Search results for "breast neoplasm"
showing 10 items of 809 documents
Nitric Oxide-Releasing Drug Glyceryl Trinitrate Targets JAK2/STAT3 Signaling, Migration and Invasion of Triple-Negative Breast Cancer Cells
2021
Triple-negative breast cancer (TNBC) is a highly aggressive disease with invasive and metastasizing properties associated with a poor prognosis. The STAT3 signaling pathway has shown a pivotal role in cancer cell migration, invasion, metastasis and drug resistance of TNBC cells. IL-6 is a main upstream activator of the JAK2/STAT3 pathway. In the present study we examined the impact of the NO-donor glyceryl trinitrate (GTN) on the activation of the JAK2/STAT3 signaling pathway and subsequent migration, invasion and metastasis ability of TNBC cells through in vitro and in vivo experiments. We used a subtoxic dose of carboplatin and/or recombinant IL-6 to activate the JAK2/STAT3 signaling path…
miR-20b modulates VEGF expression by targeting HIF-1 alpha and STAT3 in MCF-7 breast cancer cells.
2010
MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of different genes, including genes involved in cancer progression. A functional link between hypoxia, a key feature of the tumor microenvironment, and miRNA expression has been documented. We investigated whether and how miR-20b can regulate the expression of vascular endothelial growth factor (VEGF) in MCF-7 breast cancer cells under normoxic and hypoxia-mimicking conditions (CoCl(2) exposure). Using immunoblotting, ELISA, and quantitative real-time PCR, we demonstrated that miR-20b decreased VEGF protein levels at 4 and 24 h following CoCl(2) treatment, and VEGF mRNA at 4 h of treatment. In addition, miR-20b reduce…
Compromised nuclear envelope integrity drives TREX1-dependent DNA damage and tumor cell invasion
2021
Although mutations leading to a compromised nuclear envelope cause diseases such as muscular dystrophies or accelerated aging, the consequences of mechanically induced nuclear envelope ruptures are less known. Here, we show that nuclear envelope ruptures induce DNA damage that promotes senescence in non-transformed cells and induces an invasive phenotype in human breast cancer cells. We find that the endoplasmic reticulum (ER)-associated exonuclease TREX1 translocates into the nucleus after nuclear envelope rupture and is required to induce DNA damage. Inside the mammary duct, cellular crowding leads to nuclear envelope ruptures that generate TREX1-dependent DNA damage, thereby driving the …
Proteomic analysis reveals a role for Bcl2-associated athanogene 3 and major vault protein in resistance to apoptosis in senescent cells by regulatin…
2014
Senescence is a prominent solid tumor response to therapy in which cells avoid apoptosis and instead enter into prolonged cell cycle arrest. We applied a quantitative proteomics screen to identify signals that lead to therapy-induced senescence and discovered that Bcl2-associated athanogene 3 (Bag3) is up-regulated after adriamycin treatment in MCF7 cells. Bag3 is a member of the BAG family of co-chaperones that interacts with Hsp70. Bag3 also regulates major cell-signaling pathways. Mass spectrometry analysis of the Bag3 Complex revealed a novel interaction between Bag3 and Major Vault Protein (MVP). Silencing of Bag3 or MVP shifts the cellular response to adriamycin to favor apoptosis. We…
GPCALMA: A Grid-based tool for mammographic screening
2005
The next generation of High Energy Physics (HEP) experiments requires a GRID approach to a distributed computing system and the associated data management: the key concept is the Virtual Organisation (VO), a group of distributed users with a common goal and the will to share their resources. A similar approach is being applied to a group of Hospitals which joined the GPCALMA project (Grid Platform for Computer Assisted Library for MAmmography), which will allow common screening programs for early diagnosis of breast and, in the future, lung cancer. HEP techniques come into play in writing the application code, which makes use of neural networks for the image analysis and proved to be useful…
The synergistic effect of SAHA and parthenolide in MDA-MB231 breast cancer cells
2014
Abstract: The sesquiterpene lactone Parthenolide (PN) exerted a cytotoxic effect on MDA-MB231 cells, a triple-negative breast cancer (TNBC) cell line, but its effectiveness was scarce when employed at low doses. This represents an obstacle for a therapeutic utilization of PN. In order to overcome this difficulty we associated to PN the suberoylanilide hydroxamic acid (SAHA), an histone deacetylase inhibitor. Our results show that SAHA synergistically sensitized MDA-MB231 cells to the cytotoxic effect of PN. It is noteworthy that treatment with PN alone stimulated the survival pathway Akt/mTOR and the consequent nuclear translocation of Nrf2, while treatment with SAHA alone induced autophagi…
The Chaperone System in Breast Cancer: Roles and Therapeutic Prospects of the Molecular Chaperones Hsp27, Hsp60, Hsp70, and Hsp90
2022
Breast cancer (BC) is a major public health problem, with key pieces of information needed for developing preventive and curative measures still missing. For example, the participation of the chaperone system (CS) in carcinogenesis and anti-cancer responses is poorly understood, although it can be predicted to be a crucial factor in these mechanisms. The chief components of the CS are the molecular chaperones, and here we discuss four of them, Hsp27, Hsp60, Hsp70, and Hsp90, focusing on their pro-carcinogenic roles in BC and potential for developing anti-BC therapies. These chaperones can be targets of negative chaperonotherapy, namely the elimination/blocking/inhibition of the chaperone(s)…
Metabolic impact of Partial Volume Correction of [18F]FDG PET-CT oncological studies on the assessment of tumor response to treatment
2014
AIM: The aim of this work is to evaluate the metabolic impact of Partial Volume Correction (PVC) on the measurement of the Standard Uptake Value (SUV) from [18F]FDG PET-CT oncological studies for treatment monitoring purpose. METHODS: Twenty-nine breast cancer patients with bone lesions (42 lesions in total) underwent [18F]FDG PET-CT studies after surgical resection of breast cancer primitives, and before (PET-I) and after (PET-II) chemotherapy and hormone treatment. PVC of bone lesion uptake was performed on the two [18F]FDG PET-CT studies, using a method based on Recovery Coefficients (RC) and on an automatic measurement of lesion metabolic volume. Body-weight average SUV was calculated f…
Computer assisted diagnosis (CAD) in mammography. Comparison of diagnostic accuracy of a new algorithm (Cyclopus(R), Medicad) with two commercial sys…
2008
The study compares the diagnostic accuracy (correct identification of cancer) of a new computer-assisted diagnosis (CAD) system (Cyclopus) with two other commercial systems (R2 and CADx). Cyclopus was tested on a set of 120 mammograms on which the two compared commercial systems had been previously tested. The set consisted of mammograms reported as negative, preceding 31 interval cancers reviewed as screening error or minimal sign, and of 89 verified negative controls randomly selected from the same screening database. Cyclopus sensitivity was 74.1% (R2=54.8%; CADx=41.9%) and was higher for interval cancers reviewed as screening error (90.9%; R2=54.5%; CADx=81.8%) compared with those revie…
The mitotic kinase Aurora-A promotes distant metastases by inducing epithelial-to-mesenchymal transition in ERα+ breast cancer cells
2013
In this study, we demonstrate that constitutive activation of Raf-1 oncogenic signaling induces stabilization and accumulation of Aurora-A mitotic kinase that ultimately drives the transition from an epithelial to a highly invasive mesenchymal phenotype in estrogen receptor α-positive (ERα(+)) breast cancer cells. The transition from an epithelial- to a mesenchymal-like phenotype was characterized by reduced expression of ERα, HER-2/Neu overexpression and loss of CD24 surface receptor (CD24(-/low)). Importantly, expression of key epithelial-to-mesenchymal transition (EMT) markers and upregulation of the stemness gene SOX2 was linked to acquisition of stem cell-like properties such as the ab…