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Early responses to chemotherapy of normal and malignant hematologic cells are prognostic in children with acute lymphoblastic leukemia. 总被引:2,自引:0,他引:2
Stephen J Laughton Lesley J Ashton Edward Kwan Murray D Norris Michelle Haber Glenn M Marshall 《Journal of clinical oncology》2005,23(10):2264-2271
PURPOSE: Improved cure rates for children with acute lymphoblastic leukemia (ALL) have resulted from better relapse prediction, using clinical and laboratory features at diagnosis, and more intensive therapy in high-risk patients. More recently, measurements of the variation in the response of malignant lymphoblasts to chemotherapy in vivo have further improved relapse prediction. It is unknown whether the variation in the response of nonmalignant hematologic cells after chemotherapy correlates with the response of lymphoblasts or risk of relapse. PATIENTS AND METHODS: We retrospectively evaluated myelosuppression during induction and consolidation chemotherapy in 227 children uniformly treated for ALL on consecutive Australian and New Zealand Children's Cancer Study Group protocols. The early response to treatment was assessed in a representative subset (n = 62) by determining minimal residual disease (MRD) level by molecular techniques on the end-of-induction bone marrow sample. RESULTS: We found that a slow rate of myeloid recovery at the end of induction chemotherapy, reflected in a low absolute neutrophil count (ANC), was highly predictive of relapse (P < .0001). Additionally, patients with a high end-of-induction MRD level had a high risk of relapse (P = .001). Multivariate analysis confirmed the independent prognostic significance of MRD and ANC at the end of induction chemotherapy (P < .05). There was no significant association between other measures of myelotoxicity and MRD or relapse. CONCLUSION: We conclude that the responses of normal myeloid cells and malignant lymphoblasts to chemotherapy predict outcome by distinct mechanisms. While these results are promising, their use in the clinical setting needs to be examined in a future randomized controlled trial. 相似文献
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The myxozoan parasite Ceratomyxa shasta is a virulent pathogen of salmonid fish in the Klamath River, Oregon/California, USA. We previously defined four principal genotypes of the parasite (O, I, II, III) based on a trinucleotide repeat (ATC)0–3 in Internal Transcribed Spacer region 1 sequences. Genotypes occur in sympatry and show marked host preference: I in Chinook salmon (Oncorhynchus tschawytscha) and II in non-native rainbow trout (O. mykiss). In the present study, we sequenced the parasite from river water samples collected in May, June and September at three localities below, above and between the Klamath's five dams. We also sampled adult and juvenile coho salmon (O. kisutch), steelhead trout (O. mykiss, anadromous form) and native redband rainbow trout (O. mykiss, freshwater form) and additional Chinook salmon and non-native rainbow trout. We found that the C. shasta population was highly structured spatially, temporally and with respect to fish host species. Genotype O was present in water throughout the basin but detected almost exclusively in steelhead and native rainbow trout. Genotype I was in water only below the dams and detected only in Chinook salmon. Genotype II was detected in coho salmon below the dams, and in non-native rainbow trout exposed both above and below the dams. The same genotypes were detected in adult and juvenile fish of the same species. These findings have major implications for the design of effective surveillance and control programs for this economically and ecologically important fish parasite. 相似文献
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Streptolysin O enhances keratinocyte migration and proliferation and promotes skin organ culture wound healing in vitro 总被引:1,自引:0,他引:1
Marjana Tomic-Canic PhD ; Stephen W. Mamber PhD ; Olivera Stojadinovic MD ; Brian Lee MSc ; Nadezda Radoja PhD ; John McMichael PhD 《Wound repair and regeneration》2007,15(1):71-79
ML-05, a modified form of the hemolytic and cytotoxic bacterial toxin, streptolysin O, is currently being investigated as a treatment for collagen-related disorders such as scleroderma and fibrosis. Furthermore, ML-05 may be effective in promoting wound healing and alleviating the formation of hypertrophic scars and keloids. To investigate the effects of ML-05 on wound-healing processes, in vitro wound-healing scratch assays (using human primary epidermal keratinocytes and dermal fibroblasts) and a human skin organ culture wound model were utilized. ML-05 markedly enhanced keratinocyte migration and proliferation in wound scratch assays. ML-05 did not affect either proliferation or migration of dermal fibroblasts, indicating that ML-05's effects on cell migration/proliferation may be keratinocyte-specific. ML-05 was tested in a dose-dependent manner in a skin organ culture wound model using two different application methods: Through the culture media (dermal exposure) or direct topical treatment of the wound surface. ML-05 was found to accelerate wound healing as measured by reepithelialization, particularly after topical application. Therefore, ML-05 may have potential as a wound-healing agent that promotes reepithelialization through stimulation of keratinocyte migration and proliferation. 相似文献
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Philip F. Giampietro MD PhD Margaret G. E. Peterson PhD Robert Schneider MD Jessica G. Davis MD Stephen W. Burke MD Oheneba Boachie-Adjei MD Charles M. Mueller PhD RD Cathleen L. Raggio MD 《HSS journal》2007,3(1):89-92
Reduced bone mineral density (BMD) was sporadically reported in patients with Marfan syndrome. This may or may not place the
Marfan patient at increased risk for bone fracture. In comparing the BMDs of our patients with those reported in the literature,
it seemed that agreement between values, and hence the degree of osteoporosis or osteopenia reported, was dependent on the
instrumentation used. The objective of this study was to statistically assess this impression. Bone mineral density measurements
from our previously published study of 30 adults with Marfan syndrome performed on a Lunar DPXL machine were compared with
studies published between 1993–2000 measured using either Lunar or Hologic bone densitometry instruments. The differences
of our measurements compared with those made on other Lunar machines were not statistically significant, but did differ significantly
with published results from Hologic machines (P < 0.001). Before progress can be made in the assessment of BMD and fracture risk in Marfan patients and in the evidence-based
orthopedic management of these patients, standardization of instrumental bone density determinations will be required along
with considerations of height, obesity, age, and sex. 相似文献