Identifying the adaptive mechanisms of metastatic cancer cells remains an elusive question in the treatment of metastatic disease, particularly in pancreatic cancer (pancreatic adenocarcinoma, PDA). A loss-of-function shRNA targeted screen in metastatic-derived cells identified Gstt1, a member of the glutathione S-transferase superfamily, as uniquely required for dissemination and metastasis, but dispensable for primary tumour growth. Gstt1 is expressed in latent disseminated tumour cells (DTCs), is retained within a subpopulation of slow-cycling cells within existing metastases, and its inhibition leads to complete regression of macrometastatic tumours.
View Article and Find Full Text PDFGlutamine is a critical metabolite for rapidly proliferating cells as it is used for the synthesis of key metabolites necessary for cell growth and proliferation. Glutamine metabolism has been proposed as a therapeutic target in cancer and several chemical inhibitors are in development or in clinical trials. How cells subsist when glutamine is limiting is poorly understood.
View Article and Find Full Text PDFAims: The goal of this study was to examine the association of breast arterial calcification (BAC) presence and quantity with incident atrial fibrillation (AF) in a large cohort of post-menopausal women.
Methods And Results: We conducted a longitudinal cohort study among women free of clinically overt cardiovascular disease and AF at baseline (between October 2012 and February 2015) when they attended mammography screening. Atrial fibrillation incidence was ascertained using diagnostic codes and natural language processing.
Background: Prior studies support the utility of high sensitivity troponin I (hsTnI) for cardiovascular disease (CVD) risk stratification among asymptomatic populations; however, only two prior studies examined women separately. The association between hsTnI and breast arterial calcification is unknown.
Methods: Cohort study of 2896 women aged 60-79 years recruited after attending mammography screening between 10/2012 and 2/2015.
Mitochondria communicate with other cellular compartments via the secretion of protein factors. Here, we report an unexpected messenger role for heat shock protein 60 (HSP60) as a mitochondrial-releasing protein factor that couples stress-sensing signaling and cell survival machineries. We show that mild oxidative stress predominantly activates the p38/MK2 complex, which phosphorylates mitochondrial fission factor 1 (MFF1) at the S155 site.
View Article and Find Full Text PDFBackground: Breast arterial calcification (BAC), a common incidental finding in mammography, has been shown to be associated with angiographic coronary artery disease and cardiovascular disease (CVD) outcomes. We aimed to (1) examine the association of BAC presence and quantity with hard atherosclerotic CVD (ASCVD) and global CVD; (2) ascertain model calibration, discrimination and reclassification of ASCVD risk; (3) assess the joint effect of BAC presence and 10-year pooled cohorts equations risk on ASCVD.
Methods: A cohort study of 5059 women aged 60-79 years recruited after attending mammography screening between October 2012 and February 2015 was conducted in a large health plan in Northern California, United States.
J Digit Imaging
December 2021
Spectral computed tomography (CT) based on a photon-counting detector (PCD) is a promising technique with the potential to improve lesion detection, tissue characterization, and material decomposition. PCD-based scanners have several technical issues including operation in the step-and-scan mode and long data acquisition time. One straightforward solution to these issues is to reduce the number of projection views.
View Article and Find Full Text PDFSpecific tissue lengths or volumes in x-ray images are measured for diagnostic and therapeutic purposes. Measurements are used to make clinical decisions; however, the accuracy of these measurements has not been studied. In this study, based on the sources of uncertainty, an SI-traceable length standard phantom and an x-ray imaging system calibration method are proposed.
View Article and Find Full Text PDFSince vascular risk factors are implicated in cognitive decline, and breast arterial calcification (BAC) is related to vascular risk, we postulated that BAC may be associated with cognitive impairment and dementia. We used a multiethnic cohort of 3,913 asymptomatic women 60-79 years of age recruited after mammography screening at a large health plan in 2012-2015. A BAC mass score (mg) was derived from digital mammograms.
View Article and Find Full Text PDFPhysical phantoms have been widely used for performance evaluation of magnetic resonance imaging (MRI). Although there are many kinds of physical phantoms, most MRI phantoms use fixed configurations with specific sizes that may fit one or a few different types of radio frequency (RF) coils. Therefore, it has limitations for various image quality assessments of scanning areas.
View Article and Find Full Text PDFObjectives: Breast cancer is the most common cancer in women and the second leading cause of cancer death. It is well known that breast density is an important risk factor for breast cancer and also can be used to personalize screening and for assessment of treatment response. Breast density has previously been correlated to volumetric water density.
View Article and Find Full Text PDFMitochondrial dysfunction critically impairs cellular health and often causes or affects the progression of several diseases, including neurodegenerative diseases and cancer. Thus, cells must have several ways to monitor the condition of mitochondrial quality and maintain mitochondrial health. Accumulating evidence suggests that the molecular machinery responding to spontaneous changes in mitochondrial morphology is associated with the routine mitochondrial quality control system.
View Article and Find Full Text PDFContext: The association between bone mineral density (BMD) and breast arterial calcification (BAC) remains poorly understood and controversial.
Objective: The objective of this article is to examine the association between BMD and BAC in a large cohort of postmenopausal women undergoing routine mammography.
Design: A cross-sectional analysis of baseline data from a multiethnic cohort was performed.
Objective: To examine the association of breast arterial calcification (BAC) with the ankle brachial index (ABI), a sensitive metric of peripheral arterial disease (PAD), among postmenopausal women. Background: BAC is an emerging risk marker of cardiovascular disease (CVD).
Methods: MINERVA (MultIethNic study of brEast aRterial calcium gradation and cardioVAscular disease) is a cohort of women aged 60 to 79 at baseline (10/24/2012 - 2/13/2015) who were free of symptomatic CVD at baseline.
Mitochondrial morphology is known to be continuously changing via fusion and fission, but it is unclear what the biological importance of this energy-consuming process is and how it develops. Several data have suggested that mitochondrial fission executed by Drp1 is necessary to select out a damaged spot from the interconnected mitochondrial network, but the precise mechanism for the recognition and isolation of a damaged sub-mitochondrial region during mitochondrial fission is yet unclear. Recently, Cho et al.
View Article and Find Full Text PDFMitophagy, a mitochondrial quality control process for eliminating dysfunctional mitochondria, can be induced by a response of dynamin-related protein 1 (Drp1) to a reduction in mitochondrial membrane potential (MMP) and mitochondrial division. However, the coordination between MMP and mitochondrial division for selecting the damaged portion of the mitochondrial network is less understood. Here, we found that MMP is reduced focally at a fission site by the Drp1 recruitment, which is initiated by the interaction of Drp1 with mitochondrial zinc transporter Zip1 and Zn entry through the Zip1-MCU complex.
View Article and Find Full Text PDFPurpose: MultIethNic Study of BrEast ARterial Calcium Gradation and CardioVAscular Disease (MINERVA) was designed to answer the question of whether a novel continuous breast arterial calcification (BAC) mass score improves cardiovascular risk stratification among asymptomatic postmenopausal women. This article describes recruitment and baseline characteristics.
Methods: MINERVA is a multiethnic longitudinal cohort study.
Biochem Biophys Res Commun
December 2017
Variants of the SHANK3 gene, which encodes a core scaffold protein of the postsynaptic density of excitatory synapses, have been causally associated with numerous brain disorders. Shank3 proteins directly bind zinc ions through their C-terminal sterile α motif domain, which enhances the multimerization and synaptic localization of Shank3, to regulate excitatory synaptic strength. However, no studies have explored whether zinc affects the protein interactions of Shank3, which might contribute to the synaptic changes observed after zinc application.
View Article and Find Full Text PDFObjective: To evaluate the frequency and adequacy of statistical analyses in a general radiology journal when reporting a reliability analysis for a diagnostic test.
Materials And Methods: Sixty-three studies of diagnostic test accuracy (DTA) and 36 studies reporting reliability analyses published in the between 2012 and 2016 were analyzed. Studies were judged using the methodological guidelines of the Radiological Society of North America-Quantitative Imaging Biomarkers Alliance (RSNA-QIBA), and COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) initiative.
Mitochondrial division is critical for the maintenance and regulation of mitochondrial function, quality and distribution. This process is controlled by cytosolic actin-based constriction machinery and dynamin-related protein 1 (Drp1) on mitochondrial outer membrane (OMM). Although mitochondrial physiology, including oxidative phosphorylation, is also important for efficient mitochondrial division, morphological alterations of the mitochondrial inner-membrane (IMM) have not been clearly elucidated.
View Article and Find Full Text PDFHistochem Cell Biol
July 2017
Dynamin-related protein1 (Drp1) plays an essential role in mitochondrial fission: Cytosolic Drp1 is translocated to the mitochondria upon stimulus, and oligomerized Drp1 constricts mitochondria by aid of actin filaments. Drp1 completes the fission process with GTP hydrolysis by its own GTPase activity. The importance of actin filament and its interaction with Drp1 in the mitochondrial fission process have been demonstrated.
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