Clinical efficacy and safety of combination of abraxane and trastuzumab in treatment of recurrent ovarian cancer.

Present research work is carried out to compare the clinical efficacy and adverse reactions between combined medication of abraxane and trastuzumab and single medication of trastuzumab in treatment of ovarian cancer. A total of 80 recurrent ovarian cancer patients in Stage III B or IV confirmed by histopathological examination and/or cytological examination were enrolled in this study and divided into two groups, i.e. the combined medication group (n=37) and the single medication group (n=43). Patients in two groups underwent therapy for 4 cycles to evaluate the short-term efficacy and adverse reactions of these two methods. The control rates of the combined medication group and the single medication group were 86.4% and 81.4%, respectively, while the partial response rates were 45.9% and 44.2%, respectively. As for the overall survival (OS), the OS in the single medication group was 7.0 months, while that in the combined medication group was 7.3 months (p=0.63). Incidence of neutropenia in the single and combined medication groups were respectively 51.2% and 40.5%, while the incidence rates of leukopenia in Stage III or IV were 44.2% and 24.3%, respectively (p<0.001) and the differences between two groups were statistically significant. Also, comparison of the incidence rates of thrombocytopenia between the single (53.5%) and combined (23.6%) medication groups showed statistical significance. With promising efficacy, few adverse reaction and high safety, combined medication of abraxane and trastuzumab is more applicable to the treatment of recurrent ovarian cancer.

The molecular mechanism of apoptosis of human umbilical vein endothelial cells induced by monocyte chemotacitic protein-1.

The present study was aimed to investigate whether Bcl-2, Fas and Bax are involved in monocyte chemotacitic protein-1 (MCP-1)-induced apoptosis of human umbilical vein endothelial cells (hUVECs). hUVECs were cultured, and the purity was identified by immunofluorescence and immunohistochemistry with specific anti-von Willebrand factor (vWF) and anti-VEGF receptor-2 (KDR) antibodies. With 90% confluence hUVECs were serum-starved for 12 h, and then treated with different concentrations of MCP-1 (0.1, 1.0, 10, 100 ng/mL) for 24 and 48 h respectively. The expressions of apoptosis related proteins Fas, Bcl-2, Bax were detected by flow cytometry (FACS) and Western blot. As shown in our preliminary study, MCP-1 induced apoptosis of hUVECs in a dose-dependent manner at both 24 h and 48 h. FACS and Western blot analysis results in the present study indicated that MCP-1 promoted the expression of proapoptotic proteins Bax and Fas and inhibited the expression of antiapoptotic protein Bcl-2. These results suggest that MCP-1 may induce the apoptosis of hUVECs through evoking the imbalance between proapoptotic Fas/Bax and antiapoptotic Bcl-2 protein.

Characterization of D-cyclin proteins in hematolymphoid neoplasms: lack of specificity of cyclin-D2 and D3 expression in lymphoma subtypes.

D-cyclin proteins play a central role in cell-cycle regulation and are involved in the pathogenesis of lymphomas. In mantle-cell lymphoma, the t(11;14) translocation leads to overexpression of cyclin-D1, in addition to which cyclin-D1-negative mantle-cell lymphoma that overexpress cyclin-D2 or D3 have also been described. Although cyclin-D2 and D3 have been implicated in the prognosis of specific lymphoma subtypes, a thorough characterization of D-cyclin protein expression in human hematolymphoid neoplasia has not been reported. To evaluate the tissue expression patterns of D-cyclins, particularly D2 and D3, in normal and neoplastic hematolymphoid tissues, we optimized the commercially available antibodies for D-cyclins for use on paraffin-embedded tissue and stained tissue microarrays of over 700 patient samples. Our results show that cyclin-D2 and D3 proteins are expressed in many more lymphoma subtypes than cyclin-D1. Cyclin-D1, D2 and D3 were expressed in 100, 22 and 6% of mantle-cell lymphomas and 2, 49 and 20% of diffuse large B-cell lymphomas. Fluorescence in situ hybridization studies confirmed the presence of the CCND1/IGH translocation in the majority of mantle-cell lymphoma, but not in diffuse large B-cell lymphoma that expressed cyclin-D1 protein. In addition, a subset of follicular, marginal zone, lymphoplasmacytic, lymphoblastic, classical Hodgkin, mature T-cell and natural killer cell lymphomas and acute myeloid leukemias also expressed cyclin-D2 and D3. These data support the hypothesis that dysregulation of cell-cycle control by D-cyclins contribute to the pathogenesis of hematolymphoid neoplasia, and suggest a potential role for these proteins in the prognostic and therapeutic aspects of these diseases. For diagnostic purposes, however, the expression of D-cyclin proteins should be interpreted with caution in the subclassification of lymphoma types.

CD81 protein is expressed at high levels in normal germinal center B cells and in subtypes of human lymphomas.

CD81 is a tetraspanin cell surface protein that regulates CD19 expression in B lymphocytes and enables hepatitis C virus infection of human cells. Immunohistologic analysis in normal hematopoietic tissue showed strong staining for CD81 in normal germinal center B cells, a cell type in which its increased expression has not been previously recognized. High-dimensional flow cytometry analysis of normal hematopoietic tissue confirmed that among B- and T-cell subsets, germinal center B cells showed the highest level of CD81 expression. In more than 800 neoplastic tissue samples, its expression was also found in most non-Hodgkin lymphomas. Staining for CD81 was rarely seen in multiple myeloma, Hodgkin lymphoma, or myeloid leukemia. In hierarchical cluster analysis of diffuse large B-cell lymphoma, staining for CD81 was most similar to other germinal center B cell-associated markers, particularly LMO2. By flow cytometry, CD81 was expressed in diffuse large B-cell lymphoma cells independent of the presence or absence of CD10, another germinal center B-cell marker. The detection of CD81 in routine biopsy samples and its differential expression in lymphoma subtypes, particularly diffuse large B-cell lymphoma, warrant further study to assess CD81 expression and its role in the risk stratification of patients with diffuse large B-cell lymphoma.