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Chimeric antigen receptor T cell(CAR-T)therapy has produced remarkable results in the treatment of hematological tumors.The BCMA antigen is widely expressed on the surface of multiple myeloma cells and is a suitable,efficient target for CAR-T therapy.BCMA CAR-T cell therapy has a high response rate for relapsed or refractory patients in particular,and CAR-T cells are still detectable in most patients 1 year after infusion.However,drug resistance and disease recurrence remain key problems in clinical management.In this paper,we discuss the response factors and resistance induction mechanism of BCMA CAR-T cell therapy from several perspectives,such as the immune es-cape of multiple myeloma cells,CAR-T product factors,previous treatment regimens,and tumor immune microenvironment inhibition.We also propose possible optimization strategies in order to provide reference for future exploration.
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Exosome,being a kind of extracellular vesicles transporting the bioactive substances,is featured by the physiological function of anti-tumor immunity and promoting angiogenesis.Different types of cells can release different kinds of exosomes that can play a key role in the occurrence and development of a variety of diseases.In recent years,domestic and foreign research has showed that the amount and type of exosome are associated with the disease state and prognosis of multiple myeloma patients,which provides a new way for diagnosis,prognosis assessment and target therapy for multiple myeloma.This paper reviews the recent progress of exosomes in multiple myeloma.
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Objective To explore the influencing factors of therapeutic effect and prognosis in patients with angioimmunoblastic T cell lymphoma (AITL). Methods The clinical data of 48 patients with AITL were collected in order to evaluate its therapeutic effect and the influencing factors of prognosis. Results In the 48 patients with AITL, complete remission (CR) was in 15 cases, partial remission (PR) was in 16 cases, and the total effective rate was 64.58%(31/48). The recent total effective rate in patients of international prognostic index (IPI) score ≤2 scores was significantly higher than that in patients of IPI score >2 scores: 84.00% (21/25) vs. 43.48% (10/23), and there was statistical difference (P2 scores, Ki-67 ≥ 50% and using CHOP regimen: 8/13 vs. 25.71%(9/35), 52.00% (13/25) vs. 17.39% (4/23), 55.00% (11/20) vs. 21.43% (6/28) and 48.28% (14/29) vs. 3/19, and there were statistical differences (P<0.05). Conclusions AITL is a kind of disease with poor prognosis. IPI score is the important influencing factor of recent therapeutic effect. The Ann Arbor stage, IPI score, Ki-67 levels and using contained ASP chemotherapy are the important factors of prognosis in patients with AITL.
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<p><b>OBJECTIVE</b>To evaluate the effects of Embelin on HL-60 cells by the impact of oxidative stress on DNA double-strain breaks (DSBs).</p><p><b>METHODS</b>HL-60 cells were treated with Embelin in different concentration (3, 10, 30, 100, and 300 μg/ml) for 24 h, and inhibitory effects was examined by CCK-8 assay. Reactive oxygen species (ROS) levels were evaluated by flow cytometry using DCFH-DA. Comet assay was used to detect the extent of DSBs.</p><p><b>RESULTS</b>Embelin inhibited proliferation of HL-60 cells in a dose-dependent manner. At the concentration of 10, 30, 100, and 300 μg/ml, the inhibition rate was (12.74 ± 2.27)%, (23.49 ± 1.96)%, (30.30±1.89)%, and (57.55 ± 3.59)% (P<0.05). Embelin also lead to high level of intracellular ROS and deterioration of DNA damage (P<0.05). When HL-60 cells were pretreated with ROS scavenger N-acetyl-l-cysteine (NAC) for 2 h and then treated with 300 μg/ml Embelin for 24 h, the intracellular ROS level declined and DSBs relieved (P<0.05). Meanwhile, embelin-induced cell viability significantly declined to (32.75 ± 2.70)% (P<0.05).</p><p><b>CONCLUSION</b>Embelin induced the death of HL-60 cells by increasing the generation of intracellular oxidation and the oxidative stress, which drived the damage of DNA double-strand.</p>
Subject(s)
Humans , Acetylcysteine , Apoptosis , Benzoquinones , Cell Survival , Comet Assay , DNA Damage , Fluoresceins , HL-60 Cells , Oxidative Stress , Reactive Oxygen Species摘要
<p><b>INTRODUCTION</b>This study sought to investigate the immunophenotypic subtype profiles of 110 Chinese adult patients with acute lymphoblastic leukaemia (ALL) and its association to cytogenetics and the clinical features.</p><p><b>MATERIALS AND METHODS</b>A total of 110 adult patients with ALL were immunophenotyped by CD45/SSC double parameters and 4 colour flow cytometry. Seventy-three cases were also subjected to karyotype analysis by R-banding technology. The clinical and laboratory data of 110 ALL patients were retrospectively analysed.</p><p><b>RESULTS</b>Of all the patients, 21.8% were identified as T-ALL, 78.2% as B-ALL. Abnormal karyotypes were detected in 37 out of 73 (50.7%) cases and the most common cytogenetic abnormality was the Philadelphia (Ph) chromosome, which was found in 23.3% (17/73) of the cases. Myeloid antigen (MyAg) expression was documented in 47.3% of the 110 adult ALL cases analysed and CD13 was the most commonly expressed MyAg in ALL patients (32.1 %). No difference was observed in the expression of MyAg between the groups of patients with T-ALL (45.8%) and B-ALL (47.7%). Our data showed that older age, higher CD34 positivity and lower proportion of patients with splenomegaly were found to be correlated with MyAg+ ALL, and that patients with Ph+ B-ALL were older, presented with higher haemoglobin level and higher CD34 expression. No statistical difference was noted in complete remission (CR) rate, relapse rate, induction mortality or total death rate among My+ and My-, Ph+ and Ph-, or B-ALL and T-ALL patients.</p><p><b>CONCLUSION</b>Our results indicate that the distribution of ALL in Chinese adult patients was similar with the general distribution pattern in the other countries, and the expression of MyAg in patients with T-ALL and B-ALL was comparable. Both the expression of MyAg and the presence of Ph chromosome in adult ALL were significantly associated with median age and CD34 expression while not with the response to induction treatment.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Asian People , Cytogenetic Analysis , Immunophenotyping , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Diagnosis , Genetics , Allergy and Immunology , Retrospective Studies摘要
Objective To study the effects of bortezomib on the expression of NF-κB, IκB and P-gp of drug-resistant K562 cells induced by daunorubicin (K562/DNR), to explore the molecular mechanism of drug-resistant reverse. Methods The expression of NF-κB, IκB and P-gp in K562/DNR cells were detected when the cells had been treated with 100 μg/ml DNR only or together with 4 μg/L bortezomib for 12 h, 24 h and 36 h. The apoptosis rates were detected in each group respectively and the activity of NF-κB was detected by ELISA method. Results Compared with the control group, the expressions of NF-κB and P-gp in K562/DNR could be increased and IκB was decreased after being treated with DNR. When K562/DNR were cultured with bortezomib, the expressions of NF-κB and P-gp induced by DNR were significantly suppressed and IκB was increased. The activity of NF-κB were detected in different time points: (15.3±1.87) %[(23.8± 2.27) % in DNR group] at 12 h, (10.2±1.69) % [(25.4±1.98) % in DNR group] at 24 h, (6.08±2.53) % [(26.9±2.58) % in DNR group] at 36 h. There were a significant differences between DNR group and DNR+PS-341group. The apoptosis rates were increased in DNR+PS-341 group at different time points than those in DNRgroup, (35.23±5.15) % [(15.56±4.12) % in DNR group] at 12 h, (40.26±6.89) % [(17.25±2.89) % in DNR group] at 24 h, (43.58±7.69) % [(22.47±4.58) % in DNR group] at 36 h. The effccts showed the character of time-dependent pattern. Conclusion Bortezomib could downregulate the expressions of NF-κB and P-gp in K562/DNR, reverse the drug resistance and up-regulate the apoptotic rates in K562/DNR cells.
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Objective To investigate the clinic effect of hypocellular acute myelogenous leukemia (AML) patients with CAG regimen. Methods 29 cases with hypocellular AML were treated with CAG regimen. Results There were 14 cases achieved complete remission (CR), accounting for 48.3 %; 7 cases partial remission (PR), accounting for 24.1%. The total effective rate was 72.4 %, inducing 7 cases of NR, one case dead in early time. Conclusion CAG regimen has been proved to be effective in shortening the period of reduced peripheral blood granulocytes and decreasing the death rate related to chemotherapy, hence,a secure and effective therapy in treating hypocellular AML.
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<p><b>INTRODUCTION</b>The analysis of immunophenotype of the leukaemic cells has been of great importance for the diagnosis, classification and prognosis of acute lymphoblastic leukaemia (ALL).</p><p><b>MATERIALS AND METHODS</b>One hundred and thirteen Chinese patients with ALL were immunophenotyped by fl ow cytometry and 74 cases were also subjected to karyotype analysis by G-banding technology.</p><p><b>RESULTS</b>Of the 113 Chinese ALL patients, 14.2% were identified as T-ALL and 85.8% as B-ALL. Myeloid antigen (MyAg) expression was documented in 34.9% of the cases analysed and CD13 was most commonly expressed MyAg in ALL patients (23.6%). MyAg positivity was higher in adult with ALL (47.6%) than in children with ALL (26.6%). Abnormal karyotypes were detected in 39 out of 74 (52.7%) cases. The clinical and biological characteristics of ALL patients between MyAg+ and MyAg- groups showed that increased white blood count (WBC) (>50 x 109/L), higher CD34 positivity and higher percentage of adult patients were found to be correlated with MyAg+ ALL.</p><p><b>CONCLUSION</b>Our results indicate that the immunophenotype did have relevance to the abnormal cytogenetic changes and clinical features in ALL. Flow cytometry immunophenotype has become the most important method for diagnosis and typing of ALL.</p>
Subject(s)
Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Young Adult , China , Epidemiology , Cytogenetic Analysis , Diploidy , Immunophenotyping , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Classification , Diagnosis , Genetics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Classification , Diagnosis , Genetics , Translocation, Genetic摘要
Objective To investigate the clinical, pathological features of Casfleman's disease (CD)and evaluate the treatment and prognosis. Methods Twenty six cases of CD diagnosed by pathological examination from January 2003 to October 2008 were analyzed retrospectively. Results The ratio of male to (76.9 %) patients are local CD(LCD) and six (23.1%) are multicentric CD (MCD). Two of them show the inereaseot reactive plasma cells in bone marrow. One patient was complicated with autoimmunal disorder. One patient complicated diffused Interstitial lung change. According to the pathological classification, twenty four patients (92.3 %) are hyaline vascular type (HV), and two (7.7 %) are plasma cell type (PC). For treatment,ninety patients (73 %) that totally LCD type accepted completely resection, three patients (11.5 %) accepted uncompleted resection, four patients (15.4 %) accepted chemotherapy COP, CHOP, ECHOP. Follow-up toOctober 2008, all the patients are alive and average survival time is 5 years. Conclusion CD is a rare lymphoproliferative disorder, there are slightly more female patients than male in morbility, no age difference is found in CD. Lymphomegaly and no pain is the common symptoms. Single lymphomegaly is more often,system symptoms are commonly occurred in MCD. Pathological examination is the golden standard in diagnosis. HV type is more than PC. PC type can complicated reactive plasma cells and increase autoimmunal disorder. The patients of LCD would be cured with completely excision, and chemotherapy such as COP will significantly reduced the lymphomegaly but lightly to the systematical symptoms for MCD type.
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objective To investigate the immunophenotype of Chinese patients with acute lymphoblastic leukemia(ALL)and its association to cytogenetics and clinical features.Methods In this study.a total of 113 Chinese patients with ALL were immunophenotyped by flow cytometry using a panel of monoclonal antibodies.50 000 cells were acquired and analyzed with Cell Quest and abnormal populations were recognized by CD_(45)/SSC gating.Among the 113 patients enrolled in this study,bone marrow cells of 74 patients were cultured for 72 hours to prepare for conventional chromosome detection.and karyotype was analyzed with R-banding technique.Results Of 113 ALL patients,14.2%(16/113)were identified as TALL,85.8%(97/113)as B-ALL Among the 106 out of 113 ALL cases,myeloid antigen(MyAg)expression was documented in 34.9%(37/106)and CD_(13) was the most commonly expressed MyAg in ALL patients(23.6%,25/106).MyAgs were more frequently associated with T-ALL(46.2%,6/13)than with B-ALL(33.3%,31/93)but there was no significant difieFence(X~2=0.825,P>0.05)between the two groups.MyAg positivity in adult ALL patients(47.6%,20/42)was higher than that in children(26.6%,17/64).There was a significant difference between the two groups(X~2=4.948,P<0.05).Abnormal karyotypes were detected in 39 out of 74(52.7%)patients.It showed that percentage of patients with high WBC count(>50×10~9/L)in MyAg~+(48.6%,18/37)was higher than that in MyAg~-ALL types (20.3%,14/69).There was a significant difference between the two groups(X~2=9.191,P<0.01).CD34 expression was found in 83.8%(31/37)of MyAg~+ and 53.6%(37/69)of MyAg~-cages.There was a significant difference between the two groups(X~2=9.527,P<0.05).In addition,the percentage of adult ALL patients in MyAg~+ group(54.1%,20/37)was higher than that in MyAg~-group(31.9%,22/69).There was a significant difference between the two groups(X~2=4.948,P<0.05).Conclusion lmmunophenotype analysis is useful for ALL diagnosis and classification and the immunophenotype has relevance to the abnormal cytogenetic changes and clinical features in ALL patients.
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Objective To study the changes of the cellular composition in peripheral blood stem cell transplantation(PBSCT) donor with granulocyte colony stimulating factor(G-CSF)and the short-term influence of G-CSF on the donors.Methods Eighteen donors of PBSCT were administrated with G-CSF,5-10?g/(kg?d),for 4-5d.Peripheral blood mononuclear cells (MNC) were collected after the administration of the G-CSF and analyzed by flow cytometry.The side effects of G-CSF on donors were also studied.Results The peripheral white blood cell (PWBC) counts peaked on day 4 or 5 after mobilization.Compared with the number of WBC before mobilization,it increased 7 to 14 times after mobilization (P