scholarly journals IGF-I Antisense and Triple-Helix Gene Therapy of Glioblastoma

10.5772/52366 ◽  
2013 ◽  
Author(s):  
Jerzy Trojan ◽  
Ignacio Briceno
Keyword(s):  
Gene Therapy ◽  
Triple Helix ◽  
Igf I

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.

scholarly journals Maximizing Ventricular Function With Multimodal Cell-Based Gene Therapy

Circulation ◽  
2005 ◽  
Vol 112 (9_supplement) ◽  
Author(s):  
Terrence M. Yau ◽  
Christopher Kim ◽  
Guangming Li ◽  
Yaoguang Zhang ◽  
Richard D. Weisel ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Polymerase Chain Reaction ◽  
Growth Factor ◽  
Cell Survival ◽  
Left Ventricular ◽  
Border Zone ◽  
Lv Function ◽  
Chain Reaction ◽  
Igf I ◽  
Polymerase Chain

Background— Angiogenesis is enhanced after transplantation of vascular endothelial growth factor (VEGF)-expressing cells into a myocardial scar. Insulin-like growth factor I (IGF-I) may induce hypertrophy and inhibit apoptosis. We evaluated the effect of cell-based IGF-I and VEGF multigene therapy on left ventricular (LV) function, cell survival, and apoptosis after bone marrow cell (BMC) transplantation. Methods and Results— Female Lewis rats underwent left anterior descending ligation 3 weeks before transplantation with male donor BMC, BMC transfected with VEGF (BMC+VEGF), IGF-I (BMC+IGF-I), VEGF and IGF-I (BMC+VEGF+IGF-I), or medium without cells (control) (n=4 per group×5 groups×4 time points). Three days and 1, 2, and 4 weeks after transplantation, VEGF and IGF-I expression was quantitated by real-time polymerase chain reaction, cell survival by polymerase chain reaction for sry2, apoptosis by TUNEL staining, LV function by echocardiography and myosin heavy chain, and light chain and troponin I by Western blot. One week after transplantation, IGF-I expression in the scar and border zone was greatest in BMC+IGF-I and BMC+VEGF+IGF-I rats ( P <0.05). VEGF expression in the scar and border zone was greatest in BMC+VEGF and BMC+VEGF+IGF-I hearts ( P <0.05). Transplanted cell survival was lowest in BMC, intermediate in BMC+VEGF and BMC+IGF-I, and greatest in BMC+VEGF+IGF-I ( P <0.05). Apoptotic indices were significantly reduced in BMC+VEGF+IGF-I, BMC+VEGF, and BMC+IGF-I ( P <0.05). Two and 4 weeks after transplantation, LV ejection fraction was lowest in control, intermediate in BMC, BMC+VEGF, and BMC+IGF-I, and greatest in BMC+VEGF+IGF-I ( P <0.05). Conclusions— Transplantation of VEGF- and IGF-I-expressing BMC reduced apoptosis, maximized transplanted cell survival, and enhanced LV function. Multimodal cell-based gene therapy may maximize the benefits of cell transplantation.

scholarly journals IGF-I Gene Therapy in Aging Rats Modulates Hippocampal Genes Relevant to Memory Function

2017 ◽  
Vol 73 (4) ◽  
pp. 459-467 ◽  
Author(s):  
Joaquín Pardo ◽  
Martin C Abba ◽  
Ezequiel Lacunza ◽  
Olalekan M Ogundele ◽  
Isabel Paiva ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Memory Function ◽  
Aging Rats ◽  
Igf I ◽  
I Gene

Mesenchymal Stromal Cells Genetically Engineered To Overexpress Insulin-Like Growth Factor-1 Provide Paracrine Support for Cell-Based Erythropoietin Therapy of Chronic Renal Failure-Induced Anemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2598-2598
Author(s):  
Terrence Kucic ◽  
Ian B. Copland ◽  
Jessica Cuerquis ◽  
Daniel L. Coutu ◽  
Lorraine E. Chalifour ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Renal Failure ◽  
Chronic Renal Failure ◽  
Growth Factor ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Mapk Pathway ◽  
Insulin Like Growth Factor ◽  
Igf I

Abstract Mesenchymal stromal cells (MSC) are a population of non-hematopoietic progenitors native to the bone marrow that are amenable to genetic engineering, making them attractive delivery vehicles for the in vivo production of therapeutic proteins, such as erythropoietin (Epo). We have previously demonstrated that MSC engineered to secrete Epo can be used for the long-term correction of renal failure-induced anemia [Eliopoulos et al., J Am Soc Nephrol. June 2006]. However, limited long-term transplanted cell survival compromises the efficacy of MSC-based gene therapy approaches. The current study provides evidence that co-implantation of MSC overexpressing Insulin-like growth factor-1 (IGF-I) improves MSC-based gene therapy of anemia by providing paracrine support to Epo-secreting MSC within a synthetic subcutaneous organoid. The IGF-I receptor was found to be expressed in murine MSC by RT-PCR, and protein expression was confirmed by immunoblot. We also demonstrated MSC MAPK pathway responsiveness to IGF-I stimulation in vitro and subsequent improvement of MSC survival following staurosporin-induced apoptosis. Murine MSC were transduced to overexpress either Epo or IGF-I (hereafter MSC-Epo and MSC-IGF) using retroviral vectors. MSC-Epo were subsequently admixed in a collagen matrix and implanted by subcutaneous injection in both naïve mice and a murine model of chronic renal failure, in combination with either MSC-IGF or null MSC. Mice receiving MSC-Epo in conjunction with MSC-IGF experienced a greater and significantly sustained elevation in hematocrit compared to control mice. In addition, mice co-implanted with MSC-IGF and MSC-Epo demonstrated a significant improvement in cardiac function compared to controls. In conclusion, cell-based gene therapy using co-implanted MSC-IGF represents a promising new strategy for the treatment of renal failure-induced anemia, as well as for the improvement of gene-enhanced MSC survival within implanted matrices.

Mesenchymal stromal cells genetically engineered to overexpress IGF-I enhance cell-based gene therapy of renal failure-induced anemia

2008 ◽  
Vol 295 (2) ◽  
pp. F488-F496 ◽  
Author(s):  
Terrence Kucic ◽  
Ian B. Copland ◽  
Jessica Cuerquis ◽  
Daniel L. Coutu ◽  
Lorraine E. Chalifour ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Renal Failure ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Heart Function ◽  
Collagen Matrix ◽  
Genetically Engineered ◽  
Functional Protein ◽  
Igf I

We previously demonstrated that erythropoietin (EPO)-secreting mesenchymal stromal cells (MSC) can be used for the long-term correction of renal failure-induced anemia. The present study provides evidence that coimplantation of insulin-like growth factor I (IGF-I)-overexpressing MSC (MSC-IGF) improves MSC-based gene therapy of anemia by providing paracrine support to EPO-secreting MSC (MSC-EPO) within a subcutaneous implant. IGF-I receptor RNA expression in murine MSC was demonstrated by RT-PCR. Functional protein expression was confirmed by immunoblots and MSC responsiveness to IGF-I stimulation in vitro. IGF-I was also shown to improve MSC survival following staurosporin-induced apoptosis in vitro. A cohort of C57Bl/6 mice was rendered anemic by right kidney electrocoagulation and left nephrectomy. MSC-EPO were subsequently admixed in a bovine collagen matrix and implanted, in combination with MSC-IGF or MSC null, by subcutaneous injection in renal failure mice. In mice receiving MSC-EPO coimplanted with MSC-IGF, hematocrit elevation was greater and enhanced compared with control mice; heart function was also improved. MSC-IGF coimplantation, therefore, represents a promising new strategy for enhancing MSC survival within implanted matrices and for improving cell-based gene therapy of renal anemia.

Alterations in tumorigenicity of embryonal carcinoma cells by IGF-I triple-helix induced changes in immunogenicity and apoptosis

Life Sciences ◽  
2000 ◽  
Vol 68 (3) ◽  
pp. 307-319 ◽  
Author(s):  
Adama Ly ◽  
Jean C. François ◽  
Lia C. Upegui-Gonzalez ◽  
Bernadette Swiercz ◽  
Christophe Bedel ◽  
...  
Keyword(s):  
Triple Helix ◽  
Embryonal Carcinoma ◽  
Carcinoma Cells ◽  
Embryonal Carcinoma Cells ◽  
Igf I ◽  
Induced Changes

scholarly journals Hypothalamic IGF-I Gene Therapy Prolongs Estrous Cyclicity and Protects Ovarian Structure in Middle-Aged Female Rats

Endocrinology ◽  
2013 ◽  
Vol 154 (6) ◽  
pp. 2166-2173 ◽  
Author(s):  
Silvia S. Rodríguez ◽  
José I. Schwerdt ◽  
Claudio G. Barbeito ◽  
Mirta A. Flamini ◽  
Ye Han ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Positive Feedback ◽  
Female Rats ◽  
Middle Aged ◽  
Ovarian Histology ◽  
Igf I ◽  
Estrous Cyclicity ◽  
Ovarian Structure ◽  
I Gene ◽  
Estrogen Positive Feedback

Abstract There is substantial evidence that age-related ovarian failure in rats is preceded by abnormal responsiveness of the neuroendocrine axis to estrogen positive feedback. Because IGF-I seems to act as a permissive factor for proper GnRH neuronal response to estrogen positive feedback and considering that the hypothalamic content of IGF-I declines in middle-aged (M-A) rats, we assessed the effectiveness of long-term IGF-I gene therapy in the mediobasal hypothalamus (MBH) of M-A female rats to extend regular cyclicity and preserve ovarian structure. We used 3 groups of M-A rats: 1 group of intact animals and 2 groups injected, at 36.2 weeks of age, in the MBH with either a bicistronic recombinant adeno-associated virus (rAAV) harboring the genes for IGF-I and the red fluorescent protein DsRed2, or a control rAAV expressing only DsRed2. Daily vaginal smears were taken throughout the study, which ended at 49.5 weeks of age. We measured serum levels of reproductive hormones and assessed ovarian histology at the end of the study. Although most of the rats injected with the IGF-I rAAV had, on the average, well-preserved estrous cyclicity as well as a generally normal ovarian histology, the intact and control rAAV groups showed a high percentage of acyclic rats at the end of the study and ovaries with numerous enlarged cysts and scarce corpora lutea. Serum LH was higher and hyperprolactinemia lower in the treated animals. These results suggest that overexpression of IGF-I in the MBH prolongs normal ovarian function in M-A female rats.

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