ABSTRACT
Breast cancer is reported a very complex disease along with heterogeneous morphological characteristics and unrelated clinical behavior, and is a leading cancer among female. Nevertheless, chemo-resistance is frequently observed. Adriamycin (ADM) is a always employed drug to treat clinical breast cancer. However, strong resistance to ADM limited its clinical efficacy. Deregulation of HDAC6 activity is linked to various diseases including cancer resulting in accumulating interest for developing HDAC6 inhibitors. In the present study, for the first time, we found that 4-Hydroxybenzoic acid (4-HBA), as histone deacetylase 6 (HDAC6) inhibitor, could successfully reverse ADM resistance in human breast cancer cells. 4-HBA significantly promoted the anticancer effect of ADM on apoptosis induction, as evidenced by the increased expressions of Caspase-3 and PARP cleavage, which was associated with the promotion p53 and homeodomain interacting protein kinase-2 (HIPK2) expressions in ADM-resistant breast cancer cells. Furthermore, the suppressive effect of ADM on drug-resistant breast cancer cells was accelerated by 4-HBA through increasing the number of cells distributed in G2/M phase of cell cycle arrest. Inhibiting HIPK2/p53 pathway could abolish 4-HBA/ADM co-treatment-induced apoptosis and G2/M cell cycle arrest. Importantly, HDAC6 expressions were also significantly down-regulated in ADM-resistance breast cancer cells co-treated with ADM and 4-HBA. Additionally, 4-HBA clearly potentiated the anticancer role of ADM in the MCF-7 breast cancer animal model with low toxicity. Therefore, 4-HBA could be applied as an effective HDAC6 inhibitor to reverse human breast cancer resistance. Herein, the 4-HBA and ADM combination might represent as a useful therapeutic strategy to prevent human breast cancer.
Subject(s)
Breast Neoplasms/drug therapy , Doxorubicin/pharmacology , Histone Deacetylase 6/antagonists & inhibitors , Histone Deacetylase Inhibitors/pharmacology , Parabens/pharmacology , Animals , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Apoptosis/drug effects , Breast Neoplasms/metabolism , Carrier Proteins/metabolism , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Doxorubicin/administration & dosage , Female , Humans , Mice, Inbred BALB C , Parabens/administration & dosage , Protein Serine-Threonine Kinases/metabolism , Tumor Suppressor Protein p53/metabolism , Xenograft Model Antitumor AssaysABSTRACT
BACKGROUND: Rheumatoid arthritis (RA) is a chronic, inflammatory and autoimmune disease, there are many autoantibodies produced during disease progression in the patients' serum, and this work is to select a best detection scheme for RA diagnosis. METHODS: Autoantibody levels including rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP), mutated citrullinated vimentin (MCV), anti-keratin antibodies(AKA), anti-perinuclear factor (APF), and Ig heavy chain binding protein (BIP), were measured, and the sensitivity, specificity, predictive values, accuracy, and Youden's index of different combining forms were all calculated in RA patients, disease, and healthy control group. The differences in the positive rates of the three groups were compared between any two of them. RESULTS: Generally speaking, the sensitivity of the autoantibodies detected in parallel combination was higher than that in tandem, which was more specific. The sensitivity of anti-MCV and RF calculated in parallel (87.61%) was obviously better than that of anyone autoantibody (P<.05), and only increased slightly even if more autoantibodies were tested in parallel (P>.05). The specificity of anti-CCP and BIP measured in tandem (95.92%) was obviously higher than that of anyone autoantibody (P<.05). While increasing the detected number of autoantibody from two kinds to three or more, the specificity was improved insignificantly (P>.05). CONCLUSION: Anti-BIP and CCP antibodies detected in tandem combination can obtain higher specificity, and have good clinical value for the differential diagnosis of RA.
Subject(s)
Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/diagnosis , Autoantibodies/blood , Adult , Arthritis, Rheumatoid/immunology , Biomarkers/blood , Cohort Studies , Female , Humans , Male , Middle Aged , Sensitivity and SpecificityABSTRACT
PURPOSE: To assess the value of multi-tumor marker protein chips in the diagnosis and treatment of ovarian cancer. MATERIALS AND METHODS: Twelve tumor markers (CA19-9, NSE, CEA, CA242, CK19, ß-HCG, AFP, SCC, c-PSA, CA125, CA724 and CA15-3) were detected by protein biochip in 220 patients with ovarian carcinomas, 205 with benign ovarian tumors and 200 healthy subjects. RESULTS: The positivity rate was obviously higher in ovarian cancer (77.7%), than that in the benign cases (26.3%, p<0.01) and healthy subjects (4.5%, p<0.01). Serum levels of tumor markers were furthermore significantly higher in cases with lymph node metastasis (86.8%) than those without metastasis (44.7%), p<0.01. CONCLUSIONS: Multi-tumor marker protein chips provide important assistance in the diagnosis and treatment evaluation in ovarian cancers.
