Neoplastic Brain, Glioblastoma, and Immunotherapy

IGF-I, insulin-like growth factor 1, is present in normal fetal/neonatal brain development and reappears in the mature brain participating in the development of malignant tumor, glioblastoma multiforme. Targeting the IGF-I system has emerged as a useful method to reduce glial malignant development. Downregulation in the expression of IGF-I using antigene anti-IGF-I technology (antisense, AS, and triple helix, TH) applied in glioma cell culture established from glioblastoma biopsies induces the expression of B7 and MHC-I antigens in transfected cells (immunogenicity). The transfected cancer cells, “vaccines,” after subcutaneous injection, initiated an immune response mediated by T CD8+ lymphocytes, followed by tumor regression (immunotherapy). The median survival of patients treated by surgery followed by radiotherapy and immunotherapy was 21–24 months. On the other side, the experimental work has demonstrated that IGF-I AS or TH transfected tumor cells fused with activated dendritic cells, DC, showing more striking immunogenic character. Using IGF-I TH/DC “vaccination,” the efficiency in suppressing rat glioma tumors is not only relatively higher than that obtained using IGF-I TH cells but is also more rapid

Correlation of Oxidative and Antioxidative Processes in the Blood of Patients with Cervical Spinal Cord Injury

The effect of cervical spinal cord injury (CSCI) on oxidative stress parameters was assessed. The study was conducted in 42 patients with CSCI (studied group), 15 patients with cerebral concussion, without CSCI (Control II), and 30 healthy volunteers (Control I). Blood was taken from the basilic vein: before and seven days after the spinal cord decompression surgery (mean time from CSCI to surgery: 8 hours) in the studied group and once in the controls. Thiobarbituric acid reactive substances (TBARS) and conjugated dienes (CD) concentrations, and glutathione peroxidase (GPx), catalase (CAT), and creatine kinase (CK) activities before the surgery were higher in the studied group than in the controls. Reduced glutathione concentration was similar in all groups. Superoxide dismutase (SOD) in the studied group was 16% lower (P≤0.001) than in Control I. Lipid peroxidation products, and GPx and CAT activities in erythrocytes seven days after the surgery were lower (P≤0.001), while SOD was 25% higher (P≤0.001) than before the surgery. CK in blood plasma after the surgery was 34% lower (P≤0.001) than before it. CSCI is accompanied by oxidative stress. Surgical and pharmacological treatment helps to restore the oxidant-antioxidant balance

Epistemológica experiencia en la elaboración de tecnología biomolecular para estrategia de la inmunoterapia génica

We have been faced with a 40 year long challenge: how to establish tools that can be applied in the treatment of brain tumor - glioblastoma (100% fatal) - using our knowledge of evolution, chemistry of proteins, genetics, molecular biology and immunology. An efficient strategy targeting growth factor IGF-I, present in tumor development, was established by construction of vectors expressing either IGF-I antisense RNA or IGF-I RNA forming RNA-DNA triple helix. The vectors introduced in the cancer cells in vitro, enable to completely stop the synthesis of IGF-I: on translation or transcription level, respectively. When injected in vivo, these cells induce an immune anti-tumor effect (CD8+) accompanied by increase of the median survival of patients. The first thesis in Colombia describing the used technology, was presented in Distrital University in February 2016.Unos de los retos científicos de los últimos 40 años, ha sido la búsqueda de la herramienta para el tratamiento del tumor cerebral, el glioblastoma, mortales en el 100% de los casos, utilizando nuestro conocimiento de la evolución, la química de las proteínas, la genética, la biología molecular y la inmunología. Una estrategia eficiente enfocada hacia el factor de crecimiento IGF-I presente en el desarrollo tumoral, fue establecida mediante la construcción de vectores expresando el IGF-I antisentido ARN o el IGF-I ARN formando ARN-ADN triple hélice. Estos vectores introducidos en las células cancerosas in vitro, permiten detener por completo la síntesis de IGF-I en la traducción o a nivel de la transcripción respectivamente. Mientras la inyección in vivo,  inducen efecto antitumoral inmune (TCD8+) acompañado de aumento de la supervivencia media de los pacientes. La primera tesis en Colombia que describe la tecnología utilizada, fue presentada en la Universidad Distrital, en febrero de 2016

Epistemological experience in developing of biomolecular technology for immunogene therapy strategy

Unos de los retos científicos de los últimos 40 años, ha sido la búsqueda de la herramienta para el tratamiento del tumor cerebral, el glioblastoma, mortales en el 100% de los casos, utilizando nuestro conocimiento de la evolución, la química de las proteínas, la genética, la biología molecular y la inmunología. Una estrategia eficiente enfocada hacia el factor de crecimiento IGF-I presente en el desarrollo tumoral, fue establecida mediante la construcción de vectores expresando el IGF-I antisentido ARN o el IGF-I ARN formando ARN-ADN triple hélice. Estos vectores introducidos en las células cancerosas in vitro, permiten detener por completo la síntesis de IGF-I en la traducción o a nivel de la transcripción respectivamente. Mientras la inyección in vivo,  inducen efecto antitumoral inmune (TCD8+) acompañado de aumento de la supervivencia media de los pacientes. La primera tesis en Colombia que describe la tecnología utilizada, fue presentada en la Universidad Distrital, en febrero de 2016.We have been faced with a 40 year long challenge: how to establish tools that can be applied in the treatment of brain tumor - glioblastoma (100% fatal) - using our knowledge of evolution, chemistry of proteins, genetics, molecular biology and immunology. An efficient strategy targeting growth factor IGF-I, present in tumor development, was established by construction of vectors expressing either IGF-I antisense RNA or IGF-I RNA forming RNA-DNA triple helix. The vectors introduced in the cancer cells in vitro, enable to completely stop the synthesis of IGF-I: on translation or transcription level, respectively. When injected in vivo, these cells induce an immune anti-tumor effect (CD8+) accompanied by increase of the median survival of patients. The first thesis in Colombia describing the used technology, was presented in Distrital University in February 2016

Epistemological experience in developing of biomolecular technology for immunogene therapy strategy

We have been faced with a 40 year long challenge: how to establish tools that can be applied in the treatment of brain tumor - glioblastoma (100% fatal) - using our knowledge of evolution, chemistry of proteins, genetics, molecular biology and immunology. An efficient strategy targeting growth factor IGF-I, present in tumor development, was established by construction of vectors expressing either IGF-I antisense RNA or IGF-I RNA forming RNA-DNA triple helix. The vectors introduced in the cancer cells in vitro, enable to completely stop the synthesis of IGF-I: on translation or transcription level, respectively. When injected in vivo, these cells induce an immune anti-tumor effect (CD8+) accompanied by increase of the median survival of patients. The first thesis in Colombia describing the used technology, was presented in Distrital University in February 2016

Methodology for Anti Gene Anti IGI I Therapy of Malignant Tumours

13The aim of this study was to establish the criteria for methodology of cellular “anti-IGF-I” therapy of malignant tumours and particularly for glioblastoma multiforme. The treatment of primary glioblastoma patients using surgery, radiotherapy, and chemotherapy was followed by subcutaneous injection of autologous cancer cells transfected by IGF-I antisense/triple helix expression vectors. The prepared cell “vaccines” should it be in the case of glioblastomas or other tumours, have shown a change of phenotype, the absence of IGF-I protein, and expression of MHC-I and B7. The peripheral blood lymphocytes, PBL cells, removed after each of two successive vaccinations, have demonstrated for all the types of tumour tested an increasing level of CD8+ and CD8+28+ molecules and a switch from CD8+11b+ to CD8+11. All cancer patients were supervised for up to 19 months, the period corresponding to minimum survival of glioblastoma patients. The obtained results have permitted to specify the common criteria for “anti-IGF-I” strategy: characteristics sine qua non of injected “vaccines” (cloned cells IGF-I(−) and MHC-I(+)) and of PBL cells (CD8+ increased level

In vitro Technical Aspects of Anti-Gene IGF-I Vaccines against Glioma

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