[Show abstract][Hide abstract] ABSTRACT: The allogeneic hematopoietic stem cell (HSC) transplantation of mesenchymal stem cells (MSCs) contributes to the reconstitution of hematopoiesis by ameliorating acute graft‑versus‑host disease (aGVHD). However, the role of MSCs in graft‑versus‑leukemia remains to be determined. In the present study, we co‑cultured C57BL/6 mouse bone marrow (BM)‑derived MSCs with A20 murine B lymphoma, FBL3 murine erythroleukemia and P388 murine acute lymphocytic leukemia cells. Cell proliferation, apoptosis, cell cycle progression and the amount of cytokine secretion were then measured using a Cell Counting kit‑8, Annexin V/propidium iodide staining, flow cytometry and ELISA, respectively. We also established a model of allogeneic bone marrow transplantation (BMT) using BALB/c mice. Following the administration of A20 cells and MSCs, we recorded the symptoms and the survival of the mice for 4 weeks, assessed the T cell subsets present in peripheral blood, and, after the mice were sacrifice, we determined the infiltration of MSCs into the organs by histological staining. Our results revealed that the MSCs inhibited the proliferation of the mouse lymphoma and leukemia cells in vitro, leading to cell cycle arrest and reducing the secretion of interleukin (IL)‑10. In our model of allogeneic BMT, the intravenous injection of MSCs into the mice injected wth A20 cells decreased the incidence of lymphoma, improved survival, increased the fraction of CD3+CD8+ T cells, decreased the fraction of CD3+CD4+ T cells and CD4+CD25+ T cells in peripheral blood, and ameliorated the manifestation of aGVHD. The results from the present study indicate that MSCs may be safe and effective when used in allogeneic BMT for the treatment of hemotological malignancies.
International Journal of Molecular Medicine 04/2015; 36(1). DOI:10.3892/ijmm.2015.2191 · 2.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To explore the effects and possible mechanisms of decitabine on Molt4 in vitro.
Effects of decitabine on cells proliferation were detected by using CCK-8, the apoptosis by Annexin V-FITC, cell cycles by propidium iodide-FACS. Discrepancy genes were screened by RNA-seq technique. The CpG methylation of lactoferrin (LTF) gene in Molt4 cells were identified by Bisulfite sequencing PCR (BSP). The expression of LTF mRNA in Molt4 by RT-PCR and LTF protein expression were analyzed by Western blot.
Decitabine effectively inhibited proliferation and induced apoptosis for Molt4 cells by an time- and dose-dependent manners. Cell cycles were arrested at the G₀/G₁ phase. The promoter methylation degree of LTF gene in Molt4 cells was 72.3% before decitabine treatment and decreased to 45.0% after treatment with 0.50 μmol/L decitabine for 72 h. After the reduction of methylation, expression of its mRNA and protein increased, meanwhile caspase 3 and caspase 9 protein expression levels increased.
The demethylating drug decitabine can induce apoptosis, detain cell cycle at phase G₀/G₁, inhibit proliferation and up-regulate LTF gene expression in Molt4 cells. LTF may become a new target for acute T lymphoblastic leukemia.
Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 03/2015; 36(3):230-4. DOI:10.3760/cma.j.issn.0253-2727.2015.03.012
[Show abstract][Hide abstract] ABSTRACT: Bortezomib has been widely used in the treatment of various cancers; however, its exact mechanisms of action are not fully understood, particularly in acute T lymphoblast leukemia (T-ALL). Here, we visualize the anti-leukemia effect of bortezomib in both human T-ALL cell line and animal models. In vitro study, a human T-ALL cell line bearing Notch1 mutations, MOLT-4, was treated with bortezomib. At clinically achievable concentrations, bortezomib inhibited cell growth by inducing G1 phase arrest and apoptosis with a dose-dependent manner. A murine tumor xenograft model was achieved by subcutaneous injection of MOLT-4 cells for in vivo study. Administration of bortezomib significantly reduced tumor mass volume when compared with controls. Of note, bortezomib inhibited growth of leukemia cells in a Notch1-induced murine T-ALL model, and the life span of leukemia-bearing mice was markedly increased. Further studies revealed that bortezomib led to inhibited expression of Notch1 target genes. Taken together, our results demonstrate that bortezomib shows significant anti-leukemia effect in T-ALL bearing Notch1 mutations in vitro and in vivo. The present study provides evidence that bortezomib might be a candidate therapeutic reagent in the treatment of T-ALL.
Cancer Chemotherapy and Pharmacology 09/2012; 70(6). DOI:10.1007/s00280-012-1953-4 · 2.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The response to remission induction in elderly patients with acute myeloid leukemia (AML) remains poor. The purpose of this paper is to evaluate the efficacy and toxicity of a plant alkaloid, homoharringtonine, in combination with cytarabine as an induction therapy for AML in elderly patients (> or =60 years).
Twenty-three patients were treated with the HA regimen consisting of homoharringtonine (2 mg/m2/day for 7 days) and cytarabine (Ara-C, 100 mg/m2/day for 7 days). The overall response rate was 56.5% with complete remission (CR) rate of 39.1% and partial remission of 17.4%. There was no early death in this cohort of patients. The estimated median overall survival (OS) time of all patients was (12.0 +/- 3.0) months. The estimated OS time of the CR patients was 15 months. The estimated one-year OS rate of all patients treated with HA protocol was (49.3 +/- 13.5) %. The estimated one-year OS rate of the CR patients was (62.5 +/- 17.1) %.
HA is a suitable induction regimen for elderly patients with AML, with relatively low toxicity and reasonable response rate.
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to evaluate the effectiveness of bortezomib combined with epirubicin, dexamethasone, and thalidomide (BADT) for the treatment of multiple myeloma (MM). The BADT regimen consisted of a maximum of eight 4-week cycles of: intravenous bortezomib (1.0 mg/m(2)) and intravenous epirubicin (12 mg/m(2)) on days 1, 4, 8, and 11; dexamethasone (20 mg) on days 1, 2, 4, 5, 8, 9, 11, and 12; and oral thalidomide (100 mg/m(2)) on days 1-28. Twelve patients with MM were included in the study, of whom four had not been previously treated and eight had been previously treated with at least one cycle of a systemic combined regimen. All the patients completed at least two cycles of treatment, with an average of five cycles; the complete response (CR) rate was 83.3% (10/12) and stabilization of disease was 16.7% (2/12). The average number of cycles required to achieve CR was 1.9 (range 1-6). In three patients, mobilization of peripheral blood stem cells allowed a sufficient quantity of CD34+ cells to be harvested for future autotransplantation. The main adverse reactions included peripheral neuropathy (4/12), thrombocytopenia (3/12), electrocardiographic abnormalities (4/12), neutropenia (5/12), and liver function impairment (4/12), primarily grade I-II. Infection occurred in four patients with neutropenia, including one patient who developed sepsis. The estimated 1-year overall survival rate was 91.7 +/- 8.0%, and the estimated 1-year disease-free survival was 75.0 +/- 12.5%. BADT is a highly effective combined regimen, with acceptable toxicity, for the treatment of multiple myeloma.
International journal of hematology 01/2009; 89(1):34-8. DOI:10.1007/s12185-008-0218-9 · 1.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ObjectiveTo evaluate the clinical effectivity and toxicity of the regimen FMD (fludarabine, mitoxantrone, dexamethasone) in patients
with non-Hodgkin’s lymphoma.
MethodsThirty-two patients, twenty-four of whom had indolent B-cell lymphoma, 6 peripheral T-cell lymphoma, two diffuse large B-cell
lymphoma, received FMD. Treatment comprised: fludarabine 25∼30 mg/m2 days 1∼3, mitoxantrone 8∼10 mg/m2 day 1, and dexamethasone 20∼30 mg/m2 days 1∼5. At the same time, patients received prophylaxis against conditional infection with trimethoprim-sulfamethoxazole,
fluconazole, acyclovir and immunoglobulin.
ResultsOf the thirty-two patients treated, the complete response (CR) rate, partial response (PR) rate and overall response (OR)
rate were 56.3%, 21.9% and 78.2% respectively. The CR and OR rate of 24 patients with indolent B-cell lymphoma were 66.7%
and 88.3% respectively. Two of six patients with peripheral T-cell lymphoma were of complete response type and one was of
partial response type. One of two patients with diffuse large B-cell lymphoma was partial response. The dominating toxicity
was myelotoxicity and immunotoxicity. There was no treatment associated death in all patients treated with FMD. Grade 3∼4
neutropenia occurred in 43.8% patients, 12.5% patients had infections and 9.3% developed grade 3∼4 thrombocytopenia. At a
median follow-up of 24 (5∼54) months, the 2-year overall-survival rate and progression-free survival rate were (87.5 ± 1.4)%
and (83.3 ± 1.6)% respectively. The 2-year OS and PFS rates of the indolent group were (93.75 ± 6.25)% and (87.5 ± 8.54)%.
ConclusionFMD regimen was highly effective with low toxicity in the treatment of non-Hodgkin’s lymphoma, especially in indolent B-cell
lymphoma. It also helps to improve the prognosis even in some aggressive lymphoma, such as peripheral T cell lymphoma.
Chinese Journal of Clinical Oncology 11/2008; 5(6):433-436. DOI:10.1007/s11805-008-0433-4