Many millions more people than previously thought might have been given polio vaccine contaminated with a monkey virus linked to cancer.

It has been known since 1960 that early doses of polio vaccine were widely contaminated with simian virus 40, or SV40, which infects macaque monkeys. Tens of millions of people in the US and an unknown number in other countries, including the UK, Australia and the former Soviet Union, may have been exposed prior to 1963.

The contamination occurred because the kidney cells the vaccine virus was grown in came from monkeys infected with SV40. Health officials say the problem was eliminated after 1963.

Now Michele Carbone of Loyola University Medical Center in Chicago has announced results that suggest the Soviet polio vaccine was contaminated after 1963, possibly until the early 1980s. “Is there infectious virus? The short answer is, yes,” Carbone told the Vaccine Cell Substrate Conference 2004 in Rockville, Maryland, last week.

The vaccine was almost certainly used throughout the Soviet bloc and probably exported to China, Japan and several countries in Africa. That means hundreds of millions could have been exposed to SV40 after 1963. The consequences of exposure to the virus (which is not related to HIV in any way) are unclear.

There is evidence is that some of the people given contaminated vaccines were infected by SV40, and that such infections might lead to the development of certain rare types of cancer many years down the line.

But the link with cancer has neither been proved, nor shown to be false (see “Does SV40 contamination matter?”). “There are two scenarios,” says Philip Minor of the National Institute for Biological Standards and Control in the UK.

“One is that it doesn’t matter. The other is that it does.” Minor found three samples of the Soviet oral polio vaccine from the late 1960s in the NIBSC’s freezers, the only samples known to survive from this time. In 1999, he found they tested positive for SV40, whereas British samples from this period did not.

“But we did not draw any broad conclusions,” Minor says. Now Carbone has carried out further tests. He has confirmed the presence of SV40 in the Soviet vaccine samples using three separate tests. In two of the samples, he also showed that the SV40 remained infectious. In the third sample, there was no infectious poliovirus either, an indication that the sample of the live vaccine may have degraded. Yet the production process was supposed to ensure that if any SV40 was present, it would be neutralised.

When Carbone tested the Soviet neutralisation method, which relied on magnesium chloride, he found it was only 95 per cent effective. Because of this, he believes the Soviet vaccine could have remained contaminated until the early 1980s.

In 1981, the Soviet Union switched to a polio vaccine seed provided by the World Health Organization that was free from any SV40 contamination. Carbone, the first to publish evidence of a link between SV40 and the deadly lung cancer mesothelioma (New Scientist, 21 May 1994, p 4), will not discuss his results further until they have been published.

Officials from the US Food and Drug Administration who attended the conference also declined to comment, as the FDA is a defendant in lawsuits alleging that the SV40-contaminated polio vaccine used in the US has caused cancer cases. Hilary Koprowski of Jefferson University in Philadelphia, who created one of the first polio vaccines, says he is not surprised that the magnesium chloride preparation did not work.

“Nothing inactivates something 100 per cent,” he said. “I would believe there were still remnants [of SV40] left.” The contamination of the Soviet vaccine highlights the need for safer methods of growing viruses for vaccines, Koprowski says, something he is trying to tackle by using plant cells.

The US stopped using fresh monkey kidneys for polio vaccine in 2000. But the vaccine is still made in this way in several other countries. “I would say that it suggests that [old] vaccines made in different countries should be examined for possible contamination,” says Janet Butel of Baylor University College of Medicine in Houston, a leading SV40 expert.

“In any epidemiological studies where they’re comparing exposed versus non-exposed, if in fact there was any contaminated vaccine used after 1963, the control group wouldn’t be a control group.” Konstantin Chumakov of the FDA Center for Biologics Evaluation and Research, says that Carbone’s findings leave many unanswered questions.

For example, he said it is not clear from the labelling of the samples found at the NIBSC exactly when they were used in the Soviet Union or for how long. Chumakov, whose father was director of the Soviet Institute of Poliomyelitis Research during the time of the contamination, says he was told that at one point the Soviet Union was supplying more than 100 countries with its vaccine.

He travelled to Moscow in April to try to learn more about the production and testing of the Soviet vaccine. But he found no more vaccine samples from that era, and very little surviving documentation about specific batches and why they might have been contaminated. “It’s hard to explain how it happened,” he says, “but it obviously did.”

Author: Debbie Bookchin

This article appears in New Scientist issue: 10 July 2004

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1. Targeting of Calcium Channels to Active Zones
A. Ashleigh Long, Eunju Kim, Hung-Tat Leung, Elvin Woodruff III, Lingling An, R. W. Doerge, William L. Pak, and Kendal Broadie

This week, Long et al. describe a newly discovered Drosophila protein, fuseless, that is required for vesicle fusion. Fuseless is a transmembrane protein expressed in presynaptic membranes in retina and neuromuscular junctions. Synaptic transmission was impaired in fuseless mutants but was rescued by expression of the transgene exclusively in presynaptic cells. Although synapses appeared essentially normal in mutants, the number of synaptic vesicles was nearly double that in wild-type flies, indicating impairment of exocytosis. The amplitude of evoked excitatory junction potentials was greatly reduced in mutants, and raising extracellular calcium concentration increased the amplitude much less in mutants than in controls, suggesting that a defect in calcium entry underlies the defect in vesicle fusion. Indeed, the expression pattern of voltage-sensitive calcium channels (VSCCs) was disrupted in mutants – the channels were no longer clustered in active zones. Thus, Fuseless is necessary for proper targeting of VSCCs, which enables the localized calcium influx necessary for vesicle release.

2. Could Botulinum Toxin Be Bad for You?
Flavia Antonucci, Chiara Rossi, Laura Gianfranceschi, Ornella Rossetto, and Matteo Caleo

Botulinum toxins (BoNTs) are used increasingly to treat maladies from spasms and migraines to obesity and wrinkles. It has been assumed that the toxin remains localized at the injection site, where it cleaves proteins involved in vesicle fusion, thereby blocking neurotransmitter release. But now Antonucci et al. demonstrate that BoNT/A is retrogradely transported along microtubules, transcytosed, and taken up by afferent terminals. When BoNT/A was injected into one hippocampus in rats, it cleaved its target [synaptosomal-associated protein of 25 kDa (SNAP-25)] in the contralateral hippocampus, resulting in reduced neuronal activity. Similarly, when BoNT/A was injected into the superior colliculus or whisker pads, SNAP-25 was cleaved in the retina and facial nucleus, respectively. In the retina, BoNT/A remained active for at least 25 d after injection. Although cleaved SNAP-25 was detected only in afferents that projected directly to the injection site, it is not clear whether further transcytosis would occur over time.

3. The Mystery of REM Atonia
Patricia L. Brooks and John H. Peever

It has long been assumed that glycinergic inhibition of motor neurons is responsible for decreasing muscle tone during rapid eye movement (REM) sleep. Brooks and Peever have now overturned this hypothesis. Microdialysis of the glycine antagonist strychnine into the trigeminal nucleus of rats resulted in increased tone in facial muscle during wakefulness and non-REM sleep, suggesting that tonic glycinergic inhibition occurs during these states. Tonic inhibition immediately switched to phasic inhibition when the rat entered REM sleep, however, and although strychnine increased the size of muscle twitches, it had no effect on atonia during REM sleep. When REM ended, strychnine effects on tone reappeared. Thus it appears that contrary to assumptions, glycine decreases muscle tone in all states except REM sleep. Intriguingly, GABA antagonists and AMPA were also unable to decrease muscle tone during REM sleep, indicating that neither GABAergic inhibition or decreased glutamatergic excitation is responsible. What is responsible for REM atonia remains a mystery.

4. Somatostatin Receptors That Regulate Epileptiform Activity
Cuie Qiu, Thomas Zeyda, Brian Johnson, Ute Hochgeschwender, Luis de Lecea, and Melanie K. Tallent

The neuropeptide somatostatin reduces the probability of seizures in part by activating the IM current through voltage-gated potassium channels. In experiments reported in this issue, Qiu et al. identified which of the four somatostatin receptors (SST1-SST4 ) expressed in the brain are responsible for antiepileptic effects of somatostatin by comparing SST2, SST3, and SST4 knock-out mice. Although each knock-out increased susceptibility to seizures induced by a GABA receptor blocker, the effect was most severe in SST4 knock-outs. Moreover, only SST4 knockouts had more severe seizures than wild-type animals when seizures were induced by a glutamate agonist. The effects of somatostatin on bursting in hippocampal cultures in the presence or absence of IM blockers indicated that SST2 and SST4 are the main receptors mediating the antiepileptic effects of somatostatin. In addition, it appears that activation of SST4 increases IM, whereas activation of SST4 reduces epileptiform activity by a still unknown mechanism.

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The American Association for Homecare applauds U.S. Senator Max Baucus (D-Mont.) for proposing healthcare policies that “shift the focus from institutional care to services provided in the home and community” to improve quality of care and reduce costs. But the Association strongly disagrees with the idea, also put forward today in the Baucus healthcare plan, that competitive bidding is an anti-fraud program and is a sound payment methodology for home medical equipment and services.

“The underlying rationale for competitive bidding completely misrepresents the nature of home medical equipment and related services that are integral to homecare,” said Tyler J. Wilson, president and CEO of the American Association for Homecare. “Competitive bidding would reduce quality of care and access to homecare for millions of seniors and people with disabilities.”

Last month, the American Association for Homecare announced 13 specific recommendations that could eliminate most of the Medicare fraud attributed to the home medical equipment sector. The specific recommendations made by the Association include mandated site inspections for all new home medical equipment providers, unannounced site visits, a six-month trial period for new providers, proper federal funding for fraud prevention, post-payment audits, real-time claims analysis, more rigorous quality standards, and increased penalties, among other recommendations. The Association is sharing its anti-fraud recommendations with Medicare and its contractors, Congress, the Department of Justice, and the FBI. For details about the 13-point plan, visit the newsroom at aahomecare.

“The homecare sector has zero tolerance for fraudulent activity,” Wilson said. “Those who perpetrate fraud are rarely legitimate home medical equipment providers. The federal agency that oversees Medicare has done a poor job of keeping cheats, fraudsters, and other bad actors from masquerading as home medical providers.”

The Association has been working with Congress and regulators over the past year to adopt tougher, more effective measures to combat Medicare fraud. Earlier this year, the American Association for Homecare recommended to Congress several anti-fraud measures that were incorporated into the Seniors and Taxpayers Obligation Protection (STOP) Act of 2008, S. 3164, a bill to reduce Medicare fraud, which was introduced on June 19, 2008.

On July 15, Congress enhanced fraud prevention by strengthening a statutory mandate for the accreditation of home medical equipment providers and closing a loophole that would have allowed non-accredited providers to provide services to Medicare beneficiaries. The Medicare Improvements for Patients and Providers Act of 2008 (MIPPA) mandates a September 30, 2009 deadline for accreditation of all home medical equipment providers nationwide.

The Association is on record as noting that the competitive bidding program for home medical equipment, which was reformed and delayed by MIPPA, is a price-setting mechanism – not an anti-fraud measure. The Association believes that the federal government should not arbitrarily limit the number of homecare providers who furnish care to seniors and people with disabilities. The number of providers should be determined by the marketplace.

Approximately eight million Americans require some type of medical care in their home, which reduces the length of hospital stays and keeps many Americans out of hospitals and nursing homes.

The American Association for Homecare represents durable medical equipment providers, manufacturers, and other organizations in the homecare community. Members serve the medical needs of millions of Americans who require oxygen equipment and therapy, mobility assistive technologies, medical supplies, inhalation drug therapy, home infusion, and other medical equipment and services in their homes. The Association’s members operate more than 3,000 homecare locations in all 50 states.

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A collaboration between scientists at Vanderbilt University and the University of California, San Francisco has led to the first direct information about the molecular structure of prions. In addition, the study has revealed surprisingly large structural differences between natural prions and the closest synthetic analogs that scientists have created in the lab.

Prions are the infectious proteins responsible for human Creutzfeldt-Jakob disease, bovine spongiform encephalopathy, or “mad cow” disease, scrapie in sheep and several other related nervous system disorders in mammals. For a number of years, scientists have been using the tools of genetic engineering to create synthetic versions of these particles so they could study them more easily. Although researchers have made particles that appear identical to natural prions, they have had trouble duplicating their infectious behavior.

“We expected to find subtle differences, but we found major differences instead,” said Gerald Stubbs, professor of biological sciences at Vanderbilt University. “Although we cannot say for certain that the differences we’ve seen can explain why natural prions are so infectious, there is a good chance that they are closely related.”

The study, which was published online in the Proceedings of the National Academy of Sciences last week, was a joint effort of the Stubbs laboratory and that of Stanley Prusiner at the University of California, San Francisco, who received the Nobel prize for the discovery of prions.

“Our results will aid in attempts to create the infectious synthetic prions that are needed to figure out how prions work and ultimately to find cures for the diseases that they cause,” said the lead author of the study, Holger Wille, assistant adjunct professor of neurology in the Institute for Neurodegenerative Diseases, which is based at UCSF and directed by Prusiner.

Prusiner’s group was the first one that succeeded in making infectious prions in the test tube. However, they are not nearly as infectious as the real thing. Six years ago, Prusiner contacted Stubbs, who is a world authority on determining the molecular structures of fibrous materials, and asked if he was interested in collaborating on an effort to characterize the detailed structure of prions. It didn’t take much convincing. “I’ve always been interested in prions, so I readily agreed,” said Stubbs.

Prions, because of their association with mad cow disease, are the most notorious of the amyloids, which are insoluble clumps of fibrous protein that play a role in a number of neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Lou Gehrig disease, as well as some other common illnesses, including type II diabetes. “It is particularly difficult to determine the molecular structure of fibrous materials like these because they have an intrinsically high level of disorder,” Stubbs explained.

When viewed with an electron microscope, which can magnify images up to one million times, the natural and synthetic prions look nearly identical. They both clump together to form microscopic filaments. At a magnification of approximately one hundred thousand times, the only visible difference is the width of the filaments: the synthetic material shows a wider distribution of widths than the natural material.

The Stubbs lab used unconventional X-ray diffraction methods to get the first details of the molecular structures of natural prions and Prusiner’s synthetic prions. The researchers found that the synthetic prions were shaped something like a ladder. Based on electron microscopic images, the Prusiner lab had proposed that the natural prions have a more complex, three-sided cylindrical shape, and the X-ray experiments supported this proposal.

“The natural, infectious prions are folded into a much more complicated shape,” said Stubbs. Proteins are molecules that are folded into shapes that determine their biological properties. Prions and the other amyloids are cases in which proteins are misfolded into shapes that interfere with normal biological processes. “Normally, the cellular systems deal with misfolded proteins but, for some reason, these slip through the cracks,” he said.

Prions don’t have any DNA in their make-up so they don’t reproduce in a normal fashion. Instead, they spread by transforming proteins they come into contact with into prions by causing them to misfold

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“Our data on prion structure is an important step toward understanding prion infection,” said Stubbs, “and understanding the process is essential before people can design drugs that restrict or prevent it.”

The research was supported by grants from the National Institutes of Health, Fairchild Foundation, G. Harold and Leila Y. Mathers Foundation, the National Science Foundation and the U.S. Department of Energy.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

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Cell Therapeutics, Inc.’s (CTI) (NASDAQ and MTA: CTIC) subsidiary Systems Medicine (SM) has announced that planned enrollment is complete in the European Organization for Research and Treatment of Cancer (EORTC) randomized phase II clinical trial of brostallicin in patients with newly diagnosed advanced or metastatic soft tissue sarcoma who have had no prior chemotherapy. The primary endpoint of the trial is progression-free survival at six months. Patients are randomized in a 2:1 ratio either to receive brostallicin or the standard therapy, doxorubicin. The EORTC designed the study to enroll a total of 108 eligible and treated (evaluable) patients, and plans to conduct the final data analysis in early 2009.

“New therapies are needed to improve outcomes in patients with advanced non-GIST soft tissue sarcomas. This study is the second EORTC study of brostallicin in soft tissue sarcoma. The initial study used brostallicin as single agent salvage therapy in patients whose disease had progressed following initial chemotherapy. The EORTC considered the results in that trial to be of sufficient magnitude to conduct the current study, using brostallicin as first line therapy in patients with advanced or metastatic soft tissue sarcoma who have not received any prior chemotherapy,” said Jack Singer, M.D., EVP, Chief Medical Officer of Cell Therapeutics. “A standard-of-care arm (doxorubicin) is included as a reference arm, although not used to determine comparative efficacy. If the study results are encouraging, a Phase III study in soft tissue sarcoma could be initiated in 2009.”

The title of the trial is “Randomized phase II study of brostallicin (PNU-166196A) versus doxorubicin as first line chemotherapy in patients with advanced or metastatic soft tissue sarcoma.” Hans Gelderblom, M.D., Ph.D., of Leiden University Medical Center in the Netherlands, is the Principal Investigator (PI) and Jean Yves Blay, M.D., Ph.D., chair of the EORTC Soft Tissue and Bone Sarcoma Group, is overseeing it.

“Based on the results of the first EORTC study with brostallicin, we conducted the current study in patients with soft tissue sarcoma to further define the activity of this drug in this patient population,” said Blay. “In the first study, two patients treated with brostallicin had confirmed partial responses and many others had prolonged disease control. Such activity is rare in this group of patients, and we very much hope to confirm or improve on those results and to expand our knowledge of brostallicin in the treatment of these patients.”

“Brostallicin represents a promising new agent with a unique mechanism of action for patients with metastatic sarcoma where there is a clear unmet medical need,” said Gelderblom. “The current standard approach for newly diagnosed patients with sarcoma is essentially limited to doxorubicin so clearly new treatment options are needed.”

About the Study

To participate in the study, patients had to be at least 60 years of age or at least 18 years of age and non suitable for intensive chemotherapy combination treatment, with a WHO performance status 0 or 1. The EORTC’s protocol called for a maximum of 6 treatment cycles, unless the patient withdrew before completion of treatment due to disease progression, drug related event, concurrent illness, or patient refusal to continue therapy. A patient’s tumor will be re-evaluated every 6 weeks during treatment, and at least 4 weeks after the first observation of a complete or partial response. After discontinuation of protocol treatment, patients who have not progressed will be re-evaluated every 12 weeks, unless they have started a new anti-cancer therapy. The primary end-point is proportion of patients who are progression free at 6 months (26 weeks) after start of treatment according to RECIST. Secondary objectives are progression free survival (PFS), objective tumor response based on RECIST, duration of response, and overall survival. A total enrollment of 108 eligible and evaluable patients was required (36 in the doxorubicin arm, 72 in the brostallicin arm).

About Brostallicin

Brostallicin, a novel synthetic second-generation DNA minor groove binder, has potent cancer killing activity and has demonstrated synergism in combination with standard cytotoxic agents as well as with newer targeted therapies in preclinical experimental tumor models. Brostallicin binds covalently to DNA within the DNA minor groove, interfering with DNA division and leading to tumor cell death. More than 230 patients have been treated with brostallicin in single agent and combination studies. Brostallicin had predictable and predominantly hematologic toxicities. Activity was demonstrated in a number of solid tumor types. A phase II study of brostallicin in relapsed/refractory soft tissue sarcoma had sufficient activity based on 3 and 6 month progression free survival and safety profile, which resulted in the first-line phase II study that is currently being conducted by the EORTC.

Context of Vulnerability

CTI and SM are employing a new method of drug development, the “context of vulnerability” approach. Using cutting-edge genomic profiling tools, the Company creates a profile of which cells react to certain drugs in an effort to discover cells’ vulnerabilities (weak spots) and where the drugs are the strongest. With these data, investigators can target those patients with the highest probability of benefiting from a particular drug. By treating only the patients with the genetic characteristics known to react well to the drug, scientists may be able to decrease the time and money necessary to develop a drug and bring it to market. This approach also has the potential to improve the rate of treatment success and increase the number of approved drug products across the drug development industry.

About the EORTC

Created in 1962, the European Organization for Research and Treatment of Cancer (EORTC) is a not-for-profit international cancer research organization under the Belgian law. The EORTC has the mission to develop, conduct, coordinate and stimulate translational and clinical research in Europe to improve the management of cancer and related problems by increasing survival but also patients’ quality of life. The ultimate goal of the EORTC is to improve the standard of cancer treatment in Europe, through the evaluation of new drugs and other innovative approaches, and to test more effective therapeutic strategies, using drugs which are already commercially available, or surgery or radiotherapy. The EORTC has the aim to facilitate the passage of experimental discoveries into state-of-the-art treatment by keeping to a minimum the time lapse between the discovery of new anticancer agents and the implementation of their therapeutic benefit for patients with cancer.

The EORTC promotes multidisciplinary cancer research in Europe and is linked to other leading biomedical research organizations around the world. EORTC research takes place in over 300 hospitals, universities and cancer centers in 32 countries, and the unique network of investigators of the EORTC comprises more than 2000 clinicians collaborating on a voluntary basis in 19 multidisciplinary groups. eortc.be

About Systems Medicine (SM)

In July 2007, CTI acquired Systems Medicine (SM), a privately held oncology company, in a stock-for-stock merger. SM applies a systems biology approach to drug development, combining pharmacogenomics and bioinformatics with experienced preclinical, clinical and regulatory expertise to find and exploit a specific cancer’s ‘context of vulnerability.’ Specifically, SM defines the molecular and genetic alterations (context) that cause cancer cells to be particularly sensitive (vulnerable) to a drug or combination of drugs – the ‘context of vulnerability’.

About Cell Therapeutics, Inc.

Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable. For additional information, please visit celltherapeutics.

This press release includes forward-looking statements that involve a number of risks and uncertainties, the outcome of which could materially and/or adversely affect actual future results. Specifically, the risks and uncertainties that could affect the development of brostallicin include risks associated with preclinical and clinical developments in the biopharmaceutical industry in general and with brostallicin in particular including, without limitation, the potential failure of brostallicin to prove safe and effective for treatment of solid tumors, determinations by regulatory, patent and administrative governmental authorities, competitive factors, technological developments, costs of developing, producing and selling brostallicin, and the risk factors listed or described from time to time in the Company’s filings with the Securities and Exchange Commission including, without limitation, the Company’s most recent filings on Forms 10-K, 8-K, and 10-Q. In addition, there can be no guarantee that the “Context of Vulnerability” development method will prove to be cost-effective or that it will decrease the time and cost of bringing new drugs to market, or that it will be successful in improving treatment success or increase the number of drugs that can be brought to market. Except as may be required by law, CTI does not intend to update or alter its forward-looking statements whether as a result of new information, future events, or otherwise.

CTI Investors Contact:
Ed Bell and
Lindsey Jesch
celltherapeutics/investors.htm

EORTC Clinical Research Physician
Sandrine Marr?©aud
eortc.be/

EORTC Project Manager
Annick De Brauwer
eortc.be/

Study Coordinator
Hans Gelderblom
Leiden University Medical Centre
lumc.nl

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The loss of the protein VMP1 in cancer cells increases their tendency to detach from the initial tumor the first step towards metastasis. The reason for this, as scientists of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have shown, is that a loss of VMP1 causes cells to lose their capacity to establish contacts with their neighbors.

What causes tumor cells to leave the tissue and start traveling through the body via lymph or blood? As a rule, it is this change of behavior that turns cancer into a deathly disease, because it is a first seed of dangerous secondary tumors (metastases). Scientists of Professor Annemarie Poustka’s division at the DKFZ, collaborating with colleagues in G?¶ttingen and Graz, have shown that a disruption of contact formation between neighboring cells is among the causes why tumor cells become mobile.

In renal cell cancer the researchers discovered that the gene coding for VMP1 is read significantly less in metastases of the tumor than in cells of the primary tumor. Subsequently, the VMP1 gene activities of various breast cancer cell lines were examined. The investigators found that the VMP1 gene is read less in cells with “invasive potential”, which may invade other tissues, than in cells without a tendency to migrate or in cells from healthy breast tissue.

The VMP1 protein, as was shown by special dying, is responsible at the cell surface for the formation of specific contact sites between neighboring cells. When the researchers switched off the production of VMP1 in living cells, these rounded up and stopped forming their typical contacts among each other, which normally hold the tissue together. The results obtained by the Heidelberg researchers suggest that VMP1 is responsible for establishing the initial contact, but it is not permanently inserted at the site of physical contact between neighboring cells.

If VMP1 is experimentally switched off in non-invasive renal cancer cells, the cells develop a tendency to migrate. Thus, in a test that simulates the invasion of tissues in the culture dish, VMP1-negative cells showed a significantly more invasive behavior.

“Whether VMP1 production is actively switched off by the tumor or lost by mutations is something we do not know yet,” explains Annemarie Poustka. “We are now investigating whether the VMP1 content of tumor cells may be used as a reliable marker for metastasis.”

This research has been performed within the framework of the National Genome Research Network (Nationales Genomforschungsnetz, NGFN), a biomedical research program funded by the German Ministry of Education and Research (BMBF).

The task of the Deutsches Krebsforschungszentrum in Heidelberg (German Cancer Research Center, DKFZ) is to systematically investigate the mechanisms of cancer development and to identify cancer risk factors. The results of this basic research are expected to lead to new approaches in the prevention, diagnosis and treatment of cancer. The Center is financed to 90 percent by the Federal Ministry of Education and Research and to 10 percent by the State of Baden-Wuerttemberg. It is a member of the Helmholtz Association of National Research Centers (Helmholtz-Gemeinschaft Deutscher Forschungszentren e.V.).

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A tiny molecule that spurs the progression of non-small-cell lung cancer could become a player in fighting the disease, say researchers at UT Southwestern Medical Center, who published a study on how the molecule behaves in mice in the Sept. 14 issue of Cancer Cell.

Scientists have known that the molecule microRNA-21, or miR-21, is present in overabundant quantities in human tumors, including non-small-cell lung cancer (NSCLC). Until now, however, it was unclear whether miR-21 contributed to the development of lung cancer, or whether it was simply an indicator of the presence of the disease.

To find out, lead study author Dr. Mark Hatley, an instructor of pediatric hematology/oncology, and UT Southwestern colleagues used mice that had been altered specifically to harbor non-small-cell lung cancer. In some of these mice, they genetically engineered the animals to produce too much miR-21. In another group, they deleted the miR-21 gene altogether, which eliminated the molecule in the rodents.

In animals with cancer, the results showed that too much miR-21, or overexpression, promotes the formation, growth and survival of new tumors by turning off certain genes that normally allow cancer cells to die. In fact, at 18 weeks of age, the study group with overexpressed miR-21 had significantly more tumors than their lung-cancer-carrying littermates with normal levels of miR-21. Healthy rodents engineered to overexpress miR-21 did not develop cancer.

“These results indicate that overexpression of miR-21 alone is not enough to initiate tumors in a healthy animal. Instead, it appears that miR-21 enhances the growth and survival of existing lung cancer,” said Dr. Hatley, a Pediatric Scientist Development Program Fellow sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Dr. Eric Olson, chairman of molecular biology at UT Southwestern and the study’s senior author, said the experiments also show that deleting miR-21 sensitizes the animals’ cancer cells to a certain kind of chemotherapy, suggesting that inhibiting miR-21 in lung-cancer patients could be of therapeutic value.

“Methods currently exist to pharmacologically manipulate molecules like miR-21,” said Dr. Olson, who directs the Nancy B. and Jake L. Hamon Center for Basic Research in Cancer and the Nearburg Family Center for Basic and Clinical Research in Pediatric Oncology. “More research will be needed before we know whether this is applicable to humans, but it’s possible that a drug designed to inhibit miR-21 could help keep cancer at bay.”

MiR-21 is a type of molecule called a microRNA. These small snippets of RNA – the chemical cousin of DNA – normally help coordinate and regulate the production of specific proteins in cells. When miRNAs go awry, however, diseases such as cancer can result.

Other UT Southwestern researchers involved with the study were David Patrick, graduate student; Matthew Garcia, research technician; Dr. James Richardson, professor of pathology, molecular biology and plastic surgery; Dr. Rhonda Bassel-Duby, professor of molecular biology; and Dr. Eva Van Rooj, adjunct instructor in molecular biology.

The study was funded by the National Institutes of Health, the Robert A. Welch Foundation, the Leducq Foundation and the American Heart Association.

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Women suffering from recurrent ovarian cancer may have a new treatment regimen that may increase the response to treatment and prolong their lives. Doctors at H. Lee Moffitt Cancer Center & Research Institute are testing a combination of chemotherapy and the drug Avastin in these patients. Moffitt opened a clinical trial recently and is looking for new participants for the study.

“We can often get the cancer to shrink for periods of time, but ultimately, it becomes resistant to standard chemotherapies,” said Dr. Robert Wenham, member of the gynecologic oncology program at Moffitt. “The hope is that by using these targeted therapies, we can prolong and manage the cancer making it more of a chronic disease process rather than something that’s going to take the patient’s life.”

The clinical trial will address ovarian cancers that are incurable and tough to treat. It will target women whose cancer has returned in the first year after initial treatment. Some data shows the new targeted therapy leads to higher responses and better survival than traditional chemotherapy drugs alone.

“Avastin targets the molecules that cancers use to grow new blood vessels. Therefore, it chokes the cancer off,” said Wenham.

Moffitt is looking for clinical trial participants who have a recurrence or progression of ovarian cancer within a year of prior platinum chemotherapy. These women may have had up to two prior chemotherapy regimens for this malignancy. For more information on participating in the clinical trial, call (813) 745-7272.

About H. Lee Moffitt Cancer Center & Research Institute

Located in Tampa, Florida on the University of South Florida campus, H. Lee Moffitt Cancer Center & Research Institute (moffitt) is the only Florida-based cancer center with the NCI designation as a Comprehensive Cancer Center for its excellence in research and contributions to clinical trials, prevention and cancer control. Moffitt currently has 15 affiliates in Florida, one in Georgia and two in Puerto Rico. Additionally, Moffitt is a member of the National Comprehensive Cancer Network, a prestigious alliance of the country’s leading cancer centers, and is listed in U.S. News & World Report as one of America’s Best Hospitals for cancer. Moffitt’s sole mission is to contribute to the prevention and cure of cancer.

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Summaries of news about recent Medicaid developments in Maryland and New York appear below.

Maryland
The Maryland Court of Special Appeals last month ruled that some Medicaid eligibility standards used by the Department of Health and Mental Hygiene were stricter than federal laws allow, and advocates hope the broad standards outlined in the case will be applied universally, the Baltimore Sun reports. The lawsuit was filed by Diane Byus on behalf of her mother, Ida Brown, after Brown was diagnosed with Alzheimer’s disease and was unable to receive assistance through the Older Adults Waiver Program, a Medicaid program designed to provide services such as nursing and adult day care.

Maryland limits eligibility in the program to residents older than age 50 who have incomes less than $1,869 a month and require daily care from licensed health care professionals. Although Brown, who also has several chronic conditions, requires daily monitoring, she does not require constant care from a physician or nurse, the Sun reports. Attorneys from the Legal Aid Bureau and AARP argued in the case that state and federal laws limit eligibility to residents who regularly require “health-related care and services,” such as those that could be provided in a nursing home, but not necessarily daily by a skilled nurse.

The state health department has not indicated whether it would appeal the decision. State officials said that loosening eligibility requirements for the program would allow more people to receive benefits and could lead to denial of care for some of the neediest residents because of limited funding. The program costs the state about $81 million annually.

Legal Aid attorneys are working on several similar cases. According to the Sun, lawsuits were filed against at least two other states that tried to limit community- and home-based care services programs. Advocates in Kentucky succeeded in overturning restrictions, while Oregon’s restrictions were allowed to stand (Green, Baltimore Sun, 12/10).

New York
Two audits released on Monday by New York State Comptroller Thomas DiNapoli showed that the state made $5 million in Medicaid overpayments to 135 in-home health care, outpatient and laboratory service providers across the state, Long Island Newsday reports. One of the audits, which spanned a five-year period through September 2006, showed that the state overpaid home health care providers $2.1 million for Medicaid claims of beneficiaries who were living in nursing homes. The second audit, over a five-year period ending in February 2007, showed that the state overpaid $2.9 million in Medicaid to outpatient and laboratory service providers for services that should have been paid by the facilities that ordered.

DiNapoli said, “Medicaid costs are already high,” adding, “The last thing the state needs to do is pay for services not rendered or pay for the same service twice. The state should take the steps necessary to recoup these costs.”

The audits said the overpayments are due to ineffective practices of the state Office of the Medicaid Inspector General and home health care providers who either ignored or misinterpreted Medicaid billing rules. The audits also noted that the state does not have a proper Medicaid claims handling system to identify cases of overpayments (Dowdy, Long Island Newsday, 12/11).

Reprinted with kind permission from kaisernetwork. You can view the entire Kaiser Daily Health Policy Report, search the archives, or sign up for email delivery at kaisernetwork/dailyreports/healthpolicy. The Kaiser Daily Health Policy Report is published for kaisernetwork, a free service of The Henry J. Kaiser Family Foundation© 2005 Advisory Board Company and Kaiser Family Foundation. All rights reserved. Continue reading →

Scientists in Germany have discovered a gene that links the gum disease periodontitis and increased risk of coronorary heart disease (CHD) and
although they don’t yet fully understand the underlying mechanism of the link, they urged dentists to make sure they diagnose and treat cases of
periodontitis as early as possible to mimimize the risk of heart disease.

The discovery, was the work of Dr Arne Schaefer, of the Institute for Clinical Molecular Biology at the University of Kiel, and colleagues. Schaefer
presented their findings to the annual conference of the European Society of Human Genetics in Vienna on Monday 25 May.

CHD is the leading cause of human deaths worldwide, and periodontitis, a type of gum disease that results in loss of connective tissue and the bone
that supports the teeth, is the major cause of tooth loss in adults over 40 years old.

Periodontitis is very common and affects over 90 per cent of people over 60 years old.

Scientists already knew that periodontitis and CHD were linked somehow and that it was most likely genetic, but until this discovery they weren’t
certain.

Schaefer and colleagues found a gene on chromosome 9 whose variant is shared between gum and heart disease.

A genetic locus on chromosome 9p21.3 was already known to be associated with myocardial infarction (heart attack), so they decided to study it in
two groups of patients: 151 patients with aggressive early stage periodontitis, and 1,097 patients with CHD who had already had a heart
attack.

“The genetic variation associated with the clinical pictures of both diseases was identical,” said Schaefer.

The researchers confirmed the link by studying two other groups: one of 1,100 CHD patients and another of 180 periodontitis patients.

“We found that the genetic risk variant is located in a genetic region that codes for an antisense DNA called ANRIL”, said Schaefer, explaining that it
was also “identical for both diseases.”

When genes make proteins they first unravel their two strands of DNA double helix. On strand makes messenger RNA (mRNA), which goes on to
make the protein and the other reverse strand, called “antisense” DNA, often carries antisense RNA that complements the mRNA and can bind to it and
inhibit its ability to express protein.

Schaefer said they now want to find out more about how this RNA works and the pathway it uses in healthy and diseased gums.

“In the meantime, because of its association with CHD, we think that periodontitis should be taken very seriously by dentists and diagnosed and treated
as early as possible”, he cautioned.

Men and more likely to suffer from CHD and periodontitis and the two diseases share similar risk factors such as smoking, diabetes and obesity.

An imbalanced immune reaction and chronic inflammation are also features of both diseases, and scientists have also discovered for example that the
presence of specific bacteria in periodontal pockets might explain the relationship between periodontal disease and acute coronary syndrome.

This study confirms the genetic link hinted at by these factors, said Shaefer, who urged:

“Patients with periodontitis should try to reduce their risk factors and take preventive measures at an early stage.”

“We hope that our findings will make it easier to diagnose the disease at an early stage, and that in future a greater insight into the specific
pathophsyiology might open the way to effective treatment before the disease can take hold,” he added.

In January 2007, US scientists also reported a link between pancreatic cancer and
gum disease, and last month scientists in Japan suggested that periodontal
disease could act as a risk factor for reactivating latent HIV-1 in affected individuals.

Sources: European Society of Human Genetics, MNT archives.

Written by: Catharine Paddock, PhD

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