Cancer-Associated Fibroblasts (CAFs) were shown to orchestrate tumour-promoting inflammation in multiple malignancies, including breast cancer. However, the molecular pathways that govern the inflammatory role of CAFs are poorly characterised. In this study we found that fibroblasts sense damage-associated molecular patterns (DAMPs), and in response activate the NLRP3 inflammasome pathway, resulting in instigation of pro-inflammatory signalling and secretion of IL-1β.
View Article and Find Full Text PDFInt J Infect Dis
December 2019
Background: Achieving a high degree of diagnostic accuracy of infections in the emergency department (ED) is crucial since a delay in diagnosis can lead to increased mortality, whereas overdiagnosis can lead to antibiotic overprescription. Limited data are available as to ED diagnostic accuracy of infections. The aim of this study was to demonstrate the degree of discordance of an ED diagnosis of pneumonia in relation to an internal medicine ward's discharge diagnosis of hospitalized adults.
View Article and Find Full Text PDFMelanoma is the deadliest skin cancer due to its high rate of metastasis, frequently to the brain. Brain metastases are incurable; therefore, understanding melanoma brain metastasis is of great clinical importance. We used a mouse model of spontaneous melanoma brain metastasis to study the interactions of melanomas with the brain microenvironment.
View Article and Find Full Text PDFAcute leukemia is a rapidly progressing blood cancer with low survival rates. Unfavorable prognosis is attributed to insufficiently characterized subpopulations of leukemia stem cells (LSC) that drive chemoresistance and leukemia relapse. Here we utilized a genetic reporter that assesses stemness to enrich and functionally characterize LSCs.
View Article and Find Full Text PDFAcute leukemia is an aggressive blood malignancy with low survival rates. A high expression of stem-like programs in leukemias predicts poor prognosis and is assumed to act in an aberrant fashion in the phenotypically heterogeneous leukemia stem cell (LSC) population. A lack of suitable genome engineering tools that can isolate LSCs based on their stemness precludes their comprehensive examination and full characterization.
View Article and Find Full Text PDFFailure to precisely repair DNA damage in self-renewing Hematopoietic Stem and early Progenitor Cells (HSPCs) can disrupt normal hematopoiesis and promote leukemogenesis. Although HSPCs are widely considered a target of ionizing radiation (IR)-induced hematopoietic injury, definitive data regarding cell death, DNA repair, and genomic stability in these rare quiescent cells are scarce. We found that irradiated HSPCs, but not lineage-committed progenitors (CPs), undergo rapid ATM-dependent apoptosis, which is suppressed upon interaction with bone-marrow stroma cells.
View Article and Find Full Text PDFSelf-renewing and multipotent hematopoietic stem cells (HSCs) maintain lifelong hematopoiesis. Their enormous regenerative potential coupled with lifetime persistence in the body, in contrast with the Progenitors, demand tight control of HSCs genome stability. Indeed, failure to accurately repair DNA damage in HSCs is associated with bone marrow failure and accelerated leukemogenesis.
View Article and Find Full Text PDFThe molecular determinants governing escape of Acute Myeloid Leukemia (AML) cells from DNA damaging therapy remain poorly defined and account for therapy failures. To isolate genes responsible for leukemia cells regeneration following multiple challenges with irradiation we performed a genome-wide shRNA screen. Some of the isolated hits are known players in the DNA damage response (e.
View Article and Find Full Text PDFQuercetin (Que) is an abundant flavonoid in the human diet and high-concentration food supplement with reported pro- and anti-carcinogenic activities. Topoisomerase II (TopoII) inhibition and subsequent DNA damage induction by Que was implicated in the mixed lineage leukemia gene (MLL) rearrangements that can induce infant and adult leukemias. This notion raised concerns regarding possible genotoxicities of Que in hematopoietic stem and progenitor cells (HSPCs).
View Article and Find Full Text PDFAim: To examine the factors associated with placenta praevia in primigravidas and also compare the pregnancy outcomes between primigravidas and nonprimigravidas.
Method: A retrospective cohort study was conducted in women who underwent caesarean section for major placenta praevia in a tertiary university hospital from January 2007 till December 2013. Medical records were reviewed.
Biomed Res Int
April 2014
Objective. To determine the diagnostic accuracy of placental alpha microglobulin-1 assay and standard diagnostic methods for detecting rupture of membrane. Study Design.
View Article and Find Full Text PDFPurpose: Retained placenta is potentially life threatening due to possible complications associated with manual removal. Our aim was to determine whether umbilical vein injection of oxytocin in saline reduces the need for manual removal of placenta.
Methods: This was a randomised controlled trial conducted at a tertiary hospital from December 2002 to March 2004.