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L Lu

Publications and source records attributed to L Lu.

651 records · Page 37Linked to original sources

Leukemia inhibitory factor and steel factor regulate tie message stability in CD34+ cells from human umbilical cord blood.

The cell-surface receptor tyrosine kinase, Tie, is expressed in hematopoietic stem/progenitor cells. Leukemia Inhibitory Factor (LIF) and Steel Factor (SLF) have both been shown to up-regulate Tie gene expression in a population of CD34+ cells derived from human umbilical cord blood (UCB) which is enriched for hematopoietic stem/progenitor cells. In the present study, we examined the possible mechanism of Tie gene up-regulation by LIF and SLF in CD34+ cells using semi-quantitative RT-PCR analysis. In the presence of Actinomycin D (Act D) alone for 24 hrs, Tie transcripts in CD34+ cells decreased. Tie mRNA was increased by an average of 2-4 fold and remained elevated level for 24 hours in CD34+ cells prestimulated with LIF or SLF followed by Act D, compared to that in CD34+ cells treated with Act D without prestimulation. After treatment of CD34+ cells with cycloheximide, Tie mRNA levels were decreased in the presence or absence of LIF or SLF at 24 hours. These findings suggest that LIF and SLF regulate Tie gene expression in UCB CD34+ cells at least in part through an increase in Tie message stability.

Antigens, CD34↗

Expression of HER-2/neu oncogene in normal, hyperplastic, and malignant endometrium.

HER-2/neu oncogene is believed to be involved in tumorigenesis of several human malignancies. To assess the pattern of expression of this oncogene in normal, hyperplastic, and neoplastic endometrium, immunocytochemistry was applied to paraffin-embedded tissue sections obtained from 146 patients with endometrial adenocarcinoma. A spectrum of hyperplastic changes ranging from simple hyperplasia to atypical hyperplasia was seen in 15 percent (22/146) of cases. Expression for HER-2/neu oncogene was demonstrated as cell membrane staining. Normal, hyperplastic and neoplastic epithelial cells showed a heterogeneous expression for HER-2/neu oncogene. The intensity of the immunostaining and the number of cells stained for HER-2/neu oncogene had no significant association with surgical stage or histologic grade, although the proportion of patients demonstrating overexpression increased significantly as the histologic grade of their tumor increased (p = 0.030). Furthermore, in a multivariate analysis, a statistically significant correlation was found between the level of expression of HER-2/neu oncogene and overall survival (p = 0.025). This study demonstrated that HER-2/neu oncogene expression is variably present in normal and hyperplastic endometrium. Association between HER-2/neu oncogene expression, higher grade lesions and poor survival in patients with endometrial cancer may also justify assessment of HER-2/neu oncogene as a reliable prognostic indicator.

Adult↗

Comparison of proliferation activity in breast carcinoma by flow cytometry analysis of S-phase and quantitative analysis of MIB-1.

The S-phase which assesses tumor proliferation has been considered to be an independent prognostic factor for breast carcinoma. Quantitative analysis of MIB-1 immunoreactivity is a newly recognized method of determining cellular proliferation that offers some advantages over flow cytometry when limited tumor tissue is available. However, it has been controversial whether there is a significant correlation between MIB-1 immunostaining and S-phase in defining proliferation activity in breast cancer. In order to explore the usefulness of MIB-1 as an additional proliferation parameter and a potential prognostic factor for breast cancer, we analyzed 94 cases of invasive ductal carcinoma of the breast by both flow cytometry (for S-phase and DNA ploidy) and quantitative MIB-1 immunohistochemical analysis using formalin-fixed paraffin-embedded tissue. MIB-1 staining was quantitatively analyzed by image analysis and by visual scoring. Forty-six cases were diploid by flow, while the remaining 48 cases were aneuploid tumors. T-test results indicated that S-phase means were significantly greater (p = 0.0001) in aneuploid cases (mean = 18) compared to diploid cases (mean = 7). MIB-1 means were also greater in aneuploid patients, but these differences were only marginally significant (p = 0.05). S-phase was positively correlated with MIB-1 (r = 0.36, p = 0.003 for image analysis and r = 0.34, p = 0.001 for visual scoring). ROC curve analysis indicated that MIB-1 quantitation is a good predictor of high S-phase (i.e., > 10 percent) in aneuploid cases. A MIB-1 cutoff value of 25 percent for image analysis achieved 82 percent specificity and 80 percent sensitivity for aneuploid high S-phase, while a MIB-1 cutoff value of 40 percent for visual scoring was 73 percent specific and 85 percent sensitive. However, in diploid cases, no comparable MIB-1 cutoffs could be achieved for detecting high S-phase. In summary, our study demonstrated that aneuploid breast carcinomas proliferate more aggressively than diploid tumors. Although linear correlation between MIB-1 and S-phase was weak, MIB-1 was considered to be a good predictor of high S-phase in aneuploid breast cancer patients, possibly due to a threshold effect. Image analysis and visual scoring of MIB-1 immunoreactivity appeared to be comparable in analyzing proliferative activity in breast cancer. Thus MIB-1 assessed by visual scoring may be a less expensive alternative to image analysis.

Aneuploidy↗