Biological properties of mesenchymal stem cells derived from bone marrow of patients with multiple myeloma / 中国实验血液学杂志

The study was purposed to explore the role of mesenchymal stem cells (MSCs) in the pathogenesis of bone disease particularly observed in multiple myeloma (MM), the biological features of marrow derived MSCs from patients with MM have been investigated. Marrow aspirates were harvested from 11 newly diagnosed patients with MM and 5 normal adults and MSCs were isolated and culture-expanded by the cell properties of adherence to plastic flasks, The phenotype was analyzed by flow cytometric technique. The proliferation of MSCs was observed by MTT assay and their differentiation capacities into osteoblasts and adipoblasts were assessed with lineage-specific histochemical staining. The concentrations of IL-6 and SCF in the culture supernatant were detected by enzyme-linked immunosorbent assay (ELISA). MSC culture supernatants were collected and MTT assay was performed to evaluate their support on the proliferation of an MM cell line SKO007 cells. The results showed that bone marrow-derived MSCs from MM patients were homogeneously positive for CD29, CD73, CD166 and HLA-ABC and negative for hematopoietic cell marker CD45 and endothelial cell marker CD31, the phenotype of which was similar to that of marrow counterparts from normal adults. MTT assay indicated that MSCs from MM patients or normal adults proliferated at similar rates. MSCs from MM patients occupied in vitro osteogenic and adipogenic capacity as those from normal adults. The levels of IL-6 and SCF in culture supernatant were greatly up-regulated in MM patients by ELISA assay. Furthermore, MSC culture supernatants from MM bone marrow displayed enhanced activity to promote the proliferation of SKO007 cells. It is concluded that marrow-derived MSCs from bone marrow of MM patients are normal in their proliferation and differentiation capacities, and myeloma bone disease may not be ascribed to the differentiation of MSCs while the elevated secretion of IL-6 and SCF may provide necessary cues for the survival of malignant myeloma cells.

Prognostic value of thymidylate synthase, topoisomerase-1 and Ki-67 in advanced colorectal cancer patients on irinotecan and fluorouracil treatment / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the prognostic value of thymidylate synthase (TS), topoisomerase-1 (Topo-1), and proliferating index Ki-67 in advanced colorectal cancer patients on irinotecan (CPT-11) in combination with fluorouracil treatment (5-Fu).</p><p><b>METHODS</b>The biomarker expression of TS, Topo-1 and Ki-67 in 78 patients detected immunohistochemically were correlated with the clinical outcome.</p><p><b>RESULTS</b>The expressions of those biomarkers were not correlated with clinical therapeutic response, but with time to progression (TTP) and/or overall survival (OS). Patients with low expression of TS had significantly longer TTP (P < 0.05) and in OS (P < 0.05). The low expression of Ki-67 was also significantly predictive of longer survival (P < 0.05). As compared with any biomarker, the combination of any two biomarkers still possessed no predictive value to therapeutic response, but an enhanced predictive value to prognosis. The median time to progression in patients with low expression of TS, or Ki-67, or both were 9, 8 and 17 months, respectively; in patients with low expression of TS, or Topo-1, or both were 9, 9 and 13 months; in patients with low expression of Topo-1, or Ki-67, or both were 8, 9 and 11 months. TTP was significantly longer in patients with low expression of two biomarkers as compared with those with high expression (P = 0.031).</p><p><b>CONCLUSION</b>TS, Topo-1, and Ki-67 are not predictive for chemotherapy response to CPT-11 combined with 5-Fu, but valuable in predicting prognosis. The combination of any two biomarkers can provide more powerful prognostic information for advanced colorectal cancer patients.</p>