Search results for " STEM CELLS"
showing 10 items of 881 documents
Role of the Ha-ras gene in the malignant transformation of rat liver oval cells.
1997
We have shown that the oval cell line OCICDE 22 can be transformed by the highly carcinogenic fiord-region diol epoxides of benzo[c]phenanthrene. Mutational activation of the ras proto-oncogene family has been proposed to be a critical event in the formation of tumors induced by polycyclic aromatic hydrocarbons. Therefore, we investigated whether in the earlier transformed OCICDE 22 cells any point mutations were detected in the ras proto-oncogene. The results indicate that the malignant transformation of OCICDE 22 cells by the 4 stereoisomeric benzo[c]phenan-threne diol epoxides in vitro is independent of activation of the Ha-ras proto-oncogene. In addition, Northern and Western blot analy…
Mesenchymal stromal-cell transplants induce oligodendrocyte progenitor migration and remyelination in a chronic demyelination model.
2013
Demyelinating disorders such as leukodystrophies and multiple sclerosis are neurodegenerative diseases characterized by the progressive loss of myelin that may lead toward a chronic demyelination of the brain’s white matter, impairing normal axonal conduction velocity and ultimately causing neurodegeneration. Current treatments modifying the pathological mechanisms are capable of ameliorating the disease; however, frequently, these therapies are not sufficient to repress the progressive demyelination into a chronic condition and permanent loss of function. To this end, we analyzed the effect that bone marrow-derived mesenchymal stromal cell (BM-MSC) grafts exert in a chronically demyelinate…
Aldehyde Dehydrogenase 1-Positive Cancer Stem Cells Mediate Metastasis and Poor Clinical Outcome in Inflammatory Breast Cancer
2009
Abstract Purpose: To examine the role of cancer stem cells (CSC) in mediating metastasis in inflammatory breast cancer (IBC) and the association of these cells with patient outcome in this aggressive type of breast cancer. Experimental Design: CSCs were isolated from SUM149 and MARY-X, an IBC cell line and primary xenograft, by virtue of increased aldehyde dehydrogenase (ALDH) activity as assessed by the ALDEFLUOR assay. Invasion and metastasis of CSC populations were assessed by in vitro and mouse xenograft assays. Expression of ALDH1 was determined on a retrospective series of 109 IBC patients and this was correlated with histoclinical data. All statistical tests were two sided. Log-rank …
HER2 regulates the mammary stem/progenitor cell population driving tumorigenesis and invasion.
2008
The cancer stem cell hypothesis proposes that cancers arise in stem/progenitor cells through disregulation of self-renewal pathways generating tumors, which are driven by a component of 'tumor-initiating cells' retaining stem cell properties. The HER2 gene is amplified in 20-30% of human breast cancers and has been implicated in mammary tumorigenesis as well as in mediating aggressive tumor growth and metastasis. We demonstrate that HER2 overexpression drives mammary carcinogenesis, tumor growth and invasion through its effects on normal and malignant mammary stem cells. HER2 overexpression in normal mammary epithelial cells (NMEC) increases the proportion of stem/progenitor cells as demons…
Pharmacological targeting of the novel β-catenin chromatin-associated kinase p38α in colorectal cancer stem cell tumorspheres and organoids
2021
AbstractThe prognosis of locally advanced colorectal cancer (CRC) is currently unsatisfactory. This is mainly due to drug resistance, recurrence, and subsequent metastatic dissemination, which are sustained by the cancer stem cell (CSC) population. The main driver of the CSC gene expression program is Wnt signaling, and previous reports indicate that Wnt3a can activate p38 MAPK. Besides, p38 was shown to feed into the canonical Wnt/β-catenin pathway. Here we show that patient-derived locally advanced CRC stem cells (CRC-SCs) are characterized by increased expression of p38α and are “addicted” to its kinase activity. Of note, we found that stage III CRC patients with high p38α levels display…
Influence of interferon-alpha on cytokine expression by the bone marrow microenvironment--impact on treatment of myeloproliferative disorders.
1996
Myeloproliferative disorders (MPD) are characterized by several common clinical and biological features, although at the molecular level, each disease entity exhibits distinct abnormalities. IFN-alpha exerts beneficial therapeutic effects in chronic myelogenous leukemia, polycythemia vera and essential thrombocythemia, resulting in control of hematopoietic hyperplasia and, in a minority of patients, in induction of cytogenetic remission. The mechanism of action of IFN-alpha in MPD is poorly defined. Recently published in vitro findings suggest that IFN-alpha interacts with the regulation of hematopoiesis by multiple ways. Its antiproliferative activity is well known for more than a decade, …
Interleukin-6 and the soluble interleukin-6 receptor induce stem cell factor and Flt-3L expression in vivo and in vitro.
2001
Abstract Objective We recently established transgenic animals expressing either interleukin-6 (IL-6) or the soluble IL-6 receptor (sIL-6R) alone, or both components, IL-6 and the sIL-6R, in the liver. This animal model demonstrated that the expression of IL-6 in combination with its sIL-6R led to extramedullary expansion of hematopoietic progenitor cells in the spleen and liver. Materials and Methods We studied other relevant hematopoietic cytokines involved in the IL-6/sIL-6R–induced stimulation of hematopoiesis. Results Using immunohistochemistry, we showed that cell-associated stem cell factor (SCF) and Flt-3L expression were upregulated in liver and spleen only in double transgenic mice…
Tumor and its microenvironment: a synergistic interplay.
2013
The mutual and interdependent interaction between tumor and its microenvironment is a crucial topic in cancer research. Recently, it was reported that targeting stromal events could improve efficacies of current therapeutics and prevent metastatic spreading. Tumor microenvironment is a "complex network" of different cell types, soluble factors, signaling molecules and extracellular matrix components, which orchestrate the fate of tumor progression. As by definition, cancer stem cells (CSCs) are proposed to be the unique cell type able to maintain tumor mass and survive outside the primary tumor at metastatic sites. Being exposed to environmental stressors, including reactive oxygen species …
Janus-Faced role of microRNA let-7d in osteosarcoma 3AB-OS cancer stem cells
2015
Osteosarcoma (OS) is the most common malignancy of bone in children and adolescent. It is a highly invasive and metastatic bone-malignancy because of which, despite therapeutic advances, 30%-50% of patients still die of pulmonary metastasis. As a consequence, there is an urgent need to identify new therapeutic strategies to improve the clinical outcome of the patients. Advances in OS treatment are inconceivable without better understanding of molecular mechanism of osteosarmagenesis and, especially, metastatic processes. Growing evidence suggests that cancer stem cells (CSCs), which have self-renewing and malignant potential, are at the root of tumor growth and relapse. Thus, a challenge fo…
Human Embryonic Stem Cell Derived Hepatocyte-Like Cells as a Tool for In Vitro Hazard Assessment of Chemical Carcinogenicity
2011
Hepatocyte-like cells derived from the differentiation of human embryonic stem cells (hES-Hep) have potential to provide a human relevant in vitro test system in which to evaluate the carcinogenic hazard of chemicals. In this study, we have investigated this potential using a panel of 15 chemicals classified as noncarcinogens, genotoxic carcinogens, and nongenotoxic carcinogens and measured whole-genome transcriptome responses with gene expression microarrays. We applied an ANOVA model that identified 592 genes highly discriminative for the panel of chemicals. Supervised classification with these genes achieved a cross-validation accuracy of > 95%. Moreover, the expression of the response g…