ABSTRACT
OBJECTIVE@#To explore whether thrombopoietin (TPO) can rescue megakaryopoiesis by protecting bone marrowderived endothelial progenitor cells (BM-EPCs) in patients receiving chemotherapy for hematological malignancies.@*METHODS@#Bone marrow samples were collected from 23 patients with hematological malignancies 30 days after chemotherapy and from 10 healthy volunteers. BM-EPCs isolated from the samples were identified by staining for CD34, CD309 and CD133, and their proliferation in response to treatment with TPO was assessed using CCK8 assay. DiL-Ac-LDL uptake and FITC-UEA-I binding assay were performed to evaluate the amount of BM-EPCs from the subjects. Tube-formation and migration experiments were used for functional assessment of the BM-EPCs. The BM-EPCs with or without TPO treatment were co-cultured with human megakaryocytes, and the proliferation of the megakaryocytes was detected with flow cytometry.@*RESULTS@#Flow cytometry indicated that the TPO-treated cells had high expressions of CD34, CD133, and CD309. CCK8 assay demonstrated that TPO treatment enhanced the proliferation of the BM-EPCs, and the optimal concentration of TPO was 100 μg/L. Double immunofluorescence assay indicated that the number of BM-EPC was significantly higher in TPO-treated group than in the control group. The TPO-treated BM-EPCs exhibited stronger tube-formation and migration abilities ( < 0.05) and more significantly enhanced the proliferation of co-cultured human megakaryocytes than the control cells ( < 0.05).@*CONCLUSIONS@#TPO can directly stimulate megakaryopoiesis and reduce hemorrhage via protecting the function of BM-EPCs in patients following chemotherapy for hematological malignancies.
Subject(s)
Humans , Bone Marrow , Bone Marrow Cells , Cells, Cultured , Hematologic Neoplasms , Megakaryocytes , ThrombopoietinABSTRACT
<p><b>OBJECTIVE</b>To analyze the clinical efficacy and toxicity of vitamin support in lung adenocarcinoma patients treated with pemetrexed second-line chemotherapy.</p><p><b>METHODS</b>Two hundred and eighty-three patients with stage 3/4 lung adenocarcinoma treated at our hospital from August 2010 to August 2013 were included in this study. The lung adenocarcinomas in all the 283 patients were confirmed by pathology or cytology, all were EGFR-negative, and all patients received pemetrexed second line chemotherapy. The 283 patients were randomly divided into two groups: the improved treatment group (142 cases) and the conventional treatment group (141 cases). The patients of conventional treatment group received 400 µg folic acid per os daily for 7 days before the first dose of pemetrexed, and continued until 21 days after the last dose of pemetrexed. Besides, they received 1000 µg vitamin B12 injection at 7 days before the first dose of pemetrexed, and once per cycle of pemetrexed for 3 cycles after the last dose of pemetrexed. The patients of the improved treatment group took 400 µg folic acid daily per os from the day before the first dose to 21 days after the last dose of pemetrexed. They also received 500 µg vitamin B12 by injection one day before the first dose, and one day before each therapy cycle of pemetrexed therapy.</p><p><b>RESULTS</b>The mean number of cycles of pemetrexed chemotherapy was 4 in both groups. In the 142 patients of improved treatment group, complete response (CR) was observed in two cases, partial remission (PR) in 28, stable disease (SD) in 21, and progressive disease (PD) in 91 cases, with a total effective rate of 21.1%. While in the conventional treatment group, CR was observed in one case, PR in 27 cases, SD in 23 cases, and PD in 90 cases, with a total effective rate of 19.9%. The median progression-free survival (PFS) was 3.8 months in the improved treatment group and 4.2 months in the conventional treatment group (P=0.143). The toxicity of chemotherapy was mild in both groups, with no significant difference between the two groups (P>0.05). The most common side effects of hematological system were leukopenia and neutropenia, and the most common side effects of non-blood system were nausea and vomiting. The most common grade 3-4 toxic reaction in both groups was leukopenia and neutropenia, with no significant difference between the two groups (P>0.05). Multivariate analysis showed that the age of patients was an independent factor of grade 3-4 chemotherapy toxic reaction (P<0.05), while gender, the baseline level of PS score or blood system had no significant effect on the grade 3-4 chemotherapy toxic reaction (P>0.05).</p><p><b>CONCLUSIONS</b>Compared with the conventional treatment scheme, the improved treatment scheme has similar therapeutic effects and could be used more conveniently, while the toxic effects of chemotherapy are not increased at the same time. Our results indicate that pemetrexed-based chemotherapy does not need to delay the chemotherapy because of vitamin support treatment.</p>