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Abivertinib, a third-generation tyrosine kinase inhibitor, is originally designed to target epidermal growth factor receptor (EGFR)-activating mutations. Previous studies have shown that abivertinib has promising antitumor activity and a well-tolerated safety profile in patients with non-small-cell lung cancer. However, abivertinib also exhibited high inhibitory activity against Bruton's tyrosine kinase and Janus kinase 3. Given that these kinases play some roles in the progression of megakaryopoiesis, we speculate that abivertinib can affect megakaryocyte (MK) differentiation and platelet biogenesis. We treated cord blood CD34+ hematopoietic stem cells, Meg-01 cells, and C57BL/6 mice with abivertinib and observed megakaryopoiesis to determine the biological effect of abivertinib on MK differentiation and platelet biogenesis. Our in vitro results showed that abivertinib impaired the CFU-MK formation, proliferation of CD34+ HSC-derived MK progenitor cells, and differentiation and functions of MKs and inhibited Meg-01-derived MK differentiation. These results suggested that megakaryopoiesis was inhibited by abivertinib. We also demonstrated in vivo that abivertinib decreased the number of MKs in bone marrow and platelet counts in mice, which suggested that thrombopoiesis was also inhibited. Thus, these preclinical data collectively suggested that abivertinib could inhibit MK differentiation and platelet biogenesis and might be an agent for thrombocythemia.
Subject(s)
Animals , Mice , Acrylamides/pharmacology , Blood Platelets/drug effects , Cell Differentiation , Megakaryocytes/drug effects , Mice, Inbred C57BL , Piperazines/pharmacology , Pyrimidines/pharmacologyABSTRACT
This study aimed to investigate the prevalence, clinical characteristics, and prognostic impact of 1p32.3 deletion in patients with newly diagnosed multiple myeloma (MM). A retrospective analysis was conducted on 411 patients with newly diagnosed MM; among which, 270 received bortezomib-based therapies, and 141 received thalidomide-based therapies. Fluorescence in situ hybridization (FISH) was performed to detect six cytogenetic abnormalities, namely, del(1p32.3), gain(1q21), del(17p13), del(13q14), t(4;14), and t(11;14). Results showed that 8.3% of patients with MM were detected with del(1p32.3) and had significantly more bone marrow plasma cells (P = 0.025), higher β2-microglobulin levels (P = 0.036), and higher lactate dehydrogenase levels (P = 0.042) than those without del(1p32.3). Univariate analysis showed that patients with del(1p32.3) under thalidomide-based therapies (median PFS 11.6 vs. 31.2 months, P = 0.002; median OS 16.8 vs. 45.9 months, P < 0.001) were strongly associated with short progression-free survival (PFS) (P = 0.002) and overall survival (OS) (P < 0.001). Multivariate analysis revealed that del(1p32.3) remained a powerful independent factor with worse PFS (P = 0.006) and OS (P = 0.016) for patients under thalidomide-based treatments. Patients with del(1p32.3) under bortezomib-based treatments tended to have short PFS and OS. In conclusion, del(1p32.3) is associated with short PFS and OS in patients with MM who received thalidomide- or bortezomib-based treatments.
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Objective:To investigate the effect of pregnancy on endothelial progenitor cells (EPCs) in patients with rheumatoid arthritis (RA) and its mechanism.Methods:The newly treated RA patients in our hospital from January 2016 to June 2018, were included in this study. According to pregnancy or not, patients were divided into simple RA group and RA pregnancy group. They were all female patients, 30 in each group. Immunohistochemical staining was used to detect the number of lymphocyte common antigen (LCA) + lymphocytes and CD68 + macrophages in synovial tissue, flow cytometry was used to detect the proportion of EPC and endothelial cells, and enzyme-linked immunosorbent assay(ELISA) was used to detect the concentrations of vascular endothelial growth factor (VEGF), stromal cell derived factor (SDF-1), interleukin (IL)-6 and IL-10 in EPC supernatant. T-test was used for the comprarison between the two groups, and single factor analysis of variancewas used for the comparison between multiple groups. Results:Immunohistoche-mical results showed that the number of CD68 + macrophages and LCA + lymphocytes in synovium of RA with pregnancy group was significantly lower than that of non-pregnant RA group. The results of ELISA showed that the concentration of human leucocyte antigen-G (HLA-G) in peripheral blood was (8.9±1.7) pg/ml in non- pregnant RA group and (396.7±89.6) pg/ml in RA pregnancy group, the difference beween the two groups was statistically significant ( t=4.329, P<0.01). The results of flow cytometry showed that the proportion of EPC in lymphocytes was (0.13±0.03)% in non-pregnant RA group and (0.76±0.09)% in RA with pregnancy group, the difference beween the two groups was statisti-cally significant ( t=6.671, P<0.01). The results of correlation analysis showed that the proportion of EPC in peripheral blood was positively correlated with HLA-G concentration ( r=0.886 1, P<0.01). In vitro experiments showed that HLA-G could promote the recovery of EPC paracrine and differentiation function in RA patients. Conclusion:Pregnancy can improve the number and biological function of EPC in patients with RA. HLA-G may play an important role in this process.
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OBJECTIVE@#To characterize cytogenetic changes and prognosis of patients with acute myeloid leukemia (AML) from different age groups.@*METHODS@#The karyotypes of 515 AML patients were analyzed by using short-term culture of bone marrow cells and R-banding technique. Combined with FAB typing and genetic testing, cytogenetic changes and prognosis of different age groups were analyzed.@*RESULTS@#The abnormal cloning rate was 54.6% among the 515 patients. The abnormal cloning rate and adverse risk karyotype proportion of those with myeloproliferative syndromes (MDS) and secondary AML were higher than those with de novo AML (P = 0.027; P<0.01). A significant difference was found in the number of structural abnormalities and proportion of favorable risk karyotypes among different age groups (P = 0.026; P = 0.004). And there was also a significant difference in the abnormal cloning rate between different FAB types (P<0.01). In those with non-acute promyelocytic leukemia (APL), the expression level of WT1 gene seemed to affect the prognosis. The survival rate of patients with karyotypes of adverse risk was lower than those with karyotypes of favorable risk (P = 0.015). The survival rate of the ≥60-year-old group was lower than the ≤30-year-old and 31 to 59-year-old groups (P<0.01, P<0.01).@*CONCLUSION@#The karyotypes of AML patients have different age distribution characteristics. The survival rate of ≥60-years-old group and karyotype of poor prognosis is low. Patients with MDS with secondary AML have a poor prognosis.
Subject(s)
Adult , Humans , Middle Aged , Chromosome Aberrations , Cytogenetic Analysis , Cytogenetics , Karyotype , Karyotyping , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , PrognosisABSTRACT
Objective To investigate the effect and mechanism of placental protein 14 on the proliferation and differentiation of B cells.Methods The lymphocyte of human peripheral blood was separated by gradient centrifugation.Flow cytometry was used to detect the proportion of CD4+CXCR5+follicular helper T cells (Tfh cells),CD4+CXCRS+Foxp3+ follicular regulatory T cells (Tfr cells),CD3-CD19+B cells and CD3-CD38+ plasma cells.ELISA method was used to detect the concentration of IL-21,IL-10 and TGF-beta in the supernatant,and the co-culture of cells was performed by Transwell chamber;t test was used for comparison between groups.Results The proportion of Tfh cells and Tfr cells in the control group was (2.52±0.16)％ and (1.26±0.24)％,respectively,and that of the placental protein 14 groups were (0.84±0.09)％ and (4.64±0.68)％,respectively.There was a significant difference between the two groups (t=9.150,P=0.000 8 and t=4.669,P=0.009 5).Pplacental protein 14 could further inhibit the secretion of IL-21 (t=5.086,P=0.007 1),and promote the increase of IL-10 and TGF-β concentration (t=3.599,P=0.022 8 and t=6.651,P=0.002 7).The percentage of B cells and plasma cells in the placental protein 14 group were (4.87±0.20)％ and (5.41±0.54)％,which were significantly different from those in the Tfh cell group (t=4.997,P=0.007 5;t=5.110,P=0.006 9).Conclusion Placental protein 14 can inhibit the proliferation of B cells and differentiate into plasma cells by inhibiting the differentiation of Tfh cells and increasing the proportion of Tfr cells.
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Objective To explore the efficacy and safety of multiple cervical suture in treating stripping surface intractable hemorrhage after cesarean section in the patients with placenta previa centralis.Methods Twenty-three patients with stripping surface intractable hemorrhage during cesarean section caused by placenta previa centralis from January 2012 to December 2015 in this hospital were selected and conducted multiple cervical suture,and 21 patients with the same disease undergoing intraoperative conventional hemostasis method from January 2008 to December 2011 served as the control group.The operation time,intraoperative and postoperative blood loss volume,red blood cell transfusion,hysterectomy and postoperative recovery were compared between the two groups.Results The operation time,intraoperative and postoperative blood loss volume,blood transfusion volume and hysterectomy rate in the observation group were significantly less than those in the control group(P＜0.05),while There were no statistical difference in the aspects of postoperative incision infection,bloody lochiorrhea persisting time,menstrual recovery time and menstrual volume between the two groups(P＞0.05).Conclusion The application of multiple cervical suture in the treatment of stripping surface intractable hemorrhage after cesarean section in the patients with placenta previa centralis has better hemostatic effect,had no complications in short term follow up and is worthy clinical promotion and ap plication.
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Ovarian vein thrombosis (OVT) is a rare, insidious and dangerous disease mostly occurs in the postpartum period. Early diagnosis and timely treatment are very important and may avoid serious complications. Here we reported a woman who had a fever and left back pain three days after vaginal delivery. Enhanced CT suggested that thrombosis occurred in the left ovarian vein, and even the renal vein was involved. Thrombus susceptibility gene detection revealed that the plasminogen activator inhibitor-1 gene was 4G/5G heterozygous genotype and the 5,10- methylenetetra-hydrofolate reductase gene was C/T heterozygous genotype. Anticoagulant treatments with low-molecular-weight heparin and rivaroxaban were effective.
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Objective@#To study the expression of miRNA-181a in acute myeloid leukemia (AML) patients with normal karyotype to probe its prognosis significance.@*Methods@#The expression level of miRNA-181a in bone marrow mononuclear cells of 120 de novo AML patients with normal karyotype was detected by real time fluorescence quantitative PCR. The direct sequencing method was used to detect IDH1, IDH2, NPM1, FLT3-ITD, DNMT3A and CEBPα mutations in CN-AML patients after PCR. The relationship between miRNA-181a expression and gene mutation, the clinical parameters and prognosis were analyzed.@*Results@#The rates of overall surviva1 (OS) in high expression and low expression groups were 25.0 months and 15.0 months, respectively (P<0.05) . Relapse free survival (RFS) in high expression and low expression groups were 21.4 months and 11.2 months, respectively (P<0.05) . Significantly higher level hemoglobin, complete remission rate and proportion of wild type NPM1 expression in the high expression of miRNA-181a group were observed when compared with the lower expression of miRNA-181a group (P<0.05) . Multivariate Cox regression analysis showed miRNA-181a overexpression was an independent prognostic factor for CN-AML (HR=2.219, 95%CI 1.601~2.432, P=0.018) .@*Conclusion@#Higher expression of miRNA-181a was a good prognostic factor independent of clinical parameters and high frequency gene mutations, which implicated that the miRNA-181a expression level could be used as an important prognostic indicator of AML patients with normal karyotype.
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<p><b>OBJECTIVE</b>To assess the value of fluorescence in situ hybridization (FISH) for the detection of genomic abnormalities among patients with chronic lymphocytic leukemia (CLL).</p><p><b>METHODS</b>Interphase FISH was performed on bone marrow samples derived from 105 patients with CLL at the time of diagnosis using probes for D13S319/13q14, ATM/11q22, P53/17p13 and CEP12. The abnormalities and prognostic factors were analyzed. Overall survival of the patients was calculated.</p><p><b>RESULTS</b>The FISH assay has detected genomic abnormalities in 81 (77.1%) of the patients, among which D13S319/13q14 deletion was the most common (49/105, 46.67%). 24(22.86%) patients had trisomy 12, 21(20.00%) had ATM/11q deletion, and 12(11.43%) had P53/17p deletion. A significant correlation was found between Binet staging and the detected abnormalities (< 0.05). With a median follow-up time of 10 months, 11 patients (10.5%) had died. Compared with those with P53 deletion, patients with 13q deletion showed a better overall survival. However, the overall survival did not significantly differ between patients with various genomic abnormalities (> 0.05).</p><p><b>CONCLUSION</b>FISH is capable of detecting common genomic aberrations among patients with newly diagnosed CLL. Deletion of D13S319/13q14 is the most common aberration in such patients. Genomic aberrations are significantly correlated with Binet staging but not the overall survival of CLL patients.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Chromosome Aberrations , In Situ Hybridization, Fluorescence , Methods , Leukemia, Lymphocytic, Chronic, B-Cell , Diagnosis , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To explore the incidence of chromosome 1 abnormality in myelodysplastic syndrome（MDS）to couple its association with clinical presentation and prognosis.</p><p><b>METHODS</b>R- band karyotype analyses were performed in 672 cases of MDS between 2010 and 2013. Clinical data of those with abnormal chromosome l were collected and then analyzed factors affecting the prognosis.</p><p><b>RESULTS</b>Of 672 cases of patients with MDS, chromosome 1 aberration［der（1）, dup（1）, －1 were most frequent］ were found in 41（6.1%）cases. 1q trisomy was found in 18/41（43.9%）cases, and the most common patterns were duplication of the long arm as well as unbalanced translocation with other chromosomes. Of 41 patients with chromosomal 1 abnormality, 32 cases were accompanied with other chromosomal aberration, usually involving 3 or more abnormal chromosomal karyotypes, e.g., chromosome 8, 7 abnormalities. According to IPSS-R scoring system, 19 patients were diagnosed with very high risk, 10 patients high risk, 10 patients intermediate risk and 2 patients low risk MDS. 9 patients transformed into acute leukemia with median transforming time of 7.18（0.56-54.28）months. Median survival of 36 cases after 2010 was 17.48（95% CI 14.38-20.58）months. There were significant differences on median survival between RAEB and non-RAEB groups（χ²=10.398, P=0.001）, and between with more than 3 chromosome abnormalities and with less than 3 groups（χ²=3.939, P=0.047）. RAEB was identified as an independent risk factor for the prognosis of MDS with chromosome 1 abnormality.</p><p><b>CONCLUSION</b>Chromosome 1 aberration was not rare in MDS. 1q trisomy was the most common abnormal karyotype in China, which often accompanied with other chromosomal abnormalities. The prognosis of MDS patients with chromosome 1 abnormality was poor, especially worse in those diagnosed with RAEB-1, RAEB-2 and with more than 3 chromosome abnormality. For patients whose percentage of bone marrow blasts less than 5%, the prognosis of patients with 1q trisomy was better than those without 1q trisomy. RAEB was identified as an independent risk factor for the prognosis of MDS with chromosome 1 abnormality.</p>
Subject(s)
Humans , Abnormal Karyotype , Acute Disease , Anemia, Refractory, with Excess of Blasts , Bone Marrow , China , Chromosome Aberrations , Chromosome Banding , Chromosomes, Human, Pair 1 , Genetics , Karyotyping , Leukemia , Diagnosis , Genetics , Myelodysplastic Syndromes , Diagnosis , Genetics , Prognosis , Risk Factors , TrisomyABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression level of SET gene in patients with acute myeloid leukemia (AML) and evaluate its significance.</p><p><b>METHODS</b>The expression level of SET gene in 141 de novo AML patients was determined by real time quantitative PCR (RQ-PCR), and its relationship with the clinical features and outcomes of these patients were analyzed.</p><p><b>RESULTS</b>SET gene transcript level was detected in 141 AML patients with the median expression level of 0.86(range 0.02-15.69). AML patients with higher SET gene expression had a higher level of white blood cell (WBC ≥ 100 × 10⁹/L) count than of lower SET gene expression ones (31.0% vs 11.4%, P=0.005). In the 136 patients who received treatment after diagnosis, higher SET gene expression group had lower complete remission rate (50.0%) than of lower expression cohort (73.5%) after two cycles of chemotherapy (P=0.005). Survival analysis showed that patients with higher SET gene expression had significantly shorter overall survival(OS) (10 months vs 22 months, P=0.001) and event-free survival (EFS) (2 months vs 14 months, P=0.005) than of lower SET gene expression ones. Multivariate COX regression analysis showed SET overexpression was an independent prognostic factor for OS. In the patients with the normal karyotype, higher SET expression group also had significantly shorter OS (12 months vs 35 months, P=0.010) and EFS (4 months vs 14 months, P=0.026) than of lower SET expression ones.</p><p><b>CONCLUSION</b>High expression of SET gene was associated with poor prognosis and might be a prognostic molecular marker of AML.</p>
Subject(s)
Humans , Disease-Free Survival , Gene Expression Regulation, Neoplastic , Histone Chaperones , Genetics , Leukemia, Myeloid, Acute , Genetics , Prognosis , Remission Induction , Transcription Factors , GeneticsABSTRACT
OBJECTIVE@#To investigate the inhibitory effect of gonadotropin-releasing hormone II(GnRHII) and gonadotropin-releasing hormone I agonist (GnRH Ia) on the proliferation of endometrial stromal cells in vitro from endometriosis patients.@*METHODS@#Different concentrations of GnRHII or GnRH Ia were added into the cultured endometrial stromal cells in vitro to detect the cell proliferation inhibition by MTT test.@*RESULTS@#The inhibitory rate of GnRHII or GnRH Ia on eutopic and ectopic endometrial stromal cells in vitro was both dose- and time-dependent (P<0.05). Effect of GnRHII or GnRH Ia on the inhibitory rate of ectopic endometrial stromal cells was significantly higher than that of eutopic (P<0.05). GnRH II had a higher inhibitory rate on the endometrial stromal cells in vitro than did GnRH Ia (P<0.05).@*CONCLUSION@#GnRHII has more antiproliferative effect on endometrial stromal cells than GnRH Ia in vitro, especially on ectopic endometrial stromal cells, suggesting that GnRHII may be more effective than GnRH Ia on endometriosis.
Subject(s)
Adult , Female , Humans , Middle Aged , Young Adult , Cell Proliferation , Cells, Cultured , Endometriosis , Pathology , Endometrium , Metabolism , Pathology , Gonadotropin-Releasing Hormone , Pharmacology , Stromal Cells , PathologyABSTRACT
Objective To determine the effect of GnRH Ⅰ and GnRH Ⅱ on the secretion of VEGF by eutopic and ectopic endometrial stromal cells cultured in vitro, and to provide theoretical basis for exploring new treatments for endometriosis (EMs).Methods Eutopic and ectopic endometrium stromal cells cultured in vitro were treated with different concentrations of GnRH Ⅱ and a GnRH I(goserelin), and a control group was not treated by GnRH Ⅱ and GnRH Ⅰ. Enzyme linked immunosorbent assay (ELISA) was used to measure the content of vascular endothelial growth factor (VEGF) protein in the medium of the above 2 groups.Results (1)There was no difference in the VEGF protein secreted by eutopic and ectopic stromal cells in the medium after being cultured in vitro for 48 h (P＞0.05).(2)10-10, 10-8, and 10-6mol/L GnRH Ⅱ dose-dependently reduced VEGF protein secreted by endometrial stromal cells (P＜0.05),and the inhibition effect was stronger than that of GnRH Ⅰ (P＜0.05).(3)The inhibition effect of GnRH Ⅱ on VEGF in ectopic stromal cells was stronger than that of eutopic stromal cells (P＜0.05).Conclusion (1)Ectopic stromal cells cultured in vitro can secrete VEGF,which has no difference from the eutopic stromal cells, and which may play an important role in the formation and development of EMs.(2)GnRH Ⅱ can dose-dependently reduce VEGF protein secreted by ectopic and eutopic endometrial stromal cells cultured in vitro,and the inhibition effect is stronger than that of GnRH Ⅰ, providing theoretical basis for exploring new treatments for EMs.
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OBJECTIVE@#To inspect the effect of gonadotropin-releasing hormonel II (GnRH-II)on the secretion of VEGF by eutopic and ectopic endometrial stromal cells cultured in vitro.@*METHODS@#Eutopic and ectopic stromal cells cultured in vitro were treated with different concentrations (1x10(-10) - 1x10(-6) mol/L) of GnRH-II,and the control group was not treated by GnRH-II.Enzyme-linked immunosorbent assay (ELISA) was used to measure the VEGF protein in the medium of the above 2 groups.@*RESULTS@#There was no difference between the VEGF protein expressed by eutopic and ectopic stromal cells in the medium after culturing in vitro for 48 hours (P>0.05). The 1x10(-10) - 1x10(-6) mol/L GnRH-II could dose-dependently reduce VEGF protein secreted by endometrial stromal cells (P<0.01), and the inhibition to ectopic endometrial stromal cells was stronger than that to eutopic endometrial stromal cells (P<0.01).@*CONCLUSION@#Ectopic stromal cells cultured in vitro can secrete VEGF, and so can eutopic stromal cells. This may play an important role in the formation and development of endometriosis. GnRH-II can reduce VEGF protein secreted by ectopic endometrial stromal cells cultured in vitro, and its inhibition is stronger than that of eutopic endometrial stromal cells.
Subject(s)
Adult , Female , Humans , Middle Aged , Young Adult , Cells, Cultured , Endometriosis , Metabolism , Pathology , Endometrium , Metabolism , Pathology , Gonadotropin-Releasing Hormone , Pharmacology , Stromal Cells , Cell Biology , Metabolism , Vascular Endothelial Growth Factor A , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the association between trisomy 21 abnormalities and the clinical and cytogenetic features of hematologic malignancies.</p><p><b>METHODS</b>Chromosome preparations were made on bone marrow cells by using direct method and/or unstimulated short-term cultures. Karyotypes were analyzed by R-banding.</p><p><b>RESULTS</b>Thirteen patients (1.5%) with acute myeloid leukemia (AML) including 6 cases of M5b, 8 (2.2%) with acute lymphoblastic leukemia (ALL) and 4 cases with other hematologic malignancies had acquired trisomy 21, and in 13 patients it occurred as the sole cytogenetic abnormality. The remaining had combination with other abnormalities. The median survival for the 19 patients with trisomy 21 was 9 months.</p><p><b>CONCLUSION</b>M5b was the major type in AML with sole acquired trisomy 21.Trisomy 21 as the sole abnormality appeared to have a poor prognosis.</p>