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Liquid biopsy of circulating free DNA has become an auxiliary method to evaluate cancer.Because of the advantages of minimally invasive and simple, it plays an increasingly important role in the screening, diagnosis, monitoring treatment, prognosis and drug resistance detection of breast cancer.This article reviews the clinical application and related research progress of circulating free DNA (cfdna) in breast cancer.
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Objective:To investigate the expressions and significance of cyclin D2 and bcl-2 in diffuse large B-cell lymphoma (DLBCL) and their clinical significances.Methods:The tissues of 87 DLBCL patients undergoing resection and 23 patients with lymphoid tissue reactive hyperplasia (RLH) in the First Central Hospital of Baoding from January 2015 to March 2020 were collected. Immunohistochemistry method was used to detect the expressions of cyclin D2 and bcl-2 in tissues of DLBCL and RLH, and the relationship between the expressions of cyclin D2 and bcl-2 as well as the association with the clinicopathological features of DLBCL patients.Results:The positive rates of cyclin D2 protein in DLBCL and RLH were 33.3% (29/87) and 2.0% (1/23), the positive rates of bcl-2 protein in DLBCL and RLH were 60.9% (54/87) and 7.0% (3/23); the positive rates of cyclin D2 and bcl-2 in DLBCL were higher than those in RLH, and the differences were statistically significant( χ2=7.566, P=0.006; χ2=17.512, P < 0.01). The expressions of cyclin D2 and bcl-2 proteins were related to the Ann Arbor staging and immunophenotype of DLBCL patients (all P < 0.05), while not related to age, gender, cancer location, tissue type (all P > 0.05). There was a positive correlation between the expressions of cyclin D2 and bcl-2 protein in DLBCL ( r=1.000, P < 0.01). Conclusions:cyclin D2 and bcl-2 may be related to the development and progression of DLBCL, and both may have some synergies.
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Objective To study the expressions and clinical significances of activating transcription factor 3 (ATF3) and Runt-related transcription factor 2 (Runx2) in breast carcinoma tissues.Methods The expressions of ATF3 and Runx2 were detected in 105 cases of primary breast invasive ductal carcinoma (IDC) and their matched para-tumor breast tissues by immunohistochemistry.The relationships between the two transcription factors and the clinical pathological features of IDC patients were analyzed.Results The positive expression rates of ATF3 and Runx2 in IDC group were 80.95％ (85/105) and 69.52％ (73/105) respectively,much higher than those in para-tumor breast tissues 11.43 ％ (12/105) and 8.57％ (9/105),with statistically significant differences (x2 =102.097,P =0.000;x2 =11.595,P =0.001).ATF3 and Runx2 expressions showed significant relationships with histological grade (x2 =14.623,P =0.001;x2 =24.891,P =0.000),lymph node metastasis (x2 =7.059,P =0.008;x2 =6.358,P =0.012) and pTNM stage of IDC (x2 =5.807,P =0.016;x2 =4.902,P =0.027),while both were not correlated with patients' age (x2 =0.274,P =0.601;x2 =1.554,P =0.213) and tumor size (x2 =2.476,P =0.290;x2 =5.261,P =0.072).There was a significant positive relationship between ATF3 and Runx2 in breast carcinoma (C =0.498,P =0.000).Conclusion The over-expressions of ATF3 and Runx2 may participate in the tumorigenesis,invasion,metastasis and clinical stage of breast carcinoma,which suggests that they may be key factors to evaluate malignant degree and prognosis of breast carcinoma.
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Objective To study the expressions of hypoxia inducible factor-1 α (HIF-1 α) and carbonic anhydrase 9 (CA9) in different molecular subtypes of breast carcinoma and their relationships with basallike subtype.Methods The expressions of HIF-1α and CA9 were detected by immunohistochemistry in five subtypes of breast carcinoma (n =803).The relationships of the expressions of HIF-1α and CA9 with the clinicopathologic parameters of basal-like subtype and with the prognosis of patients were analyzed.Results The positive expression rates of HIF-1α and CA9 protein in breast carcinoma were much higher than those in paratumor breast tissues (43.96％ vs.3.86％,x2 =354.858,P ＜ 0.001;19.80％ vs.4.61％,x2 =86.495,P ＜ 0.001).The positive expression rates of HIF-1α in Luminal A,Luminal B,epidermal growth factor receptor-2 (HER-2) over-expression,basal-like and normal breast-like subtypes were 31.97％,25.00％,56.06％,77.89％ and 55.76％ respectively,and the positive expression rates of CA9 were 7.48％,5.56％,60.61％,40.00％ and 27.88％ respectively,with significant differences (x2 =88.628,P ＜ 0.001;x2 =147.128,P ＜0.001).The positive expression rates of HIF-1α and CA9 in estrogen receptor (ER)-negative breast carcinomas(HER-2 over-expression,basal-like and normal breast-like) were significantly higher than those in ER-positive subtypes (Luminal A and Luminal B,all P ＜ 0.005).There was a significant positive correlation between HIF-1 α and CA9 (C =0.315,P =0.001),and both were correlated with the lymph node metastasis (x2 =4.542,P =0.033;x2 =7.025,P =0.008),pTNM stage (x2 =5.390,P =0.020;x2 =10.179,P =0.001) and poor prognosis (x2 =4.353,P =0.037;x2 =6.056,P =0.014) of basal-like subtype.Conclusion Over-expressions of HIF-1α and CA9 may be related to the ER-negative breast cancer more closely,and both may play important roles in the occurrence and development of basal-like subtype.Overexpressions of HIF-1α and CA9 may suggest the poorer prognosis of patients with basal-like breast carcinoma.
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Objective To investigate the expressions of Apaf-1 and Caspase-9 protein in ovarian serous carcinoma(OSC) and their clinicopathological significance.Methods The expressions of Apaf-1 and Caspase-9 protein in 45 cases of OSC,60 cases of ovarian serous cystadenomas and 32 cases of ovarian borderline serous cystadenomas were detected by immunohistochemical SP method.The relationship between the expressions of these two proteins and the clinicopathological features of OSC and the correlation between Apaf-1 and Caspase-9 expressions in OSC were analyzed.Results The positive rates of Apaf-1 in OSC,ovarian serous cystadenoma and ovarian borderline serous cystadenoma were 24.4%(11/45),75.0%(45/60) and 46.9%(15/32),the difference was statistically significant (χ2=26.734,P<0.01).Apaf-1 expression was correlated with pathological grade,clinical stage and lymph nodes metastasis (χ2=6.318,7.565,5.554,P<0.05).The expression rates of Caspase-9 in OSC,ovarian serous cystadenoma and ovarian borderline serous cystadenoma were 28.9%(13/45),83.3%(50/60) and 56.3%(18/32),the difference was statistically significant (χ2=31.682,P<0.01).The expression of Caspase-9 was correlated with pathological grade,clinical stage and lymph nodes metastasis (χ2=5.750,4.391,5.466,P<0.05).In OSC,the expressions of Apaf-1 and Capase-9 were positively correlated (k=0.433,P=0.003).Conclusion The low expressions of Apaf-1 and Caspase-9 in OSC may be related to the occurrence and development of OSC.
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Objective To investigate the expression and clinical significance of apoptotic protease activating factor 1 (Apaf-1) and bax in prostate cancer (PCa) and benign prostatic hyperplasia (BPH). Methods Immunohistochemistry was used to detect the expression of Apaf-1 and bax in the tissues from 45 PCa patients and 60 BPH patients. Results The positive rates of Apaf-1 and bax in PCa tissues were 22.22%(10/45) and 20.00 % (9/45), respectively, while those in BPH tissues were 48.33 % (29/60) and 46.67 % (28/60). There was a statistically significant difference in the expressions of Apaf-1 and bax between two groups (P0.05), but they were correlated with the pathological grade and clinical stage of PCa (P< 0.05). The expressions of Apaf-1 and bax in PCa tissues were lower than those in BPH tissues. There was a positive correlation between the expression of Apaf-1 and bax (r=0.535, P<0.01). Conclusion Apaf-1 and bax might be correlated with the carcinogenesis and development of PCa.
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Purpose To investigate the expression of Apaf-1 and Caspase-9 in prostate cancer ( PCa) and benign prostatic hyperplasia ( BPH) , and to analyze their correlation with clinicopathological parameters of PCa. Methods Immunohistochemistry was used to de-tect Apaf-1 and Caspase-9 protein in 45 cases of PCa and 60 cases of BPH. Results The positive rate of Apaf-1 and Caspase-9 in PCa tissues was significantly lower than that in BPH (P0. 05), but it was correlated with the pathological grade and clinical stage of PCa (P<0. 05). Conclusion Apaf-1 and Caspase-9 are lowly expressed in PCa. There is positive correlation between the expression of Apaf-1 and Caspase-9 (rs =0. 645, P<0. 01). Apaf-1 and Caspase-9 might be correlated with the carcinogenesis and development of PCa.
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Purpose To study the expression of HIF-1αand Glut-1 in the molecular subtypes of breast carcinoma and their correlation with basal-like breast carcinoma. Methods 803 cases of invasive breast carcinoma from our database were identified. The clinicopath-ologic findings and the biologic markers including estrogen receptor ( ER) , progesterone receptor ( PR) , and human epidermal growth factor receptor-2 (HER-2) status were reviewed. Immunohistochemical MaxVision stains for cytokeratin 5/6 (CK5/6) and epidermal growth factor receptor ( EGFR) were performed. All breast carcinomas were subclassified into Luminal A, Lumincal B, HER-2 over-expression, normal-like, and basal-like subtypes according to Nielsen criteria. Immunohistochemical stain was also used to detect the expression of HIF-1αand Glut-1. Results Positive expression rates of HIF-1αprotein in basal-like, HER-2 over-expression, normal-like, Luminal A and Luminal B substypes were 77. 89% (74/95), 56. 06% (37/66), 55. 76% (92/165), 31. 97% (141/441), 25. 00% (9/36), respectively. The positive expression rates of Glut-1 protein were 80. 00% (76/95), 57. 58% (38/66), 58. 18%(96/165), 34. 01% (150/441), 25. 00% (9/36), respectively. The positive expression rates of HIF-1α and Glut-1 in the basal-like, HER-2 over-expressing and normal-like subtypes were remarkably higher than that in Luminal A and Luminal B subtypes ( P<0. 004 5) and the expression of HIF-1a and Glut-1 was negatively correlated with the expression of ER (P<0. 01). In the ER-negative breast cancers, the positive expression rates of HIF-1a and Glut-1 in basal-like substype were much higher than that in the other sub-types (P<0. 004 5), and the expression of HIF-1α was positively correlated with expression of Glut-1 in basal-like breast carcinoma (P<0. 01). Conclusion The overexpression of HIF-1αand Glut-1 may be closely related to the ER-negative breast cancer and HIF-1α and Glut-1 might play an important role in the development of basal-like breast carcinoma.
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Objective To investigate the expressions and significances of Bcl-2 and Bax in basal-like breast carcinoma (BLBC).Methods The expressions of Bcl-2 and Bax were detected in 43 cases of BLBC, 57 cases of non-BLBC and 60 cases of normal breast tissues by immunohistochemistry,and their relationships with physiological and pathological characteristics of patients were analysized.Results The positive rate of Bcl-2 in BLBC was 69.77%,higher than 43.86% in non-BLBC (χ2 =6.647,P =0.01 0)and 21 .67% in normal breast tissues (χ2 =23.831 ,P =0.001 ).The positive rate of Bax in BLBC was 20.93%,lower than 45.61 % in non-BLBC (χ2 =6.564,P =0.01 0)and 76.67% in normal breast tissues (χ2 =31 .270,P =0.001 ).The expressions of Bcl-2 and Bax were correlated with lymphnode metastasis (χ2 =6.927,P =0.008;χ2 =6.203,P =0.01 3)and pTNMstaging of BLBC (χ2 =6.331 ,P =0.01 2;χ2 =5.972,P =0.01 5).There was negative correlation between the expression of Bcl-2 and Bax in BLBC (r = -0.408,P <0.01 0). Conclusion High expression of Bcl-2 and low expression of Bax interact with each other leading to unbalance of cell deferation and apoptosis,resulting in promoting genesis and progress of BLBC.
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Objective To explore the application value of detecting HPV E6/E7 mRNA in cervical cancer screening and prognosis.Methods bDNA technology was used to detect the HPV E6/E7 mRNA levels in 301 cases of paraffin-embedded cervical samples that were grouped based on pathological diagnosis.Statistic differece between multiple groups were assessed by chi-square segmentation method.Results The positive detection rate of HPV E6/E7 mRNA is higher in cervical cancer group than that in CIN1-3 groups and cervicitis group,which were 94.29 ％ (66/70),30.30 ％ (20/66),50.00 ％ (19/38),59.46 ％ (44/74),5.66 ％ (3/50),respectively (all P ＜ 0.004 5).The HPV E6/E7-positive rates in all three CIN groups were higher than that in cervicitis group (P ＜ 0.004 5).The positive rates in CIN2 and CIN3 group were higher than that in CIN1 group (P ＜ 0.004 5).HPV E6/E7 mRNA levels in cervical cancer group were higher than those in CIN groups and cervicitis group (16 508.730±8 741.402,929:337±460.880,3 239.681±1 447.399,5 286.224±2 933.445,4.941±2.263,respectively,all P ＜ 0.05).CIN groups had higher copy numbers of HPV E6/E7 mRNA than cervicitis group (P ＜ 0.05).More copies of HPV E6/E7 mRNA were detected in CIN3 group than those in CIN1 group (P ＜ 0.05).Conclusions The positive rate and expression levels of HPV E6/ E7 mRNA was related to the severity of cervical diseases.HPV E6/E7 mRNA detection in paraffin-embedded samples have a high clinical application value in predicting the risk of cervical cancer.It' s an effective measure for cervical cancer screening and follow-up.
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Objective To detect the protein expressions of S100A7 and CD34 in basal-like breast carcinoma and analyze the clinical relationship between S100A7 and basal-like breast cancer and the connection with CD34 markers microvessel denisity (MVD).To study the function of S100A7 in basal-like breast cancer angiogenesis,invasion and metastasis.Methods Immunohistochemistry (IHC) was used to detect the expressions of S100A7 and CD34 in 60 cases of basal-like breast cancer,40 cases of non basal-like breast cancer and 20 cases of normal breast tissues.Results The expressions of S100A7 in basal-like breast cancer,non basallike breast cancer and normal breast tissues were 83.33％,62.50％ and 35.00％ respectively.There were significant differences among them (x2 =5.556,P ＜ 0.051; x2 =17.107,P ＜ 0.05; x2 =4.051,P ＜ 0.05).There was positive correlation between S100A7 and lymph node metastasis,TNM staging and MVD of basal-like breast cancer patients.But there was no significant correlation between S100A7 and patient's age and tumor sizes.Conclusion The up-regulation of S100A7 expressions may be associated with the occurrence and development,invasion and metastasis,angiogenesis of basal-like breast cancer.The effects of S100A7 promoting angiogenesis may be an important factor in the acceleration of the local invasion and distant metastasis in basallike breast cancer.
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Objective To detect the protein expression of Cripto-1 and CD34 in basal-like breast carcinoma and study the functions of Cripto-1 in basal-like breast cancer angiogenesis,invasion and metastasis.Methods Immunohistochemistry (IHC) was used to detect the expression of Cripto-1 and CD34 in 60 cases of basal-like breast cancer,40 cases of non basal-like breast cancer and 20 cases of normal breast tissues.The clinical relationship between Cripto-1 and basal-like breast cancer were analyzed as well as its connection with CD34 markers MVD.Results The expression of Cripto-1 protein in basal-like breast cancer (42/60,70.00 ％) was significantly higher than that of nonbasal-like breast cancer (19/40,47.50 ％) and normal breast tissue (4/20,20.00 ％) (both P ＜ 0.05).The expression of Cripto-1 protein was positively correlated with the tumor size,clinical stage,lymph nodes metastasis and MVD value in patients of basal-like breast cancer (all P ＜ 0.05),but there was no corelation with the age of the patients (P ＞ 0.05).Conclusions The up-regulation of Cripto-1 expression may be associated with angiogenesis and development in basal-like breast cancer.The effect of Cripto-1 promoting angiogenesis may be an important factor in the acceleration of the local invasion and distant metastasis in basal-like breast cancer.
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Objective To study the expression and clinical significance of FoxM1 and Cep55 protein in basal-like breast carcinoma (BLBC).Methods The expression of FoxM1 and Cep55 protein in 66 cases of BLBC,70 cases of non-BLBC and 66 cases of normal adjacent breast tissue were detected by immunohistochemistry.Their relationship with the clinical pathological factors was analyzed.Results The positive rate of FoxM1 protein in BLBC,non-BLBC and normal adjacent breast tissue was 77.3％ (51/66),60.0％(42/70) and 13.6％(9/66),Cep55 protein was 74.2％(49/66),57.1％(40/70) and 16.7％(11/66),respectively.BLBC and non-BLBC tissue were higher than normal adjacent breast tissue,and BLBC tissue was higher than non-BLBC,there was significant difference (P ＜0.05).In BLBC tissue,the positive expression of FoxM1 and Cep55 protein correlated with lymph nodes metastasis and TNM staging (P ＜0.05),while did not correlate with age,menopause,tumor size (P ＞ 0.05).There was direct correlation between the positive expression of FoxM1 and Cep55 protein (r =0.259,P ＜ 0.05).Conclusion FoxM1 and Cep55 protein may play an important role in the carcinogenesis and development of BLBC,and both of them have the synergistic effect.
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Objective To investigate the expressions of thymidylate synthase (TS) and adenosine triphosphate (ATP)-binding cassette superfamily G member 2 (ABCG2) in advanced gastric cancer (GC) and to explore their correlation with clinical pathological features.Methods A total of 80surgical specimens of advanced gastric cancer patients were collected.The expressions of TS and ABCG2 in gastric cancer tissues and adjacent normal gastric tissues were detected by immunohistochemical method.The expression of P-glycoprotein in gastric cancer tissues was also examined.The correlations between TS,ABCG2 and clinical pathological features and P-glycoprotein were analyzed.Chi-square test was performed for two groups comparison and Kruskal-Wallis H test were used for multi-groups comparison.Results The positive rates of both TS and ABCG2 in gastric cancer tissues [85.0％ (68/80) and 90.0％ (72/80)] were higher than those of adjacent normal gastric tissues [62.5 ％ (50/80) and 78.7 ％ (63/80)],the differences were statistically significant (x2 =11.466 and 16.463,P=0.009 and 0.001).There were close correlation between the expression of TS,ABCG2 and tumor TNM stage,differentiation status,invasion depth (TS:x2 =30.686,61.470 and 40.545 ; ABCG2:x2=48.192,63.150 and 47.512; all P＜0.01).The later the tumor staged,the worse the cells differentiated and the deeper the tumor invaded,the higher level they expressed.Both TS and ABCG2expressions in gastric cancer tissues were correlated with the expression level of P glycoprotein (x2 =43.977and 29.509,both P＜0.01).Conclusion TS and ABCG2 may be potential indexes to predict the degree of malignancy,progression,drug resistance and prognosis in gastric cancer.
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Objective To explore the effects of C-pseudonucleosides bearing thiazolidin-4-one as immunostimulants on differentiation and activation of human lymphocytes. Methods Peripheral blood mononuclear cells (PBMC) were isolated from healthy adults,and then incubated with immunostimulants (CH1a,CH2a,CH1b,CH2b and pidotimod).After 48 h,we collected the supernatants and then detected the concentrations of IL-2,IL-4 and IFN-γ using ELISA.After 72 h,the proliferation was detected using MTT method.PBMC incubated with immunostimulants (CH1a,CH2a,CH1b,CH2b and pidotimod),after 72 h,the cultural cells were collected and CD expressions of lymphocytes were analyzed by flow cytometry.Results All samples could stimulate proliferation of T cells.Immunostimulants CH1a,CH2a and pidotimod could elevate the expressions of CD3,CD4,CD19 and CD16CD56,and stimulate the secretions of IL-2 and IFN-γ. Immunostimulants CH1b and CH2b could elevate the expressions of CD3,CD4,CD19 and CD16CD56,and stimulate the secretions of IL-2 and IL-4. Conclusion Immunostimulants CH1a and CH2a could differentiate Th0 into Th1 and promote the proliferation of B cells as well as NK cells.However,immunostimulants CH1b and CH2b could differentiate Th0 into Th2 and promote the proliferation of B cells and NK cells.
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Objective To study the expression of S1RT1 in breast cancer with diabetes mellitus,and analyze the correlation between SIRT1 and p53,and analyze blood lipid differences in breast cancer tissue without diabetes mellitus and breast cancer tissue with diabetes mellitus,and to research its relation with type 2 diabetes mellitus and assesse the clinical value.Methods Immunohistochemistry was used to examine the expressions of SIRT1 and p53 in 30 breast cancer patients with diabetes mellitus and 30 breast cancer patients without diabetic mellitus,and their correlation was analyzed.Results The positive rate of SIRT1 in breast cancer tissue with diabetes mellitus was significantly lower than that in breast cancer tissue without diabetic mellitus(P ＜0.05).In SIRT1 positive tissue,the expression level of p53 was significantly higher than that in SIRT1 negative tissue(P ＜ 0.05 ).The expression of SIRT1 was significantly positively related with p53 expression in breast cancer tissue with diabetes( P ＜ 0.05).BMI and TG in breast cancer group with diabetes mellitus were significantly higher than those in breast cancer group without diabetic mellitus( P ＜ 0.05 ),but HDL was lower( P =0.05 ).However,CHO and LDL had no significant differences in both groups( P ＞0.05 ).Conclusions SIRT1 is up-regulated in breast cancer,but the posltive rate of SIRT1 in breast cancer tissue with diabetes mellitus is significantly lower than that in breast cancer tissue without diabetic,and is associated with the progression of diabetes mellitus.SIRT1 protein is significantly positively correlated to p53 expression and it may be involved in the adjustment process of blood lipids,SIRT1 might be a new biological target in diabetes and breast cancer.
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Serum matrix metalloproteinase-9 (MMP-9)and advanced glycation end products (AGE)levels were measured in the diabetic patients with or without foot problems as well as in healthy retired people. In diabetic patients serum MMP-9 and AGE levels were significantly higher than those in healthy subjects. Median MMP-9 level in patients with diabetic foot was higher than that in diabetic patients without foot ulcers. Increased serum MMP-9 in diabetes might predict occurance of diabetic foot and poor wound healing of the foot ulcers.