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RATIONALE: Joubert syndrome (JS) is a rare genetic disorder that presents with various neurological symptoms, primarily involving central nervous system dysfunction. Considering the etiology of JS, peripheral nervous system abnormalities cannot be excluded; however, cases of JS accompanied by peripheral nervous system abnormalities have not yet been reported. Distinct radiological findings on brain magnetic resonance imaging were considered essential for the diagnosis of JS. However, recently, cases of JS with normal or nearly normal brain morphology have been reported. To date, there is no consensus on the most appropriate diagnostic method for JS when imaging-based diagnostic approach is challenging. This report describes the case of an adult patient who exhibited bilateral peroneal neuropathies and was finally diagnosed with JS through genetic testing. PATIENT CONCERNS AND DIAGNOSIS: A 27-year-old man visited our outpatient clinic due to a gait disturbance that started at a very young age. The patient exhibited difficulty maintaining balance, especially when walking slowly. Oculomotor apraxia was observed on ophthalmic evaluation. During diagnostic workups, including brain imaging and direct DNA sequencing, no conclusive findings were detected. Only nerve conduction studies revealed profound bilateral peroneal neuropathies. We performed whole genome sequencing to obtain a proper diagnosis and identify the gene mutation responsible for JS. LESSONS: This case represents the first instance of peripheral nerve dysfunction in JS. Further research is needed to explore the association between JS and peripheral nervous system abnormalities. Detailed genetic testing may serve as a valuable tool for diagnosing JS when no prominent abnormalities are detected in brain imaging studies.
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Anormalidades Múltiplas , Cerebelo , Cerebelo/anormalidades , Anormalidades do Olho , Doenças Renais Císticas , Neuropatias Fibulares , Retina , Retina/anormalidades , Humanos , Masculino , Adulto , Doenças Renais Císticas/diagnóstico , Doenças Renais Císticas/genética , Doenças Renais Císticas/complicações , Cerebelo/diagnóstico por imagem , Anormalidades do Olho/diagnóstico , Anormalidades do Olho/genética , Neuropatias Fibulares/diagnóstico , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/genética , Retina/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
Low molecular weight collagen peptide (LMWCP) is a collagen hydrolysate derived from fish. We investigated the effects of LMWCP on hair growth using human dermal papilla cells (hDPCs), human hair follicles (hHFs), patch assay, and telogenic C57BL/6 mice, while also examining the underlying mechanisms of its action. LMWCP promoted proliferation and mitochondrial potential, and the secretion of hair growth-related factors, such as EGF, HB-EGF, FGF-4, and FGF-6 in hDPCs. Patch assay showed that LMWCP increased the neogeneration of new HFs in a dose-dependent manner. This result correlated with an increase in the expression of dermal papilla (DP) signature genes such as, ALPL, SHH, FGF7, and BMP-2. LMWCP upregulated phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and ß-catenin, and nuclear translocation of ß-catenin, and it increased the expression of Wnt3a, LEF1, VEGF, ALP, and ß-catenin. LMWCP promoted the growth of hHFs and increased the expression of ß-catenin and VEGF. Oral administration of LMWCP to mice significantly stimulated hair growth. The expression of Wnt3a, ß-catenin, PCNA, Cyclin D1, and VEGF was also elevated in the back skin of the mice. Furthermore, LMWCP increased the expression of cytokeratin and Keratin Type I and II. Collectively, these findings demonstrate that LMWCP has the potential to increase hair growth via activating the Wnt/ß-catenin signaling pathway.
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Via de Sinalização Wnt , beta Catenina , Camundongos , Humanos , Animais , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Peso Molecular , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células Cultivadas , Camundongos Endogâmicos C57BL , Folículo Piloso , Cabelo , Proliferação de CélulasRESUMO
Sarcoidosis is a systemic granulomatous disorder of unknown cause involving multiple organs. Its clinical presentation and prognosis vary among races. We identified the clinical characteristics and outcomes of Korean patients with sarcoidosis. Clinical data of 367 Korean patients with biopsy-proven sarcoidosis diagnosed in 2001-2017 were retrospectively analyzed. Treatment responses included improvement, stability, or progression based on changes in pulmonary sarcoidosis on chest images. The mean age was 47.4 years, and 67.3% of patients were women. The median follow-up period was 80 months. The highest prevalence was observed in individuals aged 50-59 years (30-39 years in men, 50-59 years in women), and the number of diagnoses showed an increasing trend. Lung involvement was the most common (93.5%), followed by the skin, eyes, and extrathoracic lymph nodes. Among patients with lung involvement and a follow-up period of ≥ 3 months, 66.8%, 31.0%, and 2.2% showed improvement, stability, and progression, respectively. Eleven patients (2.9%) died, and the 5-year survival rate was 99%. The number of diagnosed cases showed an increasing trend, and the mean age at diagnosis was increased compared with that in previous reports. Organ involvement was similar to that of Westerners, although the prognosis appeared better.
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Sarcoidose/epidemiologia , Adulto , Idoso , Biópsia , Gerenciamento Clínico , Suscetibilidade a Doenças , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , Avaliação de Resultados da Assistência ao Paciente , Prognóstico , Vigilância em Saúde Pública , Sistema de Registros , República da Coreia/epidemiologia , Sarcoidose/diagnóstico , Sarcoidose/etiologia , Sarcoidose/mortalidade , Índice de Gravidade de Doença , Avaliação de SintomasRESUMO
This study examined whether the oral administration of low-molecular-weight collagen peptide (LMCP) containing 3% Gly-Pro-Hyp with >15% tripeptide (Gly-X-Y) content could ameliorate osteoarthritis (OA) progression using a rabbit anterior cruciate ligament transection (ACLT) model of induced OA and chondrocytes isolated from a patient with OA. Oral LMCP administration (100 or 200 mg/kg/day) for 12 weeks ameliorated cartilage damage and reduced the loss of proteoglycan compared to the findings in the ACLT control group, resulting in dose-dependent (p < 0.05) improvements of the OARSI score in hematoxylin & eosin (H&E) and Safranin O staining. In microcomputed tomography analysis, LMCP also significantly (p < 0.05) suppressed the deterioration of the microstructure in tibial subchondral bone during OA progression. The elevation of IL-1ßand IL-6 concentrations in synovial fluid following OA induction was dose-dependently (p < 0.05) reduced by LMCP treatment. Furthermore, immunohistochemistry illustrated that LMCP significantly (p < 0.05) upregulated type II collagen and downregulated matrix metalloproteinase-13 in cartilage tissue. Consistent with the in vivo results, LMCP significantly (p < 0.05) increased the mRNA expression of COL2A1 and ACAN in chondrocytes isolated from a patient with OA regardless of the conditions for IL-1ßinduction. These findings suggest that LMCP has potential as a therapeutic treatment for OA that stimulates cartilage regeneration.
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Condrócitos/metabolismo , Colágeno/uso terapêutico , Matriz Extracelular/metabolismo , Osteoartrite/tratamento farmacológico , Agrecanas , Animais , Ligamento Cruzado Anterior , Células Cultivadas , Colágeno Tipo II , Citocinas , Modelos Animais de Doenças , Humanos , Masculino , Metaloproteinase 13 da Matriz , Peso Molecular , Peptídeos/uso terapêutico , Coelhos , Líquido SinovialRESUMO
PURPOSE: To investigate the incidence and clinical features of red blood cell (RBC)-coated intraocular lens (IOL) in breakthrough vitreous hemorrhage (VH) with subretinal hemorrhage (SRH) secondary to neovascular age-related macular degeneration (nAMD). SETTING: Seoul National University Bundang Hospital, Seongnam, Korea. DESIGN: Retrospective cohort analysis. METHODS: A total of 30 patients diagnosed as breakthrough VH with SRH in nAMD who underwent pars plana vitrectomy were included in this study. Demographics and clinical characteristics of the subjects, visual acuities, and SRH sizes measured as disc diameters were analyzed. The correlation analysis between SRH size and absorption duration of RBC-coated IOL were performed. RESULTS: Out of 30 eyes in 30 patients, RBC-coated IOLs were observed in 11 patients (37%). Appearance of RBC-coated IOLs was noted 1 month postoperatively, and the mean duration of SRH absorption was 8.6 ± 2.6 months. SRH sizes were significantly different between eyes with RBC-coated IOL and clear IOL (62.8 ± 20.7 vs 27.4 ± 14.2, P < .001). There was definite correlation between SRH size and absorption duration of RBC-coated IOL (correlation coefficient 0.899, P < .001, R2 = 0.831). There were no statistically significant differences according to age, sex, laterality, underlying medical conditions, preoperative lens status, history of antivascular endothelial growth factor treatment, and visual acuities. The degenerated RBC on the surface of IOL was confirmed by electron and light microscopy. CONCLUSIONS: RBC-coated IOL could develop after vitrectomy surgery for breakthrough VH with massive SRH secondary to nAMD, and it can be confused with IOL opacification. Because it spontaneously disappears gradually, observation without IOL removal is warranted.
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Lentes Intraoculares , Degeneração Macular , Eritrócitos , Humanos , Implante de Lente Intraocular , Complicações Pós-Operatórias , República da Coreia , Estudos Retrospectivos , Vitrectomia , Hemorragia Vítrea/etiologia , Hemorragia Vítrea/cirurgiaRESUMO
Licorice, the root of Glycyrrhiza glabra, has been observed to possess an anti-obesity effect. Previous research has suggested that licorice acetone extract (LE) has an influence on mitotic clonal expansion (MCE) and adenosine monophosphate-activated protein kinase (AMPK), which play a key role in regulating adipogenesis. This study sought further insight into the molecular mechanism of LE's anti-obesity effect using 3T3-L1 adipocytes in vitro. LE inhibited 3T3-L1 adipogenesis, and the inhibitory effect of LE on adipogenesis was most significant in the early stage of adipogenic differentiation. LE inhibited the protein expression of cyclins and cyclin-dependent kinases in the MCE stage and arrested cells in the G1 phase of the cell cycle. Furthermore, it activated AMPK via phosphorylation. Moreover, the expression levels of lipid metabolism-related genes were regulated by LE. These findings suggest the anti-obesity effect of LE via MCE and AMPK regulation. PRACTICAL APPLICATIONS: Although the anti-obesity effects of licorice have been studied, the application of functional food-related anti-obesity effects of licorice has been less than that of other extracts. The present study increases the reliability of the anti-obesity effect of licorice by suggesting a new mechanism of action and expands the application of functional foods related to the anti-obesity effect of licorice. A new mechanistic insight will not only improve the scientific knowledge but will also help to predict the side effects of licorice's anti-obesity application.
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Adipogenia , Glycyrrhiza , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/genética , Monofosfato de Adenosina , Animais , Camundongos , Extratos Vegetais/farmacologia , Reprodutibilidade dos TestesRESUMO
Purpose: To investigate intraocular pharmacokinetics of 10-fold dose of intravitreally injected ranibizumab compared with the conventional dose in an experimental model. Methods: Ranibizumab 30 µL at 10 mg/mL (conventional) and 100 mg/mL (10-fold) doses was injected separately into each eye of 28 rabbits. Ranibizumab concentrations in the aqueous humor, vitreous, and retina were estimated at each time period after injection, using enzyme-linked immunosorbent assay. The pharmacokinetic properties of ranibizumab were determined using a one-compartment model in all three ocular tissues. The time-concentration profile and predictive trends were plotted to determine drug efficacy in the retina. Results: Maximum concentrations after conventional and 10-fold dosing were observed in the retina at 1 and 4 days after injection, respectively. The half-life of ranibizumab after conventional and 10-fold dosing did not differ in the anterior chamber and vitreous, whereas the half-life was prolonged approximately twice with the 10-fold dose in the retina (36.74 h vs. 76.85 h) and serum (91.93 h vs. 179.01 h). Similarly, the estimated time for ranibizumab concentration in the retina over 27 ng/mL (minimum effective concentration of ranibizumab) was prolonged approximately twice with the 10-fold dose (1315 h [55 days] vs. 2393 h [100 days]). No adverse effects were observed in either group. Conclusions: The retinal half-life and concentration of ranibizumab in rabbit eyes were increased approximately twice after a 10-fold dose compared with the conventional dose. This finding indicates a possibility to lengthen the injection interval to improve the efficacy of ranibizumab in human eyes. Translational Relevance: Our results highlight the potential for clinical application of a high-dose (10-fold) of anti-VEGF agents to prolong the intravitreal injection intervals, simultaneously improving the drug efficacy.
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Inibidores da Angiogênese , Ranibizumab , Inibidores da Angiogênese/uso terapêutico , Animais , Humor Aquoso , Injeções Intravítreas , Coelhos , Corpo VítreoRESUMO
PURPOSE: This study was aimed at determining the intraocular pharmacokinetics based on molecular physicochemical properties in a rabbit model. METHODS: The entire dataset was obtained from previous literature, and research articles regarding 70 molecular compounds were investigated. The intravitreal half-lives in rabbit eyeballs of 22 macromolecules and 48 micromolecules were analyzed. Multiple linear regression analysis was carried out with non-collinear independent variables (molecular weight [MW] and lipophilicity) influencing intravitreal half-lives. The best-fit equations were selected based on the correlation coefficients and goodness-of-fit statistics. RESULTS: The best-fit models obtained from the entire dataset, macromolecules, and micromolecules suggest the correlation between molecular physicochemical properties (MW and lipophilicity) and intravitreal half-life. Exclusion of outlier molecules (amphotericin B and foscarnet) leads to a better-fit correlation. MW is the definite single factor affecting intravitreal half-lives of macromolecules (Log t1/2 = 0.148 + 0.370 Log MW, R2 = 0.769), while both MW and lipophilicity influence the intraocular pharmacokinetics of micromolecules (Log t1/2 = -1.213 + 0.762 Log MW - 0.115 Log p, R2 = 0.554). CONCLUSION: The present study indicates that intravitreal half-life could be predicted based on molecular physicochemical properties (MW and lipophilicity). Also, increasing MW while reducing lipophilicity would be a reliable method for prolonging the intravitreal half-life of small chemical drugs, while MW is the single major determinant for large biologic drugs.
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Inibidores da Angiogênese/farmacocinética , Anti-Infecciosos/farmacocinética , Anti-Inflamatórios/farmacocinética , Peso Molecular , Preparações Farmacêuticas/metabolismo , Corpo Vítreo/metabolismo , Animais , Injeções Intravítreas , Modelos Animais , Coelhos , Análise de RegressãoRESUMO
Fiber-optic-based localized surface plasmon resonance (FO-LSPR) sensors with three-dimensional (3D) nanostructures have been developed. These sensors were fabricated using zinc oxide (ZnO) nanowires and gold nanoparticles (AuNPs) for highly sensitive plasmonic biosensing. The main achievements in the development of the biosensors include: (1) an extended sensing area, (2) light trapping effect by nanowires, and (3) a simple optical system based on an optical fiber. The 3D nanostructure was fabricated by growing the ZnO nanowires on the cross-section of optical fibers using hydrothermal synthesis and via immobilization of AuNPs on the nanowires. The proposed sensor outputted a linear response according to refractive index changes. The 3D FO-LSPR sensor exhibited an enhanced localized surface plasmon resonance response of 171% for bulk refractive index changes when compared to the two-dimensional (2D) FO-LSPR sensors where the AuNPs are fixed on optical fiber as a monolayer. In addition, the prostate-specific antigen known as a useful biomarker to diagnose prostate cancer was measured with various concentrations in 2D and 3D FO-LSPR sensors, and the limits of detection (LODs) were 2.06 and 0.51 pg/ml, respectively. When compared to the 2D nanostructure, the LOD of the sensor with 3D nanostructure was increased by 404%.
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OBJECTIVES: To objectively assess pupillary involvement according to various etiologies of acquired isolated third nerve palsy using automated pupillometry, and evaluate the efficacy of digital pupillometry in discriminating compressive lesions from microvascular ischemic third nerve palsy. DESIGN: Retrospective, observational case series. METHODS: A total of 171 subjects were included in this study, consisting of 60 subjects with presumed microvascular ischemic third nerve palsy, 51 with non-ischemic third nerve palsy, and 60 controls whose pupillary light responses were measured using a dynamic automated pupillometer. Subjects with non-ischemic third nerve palsy were divided into subgroups according to their etiology; inflammatory and compressive groups including tumor and aneurysm. Pupillometry parameters including minimum and maximum pupil diameters, constriction latency and ratio, maximum and average constriction velocities and dilation velocity were noted. The diagnostic ability of pupillometry parameters for discriminating compressive vs microvascular ischemic third nerve palsy was evaluated. The inter-eye difference of the involved eye and the uninvolved fellow eye was calculated to adjust for individual variability. RESULTS: Among all parameters, reduced pupillary constriction ratio was the most specific parameter for detecting non-ischemic third nerve palsy, as a large inter-eye difference beyond the normative range of controls was found in 0% of ischemic, 20% of inflammatory and 60% of compressive third nerve palsy. With the diagnostic criteria using inter-eye differences of 1) minimum pupil diameter > 0.45 mm, or 2) pupillary constriction ratio < -7.5% compared to the fellow eye, the sensitivity and specificity for diagnosing compressive third nerve palsy were 95% and 88%, respectively. In the compressive group, positive correlations were found between the degree of external ophthalmoplegia and constriction ratio (r = 0.615, p<0.001), average constriction velocity (r = 0.591, p = 0.001) and maximum constriction velocity (r = 0.582, p = 0.001). CONCLUSIONS: Abnormal pupillary constriction ratio was highly specific for detecting compressive third nerve palsy, although the sensitivity was not high. Digital pupillometry demonstrated relatively good performance for discriminating compressive lesions from microvascular ischemic third nerve palsy.
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Doenças do Nervo Oculomotor/diagnóstico , Reflexo Pupilar , Idoso , Feminino , Humanos , Luz , Masculino , Pessoa de Meia-Idade , Doenças do Nervo Oculomotor/patologia , Doenças do Nervo Oculomotor/fisiopatologia , Pupila/fisiologia , Estudos RetrospectivosRESUMO
BACKGROUND: The prevalence and incidence of sarcoidosis varies worldwide. We estimated the prevalence and incidence of sarcoidosis in Korea using nationwide claims data from the Korean Health Insurance Review and Assessment Service. METHODS: Cases of sarcoidosis were identified for any visit between 2007 to 2016 that listed the Korean Classification of Disease, 7th edition code of sarcoidosis and rare incurable disease exempted calculation code. A narrow case definition was used as follows: 1) ≥ two sarcoidosis-coded visits within 1 year of the first claim, 2) no claims for other diseases that could form granuloma. RESULTS: A total of 4791 patients (narrow, n = 2388) visited medical institutions for sarcoidosis during the study period; 2999 patients (narrow, n = 1696) were newly identified between 2009 and 2015. The sarcoidosis prevalence was 9.37 per 105 people (narrow, 4.69) and was highest between ages 60-69 years. The incidence rate was 0.85 per 105 population at risk (narrow, 0.48), with the highest incidence rate between ages 50-59 years. For incident cases (mean age: 48.5 year), the age distribution in whole population and females showed monophasic patterns peaking at aged 50-59 years, while males had biphasic incidence peak at aged 30-39 years and 60-69 years. The annual incidence rates showed increasing trends from 0.85 per 105 population at risk in 2009 to 0.97 per 105 population at risk in 2015. CONCLUSIONS: In comparison with previous reports, the prevalence and incidence of sarcoidosis in Korea have increased and middle-aged women showed the highest risk.
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Bases de Dados Factuais/tendências , Vigilância da População , Sarcoidose/diagnóstico , Sarcoidose/epidemiologia , Adolescente , Adulto , Idoso , Broncoscopia/tendências , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , República da Coreia/epidemiologia , Sarcoidose/cirurgia , Adulto JovemRESUMO
PURPOSE: To evaluate the long-term visual outcomes and complications of cataract surgery in eyes previously treated for retinoblastoma. METHODS: We reviewed the medical records of patients who underwent cataract extraction and intraocular lens implantation at Seoul National University Children's Hospital for a secondary cataract that developed after retinoblastoma treatment. RESULTS: During the period between 1990 and 2014, 208 eyes of 147 patients received eye-salvaging treatment (radiotherapy, chemotherapy, and local therapy) for retinoblastoma at Seoul National University Children's Hospital. Among these eyes, a secondary cataract was detected in 17 eyes of 14 patients, and five eyes of five patients underwent cataract surgery. The median age of cataract formation was 97 months (range, 38 to 153 months). The medial interval between the diagnosis of retinoblastoma and cataract formation was 79 months (range, 29 to 140 months). All patients received posterior chamber intraocular lens insertion after irrigation and aspiration of the lens through a scleral tunnel incision. Anterior vitrectomy and posterior capsulotomy were performed in two eyes and a laser capsulotomy was subsequently performed in one eye. No intraoperative and postoperative complications occurred. The median follow-up after surgery was 36 months (range, 14 to 47 months). The final best corrected visual acuities were improved in all five eyes. No intraocular tumor recurrences or metastases occurred. CONCLUSIONS: After retinoblastoma regression, cataract extraction in our series was not associated with tumor recurrence or metastasis. Visual improvement was noted in every patient.
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Extração de Catarata/métodos , Catarata/etiologia , Neoplasias da Retina/terapia , Retinoblastoma/terapia , Pré-Escolar , Terapia Combinada/efeitos adversos , Feminino , Seguimentos , Humanos , Lactente , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoAssuntos
Bevacizumab/efeitos adversos , Hemangioma Capilar/tratamento farmacológico , Fotoquimioterapia/efeitos adversos , Retina/patologia , Descolamento Retiniano/induzido quimicamente , Neoplasias da Retina/tratamento farmacológico , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Bevacizumab/administração & dosagem , Seguimentos , Hemangioma Capilar/diagnóstico , Humanos , Injeções Intravítreas , Masculino , Descolamento Retiniano/diagnóstico , Neoplasias da Retina/diagnóstico , Fatores de Tempo , Adulto JovemRESUMO
The purpose of this study was to design chitosan microspheres (MS) loaded with superparamagnetic iron oxide nanoparticles (SPIO) suitable for anti-cancer embolotherapy detectable by MRI. Deformable chitosan MS loaded with varying SPIO concentrations (SPIO-chitosan MS) were prepared by ionotropic gelation and a porogenic technique using polyethylene glycol, followed by genipin crosslinking. Adding SPIO nanoparticles to chitosan MS did not significantly affect the chitosan MS morphology. An in vitro phantom study led to selecting SPIO-chitosan MS prepared with 1.0 mM SPIO for an in vivo MR traceability study. SPIO-chitosan MS could be identified following embolization in the renal artery by MRI at 18 weeks. Histological and pathological evidence also showed that SPIO-chitosan MS blocked and remained in the target vessels. Therefore, deformable SPIO-chitosan MS is MR-detectable embolic material with a possible application for anti-cancer embolotherapy.