A new putative target for antisense gene therapy of glioma: Glycogen synthase

Ardourel, Maryvonne; Blin, Marion; Moret, Jean-Luc; Dufour, Thierry; Duc, Huynh Thien; Hevor, T. K.; Trojan, Jerzy; Cloix, Jean‐François

doi:10.4161/cbt.6.5.4232

Cited by 13 publications

(19 citation statements)

References 24 publications

(49 reference statements)

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“…Additionally, an increased percentage of the lymphocytes positive for superficial interleukine-2 receptor (CD25) was observed. No changes in other CD molecules were demonstrated (Trojan et al, 2003(Trojan et al, , 2007. In our work in progress (new protocol) 4 th and 5 th injections of IGF-I TH cells in glioblastoma patients have been introduced.…”

Section: Resultsmentioning

confidence: 99%

“…Since the past decade, we observe a significant increase of AS approach for the treatment of tumors and especially of gliomas. Recently, other targets than IGF-I, as TGFbeta and their downstream signal transduction pathway elements as GS among others were proposed for treatment of malignant gliomas using AS technology (Schlingensiepen, R. et al, 2005;Ardourel et al, 2007). The approach of AS TGF-beta, similarly to that of AS IGF-I, has given satisfactory clinical results.…”

Section: Introductionmentioning

confidence: 95%

“…IGF-I, EGF, FGF, VEGF, TGF-alpha and -beta) (Baserga, 1994). Their down stream proteins and glycogen signalling elements including glycogen synthase (GS), are also involved (Patel et al, 2004;Trojan et al, 2007). In 1992 Trojan and his co-workers have demonstrated that an Insulin-like growth factor 1, IGF-I, is present in glioma cells but absent in neuroblastoma cells (Trojan et al, 1992).…”

Section: Igf-i and Tumorigenicitymentioning

confidence: 99%

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Gene Therapy of Glioblastoma: Anti – Gene Anti IGF-I Strategy

Trojan¹

2011

Targets in Gene Therapy

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Section: Igf-i and Tumorigenicitymentioning

confidence: 99%

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Gene Therapy of Glioblastoma: Anti – Gene Anti IGF-I Strategy

Trojan¹

2011

Targets in Gene Therapy

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“…IGF-I constitutes the first step of the following signal transduction pathway: IRS/PI3K-PKC/ PDK1/AKT-Bcl2/GSK3/GS [56,57] . The elements of the aforementioned IGF-I-related transduction pathway were also considered as targets for diagnostic and therapeutic purposes [37,39,54,56,[58][59][60][61][62][63][64][65][66][67][68] . The measurement of IGF-I and insulin-like growth factor-binding protein (IGFBP-3) often serves as first-line testing in children with growth disorders.…”

Section: Igf-1 Biomarkermentioning

confidence: 99%

IGF-I biomarker testing in an ethical context

Trojan¹,

Aristizábal

Jay³

et al. 2016

Adv Mod Oncol Res

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Abstract:As we have come to know, there is a connection between cancer biomarkers and genes, along with their susceptibility to a particular disease, all of which have an obvious impact on the clinical practice and development of genetic testing. In any cancer disease, the diagnosis and treatment should be related to the investigation of specific biomarkers (generally antigens and proteins) and their corresponding genes. The study of different antigens such as alpha-fetoprotein, insulin-like growth factor I (IGF-I), insulin-like growth factor II, vascular endothelial growth factor, and epidermal growth factor, as well as their presence in neoplastic cells have demonstrated that IGF-I is an essential target for gene testing and therapeutic purpose. An over-expression of the IGF-I gene in mature tissues is a sign of neoplastic processes, e.g. brain or breast malignancy. A lot of questions have arisen regarding the ethics of gene testing, particularly concerns on the selection of patients for specific growth hormone/insulin-like growth factor I (GHIIGF-I) testing. Evidently, our current society is involved in a process of geneticization -the redefinition of individuals in terms of genetic codes. As such, we should take extreme care when making ethical judgments based on "scientific evidence" derived from genetic testing (typically those involving different biomarkers such as DNA, RNA, chromosomes, and proteins) in relation to genetic abnormalities that could predict current or future diseases. In this situation, the understanding of bioethics is of utmost importance.

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“…The end result is arrest of protein synthesis. [32], c [40], d [51], e [37], f [42], g [7], h [43], i [45], j [36], k [52], l [4], m [44], n [47], o [46], p [75], r [62], s [53], t [65], u [64], w [66].…”

Section: Antisense Strategy In Malignant Gliomamentioning

confidence: 99%

Antisense Strategies in Therapy of Gliomas

Trojan¹,

Anthony

2011

CST

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The malignant brain tumour, glioblastoma, is invariably fatal with an average survival of 8-11 months (recent pharmacology has increased the median survival to 15, and rarely to 18 months). Different growth factors participate in the malignant development of the brain, especially IGF-1, EGF, TGF-beta and VEGF. Among the strategies applied to target and arrest the expression of growth factors, their receptors (tyrosine kinase) and down stream signalling pathway elements (i.e. PKC, Bcl-2, glycogen synthase) involved in cancer processes, the use of different inhibitors and especially of antisense technique has been among the leading technology proposed.Recent clinical results of glioblastomas are especially promising in situations in which antisense was used either as gene therapy (antisense anti TGF beta oligodeoxynucleotides), or as cellular gene therapy (transfection with antisense anti IGF-I expression vector), following a classical surgery, radio-and chemotherapy. Using anti -IGF-I approach, median survival in glioblastoma patients has reached 21 months. The immune anti-tumour response in treated patients was confirmed by an increase of CD8 + T level in peripheral blood lymphocytes.

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A new putative target for antisense gene therapy of glioma: Glycogen synthase

Cited by 13 publications

References 24 publications

Gene Therapy of Glioblastoma: Anti – Gene Anti IGF-I Strategy

Gene Therapy of Glioblastoma: Anti – Gene Anti IGF-I Strategy

IGF-I biomarker testing in an ethical context

Antisense Strategies in Therapy of Gliomas

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