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  • 1
    Language: English
    In: Cellular physiology and biochemistry, 2013-05, Vol.31 (4-5), p.614-624
    Description: Background/Aims: The association between postoperative infection and prolonged survival in high-grade glioma is still a matter of debate. Previously we demonstrated that the intracerebral (i.c.) injection of heat-inactivated staphylococcal epitopes (HISE) resulted in a well-defined infux of immunocompetent cells across the blood-brain barrier. The present study investigated the potential antitumoral effect of HISE-immunostimulation in an experimental glioma model. Methods: Wistar rats were intracerebrally implanted with 9L gliosarcoma cells (n=6), 9L cells mixed with HISE (n=12), or phosphate buffered saline (n=4). Tumor growth was measured by serial magnetic resonance imaging (MRI). After death due to the tumor burden, the brains were histopathologically assessed for inflammation and oncolysis. A toxicity assay was performed to quantify potential impairment of HISE on tumor cell growth in vitro. Results: Animals treated by HISE showed a significant increase in average survival and even complete regression of an already established mass in one case. Naïve 9L gliosarcomas failed to recruit significant numbers of systemic immune cells. In contrast, concomitant intracerebral HISE inoculation lead to a oncolysis and a distinct peri- and intratumoral infiltration of macrophages, CD8 and CD4 co-expressing T-lymphocytes in two thirds of the tumor-bearing animals. The toxicity screening showed HISE-mediated oncolysis to be ineffective ex vivo. Conclusion: This study describes a novel approach for combatting malignant glioma using inactivated staphylococci as potent immunomodulators. Our results provide an outline for investigating the strategic potential of bacteria as emerging future therapeutics.
    Subject(s): Original Paper ; Rats, Wistar ; Staphylococcus epidermidis - immunology ; Gliosarcoma - therapy ; Brain Neoplasms - pathology ; Kaplan-Meier Estimate ; Rats ; CD4-Positive T-Lymphocytes - physiology ; Gliosarcoma - mortality ; CD8-Positive T-Lymphocytes - physiology ; Staphylococcus epidermidis - metabolism ; Transplantation, Homologous ; CD4-Positive T-Lymphocytes - immunology ; Magnetic Resonance Imaging ; Animals ; Immunotherapy ; Brain Neoplasms - therapy ; Cell Line, Tumor ; Gliosarcoma - pathology ; Brain Neoplasms - mortality ; CD8-Positive T-Lymphocytes - immunology ; Disease Models, Animal ; Immunologic Factors - therapeutic use ; Index Medicus ; Oncolysis ; Immunostimulatory adjuvant ; Staphylococcus ; Glioblastoma
    ISSN: 1015-8987
    E-ISSN: 1421-9778
    Source: Directory of Open Access Journals
    Source: Karger Journals Archiv (DFG Nationallizenzen)
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 2
    Language: English
    In: Brain pathology (Zurich, Switzerland), 2007-04, Vol.17 (2), p.146-150
    Description: About 15% of sporadic gastrointestinal and endometrial tumors show the microsatellite instability (MSI) phenotype because of loss of DNA mismatch repair (MMR) function. The incidence of MSI in tumors of the central nervous system still remains controversial. Previous studies reported a particular high frequency of MSI (∼25%) in young patients suffering from high-grade gliomas. Based on these data and the fact that in different tumor entities MMR deficiency defines a subgroup of tumors with distinct pathogenesis and particular clinicopathological features that may have impact on prognosis and therapy, we screened 624 gliomas from 71 young and 553 adult patients for MMR deficiency by MSI analysis using three highly sensitive diagnostic markers. Alterations of MMR protein expression was examined by immunohistochemistry. A malignant glioma from an adult patient displayed MSI and concomitant loss of nuclear MSH2 and MSH6 protein expression (0.16%; 1/619). No evidence for MSI or loss of MMR protein expression was observed in 71 gliomas from young patients (0%; 0/71) including 41 high-grade astrocytic tumors. Overall, we observed a much lower incidence of MSI among high-grade pediatric gliomas than initially reported and suggest that MMR deficiency does not play a major role in the pathogenesis of glial neoplasms.
    Subject(s): Immunohistochemistry ; Microsatellite Instability ; Humans ; Brain Neoplasms - pathology ; Brain Neoplasms - genetics ; Brain Neoplasms - metabolism ; Glioma - metabolism ; DNA-Binding Proteins - metabolism ; Glioma - genetics ; Glioma - pathology ; Polymerase Chain Reaction ; Adult ; Child ; Pediatrics ; Genetic aspects ; Measles-mumps-rubella vaccine ; Gliomas ; Cancer ; Index Medicus
    ISSN: 1015-6305
    E-ISSN: 1750-3639
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 3
    Language: English
    In: Clinical cancer research, 1999-06-01, Vol.5 (6), p.1417-1425
    Description: The occurrence of distant metastases is the most feared manifestation of breast cancer, often occurring years after the primary surgery and associated with poor survival. The dominant metastatic clone is characterized by an accumulation of genetic alterations, but it is not actually known at what stage of the metastatic cascade these alterations have occurred. We investigated allelic losses during breast cancer progression in a series of 17 primary breast carcinomas and 22 corresponding brain, liver, lung, and bone metastases (mean metastasis-free interval, 31 months) by analyzing 19 microsatellite markers on seven breast cancer- or metastasis-related chromosomal regions and correlated the incidence of combined loss of heterozygosity (LOH) with metastasis-free and postmetastatic survival. We found that, in comparison with the corresponding primary tumor, additional LOH events are frequently found in metastases and that the incidence of combined LOH in the primary tumor, plus the occurrence of additional LOH events in the distant metastases, correlated significantly with decreased postmetastatic survival. Combined LOH of the three breast cancer-related chromosomal regions alone or in combination with allelic loss at the p53 gene region seems to have a specific influence on the aggressive behavior of metastases. We hypothesize that the occurrence of additional LOH events is either involved in termination of dormancy of micrometastatic tumor cells at distant organ sites or acquired during further progression of metastases.
    Subject(s): Gynecology. Andrology. Obstetrics ; Mammary gland diseases ; Biological and medical sciences ; Medical sciences ; Tumors ; Lung Neoplasms - genetics ; Bone Neoplasms - mortality ; Liver Neoplasms - genetics ; Lung Neoplasms - mortality ; Humans ; Bone Neoplasms - secondary ; Brain Neoplasms - genetics ; Survival Rate ; Liver Neoplasms - mortality ; Loss of Heterozygosity ; Disease Progression ; Microsatellite Repeats - genetics ; Neoplasm Metastasis - genetics ; Brain Neoplasms - secondary ; Breast Neoplasms - genetics ; Lung Neoplasms - secondary ; Breast Neoplasms - mortality ; Female ; Bone Neoplasms - genetics ; Brain Neoplasms - mortality ; Liver Neoplasms - secondary ; Index Medicus
    ISSN: 1078-0432
    E-ISSN: 1557-3265
    Source: HighWire Press (Free Journals)
    Source: Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 4
    Language: English
    In: Cellular physiology and biochemistry, 2011-01, Vol.26 (6), p.821-830
    Description: Dramatic cerebral responses following brain injury (TBI) comprise inflammation, cell death, and modulation of trophic factor release. These cerebral modulations might induce and /or attenuate acute neuronal damage. Here, we investigated the effect of tissue extract derived from healthy (HBE) or injured rat brain (TBE) on the differentiation of cultured embryonic stem cells in vitro. Rats were sacrificed at t = 45 minutes following lateral fluid-percussion injury and extracts of cerebral tissue were prepared from 4-6 healthy or injured rat brain hemispheres. Murine embryonic stem cells (CGR8) cultured in serum-free medium were then conditioned for a week with HBE or TBE. Omission of serum from the culture medium induced neural differentiation of CGR8 stem cells, as indicated by a significant time dependent down-regulation of oct-4 with a concomitant upregulation of nestin after 7 days. In parallel cell loss was observed that seemed to be largely due to apoptotic cell death. In TBE treated cells, on the other hand, a significant amplification of apoptotic cell death, enhancement of nestin and MAP2 expression and marked morphological changes such as axonal-like outgrowth was observed within 3 days of conditioning. Treatment of stem cells with HBE resulted in less pronounced neuronal differentiation processes. Axonal-like outgrowth was not observed. Our data suggest that during the early acute phase of traumatic injury the cerebral environment is disposed to detrimental as well as potent protective signals that seem to rapidly induce neurogenic processes.
    Subject(s): Original Paper ; Embryonic Stem Cells - metabolism ; Nestin ; Embryonic Stem Cells - cytology ; Microtubule-Associated Proteins - genetics ; Cell Survival ; Microtubule-Associated Proteins - metabolism ; Rats ; Neurons - cytology ; Brain Injuries - metabolism ; Nerve Tissue Proteins - genetics ; Brain - metabolism ; Nerve Tissue Proteins - metabolism ; Octamer Transcription Factor-3 - genetics ; Animals ; Time Factors ; Octamer Transcription Factor-3 - metabolism ; Intermediate Filament Proteins - genetics ; Cell Differentiation ; Mice ; Neurons - metabolism ; Intermediate Filament Proteins - metabolism ; Apoptosis ; Index Medicus
    ISSN: 1015-8987
    E-ISSN: 1421-9778
    Source: Directory of Open Access Journals
    Source: Karger Journals Archiv (DFG Nationallizenzen)
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 5
    Language: English
    In: Cellular physiology and biochemistry, 2013, Vol.31 (4-5), p.614-624
    ISSN: 1015-8987
    E-ISSN: 1421-9778
    Source: Directory of Open Access Journals
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  • 6
    Language: English
    In: Neurosurgery, 2008-08, Vol.63 (2), p.336-345
    Description: The reasons for neuropsychological deficits after subarachnoid hemorrhage (SAH) are fairly unknown. Cholinergic basal forebrain (BFB) neurons are essential for attention, memory, and emotion. We investigated possible changes in the cholinergic BFB and its hippocampal and neocortical terminals after experimental SAH. SAH was induced in 19 male Wistar rats by stereotactic injection of 150 microL of autologous blood into the prechiasmatic cistern. Five control animals received 150 microL of saline. Continuous monitoring of brain tissue oxygen tension, intracranial pressure, and cerebral perfusion pressure was performed. After 4 and 14 days, the BFB was analyzed for cholinergic and gamma-aminobutyric acid-ergic cell counts. The number of cholinergic terminals in the hippocampus and neocortex was calculated by optical densitometry. SAH resulted in a 20 to 30% decrease in cholinergic BFB neurons in the medial septum and diagonal band at 4 and 14 days. A similar decline in the density of hippocampal and neocortical cholinergic terminals was demonstrated. Animals treated with saline did not exhibit significant cholinergic cell loss, and gamma-aminobutyric acid-ergic neurons appeared unaffected by the SAH. Courses of intracranial pressure and cerebral perfusion pressure did not differ between animals injected with blood and saline, but brain tissue oxygen tension decreased considerably and continued to stay below baseline in SAH, although it returned to normal values after saline injection. The present study provides evidence for a decrease of cholinergic BFB neurons after SAH. The direct effect of blood in the basal cisterns seemed to result in an enduring tissue hypoxia as a significant mechanism for cholinergic degeneration.
    Subject(s): Neurons - pathology ; Rats, Wistar ; Nerve Degeneration - physiopathology ; Rats ; Male ; Subarachnoid Hemorrhage - complications ; Subarachnoid Hemorrhage - pathology ; Nerve Degeneration - pathology ; Cholinergic Fibers - pathology ; Subarachnoid Hemorrhage - physiopathology ; Animals ; Nerve Degeneration - etiology ; Prosencephalon - physiopathology ; Prosencephalon - pathology ; Index Medicus
    ISSN: 0148-396X
    E-ISSN: 1524-4040
    Source: Oxford Journals A-Z Archive
    Source: Hellenic Academic Libraries Link
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 7
    Language: English
    In: Neurosurgery, 2008, Vol.63 (2), p.336-345
    Subject(s): Biological and medical sciences ; Medical sciences ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Neurosurgery
    ISSN: 0148-396X
    E-ISSN: 1524-4040
    Source: Oxford Journals A-Z Archive
    Source: Hellenic Academic Libraries Link
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  • 8
    Language: English
    In: Human gene therapy, 2003, Vol.14 (7), p.611-626
    Description: The development and use of gene transfer techniques creates an opportunity to achieve better treatment modalities for numerous disease entities. Promising results for treatment in tumor cells in culture and in small animal models have been reported. Nevertheless, the lack of widespread vector distribution throughout tumor tissue is one of the current limitations for successful clinical application of gene therapy paradigms. The use of migratory tumor cells themselves as vector delivery vehicles may allow wider vector distribution in tumors. In addition, continuous release of retrovirus vectors on-site could generate a high local virion concentration over an extended time period with consequent increases in transduction efficiency. In this paper, we present in culture and in vivo data of a herpes simplex virus-Epstein-Barr virus hybrid amplicon vector containing retrovirus vector components (tribrid vector) that allows conversion of tumor cells into retroviral producer cells. With this method, we were able to achieve a local fourfold amplification of stable transgene expression in tumors. The application of this system, which can integrate a transgene cassette into tumors with therapeutic bystander effects, could increase the local amplification effect to a level of clinical relevance.
    Subject(s): Fundamental and applied biological sciences. Psychology ; Biological and medical sciences ; Molecular and cellular biology ; Immunohistochemistry ; Neoplasms - metabolism ; Gene Expression ; Herpesvirus 4, Human - genetics ; Transduction, Genetic ; Humans ; Reverse Transcriptase Polymerase Chain Reaction ; Glioma - metabolism ; Animals ; Cell Cycle ; Retroviridae - genetics ; Mice, Nude ; Plasmids ; Glioma - pathology ; Female ; Herpesvirus 1, Human - genetics ; Mice ; Tumor Cells, Cultured ; Virion - growth & development ; Genetic Vectors ; Neoplasms - pathology ; 3T3 Cells ; Index Medicus
    ISSN: 1043-0342
    E-ISSN: 1557-7422
    Source: Mary Ann Liebert - EIRA
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 9
    Language: English
    In: The journal of gene medicine, 2002-05, Vol.4 (3), p.229-239
    Description: Background A number of properties have relegated the use of Moloney murine leukemia virus (Mo‐MLV)‐based retrovirus vectors primarily to ex vivo protocols. Direct implantation of retrovirus producer cells can bypass some of the limitations, and in situ vector production may result in a large number of gene transfer events. However, the fibroblast nature of most retrovirus packaging cells does not provide for an effective distribution of vector producing foci in vivo, especially in the brain. Effective development of new retrovirus producer cells with enhanced biologic properties may require the testing of a large number of different cell types, and a quick and efficient method to generate them is needed. Methods Moloney murine leukemia virus (Mo‐MLV) gag‐pol and env genes and retrovirus vector sequences carrying lacZ were cloned into different minimal HSV/AAV hybrid amplicons. Helper virus‐free amplicon vectors were used to co‐infect glioma cells in culture. Titers and stability of retrovirus vector production were assessed. Results Simultaneous infection of two glioma lines, Gli‐36 (human) and J3T (dog), with both types of amplicon vectors, generated stable packaging populations that produced retrovirus titers of 0.5–1.2×105 and 3.1–7.1×103 tu/ml, respectively. Alternatively, when cells were first infected with retrovirus vectors followed by infection with HyRMOVAmpho amplicon vector, stable retrovirus packaging populations were obtained from Gli‐36 and J3T cells producing retrovirus titers comparable to those obtained with a traditional retrovirus packaging cell line, ΨCRIPlacZ. Conclusions This amplicon vector system should facilitate generation of new types of retrovirus producer cells. Conversion of cells with migratory or tumor/tissue homing properties could result in expansion of the spatial distribution or targeting capacity, respectively, of gene delivery by retrovirus vectors in vivo. Copyright © 2002 John Wiley & Sons, Ltd.
    Subject(s): packaging lines ; gene therapy ; HSV amplicons ; retroviral vectors ; hybrid vectors ; Cell Line ; Genetic Therapy ; Transduction, Genetic ; Simplexvirus - genetics ; In Situ Hybridization, Fluorescence ; Virus Assembly ; Blotting, Northern ; Animals ; Gene Amplification ; RNA, Viral - genetics ; Moloney murine leukemia virus - physiology ; Mice ; Genetic Vectors ; 3T3 Cells ; Index Medicus
    ISSN: 1099-498X
    E-ISSN: 1521-2254
    Source: Alma/SFX Local Collection
    Source: © ProQuest LLC All rights reserved〈img src="https://exlibris-pub.s3.amazonaws.com/PQ_Logo.jpg" style="vertical-align:middle;margin-left:7px"〉
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  • 10
    Article
    Article
    2011
    ISSN: 1015-8987 
    Language: English
    In: Cellular physiology and biochemistry, 2011-01, Vol.26 (6), p.I-VI
    Subject(s): Special Section
    ISSN: 1015-8987
    E-ISSN: 1421-9778
    Source: Directory of Open Access Journals
    Source: Karger Journals Archiv (DFG Nationallizenzen)
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