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BACKGROUND: Vascular malformations (VMs) arise as a result of errors in the process of angiogenesis and are usually present at birth, but may not become apparent until after birth. However, giant VMs of the head and face are uncommon, with few reported cases, and the prognosis for their surgical intervention is unclear. CASE SUMMARY: A 12-year-old girl was admitted to the hospital with findings of an enlarged right temporal scalp. After admission, computed tomography (CT) angiography of cerebral ateries showed a right occlusal gap and a right temporal artery venous malformation. Furthermore, cerebral angiography showed a right temporal lobe VM with multiple vessels supplying blood. The patient underwent surgery to remove the malformed vessels and the eroded skull. Two hours after the surgery, the patient's right pupil was dilated, and an urgent CT scan of the skull showed a right subdural haematoma under the incision, which was urgently removed by a second operation. After surgery, we gave continuous antibiotic anti-infection treatment, and the patient recovered well and was discharged two weeks later. CONCLUSION: Surgical removal of giant haemangiomas is risky and adequate preoperative (including interventional embolisation) and intraoperative preparations should be made.
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HLA-C*03:651 differs from HLA-C*03:03:01:01 by one nucleotide in exon 4.
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Antígenos HLA-C , Nucleotídeos , Humanos , Antígenos HLA-C/genética , Alelos , Sequência de Bases , China , Análise de Sequência de DNARESUMO
OBJECTIVE: To analyze the survival, prognostic factors, and prevention of relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hematological malignancies, and explore the relationship between immune reconstruction, loss of human leukocyte antigen (HLA-loss) and relapse after transplantation. METHODS: From July 2012 to June 2020, 47 patients with hematological malignancies who relapsed after allo-HSCT were retrospectively analyzed, including 20 cases undergoing matched-sibling donor transplantation (MSD), 26 cases undergoing haploidentical transplantation (HID), and 1 case undergoing matched-unrelated donor transplantation (MUD). Multivariate analysis was used to analyze the risk factors related to post-relapse overall survival (PROS). RESULTS: All the 47 patients were implanted successfully. The cumulative incidence of grade â ¡-â £, â ¢/â £ acute graft-versus-host disease (aGVHD) and chronic GVHD (cGVHD) was 40.4%, 10.6%, and 31.9%, respectively. The incidence of grade â ¡-â £ and â ¢/â £ aGVHD in HID group was 42.3% and 11.5%, while in MD group was 38.1% and 9.5% (P=0.579, P=1.000), and the incidence of cGVHD in the two groups was 34.6% and 28.6% (P=0.659). The PROS of patients with NK cell absolute count > 190 cells/µl 30 days after transplantation was higher than that of patients with NK cell absolute count ≤190 cells/µl (P=0.021). The 1-year and 3-year PROS of all the patients was 68.1% and 28.4%, respectively, while in the HID group was 78.9% and 40.3%, in the MD group was 54.4% and 14% (P=0.048). Multivariate analysis showed that grade â ¡-â £ aGVHD and time of relapse < 3 months were independent risk factors of PROS (P<0.05). CONCLUSION: The therapeutic effect of haploidentical transplantation in patients with relapsed hematological malignancies after allo-HSCT is better than that of matched donor transplantation. The high absolute count of NK cells 30 days after transplantation can increase PROS. Grade â ¡-â £ aGVHD and time of relapse < 3 months have prognostic significance for long-term survival of patients with relapsed hematological malignancies after transplantation.
Assuntos
Doença Enxerto-Hospedeiro , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos , IrmãosRESUMO
BACKGROUND: Chimeric antigen receptor T cell (CART) therapy has benefited many refractory lymphoma patients, but some patients experience poor effects. Previous studies have shown that programmed cell death protein-1 (PD-1) inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment. CASE SUMMARY: A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema. A large mass was detected in the pelvis, and pathology indicated non-Hodgkin diffuse large B-cell lymphoma. After three cycles of the R-CHOP chemotherapeutic regimen, the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine. Pathological examination of the nodules indicated DLBCL again. The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma. We recommended CAR-T cell treatment. Before treatment, the patient's T cell function and expression of immune detection points were tested. Expression of PD-1 was obviously increased (52.7%) on cluster of differentiation (CD)3+ T cells. The PD-1 inhibitor (3 mg/kg) was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide. CAR-CD19 T cells of 3 × 106/kg and CAR-CD22 T cells 1 × 106/kg were infused, respectively. The therapeutic effect was significant, and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable. Presently, the patient has been disease-free for more than 12 mo. CONCLUSION: This case suggests that the combination of PD-1 inhibitors and CAR-T cells improved therapeutic efficacy in B-cell lymphoma.
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OBJECTIVE: To report the long-term survival of a patient with maternal plasmacytoid dendritic cell tumor (BPDCN) treated by allo-HSCT. METHODS: The patient was diagnosed by skin infiltration, bone marrow involvement, skin biopsy and bone marrow cytology. CD4, CD56, and CR123 were expressed in tumor cells. The first complete remission (CR1) was achieved by CHOP-E and MA regimens before transplantation. In March 2018, HLA 5/10 matched hematopoietic stem cell transplantations were performed in the paternal donors and fathers. The pretreatment regimen was FTBI (4 Gy × 2, total lung dose 6 Gy) + CY (cyclophosphamide 1.8 g/m2 × 2 d) + Flu (30 mg/m2 × 4 d) + ATG (10 mg/kg); CSA + MMF + MTX to prevent GVHD. MNC 6.45 × 108/kg and CD34 + cells 7.40 × 106/kg were transfused back. + Granulocyte and platelet were engrafted 12 days and 14 days respectively. The donor-recipient chimerism was monitored regularly, immunosuppressive agents were regulated, and minimal residual disease (MRD) was monitored by flow cytometry. No DLI. RESULTS: Complete donor implantation and continuous remission were achieved after transplantation. After transplantation, complications such as mucositis, viral infection, hypoproteinemia, and renal dysfunction occurred. At present, the disease-free survival is 10 months. CONCLUSION: BPDCN combined with TBI in the CR1 phase can effectively control the disease; HLA haploidentical hematopoietic stem cell transplantation is also an alternative treatment, and complications should be treated in a timely manner.
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OBJECTIVE: To analyses and summarize a case of multiple myeloma with disseminated infiltration in central nervous system. METHODS: The results of laboratorial examination and clinical data were analyzed and compared in the light of published literatures. RESULTS: The headache and diplopia were caused by infiltration of multiple myeloma cells to the central nervous system. Unlike those reported in the literatures, this case was a rare case of disseminated infiltration inside the brain, and plasma cells were CD56+, this patient has not yet accepted any multiple myeloma-associated treatment as like that reported in the literatures. And different from cases reported, this patient showed a good response to the intrathecal chemotherapy. CONCLUSION: Whether this good response is due to a heterogeneity of MM or effect of treatment-associated drug is still to be decided.
Assuntos
Mieloma Múltiplo , Plasmócitos , Sistema Nervoso Central , HumanosRESUMO
This study was purposed to evaluate whether the safe concentration of magnetic nanoparticles of Fe3O4(MNPs-Fe3O4) for monocytes could induce the SKM-1 cell apoptosis. The average size and Zeta potential of MNPs-Fe3O4were determined by transmission electron microscopy and the Malvern Zetasizer 3000 HS, respectively. The cell viability after being exposed to MNPs-Fe3O4for 12, 24, 48, and 72 hours was detected by using cell count Kit-8. The cell apoptosis was evaluated by flow cytometry with Annexin V/PI double staining and Wright-Giemsa staining. The cell cycle was measured by flow cytometry. The levels of active caspase-3, survivin and bcl-rambo in cells treated with MNPs-Fe3O4and/or trolox for 48 hours were detected with Western blot. The results showed that the cell viability decreased in SKM-1 cells after exposure to 50 µmol/L and 100 µmol/L MNPs-Fe3O4(P < 0.05), but did not in monocytes (P > 0.05), compared with that of each non-MNPs-Fe3O4-treated group. This exposure also induced the SKM-1 cells to be arrested in G0/G1. Annexin V/PI staining assay showed that cell apoptotic rate induced by 100 µmol/L MNPs-Fe3O4was significantly high in SKM-1 cells while not so high in monocytes, and the pretreatment with trolox could attenuate the apoptosis. Moreover, the active caspase-3 increased in SKM-1 cells after the exposure to MNPs-Fe3O4, while that was not in monocytes, and the increased expression of BCL-rambo and the decreased expression of survivin involved in the process were also observed. It is concluded that MNPs-Fe3O4can induce the caspase 3-dependent SKM-1 cell apoptosis by increasing the BCL-rambo expression and decreasing the survivin expression, but this cytotoxic effect can not be observed in monocyte's.
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Apoptose/efeitos dos fármacos , Compostos Férricos/farmacologia , Nanopartículas Metálicas/administração & dosagem , Caspase 3 , Ciclo Celular , Linhagem Celular Tumoral , Citometria de Fluxo , Humanos , MagnetismoRESUMO
The purpose of this study was to investigate the effect of bone marrow mesenchymal stem cells (BMMSC) from patients with chronic myeloid leukemia (CML) in blastic phase (Bp) on K562 cells and the primary CML-Bp cells, and to explore its potential mechanisms. K562 cells and primary CML-Bp cells were co-cultured with BMMSC of different groups; the cell proliferation was detected by MTT method, the cell apoptosis rate and mitochondrial membrane potential were measured by flow cytometry, the expression levels of Caspase-8, Caspase-9, and activated Caspase-3 in cells were measured by Western blot. The results showed that the CML-Bp BMMSC could enhance the survival rate of K562 cells treated with adviamycin (ADM) and display protective effect on K562 cells and primary CML-Bp mononuctear cells, inhibited ADM-induced leukimia cell apoptosis (P < 0.05); as compared with CML-chronic phase (CML-Cp) BMMSC and normal BMMSC, the CML-Bp BMMSC showed the highest protective effect on leukemic cells, the mitochondrial membrane potential of co-cultured cells slightly droped (P < 0.05). In the CML-Bp BMMSC cultured with K562 cells, the expression level of caspase-3 was more down-regulated than that in K562 alone plus ADM group, while the expression of caspase-9 significantly increased (P < 0.05). It is concluded that the CML-Bp BMMSC down-regulates ADM-induced leukemia cell appoptosis, its mechanism may relate with the inhibition of mitochondrial membrane potential drop, the stabilization of unactive expression of caspase-9 and down-regulation of caspase-3 expression.
Assuntos
Medula Óssea , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Células-Tronco Mesenquimais/citologia , Apoptose , Caspase 3 , Caspase 8 , Caspase 9 , Proliferação de Células , Células Cultivadas , Regulação para Baixo , Humanos , Células-Tronco Mesenquimais/metabolismoRESUMO
The present study was purposed to investigate the inhibition effect of tumor necrosis factor-related apoptosis inducing ligand (TRAIL) on growth of RPMI8226 cells and adhesion between RPMI8226 cells and bone marrow stroma cells (BMSC), and to explore its mechanism as well. The inhibition effects of TRAIL on cells growth and adhesion were assayed by MTT; cell apoptosis was detected by Annexin V and PI; expression of genes bax, bcl-2, mcl-1, CARP1, CARP2, XIAP and cFLIP were determined by semi-quantitative RT-PCR; apoptosis-related protein expression was detected by Western blot. The results showed that TRAIL inhibited the proliferation of RPMI8226 cells in dose- and time-dependent manners. TRAIL induced apoptosis in RPMI8226 cells, the expression level of genes bcl-2, mcl-1, CARP1, CARP2, XIAP and cFLIP decreased, while the expression level of Bax increased, but the expression level of caspase-3 and NF-kappaB P65(RelA) proteins decreased. Moreover, TRAIL up-regulated the expression level of adherent molecule CXCR4 in RPMI8226 cells significantly. It is concluded that TRAIL up-regulated the expression level of adherent molecule CXCR4 in RPMI8226 cells significantly, and induced the apoptosis of RPMI8226 cells. Growth inhibition effect of TRAIL on RPMI8226 cells is in dose- and time-dependent manners.
Assuntos
Apoptose/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Mieloma Múltiplo , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Ligante Indutor de Apoptose Relacionado a TNF/genéticaRESUMO
The idiotypic determinant of surface immunoglobulin of B-cell lymphoma, as a tumor-specific antigen, has proved to be able to induce immune responses. To analyze whether an idiotypic vaccine fused with cytokine can elicit more effectively protective antitumor immunity, an eukaryotic expression plasmid was constructed, which encoded the fusion gene of single-chain variable fragment as a tumor specific antigen against B-cell lymphoma with monocyte chemotactic protein-3 (MCP3) as immunogen to elicit T-cell-dependent protective antitumor immunity, and EGFP (Enhanced Green Fluorescent Protein) gene as a marker to trace the survival, growth, differentiation and expression of the former exogenetic genes. The cDNAs for immunoglobulin (Ig) VH and IgVL were amplified by RT-PCR and assembled into the single-chain variable fragment (scFv) connected with a (Gly(4)Ser)(3) linker by recombinant PCR method. Then, the fragments of scFv and MCP3 were ligated with a NDAQAPKS spacer by the same method. The results showed that the fusion genes of scFv and MCP3-scFv were inserted into an eukaryotic expression vector pTARGET, and EGFP was cloned into the downstream of scFv and MCP3-scFv respectively. Finally the constructed plasmids were confirmed by sequencing and restriction analysis. In conclusion, a tumor-derived idiotypic DNA vaccine, encoding the fusion gene of single-chain variable fragment and monocyte chemotactic protein-3 (MCP3) to elicit a T-cell dependent, antitumor immunity, and the EGFP gene was inserted correctly. The DNA vaccine could be used for further study of DNA vaccine against B cell lymphoma in vivo.
Assuntos
Vacinas Anticâncer/genética , Quimiocina CCL7/imunologia , Linfoma de Células B/imunologia , Plasmídeos , Vacinas de DNA/genética , Animais , Vacinas Anticâncer/imunologia , Linhagem Celular Tumoral , Vetores Genéticos , Região Variável de Imunoglobulina/imunologia , Linfoma de Células B/genética , Linfoma de Células B/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Anticorpos de Cadeia Única/imunologia , Vacinas de DNA/imunologiaRESUMO
The aim of this study was to investigate the regulation of 5-aza-CdR on transcription of SHP-1 gene and effects on the proliferation and apoptosis of K562 cells. Methylation-specific PCR (MSP) was used to detect CpG island methylation in SHP-1 promoter. MTT and flow cytometry were used to detect the growth and apoptosis of K562 cells after treatment with different concentration of 5-aza-CdR. The expressions of SHP-1 mRNA and protein were determined by FQ-PCR and Western blot. The expression of p-JAK2 was assayed by Western blot. The result showed that methylation of SHP-1 gene promoter was detected in K562 cells, and the SHP-1 mRNA and protein were expressed again in K562 cells after treatment with 5-aza-CdR, meanwhile the expression of phosphorylated P-JAK2 was down-regulated; 5-aza-CdR significantly inhibited the cell growth in dose and time dependent manners. AG490 inhibited the cell proliferation. 5-aza-CdR increased the apoptosis rate of K562 cells also in dose- and time-dependent manners. The apoptosis rates of K562 cells treated with 5-aza-CdR for 1, 3 and 5 days were 9.3%, 24.2% and 37.7% respectively. After treatment with 2 micromol/L 5-aza-CdR for 24 hours, cells in G(0)/G(1) phase increased gradually, cells in G(2)/M phase decreased gradually, cells were arrested in G(0)/G(1) phase. The cell ratios in G(2)/M phase at 1, 3 and 5 days after treatment with 5-aza-CdR were 30.7%, 23.45 and 19.3% respectively. It is concluded that the 5-aza-CdR, inhibitor of specific methylation transferase, can re-express the silent SHP-1 gene in K562 cells, inhibits the proliferation of leukemia cells and induces cell apoptosis by activating JAK/STAT pathway.
Assuntos
Apoptose/efeitos dos fármacos , Azacitidina/análogos & derivados , Proliferação de Células/efeitos dos fármacos , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Azacitidina/farmacologia , Metilação de DNA/efeitos dos fármacos , Decitabina , Humanos , Células K562 , Proteína Tirosina Fosfatase não Receptora Tipo 6/genéticaRESUMO
This study was aimed to investigate the effect of recombinant mutant human TNF-related apoptosis-inducing ligand (rmhTRAIL) combined with As(2)O(3) on inducing apoptosis of adriamycin-resistant leukemia cell line K562/A02 (mdr-1(+)). The morphologic changes of cells treated with rmhTRAIL were observed by inverted microscope, taking adriamycin-sensitive cell line K562 (mdr-1(-)) as control; the inhibitory rate of cell proliferation after being treated with rmhTRAIL, As(2)O(3) alone or combined was assayed by MTT method; the apoptosis peaks of K562/AO2 and K562 were quantitatively detected by flow cytometry with PI staining after being treated with rmhTRAIL, As(2)O(3) alone or in combination. The results indicated that the inhibition effect of rmhTRAIL and As(2)O(3) in combination on K562/AO2 and K562 cells was higher than that of riTRAIL and As(2)O(3) alone (p < 0.01), rmhTRAIL combined with As(2)O(3) had synergistic effect in killing K562/AO2 and K562 cells by king's formula. The apoptosis rates of K562/AO2 and K562 cells were 34.93 +/- 0.10% and 10.53 +/- 0.16% (p < 0.01), as well as 5.95 +/- 0.07%, and 3.50 +/- 0.01% (p < 0.05), 50.95 +/- 0.91% and 20.75 +/- 0.95% (p < 0.05) respectively when their cells were treated by rmhTRAIL and As(2)O(3) alone. The apoptosis rate in K562/AO2 group was higher than that in K562 group. It is concluded that rmhTRAIL can induce K562/A02 and K562 cell apoptosis; rmhTRAIL combined As(2)O(3) had synergistic effects; the efficacy of on rmhTRAIL or As(2)O(3) inducing K562/AO2 cell apoptosis is higher than that on their parental cell line K562.
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Apoptose/efeitos dos fármacos , Arsenicais/farmacologia , Óxidos/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Trióxido de Arsênio , Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Células K562 , Proteínas Recombinantes/farmacologiaRESUMO
Angioimmunoblastic T-cell lymphoma (AILT) is a peripheral T-cell lymphoma often complicated autoimmune phenomena such as autoimmune cytopenia, and is a truly rare type of NHL. In order to investigate the clinical features, pathological manifestation of this lymphoma, and to explore its therapy protocol, a 37-years old patient with AILT was investigated. The routine blood examination, bone marrow smear, lymphonodus biopsy, Coombs test, flow cytometry for bone marrow mononuclear cells, serological test, immunochemistry method etc were performed for this patient. The results showed that the systemic lymphadenectasis and hepatosplenomegaly were seen in patient, the cervical lymphonode biopsy revealed AITL. The hematoglobin level and number of reticulocytes were very low. Coombs test was positive. Simultaneously, the bone marrow aspirate revealed erythroid aplasia. The warm type autoimmune hemolytic anemia (AIHA) and pure red cell aplasia (PRCA) were co-existed. After one course of chemotherapy with CHOP-E, infiltration sign of AITL patient with AIHA and PRCA disappeared. In conclusion, the AITL patient complicated with AIHA and PRCA was successfully diagnosed, the lymphonode biopsy and bone marrow smear showed more significant, the chemotherapy protocol of CHOP-E can give some effect to cure such angioimmunoblastic T cell lymphoma.
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Anemia Hemolítica Autoimune/diagnóstico , Linfadenopatia Imunoblástica/diagnóstico , Linfoma de Células T/diagnóstico , Aplasia Pura de Série Vermelha/diagnóstico , Adulto , Anemia Hemolítica Autoimune/complicações , Humanos , Linfadenopatia Imunoblástica/complicações , Linfoma de Células T/complicações , Masculino , Aplasia Pura de Série Vermelha/complicaçõesRESUMO
To improve the recognition of immunoglobulin D multiple myeloma and explore its clinical feature and laboratory examination characteristics, so as to reduce the the missed diagnosis and misdiagnosis, a case of IgD multiple myeloma (MM) with myelofibrosis and bone marrow necrosis is reported. The clinical feature, treatment and prognosis of IgDlambda MM were discussed. Immunoglobulin D multiple myeloma is a rare disease and predominantly occurs in young male patients, which shows an aggressive clinical course with poor response to conventional treatment and unfavorable prognosis. Immunoglobulin D multiple myeloma was usually misdiagnosed as a light chain type multiple myeloma by using routine laboratory examination. Immunoglobulin D monoclonal protein is not easy to be detected owing to its low protein level, resulting in missed diagnosis. Immunofixation electrophoresis is highly sensitive and specific for diagnosis of IgD MM, can enhance accuracy of diagnosis for this rare disease.
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Imunoglobulina D/sangue , Cadeias lambda de Imunoglobulina/sangue , Mieloma Múltiplo/diagnóstico , Mielofibrose Primária/complicações , Adulto , Diagnóstico Diferencial , Humanos , Masculino , Mieloma Múltiplo/sangue , Mieloma Múltiplo/complicações , Mielofibrose Primária/sangue , Mielofibrose Primária/diagnósticoRESUMO
The aim of study is to investigate the expression of hematopoietic cell phosphatase (SHP-1) gene and c-kit pro-oncogene in acute leukemia (AL) and its impact on prognosis in AL. Semi-quantity reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of SHP-1 mRNA and c-kit mRNA in 60 AL patients and 33 normal controls (NC). The results showed that the positive rates of SHP-1 expression from high to low level were found orderly in complete remission group, newly diagnosed group and relapsed group, there was significance difference between each group and NC group (P < 0.05). The positive rates of c-kit expression were opposite order in each groups as compared with SHP-1. there was also significance difference between each group and NC group (P < 0.05). The positive rate of SHP-1 and c-kit expressions in AML was higher than that in ALL (P < 0.05), there was negative correlation between expressions of SHP-1 and c-kit (r = -0.502, P < 0.05); The difference between the complete remission rate in SHP-1 positive and in SHP-1 negative patients from 30 newly diagnosed AML patients was significant (P < 0.05), the same result was found between c-kit(+) complete remission and c-kit(-) complete remission. It is concluded that SHP-1 gene is a potentially anti-oncogene and inhibits the growing of tumor by negatively modulating c-kit gene. Simultaneous detection of SHP-1 and c-kit gene may act as a factor for predicting prognosis in AL.
Assuntos
Leucemia Mieloide Aguda/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 6/biossíntese , Proteínas Proto-Oncogênicas c-kit/biossíntese , Adolescente , Adulto , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Prognóstico , Proteína Tirosina Fosfatase não Receptora Tipo 6/genética , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Proteínas Proto-Oncogênicas c-kit/genéticaRESUMO
OBJECTIVE: To evaluate the relationship between the expression of hematopoietic cell phosphatase (SHP-1) gene or cysteinyl aspartate-specific proteinases (Caspase-1, 3) gene and the effect of chemotherapy in leukemia patients. METHODS: The expression of SHP-1 and Caspase-1, 3 gene was measured in leukemia patients with reverse transcriptase-polymerase chain reaction. RESULTS: The positive rate of SHP-1 and Caspase-1, 3 gene in acute leukemia was 33.3%, 80.0% and 100.0%. The positive rate of SHP-1 in chronic myeloid leukemia (CML)-blastic phase and CML-chronic phase was 0.0%, 37.5%. The first complete remission (CR) rate of SHP-1 and Caspase-1, 3 positive group was 85.0%, 64.3% and 55.8%, which were higher than that of SHP-1 and Caspase-1, 3 negative group (P < 0.05). There was a positive correlation between SHP-1 and Caspase-1, 3. CONCLUSIONS: SHP-1 gene is potentially an anti-oncogene and may play a role through activation of Caspase-1, 3 gene. The expression of SHP-1 and Caspase-1, 3 is associated with remission rate and it is shown that they participate in the prognosis of leukemia. They could be used as indices for evaluating therapeutic efficacy and judging prognosis in leukemia patients.
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Caspase 1/biossíntese , Caspase 3/biossíntese , Leucemia/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 6/biossíntese , Adolescente , Adulto , Idoso , Apoptose , Células da Medula Óssea/metabolismo , Caspase 1/genética , Caspase 3/genética , Feminino , Expressão Gênica , Humanos , Leucemia/patologia , Masculino , Pessoa de Meia-Idade , Proteína Tirosina Fosfatase não Receptora Tipo 6/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
The aim of study was to investigate the combined effect of recombinant mutant human TRAIL (rmhTRAIL) with daunorubicin (DNR) or alone on K562 and U937 leukemia cell lines and its mechanism. The fibroblasts (MRC-5) of normal-human embryonic lung were used as control cells. After being treated with rmhTRAIL and DNR or only with rmTRAIL, the cytotoxic effect and the apoptosis rate in K562, U937 cells were measured by MTT assay. The expression levels of TRAIL death receptor and TRAIL decoy receptor mRNA in these three cell lines were assayed by semiquantitive RT-PCR before and after treatment with DNR. The results indicated that K562 and U937 were sensitive to rmhTRIAL. DNR had synergistic inhibitory effect with rmhTRAIL on the growth of K562 and U937 cell lines (P < 0.05). The expression level of DR4 and DR5 mRNA was significantly higher in K562 and U937 with combined treatment of rmhTRAIL and DNR than that in those alone, while the expressions of DcR1 and DcR2 mRNA were not influenced. It is concluded that in vitro, rmhTRAIL alone or in combination with DNR can obviously inhibit the growth of leukemia cell lines and induce cell apoptosis, DNR and rmhTRAIL have a synergistic inhibitory effect on growth of K562 and U937. The mechanism may correlate with the up-regulation of DR4 and DR5 of K562 and U937.
Assuntos
Apoptose/efeitos dos fármacos , Daunorrubicina/farmacologia , Ligante Indutor de Apoptose Relacionado a TNF/farmacologia , Antibióticos Antineoplásicos/farmacologia , Sinergismo Farmacológico , Humanos , Células K562 , Mutação , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/biossíntese , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Proteínas Recombinantes/farmacologia , Células U937 , Regulação para CimaRESUMO
The aim was to construct a prokaryotic expression plasmid encoding the fusion gene of single-chain variable fragment and monocyte chemotactic protein-3 (MCP-3). The cDNAs of immunoglobulin (Ig) VH and Ig VL were amplified by RT-PCR and assembled into the single-chain variable fragment (scFv) by recombinant PCR method. The cDNAs of Ig VH and Ig VL were connected by a (Gly4Ser)3 linker. Then, the fragments of scFv and MCP-3 were connected with a NDAQAPKS spacer, using recombinant PCR method again. The results indicated that the fusion gene of scFv-MCP-3 were constructed correctly and cloned into the prokaryotic expression plasmid successfully identified by sequencing and restriction endonucleases examination. Finally, the fusion protein was expressed in E coli DH5alpha under induction by arabinose. And the fusion protein was 65 kD and account for 30% of the total protein of the bacteria. In conclusion, a prokaryotic plasmid, encoding the fusion gene of single-chain variable fragment with MCP-3 and expressing idiotype protein vaccination against B cell lymphoma, was constructed correctly.
Assuntos
Vacinas Anticâncer/biossíntese , Quimiocina CCL7/imunologia , Idiótipos de Imunoglobulinas/imunologia , Região Variável de Imunoglobulina/imunologia , Linfoma de Células B/imunologia , Sequência de Aminoácidos , Animais , Vacinas Anticâncer/genética , Vacinas Anticâncer/imunologia , Quimiocina CCL7/biossíntese , Quimiocina CCL7/genética , Vetores Genéticos , Humanos , Região Variável de Imunoglobulina/biossíntese , Região Variável de Imunoglobulina/genética , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Plasmídeos/genética , Células Procarióticas/metabolismo , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , Vacinas de DNA/biossíntese , Vacinas de DNA/genética , Vacinas de DNA/imunologiaRESUMO
Hepatosplenic gammadelta T cell lymphoma represents rare, often aggressive type of malignant peripheral T-cell lymphoma, which is characterized by expressing T-cell-associated markers CD2, CD3 and gammadelta T-cell receptor, and nonactivated cytotoxic cell phenotype (TIA-1+, granzyme B-). The pathological findings of a liver biopsy specimen revealed the diffuse infiltration of lymphocytes in the sinusoids and the aspiration biopsy from spleen revealed the diffuse infiltration of lymphocytes in the red pulp, not shaped to the nodes, often resulted in the misdiagnosis. Recently, by analyzing the immunophenotype and TCR rearrangement from liver, spleen and bone marrow, a case of adult hepatosplenic gammadelta T cell lymphoma was diagnosed. In combination with references, It is belived that immunophenotype and TCR rearrangement are necessary means to diagnosis hepatosplenic gammadelta T cell lymphoma.