ABSTRACT
Interleukin (IL)-8 plays a vital role in regulating inflammation and breast cancer formation by activating CXCR1/2. We previously designed an antagonist peptide, (RF16), to inhibits the activation of downstream signaling pathways by competing with IL-8 in binding to CXCR1/2, thereby inhibiting IL-8-induced chemoattractant monocyte binding. To evaluate the effect of the RF16 peptide on breast cancer progression, triple-negative MDA-MB-231 and ER-positive MCF-7 breast cancer cells were used to investigate whether RF16 can inhibit the IL-8-induced breast cancer metastasis. Using growth, proliferation, and invasiveness assays, the results revealed that RF16 reduced cell proliferation, migration, and invasiveness in MDA-MB-231 cells. The RF16 peptide also regulated the protein and mRNA expressions of epithelial-mesenchymal transition (EMT) markers in IL-8-stimulated MDA-MB-231 cells. It also inhibited downstream IL-8 signaling and the IL-8-induced inflammatory response via the mitogen-activated protein kinase (MAPK) and Phosphoinositide 3-kinase (PI3K) pathways. In the xenograft tumor mouse model, RF16 synergistically reinforces the antitumor efficacy of docetaxel by improving mouse survival and retarding tumor growth. Our results indicate that RF16 significantly inhibited IL-8-stimulated cell growth, migration, and invasion in MDA-MB-231 breast cancer cells by blocking the activation of p38 and AKT cascades. It indicated that the RF16 peptide may serve as a new supplementary drug for breast cancer.
Subject(s)
Breast Neoplasms , Triple Negative Breast Neoplasms , Humans , Animals , Mice , Female , MDA-MB-231 Cells , Phosphatidylinositol 3-Kinases/metabolism , Interleukin-8/genetics , Interleukin-8/pharmacology , Signal Transduction , Breast Neoplasms/pathology , Cell Proliferation , Cell Line, Tumor , Cell Movement , Epithelial-Mesenchymal Transition , Triple Negative Breast Neoplasms/pathologyABSTRACT
Heart-sound auscultation is a rapid and fundamental technique used for examining the cardiovascular system. The main components of heart sounds are the first and second heart sounds. Discriminating these heart sounds under the presence of additional heart sounds and murmurs will be difficult. To recognize these signals efficiently, this study proposes a monitoring system with phonocardiogram and electrocardiogram. This system has two key points. The first is chip implementation, including capacitor coupled amplifier, transimpedance amplifier, high-pass sigma-delta modulator, and digital signal processing block. The chip in the system is fabricated in 0.18 µm standard complementary metal-oxide-semiconductor process. The second is a software application on smartphones for heart-related physiological signal recording, display, and identification. A wavelet-based QRS complex detection algorithm verified by MIT/BIH Arrhythmia Database is also proposed. The overall measured positive prediction, sensitivity, and error rate of the proposed algorithm are 99.90%, 99.82%, and 0.28%, respectively. During auscultation, doctors may refer to these physiological signals displayed on the smartphone and simultaneously listen to the heart sounds to diagnose the potential heart disease. By taking advantage of signal visualization and keeping the original diagnosis procedure, the uncertainty existing in heart sounds can be eliminated, and the training period to acquire auscultation skills can be reduced.
Subject(s)
Cardiovascular Diseases/diagnosis , Electrocardiography , Heart Auscultation/instrumentation , Phonocardiography , Algorithms , Amplifiers, Electronic , Heart Auscultation/methods , Humans , Semiconductors , Signal Processing, Computer-Assisted , Wearable Electronic DevicesABSTRACT
There is a lot of debate on the relationship between vitamin D receptor polymorphisms and risk of breast cancer. Herein, we quantitatively analyzed the published case-control studies on this relationship by meta- analysis, performing a bibliographic search from Pubmed and CNKI up to July 31, 2013. The included case- control studies for Fok1, Bsm1, Taq1, Apa1, Cdx2 and Poly-A were 16, 19, 20, 10, 4, 6, respectively. Crude and adjusted odd ratios and 95% confidence intervals were calculated to present and compare the strength of any associations. The results of combined analyses indicated that Fok1, Bsm1, Apa1, Cdx2 and Poly-A were not significantly associated with the risk of breast cancer. In contrast, the tt genotype of Taq1 was a modest risk factor for breast cancer development (tt vs. TT: OR = 1.21, 95% CI: 1.01-1.44). To further confirm the above results, adjusted effects for the six polymorphisms were pooled based on adjusted ORs reported in the original studies. Adjusted ORs of Fok1, Apa1, Cdx2 and Poly-A were similar to the crude ORs. However, Bsm1 and Taq1 showed inconsistent results. For Bsm1, OR for BB vs. bb was 0.85, 95% CI: 0.74-0.98; for Taq1, OR for tt vs. TT was 1.03, 95% CI: 0.92-1.15, and not associated with risk. Subgroup analyses for crude ORs showed some association between Bsm1, Taq1 and breast cancer in Caucasians only, but for adjusted ORs, no associations were found. This meta-analysis suggests that the roles that Fok1, Apa1, Cdx2 and Poly-A polymorphisms play in breast cancer risk are negligible, with Bsm1 and Taq1 as possible exceptions. To be conservative, we still assumed that they may play a modest role in determining breast cancer risk. Further studies are needed to validate our findings.
