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1.
Eur J Med Chem ; 180: 62-71, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31301564

RESUMO

Oxidative stress and inflammation are major causes of numerous life-threatening human diseases. In the present study, we synthesized a series of phenylacrylamide derivatives as novel anti-oxidant and anti-inflammatory agents. Biological evaluation showed that compound 6a could more potently protect HBZY-1 mesangial cells from H2O2-caused oxidative stress than positive controls resveratrol and sulforaphane by dose- and time-dependently impairing the ROS accumulation. Preliminary anti-oxidant mechanism studies indicated that compound 6a could activate Nrf2 and increase the protein and mRNA expression of downstream anti-oxidant enzymes, ie. NQO-1, HO-1, GCLM and GCLC. Notably, 6a could inhibit the production of NO and the activity of NF-κB in LPS-stimulated HBZY-1 mesangial cells, indicating its potential anti-inflammatory activity. Interestingly, both effects could be significantly attenuated by Nrf2 inhibitor TRG, HO-1 inhibitor ZnPP or GCL inhibitor BSO at non-toxic concentrations, confirming that the anti-oxidant and anti-inflammatory activity of 6a is related to the activation of Nrf2 signaling pathway. These results, together with the relatively safety profile, indicated that compound 6a could be a promising lead to develop novel anti-oxidant and anti-inflammatory agents, thus preventing diseases induced by oxidative stress and inflammation.


Assuntos
Acrilamida/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Inflamação/tratamento farmacológico , Acrilamida/síntese química , Acrilamida/química , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antioxidantes/síntese química , Antioxidantes/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Relação Estrutura-Atividade
2.
Eur J Med Chem ; 176: 41-49, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31091479

RESUMO

Hepatitis B virus (HBV) infection is a worldwide public health issue. Search for novel non-nucleoside anti-HBV agents is of great importance. In the present study, a series of quinazolinones derivatives (4a-t and 5a-f) were synthesized and evaluated as novel anti-HBV agents. Among them, compounds 5e and 5f could significantly inhibit HBV DNA replication with IC50 values of 1.54 µM and 0.71 µM, respectively. Interestingly, the selective index values of 5f was higher than that of lead compound K284-1405, suggesting 5f possessed relatively safety profile than K284-1405. Notably, 5e and 5f exhibited remarkably anti-HBV activities against lamivudine and entecavir resistant HBV strain with IC50 values of 1.90 and 0.84 µM, confirming their effectiveness against resistant HBV strain. In addition, molecular docking studies indicated that compounds 5e and 5f could well fit into the dimer-dimer interface of HBV core protein dominated by hydrophobic interactions. Notably, their binding modes were different from the lead compound K284-1405, which may be attributed to the additional substituent groups in the quinazolinone scaffold. Taken together, 5e and 5f possessed novel chemical structure and potent anti-HBV activity against both drug sensitive and resistant HBV strains, thus warranting further research as potential non-nucleoside anti-HBV candidates.


Assuntos
Antivirais/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Quinazolinonas/farmacologia , Antivirais/síntese química , Antivirais/química , Antivirais/toxicidade , Sítios de Ligação , Replicação do DNA/efeitos dos fármacos , Células Hep G2 , Antígenos do Núcleo do Vírus da Hepatite B/química , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Quinazolinonas/síntese química , Quinazolinonas/química , Quinazolinonas/toxicidade , Relação Estrutura-Atividade
3.
Eur J Med Chem ; 162: 59-69, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30408749

RESUMO

Oxidative stress plays a significant role in the pathogenesis of various human diseases. In this study, a series of bifendate derivatives bearing acrylamide moiety were synthesized and evaluated as anti-oxidant agents. Biological evaluation indicated that compounds 6a and 6e displayed more potent cytoprotective effect against H2O2-induced HBZY-1 mesangial cells death than lead compound bifendate and positive control resveratrol and sulforaphane. Preliminary anti-oxidant mechanism studies showed that compound 6e could diminish the ROS accumulation by dose- and time-dependently activating Nrf2 and increasing the expression of downstream detoxification enzymes NQO-1, HO-1, GCLM and GCLC at protein and mRNA levels, thus displaying potent anti-oxidant activity. Interestingly, the Nrf2 activating effect of 6e is achieved, at least partly, in Michael acceptor and Keap1-dependent manners. These results, together with the low intrinsic cytotoxicity, suggested that compound 6e might be a promising lead for the development of novel anti-oxidant agents to prevent diseases induced by oxidative stress.


Assuntos
Acrilamida/química , Antioxidantes/farmacologia , Compostos de Bifenilo/farmacologia , Células Mesangiais/efeitos dos fármacos , Antioxidantes/química , Compostos de Bifenilo/síntese química , Humanos , Peróxido de Hidrogênio/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio , Relação Estrutura-Atividade
4.
Medchemcomm ; 9(11): 1826-1830, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30542532

RESUMO

Multidrug resistance (MDR) and metastasis are major causes of mortality in patients with cancer. We recently reported a bifendate derivative bearing a dibenzo[c,e]azepine scaffold (4i) as a P-gp and BCRP-medicated MDR reversal agent. As a continuation of the previous research, its ability to inhibit cancer metastasis was investigated in MDA-MB-231 cells in the present work. Wound-healing and chamber migration assays showed that 4i could significantly attenuate the migration of MDA-MB-231 cells. Additionally, 4i obviously suppressed the invasive activity of MDA-MB-231 cells, thus displaying potential anti-metastasis activity. Preliminary mechanism studies indicated that the anti-metastasis activity of 4i was associated with the inhibitory effect on the activity and expression of MMP-2 and MMP-9. These results, together with the previous findings, suggest that compound 4i could be a promising lead for the development of novel anti-cancer agents with anti-MDR and metastatic activities.

5.
Int J Pharm ; 545(1-2): 117-127, 2018 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-29601975

RESUMO

As one of the classical nano drug carriers, chitosan-based nanoparticles (CsNps) are getting increasing attentions for their non-toxicity, biocompatibility and biodegradability. The ionotropic gelation is the most favorable method for CsNps preparation, while it's beset by some issues, i.e. low particle formation yield, poor physical stability and low hydrophobic drug loading capacity. To solve these problems, a simple desolvation method was attempted in this study for CsNps preparation. Using this method, an increased formation yield of CsNps (about 100%) could be obtained, and after diluting the particles by various buffers (PBS 7.0, 7.4 and 8.0, DMEM medium and 1640 medium), an improved stability in diameter could be observed. The drug loading results showed paclitaxel loading efficiency of 9.8% could be obtained when the ratio of paclitaxel to Cs was set at 0.2, higher than the ionotropic gelation method (0.43%). The particles formation mechanisms were studied by the molecular dynamics simulation, and the results showed the Lennard-Jones interaction of Cs-Cs, which could be adjusted by the pH value of system, played a great role in formation of particles with the desolvation method. This study provided an alternative preparation technology for CsNps with high process yield, physical stability and hydrophobic drug encapsulation capacity.


Assuntos
Antineoplásicos Fitogênicos/química , Quitosana/química , Portadores de Fármacos , Nanopartículas , Paclitaxel/química , Tecnologia Farmacêutica/métodos , Antineoplásicos Fitogênicos/administração & dosagem , Neoplasias da Mama/patologia , Tampões (Química) , Sobrevivência Celular/efeitos dos fármacos , Quitosana/toxicidade , Meios de Cultura/química , Composição de Medicamentos , Estabilidade de Medicamentos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Células MCF-7 , Simulação de Dinâmica Molecular , Nanotecnologia , Paclitaxel/administração & dosagem
6.
Eur J Med Chem ; 144: 424-434, 2018 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-29288943

RESUMO

As an ongoing search for potent non-nucleoside anti-HBV agents with novel structures, we described a series of phenyl propionamide derivatives (3a-b, 4a-e, 7a-g, 8a-h and 9a-b) by pharmacophore fusion strategy in the present work. All the compounds exhibited an anti-HBV activity to some extent. Among them, compounds 8d and 9b displayed most potent anti-HBV activity with IC50 values on HBV DNA replication of 0.46 and 0.14 µM, respectively. And the selective index values of 8d and 9b were more than 217.39 and 153.14, suggesting that 8d and 9b exhibited favorable safety profiles. Interestingly, 8d and 9b possessed significantly antiviral activities against lamivudine and entecavir resistant HBV mutants with IC50 values of 0.77 and 0.32 µM. Notably, preliminary anti-HBV action mechanism studies showed that 8d could inhibit intracellular HBV pgRNA and RT activity of the HBV polymerase. Molecular docking studies suggested that compound 8d could fit into the dimer-dimer interface of HBV core protein by hydrophobic interaction. In addition, in silico prediction of physicochemical properties showed that 8d conformed well to the Lipinski's rule of five, suggesting its potential for use as a drug like molecule. Taken together, 8d possessed significantly anti-HBV activity, low toxicity, diverse anti-HBV mechanism and favorable physicochemical properties, and warranted further investigation as a promising non-nucleoside anti-HBV candidate.


Assuntos
Amidas/farmacologia , Antivirais/farmacologia , Desenho de Drogas , Vírus da Hepatite B/efeitos dos fármacos , Amidas/síntese química , Amidas/química , Antivirais/síntese química , Antivirais/química , Sobrevivência Celular/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Replicação Viral/efeitos dos fármacos
7.
Chem Biodivers ; 13(11): 1584-1592, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27451105

RESUMO

A series of Matijin-Su (MTS, (2S)-2-{[(2S)-2-benzamido-3-phenylpropanoyl]amino}-3-phenylpropyl acetate) derivatives were synthesized and evaluated for their anti-HBV and cytotoxic activities in vitro. Six compounds (4g, 4j, 5c, 5g, 5h and 5i) showed significant inhibition against HBV DNA replication with the IC50 values in range of 2.18 - 8.55 µm, which were much lower than that of positive control lamivudine (IC50 82.42 µm). In particular, compounds 5h (IC50 2.18 µm; SI 151.59) and 5j (IC50 5.65 µm; SI 51.16) displayed relatively low cytotoxicities, resulting in high SI values. Notably, besides the anti-HBV DNA replication activity, compound 4j also exhibited more potent in vitro cytotoxic activity than 5-fluorouracil in two hepatocellular carcinoma cell (HCC) lines (QGY-7701 and SMMC-7721), indicating that 4j may be a promising lead for the exploration of drugs with dual therapeutic effects on HBV infection and HBV-induced HCC.


Assuntos
Antineoplásicos/farmacologia , Antivirais/farmacologia , Dipeptídeos/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Antineoplásicos/síntese química , Antineoplásicos/química , Antivirais/síntese química , Antivirais/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dipeptídeos/síntese química , Dipeptídeos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Testes de Sensibilidade Microbiana , Conformação Molecular , Relação Estrutura-Atividade
8.
Artigo em Inglês | MEDLINE | ID: mdl-26113453

RESUMO

The mesangial cell (MC) cultured with high glucose has been used to observe the protective effect of Ginkgo biloba extract (GBE) against diabetic nephropathy (DN), but the compounds interacting with cell are still unknown, which may be potential bioactive components. Based on this, the determination of GBE in MC lysates was proposed by high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) in this study. The MC was cultured with normal or high glucose with GBE for 4, 8, 12, 16, 24 and 48h. The harvested cell was extracted with 40% acetic acid in water and further analyzed by LC-MS/MS. All the validation data including linearity, intra-day and inter-day precision, limit of detection and quantification, matrix effect, and stability were within the required limits. The validated method was successfully applied to quantify 11 compounds of GBE in cell lysates. The results showed that high glucose prolonged the peak time of all observed 11 compounds and peak concentrations of bilobalide, ginkgolide C, ginkgolide B, quercetin, luteolin, kaempferol, isorhamnetin and genkwanin in cell lysates, which hinted that these compounds may be the potential bioactive components of GBE with preventive effect against DN.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ginkgo biloba/química , Células Mesangiais/metabolismo , Extratos Vegetais/análise , Extratos Vegetais/metabolismo , Espectrometria de Massas em Tandem/métodos , Técnicas de Cultura de Células , Nefropatias Diabéticas , Glucose/metabolismo , Humanos , Reprodutibilidade dos Testes
9.
Comb Chem High Throughput Screen ; 18(5): 514-23, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25924659

RESUMO

Rat renal tubular epithelial cell (RTEC) cultured with high glucose has been used to observe the protective effect of Ginkgo biloba extract (GBE) against diabetic nephropathy (DN). The compounds in GBE binding with cell membrane or entering into cell are still unknown, which may be potential bioactive components. In this paper, a powerful method for screening and analyzing the potential bioactive components from GBE was developed using cell extraction coupled with high performance liquid chromatography tandem mass spectrometry (LC-MS/MS). 8 prototype compounds and 5 metabolites were obtained, among which 6 prototype compounds and 1 metabolite were identified or tentatively characterized as rutin, bilobalide, ginkgolide B, ginkgolide C, genkwanin, apigenin and diosmetin by comparing their retention times and MS spectra with those of authentic standards or literature data. The 6 prototype compounds were further quantitatively analyzed using electrospray ionization in negative mode multiple reaction monitoring (MRM). The results showed that high glucose changed the Tmax, MRT(0-t), Cmax and AUC(0-t) of all observed compounds and decreased the t1/2 of genkwanin and apigenin, significantly. The overall findings indicate that 8 prototype compounds may be the potential bioactive components of GBE with preventive effect against DN and the method of RTEC extraction coupled with LC-MS/MS technology screening method we developed is a feasible, rapid, and useful tool for screening and analyzing potential bioactive components.


Assuntos
Células Epiteliais/química , Ginkgo biloba/química , Túbulos Renais Proximais/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Animais , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Técnicas de Química Combinatória , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Ensaios de Triagem em Larga Escala , Túbulos Renais Proximais/efeitos dos fármacos , Túbulos Renais Proximais/metabolismo , Extratos Vegetais/farmacologia , Ratos , Espectrometria de Massas em Tandem
10.
Biomed Chromatogr ; 29(2): 226-32, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24925151

RESUMO

A rapid and useful approach for screening potential bioactive components in Ginkgo biloba extract (GBE) with preventive effect against diabetic nephropathy (DN) was developed using mesangial cells extraction coupled with high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. Mesangial cells were first divided into two groups according to their treatments with high glucose or high glucose plus GBE. After incubation for 4, 8, 12, 16, 24 and 48 h, the cells were harvested and extracted with 40% acetic acid in water before LC-MS/MS analysis. Then, 19 compounds and five metabolites were found to selectively combine with mesangial cells. Notably, compounds including quercetin and rutin were identified or tentatively characterized according to the results of retention time and MS spectra, which is highly consistent with our previous reports that quercetin and rutin are potent protective agents against glomerulosclerosis in DN. Therefore, all these results indicate that target cell extraction coupled with LC-MS/MS analysis can be successfully applied for predicting the bioactive components in GBE with preventive effect against DN.


Assuntos
Cromatografia Líquida/métodos , Ginkgo biloba/química , Espectrometria de Massas em Tandem/métodos , Animais , Nefropatias Diabéticas/tratamento farmacológico , Humanos , Células Mesangiais/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia
11.
Bioorg Chem ; 56: 34-40, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24930072

RESUMO

A series of Matijin-Su (MTS, N-(N-benzoyl-l-phenylalanyl)-O-acetyl-l-phenylalanol) derivatives was synthesized and evaluated for their anti-tumor activities in hepatocellular carcinoma cells. The IC50 of compounds 1, 3, 4, 11, 13 were less than 20µM, and compound 1 and 3 showed an IC50 value of less than 9µM. Expansion inhibition could be found significantly in compound 1 and 3-treated human hepatoma cell HepG2 and PLC/PRF/5, while both compounds exhibit lower toxicity to human hepatocyte cell line L-02. Compound 1 and 3 could induce cell cycle arrest at G1/S phase. This may be attributed to increase level of intracellular reactive oxygen species (ROS). Up-regulation of p38 MAPK activity in responding the ROS stabilize p53 and activate p21 transcription, the critical regulatory in G1/S checkpoint. Observations in this study shed light on the potential of MTS derivatives compound 1 and 3 as novel suppressors to human liver cancer.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Dipeptídeos/farmacologia , Antineoplásicos/química , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dipeptídeos/síntese química , Dipeptídeos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Estrutura Molecular , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
12.
Bioorg Med Chem ; 19(18): 5352-60, 2011 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-21872478

RESUMO

A series of Matijing-Su (MTS, N-(N-benzoyl-l-phenylalanyl)-O-acetyl-L-phenylalanol) derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activity in 2.2.15 cells. The IC(50) of compounds 14a (0.71 µM), 13c (2.85 µM), 13b (4.37 µM), etc. and the selective index of 13g (161.01), 13c (90.45), 13a (85.09) etc. of the inhibition on the replication of HBV DNA were better than those of the positive control lamivudine (IC(50): 82.42 µM, SI: 41.59). Compounds 13o, 13p, and 16a also exhibited significant anti-HBV activity.


Assuntos
Antivirais/síntese química , Antivirais/farmacologia , Dipeptídeos/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Antivirais/química , Linhagem Celular , Dipeptídeos/síntese química , Dipeptídeos/química , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Estereoisomerismo , Relação Estrutura-Atividade , Replicação Viral/efeitos dos fármacos
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 27(2): 214-6, 2010 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-20376808

RESUMO

OBJECTIVE: To investigate the clinical significance of a rare chromosome abnormality der(Y)t(Y;1) in a patient with multiple myeloma (MM). METHODS: The chromosome spread was prepared after 24 h culture of bone marrow. G-banding technique was used to analyze the karyotype. Fluorescence in situ hybridization (FISH) was performed to ascertain the origin of abnormal chromosome detected by conventional karyotypic analysis. Flow cytometry was used to detect the expression of the CD38/CD138/ZAP70. Immunoelectrophore was applied to identify the type of immunoglobulin. RESULTS: A complex pattern of chromosome rearrangement was observed: 92,XXYY[3]/49,X,der(Y)t(Y;1)(q12;q21),t(11;14)(q13;q32),+18,+20,+21[47]/49,X,idem,del(13q22),ace[1]/98,XX,der(Y)t(Y;1) x 2,+18,+18,+20,+20,+21,+21[10]/46,XY[19]. The result was confirmed by metaphase-FISH. The type of immunoglobulin was IgD with the level of 6.24g/L. The CD38/CD138 was positive but ZAP70 was negative. CONCLUSION: Structural abnormality of chromosome Y is rare in blood malignancy. Most of them were described in myelodysplastic syndrome or myeloproliferative disorders. It is the first report of der(Y)t(Y;1) abnormality in multiple myeloma.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Y/genética , Mieloma Múltiplo/genética , Haplótipos , Humanos , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Resultado do Tratamento
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 17(3): 537-40, 2009 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-19549359

RESUMO

To investigate the biological characteristics of the variant translocation der ins (17;15) in a patient with acute promyelocytic leukemia (APL), the conventional G-banding technique, interphase fluorescence in situ hybridization (int-FISH), RT-PCR, gene scanning, gene sequence and flow cytometry were performed. The results indicated that the variant translocation der ins (17, 15) observed by G banding technique was a rare type, the int-FISH assay by using dual-color pml/raralpha fusion probes confirmed the cytogenetic findings. The detection results of other molecular methods demonstrated the existence of the whole pml/raralpha fusion gene, while this case had insertion variant translocation. This patient got complete remission by using combined chemotherapy, and survives with continuous complete remission during following up for 1 year. In conclusion, the variant translocation der ins (17; 15) is rare type in APL, its incidence is lower, several signal types in detection of int-FISH were observed and the combination chemotherapy for this patient showed more obvious efficacy.


Assuntos
Hibridização in Situ Fluorescente/métodos , Leucemia Promielocítica Aguda/genética , Translocação Genética , Bandeamento Cromossômico , Cromossomos Humanos Par 15 , Cromossomos Humanos Par 17 , Humanos , Interfase/genética , Masculino , Adulto Jovem
15.
Zhonghua Nei Ke Za Zhi ; 47(11): 919-22, 2008 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-19080234

RESUMO

OBJECTIVE: To deepen the understanding of chronic eosinophilic leukemia (CEL). METHODS: The course of diagnosis and treatment in a case of FIP1L1/PDGFRalpha fusion gene negative CEL was reported. Flow cytometry was used to analyze the immunophenotype of the cells in peripheral blood and pleural fluid. Karyotype was analyzed with G-banding. The expression of FIP1L1/PDGFRalpha fusion gene was detected by RT-PCR technique. Routine pathological examination of the tissues from bone marrow, lung and spleen were performed. RESULT: A sixteen-year-old girl had severe anemia, fever, splenomegaly, thrombocytopenia and dominant hypereosinophilia lasting for 22 months. Trephine biopsy showed a hypercellular marrow with eosinophilic proliferation and moderate reticular fibrosis. Eosinophilic infiltration was found in lung and spleen and embolism was also found in spleen. She had a clonal chromosomal abnormality t(5;12)(q31;p13). The expression of FIP1L1/PDGFRalpha was negative. An abnormal clone of T cells expressing CD(3)(-), CD(4)(-), CD(8)(+) was found in peripheral blood and pleural fluid, in which the clonal T cell accounted for 5.43% and 1.66% of the total lymphocytes respectively. The patient was refractory to treatment with hydroxyurea, prednisone and interferon alpha. She had poor response to a combination of therapy with low dose cytosine arabinoside, mitoxantrone, vincristine, cyclophosphamide, methotrexate and prednisone. She did not respond to imatinib and died of multiple organ failure. CONCLUSION: The present case fulfilled the WHO diagnostic criteria of FIP1L1/PDGFRalpha(-) CEL which did not respond to routine treatment and imatinib. Allogenic stem cell transplantation should be considered as early as possible in this case. It is noteworthy that clonal CD(3)(-), CD(4)(-), CD(8)(+)T-cell abnormality is related to the pathogenesis of CEL.


Assuntos
Síndrome Hipereosinofílica/genética , Adolescente , Feminino , Humanos , Síndrome Hipereosinofílica/diagnóstico , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Linfócitos T , Fatores de Poliadenilação e Clivagem de mRNA/genética
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 16(1): 22-5, 2008 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-18315893

RESUMO

To investigate the cytogenetic and clinical characteristics of inv(3q) (q21q26) and t(3;3) (q21; q26) aberrations as well as prognosis, cases were collected and chromosome specimens of bone marrow cells were prepared by 24-hour culture, while G-banding technique was used to perform karyotyping. The results showed that the simple inv(3q) and t(3; 3) aberrations were rare, they commonly combined with other chromosome aberrations such as -7/7q- and t (9; 22). The involved diseases included myelodysplastic syndromes, acute myeloid leukemia and chronic myelogenous leukemia in blast crisis. Out of 24 patients, 2 patients diagnosed with M(5) subtype did not achieve complete remission after multiple chemotherapy; 2 patients received allogenic stem cell transplantation relapsed. It is concluded that 3q21q26 aberration commonly combined with chromosome aberration 7/7q-, for these patients the efficacy of chemical therapy is poor, the efficacy of bone marrow transplant is too poor, these patients with inv(3q) and t(3; 3) aberrations have poor prognosis and short overall survival.


Assuntos
Inversão Cromossômica , Cromossomos Humanos Par 3/genética , Leucemia Mieloide Aguda/genética , Translocação Genética , Adulto , Idoso , Cromossomos Humanos Par 7/genética , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Prognóstico , Adulto Jovem
17.
Zhonghua Nei Ke Za Zhi ; 46(8): 648-50, 2007 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-17967235

RESUMO

OBJECTIVE: To investigate the change of Philadelphia chromosome-positive clone with secondary chromosomal aberrations after imatinib mesylate (IM) treatment in patients with chronic myeloid leukemia (CML) and its relation with prognosis. METHODS: 37 cases of CML in accelerated phase and blastic phase were collected and chromosome specimens of bone marrow cells were prepared by with 24-hour culture. G-banding technique was used for karyotyping. RESULTS: The major secondary chromosomal aberrations were double Ph, +8, and i (17q); the minor ones were -Y, chromosome 17 abnormalities other than i (17q) and inv (3q). The percentage of Philadelphia chromosome-positive clone with secondary chromosomal aberrations showed the following 4 types of change; amplification, no change, decrease and complete remission after treatment with IM. 2 of the 24 cases in CML in accelerated phase gained complete cytogenetic response (CCyR) and 2 of the 13 in blastic phase did so. The groups with amplification and no change showed significantly shorter overall survival and progression free survival than the groups with decrease and complete remission. CONCLUSION: The percentage of Philadelphia chromosome-positive clone with secondary chromosomal aberrations may drop in some CML patients after IM treatment and the patients may gain CCyR with accompanied prolonged survival.


Assuntos
Aberrações Cromossômicas , Leucemia Mieloide de Fase Crônica/tratamento farmacológico , Leucemia Mieloide de Fase Crônica/genética , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Benzamidas , Crise Blástica , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Bandeamento Cromossômico , Feminino , Seguimentos , Humanos , Mesilato de Imatinib , Cariotipagem , Leucemia Mieloide de Fase Crônica/patologia , Masculino , Pessoa de Meia-Idade , Cromossomo Filadélfia , Prognóstico
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 15(3): 454-7, 2007 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-17605843

RESUMO

The aim of study was to investigate the importance of chromosome aberration in differential diagnosis of eosinophilia and the chromosomal aberrations involved in patients with clonal eosinophilia. 65 cases of eosinophilia were collected and chromosome specimens of bone marrow cells were prepared by 24-hour culture, and G-banding technique was used for karyotyping. The results showed that out of 65 cases, chromosome 16 inversion was detected in 9 patients suspected as M(4Eo), and among the other 56 cases, 5 were detected with chromosomal aberrations (8.9%). Combining clinical, hematological and cytogenetical data, the 5 patients were diagnosed as acute myeloid leukemia with eosinophilia, chronic eosinophilic leukemia, 8p11 myeloproliferative syndrome, chronic myeloid leukemia in acute phase and acute myeloid leukemia-M(4Eo) respectively. The detected chromosomal aberrations were +14, t (5; 12) (q31; p13), t (8; 9) (p11; q32), t (9; 22) (q34; q11) and inv (16) (p13 q22). In conclusion, cytogenetical detection is very important in differential diagnosis of clonal eosinophilic disorders and chronic eosinophilic leukemia, which is suggested to be done routinely in clinic.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 16/genética , Eosinofilia/genética , Síndrome Hipereosinofílica/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Citogenética , Diagnóstico Diferencial , Eosinofilia/diagnóstico , Eosinofilia/patologia , Feminino , Humanos , Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/patologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 15(1): 76-8, 2007 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-17490526

RESUMO

To investigate the cytogenetic characteristics of multiple myeloma and its relationship with clinical prognosis, 68 cases were collected and chromosome specimens of bone marrow cells were prepared by 24-hour culture, and G-banding technique was used for karyotype analysis. The results showed that the detected chromosome aberration rate was 19.1% (13/68). The abnormal clones existed mosaically with normal clones. Numerous aberrations were manifested by aneuploidy, mainly by hyperdiploidy or hypodiploidy. Structural aberrations involved t (11; 14), chromosome 1 and various kinds of marker chromosomes. Cases which had very complex aberrations revealed poor prognosis. It is concluded that chromosome complex aberration is the mainly cytogenetic characteristics of multiple myeloma, and multiple numerous and structural aberrations are involved. Cytogenetic detection should be performed both at diagnosis and at disease progression so as to evaluate prognosis.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 1/genética , Mieloma Múltiplo/genética , Translocação Genética , Adulto , Idoso , Aneuploidia , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 14/genética , Análise Citogenética , Feminino , Humanos , Cariotipagem , Masculino , Pessoa de Meia-Idade , Mosaicismo , Mieloma Múltiplo/patologia
20.
Zhonghua Xue Ye Xue Za Zhi ; 28(11): 721-6, 2007 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-18457260

RESUMO

OBJECTIVES: To evaluate the efficacy and safety of imatinib mesylate (imatinib) for patients with Philadelphia chromosome-positive (Ph+ ) chronic myeloid leukemia (CML) in accelerated and blastic phase. METHODS: Seventy-five Ph+ CML patients in accelerated phase and 49 in blastic phase were treated with 400 mg or 600 mg of imatinib once daily. RESULTS: For patients in accelerated phase, the cumulative hematological response (HR) rate was 93.3%, including complete HR (CHR) rate 85.3%, and returning to chronic phase (RCP) rate 8% in a median follow-up of 23.0 (1.0 -64.0 ) months. Cumulative major cytogenetic response (MCyR) rate was 33.0%, and complete cytogenetic response (CCyR) rate 28.0%. For patients with CCyR, the major molecular response (MMoR) rate was 47.6%. The estimated 4-year progression-free survival (PFS) rate and overall survival (OS) rate were 48.2% and 52.2% in patients with HR, respectively. Severe leukocytopenia, anemia and thrombocytopenia occurred in 37.3%, 34.6% and 45.3% of all patients, respectively. For patients in blastic phase, the cumulative HR rate was 63.3%, including CHR rate 44.9%, and RCP rate 18.4% in a median follow-up of 4.5 (0.3 -63.0) months. Cumulative MCyR rate and CCyR rate were both 12.2%. For patients with CCyR, the MMoR rate was 33.3%. For patients with HR, the estimated 1-year/2-year PFS and OS rates were 32.8%/15.8% and 46.0%/ 21.0% respectively. Severe leukocytopenia, anemia and thrombocytopenia occurred in 75.5%, 71.4% and 73.5% of all patients, respectively. CONCLUSIONS: The efficiency of imatinib was decreasing, and severer hematological toxicities increasing with the disease progressing in patients with Ph+ CML. Imatinib improves progression-free survival significantly in most patients in accelerated phase, particularly in those with continuous CCyR or MMoR. The response duration in majority of blastic phase patients is short, and the relapse rate is high.


Assuntos
Antineoplásicos/uso terapêutico , Crise Blástica/tratamento farmacológico , Leucemia Mieloide de Fase Acelerada/tratamento farmacológico , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Idoso , Benzamidas , Feminino , Seguimentos , Humanos , Mesilato de Imatinib , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento
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