15 results on '"Burmakin M"'
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2. Exposure to subthreshold dose of UVR-B induces apoptosis in the lens epithelial cells and does not in the lens fiber cells
- Author
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Galichanin, K., primary, Yu, Z., additional, Talebizadeh, N., additional, Burmakin, M., additional, and Söderberg, P., additional
- Published
- 2016
- Full Text
- View/download PDF
3. Therapeutic α-1-microglobulin ameliorates kidney ischemia-reperfusion injury.
- Author
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Burmakin M, Gilmour PS, Gram M, Shushakova N, Sandoval RM, Molitoris BA, and Larsson TE
- Subjects
- Animals, Male, Disease Models, Animal, Glomerular Filtration Rate drug effects, Mice, Inbred C57BL, Humans, Mice, Heme Oxygenase-1 metabolism, Rats, Rats, Sprague-Dawley, Acute Kidney Injury pathology, Acute Kidney Injury metabolism, Acute Kidney Injury drug therapy, Acute Kidney Injury prevention & control, Tissue Distribution, Reperfusion Injury pathology, Reperfusion Injury metabolism, Reperfusion Injury prevention & control, Reperfusion Injury drug therapy, Alpha-Globulins metabolism, Alpha-Globulins pharmacology, Kidney drug effects, Kidney pathology, Kidney metabolism
- Abstract
α-1-Microglobulin (A1M) is a circulating glycoprotein with antioxidant, heme-binding, and mitochondrial protection properties. The investigational drug RMC-035, a modified therapeutic A1M protein, was assessed for biodistribution and pharmacological activity in a broad set of in vitro and in vivo experiments, supporting its clinical development. Efficacy and treatment posology were assessed in various models of kidney ischemia and reperfusion injury (IRI). Real-time glomerular filtration rate (GFR), functional renal biomarkers, tubular injury biomarkers (NGAL and KIM-1), and histopathology were evaluated. Fluorescently labeled RMC-035 was used to assess biodistribution. RMC-035 demonstrated consistent and reproducible kidney protection in rat IRI models as well as in a model of IRI imposed on renal impairment and in a mouse IRI model, where it reduced mortality. Its pharmacological activity was most pronounced with combined dosing pre- and post-ischemia and weaker with either pre- or post-ischemia dosing alone. RMC-035 rapidly distributed to the kidneys via glomerular filtration and selective luminal uptake by proximal tubular cells. IRI-induced expression of kidney heme oxygenase-1 was inhibited by RMC-035, consistent with its antioxidative properties. RMC-035 also dampened IRI-associated inflammation and improved mitochondrial function, as shown by tubular autofluorescence. Taken together, the efficacy of RMC-035 is congruent with its targeted mechanism(s) and biodistribution profile, supporting its further clinical evaluation as a novel kidney-protective therapy. NEW & NOTEWORTHY A therapeutic A1M protein variant (RMC-035) is currently in phase 2 clinical development for renal protection in patients undergoing open-chest cardiac surgery. It targets several key pathways underlying kidney injury in this patient group, including oxidative stress, heme toxicity, and mitochondrial dysfunction. RMC-035 is rapidly eliminated from plasma, distributing to kidney proximal tubules, and demonstrates dose-dependent efficacy in numerous models of ischemia-reperfusion injury, particularly when administered before ischemia. These results support its continued clinical evaluation.
- Published
- 2024
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4. Soluble Klotho protects against glomerular injury through regulation of ER stress response.
- Author
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Charrin E, Dabaghie D, Sen I, Unnersjö-Jess D, Möller-Hackbarth K, Burmakin M, Mencke R, Zambrano S, Patrakka J, and Olauson H
- Subjects
- Humans, Mice, Animals, Kidney Glomerulus, Kidney metabolism, Albuminuria metabolism, Mice, Transgenic, Mice, Knockout, Diabetic Nephropathies metabolism, Podocytes
- Abstract
αKlotho (Klotho) has well established renoprotective effects; however, the molecular pathways mediating its glomerular protection remain incompletely understood. Recent studies have reported that Klotho is expressed in podocytes and protects glomeruli through auto- and paracrine effects. Here, we examined renal expression of Klotho in detail and explored its protective effects in podocyte-specific Klotho knockout mice, and by overexpressing human Klotho in podocytes and hepatocytes. We demonstrate that Klotho is not significantly expressed in podocytes, and transgenic mice with either a targeted deletion or overexpression of Klotho in podocytes lack a glomerular phenotype and have no altered susceptibility to glomerular injury. In contrast, mice with hepatocyte-specific overexpression of Klotho have high circulating levels of soluble Klotho, and when challenged with nephrotoxic serum have less albuminuria and less severe kidney injury compared to wildtype mice. RNA-seq analysis suggests an adaptive response to increased endoplasmic reticulum stress as a putative mechanism of action. To evaluate the clinical relevance of our findings, the results were validated in patients with diabetic nephropathy, and in precision cut kidney slices from human nephrectomies. Together, our data reveal that the glomeruloprotective effects of Klotho is mediated via endocrine actions, which increases its therapeutic potential for patients with glomerular diseases., (© 2023. The Author(s).)
- Published
- 2023
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5. Editor's Note: Dual Targeting of Wild-Type and Mutant p53 by Small-molecule RITA Results in the Inhibition of N-Myc and Key Survival Oncogenes and Kills Neuroblastoma Cells In Vivo and In Vitro .
- Author
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Burmakin M, Shi Y, Hedström E, Kogner P, and Selivanova G
- Published
- 2021
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- View/download PDF
6. Pharmacological HIF-PHD inhibition reduces renovascular resistance and increases glomerular filtration by stimulating nitric oxide generation.
- Author
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Burmakin M, Fasching A, Kobayashi H, Urrutia AA, Damdimopoulos A, Palm F, and Haase VH
- Subjects
- Animals, Cross-Sectional Studies, Hypoxia-Inducible Factor-Proline Dioxygenases, Nitric Oxide, Prolyl Hydroxylases, Rats, Biological Phenomena, Renal Insufficiency, Chronic
- Abstract
Aim: Hypoxia-inducible factors (HIFs) are O
2 -sensitive transcription factors that regulate multiple biological processes which are essential for cellular adaptation to hypoxia. Small molecule inhibitors of HIF-prolyl hydroxylase domain (PHD) dioxygenases (HIF-PHIs) activate HIF-dependent transcriptional programs and have broad clinical potential. HIF-PHIs are currently in global late-stage clinical development for the treatment of anaemia associated with chronic kidney disease. Although the effects of hypoxia on renal haemodynamics and function have been studied in animal models and in humans living at high altitude, the effects of pharmacological HIF activation on renal haemodynamics, O2 metabolism and metabolic efficiency are not well understood., Methods: Using a cross-sectional study design, we investigated renal haemodynamics, O2 metabolism, gene expression and NO production in healthy rats treated with different doses of HIF-PHIs roxadustat or molidustat compared to vehicle control., Results: Systemic administration of roxadustat or molidustat resulted in a dose-dependent reduction in renovascular resistance (RVR). This was associated with increased glomerular filtration rate (GFR), urine flow and tubular sodium transport rate (TNa ). Although both total O2 delivery and TNa were increased, more O2 was extracted per transported sodium in rats treated with high-doses of HIF-PHIs, suggesting a reduction in metabolic efficiency. Changes in RVR and GFR were associated with increased nitric oxide (NO) generation and substantially suppressed by pharmacological inhibition of NO synthesis., Conclusions: Our data provide mechanistic insights into dose-dependent effects of short-term pharmacological HIF activation on renal haemodynamics, glomerular filtration and O2 metabolism and identify NO as a major mediator of these effects., (© 2021 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.)- Published
- 2021
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7. The kidney injury caused by the onset of acute graft-versus-host disease is associated with down-regulation of αKlotho.
- Author
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Amin R, He R, Gupta D, Zheng W, Burmakin M, Mohammad DK, DePierre JW, Sadeghi B, Olauson H, Wernerson A, El-Andaloussi S, Hassan M, and Abedi-Valugerdi M
- Subjects
- Acute Kidney Injury blood, Acute Kidney Injury diagnosis, Acute Kidney Injury pathology, Animals, Biomarkers analysis, Biomarkers metabolism, Disease Models, Animal, Down-Regulation immunology, Female, Fibroblast Growth Factor-23, Fibroblast Growth Factors blood, Fibroblast Growth Factors immunology, Graft vs Host Disease blood, Graft vs Host Disease immunology, Humans, Interferon-gamma blood, Interferon-gamma immunology, Kidney, Klotho Proteins, Lipocalin-2 analysis, Lipocalin-2 metabolism, Male, Mice, Transplantation, Homologous adverse effects, Tumor Necrosis Factor-alpha blood, Tumor Necrosis Factor-alpha immunology, Acute Kidney Injury immunology, Bone Marrow Transplantation adverse effects, Glucuronidase metabolism, Graft vs Host Disease complications
- Abstract
Acute graft-versus-host disease (aGVHD) and kidney injury are the major complications after allogeneic hematopoietic stem cell transplantation (HSCT). Although the underlying mechanisms for the development of these complications are not yet fully understood, it has been proposed that emergence of aGVHD contributes to the development of kidney injury after HSCT. We have shown previously that aGVHD targets the kidney in a biphasic manner: at the onset, inflammatory genes are up-regulated, while when aGVHD becomes established, donor lymphocytes infiltrate the kidney. Here, we characterize renal manifestations at the onset of aGVHD. Mice receiving allogeneic bone marrow and spleen cells displayed symptoms of aGVHD and elevated serum levels of tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) within 4 days. There was concurrent kidney injury with the following characteristics: (1) elevated expression of the kidney injury biomarker, neutrophil gelatinase-associated lipocalin (NGAL), (2) accumulation of hetero-lysosomes in proximal tubule epithelial cells, and (3) reductions in αKlotho mRNA and protein and increased serum levels of fibroblast growth factor 23 (Fgf23), phosphate and urea. This situation resembled acute renal injury caused by bacterial lipopolysaccharide. We conclude that the onset of aGVHD is associated with kidney injury involving down-regulation of αKlotho, a sight that may inspire novel therapeutic approaches., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2020
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8. Hypoxia-inducible factor prolyl-4-hydroxylation in FOXD1 lineage cells is essential for normal kidney development.
- Author
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Kobayashi H, Liu J, Urrutia AA, Burmakin M, Ishii K, Rajan M, Davidoff O, Saifudeen Z, and Haase VH
- Subjects
- Anemia blood, Anemia drug therapy, Anemia etiology, Animals, Cell Hypoxia physiology, Clinical Trials, Phase III as Topic, Disease Models, Animal, Enzyme Inhibitors therapeutic use, Forkhead Transcription Factors genetics, Forkhead Transcription Factors metabolism, Humans, Hydroxylation physiology, Hypoxia-Inducible Factor-Proline Dioxygenases antagonists & inhibitors, Hypoxia-Inducible Factor-Proline Dioxygenases genetics, Kidney cytology, Kidney metabolism, Kidney Diseases complications, Kidney Diseases drug therapy, Mice, Molecular Targeted Therapy methods, Mutation, Organ Size physiology, Procollagen-Proline Dioxygenase antagonists & inhibitors, Procollagen-Proline Dioxygenase genetics, Renal Insufficiency mortality, Renal Insufficiency pathology, Stromal Cells metabolism, Basic Helix-Loop-Helix Transcription Factors metabolism, Hypoxia-Inducible Factor-Proline Dioxygenases physiology, Kidney growth & development, Procollagen-Proline Dioxygenase physiology, Renal Insufficiency genetics
- Abstract
Hypoxia in the embryo is a frequent cause of intra-uterine growth retardation, low birth weight, and multiple organ defects. In the kidney, this can lead to low nephron endowment, predisposing to chronic kidney disease and arterial hypertension. A key component in cellular adaptation to hypoxia is the hypoxia-inducible factor pathway, which is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3. In the adult kidney, PHD oxygen sensors are differentially expressed in a cell type-dependent manner and control the production of erythropoietin in interstitial cells. However, the role of interstitial cell PHDs in renal development has not been examined. Here we used a genetic approach in mice to interrogate PHD function in FOXD1-expressing stroma during nephrogenesis. We demonstrate that PHD2 and PHD3 are essential for normal kidney development as the combined inactivation of stromal PHD2 and PHD3 resulted in renal failure that was associated with reduced kidney size, decreased numbers of glomeruli, and abnormal postnatal nephron formation. In contrast, nephrogenesis was normal in animals with individual PHD inactivation. We furthermore demonstrate that the defect in nephron formation in PHD2/PHD3 double mutants required intact hypoxia-inducible factor-2 signaling and was dependent on the extent of stromal hypoxia-inducible factor activation. Thus, hypoxia-inducible factor prolyl-4-hydroxylation in renal interstitial cells is critical for normal nephron formation., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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9. Endoglin prevents vascular malformation by regulating flow-induced cell migration and specification through VEGFR2 signalling.
- Author
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Jin Y, Muhl L, Burmakin M, Wang Y, Duchez AC, Betsholtz C, Arthur HM, and Jakobsson L
- Subjects
- Animals, Arteriovenous Malformations genetics, Arteriovenous Malformations metabolism, Arteriovenous Malformations pathology, Cell Lineage, Cell Proliferation, Cells, Cultured, Disease Models, Animal, Endoglin deficiency, Endoglin genetics, Endothelial Cells pathology, Genetic Predisposition to Disease, Humans, Kinetics, Mice, Knockout, Phenotype, Phosphatidylinositol 3-Kinase metabolism, Proto-Oncogene Proteins c-akt metabolism, RNA Interference, Stress, Mechanical, Telangiectasia, Hereditary Hemorrhagic genetics, Telangiectasia, Hereditary Hemorrhagic metabolism, Telangiectasia, Hereditary Hemorrhagic pathology, Tissue Culture Techniques, Transfection, Vascular Endothelial Growth Factor A metabolism, Vascular Endothelial Growth Factor Receptor-2 genetics, Arteriovenous Malformations prevention & control, Endoglin metabolism, Endothelial Cells metabolism, Neovascularization, Pathologic, Neovascularization, Physiologic, Signal Transduction, Telangiectasia, Hereditary Hemorrhagic prevention & control, Vascular Endothelial Growth Factor Receptor-2 metabolism
- Abstract
Loss-of-function (LOF) mutations in the endothelial cell (EC)-enriched gene endoglin (ENG) cause the human disease hereditary haemorrhagic telangiectasia-1, characterized by vascular malformations promoted by vascular endothelial growth factor A (VEGFA). How ENG deficiency alters EC behaviour to trigger these anomalies is not understood. Mosaic ENG deletion in the postnatal mouse rendered Eng LOF ECs insensitive to flow-mediated venous to arterial migration. Eng LOF ECs retained within arterioles acquired venous characteristics and secondary ENG-independent proliferation resulting in arteriovenous malformation (AVM). Analysis following simultaneous Eng LOF and overexpression (OE) revealed that ENG OE ECs dominate tip-cell positions and home preferentially to arteries. ENG knockdown altered VEGFA-mediated VEGFR2 kinetics and promoted AKT signalling. Blockage of PI(3)K/AKT partly normalized flow-directed migration of ENG LOF ECs in vitro and reduced the severity of AVM in vivo. This demonstrates the requirement of ENG in flow-mediated migration and modulation of VEGFR2 signalling in vascular patterning.
- Published
- 2017
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10. Imatinib increases oxygen delivery in extracellular matrix-rich but not in matrix-poor experimental carcinoma.
- Author
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Burmakin M, van Wieringen T, Olsson PO, Stuhr L, Åhgren A, Heldin CH, Reed RK, Rubin K, and Hellberg C
- Subjects
- Animals, Apoptosis drug effects, Cell Line, Tumor, Collagen metabolism, Colonic Neoplasms blood supply, Colonic Neoplasms pathology, Extracellular Fluid drug effects, Extracellular Fluid metabolism, Extracellular Matrix drug effects, Mice, SCID, Neoplasms, Experimental blood supply, Neoplasms, Experimental pathology, Pressure, Receptor, Platelet-Derived Growth Factor beta metabolism, Stromal Cells metabolism, Tumor Burden drug effects, Water, Colonic Neoplasms metabolism, Extracellular Matrix metabolism, Imatinib Mesylate pharmacology, Neoplasms, Experimental metabolism, Oxygen pharmacology
- Abstract
Background: Imatinib causes increased turnover of stromal collagen, reduces collagen fibril diameter, enhances extracellular fluid turnover and lowers interstitial fluid pressure (IFP) in the human colonic carcinoma KAT-4/HT-29 (KAT-4) xenograft model., Methods: We compared the effects of imatinib on oxygen levels, vascular morphology and IFP in three experimental tumor models differing in their content of a collagenous extracellular matrix., Results: Neither the KAT4 and CT-26 colonic carcinoma models, nor B16BB melanoma expressed PDGF β-receptors in the malignant cells. KAT-4 tumors exhibited a well-developed ECM in contrast to the other two model systems. The collagen content was substantially higher in KAT-4 than in CT-26, while collagen was not detectable in B16BB tumors. The pO
2 was on average 5.4, 13.9 and 19.3 mmHg in KAT-4, CT-26 and B16BB tumors, respectively. Treatment with imatinib resulted in similar pO2 -levels in all three tumor models but only in KAT-4 tumors did the increase reach statistical significance. It is likely that after imatinib treatment the increase in pO2 in KAT-4 tumors is caused by increased blood flow due to reduced vascular resistance. This notion is supported by the significant reduction observed in IFP in KAT-4 tumors after imatinib treatment. Vessel area varied between 4.5 and 7% in the three tumor models and was not affected by imatinib treatment. Imatinib had no effect on the fraction of proliferating cells, whereas the fraction of apoptotic cells increased to a similar degree in all three tumor models., Conclusion: Our data suggest that the effects of imatinib on pO2 -levels depend on a well-developed ECM and provide further support to the suggestion that imatinib acts by causing interstitial stroma cells to produce a less dense ECM, which would in turn allow for an increased blood flow. The potential of imatinib treatment to render solid tumors more accessible to conventional treatments would therefore depend on the degree of tumor desmoplasia.- Published
- 2017
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11. Dual targeting of wild-type and mutant p53 by small molecule RITA results in the inhibition of N-Myc and key survival oncogenes and kills neuroblastoma cells in vivo and in vitro.
- Author
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Burmakin M, Shi Y, Hedström E, Kogner P, and Selivanova G
- Subjects
- Animals, Antineoplastic Agents pharmacology, Blotting, Western, Cell Proliferation drug effects, Female, Humans, Immunoprecipitation, In Vitro Techniques, Mice, Mice, SCID, Mutation genetics, Neuroblastoma metabolism, Proto-Oncogene Proteins c-mdm2 antagonists & inhibitors, Proto-Oncogene Proteins c-mdm2 genetics, Proto-Oncogene Proteins c-mdm2 metabolism, Proto-Oncogene Proteins c-myc genetics, Proto-Oncogene Proteins c-myc metabolism, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Xenograft Model Antitumor Assays, Apoptosis drug effects, Neuroblastoma drug therapy, Neuroblastoma pathology, Oncogenes drug effects, Piperazines pharmacology, Proto-Oncogene Proteins c-myc antagonists & inhibitors, Tumor Suppressor Protein p53 antagonists & inhibitors
- Abstract
Purpose: Restoration of the p53 function in tumors is a promising therapeutic strategy due to the high potential of p53 as tumor suppressor and the fact that established tumors depend on p53 inactivation for their survival. Here, we addressed the question whether small molecule RITA can reactivate p53 in neuroblastoma and suppress the growth of neuroblastoma cells in vitro and in vivo., Experimental Design: The ability of RITA to inhibit growth and to induce apoptosis was shown in seven neuroblastoma cell lines. Mechanistic studies were carried out to determine the p53 dependence and the molecular mechanism of RITA-induced apoptosis in neuroblastoma, using cell viability assays, RNAi silencing, co-immunoprecipitation, qPCR, and Western blotting analysis. In vivo experiments were conducted to study the effect of RITA on human neuroblastoma xenografts in mice., Results: RITA induced p53-dependent apoptosis in a set of seven neuroblastoma cell lines, carrying wild-type or mutant p53; it activated p53 and triggered the expression of proapoptotic p53 target genes. Importantly, p53 activated by RITA inhibited several key oncogenes that are high-priority targets for pharmacologic anticancer strategies in neuroblastoma, including N-Myc, Aurora kinase, Mcl-1, Bcl-2, Wip-1, MDM2, and MDMX. Moreover, RITA had a strong antitumor effect in vivo., Conclusions: Reactivation of wild-type and mutant p53 resulting in the induction of proapoptotic factors along with ablation of key oncogenes by compounds such as RITA may be a highly effective strategy to treat neuroblastoma., (©2013 AACR.)
- Published
- 2013
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12. Combined anti-angiogenic therapy targeting PDGF and VEGF receptors lowers the interstitial fluid pressure in a murine experimental carcinoma.
- Author
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Kłosowska-Wardega A, Hasumi Y, Burmakin M, Ahgren A, Stuhr L, Moen I, Reed RK, Rubin K, Hellberg C, and Heldin CH
- Subjects
- Animals, Apoptosis drug effects, Blood Volume drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Drug Synergism, Humans, Mice, Neoplasms, Experimental blood supply, Neoplasms, Experimental pathology, Neovascularization, Pathologic drug therapy, Neovascularization, Pathologic pathology, Pericytes drug effects, Pericytes pathology, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, Angiogenesis Inhibitors pharmacology, Angiogenesis Inhibitors therapeutic use, Extracellular Fluid drug effects, Neoplasms, Experimental drug therapy, Pressure, Receptors, Platelet-Derived Growth Factor antagonists & inhibitors, Receptors, Vascular Endothelial Growth Factor antagonists & inhibitors
- Abstract
Elevation of the interstitial fluid pressure (IFP) of carcinoma is an obstacle in treatment of tumors by chemotherapy and correlates with poor drug uptake. Previous studies have shown that treatment with inhibitors of platelet-derived growth factor (PDGF) or vascular endothelial growth factor (VEGF) signaling lowers the IFP of tumors and improve chemotherapy. In this study, we investigated whether the combination of PDGFR and VEGFR inhibitors could further reduce the IFP of KAT-4 human carcinoma tumors. The tumor IFP was measured using the wick-in-needle technique. The combination of STI571 and PTK/ZK gave an additive effect on the lowering of the IFP of KAT-4 tumors, but the timing of the treatment was crucial. The lowering of IFP following combination therapy was accompanied by vascular remodeling and decreased vascular leakiness. The effects of the inhibitors on the therapeutic efficiency of Taxol were investigated. Whereas the anti-PDGF and anti-VEGF treatment did not significantly inhibit tumor growth, the inhibitors enhanced the effect of chemotherapy. Despite having an additive effect in decreasing tumor IFP, the combination therapy did not further enhance the effect of chemotherapy. Simultaneous targeting of VEGFR and PDGFR kinase activity may be a useful strategy to decrease tumor IFP, but the timing of the inhibitors should be carefully determined.
- Published
- 2009
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13. Renal clearance of absorbed intact GFP in the frog and rat intestine.
- Author
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Seliverstova EV, Burmakin MV, and Natochin YV
- Subjects
- Absorption, Animals, Female, Fluorescent Antibody Technique, Green Fluorescent Proteins administration & dosage, Green Fluorescent Proteins ultrastructure, Intestine, Small cytology, Kidney Tubules, Proximal cytology, Kidney Tubules, Proximal ultrastructure, Male, Rats, Rats, Wistar, Time Factors, Anura metabolism, Green Fluorescent Proteins metabolism, Intestine, Small metabolism, Kidney Function Tests
- Abstract
Intestine absorption of intact green fluorescent protein (GFP) and its following accumulation in the renal proximal tubule cells after its intragastric administration have been established by confocal microscopy in the rat and frog. Reabsorbed GFP was revealed in the endosomes and lysosomes of the proximal tubule cells by the methods of GFP photooxidation and immunofluorescent microscopy. The GFP intestine absorption rate and GFP accumulation in the kidney were significantly higher in the frog than in the rat. No specific fluorescence was revealed in the liver and colon cells after the GFP intragastric administration. The data obtained indicate the ability of the small intestine in the frog and rat to absorb intact proteins and an important role of the kidney in exogenous protein metabolism.
- Published
- 2007
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14. [Dynamics of absorption of yellow fluorescent protein in intestine and reabsorption in kidney in rat postnatal ontogenesis].
- Author
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Burmakin MV, Seliverstova EV, and Natochin IuV
- Subjects
- Absorption, Animals, Bacterial Proteins pharmacokinetics, Enterocytes metabolism, Intestine, Small ultrastructure, Kidney growth & development, Kidney ultrastructure, Luminescent Proteins pharmacokinetics, Nephrons growth & development, Nephrons metabolism, Rats, Rats, Wistar, Bacterial Proteins metabolism, Intestine, Small metabolism, Kidney metabolism, Luminescent Proteins metabolism
- Abstract
In experiments of the 5, 12 and 25-day old rat pups and adult rats in has been shown that after administration of yellow fluorescent protein (YFP) into stomach, its partial absorption in the non-degraded state in the small intestine takes place, with subsequent transport to kidney with blood flow and accumulation in cells of the proximal nephron segment. With age of rats, intensity of the intestinal YFP absorption decrease; the YFP accumulation in the kidney is more active in rats of the younger age groups than in adult animals. No accumulation of YFP in liver was revealed. The obtained data indicate an intensive absorption of YFP in the non-hydrolyzed form in the rat pup small intestine in early postnatal ontogenesis and an important role of kidney in protein metabolism and in proteolysis of exogenous proteins.
- Published
- 2007
15. [Kidney accumulation of yellow fluorescent protein after its absorption in the rat intestine].
- Author
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Burmakin MV, Seliverstova EV, and Natochin IuV
- Subjects
- Absorption, Animals, Enterocytes cytology, Female, Ileum cytology, Kidney Tubules, Proximal cytology, Luminescent Proteins administration & dosage, Microscopy, Confocal, Rats, Rats, Wistar, Enterocytes physiology, Ileum physiology, Kidney Tubules, Proximal physiology, Luminescent Proteins metabolism
- Abstract
Yellow fluorescent protein (3.6 ng) was administered through a catheter into the Wistar rat intestine lumen. By the method of confocal microscopy it has been established that as soon as in 3 min this protein appears in the epithelial cells of ileum, is absorbed into the blood and accumulated in cells of the nephron proximal segment, not being revealed in the liver, though. The protein accumulation in kidneys continues for several hours. The yellow fluorescent protein is homogeneously distributed in enterocytes, while in epithelial cells of the proximal tubule this protein is localized in vesicles. The data obtained indicate absorption of non-degraded yellow fluorescent protein in the intestine and role of kidney in metabolism not only of endogenous, but also of exogenous proteins.
- Published
- 2005
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