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This study was aimed to characterize clinicopathological features and prognosis of patients with adenosquamous lung carcinoma (ASC). Among the 2531 patients with lung cancer who underwent surgery between January 2000 and June 2012 in our hospital, 59 were histologically diagnosed as having ASC. The clinicopathological features and follow-up data of ASC patients were collected and analyzed statistically. Superior lobectomy was accomplished in 40 patients, middle and inferior lobectomy in 3, lobectomy plus partial resection of contralateral lung in 5, partial lung resection in 4, and pneumonectomy in 7. Moreover, 22 cases were found to be adenocarcinoma-predominant, and 18 to be squamous cell carcinoma-predominant. The median survival time was 13.6 months, and the 1-, 3-, and 5-year survival rates were 59.9%, 36.4% and 31.2%, respectively. Of the 52 cases with tissue specimens available, 11 had an EGFR mutation (21.2%) and 2 had a KRAS mutation (3.8%). Multivariate analysis showed that histology subtype, pleural invasion, TNM stage, and postoperative treatment were all independent prognostic factors. The data from the current study demonstrated that SCC-predominant histology represents a better prognosis of ASC. Histology subtype, pleural invasion, TNM stage, and postoperative treatment are independent prognostic factors for ASC and adjuvant therapy may help control the disease.
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Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Adenoescamoso , Genética , Patologia , Cirurgia Geral , Diagnóstico Diferencial , Neoplasias Pulmonares , Genética , Patologia , Cirurgia Geral , Mutação , Prognóstico , Proteínas Proto-Oncogênicas p21(ras) , Genética , Receptores ErbB , Genética , Estudos Retrospectivos , Análise de SobrevidaRESUMO
This study was aimed to characterize clinicopathological features and prognosis of patients with adenosquamous lung carcinoma (ASC). Among the 2531 patients with lung cancer who underwent surgery between January 2000 and June 2012 in our hospital, 59 were histologically diagnosed as having ASC. The clinicopathological features and follow-up data of ASC patients were collected and analyzed statistically. Superior lobectomy was accomplished in 40 patients, middle and inferior lobectomy in 3, lobectomy plus partial resection of contralateral lung in 5, partial lung resection in 4, and pneumonectomy in 7. Moreover, 22 cases were found to be adenocarcinoma-predominant, and 18 to be squamous cell carcinoma-predominant. The median survival time was 13.6 months, and the 1-, 3-, and 5-year survival rates were 59.9%, 36.4% and 31.2%, respectively. Of the 52 cases with tissue specimens available, 11 had an EGFR mutation (21.2%) and 2 had a KRAS mutation (3.8%). Multivariate analysis showed that histology subtype, pleural invasion, TNM stage, and postoperative treatment were all independent prognostic factors. The data from the current study demonstrated that SCC-predominant histology represents a better prognosis of ASC. Histology subtype, pleural invasion, TNM stage, and postoperative treatment are independent prognostic factors for ASC and adjuvant therapy may help control the disease.
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<p><b>OBJECTIVE</b>To analyze the cytogenetic characteristics of different age subgroups in patients with acute myeloid leukemia (AML), and to explore the relationship between age and cytogenetics.</p><p><b>METHODS</b>Between January 2004 and December 2011, Bone marrow (BM) samples from 640 patients with de novo AML were analyzed retrospectively. The analyses were performed according to standard culturing and banding techniques, and clonal abnormalities were defined and described according to the International System for Human Cytogenetic Nomenclature (ISCN 2009). The cytogenetic subtypes were performed as normal, balanced, and unbalanced karyotypes. In the last group, the age distribution of complex and monosome karyotypes were further analyzed. The patients were divided into 8 age groups: 0 - 9, 10 - 19, 20 - 29, 30 - 39, 40 - 49, 50 - 59, 60 - 69, and ≥ 70 year old groups.</p><p><b>RESULTS</b>The distribution of normal, balanced, and unbalanced karyotypes showed age specific characteristics. The incidence of normal karyotype increased from 6.67% (0 ∼ 9 year old) to 58.33% (≥ 70) (χ(2) = 20.68, P = 0.001) and balanced karyotype decreased from 73.33% (0 ∼ 9) to 11.11% (≥ 70) (χ(2) = 48.22, P < 0.01). The frequency of unbalanced karyotypes increased from 20.0% (0 ∼ 9) to 30.56% (≥ 70) (χ(2) = 18.963, P = 0.008). The frequency of complex karyotype was 6.67% in 0 - 9 year old group, followed by 0% in 10 - 19 and 20 - 29 year old group, and from 1.72% to 11.11% from 30 - 39 to ≥ 70 year old group (χ(2) = 8.341, P = 0.08). Monosome karyotype was only detected in patients in 30 year old or older groups. Although an increased tendency was observed with ages, there was no significant difference (χ(2) = 4.778, P = 0.311).</p><p><b>CONCLUSION</b>The different age profiles of the cytogenetic subtypes may indicate the different mechanisms of the pathogenesis of AML, which may also offer beneficial information for etiological research of AML.</p>
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Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Fatores Etários , Cariótipo , Cariotipagem , Leucemia Mieloide Aguda , Genética , Estudos RetrospectivosRESUMO
<p><b>OBJECTIVE</b>To screen serum biomarkers for minimal residual disease (MRD) monitoring according to differential peptidomics profile in the serum from the patients with acute leukemia (AL) and healthy controls.</p><p><b>METHODS</b>Serum polypeptides from 90 AL patients, 60 healthy controls and 20 patients with benign hematological disorders were enriched by copper chelate magnetic beads, and the peptidomics profile was obtained by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) analysis. And the intensities of differential peptides were calculated to assess MRD level.</p><p><b>RESULTS</b>The diagnostic models by using support vector machine (SVM) algorithm according to differential peptides between AL patients and healthy controls with P<0.01 by t-test were established. The sensitivity and specificity of distinguishing AL patients from healthy controls were 98% and 99%, respectively. The model obtained a sensitivity of 98% and a specificity of 96% for distinguishing newly-diagnosed AL patients from AL patients with hematological complete remission (AL-HCR). Then a sensitivity of 92% and a specificity of 93% were obtained for distinguishing patients with AL-CR from AL patients with molecular complete remission (AL- MR). The intensity of peptide with m/z (mass-to-charge ratio) 4468 was significantly higher in newly- diagnosed AL patients compared to healthy controls, and gradually decreased with the increase of remission degree, and it was not found increase in patients with benign hematological disorders.</p><p><b>CONCLUSION</b>The SVM diagnostic model established by differential serum peptide profile could be used to discriminate AL patients with different stages of remission and to evaluate the treatment efficacy. The peptide of m/z 4468 could be used for MRD assessment, and continuous monitoring of its expression level will play an important role in the individual treatment and recurrence prediction.</p>
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Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Doença Aguda , Biomarcadores Tumorais , Sangue , Estudos de Casos e Controles , Leucemia , Sangue , Diagnóstico , Patologia , Neoplasia Residual , Sangue , Diagnóstico , Peptídeos , Mapeamento de Interação de Proteínas , Sensibilidade e EspecificidadeRESUMO
This study was aimed to explore the anti-leukemic effect of scutellaria extract SBX in human leukemia cell lines and its mechanism. The leukemia cell lines, including HL-60, NB4, U937, K562 and Jurkat, were cultured in vitro and proliferative inhibition of these cell lines was detected by CellTiter-Glo Luminescent Cell Viability Assay in order to screen the most sensitive cell line. The effect of SBX on cell cycle was analyzed by flow cytometry and the protein expressions determined by Protein Pathway Array respectively. The results indicated that SBX (10 - 200 µmol/L, for 72 h) significantly inhibited the proliferation of different leukemia cell lines in a dose-dependent manner (r value was 0.86, 0.88, 0.95, 0.94, 0.96, respectively), the HL-60 was the most sensitive cell line. Flow cytometric analysis showed that SBX (50, 10 µmol/L, for 48 h) arrested HL-60 cells in the G(0)/G(1) phase. In addition, protein expression of p-PKC α/βII, p-p38, Cdc25B, XIAP of HL-60 cells increased, and p-AKT, p-SAPK/JNK, Notch4, Cdk4, Cdc2, cyclin E, Akt, Bcl-2, Bax, cdc42, TNF-α, p27, CaMKKa decreased after exposure to SBX (50 µmol/L, for 48 h). It is concluded that SBX can inhibit the proliferation of different leukemia cell lines, and HL-60 is a sensitive cell line. SBX significantly influences EGFR, Ras/Raf/MAPK and Notch signaling pathway, through which effects the expression of cell cycle-related proteins resulting in arrest of HL-60 cells in G(0)/G(1).
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Humanos , Ciclo Celular , Proteínas de Ciclo Celular , Metabolismo , Linhagem Celular Tumoral , Medicamentos de Ervas Chinesas , Farmacologia , Usos Terapêuticos , Leucemia , Tratamento Farmacológico , Metabolismo , Proteínas Proto-Oncogênicas c-akt , Metabolismo , Scutellaria , Transdução de Sinais , Fator de Necrose Tumoral alfa , Metabolismo , Proteína X Associada a bcl-2 , MetabolismoRESUMO
This study was aimed to construct the shRNA eukaryotic expression vectors of M2-pyruvate kinase gene (pkm2) and to investigate the effects of pkm2 gene interference on the drug resistance of acute promyelocytic leukemia (APL) cells in vitro. Three specific shRNAs of pkm2 gene were designed and cloned into PBSU6 vector containing a U6 promotor. The constructed plasmids were identified and proved by the restriction sequence analysis. Then the effect of pkm2-shRNA on the protein expression of endogenous PKM2 was detected in NB4R2 cells, a drug resistant cell line of APL by Western blot. The alteration of NB4R2 cell differentiation with the interference of pkm2 gene was also validated by nitroblue tetrazolium (NBT) reduction test. The results showed that three specific shRNA eukaryotic expression vectors targeting pkm2 were successfully constructed. The efficiency of pkm2 gene silence was proved at protein level. The interference of pkm2 gene could significantly enhance the cell differentiation in the drug resistant NB4R2 cell line. It is concluded that the DNA vector containing pkm2 targeting shRNA remarkably promotes the differentiation of NB4R2 cells, showing the prospects of developing the gene target drug.
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Humanos , Proteínas de Bactérias , Genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Genética , Vetores Genéticos , Leucemia Promielocítica Aguda , Genética , Plasmídeos , Proteínas Serina-Treonina Quinases , Genética , Interferência de RNA , RNA Interferente Pequeno , GenéticaRESUMO
The aim of this study was to explore the mechanism underlying the blast crisis of chronic myeloid leukemia. Analysis of gene expression profiles of chronic myeloid leukemia patients in chronic phase and blast crisis were analyzed by using cDNA microarray representing 4096 genes for finding the differential expression genes. The results indicated that 74 differential expression genes were identified in at least 3 gene chips in blast crisis compared with chronic phase, among them 52 genes were down-regulated and 22 genes were up-regulated in blast crisis. The differential expression genes were involved in these genes including genes related to cell structure/mobility, signal transduction, transcription factor, related immunity, metabolism, cell cycle, oncogene/anti-oncogene, cell receptor, protein translation/synthesis and some unknown functions. It is concluded that the blast crisis of CML is resulted from abnormality and interaction of multigene, among them functional abnormal genes related to signal transduction, cell cycle, cell differentiation and immunity may be the critical genes for chronic myeloid leukemia blast crisis.
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Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Perfilação da Expressão Gênica , Regulação Leucêmica da Expressão Gênica , Genes Neoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Genética , Metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Transdução de SinaisRESUMO
This study was aimed to investigate the effect of low dose radiation (LDR) on human bone marrow mesenchymal stem cells (MSCs) by using proteomic analysis. The bidirectional gel electrophoresis was used to establish the two-dimensional gel electrophoresis patterns of proteome in group of MSCs exposed to LDR and in group of sham irradiated MSCs, the matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) was used to identify the differentially expressed proteins in two groups. The results showed that among the differentially expressed proteins in the two groups, the expressions of 12 proteins were up-regulated, the expressions of 12 protein were down-regulated, 3 proteins disappeared after LDR, 12 proteins had been identified by MALDI-TOF-MS. In conclusion, the identified 12 proteins, such as prolyl 4-hydroxylase, dihydropyrimidinase-like 2 variant, ARP3 (actin-related protein 3, yeast) homolog, guanine nucleotide binding protein (G protein), phosphoglycerate mutase 1 may be related to mechanism of LDR effect. The study provides some new explanation for the mechanism of low dose radiation injury.
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Humanos , Proteína 3 Relacionada a Actina , Células da Medula Óssea , Efeitos da Radiação , Relação Dose-Resposta à Radiação , Proteínas de Ligação ao GTP , Células-Tronco Mesenquimais , Metabolismo , Efeitos da Radiação , Pró-Colágeno-Prolina Dioxigenase , Proteínas , Proteômica , Métodos , Doses de Radiação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
The study was aimed to establish a K562/NOD-SCID leukemia mouse model and to explore its growth characteristics. Nude mice exposed to total body irradiation were inoculated subcutaneously with K562 cells, then the local K562 tumor was taken out and the tumor tissues without necoosis were selected for preparing single cell suspension which was inoculated into irradiated NOD/SCID mice by intraperitoneal injection. The results indicated that the systemic disseminated leukemia model was established successfully by intraperitoneal injection. On the fourth week after inoculation the leukemia cells were found on peripheral blood smear, and the leukemia cell infiltration was observed in liver, spleen and bone marrow. On the brink of death, the count of peripheral blood WBC was 8 - 10 times as much as that before inoculation. The leukemia cells on peripheral blood smear accounted to 20% - 30% of the total WBCs on average. The local tumors appeared in the abdominal cavity or on the greater omentum, less were involved in other organs. It is concluded that the established K562/NOD-SCID mouse model with leukemia well imitates the process of leukemia in human body, so it is a good model for the research on the effects of new drugs and target or gene therapy.
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Animais , Feminino , Humanos , Masculino , Camundongos , Modelos Animais de Doenças , Células K562 , Leucemia , Camundongos Endogâmicos NOD , Camundongos Nus , Camundongos SCID , Transplante de Neoplasias , Irradiação Corporal TotalRESUMO
This study was purposed to investigate the mechanism of low dose radiation (LDR) by proteomic technology and to find the key proteins of the hormesis and adaptive response induced LDR, which provided the foundation of experimental and theoretical basis for the clinical application of LDR. Two-dimensional electrophoresis (2-DE) was used to screen protein patterns of normal serum and serum of mice exposed to LDR in different time for qualitative and quantitative differences in protein expression. And the differentially-expressed proteins between the two groups were identified by matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS). The result showed that among the differentially-expressed proteins between the group exposed to LDR and the control group (shom-irradiated group), it was found that after LDR new 4 proteins appeared, 13 proteins were up-regulated, 6 proteins were down-regulated, 3 proteins disappeared in the group exposed to LDR. In different time the quantity of some proteins was different, the protein expression had some characteristics, the estrogen receptor 2 was down-regulated, the vitamin D-binding protein and apolipoprotien were up-regulated in the group exposed to LDR. It is concluded that LDR up-regulate or down-regulate some proteins, some proteins related with LDR were found. It may provide some new explanations for the effect mechanism of the LDR.
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Animais , Masculino , Camundongos , Relação Dose-Resposta à Radiação , Receptor beta de Estrogênio , Sangue , Efeitos da Radiação , Proteoma , Efeitos da Radiação , Doses de Radiação , Soro , Efeitos da Radiação , Proteína de Ligação a Vitamina D , Sangue , Efeitos da RadiaçãoRESUMO
The current study was purposed to investigate the inhibitory effect of human soluble vascular endothelial growth factor-1 (sFLT-1) on the proliferation of leukemic cells in vitro. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the VEGF mRNA and VEGF-R1 (FLT-1) mRNA in K562, HL60, U937 leukemic cell lines and bone marrow LTC-IC. Flow cytometry was used to detect the VEGF and VEGF-R1 (FLT-1) in all above-mentioned cells. VEGF concentrations in the cell culture supernatants were determined by enzyme-linked immunosorbent assay (ELISA). Cell proliferation was determined by MTT after adding sFLT-1 to K562, HL60 and LTC-IC culture system. The result showed that expression of VEGF could be detected in K562, HL60, U937 leukemic cell lines and LTC-IC, especially K562, K562 and HL60 cell lines also expressed FLT-1, but a little expression was found in U937 and LTC-IC. sFLT-1 could effectively inhibit the growth of K562 and HL60 cell lines in dose-dependent manner. The highest inhibition rate was found at 48 hours after adding sFLT-1. It is concluded that sFLT-1 can inhibit the growth of some leukemic cell lines, and the inhibition effect enhances as the concentration of the sFLT-1 increase, but sFLT -1 not influence the proliferation of normal marrow cells.
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Humanos , Proliferação de Células , Células HL-60 , Células K562 , RNA Mensageiro , Genética , Células U937 , Fator A de Crescimento do Endotélio Vascular , Genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular , Genética , FisiologiaRESUMO
<p><b>OBJECTIVE</b>To investigate the prevalence of domestic violence (DV) in Hunan.</p><p><b>METHODS</b>Using a multi-stage sampling strategy, 9451 households involving 32 720 persons in urban, rural and industrial areas in Hunan, China were studied. Multiform clue investigation and face-to-face interviews were combined to investigate the prevalence of DV.</p><p><b>RESULTS</b>A lifetime prevalence of DV was reported by 1533 households (16.2%). A total of 1098 households (11.6%) reported at least one incident of DV in the previous year. Both lifetime and 12-month prevalence of DV varied significantly by geographic setting (P < 0.01). The lifetime prevalence abuse rates were: spousal 10.2%, child abuse 7.8%, and elder 1.5%. With regard to household structure, the lifetime prevalence of DV was highest among those remarried families (21.0%), followed by married couples with one child and extended families with several generations living together (20.1% and 20.0%, respectively). The highest rate of spousal abuse was found among remarried families (14.7%), while child and elder abuse was most prevalent among extended families (12.4% and 4.1%, respectively).</p><p><b>CONCLUSIONS</b>The findings suggested that although the prevalence of DV in Hunan was modest compared to Western countries, it remained a serious public health problem affecting over 1 in 10 households. Furthermore, the prevalence of various types of DV varied by geographic setting and family structure, suggesting that diverse geographic setting and family constellations carried different risk and protective features.</p>
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Idoso , Criança , Feminino , Humanos , Masculino , Maus-Tratos Infantis , China , Epidemiologia , Abuso de Idosos , Estudos Epidemiológicos , Família , Características da Família , Casamento , Filho Único , Prevalência , Maus-Tratos ConjugaisRESUMO
Alienation and adaptation are two of the principles and methods in translation, each possessing their own values. Alienation should be applied in translating linguistic content in order to transfer the imbedded cultural messages trustfully; while the principle of adaptation should be followed in linguistic structure translation due to the different thinking patterns between Chinese and English which results in a great linguistic structure difference. Therefore, the translator must express the original meaning trustfully, on the other hand, to make the Chinese version more smooth, linguistic structure should be transformed to conform to the thinking habit of the readers. In brief,alienation and adaptation should complement each other in translation to make it a bridge connecting the different cultures.
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Medicina Tradicional Chinesa , Publicações Periódicas como Assunto , Terminologia como Assunto , TraduçõesRESUMO
This study was aimed to analyze the different proteomes between human acute leukemia (AL) cells and normal white blood cells by proteomic technology in order to lay the basis for diagnosing AL and understanding the mechanism of leukemogenesis. The proteins from AL cells of 40 AL patients identified by FAB classification and proteins from normal lymphocytes and granulocytes of 20 normal volunteers were separated by two-dimensional electrophoresis (2-DE), and the differentially expressed proteins between the two groups were identified by both matrix assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS) and electronspray ionization (ESI)-MS/MS. The results showed that among the differentially expressed proteins between AL cells and normal lymphocytes and granulocytes, some proteins involved in the process of malignant transformation (such as Op18, NM23-H1), cell proliferation (such as PCNA) and apoptosis inhibition (such as tumor necrosis factor inhibitor protein) were found to be up regulated in AL cells. However, some proteins involved in differentiation and physiological functions of normal cells were down regulated in AL cells. It is concluded that there are many events involved in the process of leukemogenesis, expression of some proteins relating to the malignant transformation, cell proliferation and apoptosis inhibition are up-regulated in AL cells. The proteome analysis may provide a new approach to explaining the molecular mechanism underlying the pathogenesis of AL.
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Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Células da Medula Óssea , Química , Patologia , Leucócitos , Química , Proteínas de Neoplasias , Leucemia-Linfoma Linfoblástico de Células Precursoras , Metabolismo , Patologia , ProteomaRESUMO
<p><b>OBJECTIVE</b>To explore the molecular mechanisms of apoptotic NB4 cells induced by the histone deacetylase inhibitor, sodium butyrate(SB).</p><p><b>METHODS</b>SB was exposed to NB4 cells at a final concentration of 1.0 mmol/L. The untreated and treated cells were analysed with FACS and 2-dimensional electrophoresis (2-DE) at 0, 12, 24, 48 and 72 h. The changed protein spots were identified with MALDI-TOF-MS and ESI-TOF-MS/MS.</p><p><b>RESULTS</b>SB induced apoptosis of NB4 cells. Twenty-one changed proteins involving apoptotic signal transduction, immunological regulation, transcriptional control, cellular metabolism, molecular transport and so on were identified. Thirteen of them had been reported to be related to apoptosis.</p><p><b>CONCLUSION</b>SB can induce apoptosis and many functional protein changes in tumor cells. These results pave the way to further explore the anti-tumor mechanism of SB.</p>
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Humanos , Apoptose , Genética , Butiratos , Farmacologia , Linhagem Celular Tumoral , Citometria de Fluxo , ProteômicaRESUMO
<p><b>OBJECTIVE</b>To explore the effect of sodium butyrate (SB) on the expression of costimulatory molecules in acute leukemia cells and its mechanism.</p><p><b>METHODS</b>The expression of CD86 and CD80 was examined on the surfaces of NB4, HL-60, Kasumi-1, U937 and Jurkat cells by flow cytometric analysis after treated by SB or not. Allogeneic mixed lymphocyte reaction was used to evaluate the immunomodulatory effects of cells treated by SB. Activated NF-kappaB was measured with an NF-kappaB assay kit.</p><p><b>RESULTS</b>Up-regulation of CD86 and CD80 at various levels was observed on these leukemia cells treated by SB. The ratio of CD86 expressing cell in NB4 cells treated by 0.5 mmol/L SB was 36.8 times higher than that in control. Up-regulation of NF-kappaB was similar to that of CD86. Allogeneic lymphocyte proliferation was strongly stimulated by the SB treated cells.</p><p><b>CONCLUSION</b>SB can improve the expression of CD86 in acute leukemia cells. NF-kappaB was an important transcription factor involved in the up-regulation of CD86.</p>
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Humanos , Antígeno B7-1 , Antígeno B7-2 , Butiratos , Farmacologia , Linhagem Celular Tumoral , Leucemia , Metabolismo , Patologia , NF-kappa B , Metabolismo , Regulação para CimaRESUMO
To investigate the state and significance of bone marrow angiogenesis in hematological diseases, bone marrow microvascular density (BM-MVD) in plastic-embedded section was examined using acetone-fixed bone marrow tissues embedded in glycol-methacrylate (GMA) resin and by the method of immunohistochemistry. The results showed that bone marrow MVD increased greatly in newly diagnosed hematological malignancies before treatment. BM-MVD in patients with acute leukemia decreased down to the normal range as the controls at the time of complete remission. In the non-remission group, BM-MVD decreased less, but when relapsed it increased again up to the same range as the newly diagnosed hematological malignancies, significant increase of BM-MVD was found in patients with anemia, but in less degree than that in hematological malignancies. It is concluded that bone marrow angiogenesis plays a key role in the pathogenesis and development of hematological malignancy. Antiangiogenic therapy may be able to constitute a novel strategy for the treatment of hematological malignancies including leukemia.
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Humanos , Doença Aguda , Medula Óssea , Patologia , Doenças Hematológicas , Sangue , Patologia , Leucemia , Sangue , Patologia , Microcirculação , Neovascularização Patológica , Sangue , PatologiaRESUMO
Acute myelogenous leukemia (AML) cells are organized in a hierarchical fashion, with only the most primitive rare population (leukemia stem cell, LSC) of AML cells capable of maintaining the leukemic clone. A broad range of studies has indicated that AML results from mutations at the level of the stem cells of AML cells. The changes of cellular and molecular features in these malignant stem cells determine the features of leukemic clone and give rise to different subtypes of AML. LSCs share some similar characteristics with normal hematopoietic stem cells (HSC) including the ability to self-renew, and also have the potential of limited differentiation. LSCs, also have some features that are not found in normal HSC. LSCs have unique phenotype such as CD90-, CD117- and CD123+. Tumor-suppressor protein-death associated protein kinase and interferon regulatory factor 1 were overexpressed in LSCs, but not in normal HSC. Due to a predominantly G0 cell-cycle status, LSCs may not be responsive to conventional chemotherapeutic agents, compared with leukemia blasts. It is proposed that surviving LSCs are a major contributing factor to leukemic relapse. Although LSC population is likely to be drug-resistant, quiescent LSCs are preferentially susceptible to apoptosis induction while sparing normal HSC, with the appropriate stimulus such as proteasome inhibitor MG-132. This article reviewed the data emerging from the study of LSCs, and elucidated the distinct cellular and molecular characteristics of the LSC population, which may shed new light on AML therapy and leukemogenesis study.
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Humanos , Contagem de Células , Ciclo Celular , Leucemia Mieloide Aguda , Patologia , Células-Tronco Neoplásicas , Biologia Celular , Análise de Sequência com Séries de OligonucleotídeosRESUMO
To investigate the significance of duel-color fluorescence in situ hybridization (D-FISH) in monitoring the response to interferon alpha (IFN-alpha) therapy in patients with chronic myeloid leukemia (CML), the D-FISH method was employed to detect the proportion of the interphase nuclei cells with bcr/abl fusion gene in the bone marrow of patients with CML before and after IFN-alpha therapy, and the results were compared with those of bcr/abl fusion mRNA by RT-PCR and Philadephia chromosome (Ph) by conventional cytogenetic analysis. The results showed that the mean detectable rate of bcr/abl fusion gene before and after IFN-alpha therapy was 96.4% and 58.6% respectively, in 22 patients who were bcr/abl-positive before IFN-alpha therapy by D-FISH method, was 94.0% and 70.1% respectively, in 2 patients of Ph-negative before treatment. Major, minor and no responses were seen respectively in 4, 4 and 14 cases from 22 patients by D-FISH method. The results also showed a good correlation with the analysis of RT-PCR and conventional cytogenetics. In conclusion, D-FISH method could directly detect the bcr/abl fusion gene of the interphase cells in bone marrow of patients with CML. It can overcome the defect of conventional cytogenetic methods which analyze only the cells in metaphase and the drawback of RT-PCR unable to quantify the bcr/abl fusion gene. D-FISH provides a more convenient and reliable method for evaluating the degree of clone remission to patients with CML after IFN-alpha therapy.
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Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antineoplásicos , Usos Terapêuticos , Células da Medula Óssea , Metabolismo , Patologia , Proteínas de Fusão bcr-abl , Genética , Hibridização in Situ Fluorescente , Métodos , Interferon-alfa , Usos Terapêuticos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Tratamento Farmacológico , Genética , Patologia , Cromossomo Filadélfia , RNA Mensageiro , Genética , Metabolismo , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Resultado do TratamentoRESUMO
To induce the growth and differentiation of dendritic cells (DCs) from human cord blood, CD34(+) cells isolated from human cord blood by mini-MACS were cultured in a liquid culture system with rhSCF, rhGM-CSF, rhTNF-alpha and rhFL for 10 days. Then the induced cells were characterized by DC's morphological and phenotypic properties. In addition, they stimulated the proliferation of allogeneic T cells and possessed an efficient capacity for initiating T cell-dependent antitumor immune responses in vitro. It is concluded that mature DCs could be obtained from human cord blood CD34(+) cells.