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Micronuclei assay to detect arsenic-induced cancer
Newsdesk New genetic clues to predict response to tamoxifen The expression ratio of two genes, HOXB13 to IL17RB, can predict recurrence of breast cancer in patients given adjuvant tamoxifen, a new study shows (Cancer Cell 2004; 5: 607–16). “This assay may prove helpful in identifying at-risk patients who might benefit from alternative hormonal (letrozole or anastrozole) or chemotherapeutic interventions”, Dennis Sgroi (Massachusetts General Hospital, Boston, USA) explains. Most patients with oestrogen receptor (ER)-positive breast cancer receive adjuvant tamoxifen therapy. However, about 40% of patients relapse and there is no test to identify this subset of patients. Sgroi and colleagues assessed gene expression in 60 patients with ER-positive primary breast cancers who had received tamoxifen. They found that the ratio of HOXB13 to IL17RB accurately predicted recurrence of tumours, and
that HOXB13 expression was associated with cell invasiveness in vitro. “This suggests that HOXB13 may directly contribute to tumour invasion and metastasis”, says Sgroi. According to Paul Goss (University of Toronto, ON, Canada), the two-gene expression ratio as a predictor of tamoxifen response is “very important” because aromatase inhibitors are challenging the position of tamoxifen in the treatment of earlystage breast cancer. “Tamoxifen is off patent and its appropriate use in selected patients would save substantial cost worldwide”, he notes. The ratio could also help identify patients who are more likely to benefit from aromatase inhibitors. In an accompanying article, Rob Michalides (The Netherlands Cancer Institute, Amsterdam) and colleagues report that resistance to tamoxifen in patients with ER-positive breast cancer
is mediated by a modification of ER (Cancer Cell 2004; 5: 597–605). “We have identified the site in ER␣ that is modified by protein kinase A, and shown that the modified receptor is now stimulated by tamoxifen, instead of being inactivated”, says Michalides. The group also found a relation between protein kinase expression and tamoxifen resistance. Importantly, this association is seen in primary breast cancer before the start of adjuvant tamoxifen treatment, showing that this form of tamoxifen resistance is not acquired during treatment, and could be predicted by expression of protein kinase A in primary tumours. “Such patients should be identified and treated with other hormonal agents, such as aromatase inhibitors or with a pure antioestrogen such as fulvestrant”, concludes Michalides. Khabir Ahmad
Micronuclei assay to detect arsenic-induced cancer
Oncology Vol 5 July 2004
The researchers did comparative analyses of micronuclei as biomarkers in lymphocytes, oral mucosa cells, and urothelial cells in people exposed to arsenic.
© WHO/P Virot
A group of researchers from West Bengal, India, have reported that a micronuclei assay could be an effective technique for rapid risk assessment of arsenic-induced cancer and monitoring of genetic damage in populations exposed to arsenic (Cancer Epidemiol Biomarkers Prev 2004; 13: 820–27). Arsenic has emerged as a substantial contaminant to the environment in the state of West Bengal. Nearly 6 million people in the state, which borders Bangladesh, are exposed to this carcinogen through contaminated groundwater used for drinking. There is increasing evidence that chronic environmental exposure to arsenic results in genotoxic effects. Exfoliated epithelial cells can be used for cancer screening and biomonitoring of genotoxicity. The frequencies of micronuclei in exfoliated cells of oral mucosa and bladder are a good index for monitoring of genotoxicity induced by arsenic because these cells are in direct contact with the carcinogen.
Arsenic: a contaminant of groundwater in India.
The survey of 163 residents of the North 24 Parganas district by use of the micronuclei assay showed that chronic ingestion of arsenic in drinking water lead to increased presence of micronuclei compared with an unexposed group of 154 people. Slightly more micronuclei were seen in lymphocytes than in oral mucosa cells
and urothelial cells, suggesting that genotoxic effects vary between tissues. The amount of exposure to arsenic did not affect the sensitivity of micronuclei to act as biomarkers in the three cell types in the exposed group, which was probably a result of differences in water intake and duration of arsenic exposure. “Enhanced frequencies of [micronuclei] seen in all [three] cell types indicate greater susceptibility to arsenic-induced carcinogenesis in the arsenic-exposed study subjects”, says lead researcher Ashok Giri (Indian Institute of Chemical Biology, Kolkata, India). “We are not aware of any other reported assessments of micronuclei frequencies in these three cell types considered together in an arsenicexposed population group. And these results are consistent with levels of micronuclei reported for lymphocytes and exfoliated epithelial cells in other parts of the world”, concludes Giri. Dinesh C Sharma
http://oncology.thelancet.com
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393
that HOXB13 expression was associated with cell invasiveness in vitro. “This suggests that HOXB13 may directly contribute to tumour invasion and metastasis”, says Sgroi. According to Paul Goss (University of Toronto, ON, Canada), the two-gene expression ratio as a predictor of tamoxifen response is “very important” because aromatase inhibitors are challenging the position of tamoxifen in the treatment of earlystage breast cancer. “Tamoxifen is off patent and its appropriate use in selected patients would save substantial cost worldwide”, he notes. The ratio could also help identify patients who are more likely to benefit from aromatase inhibitors. In an accompanying article, Rob Michalides (The Netherlands Cancer Institute, Amsterdam) and colleagues report that resistance to tamoxifen in patients with ER-positive breast cancer
is mediated by a modification of ER (Cancer Cell 2004; 5: 597–605). “We have identified the site in ER␣ that is modified by protein kinase A, and shown that the modified receptor is now stimulated by tamoxifen, instead of being inactivated”, says Michalides. The group also found a relation between protein kinase expression and tamoxifen resistance. Importantly, this association is seen in primary breast cancer before the start of adjuvant tamoxifen treatment, showing that this form of tamoxifen resistance is not acquired during treatment, and could be predicted by expression of protein kinase A in primary tumours. “Such patients should be identified and treated with other hormonal agents, such as aromatase inhibitors or with a pure antioestrogen such as fulvestrant”, concludes Michalides. Khabir Ahmad
Micronuclei assay to detect arsenic-induced cancer
Oncology Vol 5 July 2004
The researchers did comparative analyses of micronuclei as biomarkers in lymphocytes, oral mucosa cells, and urothelial cells in people exposed to arsenic.
© WHO/P Virot
A group of researchers from West Bengal, India, have reported that a micronuclei assay could be an effective technique for rapid risk assessment of arsenic-induced cancer and monitoring of genetic damage in populations exposed to arsenic (Cancer Epidemiol Biomarkers Prev 2004; 13: 820–27). Arsenic has emerged as a substantial contaminant to the environment in the state of West Bengal. Nearly 6 million people in the state, which borders Bangladesh, are exposed to this carcinogen through contaminated groundwater used for drinking. There is increasing evidence that chronic environmental exposure to arsenic results in genotoxic effects. Exfoliated epithelial cells can be used for cancer screening and biomonitoring of genotoxicity. The frequencies of micronuclei in exfoliated cells of oral mucosa and bladder are a good index for monitoring of genotoxicity induced by arsenic because these cells are in direct contact with the carcinogen.
Arsenic: a contaminant of groundwater in India.
The survey of 163 residents of the North 24 Parganas district by use of the micronuclei assay showed that chronic ingestion of arsenic in drinking water lead to increased presence of micronuclei compared with an unexposed group of 154 people. Slightly more micronuclei were seen in lymphocytes than in oral mucosa cells
and urothelial cells, suggesting that genotoxic effects vary between tissues. The amount of exposure to arsenic did not affect the sensitivity of micronuclei to act as biomarkers in the three cell types in the exposed group, which was probably a result of differences in water intake and duration of arsenic exposure. “Enhanced frequencies of [micronuclei] seen in all [three] cell types indicate greater susceptibility to arsenic-induced carcinogenesis in the arsenic-exposed study subjects”, says lead researcher Ashok Giri (Indian Institute of Chemical Biology, Kolkata, India). “We are not aware of any other reported assessments of micronuclei frequencies in these three cell types considered together in an arsenicexposed population group. And these results are consistent with levels of micronuclei reported for lymphocytes and exfoliated epithelial cells in other parts of the world”, concludes Giri. Dinesh C Sharma
http://oncology.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
393