The Effect and Mechanism of Novel Telomerase Inhibitor Nilo 22 on Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the cytotoxic effect and its mechanism of the micromolecule compound on the leukemia cells.@*METHODS@#The cytotoxic effects of 28 Nilotinib derivatives on K562, KA, KG, HA and 32D cell lines were detected by MTT assays, and the compound Nilo 22 was screen out. Cell apoptosis and cell cycle on leukemia cells were detected by flow cytometry. The effect of compound screened out on leukemogenesis potential of MLL-AF9 leukemia mice GFP@*RESULTS@#Nilo 22 serves as the most outstanding candidate out of 28 Nilotinib derivatives, which impairs leukemia cell lines, but spares normal hematopoietic cell line. Comparing with Nilotinib, Nilo 22 could induce the apoptosis of GFP@*CONCLUSION@#Nilo 22 shows a significant cytotoxic effect on mice and human leukemia cells, especially for drug resistance cells. Nilo 22 is a promising anti-leukemia agent to solve the common clinical problems of drug resistance and relapse of leukemia.

Literature Analysis of the Selection of Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia Patients with BCR-ABL35INS Mutation / 中国药房

OBJECTIVE： To provide reference for reasonable selection of tyrosine kinase inhibitors （TKI） in chronic myeloid leukemia （CML） patients with BCR-ABL35INS mutation. METHODS： Using “BCR-ABL insertional mutation” “ABL1 35ins mutation” “BCR-ABL c.1423_1424ins35” “ABL1 p.C475Tyrfs*11” as keywords， retrieved from CNKI， Wanfang database， Medline and COSMIC database， BCR-ABL35INS mutation CML patients were summarized and analyzed in respects of general information and treatment （treatment plan， patient compliance and drug withdrawal）， therapeutic effect （molecular biological mitigation and disease progress） and safety data （ADR） during 2007-2018. RESULTS： Totally 9 related literatures were included， involving 70 patients with BCR-ABL35INS mutation， all of them were foreign cases. Among them， 39 cases were male and 31 cases were female， with a median age of 49.2 years. The median time from the diagnosis of CML to the detection of BCR-ABL35INS mutation was 19 months. After detecting gene mutation， 39 cases were treated with imatinib （initial dose of 400 mg， po， once a day）， and molecular biological remission was achieved in 5 patients （12.9％）； 15 cases （38.5％） had molecular biological response but had disease progression； 8 patients （20.5％） had no response. Seventeen patients were treated with dasatinib （100 mg， po， once a day or 2 divided dose）， and 8 cases （47.1％） achieved molecular biological response. Twenty-one patients were treated with nilotinib （400 mg， po， 2 divided dose）， and 3 patients （14.3％） achieved molecular biological response； 2 patients achieved molecular biological response， but the disease progressed. Seven， three and seven of these patients stopped taking drugs due to adverse reactions， accounting for 17.9％， 17.6％ and 33.3％ respectively. All the ADRs were classified as grade 3-4 of the National Cancer Institute’s Common Terminology Criteria for Adverse Events， and most of them were hematological toxicity. CONCLUSIONS： CML patients with BCR-ABL35INS mutation are less likely to achieve molecular response on imatinib therapy but are more sensitive to dashatinib. In the course of treatment， we should strengthen the monitoring of blood system and other related indicators to ensure the safety and effectiveness of drug use.

ADAR1 Knockout Inhibits Notch1-induced T-ALL in Mice / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the effect of ADAR1 on the occurrence and development of mouse T cell acute lymphoblastic leukemia (T-ALL).</p><p><b>METHODS</b>Lck-Cre; ADAR1lox/lox mice were generated through interbreeding. The lineage-cells of Lck-Cre; ADAR1lox/lox mice and the control were enriched respectively by the means of MACS, and the lin- cells were transfected with retrovirus carrying MSCV-ICN1-IRES-GFP fusion gene. Then the transfection efficiency was detected by the means of FACS, and the same number of GFP+ cells were transplanted into lethally irradiated recipient mice to observe the survival of mice in 2 recipient group after transplantation.</p><p><b>RESULTS</b>T cell-specific knockout ADAR1 mice were generated, and Notch1-induced T-ALL mouse model was established successfully. The leukemia with T-ALL characteristics occured in the mice of control group, but did not in the ADAR1 kmockout mice after transplantation.</p><p><b>CONCLUSIONS</b>ADAR1 plays a key role in the incidence and development of Notch1-induced T-ALL.</p>

Advances in the study of Allium macrostemon Bunge / 中国中药杂志

<p><b>OBJECTIVE</b>To review the progress in the study of chemical ingrediens, pharmacological effects and clinical application of Allium macrostemon Bunge.</p><p><b>METHOD</b>Documents of experimental and clinical study on A. macrostemon in recent 10 years were consulted and summarized.</p><p><b>RESULT</b>A. macrostemon had many active ingredients, pharmacology effects and wild clinical application.</p><p><b>CONCLUSION</b>The results provide a rational foundation for the further development and utilization of A. macrostemon.</p>

Effects of cyproheptadine on hypothalamus-pituitary-gonad axis and calmodulin gene expression in rats / 中国药理学与毒理学杂志

AIM To study whether cyproheptadine(Cyp) affects endocrine functions in reproductive system with gender difference. METHODS Sixty SD rats were randomly distributed into 3 groups according to gender, respectively, and they were administered NS(5 mL*kg-1*d-1), Cyp 2.4, 4.8 mg*kg-1*d-1 accordingly by ig for 14 d or 21 d. The serum levels of luteinizing hormone(LH), follicle stimulating hormone(FSH), testosterone(T), progesterone(P), estrodiol(E2) were measured by radio-immunoassay and the ultrastructure of gonadotropin-releasing hormone(GnRH) cells, gonadotropin cells, Leydig cells, Sertoli cells, luteal cells, granulocytes and so on were observed by electronmicroscopy and microscopy. The calmodulin(CaM) mRNA expression in hypothalamus-pituitary-testis axis(HPTA) was detected by reverse transcriptase-polymerase chain reaction. RESULTS Cyp(2.4 mg*kg-1*d-1×14 d, ig) increased serum LH concentration while decreased serum FSH, P concentrations in female rats. Cyp(4.8 mg*kg-1*d-1×14 d, ig)increased serum LH, T concentrations in males, and increased serum LH concentration while decreased serum FSH, E2 and P concentrations significantly in females. The retrograde changes of ultrastructure were observed in part of gonadotropin and ovary endocrine cells, while a stimulating one in testis endocrine cells. CaM mRNA expression levels were elevated in testis but not in hypothalamus and pituitary in male rats. CONCLUSIONCyp had a negative effect on endocrine function in females, but a positive one in males. The ultrastructure showed relevant changes in target gland. Cyp promoted CaM mRNA expression in testis,which had close connections with Cyp′s stimulative effect in HPTA.

Effects of scorpion venom active peptides on platelet aggregation, thrombosis in carotid artery and plasma 6-keto-PGF_(1?) and TXB_2 in rabbits and rats / 中成药

Objective: To investigate the mechanism of scorpion venom active peptides(SVAPs) on platelet aggregation. Methods: Platelet aggregation in vivo and vitro was determined by turbidimetry. Carotid thrombosis model was induced by electrostimulation. The determination of 6 keto PGF 1 and TXB 2 were performed by radioimmunoassay. Results: SVAPs 0.125,0.25,0.5mg?ml -1 significantly inhibited the rabbit platelet aggregation triggered by thrombase 0.03u.ml -1 , ADP 10u.ml -1 in vitro( P

Isolation of Calcium-Tolerant Cardiomyocytes from Rats / 中国药房

OBJECTIVE:To investigate the method for rapid and effective isolating of calcium-tolerant cardiomyocytes(CTC) from rats. METHODS: CTC were obtained by retrograde perfusion using modified Langendorff heart perfusion apparatus. After incubation of cardiomyocytes in KB solution, the ion currents were recorded with patch-clamp technique in whole-cell mode. RESULTS: Of the whole isolated cells, 70% were survival. Of which, 80% were CTC. A typical outward potassium current was recorded. CONCLUSIONS: A large number of CTC with normal electrophysiological characteristics can be obtained by mastering the digestion time based on variation of perfusion pressure and keeping all the factors in cell isolation under control.

Experimental research of anti-inflammatory action and immunoregulation on rabbit's brain phospholipids / 中国药理学通报

Rabbit's brain phospholipids (RBP) 100~200 mg ?kg-1 ip or sc showed anti-inflammatory action on four kind of acute inflammatory animal models. Cephalin and Lecithin were the effective component of antiin-flammatory action on the acute inflammatory animal model. But RBP did not show antiinflam-matory action on the chronic proliferative inflammatory model. RBP increased blood carbon particle clearance, perfaneal macrophage phagocytosis and enhanced lymphocyte proliferation,hemolysin antibody in normal and immunode-pression animal. RBP increased the cGMP content in the liver tissue of immunodepression animal, 0. 1~1 mg ?L-1 RBP promoted proliferation but 100 mg ?L-1 RBP inhibited proliferation induced by PHA in vitro on human lymphocyte.

Effects of cyproheptadine on pituitary-adrenalcortex axis in rats and its mechanism / 中国药理学通报

AIM To study the effects of cyproheptadine (Cyp) on endocrine functions and pituitary adrenalcortex axid in rats and its mechanism METHODS Radioimmunoassay(RIA)was used to measure the serum levels of ACTH and cortisone Ultramicrostructure of the ACTH cells and adrenalcortex and the calmodulin(CaM) mRNA expression of the pituitary and adrenalcortex were observed by electron microscope and the quantity PCR technique RESULTS Cyp 2 3 and 4 6 mg?kg -1 ?d -1 , ig for 14 d had significantly reduced the serum levels of ACTH and cortisone ( P

THE mRNA EXPRESSION OF CALCITONIN GENE RELATED PEPTIDE RECEPTORS AND THEIR ACTIVITY MODIFYING PROTEINS IN PERIAQUEDUCTAL GRAY OF RAT / 解剖学报

Objective In the present study we used real-time quantitative RT-PCR to measure the relative expression levels of CGRP,CRLR,RDC-1,RAMP1-3 in periaqueductal gray(PAG)of intact rats. Methods With ?-actin as an endogenous control,write down the C T value and calculate the relative amount of every sample against its endogenous control. Results The results showed the specific amplification of CGRP,CRLR,RAMP1-2 in PAG of rats.Furthermore,the expression of CGRP and RAMP1 is the highest,that of CRLR is higher and the RAMP2 is low;whereas no band is detected in RDC-1 and RAMP3. Conclusion These findings suggest the specific expression of CGRP,CRLR,RAMP1 and RAMP2 mRNA and indicate their functional role in the modulation in PAG of intact rats.