Triptolide downregulates human GD3 synthase (hST8Sia I) gene expression in SK-MEL-2 human melanoma cells

In this study, we have shown that gene expression of human GD3 synthase (hST8Sia I) is suppressed by triptolide (TPL) in human melanoma SK-MEL-2 cells. To elucidate the mechanism underlying the downregulation of hST8Sia I gene expression in TPL-treated SK-MEL-2 cells, we characterized the TPL-inducible promoter region within the hST8Sia I gene using luciferase constructs carrying 5'-deletions of the hST8Sia I promoter. Functional analysis of the 5'-flanking region of the hST8Sia I gene demonstrated that the -1146 to -646 region, which contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1 and NF-kappaB, functions as the TPL-inducible promoter of hST8Sia I in SK-MEL-2 cells. Site-directed mutagenesis and ChIP analysis indicated that the NF-kappaB binding site at -731 to -722 is crucial for TPL-induced suppression of hST8Sia I in SK-MEL-2 cells. This suggests that TPL induces down-regulation of hST8Sia I gene expression through NF-kappaB activation in human melanoma cells.

A clinicopathologic study on the diffuse malignant lymphoma: a morphologic and immunophenotypic analysis in 62 patients at Harbor-UCLA Medical Center

In order to compare the prognoses of patients with diffuse malignant lymphomas on the basis of histology and immunophenotypes, we retrospectively studied 62 cases of diffuse lymphoma arising in lymph nodes. We also evaluated the reactivity patterns of monoclonal antibodies (MoAb) LN1, LN2 and LN3 to determine the criteria for making a differential diagnosis in B cell lymphomas. The immunologic phenotypes were determined by the avidin biotin peroxidase complex method, using frozen or paraffin fixed tissues. The majority (66.3%) were B cell with the remaining 20.9% being T cell and 12.9% were non-B, non-T cell lineage. Immunological heterogeneity was found especially in the mixed small and large cell and the immunoblastic lymphomas. There was no significant difference between B- and T-cell lymphomas with respect to survival and death (P > 0.05). Histologically 79% (49/62) of the lymphoma was large cell and 21% (13/62), small cell lymphoma. There was a difference in prognosis between low, intermediate and high-grade of lymphomas. However there were no significant differences among the subtypes of the diffuse aggressive lymphomas. Factors associated with poor prognosis were advanced stages (P < 0.025) and histology of the malignant lymphomas. MoAb LN1, LN2 and LN3 gave positive staining in 83.3%, 91.7% and 60% of B cell lymphomas, respectively. The most common phenotypic pattern in B cell lymphomas was LN1+, LN2+, LN3+/-, suggestive of follicular center cell origin. As a panel, phenotypic patterns of MoAb LN1, LN2 and LN3 may be useful in differentiation of follicular center cell lymphoma from others.