Modulation of meningioma cell growth by sex steroid hormones in vitro

1985 ◽  
Vol 62 (5) ◽  
pp. 757-762 ◽  
Author(s):  
Jeffrey R. Jay ◽  
David T. MacLaughlin ◽  
Kathleen R. Riley ◽  
Robert L. Martuza
Keyword(s):  
Biological Activity ◽  
Cell Growth ◽  
Tumor Tissue ◽  
Growth Stimulation ◽  
Tissue Cell ◽  
Hormone Binding ◽  
Content Type ◽  
Human Meningiomas ◽  
Meningioma Cell

✓ Meningiomas were removed from four patients and estradiol binding was measured in the tumor tissue. Cell cultures were established and an in vitro system was developed to test the biological activity of physiologically relevant concentrations (10−7 M and 10−9 M) of estradiol-17pβ, progesterone, and the antiestrogen, tamoxifen, on the growth of meningioma cells in early culture (passages 3 to 5). Assays of the frozen surgical specimens demonstrated cytosolic estradiol binding, with levels of 0.3 to 26.7 femtomoles (fM)/mg protein, in all four tumors. Nuclear estradiol binding was detected in three tumors, with levels of 16.8 to 39.5 fM/mg protein. In cell culture, estradiol at either 10−7 M or 10−9 M consistently stimulated cell growth in all four cultures. When tested alone, progesterone stimulated the growth of all four tumors and tamoxifen stimulated the growth of three of the four tumors, but the levels of stimulation produced by either of these compounds were less pronounced than the level produced by estradiol. When tested in combination with estradiol, progesterone significantly inhibited the growth stimulation produced by estradiol in all four meningioma cultures and tamoxifen significantly inhibited estradiol-induced growth stimulation in three of four cultures. It is not known if these effects are mediated by a hormone receptor or by a hormone binder different from a true receptor, or if they are caused by alterations in cellular metabolism that are independent of specific hormone binding. However, the authors conclude that this in vitro technique can be used to further study the biological activity of hormones on human meningiomas in order to answer these questions.

Proto-oncogene abnormalities and their relationship to tumorigenicity in some human glioblastomas

1989 ◽  
Vol 71 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Hoi Sang U ◽  
Patricia Y. Kelley ◽  
James D. Hatton ◽  
Jin Y. Shew
Keyword(s):  
Gene Expression ◽  
Cell Growth ◽  
Growth Factor Receptor ◽  
Growth Stimulation ◽  
Soft Agar ◽  
R Gene ◽  
Primary Tumors ◽  
Content Type

✓ Human glioblastomas are highly malignant intracranial tumors, some of which demonstrate amplification of the epidermal growth factor-receptor (EGF-R) gene. Overexpression of this gene is seen in the majority of primary tumors; however, the role of the EGF-R gene in glial tumorigenesis is unknown. The authors explored the relationship between EGF-R gene expression and glioblastoma cell growth in vitro and in vivo and found that the level of EGF-R gene expression did not correlate with tumor cell growth either in soft agar or in the nude mouse. This suggests that the EGF-R gene is not involved in effecting direct growth stimulation in glial oncogenesis. Tumorigenesis involves differentiation arrest; therefore, the expression of several proto-oncogenes in neuroectodermal tumors was investigated to evaluate the potential involvement of the EGF-R gene in glial differentiation. A nonoverlapping expression of the N-myc and EGF-R genes was found in neuronal-derived and glial-derived tumors, respectively. This suggests that the EGF-R gene may be involved in differentiation or its arrest in glia.

Formation of autocrine loops in human cerebral meningioma tissue by leukemia inhibitor factor, interleukin-6, and oncostatin M: inhibition of meningioma cell growth in vitro by recombinant oncostatin M

1998 ◽  
Vol 88 (3) ◽  
pp. 541-548 ◽  
Author(s):  
Uwe M. H. Schrell ◽  
Hans Uwe Koch ◽  
Rolf Marschalek ◽  
Thomas Schrauzer ◽  
Marc Anders ◽  
...  
Keyword(s):  
Cell Growth ◽  
Interleukin 6 ◽  
Oncostatin M ◽  
Enzyme Linked Immunosorbent Assay ◽  
Autocrine Signaling ◽  
Content Type ◽  
Meningioma Cell ◽  
Leukemia Inhibitor Factor ◽  
Fine Print

Object. It has been demonstrated that growth of cerebral meningiomas found in humans is controlled by a variety of factors, including growth factors, aminergic agents, neuropeptides, and steroids. To further our knowledge of this process, the authors investigated the presence and function of the cytokines leukemia inhibitory factor (LIF), interleukin-6 (IL-6), and oncostatin M (OSM) on meningioma cell proliferation. Methods. Active transcription of LIF, IL-6, and OSM, their related receptors (LIF-R, IL-6-R, and gp130), and the consecutive signal-transducing molecules (STAT 1, STAT 3, and STAT 5a) were analyzed in reverse transcriptase—polymerase chain reaction experiments. The presence of endogenous LIF, IL-6, and OSM proteins was demonstrated in the supernatant of cultured meningioma cells using the enzyme-linked immunosorbent assay and Western blot experiments, thus indicating an autocrine signaling pathway for all three cytokines. The biological function of all three cytokines was evaluated by studying their effects on meningioma cell growth. Recombinant LIF and IL-6 showed no significant growth modulating effects; however, recombinant OSM decreased meningioma cell growth by 66%. The antiproliferative potency of OSM was demonstrated by cell count experiments, the [3H]thymidine incorporation assay, and cell cycle analysis. Conclusions. These in vitro data support the concept that growth of meningioma cells may be modulated by cytokines, and they also indicate that recombinant OSM may be one future candidate for use in the adjuvant treatment of inoperable and recurrent meningiomas.

Hormonal manipulation of meningiomas in vitro

1986 ◽  
Vol 65 (1) ◽  
pp. 99-107 ◽  
Author(s):  
Jeffrey J. Olson ◽  
David W. Beck ◽  
Janet Schlechte ◽  
Pao-Min Loh
Keyword(s):  
Cell Growth ◽  
Binding Proteins ◽  
Growth Stimulation ◽  
Content Type ◽  
Hormonal Manipulation ◽  
The Media ◽  
Estrogen Binding ◽  
Progesterone Antagonist ◽  
Fine Print

✓ Speculation that meningiomas are subject to endocrine influence is supported by their higher incidence in women, reports of exacerbation of symptoms during pregnancy, and the discovery that these tumors harbor progesterone- and estrogen-binding proteins. To evaluate if these properties could be exploited therapeutically, specimens from three convexity meningiomas were used for estrogen- and progesterone-binding protein assays and establishment of tissue cultures. Each tumor (designated A, B, and C, respectively) was grown in experimental media containing 7.5 × 10−5 to 10−12 M 17β-estradiol, 2.5 × 10−4 to 10−12 M progesterone, 10−7 to 10−9 M tamoxifen (an estrogen antagonist), and 10−6 to 10−10 M RU486 (a progesterone antagonist). After incubation, cell growth was compared to control preparations by counting the meningioma cells present in each medium. Tumors A, B, and C contained estrogen-binding proteins of 8.45, 13.6, and 26.9 fmol/mg cytosol protein and progesterone-binding proteins of 210, 130, and 126 fmol/mg cytosol protein, respectively. The media containing 17β-estradiol and progesterone caused 21% to 36% growth stimulation in Tumors A and B. In Tumor A, the addition of tamoxifen stimulated growth by 35%, while it caused only transient stimulation in Tumor B and had no effect on Tumor C. RU486, the progesterone antagonist, caused inhibition of cell growth in all three tumors, ranging from 18% to 36%. These data suggest that selected meningiomas are subject to hormonal influence in vitro. The inhibition of meningioma growth in vitro by the antiprogesterone, RU486, has not been previously reported, and serves to encourage further development of alternative modes of therapy for recurrent and unresectable meningiomas.

scholarly journals The regio-selective synthesis of 10-hydroxy camptothecin norcantharidin conjugates and their biological activity evaluation in vitro

2018 ◽  
Vol 5 (6) ◽  
pp. 172317 ◽  
Author(s):  
Chang K. Zhao ◽  
Chan Li ◽  
Xian H. Wang ◽  
Yu J. Bao ◽  
Fu H. Yang ◽  
...  
Keyword(s):  
Biological Activity ◽  
Cell Growth ◽  
Cancer Treatment ◽  
Cancer Cell ◽  
Therapeutic Potential ◽  
Selective Synthesis ◽  
Cancer Cell Growth ◽  
Activity Evaluation ◽  
Moderate Yield

A series of conjugates of 10-hydroxy camptothecin (HCPT) with functionalized norcantharidin derivatives were regio-selectively synthesized in the condition of (3-dimethylaminopropyl) ethyl-carbodiimide monohydrochloride in a moderate yield. The synthesized conjugate HCPT pro-drugs can also suppress cancer cell growth in vitro . These conjugated pro-drug constructs possess therapeutic potential as novel bi-functional conjugate platforms for cancer treatment.

Sensor system for use with low intensity pulsed ultrasound

Sensor Review ◽  
2019 ◽  
Vol 39 (6) ◽  
pp. 828-834
Author(s):  
Andreas Diermeier ◽  
Dirk Sindersberger ◽  
Peter Angele ◽  
Richard Kujat ◽  
Gareth John Monkman
Keyword(s):  
Biological Fluids ◽  
Medical Science ◽  
Excitation Frequency ◽  
Radiation Force ◽  
Cost Effective ◽  
Growth Stimulation ◽  
Future Research ◽  
Measurement Transducer ◽  
Content Type

Purpose Ultrasound is a well-established technology in medical science, though many of the conventional measurement systems (hydrophones and radiation force balances [RFBs]) often lack accuracy and tend to be expensive. This is a significant problem where sensors must be considered to be “disposable” because they inevitably come into contact with biological fluids and expense increases dramatically in cases where a large number of sensors in array form are required. This is inevitably the case where ultrasound is to be used for the in vitro growth stimulation of a large plurality of biological samples in tissue engineering. Traditionally only a single excitation frequency is used (typically 1.5 MHz), but future research demands a larger choice of wavelengths for which a single broadband measurement transducer is desirable. Furthermore, because of implementation conditions there can also be large discrepancies between measurements. The purpose of this paper deals with a very cost-effective alternative to expensive RFBs and hydrophones. Design/methodology/approach Utilization of cost-effective piezoelectric elements as broadband sensors. Findings Very effective results with equivalent (if not better) accuracy than expensive alternatives. Originality/value This paper concentrates on how very cost-effective piezoelectric ultrasound transducers can be implemented as sensors for ultrasound power measurements with accuracy as good, if not better than those achievable using radiation force balances or hydrophones.

scholarly journals Serine-Threonine Kinases Encoded by SplithipAHomologs Inhibit Tryptophanyl-tRNA Synthetase

mBio ◽  
2019 ◽  
Vol 10 (3) ◽  
Author(s):  
Stine Vang Nielsen ◽  
Kathryn Jane Turnbull ◽  
Mohammad Roghanian ◽  
Rene Bærentsen ◽  
Maja Semanjski ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Growth ◽  
Gene Family ◽  
Sequence Similarity ◽  
Trna Synthetase ◽  
Bacterial Toxin ◽  
Content Type ◽  
Multidrug Tolerance ◽  
K 12

ABSTRACTType II toxin-antitoxin (TA) modules encode a stable toxin that inhibits cell growth and an unstable protein antitoxin that neutralizes the toxin by direct protein-protein contact.hipBAofEscherichia colistrain K-12 codes for HipA, a serine-threonine kinase that phosphorylates and inhibits glutamyl-tRNA synthetase. Induction ofhipAinhibits charging of glutamyl-tRNA that, in turn, inhibits translation and induces RelA-dependent (p)ppGpp synthesis and multidrug tolerance. Here, we describe the discovery of a three-component TA gene family that encodes toxin HipT, which exhibits sequence similarity with the C-terminal part of HipA. A genetic screening revealed thattrpSin high copy numbers suppresses HipT-mediated growth inhibition. We show that HipT ofE. coliO127 is a kinase that phosphorylates tryptophanyl-tRNA synthetasein vitroat a conserved serine residue. Consistently, induction ofhipTinhibits cell growth and stimulates production of (p)ppGpp. The gene immediately upstream fromhipT, calledhipS, encodes a small protein that exhibits sequence similarity with the N terminus of HipA. HipT kinase was neutralized by cognate HipSin vivo, whereas the third component, HipB, encoded by the first gene of the operon, did not counteract HipT kinase activity. However, HipB augmented the ability of HipS to neutralize HipT. Analysis of two additionalhipBST-homologous modules showed that, indeed, HipS functions as an antitoxin in these cases also. Thus,hipBSTconstitutes a novel family of tricomponent TA modules wherehipAhas been split into two genes,hipSandhipT, that function as a novel type of TA pair.IMPORTANCEBacterial toxin-antitoxin (TA) modules confer multidrug tolerance (persistence) that may contribute to the recalcitrance of chronic and recurrent infections. The first high-persister gene identified washipAofEscherichia colistrain K-12, which encodes a kinase that inhibits glutamyl-tRNA synthetase. ThehipAgene encodes the toxin of thehipBATA module, whilehipBencodes an antitoxin that counteracts HipA. Here, we describe a novel, widespread TA gene family,hipBST, that encodes HipT, which exhibits sequence similarity with the C terminus of HipA. HipT is a kinase that phosphorylates tryptophanyl-tRNA synthetase and thereby inhibits translation and induces the stringent response. Thus, this new TA gene family may contribute to the survival and spread of bacterial pathogens.

REGULATION OF MENINGIOMA CELL GROWTH IN VITRO BY POLYAMINES

1971 ◽  
Vol 30 (4) ◽  
pp. 698-713 ◽  
Author(s):  
P. E. DUFFY ◽  
R. DEFENDINI ◽  
L. T. KREMZNER
Keyword(s):  
Cell Growth ◽  
Meningioma Cell

scholarly journals Enzymatic Synthesis and Functional Characterization of Bioactive Microcin C-Like Compounds with Altered Peptide Sequence and Length

2015 ◽  
Vol 197 (19) ◽  
pp. 3133-3141 ◽  
Author(s):  
Olga Bantysh ◽  
Marina Serebryakova ◽  
Inna Zukher ◽  
Alexey Kulikovsky ◽  
Darya Tsibulskaya ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Biological Activity ◽  
Functional Characterization ◽  
Trna Synthetase ◽  
Biologically Active ◽  
Peptide Sequence ◽  
Target Cells ◽  
Content Type ◽  
Peptide Length

ABSTRACTEscherichia colimicrocin C (McC) consists of a ribosomally synthesized heptapeptide attached to a modified adenosine. McC is actively taken up by sensitiveEscherichia colistrains through the YejABEF transporter. Inside the cell, McC is processed by aminopeptidases, which release nonhydrolyzable aminoacyl adenylate, an inhibitor of aspartyl-tRNA synthetase. McC is synthesized by the MccB enzyme, which terminally adenylates the MccA heptapeptide precursor MRTGNAN. Earlier, McC analogs with shortened peptide lengths were prepared by total chemical synthesis and were shown to have strongly reduced biological activity due to decreased uptake. Variants with longer peptides were difficult to synthesize, however. Here, we used recombinant MccB to prepare and characterize McC-like molecules with altered peptide moieties, including extended peptide lengths. We find that N-terminal extensions ofE. coliMccA heptapeptide do not affect MccB-catalyzed adenylation and that some extended-peptide-length McC analogs show improved biological activity. When the peptide length reaches 20 amino acids, both YejABEF and SbmA can perform facilitated transport of toxic peptide adenylates inside the cell. A C-terminal fusion of the carrier maltose-binding protein (MBP) with the MccA peptide is also recognized by MccBin vivoandin vitro, allowing highly specific adenylation and/or radioactive labeling of cellular proteins.IMPORTANCEEnzymatic adenylation of chemically synthesized peptides allowed us to generate biologically active derivatives of the peptide-nucleotide antibiotic microcin C with improved bioactivity and altered entry routes into target cells, opening the way for development of various McC-based antibacterial compounds not found in nature.

Novel treatment with taxol and fluvastatin effectively suppresses meningioma cell growth in vitro and induces apoptosis

2004 ◽  
Vol 112 (08) ◽  
Author(s):  
M Tichomirowa ◽  
S Miebach ◽  
J Lu ◽  
M Lange ◽  
O Almeida ◽  
...  
Keyword(s):  
Cell Growth ◽  
Novel Treatment ◽  
Meningioma Cell

Synthesis and biological activity of nucleoside analogs involving modifications in the carbohydrate ring

1985 ◽  
Vol 63 (8) ◽  
pp. 2149-2161 ◽  
Author(s):  
Walter A. Szarek ◽  
B. Mario Pinto ◽  
Masaharu Iwakawa
Keyword(s):  
Biological Activity ◽  
Cell Growth ◽  
Antitumor Activity ◽  
Nucleoside Analogs ◽  
Hela Cell Line ◽  
Biological Screening ◽  
Naturally Occurring ◽  
Derivatives Of ◽  
Substituted 1

The synthesis of a variety of nucleoside analogs involving modifications in the carbohydrate ring is described. In particular, 6-substituted purin-9-yl derivatives of 1-oxa-4-thiacyclohexane and 1,4-dioxacyclohexane have been synthesized. A number of 6-chloropurin-9-yl derivatives of substituted 1-oxa-4-thiacyclohexane have also been derived from the parent compounds by way of a Pummerer rearrangement. A route to nucleoside analogs of 1-oxa-4-thiacyclohexane from naturally occurring nucleosides is illustrated for the case of inosine. A route to nucleoside analogs in which the carbohydrate moiety is replaced by an acyclic moiety bearing α,β-unsaturated esters is also illustrated for the case of uridine. The results of biological screening of these analogs and others previously synthesized in our program against leukemia L-1210 cells in vitro are presented; some of these compounds showed marginal antitumor activity. The screening results of selected compounds against the human HeLa cell line in vitro are also presented; none of the compounds that were tested showed significant inhibitory activity of cell growth.

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