scholarly journals IGF-I: from diagnostic to triple-helix gene therapy of solid tumors.

2002 ◽  
Vol 49 (4) ◽  
pp. 979-990 ◽  
Author(s):  
Ladislas A Trojan ◽  
Piotr Kopinski ◽  
Ming X Wei ◽  
Adama Ly ◽  
Aleksandra Glogowska ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Growth Factor ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Triple Helix ◽  
Human Tumor ◽  
Igf I ◽  
I Gene

Alterations in the expression of growth factors and their receptors are associated with the growth and development of human tumors. One such growth factor is IGF-I (insulin-like growth factor I ), a 70-amino-acid polypeptide expressed in many tissues, including brain. IGF-I is also expressed at high levels in some nervous system-derived tumors, especially in glioblastoma. When using IGF-I as a diagnostic marker, 17 different tumors are considered as expressing the IGF-I gene. Malignant glioma, the most common human brain cancer, is usually fatal. Average survival is less than one year. Our strategy of gene therapy for the treatment of gliomas and other solid tumors is based on: 1) diagnostic using IGF-I gene expression as a differential marker, and 2) application of "triple-helix anti-IGF-I" therapy. In the latter approach, tumor cells are transfected with a vector, which encodes an oligoribonucleotide--an RNA strand containing oligopurine sequence which might be capable of forming a triple helix with an oligopurine and/or oligopyrimidine sequence of the promotor of IGF-I gene (RNA-IGF-I DNA triple helix). Human tumor cells transfected in vitro become down-regulated in the production of IGF-I and present immunogenic (MHC-I and B7 expression) and apoptotic characteristics. Similar results were obtained when IGF-I antisense strategy was applied. In both strategies the transfected cells reimplanted in vivo lose tumorigenicity and elicit tumor specific immunity which leads to elimination of established tumors.

ANTITUMOR EFFECT OF COLLOIDAL SILVER BISILICATE IN EXPERIMENTAL IN VITRO AND IN VIVO STUDIES

2019 ◽  
Vol 65 (5) ◽  
pp. 760-765
Author(s):  
Margarita Tyndyk ◽  
Irina Popovich ◽  
A. Malek ◽  
R. Samsonov ◽  
N. Germanov ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Human Tumor ◽  
Significant Inhibition ◽  
In Vivo Studies ◽  
Ehrlich Carcinoma ◽  
In Vivo Experiments

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.

scholarly journals MLN8054, an Inhibitor of Aurora A Kinase, Induces Senescence in Human Tumor Cells Both In vitro and In vivo

2010 ◽  
Vol 8 (3) ◽  
pp. 373-384 ◽  
Author(s):  
Jessica J. Huck ◽  
Mengkun Zhang ◽  
Alice McDonald ◽  
Doug Bowman ◽  
Kara M. Hoar ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Human Tumor ◽  
Aurora A Kinase ◽  
Aurora A ◽  
Human Tumor Cells

scholarly journals Down regulation of BRCA2 causes radio-sensitization of human tumor cells in vitro and in vivo

2008 ◽  
Vol 99 (4) ◽  
pp. 810-815 ◽  
Author(s):  
Dong Yu ◽  
Emiko Sekine ◽  
Akira Fujimori ◽  
Takahiro Ochiya ◽  
Ryuichi Okayasu
Keyword(s):  
Tumor Cells ◽  
Human Tumor ◽  
Human Tumor Cells ◽  
Down Regulation

scholarly journals Modulation of 11β-Hydroxysteroid Dehydrogenase Isozymes by Growth Hormone and Insulin-Like Growth Factor: In Vivo and In Vitro Studies1

1999 ◽  
Vol 84 (11) ◽  
pp. 4172-4177 ◽  
Author(s):  
J. S. Moore ◽  
J. P. Monson ◽  
G. Kaltsas ◽  
P. Putignano ◽  
P. J. Wood ◽  
...  
Keyword(s):  
Growth Factor ◽  
Reductase Activity ◽  
Primary Cultures ◽  
Inverse Correlation ◽  
Hydroxysteroid Dehydrogenase ◽  
Insulin Like Growth Factor ◽  
Igf I ◽  
Glucose Output

The interconversion of hormonally active cortisol (F) and inactive cortisone (E) is catalyzed by two isozymes of 11β-hydroxysteroid dehydrogenase (11βHSD), an oxo-reductase converting E to F (11βHSD1) and a dehydrogenase (11βHSD2) converting F to E. 11βHSD1 is important in mediating glucocorticoid-regulated glucose homeostasis and regional adipocyte differentiation. Earlier studies conducted with GH-deficient subjects treated with replacement GH suggested that GH may modulate 11βHSD1 activity. In 7 acromegalic subjects withdrawing from medical therapy (Sandostatin-LAR; 20–40 mg/month for at least 12 months), GH rose from 7.1 ± 1.5 to 17.5 ± 4.3 mU/L (mean ± se), and insulin-like growth factor I (IGF-I) rose from 43.0 ± 8.8 to 82.1 ± 13.7 nmol/L (both P &lt; 0.05) 4 months after treatment. There was a significant alteration in the normal set-point of F to E interconversion toward E. The fall in the urinary tetrahydrocortisols/tetrahydocortisone ratio (THF+allo-THF/THE; 0.82 ± 0.06 to 0.60 ± 0.06; P &lt; 0.02) but unaltered urinary free F/urinary free E ratio (a marker for 11βHSD2 activity) suggested that this was due to inhibition of 11βHSD1 activity. An inverse correlation between GH and the THF+allo-THF/THE ratio was observed (r = −0.422; P &lt; 0.05). Conversely, in 12 acromegalic patients treated by transsphenoidal surgery (GH falling from 124 ± 49.2 to 29.3 ± 15.4 mU/L; P &lt; 0.01), the THF+allo-THF/THE ratio rose from 0.53 ± 0.06 to 0.63 ± 0.07 (P &lt; 0.05). Patients from either group who failed to demonstrate a change in GH levels showed no change in the THF+allo-THF/THE ratio. In vitro studies conducted on cells stably transfected with either the human 11βHSD1 or 11βHSD2 complementary DNA and primary cultures of human omental adipose stromal cells expressing only the 11βHSD1 isozyme indicated a dose-dependent inhibition of 11βHSD1 oxo-reductase activity with IGF-I, but not GH. Neither IGF-I nor GH had any effect on 11βHSD2 activity. GH, through an IGF-I-mediated effect, inhibits 11βHSD1 activity. This reduction in E to F conversion will increase the MCR of F, and care should be taken to monitor the adequacy of function of the hypothalamo-pituitary-adrenal axis in acromegalic subjects and in GH-deficient, hypopituitary patients commencing replacement GH therapy. Conversely, enhanced E to F conversion occurs with a reduction in GH levels; in liver and adipose tissue this would result in increased hepatic glucose output and visceral adiposity, suggesting that part of the phenotype currently attributable to adult GH deficiency may be an indirect consequence of its effect on tissue F metabolism via 11βHSD1 expression.

Neonatal or hepatocyte growth factor–potentiated adult gene therapy with a retroviral vector results in therapeutic levels of canine factor IX for hemophilia B

Blood ◽  
2003 ◽  
Vol 101 (10) ◽  
pp. 3924-3932 ◽  
Author(s):  
Lingfei Xu ◽  
Cuihua Gao ◽  
Mark S. Sands ◽  
Shi-Rong Cai ◽  
Timothy C. Nichols ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Growth Factor ◽  
Gene Transfer ◽  
Hepatocyte Growth Factor ◽  
Retroviral Vector ◽  
Factor Ix ◽  
Hemophilia B ◽  
Hepatocyte Growth

AbstractHemophilia B is a bleeding disorder resulting from factor IX (FIX) deficiency that might be treated with gene therapy. Neonatal delivery would correct the disease sooner than would transfer into adults, and could reduce immunological responses. Neonatal mice were injected intravenously with a Moloney murine leukemia virus–based retroviral vector (RV) expressing canine FIX (cFIX). They achieved 150% to 280% of normal cFIX antigen levels in plasma (100% is 5 μg/mL), which was functional in vitro and in vivo. Three newborn hemophilia B dogs that were injected intravenously with RV achieved 12% to 36% of normal cFIX antigen levels, which improved coagulation tests. Only one mild bleed has occurred during 14 total months of evaluation. This is the first demonstration of prolonged expression after neonatal gene therapy for hemophilia B in mice or dogs. Most animals failed to make antibodies to cFIX, demonstrating that neonatal gene transfer may induce tolerance. Although hepatocytes from newborns replicate, those from adults do not. Adult mice therefore received hepatocyte growth factor to induce hepatocyte replication prior to intravenous injection of RV. This resulted in expression of 35% of normal cFIX antigen levels for 11 months, although all mice produced anti-cFIX antibodies. This is the first demonstration that high levels of FIX activity can be achieved with an RV in adults without a partial hepatectomy to induce hepatocyte replication. We conclude that RV-mediated hepatic gene therapy is effective for treating hemophilia B in mice and dogs, although the immune system may complicate gene transfer in adults.

512 BN80927: a novel homocamptothecin that inhibits proliferation of human tumor cells in vitro and in vivo

2004 ◽  
Vol 2 (8) ◽  
pp. 156
Author(s):  
D. Demarquay ◽  
M. Huchet ◽  
H. Coulomb ◽  
L. Lesueur-Ginot ◽  
O. Lavergne ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Human Tumor ◽  
Human Tumor Cells

scholarly journals Application of a simple device for "attracting" and "trapping" glioma cells in situ

2021 ◽  
Author(s):  
Haimin Song ◽  
Runwei Yang ◽  
Runbin Lai ◽  
Kaishu Li ◽  
Bowen Ni ◽  
...  
Keyword(s):  
Growth Factor ◽  
Tumor Cells ◽  
Adult Brain ◽  
Tumor Bed ◽  
In Vivo Experiments ◽  
New Strategy ◽  
New Treatment

Glioblastoma multiforme (GBM) is the most malignant adult brain tumor. The current adjuvant therapies for GBM are disappointing, which are based on cytotoxicity strategy. Thus, other ways should be explored to improve the curative effect. According to the strong invasive ability of GBM cells, we assume a new treatment strategy for GBM by developing a new cell trap device (CTD) with some kind of "attractive" medium loaded in it to attract and capture the tumor cells. The in vitro experiment showed that Hepatocyte Growth Factor（HGF）presented stronger chemotaxis on C6 and U87 cell line than the Epidermal Growth Factor (EGF) and Fibroblast Growth Factor (FGF). A simple in vitro CTD loaded with HGF was made and in vivo experiments results showed that HGF successfully attracted tumor cells from tumor bed in situ into the CTD. This study proposes the new strategy for GBM treatment of "attract and trap" tumor cells is proved to be feasible.

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