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Promising antimalarial combination highlighted
THE LANCET
SCIENCE AND MEDICINE
Protein may warn of metastatic potential of prostate cancer
R
motility, by changing the kinetics of actin polymerisation. Donald Coffey (Baltimore, USA) says in an accompanying editorial that measuring thymosin ß15 expression may be particularly useful in determining whether intermediate-grade prostate tumours (as judged histologically) are likely to be indolent or aggressive. Such tumours are now frequently Prostate cancer gene located on chromosome 1 detected because of earlier A gene that predisposes men to prostate cancer has been localised to diagnosis by prostate-specific the long arm of chromosome 1. (Science 1996; 274: 1371–74). The anti-gen screening but their gene, hereditary prostate cancer 1 (HPC1), has not been identified or behaviour is notoriously difficult to predict. As a result, cloned so its function is not yet known. The researchers said that many relatively harmless, slowabout one in 500 men in the USA carry the gene and that it may be growing tumours are treated responsible for 3% of all prostate cancers. aggressively. “Thymosin ß15 The discovery is the result of an intense genome-wide search by expression should provide the scientists in the USA and Sweden. The researchers did linkage much-needed positive marker of the metastatic potential of analysis on 66 families that had at least three first-degree relatives prostate cancer”, concludes affected by prostate cancer, using more than 340 markers. This Coffey . screen indicated a significant linkage between chromosome 1 and Zetter says that his team has hereditary disease, so additional markers were typed in this area in identified two other genes in the original 66 families and 25 more. This second survey has prostate cancer cell lines that may also serve as markers of narrowed the gene’s location to the 1q24-25 region of the metastatic potential. “I think chromosome. esearchers in Boston, USA, have identified a protein expressed in prostatic cancer cells that may help tumour cells move and so enable them to metastasise (Nat Med 1996; 2: 1322–28) The new protein, thymosin ß15, is not expressed in normal prostate cells or in cells taken from benign hypertrophic prostates. But tumour cells express thymosin ß15 and, what’s more, its expression is particularly high in poorly differentiated tumour cells and in cell lines with high metastatic potential.
Bruce Zetter, senior author on the paper, says that cellular motility is a key factor in determining a cell’s metastatic potential. In normal cells, motility involves the disassembly and reformation of the cell’s actin skeleton. According to Zetter, thymosin ß15 binds to actin and may increase cell
Promising antimalarial combination highlighted
F
or the second time in a fortnight the drug combination Malarone (atovaquone plus proguanil) has been set before the world’s tropical medicine community as a cure for malaria, this time at the 45th annual meeting of the American Society of Tropical Medicine and Hygiene (Baltimore, USA, Dec 2–4). Malarone, licensed in the UK last October for the treatment of falciparum malaria, is a fixed dose combination of two old drugs that individually are ineffective against malaria. As a schizonticide proguanil is too slow and atovaquone alone can achieve a cure rate of only 67% with a sharp rise in median inhibitory doses in recrudescent cases. By contrast, in clinical trials on Malarone in Gabon (Lancet 1996; 347: 1511–14), Thailand, Zambia, France, Kenya, Philippines, and Brazil in patients with acute uncomplicated malaria and baseline parasite counts of up to 200 000/µL, a cure rate of 99·5% was achieved.
Vol 348 • December 7, 1996
Encouraging data on malarial prophylaxis come from a trial near Lake Victoria, Kenya, that began in April. With malaria defined as slide-positive parasitaemia, the rates of disease at 10 weeks of follow-up were 0/60 and 0/62 for those who took atavaquone 250 mg/proguanil 100 mg or double that dose, respectively, for 4 weeks, and 28/56 for those on placebo. GlaxoWellcome, makers of Malarone, will be seeking registration in the rest of Europe and in Canada in 1997 but will not be applying for US approval until there are more data on Malarone’s prophylactic efficacy. Meanwhile, GlaxoWellcome said on Nov 20 that they were instigating a controlled donation programme for Malarone, making the drug free to “patients with the greatest need for the therapy and who would otherwise not have access to the drug”. A pilot programme in Kenya is planned for mid-1997. David Sharp
T tonsurans on the Thames
T
inea capitis infections in London are changing. Whereas most cases used to be caused by the zoophilic dermatophyte Microsporum canis, the most common organisms detected now are are Trichophyton tonsurans and M rivalieri—both anthropophilic cousins of M canis (Br J Dermatol 1996; 135: 955–58). Similar changes were reported last year in Birmingham, UK. Scalps were examined and scalp brushings taken from 1057 schoolchildren in southeast London. 2·5% were infected with anthropophilic organisms, another 4·9% were carriers. The examining physicians’ clinical impressions were often wrong (sensitivity 19%, specificity 98%). The investigators say “close collaboration between dermatologists, schools, and general practitioners is necessary to ensure that new cases are identified and receive prompt and appropriate treatment”.
1575
SCIENCE AND MEDICINE
Protein may warn of metastatic potential of prostate cancer
R
motility, by changing the kinetics of actin polymerisation. Donald Coffey (Baltimore, USA) says in an accompanying editorial that measuring thymosin ß15 expression may be particularly useful in determining whether intermediate-grade prostate tumours (as judged histologically) are likely to be indolent or aggressive. Such tumours are now frequently Prostate cancer gene located on chromosome 1 detected because of earlier A gene that predisposes men to prostate cancer has been localised to diagnosis by prostate-specific the long arm of chromosome 1. (Science 1996; 274: 1371–74). The anti-gen screening but their gene, hereditary prostate cancer 1 (HPC1), has not been identified or behaviour is notoriously difficult to predict. As a result, cloned so its function is not yet known. The researchers said that many relatively harmless, slowabout one in 500 men in the USA carry the gene and that it may be growing tumours are treated responsible for 3% of all prostate cancers. aggressively. “Thymosin ß15 The discovery is the result of an intense genome-wide search by expression should provide the scientists in the USA and Sweden. The researchers did linkage much-needed positive marker of the metastatic potential of analysis on 66 families that had at least three first-degree relatives prostate cancer”, concludes affected by prostate cancer, using more than 340 markers. This Coffey . screen indicated a significant linkage between chromosome 1 and Zetter says that his team has hereditary disease, so additional markers were typed in this area in identified two other genes in the original 66 families and 25 more. This second survey has prostate cancer cell lines that may also serve as markers of narrowed the gene’s location to the 1q24-25 region of the metastatic potential. “I think chromosome. esearchers in Boston, USA, have identified a protein expressed in prostatic cancer cells that may help tumour cells move and so enable them to metastasise (Nat Med 1996; 2: 1322–28) The new protein, thymosin ß15, is not expressed in normal prostate cells or in cells taken from benign hypertrophic prostates. But tumour cells express thymosin ß15 and, what’s more, its expression is particularly high in poorly differentiated tumour cells and in cell lines with high metastatic potential.
Bruce Zetter, senior author on the paper, says that cellular motility is a key factor in determining a cell’s metastatic potential. In normal cells, motility involves the disassembly and reformation of the cell’s actin skeleton. According to Zetter, thymosin ß15 binds to actin and may increase cell
Promising antimalarial combination highlighted
F
or the second time in a fortnight the drug combination Malarone (atovaquone plus proguanil) has been set before the world’s tropical medicine community as a cure for malaria, this time at the 45th annual meeting of the American Society of Tropical Medicine and Hygiene (Baltimore, USA, Dec 2–4). Malarone, licensed in the UK last October for the treatment of falciparum malaria, is a fixed dose combination of two old drugs that individually are ineffective against malaria. As a schizonticide proguanil is too slow and atovaquone alone can achieve a cure rate of only 67% with a sharp rise in median inhibitory doses in recrudescent cases. By contrast, in clinical trials on Malarone in Gabon (Lancet 1996; 347: 1511–14), Thailand, Zambia, France, Kenya, Philippines, and Brazil in patients with acute uncomplicated malaria and baseline parasite counts of up to 200 000/µL, a cure rate of 99·5% was achieved.
Vol 348 • December 7, 1996
Encouraging data on malarial prophylaxis come from a trial near Lake Victoria, Kenya, that began in April. With malaria defined as slide-positive parasitaemia, the rates of disease at 10 weeks of follow-up were 0/60 and 0/62 for those who took atavaquone 250 mg/proguanil 100 mg or double that dose, respectively, for 4 weeks, and 28/56 for those on placebo. GlaxoWellcome, makers of Malarone, will be seeking registration in the rest of Europe and in Canada in 1997 but will not be applying for US approval until there are more data on Malarone’s prophylactic efficacy. Meanwhile, GlaxoWellcome said on Nov 20 that they were instigating a controlled donation programme for Malarone, making the drug free to “patients with the greatest need for the therapy and who would otherwise not have access to the drug”. A pilot programme in Kenya is planned for mid-1997. David Sharp
T tonsurans on the Thames
T
inea capitis infections in London are changing. Whereas most cases used to be caused by the zoophilic dermatophyte Microsporum canis, the most common organisms detected now are are Trichophyton tonsurans and M rivalieri—both anthropophilic cousins of M canis (Br J Dermatol 1996; 135: 955–58). Similar changes were reported last year in Birmingham, UK. Scalps were examined and scalp brushings taken from 1057 schoolchildren in southeast London. 2·5% were infected with anthropophilic organisms, another 4·9% were carriers. The examining physicians’ clinical impressions were often wrong (sensitivity 19%, specificity 98%). The investigators say “close collaboration between dermatologists, schools, and general practitioners is necessary to ensure that new cases are identified and receive prompt and appropriate treatment”.
1575