**BIOTECH AND PHARMA NEWS**

[Preciouslife1]

Pharmasset Commences Dosing In 28-Day Combination Study Of R7128 With Pegasys(R) Plus Copegus(R) For Hepatitis C

Pharmasset, Inc. (Nasdaq: VRUS) has commenced dosing in a Phase 1 study of R7128 in combination with Pegasys (pegylated interferon) plus Copegus (ribavirin) in up to 75 treatment-naive patients chronically infected with hepatitis C virus (HCV) genotype 1. R7128 is a prodrug of PSI-6130, an oral cytidine nucleoside analog polymerase inhibitor of HCV that is being developed through Pharmasset's collaboration with Roche. The purpose of this study is a preliminary evaluation of safety, tolerability, pharmacokinetics and antiviral activity of R7128 in the clinically-relevant setting of combination therapy with the current standard of care for chronic HCV infection.

The study will include two to three oral doses of R7128 (500 mg to 1500 mg) that will be administered twice-daily with Pegasys plus Copegus for 28 days. There will be 25 patients in each dose cohort with 20 patients randomized to receive R7128 and 5 patients randomized to receive placebo, all administered in combination with the standard of care. After completing 28 days of the triple combination regimen and a follow-up period of 4 weeks of Pegasys plus Copegus, all patients will then receive 40 weeks of open-label standard of care dosing under a separate protocol.

"We are excited about the rapid pace of development of R7128, and the opportunity to evaluate its safety and potency in combination with the standard of care," stated Dr. Michelle Berrey, Pharmasset's Vice President, Clinical Development & Chief Medical Officer. "The 28-day endpoint will provide meaningful data on early viral kinetics and the proportion of patients who have undetectable HCV RNA by the end of this treatment period. We look forward to sharing the preliminary results of this combination study in the first quarter of 2008 and making plans for future studies of R7128."

About Pharmasset

Pharmasset is a clinical stage pharmaceutical company committed to discovering, developing and commercializing novel drugs to treat viral infections. Pharmasset's primary focus is on the development of oral therapeutics for the treatment of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV).

Pharmasset is currently developing three product candidates. Clevudine, an oral treatment for chronic HBV infection, is in Phase 3 clinical trials for registration in the Americas and Europe. Clevudine is already approved for HBV in South Korea and marketed by Bukwang Pharmaceuticals in South Korea under the brand name Levovir. R7128, an oral treatment for chronic HCV infection, is in a Phase 1 clinical trial through a strategic collaboration with Roche. Racivir, which is being developed for the treatment of HIV in combination with other approved HIV drugs, has completed a Phase 2 clinical trial.

About R7128

R7128 is being developed for the treatment of chronic HCV infection. R7128 is a prodrug of PSI-6130, a pyrimidine nucleoside analog inhibitor of HCV RNA polymerase. Results from an oral single ascending dose study of PSI-6130 in 24 healthy male volunteers showed that PSI-6130 was generally well tolerated with no serious adverse events in doses up to 3000 mg.

R7128 Phase 1 Study Overview

The Phase 1 clinical trial is a multiple center, observer-blinded, randomized and placebo-controlled study to investigate the pharmacokinetics, pharmacodynamics, safety, tolerability and food effect of R7128 in healthy volunteers and in patients chronically infected with HCV genotype 1. This adaptive Phase 1 study is comprised of three parts:

Part 1 is a single ascending dose study of R7128 conducted in 46 healthy volunteers. The primary objective of Part 1 is to assess the safety, tolerability and pharmacokinetics of R7128 following single ascending doses under fasting conditions. The secondary objective of Part 1 is to explore the effect of food on the pharmacokinetics of R7128. Results from the single ascending dose portion of the study indicated that all doses of R7128 studied (500 mg to 9000 mg) were generally safe and well-tolerated. All patients completed the study, and none experienced gastrointestinal adverse events or serious adverse events during the study. No hematological or laboratory abnormalities of clinical significance were noted.

Part 2 is a multiple ascending dose study of R7128 conducted in 40 patients chronically-infected with HCV genotype 1 who previously failed interferon therapy. The primary objective of Part 2 is to assess the safety, tolerability and pharmacokinetics of R7128 after once-daily (QD) or twice- daily (BID) dosing for 14 days. The secondary objective is to assess antiviral activity by measuring the change in HCV RNA. Preliminary data from the multiple ascending dose portion of the study indicated that R7128 demonstrated potent, dose-dependent antiviral activity in four patient cohorts receiving 750 mg or 1500 mg administered either once-daily or twice-daily for 14 days as monotherapy. Patients receiving 1500 mg BID demonstrated a mean 2.7 log10 IU/mL (>99%) decrease in HCV RNA. There was no evidence of viral rebound in any dose cohort during the 14 days of dosing. R7128 was generally safe and well tolerated. There were no serious adverse events, no adverse events requiring dose modification, no dose-related gastrointestinal adverse events and no clinically significant changes in hematologic or other laboratory parameters.

Part 3 is a multi-center, observer-blinded, within-cohort randomized, placebo-controlled study being conducted in up to 75 treatment-naive patients with genotype 1 hepatitis C virus. The primary objective is to assess the safety, tolerability and pharmacokinetics of R7128 in combination with Pegasys plus Copegus. The secondary objective of Part 3 is to evaluate the short-term change in HCV RNA. The study will include two to three oral doses of R7128 (500 mg to 1500 mg) that are being administered twice-daily with Pegasys plus Copegus for 28 days.

Pegasys and Copegus are registered trademarks of Roche.

About Hepatitis C

Hepatitis C is a blood-borne infectious disease of the liver and is a leading cause of chronic liver disease and liver transplants. The WHO estimates that nearly 180 million people worldwide, or approximately 3% of the world's population, are infected with hepatitis C virus (HCV). The CDC has reported that almost four million people in the United States have been infected with HCV, of whom 2.7 million are chronically infected.

[Preciouslife1]

Tumour suppressors: One faulty copy tips the balance

/**/The acetyl transferase Tip60, which regulates transcription of Myc and p53, functions as a tumor suppressor independent of Myc or p53.
TIP60 is an acetyl-transferase that co-regulates MYC and p53, and modulates the MYC-induced DNA-damage response (DDR). A new study shows that loss of a single copy of Tip60 is associated with tumorigenesis, and that this is caused by impairment of the DDR and is independent of p53.
Mice that are homozygous Tip60-null are not viable, whereas heterozygotes have no observable phenotype. However, the authors showed that Tip60 heterozygotes in the background of an overactive form of MYC, E µ -Myc, had accelerated onset of MYC-induced B-cell lymphomas. Immunostaining of components of the DDR pathway showed that it was severely impaired in these heterozygotes. This observation was confirmed in a more controlled in vitro system in which RNA interference was used to downregulate Tip60, which also caused a downregulation of DDR. This impairment was specific to MYC-induced DDR, as mice heterozygous or wild type for Tip60 did not differ in their response to ionizing radiation, which uses a different DDR pathway.
So, Tip60 is haplo-insufficient in its tumour suppression through the DDR pathway, but what about its role in regulating MYC and p53? Transcriptional analysis of MYC and p53 targets showed no effect of Tip60 heterozygosity, implying that the effects of TIP60 on DDR are independent of MYC and p53-induced transcription. However, this does not mean that TIP60 does not also have a tumour suppression role through p53 and MYC, only that such a role is not haplo-insufficient.
On the basis of these data in mice, the authors looked at TIP60 mRNA and protein levels in human tumours. In breast tumours, head and neck tumours, and various lymphomas, they found reduced TIP60 in around 40% of cases. Significantly, this proportion was much higher in high-grade breast tumours. Interestingly, immunostaining showed reduction in nuclear levels of TIP60 in tumour cells, but no reduction and even a possible increase in cytoplasmic TIP60, implying that delocalization as well as reduced expression might be important in tumorigenesis.
The results from mice had shown that the TIP60 DDR effect was independent of MYC and p53-regulated transcription. A similar phenomenon was observed in the human cells — loss of TIP60 heterozygosity correlated with TP53 mutations, showing that the two pathways act independently to promote tumorigenesis and that the effect of TIP60 heterozygosity does not depend on functional p53.
To further understand tumorigenesis, it will be necessary to unravel the molecular mechanisms through which TIP60 affects DDR. Possible mediators include ataxia-telangiectasia mutated (ATM) and ARF, but the authors were unable to confirm any direct links, implying that the relationship might be complex. However, even without this understanding TIP60 status could become a useful indicator of tumour severity.

[Preciouslife1]

MicroRNA: A new Twist on invasion and me.tastasis.

http://www.signaling-gateway.org/update/featured/index.html

The microRNA miR-10b indirectly regulates RhoC expression to promote tumor cell invasion and me.tastasis, documenting a novel role for microRNAs in regulating migration and motility, and exposing their involvement at several different stages of tumor formation and progression.

MicroRNA molecules (miRNAs) regulate many diverse cellular processes, including development, apoptosis and tumor formation. Several reports have shown that miRNAs can act as oncogenes or tumor suppressors to facilitate or repress tumorigenesis. However, a role for miRNAs in the later stages of malignancy — invasion of cancer cells into the surrounding stroma and *me.tastasis to distant sites — has not yet been found. In Nature, Weinberg and colleagues document a novel function for the miRNA miR-10b in promoting invasion and me.tastasis by regulating the expression of the prome.tastatic small GTPase RhoC.

Work from previous studies enabled the identification of several miRNAs that were substantially upregulated in breast cancer cells compared to primary human mammary epithelial cells. The expression of one of the miRNAs, miR-10b, was limited to me.tastatic cells, indicating a potential role for miR-10b in regulating me.tastasis. Indeed, mammary fat pad implantation of cells that overexpressed miR-10b resulted in tumors that invaded the surrounding stroma and frequently me.tastasized to the lungs.

Like their protein-coding genetic counterparts, the expression of miRNA molecules can be modulated by the activity of transcription factors. The transcription factor Twist is upregulated in me.tastatic cells, hinting at a potential relationship between Twist activity and miR-10b expression. Chromatin immunoprecipitation experiments found that Twist could bind to the miR-10b promoter. Inhibition of miR-10b in cells that overexpress Twist significantly reduced cell motility, confirming miR-10b as a Twist-regulated gene that relays the pro-me.tastatic effects of Twist activity.

How, then, does miR-10b promote migration and invasion? In silico and in vitro experiments found that miR-10b could bind to and inhibit translation of homeobox D10 (HOXD10) mRNA. HOXD10 is known to repress several prome.tastatic genes, including RhoC. A linear miR-10b–HOXD10–RhoC regulatory pathway unfolded upon the observation that miR-10b inhibited expression of HOXD10 and promoted expression of RhoC, and that depletion of RhoC limited miR-10b-mediated invasion and motility. Furthermore, exogenous co-expression of miR-10b in combination with a HOXD10 construct that was resistant to miR-10b-mediated silencing almost completely inhibited migration.

Together, these data define a novel pro-me.tastatic pathway in which Twist facilitates expression of miR-10b, preventing translation of HOXD10. The absence of HOXD10 potentiates the expression of RhoC, as well as several other pro-migration genes, and promotes invasion and me.tastasis. The authors suggest that other genetic targets of miR-10b could have additional roles in promoting malignant progression, hinting at the complex regulatory events that underlie tumorigenesis and me.tastasis. Future studies into the role of miRNAs in regulating these diverse cellular processes will ultimately yield a better understanding of the events that foster the development of a me.tastatic tumor from a cancer cell.


Emily J. Chenette
Signaling Gateway

Original Reference:
Li Ma, Julie Teruya-Feldstein & Robert A. Weinberg.
Tumour invasion and me.tastasis initiated by microRNA-10b in breast cancer
Nature advance online publication 26 September 2007.

[Preciouslife1]

Immunology: 'Danger' signals

/**/SOURCE: Chemotherapy-induced cell death triggers the release of the high-mobility group box 1 protein (HMGB1), which stimulates Toll-like receptor 4 (TLR4) and elicits an immune response that is required for the success of the therapy.
Toll-like receptors (TLRs) recognize exogenous and endogenous 'danger' signals, but how is an efficient immune response to dying tumour cells mounted? Guido Kroemer, Laurence Zitvogel and colleagues describe a previously unknown pathway by which tumour cells dying after treatment with chemotherapy are recognized by TLRs and trigger an immune response.
Inoculation of doxorubicin-treated or oxaliplatin-treated dying thymoma, sarcoma or colon cancer cells into the foot pad of mice wild-type for or lacking different TLRs showed that only Tlr4-/- mice were defective in T-cell priming (measured as interferon- production) after re-stimulation with tumour antigen. If dendritic cells (DCs) were depleted in wild-type mice, the priming of T cells by dying tumour cells was abrogated. Furthermore, when either wild-type or Tlr4-/- DCs were exposed to dying tumour cells and transferred into Tlr4-/- mice, only the DCs with no TLR4 failed to activate T cells, showing that TLR4+ DCs are required for the immune response. The authors then used co-precipitation assays to show that the endogenous high-mobility group box 1 protein (HMGB1) is released by dying tumour cells and constitutes a danger signal that mobilizes the immune response by binding and stimulating TLR4 on DCs. This signal is necessary because pre-incubation of tumour cells with a small interfering RNA (siRNA) or a neutralizing antibody against HMGB1 inhibited the capacity of dying tumour cells to stimulate DCs. After recognition of HMGB1, TLR4 transduces signals through the TLR adaptor myeloid differentiation primary response protein (MYD88), as Myd88-/- DCs behaved in the same way as Tlr4-/- DCs when exposed to dying tumour cells.
So, what role does the HMGB1–TLR4–MYD88 pathway have in the efficacy of anticancer drugs? Tlr4-/- mice, or dying tumour cells lacking HMGB1, could not trigger an effective anti-tumour response against the same tumour cells inoculated one week after the initial injection. If mice with established tumours lacked TLR4 or MYD88, chemotherapy or local radiotherapy was not as effective at reducing tumour growth or prolonging survival as in wild-type mice.
What relevance might these findings have for patients? 8–10% of Caucasians have a polymorphism in TLR4 (Asp299Gly), which could compromise the effectiveness of chemotherapy in breast cancer. The authors found that this polymorphism reduced the interaction between TLR4 and HMGB1, and prevented DCs from presenting antigens from dying tumour cells to cytotoxic T cells. They analysed the time to me.tastasis in 280 patients with non-me.tastatic breast cancer who had been treated with anthracyclines after surgery because of lymph node involvement. The frequency of me.tastasis by 5 years after surgery was 40% in those with mutant TLR4, compared with 26.5% in patients with wild-type TLR4, and me.tastasis-free survival of patients with mutant TLR4 was also significantly lower.
Dying tumour cells therefore elicit an immune response that is required for the success of therapy, and could possibly be exploited to improve the immunogenicity of current chemotherapy regimens.

[Preciouslife1]

Neurodegenerative disease: Micromanaging dopamine neurons

Katherine Whalley

As our understanding of the fine-tuning of neuronal gene expression has grown, microRNAs (miRNAs) have emerged as key post-transcriptional regulators. These small, non-coding RNAs prevent the translation of target mRNAs, thereby helping to determine a cell's eventual protein make-up. Abeliovich and colleagues now demonstrate the importance of miRNA activity for midbrain dopamine neuron function.
There is keen interest in understanding the genetic programmes that drive the development and maintenance of dopamine neurons, owing to the importance of these cells in the pathology of Parkinson's disease (PD). The authors set out to determine the role of miRNAs in this process. They began by creating a murine embryonic stem cell (ES) line in which Dicer, an enzyme that is crucial for miRNA production, was deleted. They were unable to generate dopamine neurons from these cells, suggesting that miRNAs have a role in dopamine neuron differentiation and/or maintenance.
To examine the importance of miRNA activity in vivo, the authors generated transgenic mice in which Dicer was specifically deleted in postmitotic midbrain dopamine neurons. As the mice aged, they progressively lost midbrain dopamine neurons and displayed reduced locomotor activity — a phenotype that is reminiscent of the symptoms of patients with PD, indicating that altered miRNA activity might contribute to PD pathology.
To determine which of the hundreds of miRNAs that are expressed in the brain are involved in maintaining midbrain dopamine neurons, the authors compared the expression of 224 miRNAs in brain samples from a small number of PD patients with controls. One particular miRNA, miR-133b, was highly expressed in the midbrain of controls, but was reduced in the midbrain of PD patients.
Lower levels of miR-133b were also found in the midbrain of two rodent models of dopamine deficiency. One of these, the Aphakia mouse, carries a mutation in the gene that encodes PITX3, suggesting that miR-133b expression might be regulated by this protein. Indeed, the authors found that PITX3 overexpression increased levels of miR-133b. They went on to show that PITX3 mRNA is itself a potential target for miR-133b. PITX3 protein levels were increased in rat midbrain cells in which miR-133b was suppressed using antisense oligodeoxynucleotides. This suggests that a negative-feedback circuit exists in which PITX3 induces miR-133b expression and then is itself downregulated by miR-133b activity.
Somewhat surprisingly, the authors found that overexpression of miR-133b in ES or primary midbrain cultures reduced the expression of markers of dopamine neuron differentiation and reduced dopamine release in response to a depolarizing stimulus. Furthermore, suppressing miR-133b activity increased the expression of dopaminergic markers and potentiated dopamine release. These results indicate that further work will be needed to understand the precise role of miR-133b in dopamine differentiation and function.
Although important questions remain to be answered regarding the full repertoire of miR-133b activity, this study provides evidence for the importance of miRNAs in the maintenance of dopamine neurons, and suggests that researchers should continue to look closely for possible links between disruptions in this form of post-transcriptional regulation and disease pathology.

References and links

ORIGINAL RESEARCH PAPER

1. Kim, J. et al. A microRNA feedback circuit in midbrain dopamine neurons. Science 317, 1220–1224 (2007)

[Preciouslife1]

Gene genie: Gene genie: Any day now Craig Venter - geneticist, yachtsman and Vietnam veteran - will announce that he has achieved one of the greatest feats in science: the creation of artificial life. He talks to Ed Pilkington

The Guardian - Oct. 06, 2007 For a room in which one of the most astonishing experiments in modern science is being conducted, the laboratory in the J Craig Venter Institute in Rockville, Maryland, is understated. It is divided into wooden workstations reminiscent of a school science lab. There are stacks of glass test tubes and pipettes, and one wall is lined with air-controlled boxes containing Petri dishes. Petri dishes! The mere sight of them sparks memories of interminable, soporific biology lessons.
But there is nothing soporific about what is going on inside these Petri dishes. If all goes according to plan - and the full expectation is that it will - their surface will bloom imminently with an array of small white spots that will herald a giant leap in scientific and human potential. Each spot will contain up to 10m bacterial cells, and in each cell there will be a chromosome that has been painstakingly stitched together by humans from lab-made chemicals.
In short, those schoolboy Petri dishes will contain the first artificial life form ever created.
Casting a paternal eye over the proceedings, like an expectant father pacing the delivery room, is the imposing figure of Craig Venter - the scientist variously described as a rebel, maverick, outsider, and the Bono of genetics. Sporting jeans ("gene man wears jeans", he quips) and cowboy boots, he hasn't dressed up to the role of playing God in which his most extreme detractors have cast him. Nor does he labour it in words, preferring to play down the significance of this milestone in science history. "It's not like baking a cake, mixing all the ingredients and putting it in the oven, and hey presto, there's new life," he says. "We're not creating life, we are creating new life forms from existing ones."
This distinction may strike many as semantic. For if Venter's experiment works, his team of 20 scientists will have artificially created chromosomes that will display all of the characteristics of life - notably the ability to divide and multiply, and to control the bacterial cells into which they have been transplanted.
Besides, Venter is more animated than he is letting on. There is an intensity in the way he looks at the labour in progress that belies his barely contained excitement. It is precisely this kind of jaw-dropping event for which Venter has been lambasted by his critics and venerated by admirers. "Hubris!" cry the first, "genius!" exclaim the latter. But both sides agree on one thing: the extraordinary sweep and scale of his ambitions.
To underscore this, in addition to being poised to declare the creation of artificial life forms, he is also unveiling two other major projects this month. The first is his autobiography, A Life Decoded, the product of five years' toil without the aid of ghost writers. It gives his account of the race to decipher the human genome - the code of 3.1bn letters that forms the instruction manual that is the basis of all human life.
On one level the book is a voyage of discovery: a description of code-breaking as mind-bogglingly complex as the cracking of ancient Egyptian hieroglyphs, and no less significant. On another level it reads like a foray into the grubbier side of human nature: how highly educated and gifted people, including some of the biggest names in science, can turn on each other out of envy and fear.
It was this grubby side - the exposed and often vicious spat between Venter's privately funded attempt to sequence the human genome and a team of government-backed scientists in America, Britain and elsewhere, that brought Venter to prominence as the bogey man of modern science. He was pilloried as the unacceptable face of science-for-profit, the man who wanted to turn the essentials of human existence into patents to enrich himself. The dispute raged for more than three years, and only ended in a shaky truce mediated by Bill Clinton. The irony was that despite all the histrionics, both Venter's and the public team's efforts were at best compromises and at worst woefully incomplete.
We are now much closer to the endgame, thanks to the second major work Venter publishes this month. It is his own genome, the first individual genetic code to be deciphered.
The genome is also an autobiography of sorts - though it is much bigger than the 390 pages of A Life Decoded. This book runs to 6bn letters - strung across the two sets of chromosomes Venter inherited from his mother and father.
The two works of self-exploration sit neatly side by side, intertwined like a double helix. As Venter writes in A Life Decoded, his literary life story is a product of his genetic one: it is "the sum of 6bn base pairs of my DNA struggling to understand itself".
While the literary book looks back on his life to date, the genetic one gives glimpses of his life ahead. It takes a brave or foolhardy person to dare to look into his own future, but Venter appears genuinely unfazed by the fact that he has done just that. He says that were the information available he would gladly know the date of his death. "Being able to predict the exact day you are going to die - I don't think that is such a horrible thing. I may not tell my family - it depends on what the news is, right? But I would like to know it."
Our understanding of how gene sequences translate into life experiences is still primitive, yet Venter's genetic code does reveal truths that would wreak havoc with a lesser soul. Top of the list is the news that he has a genetically heightened risk of early heart dis ease - a poignant subject as his father died from the condition aged 59, a year younger than Venter is now. In response to the discovery, Venter has self- prescribed a preventive health regime: he exercises, watches his diet and has started taking fat-lowering statins.
His genetic book also warns him of an enhanced risk of dementia ("ouch, indeed" is his reaction) as well as of a condition that can cause blindness. Even the prospect of losing his mind and his sight does not unhinge him: "The fact that I have a risk genetically for Alzheimer's and blindness is not great news. But the reality is that any one of us will have dozens of these risks, and what we have to learn is how to deal with them."
Disappointingly, he only has an average genetic disposition for risk-taking. Disappointing because if Venter is nothing else he is a taker of risks. He is a keen sailor who combines his passion for the sea with his scientific obsession wherever possible. He once sailed into gales in the Bermuda triangle aloft 50ft waves; not only did he live to tell the tale, but he insists he enjoyed the "exhilarating" experience.
"I think I'm a survivor," he tells me in his office overlooking a tranquil duck pond in Rockville. "I could have suffered at least 100 professional deaths. I could come up with a list of the 100 times I've come closest to death from having pneumonia as a child to car crashes."
Several of the entries on that list would undoubtedly fall within the year he spent as a navy corpsman in Vietnam. He survived constant shelling and bombing, and an attack from a deadly sea snake that now hangs skinned on his office wall. Several hundred others did not survive and died in front of him.
One soldier in particular changed the course of life. The teenager seemed normal and healthy when he was brought in, though he was unconscious. He soon went into cardiac arrest; Venter tried for more than an hour to save him but in vain. The post-mortem showed the soldier had a bullet hole in his head that left a tiny entry wound about the length of a pencil. That got Venter thinking about the nature of survival.
"My generation was raised on Dick Tracy cartoons where he could get a thousand bullet holes in him like Swiss cheese and keep on going. We have a hundred trillion cells and you would have naively thought you have to kill a lot of them to kill somebody; in fact you just have to destroy a tiny fraction and all hundred trillion are lost."
It is no exaggeration to say that without that encounter with the dying soldier, Venter would not be exploring the fundamentals of natural and artificial genes. After Vietnam he studied medicine and then biochemistry, and slipped into research. His first project - fittingly - was a study of how adrenaline affected cells, and from there he dug ever deeper into the essential building blocks of life.
What gained him the tag of bad boy of genomics was his aggressive attempt to beat some of the world's best scientists at their own game. He latched on to a 15-year, $5bn international project to sequence the human genome and staggered and outraged his colleagues by saying he could do a better job in a sliver of the time and at a fraction of the cost.
His cocky bid - *************************alent to piecing together a jigsaw puzzle with 27m pieces - turned him from an obscure researcher into a household name. But it also earned him the opprobrium of powerful individuals, institutions and the media. At points it turned ugly, with James Watson, the co-discoverer of the structure of DNA in 1953, reportedly accusing him of wanting to "own the human genome the way Hitler wanted to own the world".

End Part #1

[Preciouslife1]

Part #2

However, the full story is more complex. Venter made efforts early on in his exploration of gene sequencing to remain within the publicly funded system, but his plans were rebuffed by funding boards that lacked the imagination to keep up with his admittedly grandiose vision. His proposal to sequence the genetic code of the first living organism, Haemophilus influenzae, was turned down in 1995 by the US National Institutes of Health on the grounds that it was unworkable. Within weeks of receiving the rejection letter he had pulled it off.
Venter is now deeply suspicious of institutions. "There are several degrees of institutionalisation - from the prison to the military to academia and government. They have this in common - abrogation of decision-making and authority to others. I suppose if there's a set of genes I have, it's detesting authority."
Venter also insists that he wasn't into genome research for the money, "I was interested in money only to have the freedom to do my research."
That can't be the whole picture, I say to him. A man who contemplates buying a $15m yacht, as he did at the height of his biotech wealth, cannot be disinterested in money. "My actions are not those of someone who wants to do everything for money," he replies. "On paper I was the first biotech billionaire, but I did it the hard way - I earned it and then I lost it all. If I was truly after money I would have approached everything differently and I probably would have a billion dollars now."
It is true he lost much of his fortune after he was sacked from his then company, Celera, shortly after the human genome race ended. And it is abundantly clear in conversation with him that he is jet-propelled by the thrill of discovery and the challenge of tackling the impossible. He likes to quote Aristotle: "a likely impossibility is always more preferable to an unconvincing possibility".
The other drug that drives him is the joy of gathering a small but brilliant group of like-minded, rebellious, go-getters. He likens the Celera team to a scientific Camelot, and the same approach has been replicated in his new company, the Craig Venter Institute, with its squad of 500. "When a group of very talented people are focused on something bigger than themselves it brings out the best in them. It's a phenomenal event," he says.
Phenomenal just about sums up what the team currently has in its sights. Venter next plans to sequence up to 10,000 individuals. That would amass a database of genetic information big enough, he believes, to answer some of the truly fundamental questions of life, such as that age-old nature v nurture debate.
He has also put together his two passions - sailing and genomics - to devise a plan to sequence the genetic code of all ocean organisms. The project has already found micro-organisms in the Sargasso Sea that capture energy from the sun in a process utterly distinct from photosynthesis. Those findings, he hopes, may unlock the door to a new source of energy and provide the key to the planet's survival. He is racing against the clock, this time with global warming as competition.
All that, even before he gets to announce the creation of artificial life. Given the spanking he received when last he engaged in controversial research, you could forgive him for holding back this time. But that is not the Venter way. Batten down the hatches! Full speed ahead!
A Life Decoded: My Genome, My Life, by J Craig Venter, is published by Allen Lane on October 25. To order a copy for pounds 25 with free UK p&p go to guardian.co.uk/bookshop or call 0870 836 0875.
Craig Venter will be giving public lectures in London and Oxford during October 23-25. For further information: www. penguin.co.uk/events

'We're not creating life, we are creating new life forms from existing ones,' says Venter.

[Preciouslife1]

News From Molecular & Cellular Proteomics


Preventing neurodegenerative diseases by studying proteins in the brain

Researchers report the most complete list so far of the proteins present in the cerebral cortex -- the outermost layer of the brain that plays a central role in memory, language, cognition, and consciousness. The cerebral cortex is also the part of the brain that contains the hallmarks of many neurodegenerative diseases, so these results could help understand how such diseases develop and maybe find ways to slow it down.

Most neurodegenerative diseases develop in specific regions of the brain. For instance, loss of neurons due to Alzheimer's disease (AD) occur mostly in the cerebral cortex and hippocampus, and degeneration of neurons in Parkinson's disease largely centers on an area in the back of the brain called the brainstem -- at least in the early stage of the disease.

Jing Zhang and colleagues identified over 800 different proteins in a part of the cortex near the forehead called the frontal cortex. This region of the brain is involved in many neurodegenerative diseases in which intellectual function deteriorates over time, including AD, Parkinson's disease with dementia (PDD), and dementia with Lewy body (DLB) disease, and frontotemporal lobar degeneration (FTLD).

The proteins identified in this study perform various functions inside the cell, such as the transport of other proteins, the activation of neighboring proteins, and the catalysis of biochemical reactions. Among these proteins, the scientists found that at least half a dozen are known to be associated with neurodegenerative diseases, but examining the role of the other proteins may show that some of them also are involved in these diseases.

The scientists also found that 17 percent of the identified proteins are also present in the cerebrospinal fluid (CSF) -- a watery fluid that surrounds and protects the brain and spinal cord. Since proteins in the CSF are more accessible clinically than those in the cortex, understanding how proteins present in both the frontal cortex and CSF are involved in neurodegenerative diseases could help improve their diagnosis and assess disease progression.

Taken together, the proteins identified in this study provide important information to ultimately understand how the frontal cortex works and what goes wrong in many neurodegenerative diseases, the researchers conclude. Zhang and his team are now trying to determine the most comprehensive list of all the proteins that are working in other brain regions, such as the middle brain, which is heavily involved in movement disorders such as Parkinson's disease.

Article: "Proteomics Identification of Proteins in Human Cortex Using Multidimensional Separations and MALDI Tandem Mass Spectrometer," by Sheng Pan, Min Shi, Jinghua Jin, Roger L. Albin, Andy Lieberman, Marla Gearing, Biaoyang Lin, Catherine Pan, Xiaowei Yan, Daniel T. Kashima, and Jing Zhang

Improving cancer diagnosis

Researchers have developed a new way of detecting the abnormal presence of complexes of sugars and proteins in the blood of cancer patients, thus providing a new tool for cancer diagnosis.

Many proteins on the surface of cells have sugars attached to them, which helps the cells bind with one another and communicate among one another. But in cancer, these cell surface proteins can have an abnormally high number of sugar molecules attached to them.

Martin R. Larsen and colleagues report a method that uses titanium dioxide to isolate the parts of the cell surface proteins that are attached to sialic acid, which is the "outside" portion of some of the sugars that are attached to these proteins. The method was used to compare the number of protein-sugar structures that contain sialic acid in the blood plasma of a control individual and a patient with advanced bladder cancer. The scientists showed that the cancer patient's blood contained a significantly higher number of these sialic acid-containing structures than the control individual.

This method is a promising way to diagnose cancer and other diseases with excess sialic acid-containing protein-sugar structures, the scientists conclude.

Article: "Exploring the Sialiome Using Titanium Dioxide Chromatography and Mass Spectrometry," by Martin R. Larsen, Soren S. Jensen, Lene A. Jakobsen, and Niels H.H. Heegaard

Improving liver cancer diagnosis

Researchers have identified proteins that could be used to improve the diagnosis of hepatocellular carcinoma, the most common type of liver cancer.

Hepatocellular carcinoma causes about one million deaths each year and is especially frequent in Asia, especially in China, where it is the second most frequent fatal cancer. But the diagnostic methods and therapies are limited, which has prompted scientists to look for proteins inside the body that indicate the presence of the disease.

Fuchu He and colleagues have used a state-of-the-art technique called two-dimensional difference gel electrophoresis to look for proteins whose copies are either increased or decreased in patients with hepatocellular carcinoma. Among the many proteins they found, two proteins were validated as novel potential markers of hepatocellular carcinoma.

Article: "Proteome Analysis of Hepatocellular Carcinoma by Two-dimensional Difference Gel Electrophoresis," by Wei Sun, Baocai Xing, Yi Sun, Xiaojuan Du, Min Lu, Chunyi Hao, Zhuang Lu, Wei Mi, Songfeng Wu, Handong Wei, Xue Gao, Yunping Zhu, Ying Jiang, Xiaohong Qian, and Fuchu He

[Preciouslife1]

Australian scientist announces cancer chemotherapy breakthrough

Japan Economic Newswire - Oct. 08, 2007 SYDNEY, Oct. 8_(Kyodo) _ An Australian scientist has created a world-first chemotherapy test that could help save the lives of millions of cancer patients as well as shorten their treatment, the University of New South Wales said Monday.
Phillip Hogg, a professor and co-director of the university's Lowy Cancer Research Institute, has developed a dye that allows doctors to determine if chemotherapy treatments are working just 24 hours after they have begun.
Cancer patients now have to wait for up to six months before they find out if the painful treatment process is actually killing cancer cells.
Often, if the first round of chemotherapy does not work, new combinations of drugs are prescribed and the process begins again.
"The process, as it stands now, means cancer patients go through a lot of trauma and many don't have the time to waste on ineffective therapies," Hogg told Kyodo News.
"The dye will allow doctors to tailor their treatment by being able to objectively say whether the drugs are effectively working or not. This will lead to longer life spans and better cure rates," he said.
The dye contains a family of molecules that seek out and bind themselves to dying or dead tumor cells. The liquid is injected into the body and a scan reveals the extent of cancer cell death.
Hogg expects the dye to work on all solid tumors, including lung, breast, prostate and colon cancers.
Last week, the U.S. pharmaceutical giant Covidien Ltd. signed a deal with the university to allow it to develop the product for commercial use.
The exact value of the deal remains undisclosed, but it is reported to be "in the tens of millions of Australian dollars."
Clinical trials for the dye are set to begin next year, but it is not expected to be widely available to cancer patients for another five years.

[Preciouslife1]

MorphoSys Enters Therapeutic Research Collaboration on Novel Target Molecule with Genesis Research

Hugin - Oct. 08, 2007 MorphoSys AG (Frankfurt Stock Exchange: MOR; Prime Standard Segment) today announced the signing of a research collaboration with New Zealand-based Genesis Research and Development Corporation Ltd. (New Zealand Stock Exchange: GEN). Under the terms of the agreement, Genesis will continue to use HuCAL-based antibodies originally generated by the MorphoSys business unit AbD Serotec against the human fibroblast growth factor receptor FGFR5 for target validation and pre-clinical studies as part of its proprietary Zyrogen program.
In this program, Genesis is investigating the development of therapeutic antibodies specific for the target molecule FGFR5, which is implicated in various autoimmune and bone-related diseases. Based on the scientific data generated by Genesis during the collaboration, the parties will discuss further development of the therapeutic program. Financial details of the agreement were not disclosed.
The underlying target molecule FGFR5 (fibroblast growth factor receptor 5), a cell surface protein expressed by stromal cells of the hemopoietic system, was originally identified by Genesis from its proprietary EST databases. Genesis has carried out extensive studies to characterize the molecule's interactions with different cell types and tissues, suggesting that it is a therapeutic target for diseases such as osteoporosis, systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. With the signing of this agreement, Genesis will continue to extend its strong patent position around this molecule using the HuCAL antibodies and will further validate its approach through in vitro and in vivo studies as a necessary prelude to a clinical development program.
"The collaboration with Genesis provides us with access to an innovative and scientifically attractive target molecule which may lead to lucrative future commercial opportunities for MorphoSys," commented Dr. Simon Moroney, Chief Executive Officer of MorphoSys AG. "At the same time, it is a further example of the synergies arising between our two business segments, as satisfied AbD Serotec customers decide to partner with MorphoSys for the development of their therapeutic or diagnostic projects."
"AbD Serotec have provided excellent technical advice and service", said Stephen Hall, Chief Executive Officer of Genesis Research. "We value the opportunity to work with MorphoSys Group to develop our therapeutic monoclonal antibodies which have great potential to help treat several diseases where there are limited treatments."
For further information please contact: Dr. Claudia Gutjahr-Loser, Head of Corporate Communications, Tel: +49 (0) 89 / 899 27-122, gutjahr-loeser@morphosys.com or Mario Brkulj, Manager Public Relations, Tel: +49 (0) 89 / 899 27-454, brkulj@morphosys.com
About MorphoSys: MorphoSys is a publicly traded biotechnology company focused on the generation of fully human antibodies as a means to discover and develop innovative antibody-based drugs against life-threatening diseases. MorphoSys's goal is to establish HuCAL as the technology of choice for antibody generation in research, diagnostics and therapeutic applications. The Company currently has therapeutic and research alliances with the majority of the world's largest pharmaceutical companies including Bayer-Schering, Boehringer Ingelheim, Centocor/Johnson & Johnson, Novartis, Pfizer and Roche.
Within these partnerships, more than 40 therapeutic antibody programs are ongoing in which MorphoSys participates through exclusive license and milestones payments as well as royalties on any end products.
Additionally, MorphoSys is active in the antibody research market through its AbD Serotec business unit. The business unit has operations in Germany (Munich), the U.S. (Raleigh, NC) and U.K.
(Oxford). For further information please visit http://www.morphosys.com/

[Preciouslife1]

Future Cancer Hope May Rest In Genetics

Main Category: Cancer / Oncology News
Article Date: 09 Oct 2007

Scientists may have discovered a new way of killing tumours in what they hope could one day lead to alternative forms of cancer treatments.

The University of Manchester research has identified a key gene that appears to play a critical role in the normal process of cell division.

Cells divide creating new cells as part of the body's natural growth, renewal and healing processes but cancer results when cells divide in an uncontrolled way.

What the Manchester team has discovered is that a protein in our cells called 'Bub 1' is essential for normal cell division to take place; if the gene that generates Bub 1 is 'switched off' then the cells are unable to divide successfully.

"Bub 1 is an enzyme that controls several processes required for cell division to occur," said Dr Stephen Taylor, who led the research in the Faculty of Life Sciences.

"We have shown that mouse embryos lacking the Bub 1 gene are unable to develop. Older cell types also failed to divide when the gene is switched off, while male mice lacking Bub 1 became infertile as their sperm cells died."

In fact, deactivating Bub 1 had such a profound effect on cell division at all stages of a cell's life -- known as the 'cell cycle' -- that the team is hopeful it will have a similar effect on cancer cells.

"Before cells can divide they have to duplicate and then distribute their genetic material so that the two 'daughter' cells receive all the genetic information for further growth and development," said Dr Taylor, whose work is funded by the charity Cancer Research UK.

"The distribution phase has to be done with a high degree of accuracy -- just one chromosome segregated incorrectly, for instance, leads to Down's syndrome -- so the cell has a surveillance mechanism which acts as a brake to delay chromosome segregation until accuracy has been guaranteed."

An important part of this intricate surveillance system is Bub 1. The team found that when the gene is switched off the surveillance mechanism fails and accuracy is lost, resulting in cell death.

Now that scientists understand the precise role of Bub 1 in normal cell division, as well as what goes wrong when the gene is missing, they plan to test their theory on cancer cells.

"Unlike some other genes that become mutated in cancer cells, the Bub 1 gene appears normal indicating that it behaves in exactly the same way in cancer cells as it does in healthy cells.

"If this is the case, then we can be confident that switching it off will stop cancer cells proliferating too. And while our normal cells don't divide that often, cancer cells divide more frequently, so hopefully by targeting Bub1 we will selectively kill cancer cells."

Equally exciting, says Dr Taylor, is the fact that drugs are already being developed that are able to block the actions of Bub 1-type enzymes, known as 'protein kinases'; such kinase blockers or 'inhibitors' are already providing a whole new approach to tackling cancer and Bub1 inhibitors may be another weapon in the oncologist's arsenal.

The research, which began in 1999, is published in the journal Developmental Cell on Tuesday, October 9.

[Preciouslife1]

Synta, Glaxo Ink Melanoma Deal


http://www.boston.com/business/globe/articles/2007/10/11

By Todd Wallack
October 11, 2007

Synta Pharmaceuticals Corp., a Lexington biotech company, inked a deal to develop an experimental skin cancer treatment with British drug giant GlaxoSmithKline PLC that could be worth up to $1 billion, one of the largest agreements of its kind.

Under terms of the deal disclosed yesterday, Glaxo agreed to pay Synta $80 million up front, with another $885 million in potential milestone payments later. The deal gives Glaxo a portion of the rights to Synta's promising cancer drug, which is in clinical trials.

"It is one of the largest alliances for a single product in the history of the industry," said Safi Bahcall, Synta's chief executive. "It reflects the strength of the data we have."

Synta said the drug, known as STA-4783, has shown promising results in early trials as a treatment for me.tastatic melanoma, a deadly form of skin cancer. In a trial with 81 patients, those taking the drug lived about a year, compared to eight months for patients using more conventional treatments. Patients taking the drug also lived twice as long before the cancer grew worse.

Now Synta is beginning a larger trial with 600 patients to confirm the drug is safe and effective, a step needed to win regulatory approval to market the drug. More than 600,000 patients a year are diagnosed with skin cancer in the United States, including 30,000 to 60,000 in advanced stages who are most likely to benefit from the treatment.

Though the company, which went public in February, is still at least a couple years from winning approval from the Food and Drug Administration to market the drug, it has already sparked interest on Wall Street and in the drug industry. Bahcall said at least a dozen companies have expressed interest in developing and commercializing the drug. He said Synta decided to work with GlaxoSmithKline largely because it was committed to making the drug a high priority.

As part of the deal, Synta said, both companies will share responsibility for developing and selling the drug inside the United States, while Glaxo will have exclusive rights to market it elsewhere.

In exchange for the rights, Glaxo agreed to pay Synta $80 million in cash, plus another $585 million if the drug meets certain development and regulatory milestones, and $300 million in potential royalty payments.???
Glaxo could also purchase up to $45 million in Synta stock under the agreement.

But Synta shares, which had doubled since August, fell about 9 percent after the pact was made public yesterday, to close at $9.32. Bear Stearns & Co. Inc. analyst Mark Schoenebaum said many investors already anticipated such a deal, accounting for some of the stock's run-up in prior weeks. In an investor note on Sept. 30, Bear Stearns predicted "a partnership announcement could be imminent."

Schoenebaum said yesterday's decline fits the old saw that investors often buy on the rumor then sell when the news is formally announced and cash in their paper profits.

Bahcall also said he thought investors may not have immediately grasped the full impact of the deal, which he said puts Synta in a strong position because it won't need to raise additional cash for some time.

In addition to the skin cancer drug, Synta will retain full control over four more drugs in its pipeline, including one in clinical trials to treat rheumatoid arthritis.

Interest in the skin cancer drug it plans to jointly develop with GlaxoSmithKline has been particularly keen. In studies with rodents, the drug showed the potential to attack a wide range of cancer cells, not just melanoma, raising hopes it could eventually be used to treat many other forms of cancer.

The drug is designed to flood cancer cells with a highly reactive form of oxygen, which essentially overloads the cells and causes them to die. Bahcall likened it to revving an engine until it blows up.??????HUH?

Synta, founded seven years ago, has 160 employees, all of them in Massachusetts.

[Preciouslife1]

New Hope For HIV Patients: Potent Peptides Inhibit HIV Entry Into Cells

http://www.sciencedaily.com/releases/2007/10/071010111801.htm

Based in part on protein structures determined at the National Synchrotron Light Source (NSLS) at the U.S. Department of Energy's Brookhaven National Laboratory, scientists at the University of Utah have developed new peptides that appear to be significantly more effective at blocking HIV's entry into cells than other drugs in their class.

Structure of D-peptide inhibitors (green, yellow, and purple) bound to an HIV protein mimic in three "pockets" that are essential to the virus' ability to enter cells. Blocking the pockets thwarts entry and reduces infectivity. (Credit: Image courtesy of DOE/Brookhaven National Laboratory)Ads by Google
In a paper being published online by the Proceedings of the National Academy of Sciences the week of October 8, 2007, the researchers say these peptides are sufficiently potent to begin pre-clinical studies as a new class of agents for the prevention and treatment of HIV/AIDS.

"Our 'D-peptides' offer several potential therapeutic advantages over existing peptide entry inhibitors, which are costly, require high dose injections, and suffer from the emergence of drug-resistance," said University of Utah biochemist Michael S. Kay, lead author on the paper.
"In contrast, our D-peptides resist degradation, so they have the potential to be administered by mouth and last longer in the bloodstream. Since these inhibitors have a unique inhibitory mechanism, they should work well in combination with existing HIV inhibitors."

The researchers were particularly interested in developing drugs to bind to an essential "pocket" structure found in all HIV strains that was previously identified as a promising drug target using structures determined at Brookhaven's NSLS. Numerous previous attempts to target this pocket failed to produce potent and non-toxic pocket-specific entry inhibitors. In the current work, the researchers used a high-throughput technique to screen a "library" containing hundreds of millions of peptides to identify the rare peptides that would bind to the pocket structure and inhibit HIV entry.

After identifying the most promising candidate peptides, the researchers analyzed the structure of these peptides bound to the target protein using x-ray crystallography at the NSLS. In this technique, researchers analyze how an extremely bright beam of x-rays, available only at synchrotron sources, bounces off and is refracted by the sample to determine the positions of individual atoms. "These structures reveal details of how the peptides bind and guide the development of future inhibitors," said paper co-author Annie Heroux, a biologist and crystallography specialist at Brookhaven Lab.

This structure-assisted design led to the discovery of D-peptides with up to a 40,000-fold improved antiviral potency over previously reported D-peptides. The structures also suggest ways to engineer the peptides to reduce the chance of drug resistance.

This research was funded by the National Institutes of Health, the University of Utah Technology Commercialization Project, and by the American Cancer Society. Operational funding for the NSLS is provided by the Office of Basic Energy Sciences within the U.S. Department of Energy's Office of Science and by the National Institutes of Health.

[Preciouslife1]

Catheter Used To Deliver Adult Stem Cells For Regeneration After Heart Attacks
Main Category: Cardiovascular / Cardiology News

http://www.medicalnewstoday.com/articles/85271.php

A team of cardiologists at the University Hospital of Navarre, in collaboration with the Area of Cell Therapy at the same centre, and with the Gregorio Maranon Hospital in Madrid, have carried out clinical trials (phase II) on 50 patients in order to test the efficacy of adult stem sell transplants (in this case, myoblasts), in the hearts of patients who have suffered a myocardial attack. The great novelty of this work compared to others of a similar nature is the implantation of stem cells using a catheter instead of open surgery.
The current study is based on previous research carried out on experimental animals. This is a study approved by the Spanish Medication Agency, an official body certifying that the research complies with the legal, ethical and safety requisites of the patient.

The patients that are or will be involved in this trial are those who have suffered myocardial arrest and have ventricular dysfunction. Before subjecting them to the stem cell transplant, a series of tests are carried out such as ecocardiograms, magnetic resonance, analysis and the evaluation of spontaneous arrhythmia using Holter-ECG.

The technique begins with the extraction of myoblast cells, by means of a biopsy of muscular tissue from the leg of the patient, a procedure carried out under local anaesthetic.
From the tissue fragment obtained, the researchers isolate the adult muscle stem cells. These cellular units must be cultured for a month in order to obtain sufficient numbers of cells to carry out the transplant.

The culture of the cells is undertaken in the GMP (Good Manufacturing Practice) laboratory of the University Hospital of Navarra, a technique that is based on using the patient's own serum, unlike the cultures undertaken in other studies that use animal-origin serum -- and thus reduces the risk of adverse reactions. "In this way, possible infections, allergies or immunological reactions are avoided, given that foreign proteins are not introduced", according to doctor Juan José Gavira, cardiologist at the University Hospital of Navarra.
The serum is obtained by carrying out a plasmapheresis, a technique which obtains the plasma in which the myoblasts are cultured.

After the month required for the growth of the cell population, the cells obtained are injected into the heart of the patient by catheterism, using a special injection catheter. The cells are implanted in and around the damaged areas of cardiac muscle.

One of the requirements included in the clinical trials that patients have to meet is that no other invasive therapy should simultaneously accompany this trial. In this way, pointed out Dr Gavira, "the results obtained are much purer, given that no other treatment interferes with them". Having obtained the adult stem cells, a sample thereof is analysed in the Microbiology Laboratory in order to discard the existence of infections and to certify its perfect state.

The implant of stem cells

In order to implant myoblasts it is necessary to generate an anatomical reproduction of the left ventricle, which is the zone to be treated. This virtual reproduction is carried
out by means of a navigation system known as non-fluoroscopic electroanatomical mapping. This technique manages to reconstruct the left ventricle in a three-dimensional form, a system that enables the location and analyses of low-voltage areas. "It is these zones without electrical activity that anatomically correspond to the heart attack. With this generation of the ventricle, obtained thanks to the navigation system, we identify the zone affected by the myocardial attack", explains Doctor Ignacio García Bolao, specialist in the Cardiology Department at the University Hospital.

It is in this zone that the stem cells have to be injected. The procedure is undertaken by introducing a catheter made up of a very fine needle retractable at its end. The catheterism is carried out, as is habitual, through the femoral artery until the exact area of the heart affected is reached. Once there, between 15 and 20 injections of myoblasts are effected.
The procedure is undertaken using local anaesthetic, with the patient being conscious, and lasts three or four hours.
To date 14 patients have undergone the trials, all with satisfactory results.

The technique is part of research trials the Phase II goal of which is to see if this new treatment is effective and to improve on the cardiac function of patients who have suffered a heart attack.

[Preciouslife1]

Immune System Protein May Provide Lung Cancer Early Warning

http://www.medicalnewstoday.com/articles/85213.php

Even though lung cancer can take two decades to develop, when it is detected it is already at such an advanced stage that the chances of successful treatment are very small.
An immune system protein may offer the early warning system experts have been looking for.

You can read about this study in the journal Thorax.

Lung cancer kills approximately 900,000 people each year. No effective warning system exists which can detect lung cancer during its early stages - when it is treatable. Sadly, the long-term outlook for current lung cancer patients have not changed much during the last three decades.

In this study scientists analyzed plasma samples from 50 healthy volunteers and 104 people with lung cancer. They were testing for autoantibodies - immune system proteins that are directed at the body's own tissues in response to certain chemical signals in the body. In particular, they were looking for a panel of seven autoantibodies - they are all linked to solid tumors which are found in lung cancer, ovarian cancer, breast cancer and prostate cancer. These seven autoantibodies are triggered when cancerous changes are happening.

They found that 80% of patients with confirmed lung cancer had very high levels of at least one of the seven autoantibodies. These autoantibodies had been found in eight of the nine patients whose cancer had not infiltrated the lymph nodes - when the disease has not yet spread elsewhere and the chance of a cure is much greater. Out of all the healthy volunteers, only one had more than one of these autoantibodies in the blood.

According to previous research, these autoantibodies can be detected five years before the clinical symptoms of lung cancer start to show - in other words, five years before lung cancer is detected.

A previous study had also shown that these autoantibodies can be picked up in patients before their breast cancer is detected.

As the lungs are sensitive to radiation it is not ideal to use x-rays for detecting lung cancer. A blood test, however, has no side effects and is much cheaper than imaging. And the panel can be altered to include more or different autoantibodies for lung and other cancers.

The researchers say the test could be used for higher risk groups, such as smokers and second-hand smokers. If someone gets a positive result, he/she could be referred for more detailed scans, such as a CT (computed tomography) or MRI (magnetic resonance imaging).

"Autoantibodies in lung cancer: possibilities for early detection and subsequent care"
Thorax 2007; doi: 10.1136/thx.2007.083592
http://thorax.bmj.com