Abstract Acute myeloid leukemia (AML) is a commonly hematological malignancy with feature of rapidly increased immature myeloid cells in bone marrow. The anti‐tumor activity of matrine has been reported in various cancers. However, the functional role of matrine in AML progression still needs to be studied. Cell growth, apoptosis and cell cycle arrest in AML cells were evaluated using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay, 5‐ethynyl‐2′‐deoxyuridine (EdU) assay and flow cytometry, respectively. The levels of adenosine triphosphate (ATP)/adenosine diphosphate (ADP) ratio, lactate production and glucose consumption were detected to evaluate glycolysis. Dual‐luciferase reporter assay was conducted to determine the relationships between phosphoinositide‐dependent kinase 1 (PDK1) and microRNA‐495‐3p (miR‐495‐3p)/microRNA‐543 (miR‐543) in AML cells. The results showed that matrine inhibited cell proliferation, glycolysis, and accelerated cell apoptosis and cell cycle arrest in AML cells. MiR‐495‐3p/miR‐543 was lowly expressed, and PDK1 was highly expressed in AML. Functionally, both miR‐495‐3p and miR‐543 could reverse the effects of matrine on cell proliferation, glycolysis, apoptosis and cell cycle arrest in AML cells. Mechanistically, miR‐495‐3p/miR‐543 directly targeted PDK1, and the inhibition impacts of miR‐495‐3p/miR‐543 on AML progression could be rescued by PDK1 overexpression. Moreover, matrine also could regulate PDK1 expression to suppress AML progression. Besides, matrine modulated miR‐495‐3p/miR‐543/PDK1 axis to inhibit the Wnt/β‐catenin pathway. In summary, matrine hampered the progression of AML through targeting miR‐495‐3p and miR‐543 to attenuate PDK1 expression, thereby repressing the Wnt/β‐catenin pathway.
OBJECTIVE To investigate the effect of BRCA1/2promoter methylation status,clinical and pathological features on survival in patients with hereditary breast cancer.METHODS Seventy-four patients with breast cancer were diagnosed by pathology from January 1st,2005 to January 1st,2011 of breast surgery,Tumor Hospital Affiliated to Xinjiang Medical University.The methylation status of BRCA1/2gene promoter were detected in all the 74 patients.The related clinicopathological characteristics were collected(age,genetic background,tumor size,lymph node metastasis,molecular subtypes,tumor grade,clinical stage).Cox regression model was used to analyze the influencing factors of survival time.RESULTS The rate of BRCA1/2promoter methylation was 32.43%(24/74).BRCA1 gene promoter methylation rate was 25.68%(19/74),BRCA2 gene promoter methylation rate was 6.76%(5/74),the difference was statistically significant(χ2=9.747,P=0.002).Univariate analysis showed that tumor size(χ2=15.927,P<0.001),lymph node metastasis(χ2=20.490,P<0.001),clinical stage(χ2=39.589,P<0.001)and molecular subtypes(χ2=15.093,P=0.001)were the key factors influencing the survival time,the difference was statistically significant.Multivariate analysis showed that clinical stage and molecular subtypes were the major risk factors for survival time(The OR values were 1.436and2.181).CONCLUSIONS BRCA1/2promoter methylation status of hereditary breast cancer is not a major factor impacting survival time.HER-2over expression and late clinical stage suggests the poor prognosis in hereditary breast cancer.
Objective: To explore the expression and its clinical significance of hormone receptor and cerbB-2 in breast cancer tissue received neoadjuvant chemotherapy. Methods: The estrogen receptor(ER), progesterone recepter(PR) and cerbB-2 in breast cancer tissue of 89 patients received neoadjuvant chemotherapy were detected by immunohistochemical method, and analysed the relation with response of neoadjuvant chemotherapy. Results: The overall response rate of neoadjuvant chemotherapy on breast cancer was 89. 9%, of which the complete response was 32. 6%, partial response was 57. 3%, pathological complete response was 17. 9%, disease stable 10. 5%. Hormonal receptor expressions was significantly related to treatment response,the pathological complete response rate was 27. 2% in ER/PR negative tumors,but it was 7.1% in the positive tumors (P0. 05). No correlation was observed between the treatment response and cerbb-2 expression. Conclusions: There has higher sensitivity to neoadjuvant chemotherapy in hormonal receptor negative tumors. The hormone receptor of breast cancer in neoadjuvant chemotherapy may be provide important index in decision sensitivity of chemotherapy and clinical evaluation.
Objective:To compare adverse event profiles of three weekly combination of Docetaxel,Doxorubicin and Cyclophosphamide (TAC) versus sequential Doxorubicin/cyclophosphamide then Docetaxel (AC→T) in adjuvant chemotherapy of breast cancer patients after breast operation.Methods:A total of 60 patients after breast cancer surgery were recruited and randomized to two chemotherapy regiments between May 2007 and October 2008 in Breast Surgery Department in Affliated Tumor Hospital of Xinjiang Medical University.Two adjuvant chemotherapy initiated on the 7 day after operation.30 patients received three-weekly concurrent docetaxel (75 mg/m2),Doxorubicin (50 mg/m2) and Cyclophamide (500 mg/m2) (TAC) for 6 cycles.The other 30 patients received three weekly Doxorubicin (60 mg/m2) and Cyclophamide (600 mg/m2) for 4 cycles,followed by three weekly Docetaxel (100 mg/m2) for four cycles (AC→T).According to WHO grading criteria for adverse event of chemotherapy,analysis was performed in Grade 2～4 adverse events such as:febrile neutropenia,neutropenic infections,nausea,vomiting,diarrhea,stomatitis,weakness,amount of axillary draining.Results:Comparision of short-term adverse events (sequential AC-T versus TAC):febrile neutropenia,stomatitis,diarrhea,nausea,vomiting,weakness,neutropenic infections,amount of axillary draining were markedly lower than TAC.Conclusion:AC→T causes less Grade 2～4 short term adverse events than TAC.
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