- Email: [email protected]
New use for measles vaccine
News & Comment
Combing cancer
Listeria’s license to kill
‘Molecular combing’, a technique that stretches DNA molecules on glass slides, has detected mutations in breast cancer patients that were missed by the conventional sequencing-based screens. Dominique Stoppa-Lyonet and colleagues at the Curie Institute (Paris, France) used molecular combing to develop a four-colour bar code for the BRCA1 gene which is often mutated in familial breast and ovarian cancer. Their results, published in the June issue of the Journal of Medical Genetics, identified a large deletion, representing about 15% of the gene, in an American family with hereditary breast cancer. Aaron Bensimon, co-author and inventor of the DNA combing technique, emphasizes that these results are particularly important as they demonstrate that the technique can detect large mutations that might be missed by the industrial sequencing approach currently being employed to diagnose BRCA1 mutations. JW
When tumour cells are Abl STI-571 has been hailed as one of the first successful, rationally-designed cancer drugs. Yet when the Abl tyrosine kinase inhibitor was used to treat patients with chronic myeloid leukemia (CML), clinicians noticed that some patients responded initially and then relapsed. Now Charles Sawyers and colleagues from the University of California, Los Angeles (CA, USA) have discovered why some tumours develop clinical resistance. They found that resistance was associated with reactivation of the Bcr-Abl oncogenic signal – either by amplifying the BCR-ABL gene or by mutating the kinase domain that interacts with the drug. In a manuscript published in June on the Sciencexpress website the researchers predict that their results should ‘suggest a strategy for identifying inhibitors of STI-571 resistance’. JW http://tmm.trends.com
TRENDS in Molecular Medicine Vol.7 No.8 August 2001
Guinea pigs and mice used to be blissfully safe from infection by Listeria monocytogenes, a deadly bacterium found in contaminated food. But that was before Pascale Cossart got her hands on them. Her group at the Pasteur Institute (Paris, France) discovered that a single point mutation in their cell adhesion receptor E-cadherin explained why these animals are resistant to listeriosis. They teamed up with Charles Babinet’s laboratory to make transgenic mice expressing the human E-cadherin gene in the cells of the intestine. In the genetically modified mice, the bacteria were now able to cross the intestinal barrier using the bacterial internalin protein. The study was published in June in the journal Science. These animals will be invaluable as the first models for human listeriosis. ‘This is a very tricky bacterium’, says Cossart. ‘If it becomes resistant, as we have seen with other bacteria, then it will be critical to know precisely how the infection proceeds, in order to design new therapeutic strategies.’ JW
New gene for juvenile polyposis A team of oncologists has identified a new gene responsible for the onset of juvenile polyposis (JP), a condition affecting the colon and gastrointestinal tract, which significantly increases the risk of colorectal or stomach cancer in later life. James Howe and colleagues (University of Iowa, Iowa City, Iowa) studied four large families with histories of JP and by genetic linkage analysis narrowed down the gene search to a region on chromosome 10. The recent completion of the Human Genome Project allowed the group to identify candidate genes, and one of those, bone morphogenic protein receptor 1A, was discovered to be mutated in all the JP family members examined. Howe is now planning to create a mouse model of JP, which should be a valuable tool in the understanding of JP and in the testing of future therapies. The work was published in June’s Nature Genetics. PoN
Heart dogma quashed The widely accepted dogma that the human heart is intrinsically incapable of regeneration has been challenged by cardiologist Piero Anversa (New York Medical College, Valhalla, New York).
337
Anversa’s team of researchers detected the presence of the cellular proliferation marker Ki-67 in samples of cardiac tissue taken from patients who had suffered a heart attack. These results, detailed in June’s New England Journal of Medicine, provide the strongest evidence to date for the existence of cardiac stem cells. If proven, the exciting possibility of promoting self-repair of damaged heart tissue via stem cell activation could be within reach. PoN
Resources for AIDS As much as $10 billion might be required each year to deal with the rising cost of fighting the worldwide AIDS/HIV epidemic, according to the United Nations, which has established a Global AIDS Fund to intensify AIDS treatment and to reduce HIV prevalence. The UN General Secretary, Kofi Annan, will donate his $100 000 award prize from the Philadelphia Liberty Medal to the Fund. The Bush administration has pledged $200 million. Officials from the UNAIDS program predict that half of the resources will be needed in sub-Saharan Africa. It is thought that $4.8 billion is required for prevention programs, particularly focused at young people. An equal amount will be required for palliative care, treatment and anti-retroviral therapy. Thirty six million people are living with HIV and it has claimed the lives of over 22 million men, women and children. JW
New use for measles vaccine The virus used in the manufacture of the measles vaccine has been shown to be effective at destroying lymphoma cells in mice by researchers at the Mayo Clinic (Rochester, MN, USA). According to a report in the June edition of Blood, mice injected with human lymphoma cells develop tumours and these were seen to regress after injection with the Edmonston-B strain of the measles vaccine virus. Systemic viral injection also resulted in slowing of the progression of disease. Pilot studies are now underway to evaluate the effectiveness of this treatment in human lymphoma patients, potentially offering a vital alternative to existing therapies. PoN
1471-4914/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.
Combing cancer
Listeria’s license to kill
‘Molecular combing’, a technique that stretches DNA molecules on glass slides, has detected mutations in breast cancer patients that were missed by the conventional sequencing-based screens. Dominique Stoppa-Lyonet and colleagues at the Curie Institute (Paris, France) used molecular combing to develop a four-colour bar code for the BRCA1 gene which is often mutated in familial breast and ovarian cancer. Their results, published in the June issue of the Journal of Medical Genetics, identified a large deletion, representing about 15% of the gene, in an American family with hereditary breast cancer. Aaron Bensimon, co-author and inventor of the DNA combing technique, emphasizes that these results are particularly important as they demonstrate that the technique can detect large mutations that might be missed by the industrial sequencing approach currently being employed to diagnose BRCA1 mutations. JW
When tumour cells are Abl STI-571 has been hailed as one of the first successful, rationally-designed cancer drugs. Yet when the Abl tyrosine kinase inhibitor was used to treat patients with chronic myeloid leukemia (CML), clinicians noticed that some patients responded initially and then relapsed. Now Charles Sawyers and colleagues from the University of California, Los Angeles (CA, USA) have discovered why some tumours develop clinical resistance. They found that resistance was associated with reactivation of the Bcr-Abl oncogenic signal – either by amplifying the BCR-ABL gene or by mutating the kinase domain that interacts with the drug. In a manuscript published in June on the Sciencexpress website the researchers predict that their results should ‘suggest a strategy for identifying inhibitors of STI-571 resistance’. JW http://tmm.trends.com
TRENDS in Molecular Medicine Vol.7 No.8 August 2001
Guinea pigs and mice used to be blissfully safe from infection by Listeria monocytogenes, a deadly bacterium found in contaminated food. But that was before Pascale Cossart got her hands on them. Her group at the Pasteur Institute (Paris, France) discovered that a single point mutation in their cell adhesion receptor E-cadherin explained why these animals are resistant to listeriosis. They teamed up with Charles Babinet’s laboratory to make transgenic mice expressing the human E-cadherin gene in the cells of the intestine. In the genetically modified mice, the bacteria were now able to cross the intestinal barrier using the bacterial internalin protein. The study was published in June in the journal Science. These animals will be invaluable as the first models for human listeriosis. ‘This is a very tricky bacterium’, says Cossart. ‘If it becomes resistant, as we have seen with other bacteria, then it will be critical to know precisely how the infection proceeds, in order to design new therapeutic strategies.’ JW
New gene for juvenile polyposis A team of oncologists has identified a new gene responsible for the onset of juvenile polyposis (JP), a condition affecting the colon and gastrointestinal tract, which significantly increases the risk of colorectal or stomach cancer in later life. James Howe and colleagues (University of Iowa, Iowa City, Iowa) studied four large families with histories of JP and by genetic linkage analysis narrowed down the gene search to a region on chromosome 10. The recent completion of the Human Genome Project allowed the group to identify candidate genes, and one of those, bone morphogenic protein receptor 1A, was discovered to be mutated in all the JP family members examined. Howe is now planning to create a mouse model of JP, which should be a valuable tool in the understanding of JP and in the testing of future therapies. The work was published in June’s Nature Genetics. PoN
Heart dogma quashed The widely accepted dogma that the human heart is intrinsically incapable of regeneration has been challenged by cardiologist Piero Anversa (New York Medical College, Valhalla, New York).
337
Anversa’s team of researchers detected the presence of the cellular proliferation marker Ki-67 in samples of cardiac tissue taken from patients who had suffered a heart attack. These results, detailed in June’s New England Journal of Medicine, provide the strongest evidence to date for the existence of cardiac stem cells. If proven, the exciting possibility of promoting self-repair of damaged heart tissue via stem cell activation could be within reach. PoN
Resources for AIDS As much as $10 billion might be required each year to deal with the rising cost of fighting the worldwide AIDS/HIV epidemic, according to the United Nations, which has established a Global AIDS Fund to intensify AIDS treatment and to reduce HIV prevalence. The UN General Secretary, Kofi Annan, will donate his $100 000 award prize from the Philadelphia Liberty Medal to the Fund. The Bush administration has pledged $200 million. Officials from the UNAIDS program predict that half of the resources will be needed in sub-Saharan Africa. It is thought that $4.8 billion is required for prevention programs, particularly focused at young people. An equal amount will be required for palliative care, treatment and anti-retroviral therapy. Thirty six million people are living with HIV and it has claimed the lives of over 22 million men, women and children. JW
New use for measles vaccine The virus used in the manufacture of the measles vaccine has been shown to be effective at destroying lymphoma cells in mice by researchers at the Mayo Clinic (Rochester, MN, USA). According to a report in the June edition of Blood, mice injected with human lymphoma cells develop tumours and these were seen to regress after injection with the Edmonston-B strain of the measles vaccine virus. Systemic viral injection also resulted in slowing of the progression of disease. Pilot studies are now underway to evaluate the effectiveness of this treatment in human lymphoma patients, potentially offering a vital alternative to existing therapies. PoN
1471-4914/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.