Cytotoxic effects of targeted agent alone or with chemotherapy in the treatment of adenoid cystic carcinoma: a preclinical study.

Adenoid cystic carcinoma (ACC) is a rare malignancy characterized by high incidence of relapse. When relapsing, ACC has an indolent but relentless behaviour, thus leading to a poor long-term prognosis. The treatment of choice of relapsing ACC remains surgery followed by radiotherapy, whenever feasible.

HMGA1 negatively regulates NUMB expression at transcriptional and post transcriptional level in glioblastoma stem cells.

Glioblastoma (GBM) is a lethal, fast-growing brain cancer, affecting 2-3 per 100,000 adults per year. It arises from multipotent neural stem cells which have reduced their ability to divide asymmetrically and hence divide symmetrically, generating increasing number of cancer stem cells, fostering tumor growth. We have previously demonstrated that the architectural transcription factor HMGA1 is highly expressed in brain tumor stem cells (BTSCs) and that its silencing increases stem cell quiescence, reduces self-renewal and sphere-forming efficiency in serial passages, suggesting a shift from symmetric to asymmetric division.

Isolation and substrate specificity of an adenine nucleoside phosphorylase from adult Schistosoma mansoni.

An adenine nucleoside phosphorylase (ANP, EC none) activity was identified and partially purified from extracts of Schistosoma mansoni by chromatofocussing column chromatography and molecular sieving. The enzyme is distinct from purine nucleoside phosphorylase (PNP, EC 2.4.

Photocrystallographic identification of metastable nitrito linkage isomers in a series of nickel(II) complexes.

Single crystal photocrystallographic experiments and solid state Raman spectroscopy have been used to determine the low temperature, metastable structures of the nickel(ii) nitrito complexes [Ni(aep)(2)(η(1)-ONO)(2)] 1#O (aep = 1-(2-aminoethyl)piperidine), [Ni(aem)(2)(η(1)-ONO)(2)] 2#O (aem = 1-(2-aminoethyl)morpholine), and [Ni(aepy)(2)(η(1)-ONO)(2)] 3#O (aepy = 1-(2-aminoethyl)pyrrolidine and where the #O denotes the oxygen-bound nitrito metastable molecule). These linkage isomers of the equivalent nitro complexes [Ni(aep)(2)(η(1)-NO(2))(2)] 1, [Ni(aem)(2)(η(1)-NO(2))(2)] 2 and [Ni(aepy)(2)(η(1)-NO(2))(2)] 3 are formed by LED irradiation at temperatures below 120 K. The behavior of the three complexes upon irradiation is generally similar, but some subtle differences have been observed.

Serum IGF-1 concentrations change with soy and seaweed supplements in healthy postmenopausal American women.

Insulin-like growth factor 1 (IGF-1) is an anabolic hormone important for growth and development. However, high-circulating serum concentrations in adults are associated with increased risk of postmenopausal breast cancer. Nutritional status and specific foods influence serum IGF-1 concentrations.

Syntheses, structures and properties of cadmium benzenedicarboxylate metal-organic frameworks.

The products isolated from the reaction between Cd(NO3)2 x 4H2O and 1,4-benzenedicarboxylic acid (H2bdc) in DMF are very dependent on the conditions. At 115 degrees C, the reaction gives [Cd(bdc)(DMF)]infinity, which has a three-dimensional network structure, whereas at 95 degrees C, 1 is formed alongside [Cd3(bdc)3(DMF)4]infinity 2, which has a two-dimensional network structure. When the reaction is carried out under pressure, it yields [Cd3(bdc)3(DMF)4]infinity 3, which is a supramolecular isomer of 2.

Correlation of umbilical cord blood haematopoietic stem and progenitor cell levels with birth weight: implications for a prenatal influence on cancer risk.

We examined the relation with birth weight and umbilical cord blood concentrations of haematopoietic stem and progenitor populations in 288 singleton infants. Across the whole range of birth weight, there was a positive relation between birth weight and CD34+CD38(-) cells, with each 500 g increase in birth weight being associated with a 15.5% higher (95% confidence interval: 1.

Correlation of umbilical cord blood hormones and growth factors with stem cell potential: implications for the prenatal origin of breast cancer hypothesis.

Introduction: Prenatal levels of mitogens may influence the lifetime breast cancer risk by driving stem cell proliferation and increasing the number of target cells, and thereby increasing the chance of mutation events that initiate oncogenesis. We examined in umbilical cord blood the correlation of potential breast epithelial mitogens, including hormones and growth factors, with hematopoietic stem cell concentrations serving as surrogates of overall stem cell potential.

Methods: We analyzed cord blood samples from 289 deliveries.

Normal breast stem cells, malignant breast stem cells, and the perinatal origin of breast cancer.

Both experimental and epidemiological evidence support the concept that the in utero environment can influence an individual's risk of breast cancer in adult life. Recently identified breast stem cells may be the key to understanding the mechanism underlying this phenomenon. It has been theorized that breast cancers arise from breast stem cells.

Photocrystallographic structure determination of a new geometric isomer of [Ru(NH3)4(H2O)(eta1-OSO)][MeC6H4SO3]2.

The structure of a new metastable geometric isomer of [Ru(NH3)4(H2O)(SO2)][MeC6H4SO3]2 in which the SO2 group is coordinated through a single oxygen in an eta1-OSO bonding mode has been determined at 13 K; the new isomer was obtained as a 36% component of the structure within a single crystal upon irradiation using a tungsten lamp.

Osteopontin expression in intratumoral astrocytes marks tumor progression in gliomas induced by prenatal exposure to N-ethyl-N-nitrosourea.

To better study early events in glioma genesis, markers that reliably denote landmarks in glioma development are needed. In the present study, we used microarray analysis to compare the gene expression patterns of magnetic resonance imaging (MRI)-localized N-ethyl-N-nitrosourea (ENU)-induced tumors in rat brains with those of uninvolved contralateral side and normal brains. Our analysis identified osteopontin (OPN) as the most up-regulated gene in glioma.

Isolation of immortalized, INK4a/ARF-deficient cells from the subventricular zone after in utero N-ethyl-N-nitrosourea exposure.

Object: Brain tumors, including gliomas, develop several months after rats are exposed in utero to N-ethyl-N-nitroso-urea (ENU). Although pathological changes cannot be detected until these animals are several weeks old, the process that eventually leads to glioma formation must begin soon after exposure given the rapid clearance of the carcinogen and the observation that transformation of brain cells isolated soon after exposure occasionally occurs. This model can therefore potentially provide useful insights about the early events that precede overt glioma formation.

Neural stem cells and neuro-oncology: quo vadis?

Conventionally, gliomas are assumed to arise via transformation of an intraparenchymal glial cell that forms a mass that then expands centrifugally, eventually invading surrounding tissues. We propose an alternative model in which gliomas arise via initiation and promotion of cells within the brain's subependymal layer or subventricular zone, the source of a recently characterized pool of neural cells with the properties of self-renewal and multipotentiality (i.e.

A method for clonal analysis of epidermal growth factor-responsive neural progenitors.

Epidermal growth factor (EGF) responsive neural progenitors are defined by clonal growth from single cells. In previous studies we were unable to obtain clones at single cell densities using trypsinized cells and trituration alone always gave cellular aggregates. Here we report on single cell derived clones using a technique involving trituration of EGF responsive neurospheres, cell filtration, and single cell sorting using a MoFlo high speed fluorescence activated cell sorter.

Coexpression of oncostatin M and its receptors and evidence for STAT3 activation in human ovarian carcinomas.

The expression of oncostatin M and leukemia inhibitory factor (LIF), JAK-STAT activators and members of the interleukin-6 family of cytokines, were examined in a series of primary ovarian carcinomas using immunohistochemistry. The malignant epithelial cells of all 29 ovarian carcinomas examined expressed oncostatin M; none expressed LIF. Oncostatin M can activate two related receptors, one consisting of a low-affinity LIF receptor subunit, LIFR beta, which forms a heterocomplex with the gp130 signal transducing protein and can recognize both oncostatin M and LIF, and a second heterocomplex consisting of a subunit that specifically recognizes oncostatin M, OSMR beta, and the gp130 protein.

Neural precursor cells form rudimentary tissue-like structures in a rotating-wall vessel bioreactor.

We have analyzed the biology of embryonic, epidermal growth factor-responsive murine neural precursor cells cultured in the high-aspect ratio vessel (HARV). Within 2-3 d of rotary-cell culture, such cells formed multiple, macroscopic, three-dimensional structures that were orders of magnitude larger than the cellular clusters ("neurospheres") formed by these cells in conventional stationary-flask cultures. Each HARV structure was composed of a multilayered cellular shell surrounding one or more central cavities that were bordered by pyknotic cell nuclei.

Neurotrophin channeling of neural progenitor cell differentiation.

The act of defining neuropoietic progenitor/stem cells is still in its early phases. Epidermal growth factor (EGF) stimulates extended proliferation of aggregates of subventricular striatal cells, taken from E15 mouse striatum, termed neurospheres in liquid culture. We have shown here and in previous work, using either immunohistochemistry or RT-PCR, that neurosphere cells express 13 cytokines (32 tested) and 20 cytokine receptors (28 tested), with 11 potential paracrine and nine potential autocrine loops.

Interleukin-11 receptor expression in primary ovarian carcinomas.

Objectives: The objectives of this study were to determine (1) the frequency of expression of the interleukin-11 receptor alpha subunit (IL-11Ralpha) and its signal transducing subunit, gp130, among primary ovarian carcinomas; (2) the frequency of expression of IL-11 in ovarian carcinomas; and (3) the potential role IL-11 might have in ovarian cancer cell biology.

Methods: An immunohistochemical assay was used to determine the expression of IL-11Ralpha and the gp130 cofactor among primary ovarian carcinomas; the expression of IL-11 in ovarian malignancies was determined using reverse transcription polymerase chain reaction (RT-PCR). The ability of IL-11 to stimulate [3H]thymidine incorporation in IL-11R-expressing ovarian carcinoma cell lines (OVCAR-3 and SKOV-3) and/or abrogate cell death mediated by apoptosis-inducing agents using an ELISA assay that quantitates DNA fragmentation was also studied.

Increased expression of the interleukin-11 receptor and evidence of STAT3 activation in prostate carcinoma.

Previous investigations have shown that interleukin-6, a member of the JAK-STAT activating family of cytokines, plays an important role in prostate carcinoma. Here we demonstrate the co-expression of another member of this cytokine family, interleukin-11 (IL-11), and components of its receptor (interleukin-11 receptor; IL-11R), ie, IL-11Ralpha (involved in ligand recognition), and gp130 (involved in signal transduction) in cultured normal and malignant prostate-derived epithelial cell lines. In the DU-145 prostate carcinoma cell line, rhIL-11 stimulates a transient and dose-dependent increase in the tyrosine 705-phosphorylated, active form of STAT3 (STAT3 P-Tyr705), involved in the downstream signaling of IL-11R and other members of the gp130-dependent receptors.

Coexpression of granulocyte colony stimulating factor and its receptor in primary ovarian carcinomas.

Immunohistochemistry was used to determine the expression of granulocyte colony-stimulating factor (G-CSF) and its receptor (G-CSFR) in primary ovarian carcinomas. The expression of G-CSFR was observed in the malignant cells of each of the 46 primary carcinomas examined; G-CSF was coexpressed in both the malignant epithelial cells and the stroma of 56.5% of the specimens.

Correlates between hematopoiesis and neuropoiesis: neural stem cells.

There are many parallels between the neuropoietic and lymphohematopoietic systems. The lymphohematopoietic stem/progenitor cell system has been extensively characterized, but there are still major questions relating to the definitive stem cell assay, the structure of the system (i.e.

Expression of multiple angiogenic cytokines in cultured normal human prostate epithelial cells: predominance of vascular endothelial growth factor.

The cytokines that regulate angiogenesis in normal and malignant prostate tissue are not well studied. Using an RT-PCR-based screen, we observed that cultured, low-passage normal human prostate epithelial cells (PrECs) express a variety of cytokines which have been shown to have angiogenic and/or endothelial cell-activating properties in various systems. These include vascular endothelial growth factor (VEGF), basic fibroblastic growth factor (bFGF), transforming growth factor-alpha (TGF-alpha), transforming growth factor-beta (TGF-beta), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF).

Expression and function of colony-stimulating factors and their receptors in human prostate carcinoma cell lines.

Background: The predeliction for prostate carcinoma cells to metastasize to bone suggests the hypothesis that bone and/or bone marrow-derived factors may promote prostate carcinoma cell growth or survival, or serve as chemoattractants for these cells.

Methods: We screened three prostate carcinoma cell lines, DU-145, PC-3, and LNCaP, for the expression of several hematopoiesis-associated colony-stimulating factors (CSFs) and their receptors using RT-PCR (reverse transcriptase-polymerase chain reaction) and immunohistochemical methods, and examined their functional effects.

Results: All of these cell lines express granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), and the DU-145 and PC-3 lines express stem-cell factor (SCF), as determined by RT-PCR and ELISA.

Expression of methylthioadenosine phosphorylase cDNA in p16-, MTAP- malignant cells: restoration of methylthioadenosine phosphorylase-dependent salvage pathways and alterations of sensitivity to inhibitors of purine de novo synthesis.

5'-Deoxy-5'-methylthioadenosine phosphorylase (MTAP) is involved in the salvage of adenine and methylthio moieties of 5'-deoxy-5'-methylthioadenosine, a byproduct of polyamine synthesis, to adenine nucleotides and methionine, respectively. The gene encoding MTAP, MTAP, is frequently codeleted along with the tumor suppressor gene p16 in malignant cells bearing homozygous deletions in the chromosome 9p21 region. p16-, MTAP- malignant cells have been shown to be more susceptible to the purine de novo inhibitory actions of antifolates such as methotrexate than are p16+, MTAP+ cells.

Gene deletion chemoselectivity: codeletion of the genes for p16(INK4), methylthioadenosine phosphorylase, and the alpha- and beta-interferons in human pancreatic cell carcinoma lines and its implications for chemotherapy.

Pancreatic carcinoma cells lines are known to have a high incidence of homozygous deletion of the candidate tumor suppressor gene p16 (MTS1/CDKN2), which resides in the chromosome 9p21 region. Here we: (a)examined a series of these cell lines for the incidence of codeletion of genes located near p16, in particular, the gene for the enzyme 5'-deoxy-5'-methylthioadenosine phosphorylase (MTAP) and the genes of the IFN-alpha and -beta cluster (IFNs); and (b) investigated whether therapeutic strategies could be developed that target malignant cells that have undergone the codeletion of such genes. Five of the eight pancreatic carcinoma cell lines were p16(-), MTAP was codeleted in all five cases.