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    Mutant p53 in breast cancer: potential as a therapeutic target and biomarker
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    Objective: To evaluate the clinical value of CA15-3 in diagnosis and therapy of breast cancer.Methods: Serum level of CA15-3 was detected by chemiluminescence immunoassay(CLIA) in 79 patients with breast cancer,30 patients with benign breast disease and 20 healthy adults.Results: Serum CA15-3 was significantly elevated in patients with breast cancer and differed significantly from that of control group and benign breast disease group;serum CA15-3 was significantly elevated in patients with stage Ⅲ、Ⅳ breast cancer;serum CA15-3 was significantly elevated in patients of matasases and relapse.Conclusion: CA15-3 is not proper marker of early diagnosis for breast cancer,but can be used to estimate the degree and prognosis of breast cancer,and be helpful to find matasases and relapse.
    Breast disease
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    To study the role of p21-activated kinase-4 (PAK4) in the occurrence, progression and metastasis of breast cancer.PAK4 expression was detected in 35 cases of normal breast, 22 breast cystic hyperplasia, 28 breast adenofibroma, 37 breast cancer (including 7 non-invasive cancer, 9 early invasive cancer and 21 invasive cancer) and 13 metastatic breast cancer tissues using immunohistochemistry for a comparison of PAK4 expression and distribution.PAK4 was expressed mainly in the cytoplasm of the cancer cells, occasionally in the cell nuclei, and virtually not expressed in the matrix surrounding the breast cells. PAK4 positivity rates increased in the order of normal breast tissues, benign changes (including breast cystic hyperplasea and breast adenoma), breast cancer and metastatic cancer tissues; in the cancer tissues, the positivity rates increased in the order of non-invasive breast tumor, early invasive tumor and invasive tumor tissues.PAK4 is closely correlated to the progression and metastasis of breast cancer and may become a new diagnostic and therapeutic target of breast cancer.
    CA 15-3
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    textabstractIn the Western world, breast cancer not only is the most frequently diagnosed cancer in women, but also the second leading cause of cancer death. Clinically, breast cancer is a heterogeneous disease. About two-thirds of breast cancer patients survive their disease, whereas, one-third of breast cancer patients will die of metastases of their primary cancer within 15 years from diagnosis. Therefore, it is important for clinicians to accurately predict the prognosis and most appropriate therapy for each breast cancer patient. However, appropriate molecular targets have as yet not been identified for most breast cancer subtypes, implying suboptimal treatment for a significant fraction of the breast cancer patients. Thus, a better understanding of the disease is needed to improve upon current methods to treat breast cancer patients. In this thesis, we set out to determine the genetic basis for the two major subtypes of breast cancer, by mutation screening of 27 known cancer genes in a model of human breast cancer cell lines. Two distinct mutation profiles were identified: a “luminal mutation profile” among luminal-type breast cancer cell lines and a “basal mutation profile” among basal-type breast cancer cell lines. The gene mutation profiles give insight in the mechanisms of breast carcinogenesis. For example, we found that mutation and hypermethylation of the E-cadherin gene, two mechanisms involved in tumor suppressor gene inacativation, associated with each of the two breast cancer subtypes. This challenges the paradigm that genetic and epigenetic inactivation of a tumor suppressor gene are two means to the same end. Importantly, the results of this thesis provide a further refinement of current molecular breast cancer classification and may aid the development of new treatment modalities th! at target the here identified molecular markers.
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    The aim of the present prospective case-control study was to evaluate the putative relevance of circulating microparticles (MP) as a biomarker in breast cancer patients.Endothelial cell-(EMP) and leukocyte-derived MP (LMP) were determined by flow cytometry in breast cancer patients (n = 41) and healthy controls (n = 25) and compared to carcinoembryonic antigen (CEA), cancer antigen (CA)15-3 and von Willebrand factor antigen (vWF) levels by specificity-sensitivity profiles.LMP, CEA and CA15-3 levels differed significantly between breast cancer patients and controls, whereas EMP and vWF did not. The specificity-sensitivity profiles of LMP and CA15-3 were similar.Increasing levels of circulating LMP (CD45+), CEA and CA15-3 correlated with increasing tumor size, thus reflecting disease stage. LMP showed an equal specificity-sensitivity profile to the established marker CA15-3 and therefore might have the potential to become a new biomarker in breast cancer patients.
    Carcinoembryonic antigen
    CA 15-3
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    The incidence and mortality of breast cancer are increasing annually. Breast cancer seriously threatens women's health and quality of life. We aimed to measure the clinical value of CPN1, a new serum marker of breast cancer and to evaluate the efficacy of CPN1 in combination with CA15-3.Seventy samples of breast cancer with lymph node metastasis, seventy-three samples of nonmetastatic breast cancer and twenty-five samples of healthy human serum were collected. Serum CA15-3 concentration was determined by Roche Elecsys, and serum CPN1 concentration was determined by ELISA.In breast cancer patients, serum CPN1 concentration was positively correlated with tumour size, clinical stage and CA15-3 concentration (r = 0.376, P<0.0001). ROC curve analysis showed that the optimal critical concentration of CPN1 for breast cancer diagnosis was 32.8pg/ml. The optimal critical concentration of CPN1 in the diagnosis of metastatic breast cancer was 66.121pg/ml. CPN1 has a greater diagnostic ability for breast cancer (AUCCA15-3=0.702 vs. AUCCPN1=0.886, P<0.0001) and metastatic breast cancer (AUCCA15-3=0.629 vs. AUCCPN1=0.887, P<0.0001) than CA15-3, and the combined detection of CA15-3 and CPN1 can improve the diagnostic efficiency for breast cancer (AUCCA15-3+CPN1=0.916) and for distinguishing between metastatic and non-metastatic breast cancer (AUCCA15-3+CPN1=0.895).CPN1 can be used as a new tumour marker to diagnose and evaluate the invasion and metastasis of breast cancer. The combined detection of CPN1 and CA15-3 is more accurate and has a certain value in clinical application.
    CA 15-3
    Objective To explore the expression of cystatin M in breast cancer and its clinical significance.Methods RT-PCR was used to measure the level of cystatin M mRNA in 108 samples of breast cancer,30 samples of metastatic cancer and 24 samples of normal breast tissues.The relationship between the expression of cystatin M gene in human breast cancer and clinilcopathological features was analyzed.Results The cystatin M expression level of breast cancer samples was high in stage I/II breast cancer patients,but low in stage III/IV breast cancer patients,and there was a statistical significance between them.The systatin expression was high in5 cm tumors,but low in5 cm tumors,with a statistical significance between them.Cystatin M expression levels of breast cancer were correlated with TNM staging and clinical size of tumor.The expression levels of cystatin M in the breast cancer tissue were not significantly different from normal breast tissues and metastatic cancer tissues.Cystatin M expression levels of breast cancer were not correlated with lymph node metastasis,axillary lymph node status,histological grade or pathological type.Cystatin M expression levels of breast cancer and metastatic cancer were not correlated with HER-2,ER or PR status.Conclusion It needs to be discussed whether cystatin M can be a prognostic marker for breast cancer metastasis.
    Clinical Significance
    CA 15-3
    Cystatin
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