**BIOTECH AND PHARMA NEWS**

[Preciouslife1]

The potential role of podoplanin in tumour invasion
British Journal of Cancer (2007)

Podoplanin is a small mucin-like transmembrane protein, widely expressed in various specialised cell types throughout the body. Here, we revisit the mechanism of podoplanin-mediated tumour invasion. We compare molecular pathways leading to single and collective cell invasion and discuss novel distinct concepts of tumour cell invasion.

Invasion of cells into the surrounding tissue and destruction of normal tissue architecture are two hallmarks of malignant tumours. Morphologically, two patterns of tumour invasion can be distinguished: single cell and collective cell invasion. Investigations aimed at unravelling the molecular mechanisms underlying tumour cell invasion have identified various pathways that determine the invasive potential and the invasion pattern of tumour cells (Friedl and Wolf, 2003). The invasion of single cells and small groups of cells is often correlated with dramatic changes in the expression and function of adhesive (e.g. cadherins, immunoglobulin domain-containing cell adhesion molecules) and regulatory proteins (e.g. Snail family members, transforming growth factor ). These changes are reminiscent of early developmental processes, in particular during neurulation and gastrulation, when cells acquire a migratory, mesenchymal phenotype. During this so-called epithelial-mesenchymal transition (EMT) cells lose epithelial markers, such as E-cadherin, and gain the expression of mesenchymal markers, such as N-cadherin and vimentin. The exact role of EMT in tumour progression is still under debate, yet EMT is thought to be particularly important in cancers with single cell migration and early dissemination of tumour cells (Thiery, 2002; Lee et al, 2006). In contrast, the invasion of large cell sheets into neighbouring tissue, often called collective cell migration, is less well understood. These cell sheets maintain the expression of epithelial adhesion structures but can nonetheless invade into the surrounding tissue and thereby destroy the host organ.

Recent experimental results have demonstrated that podoplanin, a small mucin-like protein, mediates a pathway leading to collective cell migration and invasion in vivo and in vitro (Wicki et al, 2006). In this review, we will focus on the molecular basis underlying the phenomenon of cell invasion induced by podoplanin, and discuss potential implications for cancer diagnosis and treatment.

PODOPLANIN IS EXPRESSED IN MOST HUMAN TISSUES

Human podoplanin (T1-2, aggrus and gp36) is a 38 kDa type-1 transmembrane glycoprotein consisting of 162 amino acids, nine of which form the intracellular domain. The extracellular domain is highly O-glycosylated, with sialic acid, -2,3 linked to galactose, forming the main part of the protein's carbohydrate moieties. In normal human tissue, podoplanin is expressed in kidney podocytes (Breiteneder-Geleff et al, 1999), in skeletal muscle, placenta, lung and heart (Martin-Villar et al, 2005), in myofibroblasts of the breast and salivary glands, in osteoblasts and mesothelial cells (Ordonez, 2006b). It is also expressed on the apical surface of rat alveolar type I cells (Rishi et al, 1995). Occasionally, focal expression of podoplanin can be found in circumscribed areas of the basal layer of the human epidermis (Schacht et al, 2005). As podoplanin is expressed on lymphatic but not on blood vessel endothelium, it is widely used as a specific marker for lymphatic endothelial cells and lymphangiogenesis in many species (Breiteneder-Geleff et al, 1999).

The physiological function of podoplanin is still unknown. Podoplanin-deficient mice die at birth owing to respiratory failure exhibiting a phenotype of dilated, malfunctioning lymphatic vessels and lymphoedema (Ramirez et al, 2003; Schacht et al, 2003). In addition, podoplanin can induce platelet aggregation in vitro (Kaneko et al, 2006). In pathological situations studied thus far, the mouse homologue of podoplanin (PA2.26, OTS-8) is induced in mouse skin during tissue regeneration after wounding and treatment with carcinogenic phorbol 12-myristate 13-acetate (Gandarillas et al, 1997). OTS-8 is also induced by 12-O-tetradecanoylphorbol-13-acetate in mouse osteoblastic cells and is constitutively expressed in oncogenic Ras-transformed cells (Nose et al, 1990). These findings suggest a role of podoplanin in tissue development and repair as well as in carcinogenesis.

PODOPLANIN IS UPREGULATED IN THE OUTER EDGE OF THE TUMOUR MASS

The expression of podoplanin is upregulated in a number of different human cancers, including squamous cell carcinoma of the oral cavity, the larynx, the lung, the cervix, the oesophagus, and the skin, in dysgerminomas of the ovary and granulosa cell tumours, in mesothelioma, and in many tumours of the central nervous system (CNS) (Kato et al, 2005; Kimura and Kimura, 2005; Martin-Villar et al, 2005; Schacht et al, 2005; Shibahara et al, 2006; Wicki et al, 2006). The oncofetal M2A antigen expressed in testicular germ cell tumours is identical to podoplanin (Dumoff et al, 2005).

Until recently, tumours have been regarded as purely anaplastic cell masses without a tissue-like organisation. There is growing evidence, however, that the molecular expression pattern of cells in the invading front of solid tumours is different from that of cells in the tumour interior. For example, nuclear localisation of -catenin and upregulation of 1-integrin and the L1 cell adhesion molecule were specifically observed in cells of the invasive tumour front (Brabletz et al, 2001; Hegerfeldt et al, 2002; Gavert et al, 2005). We have recently reported that in about 80% of human squamous cell carcinomas (lung, larynx, cervix, skin and oesophagus) podoplanin is expressed - often in a one-cell layer - at the invasive edge of the tumours (Wicki et al, 2006). In Figure 1, a cancer with single cell invasion (panel A) is compared to a tumour with a collective-cell invasion pattern (panel B). The restricted expression of podoplanin at the front of human squamous cell carcinomas prompted the question whether factors of the surrounding tissue could influence podoplanin expression. Indeed, podoplanin expression can be induced by epidermal growth factor, basic fibroblast growth factor (FGF2) and tumour necrosis factor in MCF7 breast cancer cells, and by bradykinin in 3T3 fibroblasts (Scholl et al, 1999; Wicki et al, 2006). Thus, podoplanin expression may be modulated by the environment of the tumour. However, the exact mechanisms of podoplanin regulation remain elusive.

Human tumour samples stained for E-cadherin (brown) and podoplanin (red) show single cell (A) and collective cell invasion (B). (A) This adenocarcinoma of the colon invades into the surrounding tissue by single cell invasion. Most of the cells of the tumour bulk (TU) express E-cadherin. Single cells invading the tissue (arrows) have downregulated E-cadherin. Podoplanin is not expressed in this cancer. (B) An oesophageal carcinoma has formed an invasive cone that migrates into the surrounding tissue. Podoplanin (red) is expressed in the outer edge of the invading tumour. The tumour cells continue to express E-cadherin (brown) and migrate collectively. Size bar=50 m.

[Preciouslife1]

Part #2

PODOPLANIN BYPASSES EMT IN A MOUSE MODEL OF CARCINOGENESIS

In many mouse models of carcinogenesis, EMT is a critical event during the progression to tumour malignancy. One well-studied model of multistep tumour progression is the Rip1Tag2 mouse model of pancreatic -cell carcinogenesis (Hanahan, 1985). These mice express the simian virus large T antigen under the control of the rat insulin promotor and reproducibly develop tumours of the insulin-producing cells of the islets of Langerhans. To progress from a benign adenoma to malignant carcinoma, these tumours need to lose E-cadherin expression and express N-cadherin instead. This so-called cadherin switch, a molecular event that is part of EMT, is a rate-limiting step in the transition from adenoma to a carcinoma (Perl et al, 1998; Li and Herlyn, 2000). Interestingly, transgenic expression of podoplanin in -cell tumours of Rip1Tag2 mice led to the formation of carcinomas in the absence of a cadherin switch and EMT. In this model, podoplanin shifted the invasion pattern from single cell invasion involving EMT to the invasion of large cell sheets in the absence of EMT. This notion is supported by the finding that forced expression of podoplanin in MCF7 cells did not induce a cadherin-switch or EMT, although the cells formed filopodia and became more migratory and invasive (Wicki et al, 2006). However, although most -cell tumours did not undergo a cadherin switch in podoplanin-expressing Rip1Tag2 tumour cells, a subset of the tumours lost E-cadherin expression. These findings indicate that (i) podoplanin does not suppress the cadherin switch or EMT, but is able to mediate an independent pathway of tumour cell invasion, and (ii) two different types of tumour invasion, involving or not EMT, can coexist in one tumorigenesis pathway (Figure 2).


Two mechanisms are involved in the progression of an adenoma to a carcinoma: either the tumours undergo EMT, or they do not (non-EMT). In EMT, the expression profile of adhesion molecules, components of the cytoskeleton and transcriptional regulators is changed. Although non-EMT pathways of tumour invasion are less well studied, they also lead to alterations of the cytoskeleton and the adhesive apparatus. In addition, podoplanin and possibly other mucin-like transmembrane proteins are involved.

PODOPLANIN PROMOTES TUMOUR CELL SPREADING, MIGRATION AND INVASION

Transfection studies with cultured normal and cancer cells were employed to investigate the function of podoplanin in vitro. In both human keratinocytes and in MCF7 breast cancer cells, the forced expression of podoplanin led to a dramatic change of cellular morphology with a significant decrease of cellular stress fibres and a concomitant formation of filopodia-like membrane protrusions, even in the presence of E-cadherin expression (Scholl et al, 1999; Wicki et al, 2006). Accordingly, adhesion and spreading of cells on the extracellular matrix protein fibronectin was enhanced by podoplanin expression. Such enhanced cell spreading could be blocked by neutralising antibodies against 1-integrin. The interaction between tumour cells and the ECM is a pre-requisite for cell migration and invasion and, indeed, podoplanin increased cell migration of MCF7 cells and HaCaT keratinocytes in the presence of E-cadherin expression. In addition, invasion of podoplanin-expressing cells through a layer of matrigel was considerably enhanced in comparison to cells lacking podoplanin. Invasion of podoplanin-expressing cells appeared to rely on the activity of matrix ma.lloproteases (MMPs), as it could be repressed by TIMP2, an inhibitor of MMP. These in vitro data support the concept that podoplanin expression in human cancers promotes migration and invasion of cancer cells in the absence of a cadherin switch and EMT. However, a recent report with MDCK cells demonstrates that the expression of podoplanin leads to increased single cell migration after loss of E-cadherin expression (Martin-Villar et al, 2006). We therefore must postulate that podoplanin is capable of inducing invasion in both settings, collective and single cell migration. The molecular players and mechanisms that govern the decision which of the two invasion patterns is activated upon podoplanin expression are not known. They may depend on cellular context and certainly warrant further investigation.

PODOPLANIN MODULATES THE ACTIN CYTOSKELETON

Cancer cell migration and invasion depend on an active remodelling of the actin cytoskeleton. Yet, as podoplanin itself has not been found to directly associate with actin in immunoprecipitation assays, how then does it modulate the cytoskeleton? Membrane proteins are linked via ERM proteins (ezrin, radixin and moesin) to the actin cytoskeleton. One of the ERM proteins, ezrin, has been shown to mediate filopodia formation and to induce me.tastasis (Yu et al, 2004). Indeed, podoplanin physically associates with ezrin (Scholl et al, 1999). In addition, overexpression of podoplanin in MCF7 cells, MDCK cells and HaCaT keratinocytes leads to a marked increase in phosphorylation of ezrin and other ERM proteins without affecting ezrin or moesin protein levels (Martin-Villar et al, 2006; Wicki et al, 2006). Thus, ERM-protein phosphorylation may link podoplanin expression to the observed rearrangement of the actin cytoskeleton. Apart from ERM protein function, the activities of Rho-family GTPases, in particular RhoA, are modulated by podoplanin. In MCF7 cells, which express a high level of RhoA, podoplanin was found to downregulate RhoA activity, whereas in MDCK cells, which exhibit a low intrinsic activity of RhoA, its acitivity was enhanced by podoplanin. The basis for this unexpected finding is not clear, although it might reflect a different organisation of the cytoskeleton in different cell types (Martin-Villar et al, 2006). In both cases, inhibition of RhoA modulation led to reduced cell motility, strengthening the notion that the regulation of RhoA activity is causally involved in the pro-migratory phenotype observed in podoplanin-expressing cancer cells (Martin-Villar et al, 2006; Wicki et al, 2006).

[Preciouslife1]

Part #3

PODOPLANIN AS A TOOL FOR CANCER DIAGNOSIS AND THERAPY

The expression of podoplanin in human cancers raises the possibility to employ podoplanin expression as an immunohistochemical marker for diagnosis and prognosis. Podoplanin expression is mainly detected in squamous cell cancers, CNS tumours and germinal neoplasia. These cancers often express E-cadherin even in advanced stages, and the cancer cells tend to migrate in a collective, cone-like manner. In contrast, expression of podoplanin has not been found in the majority of adenocarcinomas, including lung, colon and prostate cancers.

CNS tumours

Podoplanin is widely expressed in tumours of the CNS, including ependymal tumours, choroid plexus papillomas, meningeomas, pilocytic astrocytomas and glioblastomas. In malignant astrocytic tumours, increased expression of podoplanin correlated with higher histological tumour malignancy (Mishima et al, 2006). However, because of its widespread expression in normal tissue, podoplanin has been found of limited use for the diagnosis of CNS tumours (Shibahara et al, 2006).

Cervix tumours

In a series of cervical cone biopsies and radical hysterectomies, podoplanin was expressed in 71% of the samples. Focal expression of podoplanin in the invading front but not in the tumour bulk was present in 59% of the samples, whereas diffuse expression was found in 12% of the cases investigated. Interestingly, focal expression of podoplanin correlated with lymphatic invasion, me.tastasis and a shorter recurrence-free survival, whereas diffuse expression did not. Hence, podoplanin was proposed as a prognostic marker for cervical cancer (Dumoff et al, 2005, 2006).

Germinal tumours

Podoplanin was found expressed in dysgerminomas of the ovary and in granulosa cell tumours. It is uniformly expressed at high levels in seminomas (98%), but also in embryonal carcinomas (69%), teratomas (29%) and yolk sac tumours (25%). Thus, no study has addressed the diagnostic or prognostic importance of these findings (Schacht et al, 2005).

Squamous cell carcinoma of the skin and the lung

Of 28 skin cancer samples analysed, 79% expressed podoplanin. Well-differentiated carcinomas did not express podoplanin, whereas moderately differentiated carcinomas expressed podoplanin exclusively in the invading front. Undifferentiated SCCs finally expressed podoplanin beyond the basal cell layer with frequent cytoplasmic staining (Schacht et al, 2005). Podoplanin is also upregulated in squamous cell cancers of the lung (Wicki et al, 2006).

Mesothelioma

In a series of 30 mesotheliomas with epitheloid growth pattern, 93% expressed podoplanin. Podoplanin expression was also observed on squamous cell carcinomas but not adenocarcinomas of the lung (Ordonez, 2006a).

CONCLUSIONS

Different lines of evidence, sustained by genetic experiments and life cell imaging, support the notion that tumour cells can invade solitarily after loss of cell-cell adhesion, or as a group without losing cell-cell contacts. Recently, we have shown that in human squamous cell cancer, but also in an animal model of insulinoma, podoplanin is involved in a pathway of collective cell migration and invasion, which is independent from EMT (Wicki et al, 2006). Interestingly, however, there is evidence that podoplanin can also promote single cell invasion of MDCK cells and human oral squamous cell carcinomas, thus contributing to EMT-mediated cell motility (Martin-Villar et al, 2006). The molecular dissection of collective and single cell invasion is a relatively new topic in cancer research, whereas numerous efforts in the past and presence attempt to distinguish these two pathways during embryonic development. TGF family members (such as Nodal), FGF, Wnt signalling, cadherin cell adhesion molecules and eomesodermin contribute to the collective migration of vertebrate embryonic tissue. Yet, other TGF family members (such as BMP), Snail family members, FGFs and Wnt play a role in embryonic single cell migration (reviewed by Locascio and Nieto, 2001). Thus, it seems that several factors capable of inducing cell migration and invasion can activate both collective and single cell migration and invasion. Further research is required to unravel the molecular circumstances that modulate the effect of pro-migratory factors on their target cells and determine the resulting invasion pattern.

Expression of podoplanin is also found upregulated in the regenerating epidermis, and we speculate that podoplanin is part of a pathway involving cell migration in the context of tissue repair and that this pathway is also utilised by cancer cells during tumour progression, giving them a selective advantage over less migratory epithelial cells. Induction of podoplanin expression results in multiple adjustments of intracellular signalling pathways, leading to the modulation of Rho family GTPase activities, the phosphorylation of ERM proteins, rearrangement of the actin cytoskeleton and, finally, enhanced cell migration and invasion.

However, some important questions concerning the function of podoplanin in tumours remain open. The function of podoplanin in human sarcomas, including angiosarcomas and Kaposi sarcoma, where the expression of podoplanin is often more diffuse and not restriced to the tumour front, needs to be elucidated (Breiteneder-Geleff et al, 1999). The role of podoplanin expression in carcinoma in situ also has to be addressed. As no expression of podoplanin was found in many biopsies of adenocarcinomas (in particular those of the colon and prostate), and these cancers often exhibit the morphological characteristics of collective cell migration, we must assume that there are podoplanin-independent pathways that also can elicit collective cell migration. Along these lines, the function of other mucin-like cell surface proteins, such as for example MUC1 (Figure 2), has to be clarified. Ultimately, further elucidation of cellular pathways leading to different forms of tumour cell invasion will help to devise new and more efficient strategies against human cancer.

[Preciouslife1]

New HIV Test May Predict Drug Resistance

Researchers at Duke University Medical Center have developed a highly sensitive test for identifying which drug-resistant strains of HIV are harbored in a patient's bloodstream.

The test identifies which drug-resistant strains of HIV are harbored in a patient's bloodstream. Viruses that have evolved resistance to HIV drugs are tagged to appear green, while those that have not are tagged to appear red. (Credit: Duke University Medical Center News Office)
The test may provide physicians with a tool to guide patient treatment by predicting if a patient is likely to become resistant to a particular HIV drug, said one of its developers, Feng Gao, M.D., associate professor of medicine. Drug resistance is one of the most common reasons why therapy for HIV, the virus that causes AIDS, fails.
The test, which detects genetic changes, or mutations, in HIV, also may help scientists understand how the constantly evolving virus develops drug resistance, Gao said. He said such knowledge ultimately may result in the development of new treatments designed to evade resistance.
The findings will appear online on Sunday, Jan. 7, 2007, in the journal Nature Methods, as well as in the journal's February 2007 print edition. The work was supported by the National Institutes of Health and the Duke Center for AIDS Research.
Duke has filed for a provisional patent on the technology, and the researchers are considering ways to establish a new company to pursue its development or to license the technology to an existing company, Gao said.
Because HIV genes mutate so easily and the virus reproduces so rapidly, most people who are infected have many different forms of the virus in their bodies. In some cases, mutated strains take on new properties that make them more resistant to the drugs used in antiretroviral therapy, the primary means of treatment for HIV infection.
During antiretroviral therapy that does not fully suppress the virus, a strain that develops drug resistance will grow more quickly than strains lacking such resistance, and the resistant strain will replicate to become the most prominent virus in the person's body.
"The viral populations found in the blood of one patient can be very different from the populations present in another," Gao said. "Which resistant viruses are at hand can have important implications for the successful treatment of that patient."
More than 20 drugs currently are available for treating HIV infection. All but one of the drugs target two of the genes that serve as blueprints for vital protein components of HIV: reverse transcriptase and protease.
The Duke test examines the genes of HIV strains for mutations at certain positions that are known to be linked to drug resistance. For example, a change at a specific spot along the genetic code -- position 46 -- of the protease gene results in resistance to the drug indinavir.
To assess the test, the researchers analyzed blood samples from three different groups of HIV patients: those who had never received antiretroviral treatment, those who had received treatment but were not currently being treated and those who were receiving treatment but the treatment was not completely successful.
After processing the blood samples and isolating the genetic material in each of them, the researchers added tiny fluorescent tags designed to stick to HIV genes in particular ways. Tags designed to stick to mutated gene locations known to produce drug resistance were labeled to appear green, while tags designed to stick to the same gene locations but where the genes had not mutated were labeled to appear red.
The researchers used a sophisticated computer program to count the number of molecules with green or red fluorescent tags in each sample. The test proved sensitive enough to detect a single mutated virus out of 10,000 nonmutated viruses in the patient samples, Gao said.
"This level of sensitivity makes the assay about 1,000 times more sensitive than the most widely used assays on the market for detecting drug-resistant HIV viruses" Gao said. "Thus, the assay may permit more accurate prediction of treatment outcomes."
The test also can detect when a virus molecule has more than one mutation, a capability that no commercially available test has achieved, Gao said. This capability may prove critical for detecting HIV strains that have become resistant to multiple drugs, a condition that occurs often as many patients are treated with many drugs at the same time.
The test may find broader medical application as well, Gao said. He said it has the potential to detect mutations that confer drug resistance in infectious agents that cause other diseases besides HIV, such as hepatitis B, hepatitis C and tuberculosis.
Other researchers participating in the study were Fangping Cai, Haifeng Chen, Charles B. Hicks, John A. Bartlett and Jun Zhu.

[Preciouslife1]

Posted by: Preciouslife1
In reply to: NoneDate:1/17/2007 11:16:37 AM
Post #of 40725
Schering-Plough, Xoma Deal Continue
Wednesday January 17, 10:18 am ET
Schering-Plough Chooses to Continue Antibody Collaboration With Xoma
http://biz.yahoo.com/ap/070117/xoma_schering_collaboration.html?.v=1
http://www.thestreet.com/_yahoo/newsanalysis/biotech/10332930.html?cm_ven=YAHOO&cm_cat=FREE&...

BERKELEY, Calif. (AP) -- Biopharmaceutical company Xoma Ltd. said Wednesday Schering-Plough Corp. exercised its right to continue its collaboration on developing antibody products.
Xoma said it received additional payments for each of the new programs and will receive research funding for each projects. The company did not release details on the additional programs or the amount paid upfront.

The companies started the collaboration May 23. Xoma is responsible for discovering antibodies selected by Schering-Plough. Additionally, Xoma is expected provide preclinical studies.

Shares of Xoma rose 14 cents, or 6 percent, to $2.49 on the Nasdaq in morning trading. Earlier in the session, shares traded as high as $2.55, topping a previous 52-week high of $2.50.

[Preciouslife1]

Statin Switches May Triple Patient Deaths

GPs should be wary of switching patients from branded to generic statins if a high dose is needed, experts have said.

In a letter to the Lancet, cardiologists from City General Hospital in Stoke-on-Trent suggest that since switching statins, a threefold increased death rate has been noted among patients with previous MI.

In October 2005, local PCTs and the North Staffordshire NHS Trust decided that prescription of 40mg and 80mg atorvastatin (Lipitor) should be suspended and 20-40mg simvastatin used.

An audit of City Hospital patients compared outcomes of 100 patients over a three-month period prior to the switch and a further 121 for three months a year later.

After the switch, the proportion of deaths increased from 5 to 17 per cent. The cardiac readmission rate also rose from 33 to 44 per cent.

But Andrew Riley, head of medicines management at Stoke-on-Trent PCT, said the switch was only recommended for patients on 10mg atorvastatin.

The DoH has called for PCTs to ensure more than 69 per cent of patients on statins are given a generic version. It could save the NHS $85 million a year. But a DoH spokesperson insisted its policy is not the same as that outlined in the letter from cardiologists in Stoke, and endorses 'switching from branded to generic statins at comparable dosages'.

A study carried out in a Hertfordshire GP practice monitored the effects of switching 70 patients from 10 or 20mg atorvastatin to an equ.ivalent dose of simvastatin and showed there was no significant change in mean cholesterol four months after the switch, and only one patient switched back because of side effects.

Comment.."""Muscle tissue wasting, rhabdomyolysis, CoQ10 depletion, collagen and elastin depletion....""" Ya think that with all these potential side effects of statin therapies, that someone would be looking at the damage that they ""Could"" be doing to heart valves, brain tissue due to the CoQ10 depletion and the dementia and transient global dementia problem that they can create......Nah, not when you have the best selling segement of drugs to combat a ficticious problem made up by the very drug companies to combat high cholesterol...now some people do have high cholesterol problems and do need to be treated, but many natural remedies exist like red yeast and cinnamon per se that have none of the toxic and damaging side effects that statin drugs can unleash on many patients, especially those with genetic makeups conducive for adverse reactions and DNA mutations.....this could make Vioxx and Celebrex cases look petty in comparison IMHO....and I will be in the forefront of any suits and campaigns to get the truth about the dangers of Statin drugs out there to the public....

[Preciouslife1]

Hungry genes?
New Scientist - Jan. 20, 2007 .....Part #1

IT SOUNDS like the ultimate in personalised medicine: a tailor-made diet that controls your weight, optimises your health and reduces your risk of heart disease, cancer and diabetes. All you have to do to get one is hand over a couple of hundred dollars, take a simple genetic test, and wait for a personalised nutrition plan based on your genes to drop through your door.

Diet plans like this are widely available from private clinics, over the internet and, in the US, even in some supermarkets. Advocates claim they take the uncertainty out of grocery shopping and provide a guaranteed route to long-term health and fitness. Critics say the tests are at best misleading and at worst potentially harmful. I was simply curious. With my family history of heart disease, I wanted to know whether a diet tailored to my DNA could help me override my genes.

In theory, yes. All other things being equal, genetics is the reason why one person can eat a poor diet without serious health repercussions while in another person the same diet leads to high blood pressure, cancer or heart disease. This is the basis of nutrigenomics ? the science of how the chemicals in food alter the regulation of genes and proteins, and how variations in certain genes might predispose people to troublesome gene-nutrient interactions and ultimately disease. Nutrigenomics is a relatively new science with genuine promise, but it has yet to yield many results of practical value. Even so, no sooner had nutrigenomics got off the ground than eager biotech companies began mining the results of newly published papers and translating them into over-the-counter tests. So does the science support such tests?

Each person has around 25,000 genes, many of which have several common variants. Some are linked to an increased risk of disease. The tests look at a handful of such genes to identify which variants the individual carries. If they have "bad" variants, the company offers advice on how nutritional and lifestyle changes could help counteract genetic flaws.

In 2001 the UK-based company Sciona broke new ground with the first such "nutrigenetic" testing service to provide personalised dietary and lifestyle advice. Nutrigenetics is the application of nutrigenomics ? which looks at the genome in general ? to the individual. However, the test soon drew criticism from the UK's Human Genetics Commission, and prompted the HGC's 2003 report "Genes Direct", which assessed genetics-testing kits sold directly to the public. The watchdog group GeneWatch UK also criticised the tests and called on major UK retailers to boycott the products.

The UK retail market soon collapsed, and Sciona focused on marketing the product to private health clinics, dieticians and nutritionists instead. The company relocated to Boulder, Colorado, in 2005, and began selling tests in the US via websites and genetic-testing companies; last year it sold about 18,000. Other companies sprang up offering the Sciona test, or something similar, for $100 to $1000.

The nutrigenetics industry has recently come under renewed fire, this time in the US. An investigation conducted by the US Government Accountability Office in July suggested that the type of nutrigenetic testing offered by four companies ? Sciona, Genelex, Market America and Suracell ? "misled consumers by making predictions that are medically unproven and so ambiguous that they do not provide meaningful information". The GAO report also criticised some companies for selling supplements supposedly tailored to a customer's genetic needs. These "nutraceuticals" cost anywhere from $1200 to $1800 per year, yet according to the report they differed little from multivitamins available at the local pharmacy.

Despite this, I wanted to know whether I had gene variants that could increase my risk of broken bones, heart disease or cancer, and was intrigued by what the nutritional advice might be. Sciona provided me with its "Cellf" test, which is the most widely sold test of its kind, available at many online drugstores and shopping sites and sold by two of the four companies scrutinised by the GAO investigation. It looks at 19 genes that the company believes provide insights into heart and bone health, the body's antioxidant and detoxification ability, plus insulin sensitivity and inflammatory response. Market America also sells a test of the same genes, but under another name. I swabbed the inside of my cheek, completed a food and lifestyle questionnaire, and slipped both in the mail.

The good and the bad
Six weeks later I received my results. First, the good news. For the two genes related to antioxidant ability, which help destroy DNA-damaging free radicals, I have no "bad" variants. Of the three genes involved in detoxification I have versions that efficiently rid my body of noxious compounds.

Now the not-so-good news. My number one priority, according to the report, is bone health. The test screened for a total of seven variants, spread over four genes, each linked to bone problems. I tested positive for four potentially damaging variants. Two hinder absorption of calcium and vitamin D ? ingredients critical for bone building ? and the other two disrupt the process of dissolving old bone and creating new bone. It sounds to me like I'm a prime candidate for osteoporosis.

Sciona's advice: increase daily intake of vitamin D to 20 micrograms and omega-3 fatty acids to 3 grams, and exercise for 45 to 60 minutes at least five times per week. I get a pat on the back for getting enough calcium, my moderate caffeine consumption, and for my healthy body mass index.

Next: heart health. The test reveals that I have variants in several genes that alter my body's ability to me.tabolise B vitamins ? like folic acid, B6 and B12. These vitamins are important for maintaining low levels of homocysteine ? high levels of which are a risk factor for cardiovascular disease. Also, my variants of the inflammatory-response genes can lead to "reactions that are too strong or inappropriate in their timing", according to Sciona, which could damage my cardiovascular system. I also have potentially problematic variants in genes that ********************bolise cholesterol and triglycerides, and another in a gene that alters blood flow, which can adversely affect "tightening of your blood vessels". Nowhere does the report say I'm at increased risk of a heart attack, but reading between the lines I feel like a time bomb.

The final segment of Sciona's report covers insulin sensitivity. In four of the five genes tested, I have variants that make my fat cells less efficient at removing sugar from my blood and storing it in the cells. That means insulin resistance, which has been linked not only to type 2 diabetes but high blood pressure and heart disease as well.

While all this sounds quite alarming Sciona's advice on how to deal with these risks seems comparatively mundane: eat more foods rich in B-vitamins and antioxidants like vitamins A, C and E, and increase the amount of omega-3 fatty acids; decrease my glycaemic load (how much sugar I pour into my blood) and eat more fibre and whole grains; cut down saturated fats and cholesterol; exercise more. The advice hardly seems personalised but Rosalynn Gill-Garrison, co-founder and chief scientific officer of Sciona, assures me the intake goals are calculated based on my particular genetic make-up.

Paranoid that my bones are disintegrating and my arteries narrowing I seek a second opinion. Jose Ordovas, director of the Nutrition and Genomics Laboratory at Tufts University in Boston, provides reassurance. "The genetic component [of a complex disease] is split among 10, 20, 50, 100 genes or more, and you are being tested for one," he says. "Remember, you can go wrong with one of your genes but you may be blessed with another set of genes that compensate."

Robert Nussbaum, chief of the medical genetics division of the Institute for Human Genetics at the University of California, San Francisco, puts it even more bluntly. "I don't think it is information worth having? I wouldn't trust any of it," he says. "Testing negative [for certain variants] doesn't mean that you are not going to develop these diseases; testing positive doesn't mean that you will. If I was asked by a patient what would I recommend based on this test, bottom line: eat right."

So if feeding my genes is as simple as eating healthily and laying off the fat and sugar, what good has it done me to find out about specific variations? According to critics of such tests, not much. Nussbaum says that the science behind the tests is often far from conclusive ? and may be based on single studies that have never been replicated.

[Preciouslife1]

Part #2

One example is California-based Consumer Genetics's "caffeine me.tabolism test", which went on the market in November. The test is based on a paper published in March 2006 in The Journal of the American Medical Association (JAMA ). It reported that depending on what version you carry of the gene CYP1A2 , which codes for the caffeine-me.tabolising enzyme cytochrome P450 1A2, you are either a "rapid" or "slow" caffeine me.taboliser. According to the JAMA report, higher caffeine intake is associated with increased risk of heart attack only in people with slow caffeine me.tabolism. Within weeks of publication, Consumer Genetics announced on its website that it would offer a caffeine me.tabolism test and give results within three days.
Hannia Campos, a nutritionist at the Harvard School of Public Health and a co-author of the JAMA paper, says that she was shocked when she discovered the findings had been translated into a genetic test. "I couldn't believe it. I thought it was a joke." She says the findings need to replicated and confirmed before they are used to guide people.
What's more, the tests lack clinical validity, says Nussbaum. That is, the gene variations that the companies are testing have a pretty low "positive predictive value", meaning that even among people who carry a "bad" variant, only a small percentage actually go on to develop the disease. "None of these genes is going to kill you," says Ordovas. "It might put you at 5 or 10 per cent higher risk than somebody [without the variant], but that's it."
Proof of the pudding In comparison, a family history of heart disease, especially the early-onset form, has been shown to increase risk 100 to 500 per cent, says Howard Levy, a physician and medical geneticist at Johns Hopkins University in Baltimore, Maryland. "Family history is the biggest thing missing from what this company has to offer." he adds.
More to the point, says Levy, even when the associations between genes and disease are fairly robust, it is far from clear whether increasing intake of specific nutrients will lower the risk. Take, for example, variants of the MTHFR gene and heart disease. Of the genes tested in the Cellf test, all the researchers I contacted agreed that this had the strongest association; individuals carrying the variation known as C677T had higher levels of homocysteine, which is associated with an increased risk of heart disease.
It is also known that folic acid and vitamins B6 and B12 lower homocysteine levels. Sciona and Genelex both advise people to consume more B vitamins if they test positive for potentially problematic variations in the MTHFR gene. But two studies published in The New England Journal of Medicine in April reported that, although supplements of B vitamins could lower homocysteine levels, this did not reduce the risk of heart attacks in patients with vascular disease.
In fact, says Philip Wood, director of the genomics division at the University of Alabama at Birmingham, no studies have demonstrated that any nutritional supplementation would actually overcome a genetic variation and reduce the risk of a complex disease. "That would require clinical trials? and those studies haven't been done."
Howard Coleman, CEO of Genelex, disagrees. "There needs to be a symmetry between the level of proof and the risk associated with something," he says. "The clinical-trial standard is the standard you need to have if you are going to give somebody a dangerous drug. Remember, this is just a harmless test. [Dietary interventions] are helpful but can do no harm."
While he acknowledges that the conclusions are "not medically proven in the sense that there's been clinical trials done", he disputes the GAO's notion that the advice is worthless. "An expert in this area? may say it is too soon or that it is not worth the money but they won't say it is worthless. We are at the early stages of this ? we are playing Pong and transitioning to Pac-Man."
Sciona's Gill-Garrison is also confident about the tests. "If we claimed we were going to make you live 100 years or prevent the development of a particular disease, I would agree with them, but on the other hand if we are providing personalised info to help you control cholesterol levels because of particular sensitivities you have based on your genetics ? absolutely there is enough information."
Genelex connected me with Carolyn Katzin, a Los Angeles-based certified nutrition specialist, for a personal consultation and interpretation of my genetic results. Genelex usually charges an additional couple of hundred dollars for this service, a total of $525 for the test plus consultation.
Katzin's analysis differed from Sciona's by ignoring the food questionnaires, which she says are not accurate indicators of nutrient intake, and instead asked about family history before focusing on my genes. She offered much the same nutritional advice as Sciona, however ? eat more of this, less of that, take a good multivitamin, add specific supplements, and "be careful with salt and avoid too many packaged or processed foods". Her knowledge of my family history, though, did lead her to suggest, after seeing my mixed bag of gene variants, that I check my levels of homocysteine, HDL and LDL cholesterol, triglyceride and C-reactive protein ? all of which have been linked to cardiovascular disease risk ? the next time I get a physical.
One of the major criticisms about nutrigenetics testing is that it may induce complacency in people who find they have "good" genes and panic in those who find theirs are "bad". The information is certainly difficult to ignore when it's there in black and white. But good genes or bad, discussing family history with a physician and taking a few blood tests will probably give you a similar or more accurate snapshot of your current health ? and without the hefty price tag. That is exactly what I'm going to do. Now if I can just get an appointment?
Bijal Trivedi is a freelance science writer based in Washington DC
Out of control? Bijal Trivedi In the European Union, the US, Australia and Canada genetic testing is coming under increasing scrutiny, and governments are making efforts to standardise regulations. However, nutrigenetic tests are considered "lifestyle" tests, largely because they do not make clinical claims.
"The EU considers most genetic tests low-risk and thus exempt from independent pre-market review. This means that as long as the company can honestly state the technical accuracy of the test, the sale of the test and the advice offered is unregulated," says Stuart Hogarth, a research associate at the University of Cambridge who specialises in policy issues with genetic testing. In Canada and Australia there are even fewer controls. Nutrigenetic tests are reviewed for neither analytical nor clinical accuracy.
In the US, the majority of tests being offered are "home brews": companies receive genetic samples directly from physicians or consumers, do the analyses, and then issue a report. Historically, the Food and Drug Administration has not regulated these tests. "That means you don't have an evaluation of the clinical validity of the test," says Kathy Hudson, director of the Washington-based Genetics and Public Policy Center.
Jose Ordovas, director of the Nutrition and Genomics Laboratory at Tufts University in Boston, supports the idea of personalised nutrition but is concerned that the current batch of nutrigenetics tests is too much, too soon. Without regulation, he cautions, jumping the gun could wipe out public support and damage the reputation of the entire field. "We are very, very early in the game," he says.

[Preciouslife1]

Eli Lilly Japan To Release New Cancer Therapy To Hospitals
Nikkei English News - Jan. 20, 2007

TOKYO (Nikkei)--The Japanese arm of U.S. pharmaceutical company Eli Lilly and Co. announced that it will begin releasing its mesothelioma treatment pemetrexed on Monday.

To ensure the safety of the drug, Eli Lilly Japan KK will first introduce it at around 400 hospitals nationwide that specialize in chemotherapy.

Pemetrexed, which will be sold under the brand name Alimta, is used in conjunction with the anti-cancer agent cisplatin. Because only a few individuals participated in clinical trials, the company will monitor the post-treatment condition of around 300 patients after the drug is released and periodically report to the Ministry of Health.

The drug will cost 240,649 yen for a 500ml bottle. Eli Lilly Japan expects peak sales of around 1.62 billion yen per year.

Mesothelioma is an aggressive form of cancer linked to asbestos exposure.

(The Nikkei Saturday morning edition)

[Preciouslife1]

Sanofi, Taiho Have Positive S-1 Cancer Drug Trials

Reuters Health - Jan. 19, 2007 PARIS (Reuters) - Sanofi-Aventis and Taiho Pharmaceutical said final-stage clinical study results of their S-1 oral stomach cancer drug showed it "significantly" improved chances of survival compared with just having surgery.
French drugmaker Sanofi-Aventis and Japanese drugmaker Taiho said on Friday that patients with early stage stomach cancer who had been treated with S-1 had a 32 percent lower risk of dying from the disease than those who were treated by surgery.
The drug had met both its trial goals, and the companies said in a joint statement it was one of the most important advances in early stage gastric cancer in 40 years.
Stomach cancer is the second most common cause of cancer death in the world, with more than 700,000 deaths a year.
The main goal of the phase III trial on 1,059 Japanese patients was to demonstrate overall survival. Its secondary endpoint was relapse-free survival and safety.
S-1 is already prescribed in Japan to treat stomach cancer as well as several other forms of the disease. It is in the final stages of health trials in the United States and Europe.
Taiho develops and markets the drug in its home country and several other Asian countries, while Sanofi develops and markets S-1 in Europe and the United States.
The results were announced at the Gastrointestinal Cancers Symposium in Orlando, the United States.

[Preciouslife1]

ImClone cancer drug does not increase side effects..

Datamonitor HealthWire - Jan. 19, 2007 According to a new study, the addition of ImClone's Erbitux to radiation therapy treatments does not increase the rate or duration of some side effects in the treatment of advanced head and neck cancers.
This study was an in-depth look at outcomes from a study published in the New England Journal of Medicine in 2006. That study showed that patients with locally advanced head and neck cancer who were given Erbitux in addition to radiation therapy, showed not only a survival benefit, but also that there was no increase in mucositis or dysphagia over patients who received radiation therapy alone. This study compared the duration of these normal tissue toxicities between the two arms from the England Journal of Medicine study. For the overall group, the median duration of any mucositis or dysphagia was three months. Of the patients with mucositis, 28% experienced this toxicity for three months. Of those with dysphagia, 31.5% experienced this toxicity for three months. Fewer than 10% suffered from these toxicities for more than 15 weeks. These findings were similar for the two treatment arms. "These findings are important because they show that the addition of this monoclonal antibody therapy has lifesaving benefits without any additional length of suffering from the primary acute side effects," said James Bonner, radiation oncologist at the University of Alabama in Birmingham.Merck KGaA, which holds the rights to Erbitux outside the US, has reported that its sales of the cancer treatment were up 55% in Q4, making the company $435.6 million.

[Preciouslife1]

Prostate Cancer Trial Halted Due to 3 Cases of Leukemia

HealthDay - Jan. 19, 2007 FRIDAY, Jan. 19 (HealthDay News) -- A trial testing whether the chemotherapy drug mitoxantrone would benefit men with prostate cancer has been stopped because three of the 488 patients who received the drug developed leukemia.
According to the Southwest Oncology Group, which was running this phase III trial, 983 patients were randomly assigned to receive hormone deprivation therapy alone or hormone deprivation therapy plus six doses of mitoxantrone.
"While it is recognized that these are only three isolated cases, the Southwest Oncology Group believes it is in the interest of patient safety to close the trial and monitor the patients for evidence of any unexpected late effects," lead investigator Dr. L. Michael Glode, of the University of Colorado, said in a prepared statement.
"Of importance, this possible increase in risk would not have been identified so early without a randomized clinical trial that allowed comparison between a group receiving standard treatment and a group receiving a novel therapy approach," Glode added.
One expert thinks the decision to end the trial was correct.
"They are doing the right thing," said Dr. Anthony D'Amico, chief of radiation oncology at Brigham and Women's Hospital, in Boston. "The initial studies of mitoxantrone were done in men with end-stage prostate cancer -- but their life expectancy was about a year and a half. The life expectancy of the men in this study is 10 to 15 years or more. Only in a study like this can you see the long-term side effects of chemotherapeutic agents like mitoxantrone."
However, another expert doesn't see anything unusual about the incidence of leukemia among men receiving mitoxantrone.
"This is the first trial that tested adjuvant chemotherapy in men with high-risk prostate cancer," said Dr. Mario Eisenberger, a professor of oncology at Johns Hopkins University. "I wouldn't be so alarmed with the very low number of leukemias in this setting, especially if you put that against the possible gain that you can get from this approach."
Mitoxantrone has been approved for use in prostate cancer as well as in breast cancer, and it is commonly used to treat multiple sclerosis. In this trial, mitoxantrone was being used to treat "poor risk" prostate cancer patients. These are men whose cancer has spread to the tissues next to the prostate, or whose cancer has a high probability of returning after surgery or radiation therapy.
The trial was stopped on Jan. 12 after the Southwest Oncology Group's Data Safety Monitoring Committee reviewed side effects and survival. The committee found that no patients in the hormone deprivation-only group developed leukemia, which suggested there was an increased risk of leukemia from mitoxantrone.
Another expert wasn't surprised that there appears to be an association between mitoxantrone and leukemia in these men.
"It is well known that mitoxantrone is associated with a small, but real, increased risk of leukemia," said Dr. Celestia Higano, an assistant professor of medicine and urology at the University of Washington. "The incidence of leukemia in this trial is on target with what has been seen in breast cancer. This is not unexpected," Higano said.
Despite closing the trial early, it still is going to take years of monitoring the patients to really determine whether or not mitoxantrone actually has a benefit for men with prostate cancer, Higano said.
"We are going to have to wait a number of years to see if there isn't, at the end of the day, some potential survival benefit, even though it was at the cost of some patients developing leukemia," Higano said.
Eisenberger thinks these trials, despite some drawbacks, are essential to find ways to save lives.
"We would like to see the continued support for the kinds of trials we are doing," Eisenberger said. "We are really trying to see if we can save more lives. People will die of the disease; people will die of the consequences of treatment, but the net benefit in the end is that you save thousands of lives at the cost of a very small proportion, which really saddens me, but life is not perfect."
Both Eisenberger and Higano are concerned that the fallout from this trial will affect other trials. "Some degree of alarm over these findings is going to make people hesitant to continue with research in this area," Higano said. In addition, Higano is concerned that doctors will stop referring patients to trials because of the halting of this trial.
More information
The U.S. National Library of Medicine can tell you more about mitoxantrone.

[Preciouslife1]

Health Canada approves Cangene's Anti-Hepatitis B product

Market News Publishing Canada - Jan. 19, 2007 CANGENE CORP
Cangene today announces that it has received a Notice of Compliance with conditions ("NOC/c") for its HepaGam B(TM) hyperimmune product from the Biologics and Genetic Therapies Directorate of Health Canada. The approved indication is for the prevention of Hepatitis B recurrence following liver transplantation in adult patients with Hepatitis B who have no or low levels of hepatitis B virus replication. This NOC/c confers marketing approval to the drug in Canada while requiring the Company to continue with a confirmatory clinical study. HepaGam B(TM) is Cangene's Hepatitis B Immune Globulin (human) Injection, which is a purified antibody or hyperimmune that is specific for the hepatitis B virus. It is the only intravenous product licensed in Canada for this indication. An NOC/c is granted to provide patients who are suffering from serious, life-threatening or severely debilitating illnesses or conditions, accelerated access to promising new therapies. "There are currently no other products licensed in Canada to prevent hepatitis B recurrence following liver transplantation and we are pleased to be able to answer the unmet medical need faced by these patients," said Dr. John Langstaff, Cangene's president and chief executive officer. Hepatitis B is a highly infectious virus that can be spread through contact with blood and other bodily fluids. Hepatitis B recurrence can occur after liver transplantation in patients who are hepatitis B surface antigen ("HBsAg")-positive at the time of transplant. Recurrence results from the infection of the liver graft with hepatitis B virus that had remained in circulation. Cangene manufactures HepaGam B(TM) in its Winnipeg facility using a process similar to that of WinRho(R) SDF, vaccinia immune globulin and VariZIG(TM), the Company's other hyperimmune products that have been approved in Canada and/or the United States. HepaGam B(TM) was approved last year by the United States Food and Drug Administration for treatment following acute exposure to blood containing HBsAg, perinatal exposure of infants born to HBsAg-positive mothers, sexual exposure to HBsAG-positive persons and household exposure to persons with acute hepatitis B virus infection. A vaccine for hepatitis B is available, yet the virus continues to cause significant disease worldwide and pose a significant public health problem. Hyperimmune products can be used in situations where a vaccine is not applicable. Approximately 60,000 new infections are seen annually. There are an estimated 1.25 million chronically infected Americans, 20-30% of whom were infected as children. Severe liver disease is seen in 15-25% of chronically infected people. About Cangene Cangene is one of Canada's largest biopharmaceutical companies. It was founded in 1984 and is headquartered in Winnipeg, Manitoba. Cangene carries out research and development in Mississauga, Ontario and in Winnipeg. It uses patented manufacturing processes to produce plasma-derived and recombinant therapeutic proteins. In addition to having four approved products, Cangene has two products that have been submitted for regulatory review and a significant clinical trial program. Cangene also provides contract research and manufacturing services using its drug-manufacturing expertise and the resources of Chesapeake Biological Laboratories, Inc. (a wholly owned subsidiary). The Company has manufacturing facilities in Winnipeg, Manitoba and Baltimore, Maryland. Cangene's website, www.cangene.com, includes product and investor information, including past news releases. Chesapeake's website is www.cblinc.com. Forward-looking information The reader should be aware that Cangene's businesses are subject to risks and uncertainties that cannot be predicted or quantified; consequently, actual results may differ materially from past results and those expressed or implied by any forward-looking statements. Factors that could cause or contribute to such risks or uncertainties include, but are not limited to: the regulatory environment including the difficulty of predicting regulatory outcomes; changes in the value of the Canadian dollar; the Company's reliance on a small number of customers including government organizations; the demand for new products and the impact of competitive products, service and pricing; cost of raw materials, especially the cost and antibody concentration in plasma; fluctuations in operating results; government policies or actions; progress and cost of clinical trials; reliance on key strategic relationships; costs and possible development delays resulting from use of legal, regulatory or legislative strategies by the Company's competitors; uncertainty related to intellectual property protection and potential cost associated with its defence; the Company's exposure to lawsuits, and uncertainties related to estimates and judgments used in preparation of financial statements in accordance with GAAP and related standards, and other matters beyond control of management. Risks and uncertainties are discussed more extensively in the MD&A section of the Company's most recent annual report and annual information form, which are available on the Company's website or on SEDAR at www.sedar.com. Scientific information that relates to unapproved products or unapproved uses of products is preliminary and investigative. No conclusions can or should be drawn regarding the safety or efficacy of such products. Only regulatory authorities can determine whether products are safe and effective for the uses being investigated. Healthcare professionals are directed to refer to approved labelling for products and not rely on information presented in news releases. The cautionary statements referred to above should be considered in connection with all written or oral statements, especially forward-looking statements, that are made by the Company or by persons acting on its behalf and in conjunction with its periodic filings with Securities Commissions, including those contained in the Company's news releases and most recently filed annual information form. Forward-looking statements can be identified by the use of words such as "expects", "plans", "will", "believes", "estimates", "intends", "may", "bodes" and other words of similar meaning (including negative and grammatical variations). Should known or unknown risks or uncertainties materialize, or should management's assumptions prove inaccurate, actual results could vary materially from those anticipated. The Company undertakes no obligation to publicly make or update any forward-looking statements, except as required by applicable law. %SEDAR: 00002351E TSX closing price for CNJ Date: 2007/01/18 Closing Price: 8.150
__________________________________________________ __________

[Preciouslife1]

elbion Acquires Late-Stage Product Candidate for Treatment of Alcohol Dependence

From the PharmaLive.com News Archive - Jan. 19, 2007
LEUVEN, Belgium, Jan. 19, 2007- elbion NV, a leading European drug discovery and development company, today announced it has acquired a number of product candidates from the French biotechnology company DrugAbuse Sciences. The most advanced candidate, Naltrexone Depot, a sustained release formulation of naltrexone, will become elbion's lead product and the company expects it to enter pivotal Phase III clinical trials in 2007. A second asset acquired is Buprenorphine Depot, a sustained release buprenorphine indicated for the treatment of opiate addiction.
The acquisition of the DrugAbuse Sciences candidates was made in return for a financial consideration comprising elbion shares. Full financial terms were not disclosed.
Naltrexone Depot is a novel, sustained release formulation of naltrexone, an antagonist that blocks receptors in the brain and is used in the treatment of opiate and alcohol abuse. Unlike conventional naltrexone dosage forms (i.e. daily tablets), Naltrexone Depot is designed as a simple once-a-month intramuscular injection which elbion believes will offer significant advantages in the treatment of alcoholism where patient treatment compliance is a major limiting factor.
Previous clinical trials with Naltrexone Depot have shown encouraging results with a trend towards greater levels of abstinence from alcohol for patients receiving treatment compared to those on placebo.
elbion intends to begin a pivotal Phase III trial in 2007 with an improved formulation of Naltrexone Depot. elbion is collaborating on formulation development work with Brookwood Pharmaceuticals, a US drug delivery company and acquired a licence to certain Brookwood technologies as part of the asset acquisition. Brookwood will supply the product for trials.
Bernd Kastler, CEO of elbion, said: "This agreement brings us another advanced clinical product to add to our pipeline and one which we believe can be a significant value driver for elbion. Alcohol dependence has a profound effect on the lives of millions of people around the world and we believe that Naltrexone Depot has the potential to play a major role in their treatment. We intend to initiate a well-designed Phase III programme with an improved formulation of the product, and then to commercialise Naltrexone Depot through our own sales and marketing operations in certain territories and through licensees in others."
Patrick Langlois, Chairman of DrugAbuse Sciences said: "Today's announcement of elbion's acquisition of the Naltrexone Depot programme and other assets from DrugAbuse Sciences is good news for the future of what we believe is a very high value product. We are confident elbion's clinical expertise and the plans they have put in place for the development and commercialisation of Naltrexone Depot will allow the full potential of the product to be realized and bring value to DrugAbuse Sciences investors through their holdings in elbion."
Arthur J. Tipton, Ph.D., President and CEO, Brookwood Pharmaceuticals said: "Brookwood Pharmaceuticals strongly believes in the technical and market potential of the long-acting naltrexone under development at elbion. We have developed a positive relationship with the senior team at elbion and are enthused to be working with such a dynamic organization. We look forward to accelerating to market important products for the treatment of alcohol and opiate abuse."
Buprenorphine depot is in pre-clinical development. elbion intends to develop the product for the treatment of opiate addiction.
Contacts elbion NV Ann De Beuckelaer PhD Phone: +32 (0) 16 31 62 84 ann.debeuckelaer@elbion.com
Media Contacts: Citigate Dewe Rogerson Chris Gardner/ Valerie Auffray/ Yvonne Alexander Phone: +44 (0) 207 638 95 71
About elbion elbion NV is a Belgian company focused on the discovery and development of new drugs for CNS and immunological diseases. The Company has its headquarters in Leuven and also has significant R&D facilities in Radebeul, Germany.
Including Naltrexone Depot, elbion has a maturing pipeline with three products in the clinic for areas of significant commercial potential and a further portfolio of high quality late pre-clinical development compounds. ELB245 is an established CNS compound that elbion is developing for overactive bladder. It is in Phase II. ELB353, a highly potent PDE4 inhibitor is in Phase I trials for chronic inflammation.
elbion's strategy is to grow its pipeline through its own integrated drug discovery activities leveraging its expertise in CNS and immunology and also by targeted in-licensing and M&A. elbion will maximise the value of its product portfolio by further partnering of its compounds and through selectively marketing products building its own sales and marketing operation.
In addition to its own clinical pipeline, elbion has a research agreement with Gilead Sciences for the discovery and development of new drugs for the treatment of hepatitis C virus (HCV).
elbion was formed in 2006 through the merger of elbion AG and 4AZA Bioscience NV. elbion AG began operations through a management buyout from Degussa Group in 2002. 4AZA was founded in 2002 as a spin-off from the Catholic University of Leuven.
About Naltrexone Depot Naltrexone Depot is a novel, sustained release formulation of naltrexone in development for the treatment of alcohol and opiate abuse. The product is formulated for once-a-month intramuscular injection. From the injection site, naltrexone is slowly released into the blood and then into the central nervous system (CNS) where it blocks endorphin receptors. The sustained release mechanism promotes an effective concentration of naltrexone in the CNS over a whole month, thereby potentially improving treatment outcomes by reducing non-compliance often reported with daily naltrexone tablet administration, a significant hurdle in addiction treatment. Alcohol abuse affects more than 20 million people in the US and Europe.
About Brookwood Pharmaceuticals Brookwood Pharmaceuticals, Inc. is a product-focused drug delivery company that applies its patented and proprietary technologies to design, formulate, and manufacture improved pharmaceutical products. The clinical applications of Brookwood technologies are diverse with current partnered programs covering ********************bolic diseases, cancer, orthopedic applications, drug/alcohol addiction, psychosis, ocular diseases and sun-induced conditions, and programs ranging from preclinical to Phase III.
The company holds more than 20 drug-delivery patents, and has expertise and facilities for feasibility studies, formulation and product analysis, scale up, clinical lot preparation, and production of final dosage forms. Brookwood Pharmaceuticals has a wide-range of delivery technologies particularly for long-acting parenterals such as injectable microparticles and injectable solid implants to deliver small molecules, peptides, proteins, nucleic acids, and other biological macromolecules. In addition to microspheres and implants, Brookwood provides drug delivery technology with solid-lipid nanoparticles, liposomes, and hydrophobic drug salts, novel biodegradable matrices, and supplies biodegradable polymers through its Lakeshore Biomaterials subsidiary. Brookwood Pharmaceuticals is a for-profit subsidiary of Southern Research Institute. For more information see http://www.brookwoodpharma.com

[Preciouslife1]

Posted by: Preciouslife1
In reply to: NoneDate:1/20/2007 8:34:55 AM
Post #of 40858

MANATEE FIRM MAKING LEAPS AT DNA'S DAWN
Bradenton Herald - Jan. 20, 2007

...and this news from my hometown, and a company that is analyzing my DNA for use in understanding and analyzing dna mutations and anomalies often associated with Rhabdomyolysis and statin drug usage. They have analyzed my dna for usage with their statinome test for statin drug tolerability and are in my camp through their research and analysis that statin drugs are dangerous to one's dna and system...

http://www.google.com/search?hl=en&q=dnaprint+genomics.com

For a company whose lab work regularly solves crimes, has made international headlines about Margaret Thatcher's family heritage and is poised for growth at the scientific frontier of medicine, the vibe at DNAPrint Genomics, Inc., is surprisingly low-key.

A single, hand-lettered sign scrawled with the company's name this week was the only indication it had moved during the holidays from downtown Sarasota to a larger building at 1621 W. University Parkway in southern Manatee County. The move was necessary to provide more space for its new subsidiary, DNAPrint Pharmaceuticals, Inc., officials said.

The company's specialty is human genetics and, in particular, the genome, the accumulation of all of an organism's hereditary information. It is a developer of genomics-based products and services.

Its forensic work and genealogy tests have made international headlines in stories broadcast on National Public Radio and in publications like The New York Times, USA Today, CBS News and London's The Sunday Times.

The company's findings figure in the investigation of sensational crimes, such as an effort to capture the so-called London Minstead Rapist, a serial rapist suspected of more than 90 assaults. Scotland Yard has turned to DNAPrint Genomics for help.

"The investigation has drawn heavily upon forensic resources for psychological and geographic crime profiles," said Matthew J. Thomas, Ph.D., the company's senior scientist and manager of laboratory operations, after a trip to London last summer. Investigators used DNA information to analyze crime scene samples, but as far as Thomas knows, they have not yet made an arrest in the case.

On Wednesday, Thomas was giving a tour of his firm's bright new laboratory and discussing one of its DNA testing products - AncestrybyDNA, a kit designed to reveal an individual's family heritage.

For a $240 fee, clients can send a swab with tissue from inside the cheek that the company uses for a basic test, which pinpoints a person's genetic heritage based on four major anthropological groups: Native American, East Asian, sub-Saharan African and Indo-European. Depending on the results, additional tests may be ordered.

The tests have produced some shocking results. One of the company's tests showed that Henry Louis Gates Jr., the famous black scholar, was half white. Another showed that Carol Thatcher, daughter of former British Prime Minister Margaret Thatcher, was of Middle Eastern descent.

Each test takes a couple days of work, Thomas said.

The company, with 20-some employees spread over the United States and Canada, stays connected to its far-flung staff through electronic communications rather than face-to-face interaction, said Emanuela I. Charlton, Ph.D., who works in customer service.

It has employees in California, Pennsylvania, Colorado and Toronto, she said, adding that it also owns a percentage of a German company called BioFrontera.

Richard Gabriel, DNAPrint Genomics' chief executive officer and president, who accepted shares of stock instead of cash compensation when he was hired in 2002, lives in Boston. Gabriel hired the company's chief medical officer and chairman of the board, Hector J. Gomez, M.D., Ph.D., who resides in Tampa.

The company's annual revenues are in the $3 million range, Gomez said in a phone interview from Tampa. He said the money the company earns is sufficient to operate its labs, but acknowledged wearily that he is "in the process of raising money all the time" for research and development.

During 2006, the company invested almost $3.2 million in research and development and $133,000 in patents to protect its technology rights, according to material the company provides investors.

Gomez said he expects the new subsidiary, DNAPrint Pharmaceuticals, Inc., launched in October 2005, will help its bottom line. It will be ramping up in the company's new quarters and the technology Gomez expects it to develop would cut by half the 12 years and $800 million currently necessary to develop a new drug.

"Now, with this technique, we can reduce the time of drug development by at least half to six years and decrease the cost by a significant number because we're minimizing mistakes," he explained.

It will attempt to design drug regimens that go beyond the one-pill-fits-all concept.

"With this technology, pharmaco-genomics, it allows us to take a sample of DNA from any patient and in the lab predict response - who is going to respond well, who will have side effects. Obviously, we can do that then by maximizing the efficiency of the drugs and minimizing the side effects, based on the person's genetic makeup," Gomez said.

Both Gomez and DNAPrint Genomics will also be part of a massive research initiative announced last month by the H. Lee Moffitt Cancer Center & Research Institute of Tampa. The center said it would partner with an affiliate of Merck & Co., Inc. pharmaceutical company to expand biotechnology research with the goal of developing personalized medicine.

Merck and Moffitt will form a for-profit company, called M2GEN, that will develop personalized cancer treatments using a patient's genetic profile.

Researchers plan to compile a database of tumor tissue and other medical information to determine why some patients respond to a treatment and others do not. The database could grow to more than 30,000 patients within five years, officials said in announcing the partnership.

"For a look at future, in 10 years, I believe you'll have (something similar to) a credit card in your pocket with all your information. It's your genetic makeup and the doctor will look at it and prescribe the medicine for you," said Gomez. "We are very excited about this."

DNAPrint Genomics was founded by Tony Frudakis, Ph.D., and acquired by another company in 2000. In 2001, Frudakis teamed with other scientists to develop new genomics products with consumer, forensic and pharmaco-genomics applications, according to Securities and Exchange Commission documents.

Since then, the company has acquired several other firms that brought scientific assets with them, such as Kenna Technologic Inc., which develops software for building computer models that mimic biological systems, and Ellipsis Biotherapeutics Corp., which specializes in genotyping and can analyze human, plant and animal tissue, SEC documents said.

Last year, the company entered into an exclusive license agreement with Harvard College at Harvard Medical School, for research and development of a diagnostic test that would identify those at risk of developing vascular diabetic complications, SEC documents reported.