ABSTRACT
HRD1 (3-hydroxy-3-methylglutaryl reductase degradation) is an E3 ubiquitin ligase. We found that HRD1 was significantly downregulated in 170 breast cancer tissues. Low tumoral HRD1 expression was correlated with clinicopathological characteristics and a shorter survival in breast cancer patients. P65 specifically bound to the HRD1 promoter and inhibited HRD1 expression. Suppression of NF-κB activity reversed IL-6-induced downregulation of HRD1 expression. HRD1 interacted with IGF-1R and promoted its ubiquitination and degradation by the proteasome. Overexpression of HRD1 resulted in the inhibition of growth, migration and invasion of breast cancer cells in vitro and in vivo. Furthermore, HRD1 attenuated IL-6-induced epithelial-mesenchymal transition in MCF10A cells. These findings uncover a novel role for HRD1 in breast cancer.
Subject(s)
Breast Neoplasms/pathology , Epithelial-Mesenchymal Transition/physiology , Receptor, IGF Type 1/metabolism , Ubiquitin-Protein Ligases/metabolism , Aged , Animals , Blotting, Western , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Cell Line, Tumor , Cell Proliferation/physiology , Chromatin Immunoprecipitation , Down-Regulation , Female , Gene Expression Regulation, Neoplastic/physiology , Heterografts , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Mice , Mice, Nude , Middle Aged , Neoplasm Invasiveness/pathology , RNA, Small Interfering , Real-Time Polymerase Chain Reaction , Tissue Array Analysis , TransfectionABSTRACT
BACKGROUND: The apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) can quantify alterations in water diffusivity resulting from microscopic structural changes from amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). PURPOSE: To investigate the ADC value for aMCI and AD using Brain Search (BS) software based on anatomical volumes of interest (AVOI). MATERIAL AND METHODS: In total, 174 aged people were screened, and 25 patients with AD, 26 patients with aMCI, and 18 normal controls (NCs) were recruited. DWI was performed at 1.5 T with a fluid-attenuated inversion recovery (FLAIR), and the independent ADC mapping was generated after imaging acquisition. Ninety regional parcellations were adopted in a Brain Search (BS) based on the automated anatomic labeling atlas. The gray scale intensities (water diffusivity) from the collected ADC mappings were analyzed with BS. The mean value of each anatomical brain region was compared among aMCI, AD, and NC. The statistically significant (P < 0.05) group differences are displayed in color. RESULTS: During the pathological process of AD, the changes of water diffusivity appeared first in the left hippocampus, then gradually progressed to the bilateral sides and eventually displayed right lateralization. The ADC values from aMCI were obviously elevated compared to the values from the NC group in the left limbic cortex. Between the AD and NC groups, the significantly different brain areas included the bilateral hippocampus, the Cingulum_Mid, the ParaHippocampal_R, and the Temporal and Frontal lobes. There was a negative correlation between the ADC values and the scores from MMSE, MoCA, the Digit test, Raven's IQ, and WAIS IQ. Additionally, the ADC values were positively correlated with the scores from CDR, ADL, and ADAS-Cog. CONCLUSION: The water diffusivity for aMCI and AD displays asymmetric anatomical lateralization. The water diffusivity alterations can be analyzed and visualized with our newly designed analytic imaging software, BS, which can be used as a good reference for examining and diagnosing aMCI and AD patients.
Subject(s)
Brain Mapping/methods , Brain/pathology , Cognitive Dysfunction/pathology , Diffusion Magnetic Resonance Imaging/methods , Image Processing, Computer-Assisted/methods , Aged , Aging/pathology , Alzheimer Disease/pathology , Amnesia , Analysis of Variance , Female , Humans , Male , Middle Aged , Neuropsychological Tests/statistics & numerical data , Reproducibility of Results , SoftwareSubject(s)
Lung Neoplasms/diagnostic imaging , Lung Neoplasms/drug therapy , Positron-Emission Tomography , Small Cell Lung Carcinoma/diagnostic imaging , Small Cell Lung Carcinoma/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/drug therapy , Female , Fluorodeoxyglucose F18 , Humans , Male , Middle Aged , Tomography, X-Ray ComputedABSTRACT
OBJECTIVE: To study the change of cerebral metabolism rate of glucose (CMRglc) of cerebral white matter in Alzheimer's Disease. METHODS: Positron emission tomography (PET) was performed on 13 AD patients, 6 with behavioral and psychological symptoms of dementia (BPSD) and 7 without BPSD, and 10 healthy controls. The regional cerebral metabolism of glucose (rCMRglc) of some brain regions and nuclei were detected. RESULTS: (1) The rCMRglc of the cerebral white matter decreased extensively in the AD patients, especially in the right frontal lobe, superior gyrus of the left frontal lobe (P = 0.001). (2) The rCMRglc of subcortical white matter of the left medial prefrontal lobe and the left cuneus of occipital lobe increased in the AD patients. (3) The levels of rCMRglc of the subcortical white matter of both side middle occipital lobe, left cuneus of occipital lobe, right inferior parietal lobule, left fusiform gyrus of temporal lobe and the left medial prefrontal lobe were all significantly higher in the AD patients with BPSD than in those without BPSD (P = 0.001). While the levels of rCMRglc of the subcortical white matter of both side paracentral lobule, right superior and middle frontal lobe, and left superior temporal lobe were all significantly lower in the AD patients with BPSD than in those without BPSD (all P = 0.001). CONCLUSION: There is diffuse abnormal rCMRglc in the cerebral white matter in the AD patients: the rCMRglc decreases in the frontal-temporal-occipital association area, and the rCMRglc of the medial prefrontal lobe and cuneus of occipital lobe increases. BPSD is correlated with the abnormal metabolism of related cerebral regions.