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Expression Of The Novel All-trans Retinoic Acid-related Resistance Gene HA117in Pediatric Tumors

Posted on:2014-11-06Degree:MasterType:Thesis
Country:ChinaCandidate:W J DuanFull Text:PDF
GTID:2254330425454398Subject:Academy of Pediatrics
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Part1Expression of the novel all-trans retinoic acid-related resistancegene HA117in pediatric solid tumorsObjective: This study aimed to detect the protein expression ofHA117coding protein in Hodgkin lymphoma(HL), Non-HodgkinLymphomas(NHL), Nephroblastoma(WT) and Neuroblastoma(NB), andcompare with P-glycoprotein (P-gp) expression in these tumors in order toexplore the significance of HA117coding protein expression in commonpediatric solid tumors.Methods: Immunohistochemistry was performed to detect theexpression of HA117coding protein and P-gp in26cases of HL,24cases ofNHL,32cases of WT and27cases of NB, and the relationship between theexpression of HA117coding protein and P-gp and the clinical characteristicsof these children was evaluated.Results: In HL, NHL, WT, and NB the positive expression rate ofHA117was65.4%,58.3%,81.3%, and74.1%, and that of P-gp was57.7%,70.8%,65.6%, and66.7%, respectively; HA117coding protein expressionwas closely related to the clinical stage of HL(P=0.004) and to the International Prognostic Index(IPI) score, mediastinal lesions, and clinicalstages of NHL (P=0.01, P=0.03, P=0.01); HA117coding protein expressionin WT was higher than in adjacent normal tissues, but there was notstatistical significant (P=0.21, P=1.00); in NB, two proteins were markedlyhigher than that in normal tissues (P=0.002, P=0.003) and closely associatedwith histological type and lymph node metastasis(P<0.05). Spearmancorrelation analysis revealed that HA117coding protein expression was notcorrelated with P-gp in these four tumors.Conclusion: This suggests that HA117coding protein and P-gp mightbe an important resistance gene in pediatric solid tumors and that themechanism underlying the resistance to All-trans retinoic acid (ATRA)conferred by HA117is different from that of P-gp. Part2Expression and significance of HA117, bcl-2and P-gp inchildren with acute leukemiaObjective: To explore the expression levels of HA117coding protein,B cell leukemia-2(bcl-2) and P-glycoprotein (P-gp) in bone marrowmononuclear cells (BMMNC) with childhood acute leukemia, and evaluate their clinical significance.Methods: The expression of HA117coding protein, bcl-2and P-gp in70AL patients and15nonmalignant hematologic patients were measured byImmunohistochemistry(S-P).Results:(1) The positive expression rates of HA117coding protein,bcl-2and P-gp was52.9%、62.9%'35.7%in AL patients; the expressionof HA117in acute myeloid leukemia (AML) and acute lymphoblastic1eukemia(ALL) patients was higher than that of the control group(P=0.048、 P=0.031); the expression rates of HA117coding protein, bcl-2and P-gp in AML and ALL patients had no significant difference(P>0.05).(2)Compared initially diagnosed patients with the control goup, uncompletedremission patients with completed remission patients, there were significantdifferent about the expression of HA117coding protein(P<0.05); thecompleted remission patients had higher expression of HA117than that ofthe control group, the uncompleted remission patients had higher expressionof HA117than that of initially diagnosed patients, but there was nosignificant difference(P>0.05).(3) The complete remission(CR) rate wasrelated to the positive expression of HA117coding protein(P=0.029).(4) Itshowed correlation between HA117coding protein and bcl-2expression inAL patients(P=0.001, r=0.577).Conclusion: New genes HA117may be involved in the drug resistanceof children with acute leukemia, and a important indicator of prognostic; the resistance of HA117gene may be associated with apoptosis related gene,which may be present in synergy in the tumors growth.
Keywords/Search Tags:HA117coding protein, P-gp, pediatric solid tumorschildhood leukemia, HA117, P–gp, bcl-2
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