cell”), a kind of white blood cell that has lots of CD4 receptors. The T4-cell is responsible for warning your immune system that there are invaders in the system.

Scientis think the virus may use this mechanism to modulate its own life cycle, and we can  use this to our advantage in developing new drugs for HIV Retroviral therapies greatly reduce viral load but cannot entirely eliminate it. This interaction between HIV and miR29 may contribute to that inability. Perhaps, by targeting miR29, we can force HIV into a more active state and improve our ability to eliminate it.

The team of Scientist managed to looked at miR29 expression levels in infected and uninfected cells and found that miR29 expression was enhanced by HIV-1 infection. Blocking the activity of miR29 with interfering RNA resulted in increased replication and infectivity of the virus. The scientists tested the association of miR29 and HIV-1 by mutating both miR29 and its target region on the HIV virus. When either was altered, miR29s suppression of HIV replication and infectivity was reduced or eliminated. In addition, the team suppressed P-bodies in the cells and noted a similar effect. This suggests that HIV may use miRNAs to become dormant and escape immune response.

A.Vissuetti

Gene that plays role in ADHD found

What is Attention Deficit Hyperactivity Disorder?

Attention Deficit Hyperactivity Disorder, ADHD, is one of the most common mental disorders that develop in children. Children with ADHD have impaired functioning in multiple settings, including home, school, and in relationships with peers. If untreated, the disorder can have long-term adverse effects into adolescence and adulthood.

Pediatric researchers have identified hundreds of gene variations that occur more frequently in children with attention-deficit hyperactivity disorder (ADHD) than in children without ADHD. Many of those genes were already known to be important for learning, behavior, brain function and neurodevelopment, but had not been previously associated with ADHD.

Unlike changes to single DNA bases, called SNPs or “snips,” the alterations examined in the current study are broader changes in structure. Called copy number variations (CNVs), they are missing or repeated stretches of DNA. CNVs have recently been found to play significant roles in many diseases, including autism and schizophrenia Everyone has CNVs in their DNA, but not all of the variations occur in locations that affect the function of a gene. The current study is the first to investigate the role of CNVs in ADHD.

ADHD is the most common neuropsychiatric disorder in children, affecting an estimated 1 in 20 children worldwide. It may include hyperactive behavior, impulsivity and inattentive symptoms, with impaired skills in planning, organizing, and maintaining focus. Its cause is unknown, but it is known from family studies to be strongly influenced by genetics.

Fruit Flies may help prevent Human Brain Tumors

Brain tumors, a condition that affects millions of people every year and in some cases with devastating if not fatal consequences.

At Duke-NUS Graduate Medical School in Singapore researchers have found a tumor-suppressing protein in the fly’s brain, with a counterpart in mammals, that can apparently prevent brain tumors from forming.

Brain tumors are categorized as primary or secondary. Primary brain tumors start in the brain and may be either benign or malignant. About 190,000 Americans are diagnosed each year with a primary brain tumor.  Children usually have primary tumors. This is the leading cause of solid tumor deaths in children under the age 20 and is the third leading cause of cancer death in young adults ages 20-39.

The fruit fly’s developing brain, stem cells called neuroblasts normally divide to create one self-renewing neuroblast and one cell that has a different fate. But neuroblast growth can sometimes spin out of control and become a brain tumor.

Follow-up experiments showed that PP2A is important for regulating Polo kinase function, and showed that these two critical brain tumor suppressors work together to control neural stem cell divisions.

This studies can help us understand not only how the brains work but also how can we prevent conditions that affect this magnificent organ and saved lives.

Combined Stem Cell Gene Therapy Approach Cures Human Genetic Disease In Vitro

A study led by researchers at the Salk Institute for Biological Studies, has catapulted the field of regenerative medicine significantly forward, proving in principle that a human genetic disease can be cured using a combination of gene therapy and induced pluripotent stem (iPS) cell technology. The study, published in the May 31, 2009 early online edition of Nature, is a major milestone on the path from the laboratory to the clinic.

“It’s been ten years since human stem cells were first cultured in a Petri dish,” says the study’s leader Juan-Carlos Izpisúa Belmonte, Ph.D., a professor in the Gene Expression Laboratory and director of the Center of Regenerative Medicine in Barcelona (CMRB), Spain. “The hope in the field has always been that we’ll be able to correct a disease genetically and then make iPS cells that differentiate into the type of tissue where the disease is manifested and bring it to clinic.”

Although several studies have demonstrated the efficacy of the approach in mice, its feasibility in humans had not been established. The Salk study offers the first proof that this technology can work in human cells.

Belmonte’s team, working with Salk colleague Inder Verma, Ph.D., a professor in the Laboratory of Genetics, and colleagues at the CMRB, and the CIEMAT in Madrid, Spain, decided to focus on Fanconi anemia (FA), a genetic disorder responsible for a series of hematological abnormalities that impair the body’s ability to fight infection, deliver oxygen, and clot blood. Caused by mutations in one of 13 Fanconi anemia (FA) genes, the disease often leads to bone marrow failure, leukemia, and other cancers. Even after receiving bone marrow transplants to correct the hematological problems, patients remain at high risk of developing cancer and other serious health conditions.

After taking hair or skin cells from patients with Fanconi anemia, the investigators corrected the defective gene in the patients’ cells using gene therapy techniques pioneered in Verma’s laboratory. They then successfully reprogrammed the repaired cells into induced pluripotent stem (iPS) cells using a combination of transcription factors, OCT4, SOX2, KLF4 and cMYC. The resulting FA-iPS cells were indistinguishable from human embryonic stem cells and iPS cells generated from healthy donors.

Since bone marrow failure as a result of the progressive decline in the numbers of functional hematopoietic stem cells is the most prominent feature of Fanconi anemia, the researchers then tested whether patient-specific iPS cells could be used as a source for transplantable hematopoietic stem cells. They found that FA-iPS cells readily differentiated into hematopoietic progenitor cells primed to differentiate into healthy blood cells.

“We haven’t cured a human being, but we have cured a cell,” Belmonte explains. “In theory we could transplant it into a human and cure the disease.”

Although hurdles still loom before that theory can become practice – in particular, preventing the reprogrammed cells from inducing tumors – in coming months Belmonte and Verma will be exploring ways to overcome that and other obstacles. In April 2009, they received a $6.6 million from the California Institute Regenerative Medicine (CIRM) to pursue research aimed at translating basic science into clinical cures.

“If we can demonstrate that a combined iPS-gene therapy approach works in humans, then there is no limit to what we can do,” says Verma.

Medical trial in animals proves it can safe human lives

The news went out today from the group of  Scientist involved in the study.

While i was reading the story i couldn’t be more surprised from the fact that the animals right, don’t kill the wales, stop research in animals let the humans die and so and so groups did not protest regarding this, and then i found out why, it is not a very known disease.

A dog born with a deadly disease that prevents the body from using stored sugar has survived 20 months and is still healthy after receiving gene therapy at the University of Florida – putting scientists a step closer to finding a cure for the disorder in children. Called glycogen storage disease type 1A, the genetic disease stops the body from being able to correctly store and use sugar between meals. In order to survive, children and adults with this disease must receive precise doses of cornstarch every few hours. The disease is even more dire in dogs, which must be fed sugar every 30 minutes to survive.

“Without treatment, these dogs all die,” said David Weinstein, M.D., M.M.Sc., director of the UF Glycogen Storage Disease Program and co-investigator on the study. “People usually survive because they are fed so much as infants. But by 4 to 6 months of age, they will have developmental delays and a big liver. If it is diagnosed at that point, the kids can do fine. If it is not diagnosed, then the kids get exposed to recurrent low sugars, and they will end up with brain damage, seizures or they will die.”

This is very good news for all the parents and childrens that have to deal with this disease.

We humans and please don’t take this the wrong way but we want to save all the plants, trees, animals or bugs out there and this is good, if we are good with earth earth will be good with us, but what about being good with our fellow humans, with our children’s, with our brothers and sisters who also share this earth, don’t they deserved the same respect and the same right to live.

I´m not pro hurting animals in fact i think that anyone who hurts an animal should go to prision because it is a crime, but it is also a crime to let people die because some people just dont like the fact that we need to use, monkeys, or pigs, or dogs to do this research and be able to save human lives.

At the end it depends on you… What do you think Scientist should do? and would you rather have a golden retriever playing with you or a child.

A. Vissuetti

About Science, Politics & what really matters

Here i am, once again sitting in front of my computer and i found my self thinking about science, life and Politics, now don’t get me wrong i´m very concerned about politics, i think a lot about the decisions that i make when voting, who is the best candidate?, who has better references?, who i think would make a good leader? but are the people that i vote for caring about there decisions? I don’t want anyone to think this is in concern to an specific country because is not, this is world wide because when a small country decides to approved a law that might say that they will allow stem cell research or Human DNA investigations all the big ones reunite and make a decision that basically is “No, you are wrong and we are not letting you do that even thought that research can saved lives”.

Science and Politics, this is a very delicate subject, should the politicians have some control over it?, Yes for sure, should they decide for us taking in consideration that most of the time the general public is not well informed and because of this unable to take a conscious position about the subject? well i think they shouldn´t.

We only hear one side of the story and it is important that we demand to know all the facts. When it comes to Researches or new discoveries we only hear from our governments the scary part of the story we only listen to alarmist or the very religious person with no more grounds that their faith  or even worst the man with no knowledge at all that just like to listen to the sound of his own voice.

What would you say if you where a cancer patient and i tell you that we could have save you, event prevent the cancer from happening but the government didn’t let the studies to continue because it was dangerous to play God. What if i tell you that we could be saving millions of innocent childrens lives around the world but we wont because a group of narrow mind miss informed politicians around the globe decided that it was for the best of all nations not to do the research that could save them.

Is not that the consequences to pay if something goes wrong are not huge, because they are, but so where the consequences of discovering the X-rays, or the consequences of discovering the vaccine for the yellow fever or malaria, there are always consequences, the question is are we willing to pay the price of not accepting the consequences for those researches.  Are you ready to let someone else take those decisions for you?

A.Vissuetti

A Newer, Better Way to prevent Cervical Cancer

Cervical cancer is caused mostly when a woman is infected in her cervical area with the human papillomavirus. There is now a DNA test that will permit the identification and prevention of cervical cancer.

These days most women know that they should go to their doctor about once a year and have a test done, known as a pap smear, that is used to identify the possible onset of cervical cancer. This test should be d one every year from the moment she becomes sexually active, and it consists of smearing a biological sample from the woman’s cervix onto a growth medium to see if there are any cancerous cells.

“Pap smears check for cell changes caused by the cancer, but it is not foolproof. That’s why it’s done every year because it can miss some cell changes, which it might pick up the next year.

There are many reports of Pap smears not detecting abnormal cells until it’s too late and the cancer is advanced. The DNA test, on the other hand, tests for the actual virus, which makes it much more effective as a test for cervical cancer because we now know that all cervical cancer is caused by this virus.” - ‘Good Morning America’ medical contributor Dr. Marie Savard

Cervical Cancer kills about 4,000 women a year in the US, however the incidence rate is much much higher.

The Bill and Melinda Gates Foundation funded an 8 year study that has categorically shown the greater effectiveness of this method.