RESUMEN
Metabolic syndrome is increasingly common, and closely related with overweight or obesity. In the obese state, macrophages infiltrate to the adipose tissue (AT), resulting in chronic inflammation and insulin resistance in the AT cells. Recently, attention has been paid to the role of AT macrophages in metabolic disorders should be applied to the initial drug screening step, but it was difficult to mimic the inflammatory adipocytes using the traditional 2-dimensional (2D) culture. In this study, we developed the 3-dimensional (3D) culture system to overcome this limitation. After adipogenic differentiation, lipid droplets were highly accumulated in cells, and differentiation of preadipocytes was not declined by macrophage co-culture. However, only co-cultured cells expressed the insulin resistance features. Compare to mono-cultured adipocytes, co-cultured adipocytes showed reduced glucose uptake and GLUT4 did not translocated to cell membrane even though treatment of high concentration of insulin. Using 3D co-culture model, we develop a microwell-scale drug screening protocol to test anti-obesity effect. 3D cultured cells reacted more sensitive to drugs, and PPARγ antagonist GW9662 (10, 20 µM) repressed adipogenic differentiation in a concentration-dependent manner in 3D co-cultured cells.
Asunto(s)
Síndrome Metabólico , Adipocitos , Adipogénesis , Evaluación Preclínica de Medicamentos , Humanos , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/etiología , Síndrome Metabólico/metabolismo , Obesidad/tratamiento farmacológicoRESUMEN
As DYRK1A and 1B inhibitors, 1H-pyrazolo[3,4-b]pyridine derivatives were synthesized. Mostly, 3-aryl-5-arylamino compounds (6) and 3,5-diaryl compounds (8 and 9) were prepared and especially, 3,5-diaryl compound 8 and 9 showed excellent DYRK1B inhibitory enzymatic activities with IC50 Values of 3-287 nM. Among them, 3-(4-hydroxyphenyl), 5-(3,4-dihydroxyphenyl)-1H-pyrazolo[3,4-b]pyridine (8h) exhibited the highest inhibitory enzymatic activity (IC50 = 3 nM) and cell proliferation inhibitory activity (IC50 = 1.6 µM) towards HCT116 colon cancer cells. Also compound 8h has excellent inhibitory activities in patient-derived colon cancer organoids model as well as in 3D spheroid assay model of SW480 and SW620. The docking study supported that we confirmed that compound 8h binds to DYRK1B through various hydrogen bonding interactions and hydrophobic interactions.
Asunto(s)
Antineoplásicos/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Pirazoles/farmacología , Piridinas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Pirazoles/síntesis química , Pirazoles/química , Piridinas/síntesis química , Piridinas/química , Relación Estructura-Actividad , Quinasas DyrKRESUMEN
Dry eye syndrome is the most common eye disease and it is caused by various reasons. As the balance of the tear film that protects the eyes is broken due to various causes, it becomes impossible to properly protect the eyes. In this study, the protective effects and underlying mechanisms of topical (E)-4-(2-(6-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-methyl-1,1-dioxido-1,2,6-thiadiazinan-2-yl)acetamido)adamantan-1-carboxamide (KR-67607), a novel selective 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) inhibitor, were investigated in benzalkonium chloride (BAC)-induced dry eye syndrome. BAC-treated rat eyes induced significant increases in ocular surface damage, decreased corneal thickness, corneal basement membrane destruction in the conjunctival epithelium, and expression of pro-inflammatory cytokines tumor necrosis factor-α and 11ß-HSD1. These effects of BAC were reversed by topical KR-67607 treatment. Furthermore, KR-67607 decreased 4-hydroxynonenal expression and increased antioxidant and mucus secretion in BAC-treated rat eyes. Taken together, a novel selective 11ß-HSD1 inhibitor can prevent BAC-induced dry eye syndrome by inhibiting pro-inflammatory cytokine and reactive oxygen species expression via the inhibition of both 11ß-HSD1 activity and expression.
Asunto(s)
Adamantano/análogos & derivados , Antioxidantes/uso terapéutico , Síndromes de Ojo Seco/tratamiento farmacológico , Inhibidores Enzimáticos/uso terapéutico , Tiadiazinas/uso terapéutico , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/antagonistas & inhibidores , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/metabolismo , Adamantano/farmacología , Adamantano/uso terapéutico , Animales , Antioxidantes/farmacología , Compuestos de Benzalconio/toxicidad , Conjuntiva/efectos de los fármacos , Conjuntiva/metabolismo , Síndromes de Ojo Seco/etiología , Síndromes de Ojo Seco/prevención & control , Inhibidores Enzimáticos/farmacología , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Tiadiazinas/farmacologíaRESUMEN
AIM: Insulin resistance is a metabolic state where insulin sensitivity is lower than normal condition and strongly related to type 2 diabetes. However, an in vitro model mimicking insulin resistance is rare and thus screening drugs for insulin resistance severely depends on an in vivo model. Here, to increase anti-diabetic drug selectivity for humans, 3D ADMSCs and macrophages were co-cultured with in-house fabricated co-culture plates. MATERIAL AND METHODS: 3D co-culture plates were designed to load ADMSCs and RAW264.7 cells containing hydrogels in separate wells while allowing cell-cell interaction with co-culturing media. Hydrogels were constructed using a 3D cell-printing system containing 20 mg/ml alginate, 0.5 mg/ml gelatin and 0.5 mg/ml type I collagen. Cells containing hydrogels in 3D co-culture plates were incubated for 10 min to allow stabilization before the experiment. 3D co-culture plates were incubated with the CaCl2 solution for 5 min to complete the cross linking of alginate hydrogel. Cells in 3D co-culture plates were cultured for up to 12 days depending on the experiment and wells containing adipocytes and macrophages were separated and used for assays. RESULTS: KR-1, KR-2 and KR-3 compounds were applied during differentiation (12 days) in 3D co-cultured mouse 3T3-L1 adipocytes and 3D co-cultured human ADMSCs. Glucose uptake assay using 2-DG6P and 2-NBDG and western blot analysis were performed to investigate changes of insulin resistance in the 3D co-cultured model for interspecies selectivity of drug screening. KR-1 (mouse potent enantiomer) and KR-3 (racemic mixture) showed improvement of 2-DG and 2-NBDG uptake compared with KR-2 (human potent enantiomer) in 3D co-cultured 3T3-L1 adipocytes. In connection with insulin resistance in a 3D 3T3-L1 co-cultured model, KR-1 and KR-3 showed improvement of insulin sensitivity compared to KR-2 by markedly increasing GLUT4 expression. In contrast to the result of 3D co-cultured 3T3-L1 adipocytes, KR-1 failed to significantly improve 2-DG and 2-NBDG uptake in 3D co-cultured ADMSC adipocytes. Results of 2-NBDG accumulation and western blot analysis also showed that KR-2 and KR-3 improved insulin sensitivity relatively better than KR-1. CONCLUSIONS: Our 3D co-culture model with/without 3D co-culture plates can successfully mimic insulin resistance while allowing investigation of the effects of anti-obesity or anti-diabetic drugs on human or mouse co-culturing cell type. This 3D co-culture system may accelerate screening of drugs for insulin resistance depending on species.
Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Preparaciones Farmacéuticas , Células 3T3-L1 , Adipocitos , Animales , Técnicas de Cocultivo , Glucosa , Humanos , Insulina , RatonesRESUMEN
The 11ß-hydroxysteroiddehydrogenase type 1(11ß-HSD1), acortisolregenerating enzyme that amplifies tissue glucocorticoidlevels, plays an important role in diabetes, obesity, and glaucoma and is recognized as a potential therapeutic target for various disease conditions. Moreover, a recent study demonstrated that selective 11ß-HSD1 inhibitor can attenuate ischemic brain injury. This prompted us to optimize cyclic sulfamide derivative for aiming to treat ischemic brain injury. Among the synthesized compounds, 6e has an excellent in vitro activivity with an IC50 value of 1â¯nM toward human and mouse 11ß-HSD1 and showed good 11ß-HSD1 inhibition in ex vivo study using brain tissue isolated from mice. Furthermore, in the transient middle cerebral artery occlusion model in mice, 6e treatment significantly attenuated infarct volume and neurological deficit following cerebral ischemia/reperfusion injury. Additionally, binding modes of 6e for human and mouse 11ß-HSD1 were suggested.
Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/antagonistas & inhibidores , Amidas/química , Inhibidores Enzimáticos/química , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/metabolismo , Amidas/metabolismo , Animales , Encéfalo/metabolismo , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Encefálicas/patología , Ciclización , Inhibidores Enzimáticos/metabolismo , Inhibidores Enzimáticos/uso terapéutico , Humanos , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/patología , Inyecciones Intraperitoneales , Ratones , Relación Estructura-ActividadRESUMEN
Glaucoma is one of the leading causes of preventable blindness, affecting > 2 million people in the United States. Recently, 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitors were found to exert preventive effects against glaucoma. However, there is no evidence for the role of 11ß-HSD1 inhibitors against glaucoma. Here, we developed a novel 11ß-HSD1 inhibitor, (1R,2S,3S,5R,6S,7S)-6-(2-(6-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-methyl-1,1-dioxido-1,2,6-thiadiazinan-2-yl)acetamido)-adamantane-2-carboxamide (KR-67607) and showed its protective effects against ischemia-reperfusion-induced eye injury. We demonstrate that KR-67607 effectively reduced cortisol levels in mouse eyes and maintained the trabecular meshwork (TM) structure in the presence of transient ischemic stress. Furthermore, KR-67607 reversed the elevation of intra-ocular pressure (IOP), suggesting that the TM structure maintained by KR-67607 prevented the excessive rise in IOP that exacerbates glaucoma. KR-67607 was shown to have a higher specificity for 11ß-HSD1 than carbenoxolone (CBX) in vitro. Moreover, KR-67607 reduced apoptosis and the structural disruption of TM cells. Antioxidation was the major protective pathway of KR-67607 against chemically-induced ischemia-reperfusion in TM cells and the glucocorticoid receptor (GR) was closely associated with this pathway. When TM cells undergo ischemic stress, GR is activated and then translocates to the cell nucleus where it interferes with Nrf-2-mediated antioxidant gene expression. However, when KR-67607 inhibited GR translocation, Nrf-2 was able to induce antioxidant gene transcription, which consequently, enhanced the antioxidant capacity of the cells. In conclusion, our current work describes a novel selective 11ß-HSD1 inhibitor for glaucoma treatment and provides evidence of its physiological role in anti-oxidative pathways in the TM.
Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/antagonistas & inhibidores , Adamantano/análogos & derivados , Ojo/irrigación sanguínea , Glaucoma/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Tiadiazinas/farmacología , Adamantano/farmacología , Adamantano/uso terapéutico , Animales , Carbenoxolona/farmacología , Presión Intraocular/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/fisiología , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Receptores de Glucocorticoides/fisiología , Tiadiazinas/uso terapéutico , Malla Trabecular/efectos de los fármacosRESUMEN
Dry eye syndrome (DES) is a disorder of the eye due to tear deficiency or excessive evaporation that causes damage to the eye and is associated with discomfort and dryness. 11ß-Hydroxysteroid dehydrogenase 1 (11ß-HSD1) is an enzyme that converts inactive cortisone to active cortisol. Recently, 11ß-HSD1 has been expressed in human and rodent eyes and has been recognized as a target of glaucoma. In this study, the therapeutic effects and underlying mechanisms of topical carbenoxolone, an 11ß-HSD1 inhibitor, were investigated in benzalkonium chloride (BAC)-treated human conjunctival epithelial cells and a rat DES model. In the in vitro study, carbenoxolone dose-dependently inhibited cell death and 11ß-HSD1 activity in BAC-treated human conjunctival epithelial cells. For the in vivo study, carbenoxolone or a solvent was administered to the BAC-induced DES model twice daily. BAC-treated rat eyes showed significant increases in ocular surface damage, a reduction of tears, decrease corneal thickness, corneal basement membrane destruction, apoptosis in the conjunctival epithelium, and expression of pro-inflammatory cytokines (TNF-α and IL-6) and 11ß-HSD1. These effects of BAC were reversed by topical carbenoxolone treatment. These results demonstrate that carbenoxolone can prevent DES by inhibiting pro-inflammatory cytokine expression and cell death of the corneal and conjunctival epithelium via inhibition of both 11ß-HSD1 activity and expression in the eyes of BAC-treated rats. It is suggested that topical 11ß-HSD1 inhibitors may provide a new therapeutic window in the prevention and/or treatment of DES.
Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/antagonistas & inhibidores , Carbenoxolona/farmacología , Conjuntiva/efectos de los fármacos , Síndromes de Ojo Seco/tratamiento farmacológico , Inhibidores Enzimáticos/farmacología , Soluciones Oftálmicas/farmacología , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/genética , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/metabolismo , Animales , Apoptosis/efectos de los fármacos , Compuestos de Benzalconio/administración & dosificación , Línea Celular , Conjuntiva/citología , Conjuntiva/metabolismo , Relación Dosis-Respuesta a Droga , Síndromes de Ojo Seco/inducido químicamente , Síndromes de Ojo Seco/genética , Síndromes de Ojo Seco/patología , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Regulación de la Expresión Génica , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Glaucoma is one of the leading causes of preventable blindness diseases, affecting more than 2 million people in the United States. Recently, 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) inhibitors were found to exert preventive effects against glaucoma. Therefore, we investigated whether carbenoxolone (CBX), an 11ß-HSD1 inhibitor, prevents chemical ischemia-reperfusion-induced cell death in human trabecular meshwork (HTM) cells. The present study demonstrated that CBX inhibited cell death caused by iodoacetic acid (IAA)-induced ischemia-reperfusion, and its effect was associated with the inhibition of 11ß-HSD1 expression and activity. Furthermore, CBX reversed the IAA-induced structural damage on filamentous actin in HTM cells. In IAA-treated cells, the levels of 11ß-HSD1 and the apoptosis-related factors Bax and FASL were increased throughout the reperfusion period, and CBX was able to attenuate the expression of 11ß-HSD1 and the apoptosis-related factors. CBX also effectively suppressed IAA-induced intracellular ROS formation and cytochrome c release, which are involved in the mitochondrial apoptosis pathway. In addition, IAA-induced chemical ischemia-reperfusion stimulated TNF-α expression and NF-κB p65 phosphorylation, and these effects were attenuated by CBX. 11ß-HSD1 RNAi also suppressed IAA-induced cell apoptosis via reduction of oxidative stress and inhibition of the pro-inflammatory pathway. Taken together, the present study demonstrated that the inhibition of 11ß-HSD1 protected the TM against chemical ischemia-reperfusion injury, suggesting that the use of 11ß-HSD1 inhibitors could be a useful strategy for glaucoma therapy.
Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/antagonistas & inhibidores , Carbenoxolona/farmacología , Lesiones Oculares/prevención & control , Sustancias Protectoras/farmacología , Daño por Reperfusión/prevención & control , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/metabolismo , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Citocromos c/metabolismo , Lesiones Oculares/inducido químicamente , Lesiones Oculares/metabolismo , Humanos , Ácido Yodoacético , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/inducido químicamente , Daño por Reperfusión/metabolismo , Malla Trabecular/citología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The BMB Reports would like to correct in the ACKNOWLEDGEMENTS of BMB Rep. 45(12), 713-718 titled "Ganglioside GM1 influences the proliferation rate of mouse induced pluripotent stem cells".
RESUMEN
11ß-Hydroxysteroid dehydrogenase type 1 (11ß-HSD1) converts inactive cortisone to the active cortisol. 11ß-HSD1 may be involved in the resolution of inflammation. In the present study, we investigate the anti-inflammatory effects of 2-(3-benzoyl)-4-hydroxy-1,1-dioxo-2H-1,2-benzothiazine-2-yl-1-phenylethanone (KR-66344), a selective 11ß-HSD1 inhibitor, in lipopolysaccharide (LPS)-activated C57BL/6J mice and macrophages. LPS increased 11ß-HSD1 activity and expression in macrophages, which was inhibited by KR-66344. In addition, KR-66344 increased survival rate in LPS treated C57BL/6J mice. HO-1 mRNA expression level was increased by KR-66344, and this effect was reversed by the HO competitive inhibitor, ZnPP, in macrophages. Moreover, ZnPP reversed the suppression of ROS formation and cell death induced by KR-66344. ZnPP also suppressed animal survival rate in LPS plus KR-66344 treated C57BL/6J mice. In the spleen of LPS-treated mice, KR-66344 prevented cell death via suppression of inflammation, followed by inhibition of ROS, iNOS and COX-2 expression. Furthermore, LPS increased NFκB-p65 and MAPK phosphorylation, and these effects were abolished by pretreatment with KR-66344. Taken together, KR-66344 protects against LPS-induced animal death and spleen injury by inhibition of inflammation via induction of HO-1 and inhibition of 11ß-HSD1 activity. Thus, we concluded that the selective 11ß-HSD1 inhibitor may provide a novel strategy in the prevention/treatment of inflammatory disorders in patients.
Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/antagonistas & inhibidores , Antiinflamatorios/farmacología , Óxidos S-Cíclicos/farmacología , Hemo-Oxigenasa 1/metabolismo , Lipopolisacáridos/inmunología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Tiazinas/farmacología , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/metabolismo , Animales , Muerte Celular/efectos de los fármacos , Línea Celular , Óxidos S-Cíclicos/antagonistas & inhibidores , Ciclooxigenasa 2/biosíntesis , Interacciones Farmacológicas , Hemo-Oxigenasa 1/biosíntesis , Inflamación/inducido químicamente , Ratones , Óxido Nítrico Sintasa de Tipo II/biosíntesis , Fosforilación/efectos de los fármacos , Protoporfirinas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Tasa de Supervivencia , Tiazinas/antagonistas & inhibidoresRESUMEN
BACKGROUND/AIMS: Helicobacter pylori cytotoxin-associated gene A (CagA) has been suggested to be involved in the inactivation of Runt-related transcription factor 3 (RUNX3), a known gastric carcinoma tumor suppressor gene. It remains unclear how H. pylori CagA initiates or maintains RUNX3 promoter methylation and inactivates its protein expression in gastric carcinoma. METHODS: RUNX3 promoter methylation status, RUNX3 expression, and H. pylori CagA were investigated in 76 sample pairs of gastric carcinoma tissue. The patients' medical records were reviewed. The association between RUNX3 methylation or loss of RUNX3 expression and clinicopathologic variables according to H. pylori CagA status were investigated. RESULTS: In gastric carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation did not show association with lymphatic invasion, venous invasion, and TNM stages. However RUNX3 methylation was observed more frequently in poorly differentiated adenocarcinoma and signet ring cell carcinoma (77.8% vs. 20.0%, p=0.023) in early stage. In gastric carcinoma patients with H. pylori CagA-positive infection, loss of RUNX3 expression did not show association with lymphatic invasion, venous invasion, and TNM stages. However loss of RUNX3 expression was observed more frequently in early gastric carcinoma than in advanced gastric carcinoma (84.2% vs. 75.0%, p=0.51), but this difference was not significant. CONCLUSIONS: In gastric carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation or loss of RUNX3 expression did not show correlation with lymphovascular invasion and TNM stages. In early gastric carcinoma patients with H. pylori CagA-positive infection, RUNX3 methylation was observed more in poorly differentiated adenocarcinoma and signet ring cell carcinoma.
Asunto(s)
Antígenos Bacterianos/metabolismo , Proteínas Bacterianas/metabolismo , Subunidad alfa 3 del Factor de Unión al Sitio Principal/metabolismo , Regulación Neoplásica de la Expresión Génica , Helicobacter pylori/metabolismo , Neoplasias Gástricas/patología , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Femenino , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/microbiología , Helicobacter pylori/aislamiento & purificación , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Metilación , Persona de Mediana Edad , Estadificación de Neoplasias , Regiones Promotoras Genéticas , Estudios Retrospectivos , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/microbiologíaRESUMEN
Gangliosides play important roles in the control of several biological processes, including proliferation and transmembrane signaling. In this study, we demonstrate the effect of ganglioside GM1 on the proliferation of mouse induced pluripotent stem cells (miPSCs). The proliferation rate of miPSCs was lower than in mouse embryonic stem cells (mESCs). Fluorescence activated cell sorting analysis showed that the percentage of cells in the G2/M phase in miPSCs was lower than that in mESCs. GM1 was expressed in mESCs, but not miPSCs. To confirm the role of GM1 in miPSC proliferation, miPSCs were treated with GM1. GM1-treated miPSCs exhibited increased cell proliferation and a larger number of cells in the G2/M phase. Furthermore, phosphorylation of mitogen-activated protein kinases was increased in GM1- treated miPSCs.
Asunto(s)
Proliferación Celular/efectos de los fármacos , Gangliósido G(M1)/farmacología , Células Madre Pluripotentes Inducidas/citología , Animales , Células Cultivadas , Células Madre Embrionarias/citología , Células Madre Embrionarias/metabolismo , Citometría de Flujo , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Células Madre Pluripotentes Inducidas/metabolismo , Puntos de Control de la Fase M del Ciclo Celular/efectos de los fármacos , Sistema de Señalización de MAP Quinasas , RatonesRESUMEN
We describe a 58-year-old woman who was incidentally found to have gastric and colonic polyposis, hypoalbuminemia, cutaneous hyperpigmentation and onychodystrophy (Cronkhite-Canada syndrome). Histology of polyps from the stomach showed features of juvenile or retention type (hamartomatous) polyps with Helicobacter pylori (H. pylori) infection. The large pedunculated colonic polyps showed hamartomatous polyps with adenomatous component and polypectomy was performed. After the treatment with H. pylori eradication and omeprazole, the gastric polyposis, hypoalbuminemia and anemia regressed, and endoscopic polypectomy of gastric polyps were performed. After the continuous use of omeprazole for 14 months, the patient showed complete resolution of clinical features of Cronkhite-Canada syndrome. The experience of this case suggests that eradication of H. pylori and proton pump inhibitor treatment might be considered in patients with gastric polyposis combined with Cronkhite-Canada syndrome.