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1.
BMJ Open Ophthalmol ; 8(1)2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-37278416

RESUMO

OBJECTIVE: This study aimed to evaluate the preference for antivascular endothelial growth factor (anti-VEGF) versus laser ablation therapy as primary and additional treatment in aggressive retinopathy of prematurity (ROP) and type 1 ROP. METHODS: This multicentre retrospective study was conducted at nine medical centres across South Korea. A total of 94 preterm infants with ROP who underwent primary treatment between January 2020 and December 2021 were enrolled. All eyes were classified as having type 1 ROP or aggressive ROP. Data on the zone, primary treatment chosen, injection dose, presence of reactivation and additional treatment were collected and analysed. RESULTS: Seventy infants (131 eyes) with type 1 ROP and 24 infants (45 eyes) with aggressive ROP were included. Anti-VEGF injection was selected as the primary treatment in 74.05% of the infants with type 1 ROP and 88.89% with aggressive ROP. Anti-VEGF injection was selected as the ROP was located in zone I or posterior zone II, and laser ablation was selected when it was located in zone II. The anti-VEGF injection doses varied and tended to be higher in the aggressive ROP group. Infants with aggressive ROP were 2.08 times more likely to require additional treatment than those with type 1 ROP. When ROP reactivation occurred, laser therapy was preferred as an additional treatment. CONCLUSION: In Korea, the preference for anti-VEGF therapy or laser therapy differed according to ROP subtype, zone and primary or secondary treatment. These findings suggest that ROP treatment are considered according to ROP subtype, location and reactivation.


Assuntos
Retinopatia da Prematuridade , Lactente , Recém-Nascido , Humanos , Retinopatia da Prematuridade/terapia , Inibidores da Angiogênese/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Recém-Nascido Prematuro , Estudos Retrospectivos , Injeções Intravítreas , Fatores de Crescimento Endotelial/uso terapêutico
2.
Medicine (Baltimore) ; 101(27): e29368, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35801764

RESUMO

Prenatal and perinatal infections and inflammation appear to associated with the development of retinopathy of prematurity (ROP). In this study, we evaluated whether inflammatory mediators in amniotic fluid (AF) retrieved during cesarean delivery influence the development of ROP in very low birth weight (VLBW) infants. This retrospective study included 16 and 32 VLBW infants who did and did not develop any stage of ROP, respectively. Each infant with ROP was matched with 2 infants without ROP based on days of ventilation care, gestational age, and birth weight. AF was obtained during cesarean delivery, and the levels of intra-amniotic inflammatory mediators such as interleukin (IL)-1ß, IL-2, IL-6, IL-8, IL-10, matrix metalloproteinase (MMP)-2, MMP-8, MMP-9, and tumor necrosis factor (TNF)-α were measured using a Human Magnetic Luminex assay (R&D Systems, Minneapolis, MN). The differences in the levels of inflammatory mediators according to the presence or absence of ROP were compared. In patients who developed ROP, the level of MMP-2 in the AF was significantly increased (P = .011), whereas the levels of IL-10 and TNF-α were significantly decreased (P = .028 and .046, respectively) compared with those in infants who did not develop ROP. The levels of the other mediators were not significantly different between the 2 groups. Multivariate regression analysis showed that MMP-2 was a risk factor for the development of ROP (odds ratio, 2.445; 95% confidence interval, 1.170-5.106; P = .017). The concentration of MMP-2 in AF is an independent factor in the development of ROP. Further studies are needed to determine whether the levels of inflammatory mediators in AF affect the ROP severity.


Assuntos
Retinopatia da Prematuridade , Líquido Amniótico , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Mediadores da Inflamação , Interleucina-10 , Metaloproteinase 2 da Matriz , Gravidez , Retinopatia da Prematuridade/epidemiologia , Retinopatia da Prematuridade/etiologia , Estudos Retrospectivos , Fatores de Risco
3.
Int Ophthalmol ; 42(9): 2811-2818, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35352292

RESUMO

PURPOSE: This retrospective study aimed to evaluate the prognostic factors associated with the success of fluid-gas exchange in patients who had undergone failed primary idiopathic macular hole (IMH) surgery. METHODS: In total, 19 eyes of 19 patients with failed IMH surgery who then underwent fluid-gas exchange were included. Of those, 18 eyes had macular hole (MH) closure (successful, 15 eyes; unsuccessful, 3 eyes). Demographics, pre-operative characteristics, and pre-procedural characteristics were assessed. The patients were divided into successful (U or V-type closure) and unsuccessful groups (W-type or unclosed), following fluid-gas exchange. One eye was unclosed after fluid-gas exchange; therefore, this patient underwent additional vitrectomy for MH closure (unsuccessful). RESULTS: The outcomes of the fluid-gas exchange were categorized as unclosed or as U-type, V-type, or W-type closure. None of the patients experienced complications after the procedure. The successful group showed a significantly lower pre-operative and pre-procedural minimum diameter, base diameter, and macular hole volume, and higher pre-operative and pre-procedural macular hole index, hole form factor, and tractional hole index values. Moreover, a better visual prognosis was observed in the successful group. CONCLUSION: These findings suggest that indices predicting favorable results of primary surgery for IMH are useful for predicting the success of fluid-gas exchange in patients with failed primary MH surgery.


Assuntos
Fluorocarbonos , Perfurações Retinianas , Humanos , Prognóstico , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual , Vitrectomia
4.
J Ethnopharmacol ; 276: 114122, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-33964359

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional herbal medicines have diverse efficacy and are increasingly used worldwide. However, some of these herbal medicines have toxicities or side effects, but the scientific understanding of traditional herbal medicine toxicity has not yet been established. Asiasari Radix et Rhizoma (ARE) is known as a herbal medicine used to relieve pain, and recent studies have shown that ARE has anticancer and antimelanogenesis efficacy. AIM OF THE STUDY: Current study was conducted to assess the potential genotoxicity of an ethanolic extract of ARE. MATERIALS AND METHODS: The genotoxixity of ARE was confirmed by the bacterial reverse mutation assay (Ames test), a mammalian chromosomal aberration test, and a micronucleus test in vivo using ICR mice and comet assay using Sprague-Dawley rats. RESULTS: ARE showed no genotoxicity in a micronucleus test up to 2000 mg/kg body weight in vivo. By contrast, the chromosomal aberration test showed that ARE induced an increase in the number of chromosomal aberrations after treatment for 6 h with a metabolic activation system and for 6 and 22 h without the metabolic activation system when compared with vehicle control. In the Ames test, all strains except TA1535, with or without a metabolic activation system, showed an increase in the number of revertant mutant colonies in the ARE-treated group. In comet assay, DNA damage was observed in the stomach when ARE was administered. CONCLUSION: ARE potentially shows genotoxicity by inducing DNA damage.


Assuntos
Aristolochiaceae/química , Dano ao DNA , Medicamentos de Ervas Chinesas/toxicidade , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Peso Corporal/efeitos dos fármacos , Aberrações Cromossômicas/induzido quimicamente , Ensaio Cometa , Cricetulus , Etanol , Fígado/efeitos dos fármacos , Masculino , Camundongos Endogâmicos ICR , Testes para Micronúcleos , Testes de Mutagenicidade , Ratos Sprague-Dawley , Estômago/efeitos dos fármacos
5.
Biomolecules ; 11(3)2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33801497

RESUMO

There is growing evidence that the accumulation of DNA damage induced by fine particulate matter (PM2.5) exposure is an underlying mechanism of pulmonary disease onset and progression. However, there is a lack of experimental evidence on whether common factors (age, gender) affect PM2.5 induced genomic damage. Here, we assessed the DNA damage potency of PM2.5 using conventional genotoxicity testing in old male and female mice aged 8 and 40 weeks. Mice were intratracheally instilled with diesel exhaust PM2.5 (DEP, NIST SRM 1650b), twice a week for 4 weeks. Exposure to DEP was not associated with an increase in the frequency of micronucleated polychromatic erythrocytes and did not induce a systemic genotoxic effect in the bone marrow. Meanwhile, the results from the comet assay showed a significant increase in DNA damage in DEP exposed mouse lung specimens. The positive relationship between DEP exposure and DNA damage is stronger in the older than in the younger group. Statistical analysis showed that there was a modifying effect of age on the association between PM2.5 exposure and DNA damage. Our results suggest that the age factor should be considered to better understand the cellular adverse effects of PM2.5.


Assuntos
Envelhecimento/fisiologia , Mutagênicos/toxicidade , Emissões de Veículos/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Ensaio Cometa , Dano ao DNA , Feminino , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Testes para Micronúcleos
6.
Biomolecules ; 11(2)2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33669250

RESUMO

Several epidemiological studies concluded that inhalation of diesel exhaust particles (DEP) is associated with an increase in the relative risk of lung cancer. In vitro research evaluating the genetic damage and/or changes in gene expression have been attempted to explain the relationship between DEP exposure and carcinogenicity. However, to date, investigations have been largely confined to studies in immortalized or tumorigenic epithelial cell models. Few studies have investigated damage at the chromosomal level to DEP exposure in normal cell lines. Here, we present the genotoxic effects of DEP in normal cells (embryonic human lung fibroblasts) by conventional genotoxicity testing (micronuclei (MN) and comet assay). We show the differentially expressed genes and enriched pathways in DEP-exposed WI-38 cells using RNA sequencing data. We observed a significant increase in single-strand DNA breaks and the frequency of MN in DEP-exposed cells in a dose-dependent manner. The differentially expressed genes following DEP exposure were significantly enriched in the pathway for responding to xenobiotics and DNA damage. Taken together, these results show that DEP exposure induced DNA damage at the chromosomal level in normal human lung cells and provide information on the expression of genes associated with genotoxic stress.


Assuntos
Células Epiteliais/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/embriologia , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/metabolismo , Emissões de Veículos , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Dano ao DNA , Expressão Gênica , Humanos , Mutagênicos/farmacologia , Óxido Nítrico/metabolismo , RNA-Seq , Espécies Reativas de Oxigênio
7.
Taehan Yongsang Uihakhoe Chi ; 82(1): 225-230, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36237462

RESUMO

Isolated metastasis in the extraocular muscle (EOM) is uncommon, while metastases in bilateral multiple EOMs is even rarer. Rhabdomyosarcoma (RMS) is a rare soft-tissue malignancy that usually occurs in the pediatric population and is one of the primary malignancies of isolated EOM metastasis. Here, we present a case of sinonasal RMS metastasis to multiple bilateral EOMs along with a brief review of 10 previously reported cases of RMS metastasis in EOMs.

8.
J Nutr Biochem ; 85: 108469, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32735936

RESUMO

15-Hydroxyprostaglandin dehydrogenase (15-PGDH) catalyzes the conversion of oncogenic prostaglandin E2 to non-tumerigenic 15-keto prostaglandin E2. In the present study, we found that curcumin, a yellow coloring agent present in the rhizome of Curcuma longa Linn (Zingiberaceae), induced expression of 15-PGDH at the both transcriptional and translational levels in normal rat gastric mucosal cells. By using deletion constructs of 15-PGDH promoter, we were able to demonstrate that activator protein-1 (AP-1) is the principal transcription factor responsible for regulating curcumin-induced 15-PGDH expression. Curcumin enhanced the expression of c-Jun and c-Fos that are functional subunits of AP-1, in the nuclear fraction of cells. Silencing of c-Jun suppressed curcumin-induced expression of 15-PGDH. Moreover, the chromatin immunoprecipitation assay revealed curcumin-induced binding of c-Jun to the AP-1 consensus sequence present in the 15-PGDH promoter. Curcumin increased phosphorylation of ERK1/2 and JNK, and pharmacologic inhibition of these kinases abrogated the curcumin-induced phosphorylation of c-Jun and 15-PGDH expression. In contrast, tetrahydrocurcumin which lacks the α,ß-unsaturated carbonyl group failed to induce 15-PGDH expression, suggesting that the electrophilic carbonyl group of curcumin is essential for its induction of 15-PGDH expression. Curcumin restored the expression of 15-PGDH which is down-regulated by Helicobacter pylori through suppression of DNA methyltransferase 1. In addition, oral administration of curcumin increased the expression of 15-PGDH and its regulators such as p-ERK1/2, p-JNK, and c-Jun in the mouse stomach. Taken together, these findings suggest that curcumin-induced upregulation of 15-PGDH may contribute to chemopreventive effects of this phytochemical on inflammation-associated gastric carcinogenesis.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Curcumina/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Hidroxiprostaglandina Desidrogenases/genética , Regulação para Cima/efeitos dos fármacos , Animais , Linhagem Celular , Feminino , Mucosa Gástrica/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Estômago/efeitos dos fármacos
9.
BMC Ophthalmol ; 20(1): 341, 2020 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-32831053

RESUMO

BACKGROUND: The aim of this study was to evaluate the correlation between changes in the macular capillary network and macular edema (ME) recurrence with branch retinal vein occlusion (BRVO) using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: We reviewed the data for 43 patients with treatment-naïve ME associated with BRVO. Patients who received intravitreal bevacizumab injection were divided into two groups based on ME recurrence at 6 months after edema resolution. The perifoveal capillary morphology and the macular capillary vessel density (VD) were retrospectively analyzed using en face SS-OCTA after ME resolution. RESULTS: The perifoveal capillary ring loss in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) was more common in the ME recurrence group (n = 22) than in the no ME recurrence group (p = 0.047 and p = 0.002). Relative to the findings in the no ME recurrence groups, the destruction of the perifoveal capillary ring was more severe in the DCP (30.0° vs 87.3°, p = 0.001) than in the SCP (17.3° vs 69.5°, p = 0.006) in the ME recurrence group. The hemi-VD disparity between the affected and the unaffected areas in the SCP and DCP showed significant differences (p = 0.031 and p = 0.017), while macular VD showed no differences between the groups. CONCLUSIONS: Destruction of the perifoveal capillary ring and hemi-VD disparity could be related to ME recurrence in BRVO. Therefore, these factors may be helpful in predicting ME recurrence.


Assuntos
Edema Macular , Oclusão da Veia Retiniana , Angiofluoresceinografia , Fundo de Olho , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Oclusão da Veia Retiniana/diagnóstico , Oclusão da Veia Retiniana/tratamento farmacológico , Vasos Retinianos/diagnóstico por imagem , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual
10.
Medicine (Baltimore) ; 99(29): e21277, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702918

RESUMO

To report the clinical characteristics and retinal abnormalities associated with orbital infarction syndrome after cerebral aneurysm clipping surgery.In this retrospective case series, we evaluated 4 cases of orbital infarction syndrome using fluorescein angiography, optical coherence tomography, and computed tomography images from January 2011 to May 2014. The medical records of these patients including age, sex, laterality of the eyes, visual acuity, intraocular pressure, duration of the operation, location of the aneurysms, and surgical method with the type of approach used to reach the aneurysmal lesions were evaluated.Aneurysms were located in either the anterior or the posterior communicating artery. Two patients had subarachnoid hemorrhage arising from a ruptured aneurysm, whereas 2 other patients had unruptured aneurysms. Clipping was performed by 3 different surgeons using the pterional craniotomy. The mean time interval from aneurysmal clipping to awareness of vision loss was 10.75 ±â€Š13.8 days. In all patients, optic atrophy and irreversible deterioration of visual acuity ensued. Retinal edema, retinal vascular abnormality, or choroidal hypoperfusion was identified in these patients.Orbital infarction syndrome is a rare but devastating complication of brain aneurysm clipping surgery. The associated retinal ischemia is not only due to the involvement of the retinal vessels, but also the choroidal circulation.


Assuntos
Infarto/etiologia , Aneurisma Intracraniano/cirurgia , Órbita/irrigação sanguínea , Feminino , Angiofluoresceinografia , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome , Tomografia de Coerência Óptica , Tomografia Computadorizada por Raios X , Transtornos da Visão/etiologia
11.
J Immunol ; 202(2): 527-538, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30530591

RESUMO

G2A is a GPCR abundantly expressed in immune cells. G2A-/- mice showed higher lethality, higher plasma cytokines, and an impaired bacterial clearance in response to a murine model of sepsis (cecal ligation and puncture), which were blocked by GdCl3, an inhibitor of Kupffer cells. Anti-IL-10 Ab reversed the impaired bacterial clearance in G2A-/- mice. Indomethacin effectively blocked both the increased i.p. IL-10 levels and the impaired bacterial clearance, indicating that disturbed PG system is the proximal cause of these phenomena. Stimulation with LPS/C5a induced an increase in Escherichia coli phagocytosis and intracellular cAMP levels in G2A+/+ peritoneal macrophages but not G2A-/- cells, which showed more PGE2/nitrite release and intracellular reactive oxygen species levels. Heterologous coexpression of G2A and adenosine receptor type 2b (A2bAR) induced a synergistic increase in cAMP signaling in a ligand-independent manner, with the evidence of physical interaction of G2A with A2bAR. BAY 60-6583, a specific agonist for A2bAR, increased intracellular cAMP levels in Kupffer cells from G2A+/+ but not from G2A-/- mice. Both G2A and A2bAR were required for antiseptic action of lysophosphatidylcholine. These results show inappropriate activation of G2A-/- Kupffer cells to septic insults due to an impaired cAMP signaling possibly by lack of interaction with A2bAR.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Infecções por Escherichia coli/imunologia , Escherichia coli/fisiologia , Células de Kupffer/imunologia , Macrófagos Peritoneais/fisiologia , Receptor A2B de Adenosina/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Sepse/metabolismo , Animais , Anticorpos Bloqueadores , Proteínas de Ciclo Celular/genética , Células Cultivadas , AMP Cíclico/metabolismo , Modelos Animais de Doenças , Humanos , Interleucina-10/imunologia , Interleucina-10/metabolismo , Macrófagos Peritoneais/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fagocitose , Ligação Proteica , Espécies Reativas de Oxigênio/metabolismo , Receptor Cross-Talk , Receptor A2B de Adenosina/genética , Receptores Acoplados a Proteínas G/genética , Sepse/genética , Transdução de Sinais
12.
Int J Mol Sci ; 19(4)2018 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-29614819

RESUMO

Tumor necrosis factor alpha (TNFα) is a pro-inflammatory cytokine that triggers the expression of inflammatory molecules, including other cytokines and cell adhesion molecules. TNFα induces the expression of intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 (VCAM-1). VCAM-1 was originally identified as a cell adhesion molecule that helps regulate inflammation-associated vascular adhesion and the transendothelial migration of leukocytes, such as macrophages and T cells. Recent evidence suggests that VCAM-1 is closely associated with the progression of various immunological disorders, including rheumatoid arthritis, asthma, transplant rejection, and cancer. This review covers the role and relevance of VCAM-1 in inflammation, and also highlights the emerging potential of VCAM-1 as a novel therapeutic target in immunological disorders and cancer.


Assuntos
Neoplasias/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo , Animais , Humanos , Inflamação/metabolismo , Inflamação/patologia , Neoplasias/patologia , Fator de Necrose Tumoral alfa/metabolismo
13.
Nutrients ; 10(4)2018 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-29690562

RESUMO

The dried fruits of Evodia rutaecarpa Bentham have been used widely as a herbal medicine for the treatment of inflammatory disorders and abdominal pain. Benign prostatic hyperplasia (BPH) is a nonmalignant disease characterized by overgrowth of prostates. Despite the pharmacological efficacy of the fruits of E. rutaecarpa against various diseases, their effects against BPH have not been reported. Here, we investigated the inhibitory activity of a 70% ethanol extract of E. rutaecarpa (EEER) against BPH, and its underlying mechanisms regarding cell growth of BPH using BPH-1 cells. An in vitro 5α-reductase activity assay showed that EEER exhibited inhibitory activity against 5α-reductase. In BPH-1 cells, EEER treatment inhibited cell viability and reduced the expression of the proliferating cell nuclear antigen proliferating cell nuclear antigen (PCNA), cyclin D1, and phosphor-ERK1/2 proteins. Moreover, EEER also induced apoptosis, with chromatin condensation, apoptotic bodies, and internucleosomal DNA fragmentation. Regarding its underlying mechanisms, EEER exacerbated the activation of caspase-8 and caspase-3 in a concentration-dependent manner and eventually caused the cleavage of PARP. Taken together, these data demonstrated that EEER had a potent 5α-reductase inhibitory activity and that EEER treatment in BPH-1 cells inhibited cell viability via caspase-8- and caspase-3-dependent apoptosis. Therefore, EEER may be a potential phytotherapeutic agent for the treatment of BPH.


Assuntos
Inibidores de 5-alfa Redutase/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Caspase 8/metabolismo , Proliferação de Células/efeitos dos fármacos , Evodia , Extratos Vegetais/farmacologia , Próstata/efeitos dos fármacos , Hiperplasia Prostática/tratamento farmacológico , Inibidores de 5-alfa Redutase/isolamento & purificação , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Evodia/química , Frutas , Humanos , Masculino , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Próstata/enzimologia , Próstata/patologia , Hiperplasia Prostática/enzimologia , Hiperplasia Prostática/patologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
14.
Sci Rep ; 7(1): 11118, 2017 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-28894284

RESUMO

TREM2 plays a critical role in the alleviation of Alzheimer's disease by promoting Aß phagocytosis by microglia, but the detailed molecular mechanism underlying TREM2-induced direct phagocytic activity of Aß remains to be revealed. We found that learning and memory functions were improved in aged TREM2 TG mice, with the opposite effects in KO mice. The amount of phagocytosed Aß was significantly reduced in the primary microglia of KO mice. CD36 expression in primary microglia was greater in TG than in WT mice but was substantially decreased in KO mice. The expression of C/EBPα, an upstream transcriptional activator of CD36, was also elevated in primary microglia of TG mice but decreased in KO mice. The transcription of CD36 was markedly increased by TREM2 overexpression, and this effect was suppressed by a mutation of the C/EBPα binding site on the CD36 promoter. The TREM2-induced expression of CD36 and C/EBPα was inhibited by treatment with PI3K/AKT signaling blockers, and phosphorylation of AKT was elevated in TREM2-overexpressing BV2 cells. The present study provides evidence that TREM2 is required for preventing loss of memory and learning in Alzheimer's disease by regulating C/EBPα-dependent CD36 expression and the consequent Aß phagocytosis.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Antígenos CD36/genética , Glicoproteínas de Membrana/genética , Microglia/fisiologia , Fagocitose , Receptores Imunológicos/genética , Animais , Biomarcadores , Regulação Neoplásica da Expressão Gênica , Imuno-Histoquímica , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Neurônios/metabolismo , Fagócitos/imunologia , Fagócitos/metabolismo , Receptores Imunológicos/metabolismo
15.
Int J Mol Sci ; 18(8)2017 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-28817103

RESUMO

Tumor angiogenesis is a key event that governs tumor progression and metastasis. It is controlled by the complicated and coordinated actions of pro-angiogenic factors and their receptors that become upregulated during tumorigenesis. Over the past several decades, vascular endothelial growth factor (VEGF) signaling has been identified as a central axis in tumor angiogenesis. The remarkable advent of recombinant antibody technology has led to the development of bevacizumab, a humanized antibody that targets VEGF and is a leading clinical therapy to suppress tumor angiogenesis. However, despite the clinical efficacy of bevacizumab, its significant side effects and drug resistance have raised concerns necessitating the identification of novel drug targets and development of novel therapeutics to combat tumor angiogenesis. This review will highlight the role and relevance of VEGF and other potential therapeutic targets and their receptors in angiogenesis. Simultaneously, we will also cover the current status of monoclonal antibodies being developed to target these candidates for cancer therapy.


Assuntos
Anticorpos Monoclonais Humanizados/imunologia , Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/imunologia , Inibidores da Angiogênese/imunologia , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Bevacizumab/uso terapêutico , Carcinogênese/efeitos dos fármacos , Carcinogênese/imunologia , Humanos , Imunoterapia , Neoplasias/imunologia , Neoplasias/patologia , Neovascularização Patológica/imunologia , Neovascularização Patológica/patologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
16.
PLoS One ; 12(7): e0181169, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28742156

RESUMO

OBJECTIVE: The purpose of this study was to determine whether a CT interpretation with imaging pattern analysis differentiates Kikuchi disease (KD) from the two more frequently encountered differential lymph nodes diagnoses of tuberculous lymphadenopathy (TL) and reactive hyperplasia (RH). MATERIALS AND METHODS: Between January 2012 and July 2015, 20 patients with KD (6 men, 14 women; mean age, 27.80 years), 36 patients with RH (10 men, 26 women; mean age, 33.08 years) and 34 patients with TL (17 men, 17 women; mean age, 39.82 years) were pathologically diagnosed using US-guided fine needle aspiration biopsy, core needle biopsy, or surgical excisional biopsy. We recorded the total number, location, and size of the affected cervical lymph nodes, and two radiologists reviewed the characteristic imaging findings, including the presence of necrosis, cortical enhancement pattern, perinodal infiltration, conglomeration and nodal calcification, to form a consensus. In addition, we compared two attenuation indices on the nonnecrotic portion of the affected lymph nodes, nodal cortical attenuation (NCA) and the ratio of NCA to the adjacent muscle (NCA/M). RESULTS: Conglomeration, enhancement pattern and NCA/M values were independent predictive CT features to distinguish KD from RH. Age and enhancement pattern discriminated KD from TL. Only the mean NCA/M value was a statistically significant CT feature (p = .008) in differentiating KD from both RH+TL. The mean NCA/M of KD (1.67 ± 0.20) was significantly higher than that of RH (1.49 ± 0.20) or TL (1.47 ± 0.21). CONCLUSION: Our results indicate that in case of nonnecrotic lymphadenopathy, a higher NCA/M index can differentiate KD from RH and TL. In addition, the enhancement pattern according to the degree of necrosis discriminated between KD and TL in the case of necrotic lymphadenopathy.


Assuntos
Linfadenite Histiocítica Necrosante/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Adolescente , Adulto , Idoso , Biópsia , Diagnóstico Diferencial , Feminino , Linfadenite Histiocítica Necrosante/patologia , Humanos , Modelos Logísticos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Necrose , Pseudolinfoma/diagnóstico por imagem , Pseudolinfoma/patologia , Tomografia Computadorizada por Raios X , Tuberculose dos Linfonodos/diagnóstico por imagem , Tuberculose dos Linfonodos/patologia , Adulto Jovem
17.
Int J Mol Sci ; 18(3)2017 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-28272300

RESUMO

Vascular cell adhesion molecule-1 (VCAM-1) is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung tissue, and high VCAM-1 expression correlated with poor survival in lung cancer patients. VCAM-1 knockdown reduced migration of A549 human lung cancer cells into Matrigel, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6) demonstrated that the VCAM-1-D6 domain was critical for VCAM-1 mediated A549 cell migration into Matrigel. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab), which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed the migration of A549 and NCI-H1299 lung cancer cell lines into Matrigel. Taken together, these results suggest that VCAM-1-D6 is a key domain for regulating VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.


Assuntos
Anticorpos Monoclonais/imunologia , Movimento Celular/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Molécula 1 de Adesão de Célula Vascular/imunologia , Animais , Anticorpos Monoclonais/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Humanos , Camundongos , Molécula 1 de Adesão de Célula Vascular/química
18.
Asian Pac J Cancer Prev ; 16(8): 3203-11, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25921121

RESUMO

This study identified the actual conditions for safe anticancer drug management among nurses and the relationship between level of awareness and performance of anticancer drug safety regulations in terms of preparation, administration, and disposal. The respondents were 236 nurses working with chemotherapy in wards and outpatient clinics in five hospitals in and near Seoul. Safety regulations provided for the anticancer drug the Occupational Safety Health Administration (OSHA, 1999), as modified for an earlier study, were used. The results showed that the level of awareness and performance on the anticancer drug safety regulations indicate their preparation (3.38±0.55, 2.38±0.98), administration (3.52±0.46, 3.17±0.70), general handling and disposal (3.33±0.54, 2.42±0.90) on a scale 0 to 5. Also, there were significant differences in job positions, work experience, type of preparation, and continuing education and a positive relationship between the level of awareness and nursing performance. Thus, nurses should receive continuing education on the handling of anticancer drugs to improve the level of performance following safety regulations.


Assuntos
Antineoplásicos/uso terapêutico , Fidelidade a Diretrizes/estatística & dados numéricos , Recursos Humanos de Enfermagem Hospitalar/educação , Exposição Ocupacional/prevenção & controle , Guias de Prática Clínica como Assunto , Roupa de Proteção/estatística & dados numéricos , Gestão da Segurança , Conscientização , Saúde Ambiental , Necessidades e Demandas de Serviços de Saúde , Humanos , Eliminação de Resíduos de Serviços de Saúde , Enfermagem Oncológica/educação
19.
J Hepatocell Carcinoma ; 2: 123-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-27508201

RESUMO

Transarterial chemoembolization (TACE) is the standard treatment for patients with Barcelona Clinic Liver Cancer-intermediate stage hepatocellular carcinoma (HCC). The concept of drug-eluting bead TACE builds on the rationale of intratumoral drug delivery, and drug-eluting bead TACE has been shown to provide consistent and reliable results and to significantly diminish systemic drug exposure, liver toxicity, and drug-related adverse events as compared with conventional TACE. Based on the belief that combinations of TACE and other local or systemic therapies have several theoretical advantages, many clinical trials have been conducted to evaluate the effectiveness of TACE in combination with local treatment such as radiofrequency ablation or radiotherapy, and systemic therapy such as sorafenib or another molecular therapy. TACE has also been used as a preoperative adjuvant chemotherapy in patients with HCC to improve survival and as a bridging therapy before liver transplantation to downstage HCC. In the present evidence-based review, the authors summarize the current status of these transcatheter arterial embolic therapies in HCC.

20.
J Ultrasound Med ; 33(11): 1931-7, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25336480

RESUMO

OBJECTIVES: Polyethylene liner dissociation from an acetabular component is a complication of total-hip arthroplasty (THA) caused by slippage of the liner, which causes pain and requires a revision. The aim of this study was to evaluate sonographic features of liner dissociation and detect useful sonographic findings compared to conventional radiography and computed tomography (CT). METHODS: Among a total of 226 patients who underwent revision THA at our institution between September 2008 and June 2012, 10 patients (6 male and 4 female; mean age, 56.2 years) who showed severe narrowing of the superior joint space on the THA side and underwent sonography were retrospectively reviewed by evaluating radiographic, CT, and sonographic findings. In evaluation of the images, we put more emphasis on the "radiographic crescent sign," "CT crescent sign," and "sonographic tram track sign." RESULTS: At surgery, 7 patients showed liner dissociation, and 3 showed severe liner wear. On radiography, 8 of 10 patients (80%) had a correct diagnosis of the presence or absence of liner dissociation; on sonography, all 10 patients (100%) had a correct diagnosis. The sensitivity, specificity, and accuracy for diagnosis of liner dissociation by pelvic radiography and sonography were 100% (7 of 7), 33% (1 of 3), and 80% (8 of 10) and 100% (7 of 7), 100% (3 of 3), and 100% (10 of 10), respectively. CONCLUSIONS: Liner dissociation can be easily and well visualized by sonography, especially compared to pelvic radiography and CT. The sonographic tram track sign should be a very useful feature in the early diagnosis of liner dissociation.


Assuntos
Acetábulo/ultraestrutura , Artroplastia de Quadril/efeitos adversos , Migração de Corpo Estranho/diagnóstico por imagem , Migração de Corpo Estranho/etiologia , Prótese de Quadril/efeitos adversos , Polietileno , Falha de Prótese , Ultrassonografia/métodos , Acetábulo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
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