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OBJECTIVE@#To explore the expression of cellular apoptosis susceptibility protein （CAS） in acute myeloid leukemia （AML） and its correlation with clinical characteristics.@*METHODS@#The expression of CAS in bone marrow tissue of 54 patients with AML and 24 patients with non-hematological malignant diseases was detected by Western blot and immune-histochemical method, and compared between AML group and control group. Also the relationship of CAS expression in AML and sex, age, WBC count, Hb, platelet count, bone marrow blast cell ratio, ki-67 index, cytogenetic and molecular biological prognostic risk stratification, extramedullary infiltration and other clinical characteristics was analyzed.@*RESULTS@#Western blot showed that the expression of CAS protein in bone marrow biopsies of AML patients was significantly higher than that in control group (P<0.05). Immune-histochemical method revealed that CAS was mainly located in the cytoplasm in both AML group and control group. Among 54 AML patients, 14 patients (25.9%) showed high expression of CAS, while all the 24 patients in the control group showed low expression of CAS. The high expression rate of CAS in AML patients was significantly higher than that in the control group (P<0.05). There were statistically significant differences in prognostic risk stratification and the remission rate of the first chemotherapy between CAS high expression group and CAS low expression group in AML (P<0.05). The proportion of high risk patients and unremission patients after the first chemotherapy in CAS high expression group were significantly higher than those in CAS low expression group (57.1% vs 27.5%, 30.8% vs 7.9%), while the proportion of low risk patients and complete remission patients after the first chemotherapy were significantly lower than those in CAS low expression group (14.3% vs 37.5%, 53.8% vs 84.2%). In AML patients, the ki-67 index of bone marrow tissue in CAS high expression group was higher than that in CAS low expression group (60% vs 50%) (P<0.05).@*CONCLUSION@#CAS is localized in cytoplasm in both AML and non-hematological malignant diseases, and its expression increases in AML. CAS is related to the risk stratification of cytogenetics and molecular biology, the remission rate after the first chemotherapy and ki-67 index in AML, which suggests that CAS may be involved in the occurrence and development of AML.
Subject(s)
Humans , Bone Marrow/metabolism , Cellular Apoptosis Susceptibility Protein/metabolism , Ki-67 Antigen/metabolism , Leukemia, Myeloid, Acute/drug therapy , Prognosis , Remission InductionABSTRACT
Objective To analyze the relationship of CAS protein expression with proliferative index, apoptosis index and clinical parameters in breast cancer tissues. Methods Immunohistochemistry for CAS expression, ki-67 (proliferative index) and TUNEL (apoptosis index) were examined in 20 usual ductal hyperplasia (UDH), 20 atypical ductal hyperplasia (ADH), 10 ductal carcinoma in situ (DCIS), 53 invasive ductal carcinoma(IDC) and 14 normal breast tissues. Results CAS expression increased in order in the normal breast tissues, UDH, ADH, DCIS and IDC, with the positive rates of CAS protein being 14.3% (2/14), 25.0% (0/20), 40.0% (8/20), 60.0% (6/10), and 75. 5% (40/53), respectively {χ2 = 29. 382, P = 0. 000). CAS protein expression was correlated with histological grade, mitotic activity, and lymph node metastasis of IDC (P<0. 01, P<0. 05), and not with patient age, tumor volume or grade. CAS protein expression was positively correlated with ki-67 index (r = 0. 439, P = 0. 003), and not with the apoptosis index (r=0. 248, P = 0. 083). Conclusion CAS protein expression is associated with cell proliferation index in breast cancer tissues.
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Objective To analyze the apoptosis-related spots like protein (ASC) and caspase -1 in HCC and adjacent noncancerous tissues and its clinical significance. Methods ASC and Caspase 1 were determined with immunohistochemistry LSAB method and the various indexes were analyzed in 30 cases of liver cancer and adjacent tissues which did not receive preoperative radiotherapy and chemotherapy. Results The positive rate of ASC in HCC and adjacent noncancerous tissues was 10.00% (3/30) and 73.33% (22/30). Positive rate between the groups had significant difference (P＜0.01). Caspase-1 positive rate had significantly difference between the groups (23.33% (7/30) vs. 66.67% (20/30), P＜0.01). ASC and the two indicators of Caspase-1 expression in cancer tissues were low, but no significant correlations between the two groups (P＞0.05). ASC and the two indicators of Caspase-1 expression in adjacent tissue were significantly increased, and it showed a very significant correlation (r＝0.722,P＜0.01). Conclusions ASC, Caspase-1 expression in liver cancer were low expressed, and significantly lower than the adjacent tissues, which suggested that ASC and Caspase-1 were closely related to the occurrence and development of the apoptosis of liver cancer, and it might be used as diagnosis and treatment of targets in liver cancer.
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Objective To study the activation effect of HBV RNase H protein on the transcription of cellular apoptosis susceptibility gene (CAS). Methods The promoter of DNA sequence of CAS gene was identified in GenBank by bioinformatics and amplified from HepG2 genome by PCR using sense (5′-GGTACCCGATTACATGTTGTACATGAAGG-3′) and antisence (5′-CTCGAGGCTGAGTTCCATTGCTATAG-3′) primers. As these primers contained Kpn I and Xho I recognition sites on their respective 5′-ends, the amplified DNA fragments were tested by sequencing and then subcloned into Kpn I/Xho I sites of pCAT3-Basic reporter vector by routine molecular biological methods. The reconstructed plasmid named pCAT3-CASp was identified by enzyme digestion of Kpn I/Xho I, in which the expression of chloramphenical acetyltransferase (CAT) was under the control of the promoter of CAS. The HepG2 cells were transfected by pCAT3-CASp, and then co-transfected by pCAT3-CASp and pcDNA3.1(-)-RH plasmids. At the same time, the empty pCAT3-basic and pCAT3-TXNRD1p were transfected (self-contructed by the authors) as controls. After 24h culturing, cells were collected and the expression of CAT activity was detected by ELISA according to the manufacturer′s protocol. Results The optical density of expression of CAT of pCAT3-CASp was 0.043 by ELISA, in contrast, the optical density of expression of pCAT3-Basic was 0.024. The expression of CAT in co-transfection of pCAT3-CASp and pcDNA3.1(-)-RH(0.065) was 1.5 times as higher as pCAT3-CASp plasmid (0.043), and 2.7 times as higher as pCAT3-Basic. Conclusions The CAS gene promoter identified in present study has transcription activity and HBV RNase H protein may activate the expression of CAS gene.