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1.
Heliyon ; 10(11): e31487, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38828323

RESUMO

Background: Cervical cancer is one of the most common malignancies in women worldwide. As a RING type ubiquitin ligase, SIAH2 has been reported to promote the progression of a variety of tumors by interacting with and targeting multiple chaperones and substrates. The aim of this study was to further identify the role and the related molecular mechanisms involved of SIAH2 in cervical carcinogenesis. Methods and results: Cellular assays in vitro showed that knockdown of SIAH2 inhibited the proliferation, migration and invasion of human cervical cancer cells C33A and SiHa, induced apoptosis, and increased the sensitivity to cisplatin treatment. Knockdown of SIAH2 also inhibited the epithelial-mesenchymal transition and activation of the Akt/mTOR signaling pathway in cervical cancer cells, which were detected by Western blot. Mechanistically, SIAH2, as a ubiquitin ligase, induced the ubiquitination degradation of GSK3ß degradation by using coIP. The results of complementation experiments further demonstrated that GSK3ß overexpression rescued the increase of cell proliferation and invasion caused by SIAH2 overexpression. Specific expression of SIAH2 appeared in precancerous and cervical cancer tissues compared to inflammatory cervical lesions tissues using immunohistochemical staining. The more SIAH2 was expressed as the degree of cancer progressed. SIAH2 was significantly highly expressed in cervical cancer tissues (44/55, 80 %) compared with precancerous tissues (18/69, 26.1 %). Moreover, the expression level of SIAH2 in cervical cancer tissues was significantly correlated with the degree of cancer differentiation, and cervical cancer tissues with higher SIAH2 expression levels were less differentiated. Conclusion: Targeting SIAH2 may be beneficial to the treatment of cervical cancer.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 207-212, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554821

RESUMO

OBJECTIVE: To explore the relationship between the change of lymphocyte subsets before and after immunosuppressive therapy (IST) with disease severity of severe aplastic anemia (SAA) and hematologic response to IST. METHODS: The clinical data of 94 patients with SAA/VSAA treated by r-ATG and CsA in our hospital from December 2009 to October 2011 was analyzed retrospectively. Among them, 26 patients who had sequential data of lymphocyte subsets and cytokines before and after treatment were enrolled. The relationship between lymphocyte subsets, cytokine level before IST and disease severity, as well as the relationship between changes if lymphocyte subsets, changes of cytokine and the HR after IST for 6 months was analyzed. RESULTS: There were no statistical differences in the ratio and absolute count of lymphocyte, the ratio and absolute count of each lymphocyte subsets, including CD3+T cells, CD3+CD4+T cells, CD3+CD8+T cells, CD3-CD16+1CD56+NK cells, and CD19+B cells, and the level of cytokines, such as IL-1, IL-2, IL-4, IL-6 and TNF-α before IST between SAA and VSAA groups. Also, there were no statistical difference in the levels of above-motional parameter at 3 and 6 months after IST. The ratio and absolute count of Lym, absolute count of CD3+T cells, absolute count of B cells and IL-2 level in response group after IST for 3 and 6 months was significant lower than those before IST. However, only ratio of Lym showed significant decrease after IST for 3 and 6 months in non-response group. After IST for 3 months, the absolute count of CD3+T and CD4+T cells in response group was significant higher than those in non-response group. CONCLUSION: The hematopoietic recovery and early hematologic remission may be affected by the intensity of immune suppression reflected from the changes of lymphocyte subsets and the immune reconstruction reflected from the recovery of lymphocyte subsets. The immune reconstruction is most significant within 3 months after IST.


Assuntos
Anemia Aplástica , Humanos , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Subpopulações de Linfócitos , Estudos Retrospectivos
3.
World J Clin Cases ; 7(20): 3303-3309, 2019 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-31667183

RESUMO

BACKGROUND: Hereditary spherocytosis (HS) is a hereditary disease of hemolytic anemia that occurs due to the erythrocyte membrane defects. Dubin-Johnson syndrome (DJS), which commonly results in jaundice, is a benign hereditary disorder of bilirubin clearance that occurs only rarely. The co-occurrence of HS and DJS is extremely rare. We recently diagnosed and treated a case of co-occurring HS and DJS. CASE SUMMARY: A 21-year-old female patient presented to our department because of severe jaundice, severe splenomegaly, and mild anemia since birth. We eventually confirmed the diagnosis of co-occurring DJS and HS by next generation sequencing (NGS). The treatment of ursodeoxycholic acid in combination with phenobarbital successfully increased hemoglobin and reduced total bilirubin and direct bilirubin. CONCLUSION: The routine application of NGS can efficiently render a definite diagnosis when inherited disorders are suspected.

4.
Chem Sci ; 9(14): 3523-3530, 2018 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-29780483

RESUMO

A strategy using a mesoporous amine-tagged porous aromatic framework (PAF70-NH2 ) to immobilize a palladium (Pd)-based molecular catalyst has been developed. The resulting immobilized catalyst PAF70-Pd, in which the framework is entirely constructed by phenyl rings linked with stable carbon-carbon bonds, has high structural rigidity and stability. Compared with the known porous organic material immobilized Pd-based catalysts, PAF70-Pd has the highest Pd content so far. Moreover, PAF70-Pd has extremely high catalytic activity with good size selectivity and very easy recyclability in catalyzing the Suzuki-Miyaura coupling reaction. In the current system, the catalyst loading could be as low as 0.001 mol% and the TOF value could go up to 28 800 h-1 which is far higher than those of the known porous organic material immobilized Pd-based catalysts. In order to elucidate the particularly high catalytic efficiency of PAF70-Pd, we prepared PAF1-Pd from PAF1-NH2 for comparison. PAF1-Pd has a higher Pd content than PAF70-Pd. However, due to the absence of large enough mesopores in PAF1-NH2 , PAF1-Pd has almost no catalytic activity under the same conditions, which definitely demonstrated that the intrinsic mesoporosity of PAF70-NH2 plays a crucial role in the superb catalytic efficiency of PAF70-Pd. This strategy to immobilize Pd-based molecular catalysts has very good expansibility to be applied in the immobilization of different organometallic catalysts into the pores of PAFs, which also has very high potential in the chemical and pharmaceutical industry.

5.
Chem Commun (Camb) ; 54(13): 1603-1606, 2018 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-29368767

RESUMO

An amine-tagged hierarchical porous aromatic framework PAF70-NH2 with ultra-stability and narrowly distributed mesopores was synthesized. PAF70-NH2 has high potential for covalently immobilizing a relatively large-sized catalyst inside its pores. This work gave a perfect example of using PAF70-NH2 as a platform for completely recyclable heterogeneous organocatalysis.

6.
Zhonghua Xue Ye Xue Za Zhi ; 34(8): 709-13, 2013 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-23978026

RESUMO

OBJECTIVE: To evaluate the value of serum soluble transferrin receptor (sTfR) concentration in predicting early response to immunosuppressive therapy (IST) in severe aplastic anemia (SAA). METHODS: Clinical data and hematologic responses of 140 SAA patients treated with rabbit antithymocyte globulin (rATG) combination with cyclosporine in our hospital were retrospectively analyzed. Correlation of pre-IST baseline of sTfR and IST responses was statistically analyzed and receiver operating characteristic (ROC) curve was used to estimate the sensitivity and specificity of sTfR in prediction of early responses. RESULTS: Serum concentration of sTfR in very SAA (VSAA) patients were significantly lower than SAA and transfusion dependent non-SAA cases (P=0.001). The responders, especially at 3 months, had significantly higher pre- IST baseline of sTfR [median, 0.89 (range, 0.21-2.42) mg/L] than that [median, 0.58 (range, 0.13-1.88) mg/L] of non-responders (P=0.005). The cutoff level of 0.91 mg/L and 0.88 mg/L for predicting responses at 3 and 6 months were established based on the ROC curve, with the degree of accuracy of 65.0% and 60.7% respectively. Multivariate analysis showed that pre-IST baseline of sTfR was the independent factor of predicting response at 3 months (P=0.007) and at 6 months (P=0.021). CONCLUSION: As a indicator of bone marrow failure severity, sTfR could predict early response to IST therapy in aplastic anemia.


Assuntos
Anemia Aplástica/terapia , Terapia de Imunossupressão , Receptores da Transferrina/uso terapêutico , Adolescente , Adulto , Idoso , Soro Antilinfocitário/uso terapêutico , Criança , Pré-Escolar , Ciclosporina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores da Transferrina/imunologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto Jovem
7.
Zhonghua Xue Ye Xue Za Zhi ; 34(6): 532-5, 2013 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-23827114

RESUMO

OBJECTIVE: To investigate the clinical features and therapeutic method for severe aplastic anemia (SAA) associated with ß-thalassemia, and to improve the recognition of the disease. METHODS: One patient hospitalized for pancytopenia was reported and the related literatures were reviewed. RESULTS: A 14-years old girl who presented with anemia from her childhood was hospitalized for acute onset of pancytopenia. Routine blood test showed that WBC count was 1.28×109/L, hemoglobin 65 g/L, platelet count 18×109/L, reticulocyte count 2×109/L, neutrophil count 0.03×109/L and mean corpuscular volume 59.6 fl, respectively. Both bone marrow aspiration and biopsy showed hypoplasia. Her red blood cells presented as microcytic hypochromic and target erythrocytes were common on peripheral blood smear. DNA analysis of the patient and her mother showed exon 17 heterozygous ß-thalassemia (c.52 A>T). A diagnosis of SAA associated with ß-thalassemia was clarified and high-dose cyclophosphamide (HD-CTX, 1.2 g/d×4 d) plus cyclosporine were offeved, which eventually led to a complete hematologic remission 12 months later. CONCLUSION: This was the first report of SAA associated with ß-thalassemia, and the regimen of HD-CTX led to a complete hematologic remission.


Assuntos
Anemia Aplástica/tratamento farmacológico , Ciclofosfamida/administração & dosagem , Imunossupressores/administração & dosagem , Talassemia beta/tratamento farmacológico , Adolescente , Anemia Aplástica/complicações , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Talassemia beta/complicações
8.
Zhonghua Xue Ye Xue Za Zhi ; 34(6): 536-9, 2013 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-23827115

RESUMO

OBJECTIVE: To investigate the clinical and laboratory features of 2 cases of pure red cell aplasia (PRCA) with thymoma/T-cell large granular lymphocyte leukemia (T-LGLL), and to improve the recognition of the disease and the role of lymphocyte in its mechanism. METHODS: Two cases of PRCA with thymoma/T-LGLL were reported and the related literatures were reviewed. RESULTS: Case 1 was a 63-years old male with hemoglobin level of 54 g/L at admission. Case 2 was a 52-years old female with hemoglobin level of 79 g/L at admission. They were both diagnosed as PRCA with thymoma before admission to our hospital and had no benefit from their thymectomy. Further examinations in our hospital showed that CD3⁺CD4⁻CD8⁺CD57⁺ large granular lymphocytes amplified with clonal TCR rearrangement in their peripheral blood. The diagnosis of PRCA with thymoma/T-LGLL was clarified. Case 1 did not respond to any of the frontline therapies while case 2 responded completely to cyclosporine. CONCLUSION: Both thymoma and T-LGLL could be the cause of secondary PRCA, lymphocyte proliferation may play critical role in the pathogenesis.


Assuntos
Leucemia Linfocítica Granular Grande/complicações , Aplasia Pura de Série Vermelha/complicações , Timoma/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Zhonghua Xue Ye Xue Za Zhi ; 33(4): 270-3, 2012 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-22781715

RESUMO

OBJECTIVE: To investigate the clinical and laboratory features of congenital dyserythropoietic anemia type II (CDA-II) in order to improve the recognition of the disease. METHODS: A case of CDA-II was reported and the related literatures were reviewed. RESULTS: The 32-years old female presented with moderate anemia, jaundice and hepatosplenomegaly from her childhood and was misdiagnosed as hereditary spherocytosis for a long time. There were no increased reticulocytes in the peripheral blood and her bone marrow showed erythroid hyperplasia with 43% of binucleated erythroblasts. Electron microscopy examination revealed stretches of double membrane lining the inner surface of the erythroblast cell membrane. CONCLUSIONS: CDA-II is a rare congenital anemia characterized by ineffective erythropoiesis with unique laboratory features, and is relatively easy to be misdiagnosed. It is necessary to improve the awareness of CDA-II, and to set-up its responsible gene analysis, i.e., CDAN2 gene and SEC23B gene detection.


Assuntos
Anemia Diseritropoética Congênita/diagnóstico , Anemia Diseritropoética Congênita/genética , Adulto , Feminino , Humanos , Proteínas de Transporte Vesicular/genética
11.
Zhonghua Xue Ye Xue Za Zhi ; 32(1): 38-42, 2011 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-21429400

RESUMO

OBJECTIVE: To analyze the efficacy and side-effects of combination of rabbit antithymocyte globulin (ATG) and cyclosporine A (CsA) as the first-line immunosuppressive therapy (IST) for adult severe aplastic anemia (SAA) patients. METHODS: Adult SAA or very severe aplastic anemia (VSAA) patients treated with rabbit ATG + CsA as first line therapy in our hospital from 2003 to 2008 were retrospectively analysed and the therapeutic response relevant factors were analysed. RESULTS: Seventy-nine patients were enrolled. Of all these patients, 6 died within 3 months after IST. The overall response rate was 82.2% and the median time to transfusion independent was 60 days. The therapeutic response rate in 32 SAA patients (100%) was significantly higher than that in 41 VSAA cases (68.3%) (P = 0.001). Patients with neutrophil response to G-CSF treatment had a higher IST response rate than those without response to G-CSF (100% vs 67.5%, P = 0.001). Sixty-one patients (77.2%) occurred serum sickness reaction. Three patients relapsed and two developed clonal hematological abnormalities after IST. The 3-year overall survival for all the patients was 88.9%. CONCLUSIONS: Rabbit ATG in combination with CsA as first-line IST for adult SAA can lead to excellent treatment outcomes with minor adverse effects.


Assuntos
Anemia Aplástica/tratamento farmacológico , Soro Antilinfocitário/uso terapêutico , Ciclosporina/uso terapêutico , Imunossupressores/uso terapêutico , Adolescente , Adulto , Animais , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Coelhos , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
12.
Zhonghua Xue Ye Xue Za Zhi ; 32(11): 766-71, 2011 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-22339914

RESUMO

OBJECTIVE: To evaluate the effects of cyclosporine A (CsA) whole-blood concentration on the early response to immunosuppressive therapy (IST) in severe and very severe aplastic anemia (SAA/VSAA). METHODS: Ninety SAA/VSAA patients treated with rabbit antithymocyte globulin (ATG) plus CsA as first line therapy in our hospital were retrospectively analysed. CsA levels between the response group and non-response group, and response rates of patients with variant CsA levels were compared respectively. RESULTS: (1) There was no significant difference in the beginning unmodified CsA blood concentration between IST responded and non-responded SAA/VSAA patients. The beginning unmodified C(0) 133.91 ug/L in IST 2-month responders was higher than that of 49.9 ug/L in non-responded SAA patients (P = 0.009); (2) The mean CsA C(0) and C(2) levels during the third month following IST were significantly different in responders and non-responders(197.52 µg/L vs 161.49 µg/L, P = 0.024, and 738.76 µg/L vs 615.46 µg/L, P = 0.009), and no significant difference in other periods of IST (P > 0.05); (3) The response rate (87.5%) was significantly higher in patients with CsA C(0) ≥ 200µg/L the third month following IST than those of 55.6% in patients with CsA C(0) 150 - 200 µg/L (P = 0.023) and 59.3% in patients with CsA C(0) < 150 µg/L (P = 0.046), respectively. The response rate was significantly higher of C(2) ≥ 700 µg/L group than that of C(2) < 700 µg/L group (80.5%vs 55.3%, P = 0.012). CONCLUSIONS: The CsA concentration related to the early IST response. The third month CsA concentrations was the most important for the response and maintaining CsA levels with C(0) ≥ 200 µg/L and C(2) ≥ 700 µg/L may improve the response to IST in SAA/VSAA.


Assuntos
Anemia Aplástica/sangue , Anemia Aplástica/terapia , Ciclosporina/sangue , Imunossupressores/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
13.
Zhonghua Xue Ye Xue Za Zhi ; 30(6): 377-80, 2009 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-19951529

RESUMO

OBJECTIVE: To analyze the clinical and laboratory features of patients with congenital dyserythropoietic anemia type I (CDA-I), and improve the clinical diagnostic accuracy. METHODS: The clinical and hematological features of 5 patients diagnosed as CDA-I in our hospital between July 2002 and July 2007 were analyzed retrospectively, and the related literatures was reviewed. RESULTS: Five CDA-I patients, 1 male and 4 females, all had a long history of varied degree of chronic anemia. One patient had congenital malformations, 3 jaundice and 4 hepatosplenomegaly. Bone marrow specimens invariably showed hypercellularity due to erythroid hyperplasia with megaloblastic changes, irregularly shaped nuclear, and chromatin bridges in 0.2% to 0.6% of all erythroblasts. All the 5 patients' bone marrow erythroblasts showed spongy heterochromatin appearances (swiss-cheese) with electron microscopy examination. There was no morphologic abnormality in the granulocytes and megakaryocytes. Serum ferritin levels were increased in 3/4 patients. One patient had been misdiagnosed as hereditary spherocytosis and performed splenectomy in the local hospital with no improvement in Hb level. CONCLUSIONS: CDA-I is a rare congenital anemia characterized by ineffective erythropoiesis, jaundice, hepatosplenomegaly and iron overload, and may be misdiagnosed. Keeping these manifestations in mind should avoid misdiagnosis.


Assuntos
Anemia Diseritropoética Congênita/diagnóstico , Adolescente , Adulto , Anemia Diseritropoética Congênita/sangue , Feminino , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
14.
Zhonghua Xue Ye Xue Za Zhi ; 30(3): 179-82, 2009 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-19642367

RESUMO

OBJECTIVE: To analyze the characteristics of T-cell large granular lymphocyte leukemia (T-LGLL). METHODS: Retrospectively analyze the clinical and laboratory data of 27 patients with T-LGLL diagnosed between 1999 and 2007 in our hospital. RESULTS: The median age at diagnosis was 48 years. All patients were symptomatic, mainly complaining of fatigue. Of the 27 patients, 14 (51.9%) had splenomegaly, and 4(14.8%) hepatomegaly. Rheumatoid arthritis was not present in any patients. The most frequent hematological abnormality was anemia (24 patients, 88.9%) with a median Hb level of 57.5 g/L. Pure red cell aplasia was found in 18 patients (66.67%). The median WBC count was 4.24 x 10(9)/L and 19 cases were neutropenia (ANC < 1.5 x 10(9)/L). The median LGL count in peripheral blood was 1.45 x 10(9)/L and most of them (77.8%) were less than 2.0 x 10(9)/L. Twenty-two patients (81.5%) showed the CD3+ CD8+ CD57+ CD56(-) LGL phenotype. With immunosuppressive therapy, 91.3% of patients responded and complete hematological remission rate was 65.2%. CONCLUSION: T-LGLL mainly presented with anemia and complete hematological remission rate was 65.2%. Pure red cell aplasia was commonly associated with the disease. The patients had a good response to immunosuppressive therapy.


Assuntos
Leucemia Linfocítica Granular Grande/diagnóstico , Leucemia Linfocítica Granular Grande/imunologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Imunofenotipagem , Terapia de Imunossupressão , Leucemia Linfocítica Granular Grande/complicações , Masculino , Pessoa de Meia-Idade , Aplasia Pura de Série Vermelha/etiologia , Estudos Retrospectivos , Adulto Jovem
15.
Zhonghua Xue Ye Xue Za Zhi ; 30(11): 749-53, 2009 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-20137310

RESUMO

OBJECTIVE: To analyse the efficacy and side-effects of rabbit antithymocyte globulin (ATG) and cyclosporin A (CsA) as the first-line therapy for childhood severe aplastic anemia (SAA). METHODS: Seventy-one childhood SAA patients treated with rabbit ATG + CsA as first line therapy were retrospectively analysed. RESULTS: Seventy-one SAA patients, including 38 SAA and 33 very severe aplastic anemia (VSAA), were enrolled. The median age was 12 years. Of these patients, 3 died within 3 months after the immunosuppressive therapy (IST). The overall response rate was 67.6% (46/68) and the median time to transfusion independent was 53 days. Thirty-three patients (48.5%) obtained remission in 3 months after the IST and 45 (67.2%) in 6 months. The response rates were 57.7% (15/26), 56.5% (13/23) and 94.7% (18/19) for patients less than 10 years old, 10 - 15 year-old and 15 - 18 year-old, respectively. Sixty patients suffered from serum sickness on the IST. Three patients relapsed and another 3 unrespond patients received retreatment of IST, and one patient progressed to myelodysplastic syndromes (MDS). CONCLUSION: Rabbit ATG in combination with CsA as first line therapy for childhood SAA/VSAA can lead to overall response rate of 67.6% with minor adverse effects.


Assuntos
Soro Antilinfocitário , Ciclosporina , Anemia Aplástica/terapia , Animais , Ciclosporina/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Coelhos , Resultado do Tratamento
16.
Zhonghua Xue Ye Xue Za Zhi ; 29(5): 312-5, 2008 May.
Artigo em Chinês | MEDLINE | ID: mdl-18844068

RESUMO

OBJECTIVE: To analyze the characteristics of acquired pure red cell aplasia (PRCA) secondary to T cell large granular lymphocyte leukemia (T-LGLL). METHODS: Fourteen patients with T-LGLL associated with PRCA between 2000 and 2006 in our hospital were retrospectively analyzed. RESULTS: The median age at diagnosis was 61 years with equal gender distribution. The PRCA had indolent process, mainly presenting with anemia. Of the 14 patients, 9 had mild to moderate splenomegaly, one hepatomegaly and one lymphadenopathy. The median Hb level was 61.5 g/L and the median WBC count 4.3 x 10(9)/L. The median percentage and count of LGL in peripheral blood were 0.36 and 1.9 x 10(9)/L respectively. The median percentage of LGL in BM was 0.165 (0.085 - 0.410). Some patients had serologic abnormalities. All the 12 cases with available bone marrow cell cytogenetics showed normal karyotypes. With cyclosporine A or glucocorticoid immunosuppressive therapy, the overall response was 91%. CONCLUSION: T-LGLL was one of the major causes of acquired PRCA. This type of PRCA has the similar clinical and laboratory feature to that of other type of PRCA and has a good response to immunosuppressive therapy.


Assuntos
Leucemia Linfocítica Granular Grande/complicações , Aplasia Pura de Série Vermelha/complicações , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
17.
Zhonghua Nei Ke Za Zhi ; 44(5): 366-9, 2005 May.
Artigo em Chinês | MEDLINE | ID: mdl-16009009

RESUMO

OBJECTIVE: To investigate retinoic acid-resistant acute promyelocytic leukemia (APL) cell differentiation induced by tanshinone IIA (Tan IIA) and its molecular mechanism. METHODS: NB4 cells treated with 0.5 mg/L Tan IIA was regarded as positive control. After in vitro incubation of MR-2 cells with Tan IIA at the concentration of 1.0 mg/L for 4 days, the cell differentiation was observed by growth status, cytomorphology, and nitroblue tetrazolium test. Cell cycle, membrane cluster differentiation (CD) antigens (CD(33), CD(11b)) and expression of some oncogene (c-myc, c-fos, p53 and bcl-2) were analysed by flow cytometry. RESULTS: The growth of MR-2 and NB4 cells was inhibited after Tan IIA treatment, the inhibition rate were 73.5% and 67.7% respectively (P < 0.01, P < 0.01) without significant difference. After Tan IIA treatment, MR-2 and NB4 cells were induced to undergo morphological differentiation, which exhibited small cell bulk decreased nucleus/cytoplasm proportion, rough chromatin, disappearance of nucleolus and formation of azurophil granules and anomalous nucleus. MR-2 cells could be induced to metamyelocyte while NB4 could be induced to band form. NBT reduction of MR-2 and NB4 cells treated with Tan IIA showed that positive cells accounted for (95.30 +/- 0.76)% and (93.20 +/- 1.04)% respectively; but the positive rate of either group of the treated positive cells was significantly higher than that of untreated, being (3.50 +/- 1.32)% and (2.80 +/- 0.29)% respectively (P < 0.01). Flow cytometry showed that the expression of CD(33) was reduced, while that of CD(11b) was increased. The quantity of treated cells in G(0)/G(1) phase increased but that in S phase decreased. The proliferous index was also decreased. After treated with Tan IIA, the expressions of anti-oncogene p53 and c-fos were up-regulated while those of oncogene bcl-2 and c-myc were down-regulated (P < 0.01). CONCLUSIONS: 1.0 mg/L Tan IIA could inhibit proliferation of MR-2 cells and induce differentiation of MR-2 cells into mature granulocyte, the effectivity was the same as 0.5 mg/L Tan IIA treated NB4 cells. Its possible molecular mechanism might be related to modulation of oncogene expressions associated proliferation and differentiation as well as inhibition of DNA synthesis. Tan IIA probably can be applied to treat the patients with APL, particularly to the relapsed and drug resistant patients with broad prospect.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Leucemia Promielocítica Aguda/patologia , Fenantrenos/farmacologia , Tretinoína/farmacologia , Abietanos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Humanos
19.
Zhonghua Xue Ye Xue Za Zhi ; 25(11): 641-4, 2004 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-15634564

RESUMO

OBJECTIVE: To study the characteristics of cell cycle and proliferation of CD34+ hematopoietic stem cells in patients with myelodysplastic syndromes (MDS). METHODS: Propidium iodide staining was used to examine cell cycle parameters (G(0)/G(1), S and G(2)/M) of bone marrow mononuclear cells (BMMNCs) while immunofluorescent double staining and FACS techniques were used to measure Ki67 expression in BM CD34+ cells from normal control, patients with MDS, acute myeloid leukemia preceded by MDS (MDS-AML) and primary AML. RESULTS: There was a statistical up-tendency in G(0)/G(1) phase proportion of BMMNCs whereas a statistical down-tendency in S and G(2)/M phase proportions among normal control, MDS and primary AML. Compared to primary AML, MDS-AML had significantly higher ratios of S (P < 0.05), G(2)/M (P < 0.05) and S + G(2)/M (P < 0.05) phase cells while lower ratio of G(0)/G(1) phase cells (P < 0.05). The proportion of CD34+Ki67+ cells in MDS patients was significantly higher than that in normal control (P = 0.004). So were the percentages of CD34+Ki67+ cells in low-risk [(0.54 +/- 0.49)%, P < 0.05] and high-risk MDS patients [(1.69 +/- 1.66)%, P = 0.022]. Furthermore, there was statistical difference between low-risk and high-risk MDS (P < 0.05). Compared to normal control and primary AML, MDS-patients had the highest proportion of CD34+Ki67+ cells [(16.75 +/- 13.58)%, P < 0.05]. The proportion of CD34+Ki67+ cells in CD34+ cells in MDS patients [(48.50 +/- 20.49)%] was significantly higher than that in normal control [(27.71 +/- 16.04)%, P < 0.01]. So were the low-risk [(51.85 +/- 21.80)%, P = 0.002] and high-risk MDS [(43.93 +/- 18.57)%, P < 0.05]. The proportion of CD34+Ki67+ cells in CD34+ cells in MDS-AML patients [(60.92 +/- 30.12)%] was the highest, and was statistically higher than that in both normal control (P < 0.01) and primary AML patients [(17.01 +/- 15.93)%, P < 0.001]. The proportion of CD34+Ki67+ cells in Ki67+ cells in MDS patients [(4.91 +/- 4.68)%, P < 0.01] was significantly higher than that [(2.43 +/- 2.37)%] in normal controls. In the low-risk MDS group it was (4.11 +/- 3.94)%, (P > 0.05) and in high-risk MDS group it was (5.76 +/- 5.38)%, (P < 0.05). CONCLUSION: High proportion of G(0)/G(1) cells and G(1) phase arrest occurred in MDS. High proliferation capacity of MDS clone, especially that derived from CD34+ cells, might play an important role in the clonal expansion, diseases deterioration and worse prognosis of MDS.


Assuntos
Células da Medula Óssea/patologia , Ciclo Celular , Proliferação de Células , Síndromes Mielodisplásicas/sangue , Doença Aguda , Adolescente , Adulto , Idoso , Antígenos CD34/sangue , Células da Medula Óssea/metabolismo , Feminino , Citometria de Fluxo , Imunofluorescência , Humanos , Antígeno Ki-67/sangue , Leucemia Mieloide/sangue , Masculino , Pessoa de Meia-Idade , Adulto Jovem
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