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1.
Article in Chinese | WPRIM | ID: wpr-880105

ABSTRACT

OBJECTIVE@#To study the effect of PX-12 on apoptosis of multiple myeloma (MM) cell line induced by bortezomib.@*METHODS@#MM cell line H929 cells were divided into PX-12 group, bortezomib group, combination group, and control group. 5.0 μmol/L PX-12, 20 nmol/L bortezomib, combination of the two drugs, and DMSO were given to the above mentioned group, respectively. After culture for 24, 48, and 72 hours, the changes of cell viability were observed, the MM cell activity was detected by MTT method, and the cell cycle distribution and apoptosis of each group was detected by flow cytometry. The intracellular ROS level was measured by H@*RESULTS@#MTT assay showed that after culture for 72 hours, the activity of H929 cells in PX-12 group (P<0.05) and bortezomib group (P<0.01) was significantly lower than that in the control group, while that in the combination group was decreased most significantly (P<0.01). After culture for 48 hours, cells in G1 phase in PX-12 group was decreased to 40%, while cells in S phase and G@*CONCLUSION@#PX-12 can increase the apoptosis of MM cell line H929 induced by bortezomib, which may be caused by increasing of ROS level.


Subject(s)
Apoptosis , Bortezomib/pharmacology , Cell Line, Tumor , Cell Proliferation , Humans , Multiple Myeloma
2.
Journal of Experimental Hematology ; (6): 1419-1423, 2020.
Article in Chinese | WPRIM | ID: wpr-827101

ABSTRACT

Venetoclax is a selective inhibitor of the anti-apoptotic protein B-cell lymphoma 2(BCL-2)and has great potential in treating a variety of hematological tumors. In recent years, domestic and foreign scholars have tried to use venetoclax singal or in combination with some drugs to treat the patients with hematological tumors, including elderly acute myeloid leukemia(AML)patients un suitable for intensive chemotherapy, relapsed or refractory chronic lymphocytic leukemia(CLL), Non-Hodgkin's lymphoma(NHL)and multiple myeloma(MM)patients, these studies have achieved good results.At the same time,some scholars found that the secondary drug-resistance occurred in some patients who continuous treated with Venetoclax, and explored the Venetoclax-resistant mechanism. In this review, the research advance of Venetoclax in hematological tumors and the mechanisms of drug resistance are summarized and discussed briefly.


Subject(s)
Aged , Antineoplastic Agents , Therapeutic Uses , Bridged Bicyclo Compounds, Heterocyclic , Therapeutic Uses , Hematologic Neoplasms , Humans , Leukemia, Lymphocytic, Chronic, B-Cell , Drug Therapy , Sulfonamides
3.
Chinese Medical Journal ; (24): 1767-1775, 2018.
Article in English | WPRIM | ID: wpr-775145

ABSTRACT

Background@#Prospective real-life data on the safety and effectiveness of rituximab in Chinese patients with diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) are limited. This real-world study aimed to evaluate long-term safety and effectiveness outcomes of rituximab plus chemotherapy (R-chemo) as first-line treatment in Chinese patients with DLBCL or FL. Hepatitis B virus (HBV) reactivation management was also investigated.@*Methods@#A prospective, multicenter, single-arm, noninterventional study of previously untreated CD20-positive DLBCL or FL patients receiving first-line R-chemo treatment at 24 centers in China was conducted between January 17, 2011 and October 31, 2016. Enrolled patients underwent safety and effectiveness assessments after the last rituximab dose and were followed up for 3 years. Effectiveness endpoints included progression-free survival (PFS) and overall survival (OS). Safety endpoints were adverse events (AEs), serious AEs, drug-related AEs, and AEs of special interest. We also reported data on the incidence of HBV reactivation.@*Results@#In total, 283 previously untreated CD20-positive DLBCL and 31 FL patients from 24 centers were enrolled. Three-year PFS was 59% (95% confidence interval [CI]: 50-67%) for DLBCL patients and 46% (95% CI: 20-69%) for FL patients. For DLBCL patients, multivariate analyses showed that PFS was not associated with international prognostic index, tumor maximum diameter, HBV infection status, or number of rituximab treatment cycles, and OS was only associated with age >60 years (P < 0.05). R-chemo was well tolerated. The incidence of HBV reactivation in hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative/hepatitis B core antibody-positive patients was 13% (3/24) and 4% (3/69), respectively.@*Conclusions@#R-chemo is effective and safe in real-world clinical practice as first-line treatment for DLBCL and FL in China, and that HBV reactivation during R-chemo is manageable with preventive measures and treatment.@*Trial Registration@#ClinicalTrials.gov, NCT01340443; https://clinicaltrials.gov/ct2/show/NCT01340443.


Subject(s)
Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , China , Cyclophosphamide , Doxorubicin , Female , Follow-Up Studies , Humans , Lymphoma, Follicular , Drug Therapy , Lymphoma, Large B-Cell, Diffuse , Drug Therapy , Male , Middle Aged , Prospective Studies , Rituximab , Therapeutic Uses , Vincristine
4.
Journal of Experimental Hematology ; (6): 1414-1419, 2018.
Article in Chinese | WPRIM | ID: wpr-689921

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the clinical efficacy and possible influencing factors of autologous hematopoietic Stem cell transplantation (auto-HSCT) in the treatment of patients with multiple myeloma (MM).</p><p><b>METHODS</b>Clinical data of 40 MM patients received auto-HSCT in the Department of Hematology of Henan Cancer Hospital from September 2010 to November 2017 were retrospectively analyzed, the clinical curative efficiency was summarized and the related factors were analyzed.</p><p><b>RESULTS</b>The curative efficiency of the patients before transplantation was 9(22.5%) with complete remission(CR), 5(12.5%) with very good partial remission(VGPR), 26(65%) with partial remission(PR), respectively, one of them was PR after 3 recurrences. The curative efficiency after transplantation was 22(55%) with complete remission(CR), 12(30%) with very good partial remission(VGPR), 6(15%) with partial remission(PR), respectively. And 2 cases were CR after double transplantation. Median follow-up time was 28.4 (3.1 to 88) months,15 cases presented disease progression, 7 cases were dead, 3-year estimated progression-free survival(PFS) and overall survival(OS) rate were 45.1% and 82% respectively. Unvariate analysis showed that the OS was affected by ISS stage (P<0.05), CR and VGPR (P<0.05) after transplantation; PFS was affected by ISS stage (P<0.01), before transplantation induction therapy (27 cases with bortezomizomi or thalidomide) (P<0.05), disease risk stratification (6 cases in high risk group) (P<0.05) , CR and VGPR (P<0.05) before transplantation, CR and VGPR (P<0.01) after transplantation. Cox multivariate regression analysis showed that the independent prognostic factors for OS were ISS stage, CR and VGPR after transplantation; the independent prognostic factors for PFS were the CR, VGPR, ISS stage after transplantation and induction therapy before transplant.</p><p><b>CONCLUSION</b>Auto-HSCT can improve the clinical efficacy and survival rate of MM patients; ISS stage, CR and VGPR after transplantation are independent prognostic factors for OS and PFS, and induction therapy before transplantation is also an independent prognostic factor for PFS.</p>

5.
Article in Chinese | WPRIM | ID: wpr-271922

ABSTRACT

<p><b>OBJECTIVE</b>To explore the clinical efficacy and safety of EPOCH±R followed by DICE±R regimen for primary breast diffuse large B-cell lymphoma.</p><p><b>METHODS</b>Forty-three patients with primary breast diffuse large B-cell lymphoma were admitted in our hosptial from January 2000 to April 2016. Among them 24 patients were treated with CHOP±R regimen, 19 patients were treated with EPOCH±R followed by DICE±R regimen. The clinical efficacy, survival rate and adverse effects were observed and compared between them.</p><p><b>RESULTS</b>The complete rate in EPOCH±R followed by DICE±R regimen group was higher than that in the CHOP±R group (84.2% vs 70.8%), and the relapsed rate was lower in EPOCH±R followed by DICE±R regimen group than that in the CHOP±R group (6.25% vs 35.3%). Progression-free survival (PFS) and overall survival (OS) rates of 5 years after diagnosis in the EPOCH±R followed by DICE±R group were significantly higher as compared with that in CHOP±R group (PFS, 75% vs 47.4%, P=0.035; OS, 73.3% vs 45.2%, P= 0.043). Treatment-related hematologic adverse events were more serious in the EPOCH±R followed by DICE±R group(63.2% vs 25%). However, these adverse events were controlled and no treatment-related deaths were observed. Multivariate analysis showed that age (P=0.008; 95% CI, 0.026 to 0.579), radiotherapy (P=0.045; 95% CI, 1.028 to 14.719) and LDH level (P=0.007; 95% CI, 0.017 to 0.531) were independent prognostic factors for 5 year overall survival.</p><p><b>CONCLUSION</b>EPOCH±R followed by DICE±R regimen is an effective and safe treatment regimen for PB-DLBCL. Prognostic factors for survival are age, LDH level and radiotherapy.</p>

6.
Article in Chinese | WPRIM | ID: wpr-272485

ABSTRACT

<p><b>OBJECTIVE</b>To evaluate the efficiency and safety of rituximab and dexamethasone combined with cyclophosphamide for treating patients with relapsed and refractory immune thrombocytopenia (ITP).</p><p><b>METHODS</b>Twelve patients with relapsed and refractory immune thrombocytopenia were prospectively enrolled in this study, and received rituximab 375 mg/m(2) once a week for 4 weeks, dexamethasone 40 mg once a day for consecutive 4 days, and cyclophosphamide 500 mg/m(2) biweekly for 2 weeks. The levels of IFN-r and IL-4 in peripheral blood of patients were measured by enzyme-linked immunosorbent assay (ELISA), and the percentages of Breg, Treg and Th17 cells were detected by flow cytometry before and after treatment. Efficiency was evaluated according to platelet counts, and side effects were observed.</p><p><b>RESULTS</b>Six out of 12 patients reached to complete remission and 4 patients reached to partial remission, with the total response rate 83.33%. The platelet counts [(115.42 ± 76.60) × 10(9)/L] after treatment were significantly higher than that before treatment [(115.42 ± 76.60) × 10(9)/L] (P < 0.001). The ratio of IFN-r/ IL4 after treatment (5.89 ± 2.30) was very significantly lower than that before treatment (7.00 ± 2.73) (P = 0.002). The percentage of Breg cells after treatment [(21.27 ± 4.28)%] were much significantly higher than that before treatment [(15.48 ± 1.67)%] (P < 0.001). The ratio of Treg/Th17 after treatment (3.07 ± 1.50) was significantly higher than that before treatment (0.98 ± 0.45) (P < 0.001). Infusion reaction was observed in 1 patient, secondary hypertension and hyperglycemia were in 1 patient, and pneumonia in 2 patients.</p><p><b>CONCLUSION</b>Rituximab and dexamethasone combined with cyclophosphamide can improve the outcomes of patients with relapsed and refractory immune thrombocytopenia patients and they were well tolerated, its mechanism may be related with the balance between T cell sunsets and Treg cells.</p>


Subject(s)
Antibodies, Monoclonal, Murine-Derived , B-Lymphocytes, Regulatory , Cell Biology , Cyclophosphamide , Therapeutic Uses , Dexamethasone , Therapeutic Uses , Enzyme-Linked Immunosorbent Assay , Humans , Interferon-gamma , Blood , Interleukin-4 , Blood , Platelet Count , Prospective Studies , Purpura, Thrombocytopenic, Idiopathic , Drug Therapy , Remission Induction , Rituximab , Therapeutic Uses , T-Lymphocytes, Regulatory , Cell Biology , Th17 Cells , Cell Biology
7.
Journal of Experimental Hematology ; (6): 1667-1672, 2014.
Article in Chinese | WPRIM | ID: wpr-340439

ABSTRACT

This study was aimed to explore the regulation of arsenic trioxide (As₂O₃) on imbalance between adipogenic and osteogenic differentiation of BM-MSC from patients with aplastic anemia(AA). The BM-MSC from AA patients were separated and purified, placed into the adipogenic and osteogenic differentiation culture system, then added the As₂O₃, CsA, As₂O₃combined with CsA were added to corresponding differentiation culture system, the concentration of As₂O₃and CsA were set at 0.001 µmol/ml and 2.5 mmol/ml respectively, the cells were divided into As₂O₃group, the CsA group, combined group and control group (no drug). The cell morphological observation, oil red 'O' staining, Von-Kossa staining, and RT-PCR were used to detect corresponding differentiation marks. The results indicated that in respect to adipogenic differentiation, cellular morphology observing and oil red 'O' staining showed that the rate of adipocyte differentiation in As₂O₃group was (18.3 ± 1.9)%, which was lower than the (91.8 ± 2.7)% in the CsA group and (92.1 ± 1.2)% in control group (P < 0.05), there was no significant difference in comparison with (8.3 ± 1.9)% in the combined group (P > 0.05), but the rate of differentiation in CsA group was higher than that in combined group (P < 0.05), and there was no significant difference in comparison wtih control group. RT-PCR showed that the LPL-mRNA expression level in As₂O₃group were significantly lower than that in the CsA group and the control group (P < 0.05), no difference was observed while compared with the combined group (P > 0.05), but the LPL-mRNA expression level in CsA group was significantly higher than that in the combined group (P < 0.05). In terms of osteogenetic differentiation, the calcium deposition in As₂O₃group and combined group was obviously observed while rarely in the CsA group and the control group when detected by the Von-Kossa staining. OST-mRNA expression level in As₂O₃group were higher than that in CsA group and the control group (P < 0.05), while compared with the combined group, there was no significant difference (P > 0.05), but the OST-mRNA expression level in the CsA group was lower than that in the combined group (P < 0.05). It is concluded that As₂O₃can significantly enhance the ability of BM-MSC from AA patients to differentiate into osteoblast, also can inhibit the adipogenic differentiation, in contrast, the CsA can not promote the osteoblast differentiation of BM-MSC from AA patients.


Subject(s)
Adipocytes , Cell Biology , Anemia, Aplastic , Pathology , Arsenicals , Pharmacology , Bone Marrow , Cell Differentiation , Cells, Cultured , Humans , Mesenchymal Stem Cells , Cell Biology , Osteoblasts , Osteogenesis , Oxides , Pharmacology
8.
Chinese Journal of Hematology ; (12): 55-59, 2013.
Article in Chinese | WPRIM | ID: wpr-323449

ABSTRACT

<p><b>OBJECTIVE</b>To detect the changes of naive T cell level of thymic recent output at different stages of treatment in patients with diffuse large B-cell lymphoma (DLBCL), thereby to evaluate the relationship of thymic recent output function with prognosis and the impact of chemotherapy on the potential of immunological recovery.</p><p><b>METHODS</b>The levels of T-cell receptor rearrangement excision circles (TREC) in DNA of peripheral blood mononuclear cells (PBMNC) from 30 DLBCL patients were monitored before, during, until 3 months and 6 months after chemotherapy by real-time PCR (TaqMan), and TREC-level was detected according to the number of CD3 positive(CD3(+)) cells. Twelve normal individuals who matched in age were served as controls.</p><p><b>RESULTS</b>There was a dramatic reduction of TREC values in all DLBCL patients among which TREC values in germinal center B-cell-like-DLBCL (GCB-DLBCL) were higher than those in non-GCB-DLBCL, as compared with TREC values of normal individual in peripheral blood. The mean values of TREC were 0.91 ± 0.15/1000 PBMNCs and (1.22 ± 0.69)/1000 CD3(+) cells in GCB-DLBCL, (0.43 ± 0.29)/1000 PBMNCs and (0.64 ± 0.44)/1000 CD3(+) cells in non-GCB-DLBCL before chemotherapy. TREC values were significantly associated with lower international prognostic index (IPI) grade (r = -0.441, P = 0.015). TREC-level in DLBCL patients was further decreased after chemotherapy, and reached to the lowest level after the 6th cycle of chemotherapy, and during the corresponding period, the mean values of TREC were (0.63 ± 0.34)/1000 PBMNCs and (0.89 ± 0.65)/1000 CD3(+)cells in GCB-DLBCL, (0.19 ± 0.11)/1000 PBMNCs and (0.27 ± 0.25)/1000 CD3(+) cells in non-GCB-DLBCL. TREC-level began to rise obviously 3 months after the last cycle of chemotherapy in most of the DLBCL patients, and came close to normal level in five cases of patients 6 months after the last cycle of chemotherapy.</p><p><b>CONCLUSIONS</b>Thymic recent output function was impaired severely in DLBCL patients. There was an important relationship between thymic recent output function before chemotherapy and prognosis, and chemotherapy had influenced the potential of immunological recovery.</p>


Subject(s)
Adult , Aged , Case-Control Studies , Female , Gene Rearrangement, T-Lymphocyte , Germinal Center , Allergy and Immunology , Humans , Lymphoma, Large B-Cell, Diffuse , Drug Therapy , Allergy and Immunology , Pathology , Male , Middle Aged , Receptors, Antigen, T-Cell , Allergy and Immunology , Thymus Gland , Allergy and Immunology , Young Adult
9.
Chinese Journal of Hematology ; (12): 417-420, 2013.
Article in Chinese | WPRIM | ID: wpr-235435

ABSTRACT

<p><b>OBJECTIVE</b>To study the effect of transforming growth factor-β activated kinase-1 (TAK1) gene silencing on the proliferation and apoptosis of Kasumi-1 cells induced by arsenic trioxide (As₂O₃).</p><p><b>METHODS</b>Acute myeloid leukemia with t(8;21) cell line Kasumi-1 cells were treated with As₂O₃ or in combination with TAK1 siRNA interference technology. The experiment was divided into four groups: Kasumi-1 cells without any treatment, TAK1 specific siRNA transfection alone, Kasumi-1 cells treated with different concentration of As₂O₃, TAK1siRNA transfection combined with As₂O₃. CCK-8 was used to detect the cell viability. The expression of phosphorylated c-Jun N-terminal kinase (P-JNK) was determined by Western Blot. Cell apoptosis and growth were examined by morphological and colony formation assay.</p><p><b>RESULTS</b>After Kasumi-1 cells were treated with As₂O₃, the rate of cell inhibition was concentration-dependent, and the 50% inhibitory concentration was 3.5 μmol/L. The highest expression level of P-JNK appeared in 30 minutes after cells were treated with As₂O₃. The apoptosis rates of Kasumi-1 cells without any treatment, TAK1 siRNA interference alone group, As₂O₃ alone group and the combined group were (5.02 ± 1.13)%, (6.18 ± 0.28)%, (48.33 ± 2.70)% and (86.07 ± 2.21)%; colony formation rates were (73.83 ± 2.78)%, (76.03 ± 1.46)%, (55.07 ± 1.50)% and (22.20 ± 1.15)%; apoptosis rate of TAK1 siRNA group and the untreated group has no significant difference (P = 0.052); colony formation rate between TAk1 siRNA group and the untreated group has no significant difference (P = 0.179), but the difference in other groups was significant (P = 0.000).</p><p><b>CONCLUSION</b>Silencing the expression of TAK1 can enhance the anti-proliferative and pro-apoptotic effect of As₂O₃ on Kasumi-1 cells, and its mechanism may be through the TAK1 downstream JNK signal pathway.</p>


Subject(s)
Apoptosis , Arsenicals , Pharmacology , Cell Line, Tumor , Humans , JNK Mitogen-Activated Protein Kinases , Metabolism , Leukemia, Myeloid, Acute , Pathology , MAP Kinase Kinase Kinases , Genetics , Metabolism , Oxides , Pharmacology , RNA Interference , RNA, Small Interfering , Genetics , Signal Transduction
10.
Chinese Medical Journal ; (24): 2663-2670, 2012.
Article in English | WPRIM | ID: wpr-244375

ABSTRACT

<p><b>BACKGROUND</b>Chromosomal abnormalities have been shown to play an important prognostic role in multiple myeloma (MM). Interphase fluorescence in situ hybridization (i-FISH) has been much more effective to identify cytogenetic aberrations in MM than conventional cytogenetic technique (CC). To clearly determine the cytogenetic features of Chinese MM patients and identify their prognostic implications, we designed a multicenter study based on i-FISH including 672 patients from 52 hospitals in China.</p><p><b>METHODS</b>All 672 patients were systematically screened for the following genomic aberrations: del(13q), IgH rearrangement, del(p53) and 1q21 amplifications.</p><p><b>RESULTS</b>The analysis showed that the chromosomal changes were detected in 22.1% patients by CC and in 82.3% patients by i-FISH. The most common abnormalities by CC were chromosome 1 aberrations (48.4%), -13/13q- (37.6%), hyperdiploidy (36.6%), hypodiploidy (30.1%) and IgH rearrangements (23.7%). The most frequent abnormalities by FISH was del(13q), which was found in 60.4% patients, whereas IgH rearrangement, 1q21 amplification and p53 deletions were detected in 57.6%, 49.0% and 34.7% cases, respectively. By statistical analysis, -13/13q- by CC was associated with low level of platelet (P = 0.015), hyperdiploidy was associated with low level of serum albumin (P = 0.028), and IgH rearrangement by FISH was associated with high level of β2 microglobulin (P = 0.019). Moreover, 1q21 amplification and del(p53) by FISH conferred a high incidence of progressive disease (PD) after initial therapy. Metaphase detection of IgH rearrangements and chromosome 1 aberrations concurrently was associated with a short progression free survival (PFS) (P = 0.036). No significant prognostic implications of other cytogenetic abnormalities were found associated with overall survival and PFS.</p><p><b>CONCLUSIONS</b>Chinese MM patients had similar cytogenetic abnormalities compared with the previous reported studies. However, the prognostic significance of FISH aberrations were not clearly determined and further study is required.</p>


Subject(s)
Adult , China , Chromosome Aberrations , Chromosomes, Human, Pair 1 , Genetics , Cytogenetic Analysis , Female , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Male , Middle Aged , Multiple Myeloma , Genetics , Pathology
11.
Chinese Journal of Hematology ; (12): 610-613, 2011.
Article in Chinese | WPRIM | ID: wpr-251515

ABSTRACT

<p><b>OBJECTIVE</b>To assess the frequencies and prognostic significance of the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) mutations in acute myeloid leukemia (AML) and to explore their relevance to clinical, cytogenetic and molecular feature.</p><p><b>METHODS</b>Genomic DNA from 96 newly diagnosed AML patients from Sep. 2009 to Jan. 2011 was screened by RT-PCR and sequencing for IDH1 and 1DH2 mutation.</p><p><b>RESULTS</b>The prevalence of IDH1 (p. P127 and p. I130) and IDH2 mutations (p. R140) was 14.6% (14/ 96) and 2.17% (2/96) respectively. The IDH1 mutations of p. P127 and p. I130 were not reported so far in literature. Of 14 IDH1 mutation patients, 10 were with normal karyotype and the differences had statistical significance (P=0.021). Two patients with IDH2 mutation were also with normal karyotype. IDH2 mutations were in older patients at diagnosis. Patients with IDH mutation had higher white blood cell counts, lower platelet counts, expression of HLA-DR, CD34, CD33 and CD13, lower remission rate and higher relapse rate.</p><p><b>CONCLUSION</b>IDH mutation is recurring genetic change in AML and indicates poor prognosis.</p>


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , DNA Mutational Analysis , Female , Humans , Isocitrate Dehydrogenase , Genetics , Karyotype , Leukemia, Myeloid, Acute , Diagnosis , Genetics , Male , Middle Aged , Mutation , Prognosis , Young Adult
12.
Article in Chinese | WPRIM | ID: wpr-313917

ABSTRACT

This study was purposed to explore the effect of hyperthermia on sensitivity of multiple myeloma cells RPMI 8226 to adriamycin (ADM) and its mechanism. The working concentration of ADM against RPMI 8226 cells was defined by MTT assay. RPMI 8226 cells were divided into 4 groups: control group, hyperthermia (42°C) group, chemotherapy (ADM) group and combination group (42°C + ADM), the survival rate of RPMI 8226 cells in 4 groups was detected by trypan blue exclusion, the inhibitory effect of hyperthermia on proliferation of RPMI 8226 cells was detected by MTT assay, the cell cycle distribution, apoptosis rate of cells, intracellular ADM concentration and P-gp expression level were measured by flow cytometry. The 1/4 IC(50) of ADM was defined as the working concentration in the experiment. The results indicated that the hyperthermia promoted the entering the cells from in G(0)/G(1) phase into S and G(2)/M phases, the expression of P-gp protein on cells in hyperthermia and combination groups was down-regulated, the intracellular ADM concentration in combination group obviously increased. It is concluded that the hyperthermia combined with ADM obviously enhance the inhibitory effect on proliferation of RPMI 8226 cells. The hyperthermia increases the sensitivity of RPMI 8226 cells to chemotherapy through down-regulating the expression of P-gp protein on cells and increasing the intracellular ADM concentration.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1 , Metabolism , Cell Line, Tumor , Cell Proliferation , Cold Temperature , Doxorubicin , Pharmacology , Drug Resistance, Neoplasm , Humans , Hyperthermia, Induced
13.
Journal of Experimental Hematology ; (6): 1479-1483, 2010.
Article in Chinese | WPRIM | ID: wpr-332334

ABSTRACT

This study was purposed to explore the biological effects suppressing growth and inducing apoptosis of Chinese medicine compound FFJZ on leukemia cell line K562 and its possible mechanisms of FFJZ. The growth status of K562 cells cultured in vitro was determined by trypan blue exclusion test; the suppressive effect of FFJZ on K562 cells was assayed by MTT method; the inducing apoptosis of FFJZ on K562 cells was detected by flow cytometry. The results showed that after K562 cells were treated with FFJZ in certain concentration range, the inhibited rate of FFJZ on K562 cell growth was remarkably increased along with enhancement of FFJZ, the IC(50) value of FFJZ on K562 cells was 5.6 mg/ml after treatment for 48 hours. At 4 mg/ml of FFJZ the early apoptosis predominated in K562 cells, at 8 mg/ml of FFJZ the late apoptosis ratio significantly increased. As compared with control group without FFJZ, there was significant difference (p < 0.01). It is concluded that the FFJZ in range of certain concentration can suppress growth and proliferation of K562 cells and induce their apoptosis in concentration-dependent manner, the mechanism of which may be associated to inducing apoptosis of K562 cells.


Subject(s)
Apoptosis , Cell Proliferation , Drugs, Chinese Herbal , Pharmacology , Humans , K562 Cells
14.
Journal of Experimental Hematology ; (6): 1128-1131, 2010.
Article in Chinese | WPRIM | ID: wpr-237580

ABSTRACT

The purpose of study was to investigate the feasibility for establishing erythroleukemia model in CB6F1 mice by transplant with haploidentical mouse leukemic cell line FBL-3 and to explore the biological characteristics of FBL-3 cells in CB6F1 mice, CB6F1 and C57BL/6 mice were inoculated intravenously at doses of 1×10(3)-1×10(7) FBL-3 cells respectively. The survival time, the count of peripheral white blood cells, the percentage of erythroblasts and chromosome of these mice were observed. The liver, spleen, lung and kidney were obtained from the dying CB6F1 mice for pathological examination. The ultrastructure of erythroblasts in bone marrow and spleen was observed by transmission electron microscopy as soon as these mice died. Expression of MHC molecules and karyotype of spleen and bone marrow cell were measured. The results showed that 100% and 92.5% incidences of erythroleukemia were observed when 1×10(3)-1×10(7) FBL-3 cells had been administrated intravenously to CB6F1 and C57BL/6 mouse, respectively. There was a linear relationship between the survival time and the number of inoculated leukemic cells. The survival time of CB6F1 was longer than C57BL/6 mice inoculated the same number cell. The main targets for FBL-3 cell infiltration were liver, spleen, marrow, lung and kidney. The reaction of FBL-3 cells to glycogen staining was positive, while the to reaction peroxidase, alkaline phosphatase and butyric acid staining were negative, reaction to chloroacetic acid staining partially was positive. Virus-like particles were found in the spleen and bone marrow cells under electron microscope. Chromosomes of spleen and bone marrow cells in the majority were non-diploid, and the expression of H-2b increased, H-2d expression decreased. It is concluded that the erythroleukemia mouse model can be established in CB6F1 mice transplanted with leukemic FBL-3 cells, that provides a convenience experimental erythroleukemia model for study.


Subject(s)
Animals , Cell Line, Tumor , Disease Models, Animal , Female , Leukemia, Erythroblastic, Acute , Male , Mice , Mice, Inbred C57BL , Neoplasm Transplantation
15.
Chinese Medical Journal ; (24): 2199-2205, 2010.
Article in English | WPRIM | ID: wpr-237480

ABSTRACT

<p><b>BACKGROUND</b>Despite its widespread use in the management of HIV-related cytomegalovirus (CMV) infection, there have been surprisingly few reports of the use of valganciclovir (VGC) in the post-allotransplant setting. So far, no multi-center, non-crossover trial data have been available with the use of this drug as the primary pre-emptive. The present study evaluated the efficacy and safety of VGC for preemptive therapy of CMV infection after allogeneic hematopoietic stem cell transplantation (HSCT).</p><p><b>METHODS</b>From January to April 2007, VGC was adopted in eleven centers in mainland China for pre-emptive therapy of CMV infection in consecutive patients undergoing allogeneic HSCT. Allogeneic HSCT recipients were followed weekly via CMV pp65 antigenemia assay or real-time quantitative polymerase chain reaction (PCR) for detection of CMV-DNA. Patients with a positive assay were treated with VGC, 900 mg P.O. twice a day for 14 days followed by 900 mg P.O. once a day for 14 days after a negative result or the CMV-DNA load was lower.</p><p><b>RESULTS</b>A total of 54 patients (15 siblings, 28 mismatched related donors, 11 unrelated donors) had a positive assay treated with oral VGC. The seroconversion rate was 89% (48/54) as confirmed by a negative assay; six patients failed oral VGC. No significant toxicity was encountered. No case of CMV disease was diagnosed in the responding patients with a median follow-up of 5.3 months after the drug administration.</p><p><b>CONCLUSION</b>Pre-emptive therapy of CMV viraemia with oral VGC is safe and effective in allogeneic HSCT.</p>


Subject(s)
Adolescent , Adult , Antiviral Agents , Therapeutic Uses , China , Cytomegalovirus Infections , Drug Therapy , Female , Ganciclovir , Therapeutic Uses , Hematopoietic Stem Cell Transplantation , Humans , Male , Middle Aged , Viremia , Drug Therapy , Virology , Young Adult
16.
Article in Chinese | WPRIM | ID: wpr-343362

ABSTRACT

This study was purpused to analyze the characteristics of T cell receptor repertoire in target organs of murine graft-versus-host after haploidentical bone marrow transplantation (hiBMT) and the molecular characteristics of complementarity determining region3 (CDR3) repertoires of monoclonal T cell in liver, skin and ileum in murine after hiBMT. Murine haploidentical BMT model was established, CDR3-size spectratyping was used to study TCRBV repertoires in recipient liver, skin, ileum, spleen and a group of CDR3 molecules was obtained from GVHD-target tissues. The results showed that GVHD occurred as early as days 14 after transplantation and was proven by histology in liver, skin and ileum. A number of new monoclonal and oligoclonal T cells emerged in GVHD-target tissue. 45 CDR3 molecules had six C'-terminal motifs, which obtained from liver, skin, ileum in different times after hiBMT. It is concluded that target organs of murine graft-versus-host disease after hiBMT emerged a number of clonal or oligoclonal T cells, part of this T cell clones commonly uses some conserved CDR3 motifs and may recognize similar antigen.


Subject(s)
Amino Acid Sequence , Animals , Bone Marrow Transplantation , Complementarity Determining Regions , Genetics , Graft vs Host Disease , Genetics , Allergy and Immunology , Immunoglobulin Variable Region , Genetics , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Molecular Sequence Data , Receptors, Antigen, T-Cell , Genetics
17.
Article in Chinese | WPRIM | ID: wpr-253364

ABSTRACT

This study was purposed to compare the biological characteristics of umbilical cord-derived mesenchymal stem cells (UC-MSCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs). The frequency of successful isolation, cell yield, colony-forming units-fibroblastics (CFU-F), proliferation capacity, immunophenotype and multi-differentiation potentials of UC-MSCs and BM-MSCs were determined by limiting dilution assay, flow cytometry, invert microscopy, RT-PCR and so on, the determined results were compared. The results showed that MSCs were successfully isolated from all the 36 portion of UC tissue and 8 portion of BM. Although the mean number of nucleated cells isolated from UC tissue was significantly lower than that from BMs (1 x 10(6)/cm vs 5.5 x 10(7)/ml) (p=0.0002), no significant differences of the yield of adherent cells were observed (8.6 x 10(5)/cm vs 8.4 x 10(5)/ml) (p>0.05). UC-MSCs shared the most of the characteristic of BM-MSC, including fibroblastic-like morphology, typical immunophenotype, cell cycle status, adipogenic and osteogenic differentiation potentials. However, the CFU-F frequency was higher in UC (1:1609+/-0.18) than that in BM (1:35700+/-0.01) (p<0.05). Furthermore, the proliferation capacity of UC-MSCs was higher than that of BM-MSCs; the expressions of CD106 and HLA-class I in UC-MSCs were lower than those in BM-MSCs (p<0.05). It is concluded that the cell yield and most biological characteristics of UC-MSCs are similar to BM-MSCs, but UC-MSCs possess the higher proliferation capacity, and the lower expression of HLA-class I and HLA-DR as compared with BM-MSCs, therefore the human umbilical cord tissue may be considered as a promising alternative to bone marrow as a source of MSCs.


Subject(s)
Bone Marrow Cells , Cell Biology , Physiology , Cell Differentiation , Cells, Cultured , Humans , Mesenchymal Stem Cells , Cell Biology , Physiology , Organ Specificity , Physiology , Umbilical Cord , Cell Biology , Physiology
18.
Chinese Journal of Hematology ; (12): 110-112, 2008.
Article in Chinese | WPRIM | ID: wpr-262920

ABSTRACT

<p><b>OBJECTIVE</b>To compare the efficacy of high-dose cytarabine (HD-Ara-C) based chemotherapy for post-remission treatment in patients with t(8;21) (q22;q22) AML-M2 and those with normal karyotype AML-M2.</p><p><b>METHODS</b>AML-M2 patients were grouped into with (21 cases) or without (23 cases) t(8;21) (q22;q22) karyotype groups. After achieved remission by induction therapy, all patients received four cycles of HD-Ara-C (3 mg/m2 per 12 hours by three-hour infusion day 1 to day 3) with either mitoxantrone (7 mg m(-2) d(-1)) or aclarubicin (30 mg m(-2) d(-1)) or etoposide (70 mg m(-2) d(-1)) for 3d as post-remission treatment.</p><p><b>RESULTS</b>Relapse rate in the t(8;21) and the normal karyotype groups was 29% and 57% respectively (P<0.05); 3 year disease-free survival (DFS) rate was 71% and 43% respectively (P < 0.05). and 3 year over-all survival (OS) rate was 76% and 65% respectively (P >0.05).</p><p><b>CONCLUSION</b>Four cycles of high-dose cytarabine based combination chemotherapy as post-remission treatment improves long-term disease-free survival in patients with t(8;21) (q22;q22) AML-M2.</p>


Subject(s)
Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols , Therapeutic Uses , Child , Chromosomes, Human, Pair 21 , Genetics , Chromosomes, Human, Pair 8 , Genetics , Cytarabine , Female , Humans , Karyotyping , Leukemia, Myeloid, Acute , Drug Therapy , Genetics , Male , Middle Aged , Treatment Outcome , Young Adult
19.
Article in Chinese | WPRIM | ID: wpr-267867

ABSTRACT

The objective of this study was to explore the feasibility of intestinal epithelial cell and human source vector used in gene therapy for hemophilia B. The intestinal epithelial sw480 cells were transfected with human source vector plasmid pHrnF9 which contained human coagulation factor IX gene. Transcription of its mRNA were measured by RT-PCR. The transfection efficiency were observed under fluorescence microscope. The expression of its protein and coagulant activities in the transfected sw480 cells were measured by ELISA and one-stage method. The results showed that the expression of hFIX mRNA could be detected after transfection. The transfection efficiency reached to the maximum at 48 hour. The hFIX protein amount was 11.3 +/- 0.23 ng/(10(6) cells.24 h) at 24 hours after transfection and reached to 29.34 +/- 1.00 ng/(10(6) cells.24 h) at 48 hours and decreased to 12.45 +/- 0.15 ng/(10(6) cells.24 hr) at 72 hours. Sw480 cells transfected with pHrnF9 were capable of producing hFIX with coagulant activity. The coagulant activity reached to (6.07 +/- 0.17)%/10(6) cells at 48 hours and decreased to 1.81 +/- 0.06%/10(6) cells at 72 hours. It is concluded that the sw480 cells transfected with pHrnF9 plasmid can express hFIX with coagulant activity, the intestinal epithelial cells may become target cells in the gene therapy for hemophilia B.


Subject(s)
Cell Line, Tumor , Epithelial Cells , Metabolism , Factor IX , Genetics , Metabolism , Genetic Vectors , Genetics , Hemophilia B , Therapeutics , Humans , Intestines , Pathology , RNA, Messenger , Genetics , Metabolism , Transfection
20.
Journal of Experimental Hematology ; (6): 1158-1161, 2008.
Article in Chinese | WPRIM | ID: wpr-234278

ABSTRACT

The objective of study was to investigate the relationship between expressions of CIITA and MHC molecules in five human cell lines. The expressions of MHC molecules and CIITA protein were detected by Western blot, immunohistochemistry and flow cytometry. The expression of CIITA gene was measured by RT-PCR. The results indicated that the expression of MHC-II molecules in 5 human cell lines was consistent with expression of CIITA. The cell lines constitutively expressed CIITA also expressed MHC-II molecules, the expression of MHC-II molecules in cell lines expressed CIITA after induction with IFN-gamma also recovered; the cell lines unexpressed CIITA after induction with IFN-gamma did not respond to IFN-gamma-promoting expression of MHC-II molecules. It is concluded that some cell lines cannot express MHC-II molecules which may be related with deficiency of CIITA expression. It suggest that CIITA participates in regulation of MHC-II molecule expression, which may plays a certain role in escape from carcinogenesis under surveillance of immune system.


Subject(s)
Cell Line , Genes, MHC Class II , Humans , Interferon-gamma , Pharmacology , Nuclear Proteins , Metabolism , Trans-Activators , Metabolism , Tumor Cells, Cultured
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