10 results on '"Kindy, Mark S."'
Search Results
2. GM604 regulates developmental neurogenesis pathways and the expression of genes associated with amyotrophic lateral sclerosis
- Author
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Swindell, William R., Bojanowski, Krzysztof, Kindy, Mark S., Chau, Raymond M. W., and Ko, Dorothy
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- 2018
- Full Text
- View/download PDF
3. Impact of nutrition on inflammation, tauopathy, and behavioral outcomes from chronic traumatic encephalopathy
- Author
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Yu, Jin, Zhu, Hong, Taheri, Saeid, Mondy, William, Perry, Stephen, and Kindy, Mark S.
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- 2018
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4. Inhibition of Amyloidosis Using Low-Molecular-Weight Heparins
- Author
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Zhu, Hong, Yu, Jin, and Kindy, Mark S.
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- 2001
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5. A therapeutic cancer vaccine against GL261 murine glioma.
- Author
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Kindy, Mark S., Jin Yu, Hong Zhu, Smith, Michael T., Gattoni-Celli, Sebastiano, Yu, Jin, and Zhu, Hong
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CANCER vaccines , *GLIOBLASTOMA multiforme treatment , *IMMUNOTHERAPY , *BIOLUMINESCENCE , *KAPLAN-Meier estimator , *LABORATORY mice , *ANIMAL experimentation , *BRAIN , *BRAIN tumors , *CELL lines , *CELL membranes , *GLIOMAS , *IMMUNIZATION , *LUMINESCENCE spectroscopy , *MICE , *OXIDOREDUCTASES , *RESEARCH funding , *STAINS & staining (Microscopy) , *VACCINES - Abstract
Background: Glioblastoma (GBM) is the deadliest of brain tumors. Standard treatment for GBM is surgery, followed by combined radiation therapy and chemotherapy. Current therapy prolongs survival but does not offer a cure. We report on a novel immunotherapy against GBM, tested in an animal model of C57BL/6 mice injected intra-cranially with a lethal dose of murine GL261 glioma cells.Methods: Ten week-old C57BL/6 mice were anesthetized before injection of 2 × 10(4) GL261 cells in the right cerebral hemisphere and after 3 days half of the mice were administered a single subcutaneous (s.c.) injection of irradiated semi-allogeneic vaccine, while mock-vaccinated mice received a s.c. injection of phosphate-buffered saline (PBS). Tumor engraftment was monitored through bioluminescence imaging (BLI). Length of animal survival was measured by Kaplan-Meier graphs and statistics. At time of sacrifice brain tissue was processed for estimation of tumor size and immunohistochemical studies.Results: Overall survival of vaccinated mice was significantly longer compared to mock-vaccinated mice. Five to ten percent of vaccinated mice survived more than 90 days following the engraftment of GL261 cells in the brain and appeared to be free of disease by BLI. Tumor volume in the brain of vaccinated mice was on average five to ten-fold smaller compared to mock-vaccinated mice. In vaccinated mice, conspicuous microglia infiltrates were observed in tumor tissue sections and activated microglia appeared to form a fence along the perimeter of the tumor cells. The results of these animal studies persuaded the Office of Orphan Products Development of the Food and Drug Administration (FDA) to grant Orphan Drug Designation for treatment of GBM with irradiated, semi-allogeneic vaccines.Conclusions: Our preclinical observations suggest that semi-allogeneic vaccines could be tested clinically on subjects with GBM, as an adjuvant to standard treatment. [ABSTRACT FROM AUTHOR]- Published
- 2016
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6. Modulation of post-stroke degenerative and regenerative processes and subacute protection by site-targeted inhibition of the alternative pathway of complement.
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Alawieh, Ali, Elvington, Andrew, Hong Zhu, Jin Yu, Kindy, Mark S., Atkinson, Carl, Tomlinson, Stephen, Zhu, Hong, and Yu, Jin
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STROKE patients ,ETIOLOGY of stroke ,CENTRAL nervous system diseases ,CEREBRAL ischemia ,CELL death ,CELL metabolism ,STROKE prevention ,ANIMAL experimentation ,CELL receptors ,GENETIC techniques ,IMMUNITY ,MICE ,REGENERATION (Biology) ,RESEARCH funding ,STROKE - Abstract
Background: Complement promotes neuroinflammation and injury in models of stroke. However, complement is also being increasingly implicated in repair and regeneration after central nervous system (CNS) injury, and some complement deficiencies have been shown to provide acute, but not subacute, protection after murine stroke. Here, we investigate the dual role of complement in injury and repair after cerebral ischemia and reperfusion.Methods: We used complement-deficient mice and different complement inhibitors in a model of transient middle cerebral artery occlusion to investigate complement-dependent cellular and molecular changes that occur through the subacute phase after stroke.Results: C3 deficiency and site-targeted complement inhibition with either CR2-Crry (inhibits all pathways) or CR2-fH (inhibits alternative pathway) significantly reduced infarct size, reduced apoptotic cell death, and improved neurological deficit score in the acute phase after stroke. However, only in CR2-fH-treated mice was there sustained protection with no evolution of injury in the subacute phase. Whereas both inhibitors significantly reduced microglia/macrophage activation and astrogliosis in the subacute phase, only CR2-fH improved neurological deficit and locomotor function, maintained neurogenesis markers, enhanced neuronal migration, and increased VEGF expression. These findings in CR2-fH-treated mice correlated with improved performance in spatial learning and passive avoidance tasks. The complement anaphylatoxins have been implicated in repair and regenerative mechanisms after CNS injury, and in this context CR2-fH significantly reduced, but did not eliminate the generation of C5a within the brain, unlike CR2-Crry that completely blocked C5a generation. Gene expression profiling revealed that CR2-fH treatment downregulated genes associated with apoptosis, TGFβ signaling, and neutrophil activation, and decreased neutrophil infiltration was confirmed by immunohistochemistry. CR2-fH upregulated genes for neural growth factor and mediators of neurogenesis and neuronal migration. Live animal imaging demonstrated that following intravenous injection, CR2-fH targeted specifically to the post-ischemic brain, with a tissue half-life of 48.5 h. Finally, unlike C3 deficiency, targeted complement inhibition did not increase susceptibility to lethal post-stroke infection, an important consideration for stroke patients.Conclusions: Ischemic brain tissue-targeted and selective inhibition of alternative complement pathway provide self-limiting inhibition of complement activation and reduces acute injury while maintaining complement-dependent recovery mechanisms into the subacute phase after stroke. [ABSTRACT FROM AUTHOR]- Published
- 2015
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7. Semi-allogeneic vaccine for T-cell lymphoma.
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Jin Yu, Kindy, Mark S., and Gattoni-Celli, Sebastiano
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VACCINATION , *LYMPHOMAS , *LYMPHOID tissue , *IMMUNE response , *CELL lines , *CELL culture , *CANCER cells - Abstract
Background: Experimental results from studies with inbred mice and their syngeneic tumors indicated that the inoculation of semi-allogeneic cell hybrids (derived from the fusion between syngeneic tumor cells and an allogeneic cell line) protects the animal host from a subsequent lethal challenge with unmodified syngeneic tumor cells. Methods: Semi-allogeneic somatic cell hybrids were generated by the fusion of EL-4 T lymphoma cells (H-2b) and BALB/c-derived renal adenocarcinoma RAG cells (H-2d). Cell hybrids were injected intra-peritoneally (i.p.) in C57BL/6 mice (H-2b) before challenging the mice with a tumorigenic dose of EL-4 cells. Results: Semi-allogeneic tumor cell hybrids could not form a tumor in the animal host because they expressed allogeneic determinants (H-2d) and were rejected as a transplant. However, they conferred protection against a tumorigenic challenge of EL-4 cells compared to control mice that were mock-vaccinated with i.p.-injected phosphate-buffered saline (PBS) and in which EL-4 lymphomas grew rapidly to a large size in the peritoneal cavity. Screening of spleen-derived RNA by means of focused microarray technology revealed up-regulation of genes involved in the Th-1- type immune response and in the activation of dendritic antigen-presenting cells (APC). Conclusion: The results of our studies are entirely consistent with the concept that CD80- and CD86-expressing APC play a central role in mediating the immune protection induced by semiallogeneic vaccines by activating a Th-1 response and instructing T cells responsible for killing autologous tumor cells. [ABSTRACT FROM AUTHOR]
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- 2007
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- View/download PDF
8. Semi-allogeneic vaccines and tumor-induced immune tolerance.
- Author
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Yu J, Kindy MS, Gattoni-Celli S, Yu, Jin, Kindy, Mark S, and Gattoni-Celli, Sebastiano
- Abstract
Experimental results from studies with inbred mice and their syngeneic tumors indicated that the inoculation of semi-allogeneic cell hybrids (derived from the fusion between syngeneic tumor cells and an allogeneic cell line) protects the animal host from a subsequent lethal challenge with unmodified syngeneic tumor cells. Semi-allogeneic somatic cell hybrids were generated by the fusion of EL-4 T lymphoma cells (H-2b) and BALB/c-derived renal adenocarcinoma RAG cells (H-2d). Cell hybrids were injected intra-peritoneally (i.p.) in C57BL/6 mice (H-2b) before challenging the mice with a tumorigenic dose of EL-4 cells. Semi-allogeneic tumor cell hybrids could not form a tumor in the animal host because they expressed allogeneic determinants (H-2d) and were rejected as a transplant. However, they conferred protection against a tumorigenic challenge of EL-4 cells compared to control mice that were mock-vaccinated with i.p.-injected phosphate-buffered saline (PBS) and in which EL-4 lymphomas grew rapidly to a large size in the peritoneal cavity. Screening of spleen-derived RNA by means of focused microarray technology showed up-regulation of genes involved in the Th-1-type immune response and in the activation of dendritic antigen-presenting cells (APC). The results of our studies confirm the role of APC in mediating the immune protection induced by semi-allogeneic vaccines by activating a Th-1 response; these studies also reveal that semi-allogeneic vaccines are able to interfere with or even block the tumor-mediated induction of immune tolerance, a key mechanism underlying the suppression of anti-tumor immunity in the immune competent host. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
9. Focal cerebral ischemia in the TNFalpha-transgenic rat.
- Author
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Pettigrew LC, Kindy MS, Scheff S, Springer JE, Kryscio RJ, Li Y, and Grass DS
- Subjects
- Animals, Apoptosis genetics, Apoptosis immunology, Brain pathology, Brain physiopathology, Brain Infarction pathology, Brain Infarction physiopathology, Brain Ischemia physiopathology, Caspase 3 metabolism, Cerebral Arteries immunology, Cerebral Arteries pathology, Cerebral Arteries physiopathology, Disease Models, Animal, Encephalitis pathology, Encephalitis physiopathology, Female, Infarction, Middle Cerebral Artery immunology, Infarction, Middle Cerebral Artery physiopathology, Male, Microcirculation genetics, Microcirculation immunology, Neurons immunology, Neurons pathology, RNA, Messenger metabolism, Rats, Rats, Sprague-Dawley, Rats, Transgenic, Regional Blood Flow genetics, Regional Blood Flow immunology, Tumor Necrosis Factor-alpha genetics, Up-Regulation genetics, Brain immunology, Brain Infarction immunology, Brain Ischemia immunology, Encephalitis immunology, Tumor Necrosis Factor-alpha immunology, Up-Regulation immunology
- Abstract
Background: To determine if chronic elevation of the inflammatory cytokine, tumor necrosis factor-alpha (TNFalpha), will affect infarct volume or cortical perfusion after focal cerebral ischemia., Methods: Transgenic (TNFalpha-Tg) rats overexpressing the murine TNFalpha gene in brain were prepared by injection of mouse DNA into rat oocytes. Brain levels of TNFalpha mRNA and protein were measured and compared between TNFalpha-Tg and non-transgenic (non-Tg) littermates. Mean infarct volume was calculated 24 hours or 7 days after one hour of reversible middle cerebral artery occlusion (MCAO). Cortical perfusion was monitored by laser-Doppler flowmetry (LDF) during MCAO. Cortical vascular density was quantified by stereology. Post-ischemic cell death was assessed by immunohistochemistry and regional measurement of caspase-3 activity or DNA fragmentation. Unpaired t tests or analysis of variance with post hoc tests were used for comparison of group means., Results: In TNFalpha-Tg rat brain, the aggregate mouse and rat TNFalpha mRNA level was fourfold higher than in non-Tg littermates and the corresponding TNFalpha protein level was increased fivefold (p
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- 2008
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10. Semi-allogeneic vaccine for T-cell lymphoma.
- Author
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Yu J, Kindy MS, and Gattoni-Celli S
- Subjects
- Animals, Cell Line, Tumor, Dendritic Cells immunology, Eosine Yellowish-(YS), Gene Expression Regulation, Neoplastic, Genes, Neoplasm, Hematoxylin, Lymphoma, T-Cell genetics, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Oligonucleotide Array Sequence Analysis, Spleen immunology, Cancer Vaccines immunology, Lymphoma, T-Cell immunology, Lymphoma, T-Cell prevention & control
- Abstract
Background: Experimental results from studies with inbred mice and their syngeneic tumors indicated that the inoculation of semi-allogeneic cell hybrids (derived from the fusion between syngeneic tumor cells and an allogeneic cell line) protects the animal host from a subsequent lethal challenge with unmodified syngeneic tumor cells., Methods: Semi-allogeneic somatic cell hybrids were generated by the fusion of EL-4 T lymphoma cells (H-2b) and BALB/c-derived renal adenocarcinoma RAG cells (H-2d). Cell hybrids were injected intra-peritoneally (i.p.) in C57BL/6 mice (H-2b) before challenging the mice with a tumorigenic dose of EL-4 cells., Results: Semi-allogeneic tumor cell hybrids could not form a tumor in the animal host because they expressed allogeneic determinants (H-2d) and were rejected as a transplant. However, they conferred protection against a tumorigenic challenge of EL-4 cells compared to control mice that were mock-vaccinated with i.p.-injected phosphate-buffered saline (PBS) and in which EL-4 lymphomas grew rapidly to a large size in the peritoneal cavity. Screening of spleen-derived RNA by means of focused microarray technology revealed up-regulation of genes involved in the Th-1-type immune response and in the activation of dendritic antigen-presenting cells (APC)., Conclusion: The results of our studies are entirely consistent with the concept that CD80- and CD86-expressing APC play a central role in mediating the immune protection induced by semi-allogeneic vaccines by activating a Th-1 response and instructing T cells responsible for killing autologous tumor cells.
- Published
- 2007
- Full Text
- View/download PDF
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