MET and FASN as Prognostic Biomarkers of Triple Negative Breast Cancer: A Systematic Evidence Landscape of Clinical Study

BackgroundTo know the expression of Mesenchymal–Epithelial Transition factor (MET) and Fatty Acid Synthase (FASN) in Triple Negative Breast Cancer (TNBC) patients, as well as its relationship with clinical pathological characteristic and prognosis.Methodswe used immunohistochemistry staining to detect the expression of MET and FASN for those 218 TNBC patients, and analyze their relationship with the clinical pathological characteristic and prognosis.Results130 and 65 out of 218 TNBC patients were positive for MET in the cancer and adjacent tissues respectively. 142 and 30 out of 218 TNBC patients were positive for FASN in the cancer and adjacent tissues respectively. Positive expression of MET and FASN were significantly correlated with lymph node metastasis, pathological TNM, and pathological Stage. In addition, the positive expression of MET and FASN were correlated with recurrence and metastasis. The combined use of MET and FASN can better predict the survival condition.ConclusionsOur results indicated that MET and FASN showed good predictive ability for TNBC. Combined use of MET and FASN were recommended in order to make a more accurate prognosis for TNBC.

RNAi Targeting-STIL Suppresses Cell Growth and Induces Apoptosis of Lung Cancer NCI-H1299 Cells via Inactivation of Akt/SAPK/TAK1 Pathways

Background: Gradually emerged studies demonstrated that SCL/TAL1 interrupting locus (STIL or SIL) is upregulated in multiple kinds of fatal tumors; at present, there is no clean understanding about the role of STIL in lung adenocarcinoma cells. This study aimed to discover the significance of STIL in lung adenocarcinoma, so as to find a potential gene target for diagnosis and therapy. Methods: STIL expression in lung adenocarcinoma tissue and clinical pathological characteristic was analyzed using the online databases, UALCAN and GEPIA. Lentivirus STIL-shRNA was manufactured and transducted into lung adenocarcinoma cells to seek and analyze the effects on tumor phenotype. The cell proliferation was assessed using Cellomics Array Scan imaging assay, and colony-formation assay, respectively. The apoptosis was detected by flow cytometry assay. Moreover, the antibody array of PathScan Cancer Phenotype, PathScan stress and apoptosis pathway was used to explore relevant molecular mechanisms following STIL knockdown in NCI-H1299 cells. Results: The clinical pathological characteristic assay showed that STIL is upregulated in lung adenocarcinoma tissues, and this trend was associated with cancer stage1 and histological subtypes. Silencing experiment showed that downregulation of STIL could inhibit cell growth and colony formation, induce cell apoptosis, and a G2 phase arrest effect significantly, and antibody array detection revealed that p-Bad were upregulated, and p-Akt, p-Bad, p-HSP27, p-SAPK/JNK, p-TAK1, Vimentin, CD45, PCNA and Ki-67 were downregulated significantly after STIL silenced in NCI-H1299 cells.Conclusions: In conclusion, STIL is overexpressed in lung adenocarcinoma tissues compared with normal lung tissue. Knockdown of STIL could inhibit cell growth and colony formation ability, promote apoptosis via Akt/SAPK/TAK1 signal pathways inactivation.

Annexin A2 Promotes Development of Retinal Neovascularization through PI3K/ AKT Pathway

Background RNV is a pathological characteristic of PDR and ANXA2 play an important role in the process of RNV while the mechanism remains unclear. We explore the role and molecular basis of ANXA2 in the formation of RNV and seek for new potential targets for the prevention and treatment of PDR. Methods Lentivirus containing plasmids which can interfere ANXA2 and overexpress ANXA2 were packaged and infected HRECs, dividing HRECs into 4 groups. Moreover, 1ul SC79 solution was added in shA2 group and 1ul LY294002 solution was added into lentiA2 group. Western Blot was used to detect expression of ANXA2 and changes in phosphorylation degree of major proteins in PI3K/AKT signaling pathway in each group of HRECs. HRECs of all groups were used to perform EDu cell proliferation assay, Transwell cell migration assay and Matrix tube formation assay. C57BL/6J mice were randomly divided into 3 groups. Mice of OIR group were injected intraperitoneally with 0.05ml PBS every day from 7th to 10th day while mice of LY294002 treatment group were injected with 0.05ml LY294002 solution and no treatment in the control group. Lectin GS-IB4 fluorescence staining was used to observe RNV in mice in all groups. The expression of ANXA2 in mouse retinas was detected by Westen-blot. Results The proliferation, immigration and angiogenesis ability of HRECs is lower in shA2 group than shNC and SC79 treatment group while higher in lentiA2 group than lenti-EGFP and LY294002 treatment group. ANXA2 expression is significantly higher in retina of mice in OIR group and LY294002 treatment group. RNV is significantly less severe in LY294002 treatment group than that in OIR group. Conclusions ANXA2 can promote development of RNV through PI3K/ AKT Pathway.

IL-6-driven FasL promotes NF-κBp65/PUMA-mediated apoptosis in portal hypertensive gastropathy

Mucosal epithelial apoptosis with non-specific inflammation is an essential pathological characteristic in portal hypertensive gastropathy (PHG). However, whether a coordinated crosstalk between myeloid cells and epithelial cells involved in PHG remains unclear. IL-6, which is induced in the mucosa of PHG patients and mice, promotes FasL production via enhancing NF-κBp65 activation in myeloid cells, while blockage of IL-6 signaling by Tocilizumab or deletion of NF-κBp65 in myeloid cells attenuates the inflammatory response and Fas/FasL-mediated epithelial apoptosis in PHG. IL-6-driven FasL from myeloid cells combines with epithelial Fas receptor to encourage NF-κBp65/PUMA-mediated epithelial apoptosis in PHG, and inhibition of NF-κBp65 or knockout of PUMA alleviates Fas/FasL-mediated epithelial apoptosis in PHG. These results indicate that IL-6 drives FasL generation via NF-κBp65 in myeloid cells to promote Fas/NF-κBp65/PUMA-mediated epithelial apoptosis in PHG, and this coordinated crosstalk between myeloid cells and epithelial cells may provide a potential therapeutic target for PHG.

The Aging Brain

Neurodegeneration is the progressive and gradual dysfunction and loss of axons in the central nervous system. It is the main pathological characteristic of chronic and acute neurodegenerative conditions like Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). The usual aspects of pathogenesis of disease can be abridged with regards to the downstream implications of uncontrollable protein oligomerization and aggregation from postmitotic cells. The brain structure constantly changes in normal aging without any dysfunction accompanying the structural changes in brain. The decline in cognitive capabilities, for example, processing speed, memory, and functions related to decision making are the sign of healthy aging. The reduction in brain volume in healthy aging is possibly related to neuronal loss at some marginal extent. The following chapter discusses the structural and functional alterations in the brain in ageing and neurodegeneration.

PA/US dual-modality imaging to guide VEGFR-2 targeted photothermal therapy using ZnPc-/PFH-loaded polymeric nanoparticles

Angiogenesis is a common pathological characteristic of many solid tumors and vulnerable atherosclerotic plaques.