This study was aimed to investigate the expression, protein localization and function of Ahi-1 gene and its encoding protein in Jurkat cells. The expression of Ahi-1 mRNA and protein were measured by Northern and Western blot respectively. The plasmid containing prototype Ahi-1 was constructed and transfected into Jurkat cells. The Jurkat-A and Jurkat-C cells which either over-expressed the prototype Ahi-1 or not were obtained by selection with G418. The proliferation of the cells was assayed by XTT. The colony formation potential of the leukemia cells was checked by semisolid agarose culture. The results showed that three different transcripts of Ahi-1 (6.5,4.2 and 2 kb) were expressed in peripheral blood lymphocytes (PBLs), Jurkat and HUT78 cells. Ahi-1 protein with 140 kD localized in the cytoplasm majorly while traceless in the nucleus of Jurkat cells and PBLs from normal donor. Ahi-1 protein with 120 kD could be detected in the nucleus fraction of PBLs. Very low level of Ahi-1 protein with 120 kD was expressed in Jurkat cells. Up-regulating expression of Ahi-1 protein with 140 kD in the nucleus was found in Jurkat cells after exposure to meisoindigo, cytarabine, homoharringtonine, methotrexate and etoposide, down-regulating expression of Ahi-1 with 140 kD in the cytoplasm was observed after treatment with meisoindigo. The growth and colony formation potential were inhibited in the Jurkat-A cells, as compared to Jurkat-C cells. Total c-myb and phosphorylated AKT protein were continuously expressed in the Jurkat-C and Jurkat-A cells at similar level, but more phosphorylated c-myb was observed in Jurkat-A cells. It is concluded that three different transcripts of Ahi-1 at 6.5, 4.2 and 2 kb are detected in Jurkat cells; the Ahi-1 protein with 140 kD majorly expresses in the cytoplasm fraction and exposure to multiple chemotherapeutic compounds increased its expression in nucleus fraction. Over-expression of exogenous Ahi-1 can not only inhibit the growth and colony formation potential of Jurkat cells, but also induce the phosphorylation of c-myb in Jurkat cells.
Adaptor Proteins, Signal Transducing ; genetics ; Cell Proliferation ; Gene Expression ; Humans ; Jurkat Cells ; Plasmids ; Proto-Oncogene Proteins c-myb ; metabolism ; RNA, Messenger ; genetics ; Transfection

Endothelial to mesenchymal transition(EndMT) plays a major role during organism development, and also contributes to several adult cardiovascular diseases.EndMT-derived fibroblast-like cells are common in atherosclerotic lesions.Pro-atherosclerosis factors, such as oxidative stress, hypoxia, inflammatory cytokines and oscillatory fluid shear stress can promote EndMT.EndMT is closely associated with plaque calcification, and unstable and ruptured plaque phenotype that may prone to cause clinical events.EndMT may be another key step in the prevention and treatment of atherosclerosis.Here, we reviewed the role played by endothelial-to-mesenchymal transition(EndMT) and its key regulators in atherosclerosis.

Acute Disease ; Adult ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Prognosis

Adult ; China ; Humans ; Leukemia, Lymphoid ; diagnosis ; therapy ; Prognosis

OBJECTIVETo evaluate the safety and therapeutic effect of high-dose daunorubicin-based (HD-DNR) chemotherapy in the treatment of acute leukemia (AL).

METHODSThe clinical data of 25 AL patients, including 14 cases for induction chemotherapy, 8 for consolidation chemotherapy and 3 for reinduction therapy, which were treated with HD- DNR (DNR dosage of 90 mg/m(2)× 3 d) between June 2010 and August 2012 in our hospital were retrospectively analyzed, the adverse reaction of chemotherapy, especially cardiac toxicity and therapeutic effect were evaluated.

RESULTSMost of the adverse reactions were mild, including cardiac toxicity, and no patient discontinued therapy because of HD-DNR related toxicities. Grade 3 or higher adverse reactions occurred only in the infection (56%) and diarrhea (12%). Withdrawal or dose reduction due to strong adverse reactions was not observed in all patients. Adverse reactions of infections (92%), lower ejection fraction(52.6%), diarrhea (48%), nausea (36%), vomiting (36%), dental ulcer (36%) and myocardial ischemia (32%) were relatively more common. The median time of neutrophil count reached to ≥ 0.5 × 10(9)/L and platelet ≥ 20 × 10(9)/L were both 21 days(ranged 9-31 and 9-38 days). Nine patients were complicated with infections before chemotherapy and 14 after chemotherapy, mainly occurred in gastrointestinal tract and respiratory system. Gastrointestinal, liver and kidney toxicity was slight. The cardiac ejection decreased in 10 cases, but only 1 reached grade 2 without clinical symptoms. Of the 14 AL patients for induction chemotherapy, 13 achieved hematological complete remission. Eight patients received HD-DNR as consolidation chemotherapy remained complete remission, while 3 refractory/relapsed patients remained non-remission.

CONCLUSIONThe adverse reaction of HD-DNR based chemotherapy for AL treatment was mild, no obvious cardiac adverse reaction occurred. The treatment dose of DNR at 90 mg/m(2) × 3 d can be safely and effectively used to treat acute leukemia.

Acute Disease ; Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; therapeutic use ; Daunorubicin ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Humans ; Leukemia ; drug therapy ; Male ; Middle Aged ; Retrospective Studies ; Young Adult

To study the expression of angiotensin converting enzyme 2 (ACE2) and angiotensin (Ang) 1-7 specific receptor Mas protain in renal blood vessels of metabolic syndrome ( MS) rats and its anti-oxidative effect. A total of 80 male SD rats were divided into four groups: the normal control group (NC, the same volume of normal saline), the MS group (high fat diet), the MS + Astragali Radix group (MS + HQ, 6 g x kg(-1) x d(-1) in gavage) and the MS + Valsartan group (MS + XST, 30 mg x kg(-1) x d(-1) in gavage). After four weeks of intervention, their general indexes, biochemical indexes and blood pressure were measured; plasma and renal tissue Ang II, malondialdehyde (MDA) and superoxide demutase (SOD) levels were measured with radioimmunoassay. The protein expressions of Mas receptor, AT1R, ACE and ACE2 were detected by western blot analysis. According to the result, compared with the NC group, the MS group and the MS + HQ group showed significant increases in systolic and diastolic pressures, body weight, fasting glucose, fasting insulin, triglycerides, free fatty acid and Ang II level of MS rats (P < 0.05). The MS + XST group showed notable decreases in systolic and diastolic pressures than that of the MS group. The MS group showed significant increases in the SOD activity and NO level and decrease in the MDA level after being intervened with Astragali Radix. ACE and AT1R protein expressions in renal tissues of the MS group were higher than that in the NC group, but with lower ACE2 and -Mas receptor expressions (all P < 0.05). Compared with the MS group, the MS + HQ group showed significant increase in Mas receptor expression in renal tissues, whereas the MS + XST group showed notable decrease in AT1R (all P < 0.05). In conclusion, Astragali Radix can increase the Mas receptor expressions in renal tissues, decrease ACE expression and change local Ang II, MDA, NO and SOD in kidneys, so as to protect early damages in renal tissues.
Angiotensin I ; metabolism ; Animals ; Astragalus Plant ; chemistry ; Blood Glucose ; metabolism ; Blood Pressure ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Kidney ; drug effects ; injuries ; metabolism ; Male ; Malondialdehyde ; metabolism ; Metabolic Syndrome ; drug therapy ; genetics ; metabolism ; physiopathology ; Peptide Fragments ; metabolism ; Peptidyl-Dipeptidase A ; genetics ; metabolism ; Proto-Oncogene Proteins ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; genetics ; metabolism ; Signal Transduction ; drug effects

Objective of this study was to detect the expression of HtrA2 and WT1 mRNA in acute myeloid leukemia (AML) and investigate the relationship of their expression levels with clinical variates and correlation between them. The expression levels of HtrA2 and WT1 were measured by RQ-PCR in bone marrow cells in 104 newly diagnosed AML patients and leukemia cell lines (K562, HL-60, NB4, Kasumi-1, U937), and the relationship between expression level and clinical parameters (age, sex, WBC count, diagnosis and prognosis) was investigated. The results showed that (1) the expression of HtrA2 gene in newly diagnosed AML was lower than that of the normal controls (P < 0.01), while expression of WT1 gene in newly diagnosed AML was higher than that of the normal controls (P < 0.01), the expression levels of HtrA2 and WT1 genes both did not correlate with age, sex and WBC counts of patients. There were no significant difference of HtrA2 gene expression between different NCCN prognosis group, while WT1 gene expression in better-risk group was significantly lower than that in intermediate-risk group (P = 0.003). The HtrA2 expression level rose after treatment in both CR group and non-CR group (P < 0.05), while WT1 expression level significantly decreased after treatment only in CR group (P < 0.01). Negative correlation between HtrA2 and WT1 expression was also observed (r = -0.249, P = 0.011). It is concluded that the low expression of HtrA2 and high expression of WT1 are closely related with occurrence and development of acute leukemia, so up-regulating expression of HtrA2 and interfering expression of WT1 may become the targets for leukemia therapy in the future.
Adolescent ; Adult ; Aged ; Cell Line, Tumor ; Female ; High-Temperature Requirement A Serine Peptidase 2 ; Humans ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Male ; Middle Aged ; Mitochondrial Proteins ; genetics ; metabolism ; Serine Endopeptidases ; genetics ; metabolism ; WT1 Proteins ; genetics ; metabolism ; Young Adult

OBJECTIVETo analyze the treatment outcome and impact of cytogenetic abnormalities on the response and survival of acute monocytic leukaemia (AMOL) patients received (m)HAD regimen as induction chemotherapy.

METHODSSeventy-nine AMOL patients were treated with (m)HAD regimen as induction therapy (HHT 2 mg/m(2), d 1-7; Ara-C 100 mg/m(2), d 1-7 and increasing to 1.5 g×m(-2)×(12 h)(-1), d 5-7 in some patients; DNR 40 mg/m(2), d 1-3). The treatment outcome and prognostic factors were analyzed.

RESULTS(1) The complete remission (CR) rate was 79.7% (63/79), partial remission (PR) rate was 6.3% (5/79), overall rate was 86.0%. (2) The chromosome karyotypes were analyzed in 75 patients, of whom 43 with normal karyotypes (NCR) and 30 abnormal karyotypes (ACR). For the cytogenetic prognostic groups, 49 patients were intermediate, 18 poor and 6 unknown. The CR, 1-year and 3-year overal survival (OS) rates in NCR group were significantly higher than those in ACR group (P < 0.05); but there was no significantly statistical difference in disease free survival (DFS) between the two groups (P > 0.05). The CR, 1-year OS, 3-year OS and 1-year DFS and 3-year DFS rates in intermediate prognostic group were significantly higher than those in poor prognostic group (85.7% vs 61.1%, 75.9% vs 51.3%, 65.4% vs 25.6%, 82.2% vs 66.7%, and 77.9% vs 26.7%, respectively) (P < 0.05). (3) Chromosome karyotype and the number of consolidation therapy courses had more important influence on survival in COX analysis.

CONCLUSION(m)HAD regimen as induction chemotherapy for AMOL patients achieves a high CR rate. It has an important influence on survival for the patients to received adequate consolidation therapy. The frequency of cytogenetic abnormalities in AMOL is similar to that in other AMLs. The prognosis of AMOL patients with chromosome karyotype in intermediate prognostic group is significantly better than that in poor prognostic group.

Adolescent ; Adult ; Female ; Humans ; Induction Chemotherapy ; Karyotype ; Leukemia, Monocytic, Acute ; drug therapy ; genetics ; Male ; Middle Aged ; Neoadjuvant Therapy ; Prognosis ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate factors that affect survival and prognosis of acute myeloid leukemia (AML)-M(4).

METHODSSeventy AML-M(4) patients were divided into three groups, neither eosinophilia nor inv(16)\[Eos(-)\], eosinophilia with inv (16)\[Eos(+) inv(16)(+)\], and eosinophilia with no inv(16)\[Eos(+) inv(16)(-)\]. Clinical features, immunophenotype, chromosome karyotype, overall survival (OS) and relapse-free survival (RFS) were analyzed.

RESULTSThe total complete remssion (CR) rate was 85.7%, CR rate after the first course of induction therapy was 71.4%. The median OS was 20 (1.2 - 162.4) months, and median RFS 78.0 (1.2 - 129.5) months. The 3 and 5 year OS rates were 42% and 42%, and 3 and 5 year RFS rates were 59% and 54%, respectively. The CR rate, CR after the first course of induction therapy and the median OS for the Eos(-) group were 76.9%, 61.5% and 11.2 (1.2 - 162.4) months; for the Eos(+) group were 96.8%, 89.6% and did not reach; for the Eos(+)inv16(+) group were 100%, 94.4% and did not reach; and for the Eos(+) inv(16)(-) group were 91.7%,69.2% and 14.3 months respectively. The statistical assay showed significant difference between Eos(+)inv(16)(-) and Eos(+)inv(16)(+) groups in OS. The Eos(+) patients present with early onset and low count of platelets.

CONCLUSIONEosinophilia emerged as a favorable prognostic factor, and the concomitant presence of both eosinophilia and inv(16) is associated with a significantly favorlable prognosis.

Humans ; Karyotype ; Karyotyping ; Leukemia, Myeloid, Acute ; genetics ; Prognosis ; Survival Rate