A VERY PROMISING NEW DRUG AGAINST CANCER

A Very Promising New Drug Against Cancer

British researchers (from The Institute of Cancer Research) announce that they have obtained through a new drug against certain cancers, genetic, very promising results in preliminary clinical trials. The results were published in the medical journal The New England Journal of Medicine dated June 24, 2009 (Reference below).

A drug that targets cancer cells and leave normal cells intact
This new drug Olaparib was given to patients with advanced forms of cancer (breast, ovarian or prostate) inherited a mutation in the genes BRCA1 and BRCA2 (this genes were thought to be responsible for about 5% of breast and ovarian cancers, and about 1-2% of early onset prostate cancers). The Olaparib blocks the action of enzymes called PARP [Poly(ADP-Ribose)polymerase] involved in the mechanisms reparatinon DNA. Thanks to this drug in more than half of patients, the tumor had either stabilized or decreased in size. These patients had not responded favorably to standard treatment against cancer. The study shows that patients remained in remission two years after receiving treatment.

The Olaparib target cancer cells but leave normal cells intact. This medication has also very few side effects and some patients have reported that treatment was more bearable than chemotherapy.

Dr Johann de Bono, a researcher of the Institute of Cancer Research who led the clinical trials Phase I with the assistance of AstraZeneca / KuDOS said that positive results should permit completion of ESSI greater extent .

"This drug has shown very impressive to reduce the size of tumors in patients. It gives patients who have already tried many conventional treatments for long periods of remission, free of any symptoms or side effects " said the researcher.

Synthetic Lethality
Olaparib is the first successful example of a new type of personalized medicine using the principle of "synthetic lethality" (synthetic lethality in English), the medicine works effectively with molecular defect of the patient. This treatment is based on experiments conducted in this institute have shown that some cancers had Achilles' heels: if drugs - as olaparib - are used to block an enzyme called PARP in the body, DNA the tumor cell is broken and the cell dies.

Cancers with BRCA1 or BRCA2 mutations were first discovered as being sensitive to inhibition of PARP but there are evidences which suggest that olaparib will be effective in other cancers with defects in machinery repair of DNA. This could apply to certain cancers of non-inherited breast or prostate cancers and up to half of the most common forms of ovarian cancer.

"It is a very important drug for the treatment of cancers associated with BRCA1 / 2. The next step is to test the drug on a more common form of cancer of the ovaries or breast or we hope that this drug will be equally effective." said Professor Stan Kaye who co-led the study.

Professor Alan Ashworth who now runs the charity Breakthrough Breast Cancer Research Center participates in the financing of this research is the source of the work of targeting mechanisms réapration DNA in cancer.

"We are extremely pleased that the work that we conducted in the laboratory are translated as quickly as benefits to patients. This concept is now tested in clinical trials deifferents worldwide." said the professor.

The mode of action of this drug
The concept behind this new approach is called "synthetic lethality". Normal cells have different ways of repairing damage to their DNA. In the case of BRCA tumors, a means of compensation is absent. Olaparib the drug blocks a different path involving the enzyme PARP, normal cells are not affected by this medication because they can use the BRCA genes. When the drug is used on the BRCA tumors, they have no means to repair their DNA when they die. Therefore, this drug is so effective at killing cancer cells and do not affect normal cells.
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Reference:
Article: Inhibition of Poly (ADP-Ribose) Polymerase in Tumors from BRCA Mutation Carriers
Authors: Peter C. Fong, David S. Boss, Timothy A. Yap, Andrew Tutt, Peijun Wu, Mergui-Marja Roelvink, Peter Mortimer, Helen Swaisland, Alan Lau, Mark J. O'Connor, Alan Ashworth, James Carmichael, Stan B. Kaye, Mr. Jan H. Schellens, and Johann S. Bono
Journal Publication:
DOI: 10.1056/NEJMoa0900212
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Source : BBC Health

NEW THERAPIES AGAINST HIV-AIDS : COMBINATION ANTIRETROVIRAL THERAPY WITH CHEMOTHERAPY TARGETED

New Therapies Against HIV-AIDS : Combination Antiretroviral Therapy With Chemotherapy Targeted
The discovery opens the way for new therapies against HIV-AIDS. Now, it might be possible to treat HIV / AIDS adding chemotherapy targeted to current treatment called HAART (Highly Active Anti-Retroviral). This new solution would destroy all the viruses circulating in the body than those hidden in immune cells.

The work was led by Dr. Sekaly of the University of Montreal (Canada) and were published in the journal Nature Medicine.

So far the treatment against AIDS is still hampered by the elimination of "reservoirs of HIV" of immune system cells where the virus is hiding and where the current HAART regimens can not achieve. The researchers were able to identify cells where HIV hides and mechanisms that allow the virus to evade current treatments. They thus paved the way for new therapies completely different from what is currently used.

"Our results support a strategy similar to that used against leukemia: chemotherapy, combined with targeted immune therapy,"

said Dr. Sekaly, professor at the University of Montreal, a researcher at the Research Center of Hospital of the University of Montreal, Director INSERM 743 and Scientific Director of the Vaccine and Gene Therapy Institute in Florida.

"This would destroy the cells containing a virus, while giving the immune system time to regenerate itself with healthy cells."

"For the first time, this study shows that the reservoirs of HIV are not due to insufficient power antiretrovirals but the persistence of the virus in two types of immune CD4 cells for life long memories"

said Dr. Jean-Pierre Routy, hematologist at the MUHC researcher Infection and Immunity Research Institute of the MUHC, and Professor of Hematology at McGill University.

"There are so many types of reservoirs of HIV, each requiring different treatment to be eliminated. "

Indeed, once the virus is hidden in these reservoir cells it becomes dependent: if the cell lives, but the virus lives when the cell dies, the virus dies too. Destroying these immune cells is therefore to eliminate the party best hidden virus. The current HAART regimens effectively destroy viruses circulating in the body but can not reach those hidden in the cell reservoir.

"We now have all new options to explore in the coming years to combat HIV,"

concludes Nicolas Chomont, post-doctoral fellow in the Department of Microbiology and Immunology at the University of Montreal and one of the co-authors of this study.

"The combination of basic and clinical approaches has led to surprising results that allow us to solve another of the mysteries of this virus with a thousand faces."

These new therapeutic options require many years of research before being validated and to become a reality for patients. However, this study represents an invaluable work plan that will guide many laboratories around the world.
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Reference:
Article: HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation
Authors: Nicolas Chomont, Mohamed El-Far, Petronela Ancuta, Lydie Trautmann, Francesco A Procopio, Bader Yassine-Diab, Genevieve Boucher, Mohamed-Rachid Boulassel, Georges Ghattas, Jason M Brenchley, Timothy W Schacker, Brenna J Hill, Daniel C Douek, Jean-Pierre Routy, Elias K Haddad & Sekaly
Journal publication: Nature Medicine
DOI: 10.1038/nm.1972
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Source: Eurekalert

GENE THERAPY SHOWS PROMISING RESULTS AGAINST HIV

Gene Therapy Shows Promising Results Against HIV
The uses gene therapy to treat HIV patients shows promising results in clinical trial phase 2.

The results on 74 volunteers show that the technique is safe and has reduced the effects of viruses on the immune system. The research was conducted by the University of California (USA) and results are published in the medical journal Nature Medicine.

Gene therapy could theoretically afford to replace it with a single treatment the anti-viral combination therapies administered to HIV-positive life.

The team led by Dr. Ronald Mitsuyasu, University of California at Los Angeles (USA) conducted the test on 74 volunteers infected with HIV. These were divided into two groups by drawing lots.

Stem Cells
Patients were well received either placebo or blood stem cells carrying a molecule called "OZ1", a kind of enzyme ( "ribozime"), designed to prevent viral replication by targeting two proteins of the virus for its proliferation .

The use of blood stem cells is to ensure future generations of cells containing the same genetic program modified for therapeutic purposes.

The molecule OZ1 did not cause any unwanted side effects during the trial.

After 48 weeks, no statistical difference in viral load (concentration of virus in the blood) between the two groups. After 100 weeks, the number of CD4 +-cells, which decreases immune from the virus - was higher in the group treated with gene therapy than in placebo.

According to Dr. Ronald Mitsuyasu

"Gene therapy is a treatment that is administered only once and allow the body to defend themselves against the virus without the ongoing contribution of anti-viral field. "

"The treatment is far from perfect and is not as effective as anti-viral therapies, but the current study is a proof of concept, that advertise and administer a single gene in the patient's stem cells that reinjected it into the blood reduces virus replication. "

A long-term monitoring would still be necessary, according to Dr. Mitsuyasu, to ensure that there is no danger to the patient.

Source: University of California - Los Angeles

CURE DIABETES : HOPE TO TRANSPLANT PANCREATIC CELLS

Cure Diabetes : Hope To Transplant Pancreatic Cells
U.S. researchers from the Albert Einstein College of Medicine of Yeshiva University have developed a technique for transplanting pancreatic cells secreting insulin, which causes only a very moderate response of the immune system. This discovery could have important repercussions on how to treat type 1 diabetes. This work was published in the online version of the journal Gene Therapy.

The type 1 diabetes is an autoimmune disease incurable. In patients suffering from this disease, the immune system attacks the beta cells producing insulin in the pancreas. Insulin helps to lower blood glucose (sugar) in blood. People with type 1 diabetes must constantly monitor their blood sugar and need daily injections of insulin.

Transplantation of pancreatic cells represents a promising alternative. Cells taken from deceased donors are injected into the patient. These new cells replace destroyed cells. The disadvantage of this method is that patients must take powerful immunosuppressive drugs to prevent rejection. Most transplant patients still end up rejecting the transplanted cells.

In this study the researchers have successfully transplanted cells make invisible recipient's immune system and protecting the rejection. They managed this by using the natural usability of a virus (adenovirus) to escape the immune system. Pancreatic cells producing insulin were transfect with three genes of adenovirus.

These modified cells were then transplanted to diabetic mice. These transplanted mice were able to maintain glucose levels in normal blood until three months after transplantation. In normal cells grafted restore normal blood sugar levels but only for a few days.

Professor Harris Goldstein, who is the principal investigator of the study, acknowledges that the concept is valid but admits he must improve technology in achieving a combination of all genes that prevent rejection.

Source: EurekAlert

GENE THERAPY GIVES PROMISING RESULTS IN TREATING OBESITY

Gene Therapy Gives Promising Results In Treating Obesity
U.S. researchers from Ohio State University (USA) showed in mice that gene therapy allowed a sustainable weight loss and improved metabolic parameters of the animal. They want to turn to clinical trials in humans. This research is published in the online scientific journal Nature Medicine, 8 March 2009.

A substance called BDNF (Hypothalamic brain-derived neurotrophic factor), produced in the brain called the hypothalamus, plays a major role in weight regulation. It exists both in animals and humans. The absence of the BDNF gene (which produces the molecule BDNF) in mice makes obese.

Left mouse obese untreated.

Right obese mice treated with gene therapy.

The researchers then injected the gene BDNF directly into the hypothalamus of normal mice, diabetic and subjected to a diet rich in fat. Researchers have also developed a system that can negatively regulate the gene. This system is automatically activated when the mice reached a normal weight.

The gene has been active in the obese mice and progressively as the mice lost weight the expression of BDNF protein was reduced by the automatic activation of negative regulatory system put in place to also wait and stabilize at a normal weight. The researchers then restored a normal regulation of weight, a balance between weight gain and weight loss.

Researchers have found, by observing the mice for the long term, there were no adverse side effects on bone density, the circadian rhythm or the general behavior of mice. The diabetic mice saw their health, their parameters and their physical condition improved.

This method has shown very encouraging results in mice, researchers have made an application to the FDA (U.S. regulatory authority of the drug) to conduct clinical trials in humans. They think they can start them within a year.
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Article: Molecular Therapy of obesity and diabetes by a physiological autoregulatory Approach
Authors: Lei Cao, En-Ju D Lin, C Michael Cahill, Chuansong Wang Xianglan Liu & Matthew J During
Journal publication: Nature Medicine
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Credit Nature.

BIOTECHNOLOGY APPLICATIONS

Biotechnology
Biotechnology is a set of methods and techniques using genetic and physiological capabilities of living organisms to develop new products.



Biotechnology progress integrate several disciplines such as microbiology, biochemistry, genetics, molecular biology and computing, and generate a variety of tools to disrupt multiple industries and to modify the environment.

Biotechnology Applications
Pharmaceutical Research (Health)
Health is the first application of biotechnology. They bring new life to the entire pharmaceutical research. Because many drugs are created through a better understanding of micro-organisms and study of DNA, biotechnology and pharmaceuticals can not happen from one another.

Antibiotics
Some infectious diseases have been controlled since the 1940s by antibiotics, partially or wholly obtained by fermentation and vaccines through genetic engineering.

Polymerase Chain Reaction
New diagnostic biotechnology emerged in the years 1980-1990: the technique of molecular probes and the polymerase chain reaction. In a sequence to combine with inherited their complements, these probes may indicate the presence of a defective gene or a gene intruder, due to an invasion of microbes in the body. Similarly, antibodies are able to identify with precision the non-compliant cells (cancerous) or foreign to the body such as bacteria. Thus was born the industry kits for rapid diagnosis based on the use of antibodies. In the case of pregnancy tests, which detect the presence of a specific hormone of the fetus in the urine of women.

Sequencing of Human Genone (Proteomics / Genomics)
The sequencing of the human genome heralds a new era in pharmaceutical research. Of more effective drugs can now be considered as the knowledge of the genome offers the possibility of targeting one or a few genes directly associated with a disease. Proteomics takes over from genomics to determine the role of proteins produced by each gene.

Gene Therapy
Some conditions are related to an anomaly or a lack of synthesis in the body of one or more molecules, as in cases of diabetes or hemophilia. It is now possible to produce large quantities of therapeutic substances similar to those produced by the body through bacteria, yeasts, insect cells or genetically altered mammals that are then injected in the patient. You can also transfer the gene responsible for production of the active molecule missing the individual in need is gene therapy.

Agriculture and Agri-Food (Plant Biotechnology)
The second major application of biotechnology is the agricultural research in which there are three application fields: agriculture, food and environment. Of transgenic varieties (GMOs) are created to increase resistance to pests and diseases or to improve the nutritional quality of products. Many plant varieties are being tested such as those owned by naturally secrete their own insecticides or genes controlling the quality of growth and conservation. When all the genes involved will be identified, transgenic plants may be resistant to cold, frost, drought and salty soil.

Transgenic Animals (Animal Biotechnology)
Transgenic animals in which genetic heritages have been introduced one or more foreign genes, are employed in research laboratories for studying the mechanisms of genesis of cancer, cardiovascular diseases, diseases of bacterial or viral.

STEM CELLS

Stem cells
A stem cell is an undifferentiated cell is characterized by its ability to generate specialized cells in differentiating and its ability to grow almost infinitely to the same (self), particularly in culture.

A cell is said to stem cell (or undifferentiated cell) in two conditions:
1. It can provide specialized cell by cell differentiation and
2. It can virtually be renewed indefinitely.

They are present in the embryonic stage and in the adult organism, but they are much more rare in the adult organism (such as hematopoietic stem cells continuously regenerate blood cells, intestinal stem cells, neural stem cells in regions specific regions of the brain (hippocampus, an area subventriculaire)). In general, stem cells are present in all living multicellular. They play a very important role in the development of organisms and in maintaining them.

The most undifferentiated cell is the zygote or fertilized egg, since the egg will produce all the cells of an organism. We talk about stem cells in animals, but the plant meristems are also formed. In a more comprehensive, all multicellular organisms have stem cells.

Stem cells of animals and in particular human stem cells are the subject of much current research, including medicine to regenerate tissues or create any piece of tissue and organs is the goal of therapy Cell. The origin of stem cells used in research also raises ethical issues: indeed, they come mostly from embryos, although it has recently discovered the possibility of using other sources such as blood cells umbilical cord, or stem cells from adipose tissue. When they allow research on stem cells, the legal limit it to cells from spare embryos from procedures for medically assisted procreation (PMA), prohibiting in particular the creation of embryos solely for the purpose of search. Moreover, given the potential benefits that they seemed to present, trials of therapeutic cloning have been developed to control the production in large numbers.

Stem cell culture


Origin of stem cells
For medical or scientific research, human stem cells (and more generally mammalian) may also be classified in relation to their origin: embryonic, fetal or adult.

Embryonic Stem Cells
Also called ES cells are pluripotent stem cells present in the embryo shortly after fertilization until the stage of blastocyst development said they are still the inner cell mass (the other cells of the blastocyst are the cells of the trophectoderm).

These cells are the source of all tissues of the adult organism and are pluripotent. They can be isolated and cultured in vitro in the undifferentiated state. In terms of specific cultures (on suspension growth ...), individuals can direct their differentiation to a given cell type (neurons, melanocytes, muscle cells, blood cells ...).

Embryonic stem cells were isolated and grown in mice from the early 1980s and helped develop the technique of gene invalidation by homologous recombination (or knock-out) which, after reintroduction of these cells mutated into a recipient embryo and crossings, to obtain mice homozygous for a mutation in a gene.

They are in practice taken from cells of the internal mass of the blastocyst (an embryo that is less than 150 cells), which requires the destruction of the embryo. They can be obtained from frozen embryos from in vitro fertilization or by cloning (by transferring the nucleus of a cell into an egg).

These cells could enable the development of a cell therapy for many degenerative diseases (eg regeneration of injured dopamine neurons in Parkinson's disease after reintroduction into the brain, repair of damaged heart muscle tissue after a heart attack ... ).

Research on embryonic stem cells are currently not very advanced, mainly because of ethical and legal.

Fetal stem cells
A fetal stem cell is a type of multipotent stem cells of fetal origin. They can be harvested from fetuses from a voluntary interruption of pregnancy. Fetal stem cells have the characteristic of being directed to a particular cell type.





Adult Stem Cells
Adult stem cells are undifferentiated cells that are found in tissues that are composed mainly of differentiated cells in most adult tissues and organs. These are generally multipotent cells. They are capable of giving rise to different cell lines of a given tissue. They are the basis of a natural renewal and tissue repair in response to injury.

They are already used in the processing of more than one hundred diseases. They are called "somatic" as opposed to germ cells, and can be found not only among adults but also among children and even in the umbilical cord.










Interest in Research

1. Molecular Study on the human embryo in its early stage of development.
2. Interest of such cell lines to study the process of biological development from its initial phase and see how far back and the defects that cause chromosomal abnormalities like Down syndrome (or trisomy 21).
3. These cells, in some of its features (speed of division, biochemical reactions, expressions of genes), closely akin to precancerous cells. They are thus by their unstable state, an interesting model to address a situation in which a cell can switch to the cancerous condition, in conjunction with genomic research.
4. The research on human pluripotent stem cells may also induce changes in the way of drug development and to test them in a safe and healthy by testing for varieties cellular many more.

Therapeutic application
1. Pluripotent stem cells have the potential for practitioners unlimited source of tissues or specific cells. It hopes to expand the scope for interventions cell therapy for diseases such as Alzheimer's, Parkinson's disease of the bone marrow, heart attack or stroke, burns, diabetes, osteoarthritis or rheumatoid arthritis.
2. It is hoped that these cells can replace cells destroyed (ischemia, irradiation, self, chemotherapy, ...) or overcome cellular functional deficits (Parkinson enzymopathies, etc.)..
3. Stem cells could also contribute to the development of tissue engineering. They have proven their ability to produce four types of muscle fibers exist and could be located on the substrate or tissue on smooth muscle of blood vessels of the heart.
4. Hopes for gene therapy are numerous:

• first applied to abnormal tissues or organs due to the presence of a gene mutated in individuals or young adults.
• second consists in the correction, by somatic gene therapy, an abnormal gene carried by the parents and sent to the fertilized egg. The aim would be that the child does not have the disease resulting from abnormal gene from his parents.
• third is to correct an abnormal gene cloned intra-couple, ie to obtain a cure through cloning: cloning from oocytes of women through nuclear transfer cell, corrected and from a couple of the blastocyst. This solution is the only way to eliminate and certainly the gene abnormality, while creating an egg reconstituted from the genomes of both parents. It is both a cloning and germ line therapy, but within the couple. This means that embryos used to produce the cells will not be sacrificed but will, instead, his chances of leading to the birth of a child free from the anomaly.