Large cell neuroendocrine carcinoma(LCNEC)in the biliary system is a poorly differentiated,high-grade neuroendocrine tumor.These tumors exhibit aggressive behavior and an increased tendency for early nodal and distant...Large cell neuroendocrine carcinoma(LCNEC)in the biliary system is a poorly differentiated,high-grade neuroendocrine tumor.These tumors exhibit aggressive behavior and an increased tendency for early nodal and distant metastases.Herein,we report an unusual case of a pure primary LCNEC of the common bile duct(CBD).A 75-year-old female presented with nausea and jaundice.The patient underwent a CBD excision with lymph node dissection.Upon histological and immunohistochemical examination,the tumor exhibited pure large cell-type neuroendocrine features.Metastases were noted in two of the eight lymph nodes.The patient was administered adjuvant chemotherapy.The patient’s cancer recurred 7 mo after surgery,and the patient died from liver failure 5 mo after recurrence.The prognosis of LCNEC of CBD remains poor despitecurative resection and adjuvant chemotherapy.The role of additional therapies,such as multimodal treatment including radiation therapy,must be further studied to improve the prognoses of patients.展开更多
Calbindin D-28K (CB), a Ca2+-binding protein, maintains Ca2+ homeostasis and protects neurons against various insults. Hyperthermia can exacerbate brain damage produced by ischemic insults. However, little is repo...Calbindin D-28K (CB), a Ca2+-binding protein, maintains Ca2+ homeostasis and protects neurons against various insults. Hyperthermia can exacerbate brain damage produced by ischemic insults. However, little is reported about the role of CB in the brain under hyperthermic condition during ischemic insults. We inves- tigated the effects of transient global cerebral ischemia on CB immunoreactivity as well as neuronal damage in the hippocampal formation under hyperthermic condition using immunohistochemistry for neuronal nuclei (NeuN) and CB, and Fluoro-Jade B histofluorescence staining in gerbils. Hyperthermia (39.5 + 0.2~C) was induced for 30 minutes before and during transient ischemia. Hyperthermic ischemia resulted in neu- ronal damage/death in the pyramidal layer of CA1-3 area and in the polymorphic layer of the dentate gyrus at 1, 2, 5 days after ischemia. In addition, hyperthermic ischemia significantly decreaced CB immunoreac- tivity in damaged or dying neurons at 1, 2, 5 days after ischemia. In brief, hyperthermic condition produced more extensive and severer neuronal damage/death, and reduced CB immunoreactivity in the hippocampus following transient global cerebral ischemia. Present findings indicate that the degree of reduced CB immu- noreactivity might be related with various neuronal damage/death overtime and corresponding areas after ischemic insults.展开更多
Quercetin(QE; 3,5,7,3′,4′-pentahydroxyflavone), a well-known flavonoid, has been shown to prevent against neurodegenerative disorders and ischemic insults. However, few studies are reported regarding the neuroprot...Quercetin(QE; 3,5,7,3′,4′-pentahydroxyflavone), a well-known flavonoid, has been shown to prevent against neurodegenerative disorders and ischemic insults. However, few studies are reported regarding the neuroprotective mechanisms of QE after ischemic insults. Therefore, in this study, we investigated the effects of QE on ischemic injury and the expression of antioxidant enzymes in the hippocampal CA1 region of gerbils subjected to 5 minutes of transient cerebral ischemia. QE was pre-treated once daily for 15 days before ischemia. Pretreatment with QE protected hippocampal CA1 pyramidal neurons from ischemic injury, which was confirmed by neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence staining. In addition, pretreatment with QE significantly increased the expression levels of endogenous antioxidant enzymes Cu/Zn superoxide dismutase, Mn superoxide dismutase, catalase and glutathione peroxidase in the hippocampal CA1 pyramidal neurons of animals with ischemic injury. These findings demonstrate that pretreated QE displayed strong neuroprotective effects against transient cerebral ischemia by increasing the expression of antioxidant enzymes.展开更多
Low survival rate occurs in patients who initially experience a spontaneous return of circulation after cardiac arrest(CA). In this study, we induced asphyxial CA in adult male Sprague-Daley rats, maintained their b...Low survival rate occurs in patients who initially experience a spontaneous return of circulation after cardiac arrest(CA). In this study, we induced asphyxial CA in adult male Sprague-Daley rats, maintained their body temperature at 37 ± 0.5°C, and then observed the survival rate during the post-resuscitation phase. We examined neuronal damage in the hippocampus using cresyl violet(CV) and Fluore-Jade B(F-J B) staining, and pro-inflammatory response using ionized calcium-binding adapter molecule 1(Iba-1), glial fibrillary acidic protein(GFAP), and tumor necrosis factor-alpha(TNF-α) immunohistochemistry in the hippocampus after asphyxial CA in rats under normothermia. Our results show that the survival rate decreased gradually post-CA(about 63% at 6 hours, 37% at 1 day, and 8% at 2 days post-CA). Rats were sacrificed at these points in time post-CA, and no neuronal damage was found in the hippocampus until 1 day post-CA. However, some neurons in the stratum pyramidale of the CA region in the hippocampus were dead 2 days post-CA. Iba-1 immunoreactive microglia in the CA1 region did not change until 1 day postCA, and they were activated(enlarged cell bodies with short and thicken processes) in all layers 2 days postCA. Meanwhile, GFAP-immunoreactive astrocytes did not change significantly until 2 days post-CA. TNF-α immunoreactivity decreased significantly in neurons of the stratum pyramidale in the CA1 region 6 hours post-CA, decreased gradually until 1 day post-CA, and increased significantly again 2 days post-CA. These findings suggest that low survival rate of normothermic rats in the early period of asphyxia-induced CA is related to increased TNF-α immunoreactivity, but not to neuronal damage in the hippocampal CA1 region.展开更多
Ischemic preconditioning elicited by a non-fatal brief occlusion of blood flow has been applied for an experimental therapeutic strategy against a subsequent fatal ischemic insult. In this study, we investigated the n...Ischemic preconditioning elicited by a non-fatal brief occlusion of blood flow has been applied for an experimental therapeutic strategy against a subsequent fatal ischemic insult. In this study, we investigated the neuroprotective effects of ischemic preconditioning(2-minute transient cerebral ischemia) on calbindin D28k immunoreactivity in the gerbil hippocampal CA1 area following a subsequent fatal transient ischemic insult(5-minute transient cerebral ischemia). A large number of pyramidal neurons in the hippocampal CA1 area died 4 days after 5-minute transient cerebral ischemia. Ischemic preconditioning reduced the death of pyramidal neurons in the hippocampal CA1 area. Calbindin D28k immunoreactivity was greatly attenuated at 2 days after 5-minute transient cerebral ischemia and it was hardly detected at 5 days post-ischemia. Ischemic preconditioning maintained calbindin D28 k immunoreactivity after transient cerebral ischemia. These findings suggest that ischemic preconditioning can attenuate transient cerebral ischemia-caused damage to the pyramidal neurons in the hippocampal CA1 area through maintaining calbindin D28k immunoreactivity.展开更多
文摘Large cell neuroendocrine carcinoma(LCNEC)in the biliary system is a poorly differentiated,high-grade neuroendocrine tumor.These tumors exhibit aggressive behavior and an increased tendency for early nodal and distant metastases.Herein,we report an unusual case of a pure primary LCNEC of the common bile duct(CBD).A 75-year-old female presented with nausea and jaundice.The patient underwent a CBD excision with lymph node dissection.Upon histological and immunohistochemical examination,the tumor exhibited pure large cell-type neuroendocrine features.Metastases were noted in two of the eight lymph nodes.The patient was administered adjuvant chemotherapy.The patient’s cancer recurred 7 mo after surgery,and the patient died from liver failure 5 mo after recurrence.The prognosis of LCNEC of CBD remains poor despitecurative resection and adjuvant chemotherapy.The role of additional therapies,such as multimodal treatment including radiation therapy,must be further studied to improve the prognoses of patients.
基金supported by the Biomedical Technology Development Program of the NRF funded by the Korean Government,MSIP(NRF-2015M3A9B6066835)by the Bio-Synergy Research Project(NRF-2015M3A9C4076322)of the Ministry of Science,ICT and Future Planning through the National Research Foundation
文摘Calbindin D-28K (CB), a Ca2+-binding protein, maintains Ca2+ homeostasis and protects neurons against various insults. Hyperthermia can exacerbate brain damage produced by ischemic insults. However, little is reported about the role of CB in the brain under hyperthermic condition during ischemic insults. We inves- tigated the effects of transient global cerebral ischemia on CB immunoreactivity as well as neuronal damage in the hippocampal formation under hyperthermic condition using immunohistochemistry for neuronal nuclei (NeuN) and CB, and Fluoro-Jade B histofluorescence staining in gerbils. Hyperthermia (39.5 + 0.2~C) was induced for 30 minutes before and during transient ischemia. Hyperthermic ischemia resulted in neu- ronal damage/death in the pyramidal layer of CA1-3 area and in the polymorphic layer of the dentate gyrus at 1, 2, 5 days after ischemia. In addition, hyperthermic ischemia significantly decreaced CB immunoreac- tivity in damaged or dying neurons at 1, 2, 5 days after ischemia. In brief, hyperthermic condition produced more extensive and severer neuronal damage/death, and reduced CB immunoreactivity in the hippocampus following transient global cerebral ischemia. Present findings indicate that the degree of reduced CB immu- noreactivity might be related with various neuronal damage/death overtime and corresponding areas after ischemic insults.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Education(NRF-2015R1D1A1A01059728)Hallym University Research Fund 2014(HURF-2014-25)
文摘Quercetin(QE; 3,5,7,3′,4′-pentahydroxyflavone), a well-known flavonoid, has been shown to prevent against neurodegenerative disorders and ischemic insults. However, few studies are reported regarding the neuroprotective mechanisms of QE after ischemic insults. Therefore, in this study, we investigated the effects of QE on ischemic injury and the expression of antioxidant enzymes in the hippocampal CA1 region of gerbils subjected to 5 minutes of transient cerebral ischemia. QE was pre-treated once daily for 15 days before ischemia. Pretreatment with QE protected hippocampal CA1 pyramidal neurons from ischemic injury, which was confirmed by neuronal nuclear antigen immunohistochemistry and Fluoro-Jade B histofluorescence staining. In addition, pretreatment with QE significantly increased the expression levels of endogenous antioxidant enzymes Cu/Zn superoxide dismutase, Mn superoxide dismutase, catalase and glutathione peroxidase in the hippocampal CA1 pyramidal neurons of animals with ischemic injury. These findings demonstrate that pretreated QE displayed strong neuroprotective effects against transient cerebral ischemia by increasing the expression of antioxidant enzymes.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)the Ministry of Education(NRF-2014R1A1A2057263)+2 种基金by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT&Future Planning(NRF-2017R1A2B4009079&NRF-2017R1A2B4008403)by the Bio-Synergy Research Project(NRF-2015M3A9C4076322)of the Ministry of ScienceICT and Future Planning through the National Research Foundation
文摘Low survival rate occurs in patients who initially experience a spontaneous return of circulation after cardiac arrest(CA). In this study, we induced asphyxial CA in adult male Sprague-Daley rats, maintained their body temperature at 37 ± 0.5°C, and then observed the survival rate during the post-resuscitation phase. We examined neuronal damage in the hippocampus using cresyl violet(CV) and Fluore-Jade B(F-J B) staining, and pro-inflammatory response using ionized calcium-binding adapter molecule 1(Iba-1), glial fibrillary acidic protein(GFAP), and tumor necrosis factor-alpha(TNF-α) immunohistochemistry in the hippocampus after asphyxial CA in rats under normothermia. Our results show that the survival rate decreased gradually post-CA(about 63% at 6 hours, 37% at 1 day, and 8% at 2 days post-CA). Rats were sacrificed at these points in time post-CA, and no neuronal damage was found in the hippocampus until 1 day post-CA. However, some neurons in the stratum pyramidale of the CA region in the hippocampus were dead 2 days post-CA. Iba-1 immunoreactive microglia in the CA1 region did not change until 1 day postCA, and they were activated(enlarged cell bodies with short and thicken processes) in all layers 2 days postCA. Meanwhile, GFAP-immunoreactive astrocytes did not change significantly until 2 days post-CA. TNF-α immunoreactivity decreased significantly in neurons of the stratum pyramidale in the CA1 region 6 hours post-CA, decreased gradually until 1 day post-CA, and increased significantly again 2 days post-CA. These findings suggest that low survival rate of normothermic rats in the early period of asphyxia-induced CA is related to increased TNF-α immunoreactivity, but not to neuronal damage in the hippocampal CA1 region.
基金supported by Hallym University Research Fund,2016(HRF-201605-012)Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(NRF-2016R1A6A3A01011698)
文摘Ischemic preconditioning elicited by a non-fatal brief occlusion of blood flow has been applied for an experimental therapeutic strategy against a subsequent fatal ischemic insult. In this study, we investigated the neuroprotective effects of ischemic preconditioning(2-minute transient cerebral ischemia) on calbindin D28k immunoreactivity in the gerbil hippocampal CA1 area following a subsequent fatal transient ischemic insult(5-minute transient cerebral ischemia). A large number of pyramidal neurons in the hippocampal CA1 area died 4 days after 5-minute transient cerebral ischemia. Ischemic preconditioning reduced the death of pyramidal neurons in the hippocampal CA1 area. Calbindin D28k immunoreactivity was greatly attenuated at 2 days after 5-minute transient cerebral ischemia and it was hardly detected at 5 days post-ischemia. Ischemic preconditioning maintained calbindin D28 k immunoreactivity after transient cerebral ischemia. These findings suggest that ischemic preconditioning can attenuate transient cerebral ischemia-caused damage to the pyramidal neurons in the hippocampal CA1 area through maintaining calbindin D28k immunoreactivity.