Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate epithelial stem cells are self-renewing cells capable of differentiation into prostate epithelium, and are thought to contribute towards both benign and malignant conditions in the human prostate. We have previously demonstrated that prostate epithelial basal cells express high levels of integrin alpha2beta1 and this population can be subdivided into stem (alpha2beta1(hi) CD133+) and transient-amplifying population (TAP) cells (alpha2beta1(hi) CD133-). However, the molecular mechanism(s) controlling the commitment and regulation of these cells towards differentiated epithelium remains unclear. Here, we demonstrate that beta1 integrin function is required for the maintenance of basal prostatic epithelial cells and suppression of its function by either methylcellulose or, more specifically, beta1-blocking antibody (80 microg/ml) induces differentiation, with associated expression of the differentiation-specific markers prostate acid phosphatase (PAP) and cytokeratin 18 (CK18). Keratinocyte growth factor (KGF), a stromal-derived growth factor, has previously been implicated in prostate organogenesis using in vitro tissue recombination experiments. We show that treatment with KGF (10 ng/ml) potently induces epithelial differentiation with concomitant suppression of alpha2beta1 integrin expression as well as the induction of androgen receptor expression. Specifically, p38-MAPK appears to be involved and the presence of SB202190, a p38 inhibitor, significantly blocks KGF-induced differentiation. Furthermore, the expression of the high-affinity receptor tyrosine kinase to KGF (FGFR2) is predominantly detectable in alpha2beta1(hi) CD133- TAP cells when compared with stem cells (alpha2beta1(hi) CD133+), which would therefore be relatively unresponsive to the differentiating effect of KGF. Taken together, using a human primary culture model, we have demonstrated key roles for interactions between KGF and integrin-mediated function in the regulation of prostate epithelial differentiation.
...
PMID:KGF suppresses alpha2beta1 integrin function and promotes differentiation of the transient amplifying population in human prostatic epithelium. 1655 39

This study evaluated the significance of circulating bone marrow-derived endothelial progenitor cells (EPCs) in patients with hepatocellular carcinoma (HCC), a solid tumor with rich neovasculature. Eighty patients with HCC were recruited for the study, and 16 patients with liver cirrhosis and 14 healthy subjects were also included for comparison. Blood samples were taken before treatment. Total mononuclear cells were isolated from peripheral blood, preplated to eliminate mature circulating endothelial cells, and colony-forming units (CFUs) formed by circulating EPCs were counted. To validate the CFU scores, FACS quantification of EPCs using CD133, VEGFR2, and CD34 as markers was performed in 30 cases. Our study showed significantly higher mean CFU scores in patients with HCC compared to patients with cirrhosis and healthy controls (P = .001 and .009, respectively). Furthermore, the CFU scores of patients with HCC positively correlated with levels of serum alpha-fetoprotein (r = .303, P = .017), plasma VEGF (r = .242, P = .035), and plasma interleukin-8 (IL-8) (r = .258, P = .025). Patients with unresectable HCC had higher CFU scores than patients with resectable tumors (P = .027). Furthermore, for those who underwent curative surgery, higher preoperative CFU scores were observed in patients with recurrence within 1 year compared with those who were disease-free after 1 year (P = .013). In conclusion, higher circulating levels of EPCs are seen in patients with advanced unresectable HCC as compared to patients with resectable HCC or those with liver cirrhosis. Our evidence supports the potential use of circulating level of EPCs as a prognostic marker in patients with HCC.
...
PMID:Significance of circulating endothelial progenitor cells in hepatocellular carcinoma. 1700 19

The hierarchy of endothelial progenitor cells (EPCs) in human umbilical cord blood has been disclosed. In this study we compare, for the first time, the angiogenic potential difference between two types of EPCs. We cultured mononuclear cells (MNCs) isolated from human umbilical cord blood using endothelial cell-conditioned medium and obtained two types of EPCs, referred to as circulating angiogenic cells (CACs) and high proliferative potential endothelial progenitor cells (HPP-EPCs). Both types of cells possess characteristics of EPCs, including expressing CD31, VE-cadherin, KDR and von Willebrand factor, uptake of Ac-LDL and binding to lectin. However, unlike CACs, which express CD14 but not CD133, HPP-EPCs express CD133 but not CD14. Also, unlike CACs, HPP-EPCs display stronger proliferation and clonogenic potential in vitro and show stronger ability to promote vascular growth in the hind-limb model of ischemia in mice (BALB/C-nu) in vivo.
...
PMID:Angiogenic potential difference between two types of endothelial progenitor cells from human umbilical cord blood. 1702 Aug 9

Blood-derived adult stem cells were previously considered impractical for therapeutic use because of their small numbers. This report describes the isolation of a novel human cell population derived from the peripheral blood, termed synergetic cell population (SCP), and defined by the expression of CD31Bright, CD34+, CD45-/Dim and CD34Bright, but not lineage-specific features. The SCP was capable of differentiating into a variety of cell lineages upon exposure to defined culture conditions. The resulting cells exhibited morphological, immunocytochemical and functional characteristics of angiogenic, neural or myocardial lineages. Angiogenic cell precursors (ACPs) expressed CD34, CD133, KDR, Tie-2, CD144, von Willebrand factor, CD31Bright, concomitant binding of Ulex-Lectin and uptake of acetylated low density lipoprotein (Ac-LDL), secreted interleukin-8, vascular endothelial growth factor and angiogenin and formed tube-like structures in vitro. The majority of CD31Bright ACP cells demonstrated Ac-LDL uptake. Neural cell precursors (NCPs) expressed the neuronal markers Nestin, betaIII-Tubulin, and Neu-N, the glial markers GFAP and O4, and responded to neurotransmitter stimulation. Myocardial cell precursors (MCPs) expressed Desmin, cardiac Troponin and Connexin 43. In conclusion, the simple and rapid method of SCP generation and the resulting considerable quantities of lineage-specific precursor cells makes it a potential source of autologous treatment for a variety of diseases.
...
PMID:Isolation of an adult blood-derived progenitor cell population capable of differentiation into angiogenic, myocardial and neural lineages. 1705 54

To detect endothelial progenitor cells in human umbilical veins and isolated endothelial cells, the authors examined protein and mRNA expression levels of cell surface markers for endothelial progenitor cells in human umbilical veins before and after trypsin treatment and at different passages of the isolated endothelial cells. CD133(+) (2.14 +/- 0.57 per mm) and KDR(+) (35.74 +/- 8.28 per mm) cells were observed in the intima of umbilical veins. The amounts of CD133(+), KDR(+), CD34(+), and CD105(+) cells decreased in the intima after trypsin treatment, whereas the percent of CD133(+) and KDR(+)cells in the media did not change significantly. Moreover, similar protein and mRNA expression levels of CD133 and KDR were detected in the umbilical veins before and after trypsin treatment. In the isolated cells from umbilical veins, the percent of CD133(+) and CD34(+) cells in P1 was 3.43% +/- 3.85%, which was higher than those in P3 (0.17% +/- 0.21%, p = 0.005) and P6 (0.14% +/- 0.18%, p = .001). The mRNA expression levels of CD133 and CD105 were down-regulated in later passages compared to those in P1, whereas the expression level of KDR was up-regulated in late passages. Thus it is suggested that endothelial progenitor cells reside in the distinct zone (e.g., initma and media) of human umbilical veins, and retain the capacity of differentiation to endothelial cells in vitro.
...
PMID:Validation of endothelial progenitor cells in human umbilical veins and the isolated endothelial cells. 1757 8

Estrogen has been demonstrated to promote therapeutic reendothelialization after vascular injury by bone marrow (BM)-derived endothelial progenitor cell (EPC) mobilization and phenotypic modulation. We investigated the primary hypothesis that estrogen regulates physiological postnatal vasculogenesis by modulating bioactivity of BM-derived EPCs through the estrogen receptor (ER), in cyclic hormonally regulated endometrial neovascularization. Cultured human EPCs from peripheral blood mononuclear cells (PB-MNCs) disclosed consistent gene expression of ER alpha as well as downregulated gene expressions of ER beta. Under the physiological concentrations of estrogen (17beta-estradiol, E2), proliferation and migration were stimulated, whereas apoptosis was inhibited on day 7 cultured EPCs. These estrogen-induced activities were blocked by the receptor antagonist, ICI182,780 (ICI). In BM transplanted (BMT) mice with ovariectomy (OVX) from transgenic mice overexpressing beta-galactosidase (lacZ) regulated by an endothelial specific Tie-2 promoter (Tie-2/lacZ/BM), the uterus demonstrated a significant increase in BM-derived EPCs (lacZ expressing cells) incorporated into neovasculatures detected by CD31 immunohistochemistry after E2 administration. The BM-derived EPCs that were incorporated into the uterus dominantly expressed ER alpha, rather than ER beta in BMT mice from BM of transgenic mice overexpressing EGFP regulated by Tie-2 promoter with OVX (Tie-2/EGFP/BMT/OVX) by ERs fluorescence immunohistochemistry. An in vitro assay for colony forming activity as well as flow cytometry for CD133, CD34, KDR, and VE-cadherin, using human PB-MNCs at 5 stages of the female menstrual-cycle (early-proliferative, pre-ovulatory, post-ovulatory, mid-luteal, late-luteal), revealed cycle-specific regulation of EPC kinetics. These findings demonstrate that physiological postnatal vasculogenesis involves cyclic, E2-regulated bioactivity of BM-derived EPCs, predominantly through the ER alpha.
...
PMID:Estrogen-mediated endothelial progenitor cell biology and kinetics for physiological postnatal vasculogenesis. 1765 79

Seminomas are characterized by expression of several stem cell markers, supporting their origin from germ cells. The current study focuses on novel germ cell markers in normal testes compared to those in fetal testes and different progression stages of seminomas. Microarray data were followed by RT-PCRs and immunohistochemistry on pure seminomas (pT1 to pT3) compared to adult and fetal testis. An upregulation of known germ cell markers, KIT, OCT4 and NANOG, was confirmed in seminoma specimens. We also identified novel germ cell markers such as BOB1 (POU2AF1, OBF1) and prominin 1 (PROM1, CD133), which were significantly upregulated in seminoma specimens, compared to normal testes. Furthermore, two Sertoli cell markers, SCGF (SCF) and the newly identified neuronal stem cell factor, MCFD2 (SDNSF), were expressed in seminoma cells. While BOB1 was expressed in fetal testis of second and third trimester of gestation, MCFD2 and PROM1 were only present in gonocytes up to the second trimester. All marker genes investigated were not further regulated in progressing tumour stages between pT1 and pT3. In conclusion, the germ cell markers described here provide evidence for the origin of seminoma cells, which could be from the developmental stage of early gonocytes or from spermatogonia re-expressing markers of the developing germ cells.
...
PMID:Novel germ cell markers characterize testicular seminoma and fetal testis. 1778 71

Endothelial progenitor cells (EPC) predict morbidity and mortality in patients at cardiovascular risk.Patients with low EPC counts and impaired endothelial colony forming activity have a higher incidence for cardiovascular events compared to patients with high EPC counts and favorable colony forming activity. The pathophysiological basis for this finding may be an insufficient endothelial cell repair by EPC.We postulate that EPC influence coronary endothelial function which itself is relevant for the outcome of patients at cardiovascular risk. To test this hypothesis in humans, endothelial function was invasively assessed in 90 patients with coronary heart disease by quantitative coronary angiography during intracoronary acetylcholine infusion. Flow cytometry of mononuclear cells isolated from peripheral blood was performed to assess CD133(+) or CD34(+)/KDR(+) EPC. EPC function was assessed ex vivo by determination of endothelial colony forming units. Low EPC number as well as impaired endothelial colony forming activity correlated with severely impaired coronary endothelial function in univariate analysis. Multivariate analysis revealed that only the number of EPC predicts severe endothelial dysfunction independent of classical cardiovascular risk factors. Endothelial function closely correlates with the number of circulating EPC providing new mechanistic insights and options for risk assessment in patients with coronary heart disease.
...
PMID:Endothelial progenitor cells correlate with endothelial function in patients with coronary artery disease. 1793 8

Basal-like breast carcinoma is an aggressive form of breast cancer, characterized by the absence of oestrogen receptor and HER2 expression, the presence of cytokeratin 5 and epidermal growth factor receptor expression, and by the up-regulation of stem cell regulatory genes. We show here that tumour tissues expressing high levels of SLUG mRNA show a basal-like breast carcinoma phenotype and that such tumours also express high levels of stem cell-regulatory genes, ie CD133, Bmi1. Further, we show that stem/progenitor cells, isolated from ductal breast carcinoma and from normal mammary gland as mammospheres, express SLUG, CD133, and Bmi1 mRNA and show a phenotype similar to that of basal-like breast carcinoma. We also report that SLUG expression in tumour tissues correlates with that of the hypoxia survival gene carbonic anhydrase IX. In this regard, we report that the exposure of SLUG-negative/luminal-like MCF-7 cells to a hypoxic environment promotes the onset of the basal-like breast carcinoma phenotype, together with up-regulation of the SLUG gene, which in turn blunts oestrogen receptor-alpha and boosts carbonic anhydrase IX gene expression. Finally, we show that SLUG expression promotes the invasiveness of MCF-7 cells exposed to hypoxia and sustains the in vivo aggressiveness of hypoxia-selected, MCF-7-derived cells in xenografts. These data indicate that SLUG gene expression is part of a hypoxia-induced genetic programme which sets up a basal/stem cell-like, aggressive phenotype in breast cancer cells.
...
PMID:The basal-like breast carcinoma phenotype is regulated by SLUG gene expression. 1797 39

Tumor growth and metastasis is dependent on the formation and assembly of new blood vessels, a process known as neo-angiogenesis. Both pre-existing and circulating vascular cells have been shown to contribute to the assembly of tumor neo-vessels in specific tumors. Mobilization of endothelial progenitor cells (EPCs) from the bone marrow constitutes a crucial step in the formation of de novo blood vessels, and levels of peripheral blood EPCs have been shown to be increased in certain malignant states. However, the role of circulating EPCs in breast cancer is largely unknown. We recruited twenty-five patients with biopsy-proven invasive breast cancer at Weill Cornell Breast Center to participate in a pilot study investigating the correlation of circulating EPCs to extent of disease and initiation of chemotherapy. For each patient, a baseline sample was drawn before systemic treatment, and for seventeen of those patients, a second sample was taken after the first round of chemotherapy. Levels of peripheral blood EPCs, as defined by co-expression of CD133 and VEGFR2, were quantified by flow cytometry. Breast cancer patients with stage III & IV disease had statistically higher levels of circulating EPCs than did patients with stage I & II disease (median = 165,000 EPCs/5 x 10(6)MNCs vs. median = 6,920 EPCs/5 x 10(6)MNCs, respectively, P < 0.0001). In addition, in late-stage patients, levels of EPCs demonstrated a statistically significant drop after initiation of chemotherapy (median = 162,500 EPCs/5 x 10(6)MNCs [pre] vs. median = 117,500 EPCs/5 x 10(6)MNCs [post], P = 0.01). These results suggest that circulating EPCs may serve as a potential tumor biomarker in breast cancer and that EPCs may represent a plausible target for future therapeutic intervention.
...
PMID:Circulating endothelial progenitor cells correlate to stage in patients with invasive breast cancer. 1804 99


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---