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2.
Zhonghua Xue Ye Xue Za Zhi ; 39(1): 78-82, 2018 Jan 14.
Artigo em Chinês | MEDLINE | ID: mdl-29551045
3.
Leukemia ; 31(5): 1079-1086, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27807368

RESUMO

The origin of cancers is associated with etiology as well as therapeutics. Several studies reveal that malignancies in children can originate in utero. However, a diagnostic approach to distinguish between cancers initiated pre- or postnatally is absent. Here we identified a transcriptional factor FEV (fifth Ewing variant) that was expressed in fetal hematopoietic cells and became silent after birth. We characterized that FEV was essential for the self-renewal of hematopoietic stem cells (HSCs). We next found that FEV was expressed in most infant leukemia samples, but seldom in adult samples, in accord with the known prenatal origins of the former. We further determined the majority of pediatric acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML) were FEV positive. Moreover, FEV knockdown markedly impaired the leukemia-propagating ability of leukemic stem cells. We therefore identified FEV is unique to fetal HSCs and stably expressed in leukemic cells of prenatal origin. It may also provide a tractable therapeutic target.


Assuntos
Proteínas de Ligação a DNA/análise , Doenças Fetais/diagnóstico , Células-Tronco Hematopoéticas/metabolismo , Leucemia/etiologia , Proteínas Nucleares/análise , Animais , Células Cultivadas , Proteínas de Ligação a DNA/biossíntese , Feminino , Doenças Fetais/metabolismo , Expressão Gênica , Xenoenxertos , Humanos , Leucemia/diagnóstico , Leucemia/metabolismo , Leucemia Mieloide Aguda , Camundongos , Proteínas Nucleares/biossíntese , Leucemia-Linfoma Linfoblástico de Células Precursoras , Gravidez , Fatores de Transcrição
4.
Zhonghua Xue Ye Xue Za Zhi ; 37(5): 437-40, 2016 May 14.
Artigo em Chinês | MEDLINE | ID: mdl-27210886
5.
J Intern Med ; 278(6): 627-42, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26058416

RESUMO

Acute promyelocytic leukaemia (APL), the M3 subtype of acute myeloid leukaemia, was once a lethal disease, yet nowadays the majority of patients with APL can be successfully cured by molecularly targeted therapy. This dramatic improvement in the survival rate is an example of the advantage of modern medicine. APL is characterized by a balanced reciprocal chromosomal translocation fusing the promyelocytic leukaemia (PML) gene on chromosome 15 with the retinoic acid receptor α (RARα) gene on chromosome 17. It has been found that all-trans-retinoic acid (ATRA) or arsenic trioxide (ATO) alone exerts therapeutic effect on APL patients with the PML-RARα fusion gene, and the combination of both drugs can act synergistically to further enhance the cure rate of the patients. Here, we provide an insight into the pathogenesis of APL and the mechanisms underlying the respective roles of ATRA and ATO. In addition, treatments that lead to more effective differentiation and apoptosis of APL cells, including leukaemia-initiating cells, and more thorough eradication of the disease will be discussed. Moreover, as a model of translational research, the development of a cure for APL has followed a bidirectional approach of 'bench to bedside' and 'bedside to bench', which can serve as a valuable example for the diagnosis and treatment of other malignancies.


Assuntos
Arsenicais/farmacologia , Leucemia Promielocítica Aguda , Terapia de Alvo Molecular/métodos , Proteínas de Fusão Oncogênica/genética , Óxidos/farmacologia , Tretinoína/farmacologia , Antineoplásicos/farmacologia , Trióxido de Arsênio , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/genética , Pesquisa Médica Translacional
6.
Blood Cancer J ; 3: e133, 2013 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-23955588

RESUMO

Minimal residual disease (MRD) is of the most important factor for predicting prognosis and guiding treatment of acute lymphoblastic leukemia (ALL). In this study, we investigated the prognostic significance of leukemia-associated immunophenotypes (LAIPs) as assessment of index of MRD in 125 adult B-lineage ALL (B-ALL) patients by eight-color flow cytometry. The LAIPs could be identified in 96% and 81.6% of patients with the sensitivity of 10(-4) and 10(-5), respectively. MRD-negative status could clearly predict a favorable 2-year relapse-free survival (RFS) and overall survival (OS) at the end of induction of complete remission and one cycle of consolidation treatment. Moreover, we identified a group of cases with MRD of 0.001% to <0.01%, which showed significantly higher 2-year relapse rate than those with undetectable one. In multivariate analysis, MRD status was associated with RFS or OS independently. Furthermore, MRD assessed by LAIPs and RQ-PCR assay for patients with BCR-ABL fusion gene yielded concordant results in 89.7% of cases. In conclusion, MRD evaluated by eight-color flow cytometry could provide an important tool to assess treatment response and prognosis precisely in adult B-ALL.

7.
Leukemia ; 26(7): 1608-16, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22382891

RESUMO

It has been generally acknowledged that the diagnosis, treatment and prognosis evaluation of leukemia largely rely on an adequate identification of genetic abnormalities. A systemic analysis of genetic aberrations was performed in a cohort of 1346 patients with newly diagnosed acute lymphoblastic leukemia (ALL) in China. The pediatric patients had higher incidence of hyperdiploidy and t(12;21) (p13;q22)/ETV6-RUNX1 than adults (P<0.0001); in contrast, the occurrence of Ph and Ik6 variant of IKZF1 gene was much more frequent in adult patients (all P<0.0001). In B-ALL, the existence of Ik6 and that of BCR-ABL were statistically correlated (P<0.0001). In comparison with Western cohorts, the incidence of t(9;22) (q34;q11)/BCR-ABL (14.60%) in B-ALL and HOX11 expression in T-ALL (25.24%) seemed to be much higher in our group, while the incidence of t(12;21) (p13;q22)/ETV6-RUNX1 (15.34%) seemed to be lower in Chinese pediatric patients. The occurrence of hyperdiploidy was much lower either in pediatric (10.61% vs 20-38%) or adult patients (2.36% vs 6.77-12%) in our study than in Western reports. In addition, the frequencies of HOX11L2 in adult patients were much higher in our cohort than in Western countries (20.69% vs 4-11%). In general, it seems that Chinese ALL patients bear more adverse prognostic factors than their Western counterparts do.


Assuntos
Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Aberrações Cromossômicas , Transtornos Cromossômicos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China , Estudos de Coortes , Feminino , Humanos , Imunofenotipagem , Cariotipagem , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Prognóstico , Taxa de Sobrevida , Ocidente , Adulto Jovem
8.
Leukemia ; 26(8): 1743-51, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22422168

RESUMO

Acute promyelocytic leukemia (APL) is a unique subtype of acute myeloid leukemia (AML). The prognosis of APL is changing, from the worst among AML as it used to be, to currently the best. The application of all-trans-retinoic acid (ATRA) to the induction therapy of APL decreases the mortality of newly diagnosed patients, thereby significantly improving the response rate. Therefore, ATRA combined with anthracycline-based chemotherapy has been widely accepted and used as a classic treatment. It has been demonstrated that high doses of cytarabine have a good effect on the prevention of relapse for high-risk patients. However, as the indications of arsenic trioxide (ATO) for APL are being extended from the original relapse treatment to the first-line treatment of de novo APL, we find that the regimen of ATRA, combined with ATO, seems to be a new treatment option because of their targeting mechanisms, milder toxicities and improvements of long-term outcomes; this combination may become a potentially curable treatment modality for APL. We discuss the therapeutic strategies for APL, particularly the novel approaches to newly diagnosed patients and the handling of side effects of treatment and relapse treatment, so as to ensure each newly diagnosed patient of APL the most timely and best treatment.


Assuntos
Antineoplásicos/uso terapêutico , Arsenicais/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Óxidos/uso terapêutico , Tretinoína/uso terapêutico , Animais , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Trióxido de Arsênio , Arsenicais/administração & dosagem , Arsenicais/efeitos adversos , Transformação Celular Neoplásica/genética , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/secundário , Quimioterapia de Consolidação , Sinergismo Farmacológico , Humanos , Quimioterapia de Indução , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/patologia , Quimioterapia de Manutenção , Óxidos/administração & dosagem , Óxidos/efeitos adversos , Recidiva , Tretinoína/administração & dosagem
9.
J Int Med Res ; 40(1): 56-66, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22429345

RESUMO

OBJECTIVE: The effects of celecoxib, a selective cyclo-oxygenase-2 (COX-2) inhibitor, on HeLa cervical cancer cell growth and radiosensitivity were investigated. METHODS: Cytotoxicity was quantified using a 3-(4,5-dimethyl thiazol-2-yl)-2,5-diphenyltetrazolium assay and effects on radiosensitivity were assessed using the lethal dose, quasithreshold dose, fraction surviving after 2 Gy irradiation and the radiosensitization ratio (SER, based on average lethal dose) determined using a single-hit multitarget model. RESULTS: Celecoxib inhibited HeLa cell proliferation in a concentration- and time-dependent manner, with a half-maximal inhibitory concentration at 72 h of 44 µmol/l. Treatment with 20 µmol/l celecoxib for 72 h before irradiation was associated with an SER of 2.01. The SER of irradiated cells was 2.41 when treated with 40 µmol/l celecoxib before irradiation, 1.89 when treated simultaneously and 1.44 when treated after irradiation. Celecoxib downregulated COX-2 and vascular endothelial growth factor C (VEGF-C) expression evaluated immunohistochemically. CONCLUSION: Celecoxib pretreatment radiosensitizes HeLa cells via a mechanism dependent on down-regulation of COX-2 and VEGF-C.


Assuntos
Ciclo-Oxigenase 2/metabolismo , Pirazóis/farmacologia , Tolerância a Radiação/efeitos dos fármacos , Radiossensibilizantes/farmacologia , Sulfonamidas/farmacologia , Neoplasias do Colo do Útero/enzimologia , Fator C de Crescimento do Endotélio Vascular/metabolismo , Celecoxib , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Feminino , Células HeLa , Humanos , Imuno-Histoquímica , Tolerância a Radiação/efeitos da radiação , Fatores de Tempo , Neoplasias do Colo do Útero/patologia , Raios X
10.
Leukemia ; 26(7): 1507-16, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22297722

RESUMO

The molecular characterization of cytogenetic abnormalities has not only provided insights into the mechanisms of leukemogenesis but also led to the establishment of new treatment strategies targeting these abnormalities and thereby further improve the prognosis of patients. We analyzed the prognosis of 1091 Chinese patients with newly diagnosed acute lymphoblastic leukemia (ALL) and explored the prognostic impacts of a large number of cytogenetic/molecular abnormalities. It was demonstrated that, in both B- and T-ALL settings, the prognosis was negatively correlated to the age as reported to date. For childhood T-ALL patients, it was also documented that the HOX11 expression represented a favorable prognostic factor as it was in adult ones. We identified CRLF2 overexpression as an intermediate-risk marker and Ik6 variant of IKZF1 gene as a high-risk one when stratifying pediatric B-ALL cases according to cytogenetic/molecular risks. We also found that Ik6 variant and CRLF2 overexpression had an important role in dictating the prognosis of Ph-negative patients, which may be useful markers in guiding the treatment of ALL in the future, with tyrosine kinase inhibitors on the other hand reversing the fate of Ph-positive ALL patients.


Assuntos
Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Aberrações Cromossômicas , Transtornos Cromossômicos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , China , Feminino , Humanos , Imunofenotipagem , Lactente , Recém-Nascido , Cariotipagem , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Prognóstico , Taxa de Sobrevida , Adulto Jovem
11.
J Hematother Stem Cell Res ; 10(3): 405-9, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11454315

RESUMO

Diagnosis of essential thrombocythemia (ET) is controversial and remains mainly an exclusion diagnosis. Endogenous megakaryocyte colony (EMC) formation have been largely evaluated to identify specific criteria for ET, but results are impeded by the lack of medium standardization. We evaluated megakaryocyte (MK) colony formation in a serum-free collagen-based medium, without cytokine and in the presence of various concentrations of thrombopoietin (TPO). Thirty-six bone marrows from patients diagnosed with ET (n = 11), polycythemia vera (PV; n = 12), reactive thrombocytosis (RT; n = 6) and healthy donors (n = 7) were assessed. We demonstrate that 11 out 11 of the ET patients had spontaneous megakaryocyte colony-forming unit (CFU-MK) formation, in contrast to none of the RT patients and healthy donors. MK progenitors from ET patients remained responsive to TPO, because exogenous addition of TPO significantly increased cloning efficiency. Moreover, at low doses of TPO (0.5 ng/ml and 5 ng/ml), the number of positive cultures and mean number of TPO stimulated CFU-MK were significantly higher in cultures of cells from patients with ET than in patients with RT. In summary, we have described a standardized serum-free, collagen-based assay that allows differential diagnosis of ET and RT, according to endogenous CFU-MK formation and sensitivity to TPO.


Assuntos
Células-Tronco Hematopoéticas/patologia , Megacariócitos/patologia , Trombocitemia Essencial/diagnóstico , Trombocitose/diagnóstico , Trombopoetina/farmacologia , Medula Óssea/patologia , Colágeno , Ensaio de Unidades Formadoras de Colônias , Meios de Cultura Livres de Soro , Diagnóstico Diferencial , Resistência a Medicamentos , Feminino , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Masculino , Megacariócitos/efeitos dos fármacos , Policitemia Vera/patologia , Trombocitemia Essencial/patologia , Trombocitose/patologia
12.
World J Gastroenterol ; 3(2): 122, 1997 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-27041970

RESUMO

AIM: To study the relationship between the expression of the c-erbB-2 proto-oncogene product with gastric mucosal carcinogenesis and the behavior of gastric carcinoma. METHODS: Specimens from nine normal gastric mucosa, 23 gastric mucosal dysplasia (10 slight, six moderate, seven severe), 18 early gastric carcinoma, and 30 advanced gastric carcinoma were marked with P185 monoclonal antibody using the immunohistochemical peroxidase-avidin-biotin complex method. The relation between P185 expression with histological type, size, and lymph node metastasis of gastric carcinoma were analyzed. RESULTS: Normal gastric mucosa was negative for P185; Only a few cells in the neck region of the mucosal glands were very weakly positive. Relatively high positive rates were found in the slight, moderate, and severe dysplasia specimens (50%, 83.3%, and 85.7%, respectively). A 22.2% and 56.7% P185-positive rate was found in early gastric carcinoma and in advanced gastric carcinoma, respectively. Statistically, the P185-positive rates in severe dysplasia and advanced gastric carcinoma were significantly higher than that in early gastric carcinoma (P < 0.05). The P185-positive rate in the group with lymph node metastasis was significantly higher than that of the group without lymph node metastasis (59.3% vs 23.8%, P < 0.05), but P185 expression was not related to histological type and size of gastric carcinoma. CONCLUSION: The c-erbB-2 proto-oncogene might participate in gastric mucosal proliferation, repair, and carcinogenesis, and gastric carcinoma with P185 expression might have a stronger potential of infiltration and metastasis.

13.
Zhonghua Zhong Liu Za Zhi ; 15(3): 192-4, 1993 May.
Artigo em Chinês | MEDLINE | ID: mdl-8261863

RESUMO

The expression of epidermal growth factor receptor (EGF-R) in normal gastric mucosa, gastric mucosal dysplasia, early and advanced gastric carcinoma was studied with the monoclonal antibody to EGF-R by using immunohistochemical ABC method. Normal gastric mucosa was negative for EGF-R, but a relatively high positive rate was found in dysplasia. When gastric carcinoma occurred, the positive rate decreased. The expression of EGF-R was related to the poor differentiation and strong infiltration of gastric carcinoma. The carcinoma with the expression of EGF-R was easy to metastasize to lymph nodes. The result suggests that EGF-R might play some role in the process of carcinogenesis of gastric mucosa, and be used as a useful marker for the assessment of the biological behavior of gastric carcinoma.


Assuntos
Adenocarcinoma/química , Biomarcadores Tumorais/análise , Receptores ErbB/análise , Lesões Pré-Cancerosas/química , Neoplasias Gástricas/química , Adenocarcinoma/patologia , Anticorpos Monoclonais , Mucosa Gástrica/química , Humanos , Metástase Linfática , Invasividade Neoplásica , Neoplasias Gástricas/patologia
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