Aqueous Misdirection Syndrome after Laser Iridotomy in a Patient with Intermediate Uveitis

Purpose@#We report a case of aqueous misdirection syndrome triggered by pilocarpine use after laser iridotomy, which was treated by pars plana vitrectomy and phacoemulsification.Case summary: A 48-year-old female patient presented with sudden-onset right eye pain and decreased vision. The patient had presented to another institute with similar symptoms 20 days prior; she had been diagnosed with acute angle closure. Laser iridotomy was performed, followed by administration of pilocarpine twice daily. In the right eye, visual acuity was hand motion, and intraocular pressure was 31 mmHg. The laser iridotomy site was located at the 11 o’clock position; microcysts, anterior chamber cells, corneal endothelium precipitates, and glaukomflecken were observed. The anterior chamber was shallow due to forward movement of the lens and iris. Despite the application of atropine and pressure-lowering eyedrops, anterior chamber shallowing continued along with a progressive myopic shift of -4.5 diopters. Therefore, the patient was diagnosed with aqueous misdirection syndrome. Pars plana vitrectomy was performed, followed by phacoemulsification, intraocular lens insertion, and posterior capsulotomy. During surgery, vitreous inflammation, a peripheral snowball, and an anterior hyaloid inflammatory membrane were observed, indicating the presence of intermediate uveitis. @*Conclusions@#The administration of miotics after laser iridotomy, intraocular inflammation, and uveitis can lead to aqueous misdirection syndrome. Effective treatment of aqueous misdirection syndrome involves controlling inflammation and performing surgery.

Acellular dermal matrix and bone cement sandwich technique for chest wall reconstruction

The authors performed rigid reconstruction using the sandwich technique for full-thickness chest wall defects by using two layers of acellular dermal matrix and bone cement. We assessed six patients who underwent chest wall reconstruction. Reconstruction was performed by sandwiching bone cement between two layers of acellular dermal matrix. In all patients, there was no defect of the overlying soft tissue, and primary closure was performed for external wounds. The average follow-up period was 4 years (range, 2–8 years). No major complications were noted. The sandwich technique can serve as an efficient and safe option for chest wall reconstruction.

Quality of Life and Characteristics of Depression with Subjective Cognitive Decline in Korean Adults :Data from the Seventh Korea National Health and Nutrition Examination Survey / 정신신체의학

Objectives@#：This study aimed to investigate quality of life, severity of depression, suicidality, subjective health and subjective stress of depression with subjective cognitive decline in Korean adults. @*Methods@#：We used the 7th KNHANES data to enroll 415 participants with a score of 10 or higher on Patient Health Questionnaire-9 (PHQ-9), aged 20-64. Depression was divided into two groups based on the presence/absence of subjective cognitive decline. Demographic and psychological characteristics were compared between two groups. Correlation analysis of subjective cognitive decline, quality of life, depression, suicidal idea was car-ried out. To detect which variables influenced quality of life, a multiple regression analysis was carried out. @*Results@#：Among the 415 participants, 98 had depression with subjective cognitive decline. We identified sig-nificant differences in age, marital status, education, employment between the two groups. After adjusting for these variables, depression with subjective cognitive decline had lower EuroQol-5D index scores, more severe depressive symptoms without cognition and worse subjective health than depression without cognitive decline. There was a significant correlation between subjective cognitive decline and quality of life (r=-0.236, p<0.001), suicidal idea (r=0.182, p<0.001), depression score without cognition (r=0.108, p=0.028). Through multiple regression analysis, subjective cognitive decline was predictor of reduced quality of life (β=-0.178, p<0.001). @*Conclusions@#：Depression with subjective cognitive decline has poor quality of life and severe depression. Cognitive decline should be considered to improve treatment result in depression.

Visual Field Patterns of Pseudo-optic Discs in Chorioretinal Coloboma

Purpose@#We report three cases of asymptomatic pseudo-optic discs in chorioretinal colobomas highlighted on visual fields patterns.Case summary: (Case 1) A 36-year-old man was found to have a pseudo-optic disc below the optic nerve with a relatively intact neurosensory retina over the lesion. There were no obvious abnormalities on the visual field test, so he underwent no treatment and was followed up every 6 months. (Case 2) A 37-year-old woman diagnosed with glaucoma had abrupt convergence of the neurosensory retinal layers on the boundary of the pseudo-optic disc and a focal retinal nerve fiber layer defect in the inferior sector. An antiglaucoma eyedrop was used to manage the superior hemifield defect, and no significant progression was observed in the structural and functional tests during the 5-year follow-up. (Case 3) A 57-year-old man had a pseudo-optic disc with diffuse retinal nerve fiber layer atrophy in both the superior and inferior sectors. The pseudo-optic disc had protruded into the vitreous cavity. Antiglaucoma eyedrops were used to manage both the superior and inferior hemifield defects, and no significant progression was observed using the structural and functional tests during the 6-year follow-up period. @*Conclusions@#Various visual field results may occur with pseudo-optic discs in chorioretinal colobomas depending on the status of residual retinal tissues and underlying glaucoma. Further evaluations and management options should be considered according to the patient’s condition.

BellaGel breast implant: 6-Year results of a prospective cohort study

Background@#This is the first clinical study conducted among Asian women using breast implants manufactured by an Asian company. Four-year data regarding the safety and efficacy of BellaGel breast implants have already been published, and we now report 6-year data. @*Methods@#This study was designed to take place over 10 years. It included 103 patients who underwent breast reconstruction or augmentation using BellaGel breast implants. The rates of implant rupture and capsular contracture were measured and analyzed to evaluate the effectiveness of the breast implant. @*Results@#At patients’ 6-year postoperative visits, the implant rupture and capsular contracture rates were 1.15% and 2.30%, respectively. The implant rupture rate was 3.77% among reconstruction cases and 0% among augmentation cases. The capsular contracture rate was 5.66% among reconstruction cases and 0.83% among augmentation cases. @*Conclusions@#The 6-year data from this planned 10-year study suggest that the BellaGel cohesive silicone gel-filled breast implant is an effective and safe medical device that can be used in breast reconstruction and augmentation.

Relationship between Disability Self-Awareness and Insight in Patients with Schizophrenia / 생물치료정신의학

Objectives@#：We aimed to evaluate the relationship between disability self-awareness and insight in patients with schizophrenia. @*Methods@#：We enrolled 58 clinically stable patients with schizophrenia. The World Health Organization Disability Assessment Schedule (WHODAS) self-report was used to identify self-awareness of functional ability. The Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Schizophrenia Scale (CGI-SCH), and Personal and Social Performance Scale (PSP) were utilized to evaluate clinical symptoms and global function. Whereas Insight Scale for Psychosis (ISP) was applied for insight. Statistical analyses were performed using correlation and linear regression. @*Results@#：The WHODAS had a significant correlation with the general psychopathology subscale and total score of PANSS, CGI-SCH, and PSP. Moreover, ISP had a strong correlation with the overall WHODAS score and all domains. In the linear regression analysis, ISP had significant effects on the overall WHODAS score after adjusting for additional variables. @*Conclusion@#：Disability self-awareness was significantly correlated with the level of insight in patients with schizophrenia. Clinicians need to consider patients’ insight during the discussion of functional ability.

The Effectiveness on Prevention of Rehospitalization with Long-Term Psychosocial Interventions for Patients with Major Psychiatric Disorders / 대한정신분열병학회지

OBJECTIVES: This study aimed to elucidate the effectiveness of long-term psychosocial intervention in reducing the disabling period of patients with major psychiatric disorders by their rehospitalization rate. METHODS: Of the 210 patients with major psychiatric disorders received psychosocial interventions in a Mental Health and Welfare Center, 192 patients (147 with schizophrenia spectrum disorders, 45 with mood disorders) who received interventions more than 6 months were selected. Review of case management records was conducted to obtain information. RESULTS: The number and length of hospitalization and the hospital days per year significantly decreased after psychosocial intervention. Additional analysis of 102 patients followed up for more than 5 years suggested that the effectiveness of the intervention persisted for a sufficient period. However, no significant difference was observed in the number of rehospitalization in 45 patients with mood disorders, though the length of hospitalization significantly decreased. In addition, the hospital days per year of 21 patients with mood disorder followed up for more than 5 years also showed no significant decrease. CONCLUSION: Long-term psychosocial intervention had a significant effect on reducing the number and length of hospitalization for patients with major psychiatric disorder and the effectiveness maintained for more than 5 years.

The Anti-fibrotic Effect of Nilotinib on Tenon's Capsule Fibroblasts in Vitro

PURPOSE: To evaluate the anti-fibrotic effects of nilotinib on the survival of cultured human Tenon's capsule fibroblasts (HTFs). METHODS: HTF primary cultures were obtained from samples following glaucoma surgery. Primarily cultured HTFs were exposed to 1, 5, 10, and 20 µM nilotinib for 24 hours. The effects of nilotinib on HTF proliferation and cell viability were determined using the 3-(4,5-dimethylthiazone-2-yl)-2,5-diphenyl tetrazolium (MTT) assay, and apoptosis was determined by flow cytometry using annexin-V/propidium iodide (PI) double staining. Apoptosis-related proteins were detected by western blotting. RESULTS: The MTT assay showed that nilotinib induced an inhibition of HTF proliferation at concentrations of 10 and 20 µM (p < 0.001 and p < 0.001, respectively). Annexin V/PI double staining showed significantly increased apoptosis in cells treated with nilotinib. Nilotinib activated caspase-3, -9, and poly adenosine diphosphate ribose polymerase cleavage, and downregulated the expression of B-cell lymphoma-extra large and Bax, which indicated that nilotinib-induced apoptosis was partly mediated through the mitochondrial pathway. In addition, treatment with nilotinib decreased the expression of α-smooth muscle actin and transforming growth factor-β. CONCLUSIONS: Nilotinib decreased cell survival of cultured HTFs and induced mitochondria-mediated apoptosis. The results suggested that nilotinib may exert antiproliferative effects on HTFs, making it a possible agent to control postoperative fibrosis in patients undergoing glaucoma surgery.

ACN9 Regulates the Inflammatory Responses in Human Bronchial Epithelial Cells / 결핵및호흡기질환

BACKGROUND: Airway epithelial cells are the first line of defense, against pathogens and environmental pollutants, in the lungs. Cellular stress by cadmium (Cd), resulting in airway inflammation, is assumed to be directly involved in tissue injury, linked to the development of lung cancer, and chronic obstructive pulmonary disease (COPD). We had earlier shown that ACN9 (chromosome 7q21), is a potential candidate gene for COPD, and identified significant interaction with smoking, based on genetic studies. However, the role of ACN9 in the inflammatory response, in the airway cells, has not yet been reported. METHODS: We first checked the anatomical distribution of ACN9 in lung tissues, using mRNA in situ hybridization, and immunohistochemistry. Gene expression profiling in bronchial epithelial cells (BEAS-2B), was performed, after silencing ACN9. We further tested the roles of ACN9, in the intracellular mechanism, leading to Cd-induced production, of proinflammatory cytokines in BEAS-2B. RESULTS: ACN9 was localized in lymphoid, and epithelial cells, of human lung tissues. ACN9 silencing, led to differential expression of 216 genes. Pathways of sensory perception to chemical stimuli, and cell surface receptor-linked signal transduction, were significantly enriched. ACN9 silencing, further increased the expression of proinflammatory cytokines, in BEAS-2B after Cd exposure. CONCLUSION: Our findings suggest, that ACN9 may have a role, in the inflammatory response in the airway.

miR-24-mediated knockdown of H2AX damages mitochondria and the insulin signaling pathway

Mitochondrial deficits or altered expressions of microRNAs are associated with the pathogenesis of various diseases, and microRNA-operated control of mitochondrial activity has been reported. Using a retrovirus-mediated short-hairpin RNA (shRNA) system, we observed that miR-24-mediated H2AX knockdown (H2AX-KD) impaired both mitochondria and the insulin signaling pathway. The overexpression of miR-24 decreased mitochondrial H2AX and disrupted mitochondrial function, as indicated by the ATP content, membrane potential and oxygen consumption. Similar mitochondrial damage was observed in shH2AX-mediated specific H2AX-KD cells. The H2AX-KD reduced the expression levels of mitochondrial transcription factor A (TFAM) and mitochondrial DNA-dependent transcripts. H2AX-KD mitochondria were swollen, and their cristae were destroyed. H2AX-KD also blocked the import of precursor proteins into mitochondria and the insulin-stimulated phosphorylation of IRS-1 (Y632) and Akt (S473 and T308). The rescue of H2AX, but not the nuclear form of ΔC24-H2AX, restored all features of miR-24- or shH2AX-mediated impairment of mitochondria. Hepatic miR-24 levels were significantly increased in db/db and ob/ob mice. A strong feedback loop may be present among miR-24, H2AX, mitochondria and the insulin signaling pathway. Our findings suggest that H2AX-targeting miR-24 may be a novel negative regulator of mitochondrial function and is implicated in the pathogenesis of insulin resistance.

Influence of Myopia on Size of Optic Nerve Head and Retinal Nerve Fiber Layer Thickness Measured by Spectral Domain Optical Coherence Tomography

PURPOSE: To investigate optic nerve head size and retinal nerve fiber layer (RNFL) thickness according to refractive status and axial length. METHODS: In a cross-sectional study, 252 eyes of 252 healthy volunteers underwent ocular biometry measurement as well as optic nerve head and RNFL imaging by spectral-domain optical coherence tomography. Correlation and linear regression analyses were performed for all subjects. The magnification effect was adjusted by the modified axial length method. RESULTS: Disc area and spherical equivalent were positively correlated (r = 0.225, r² = 0.051, p = 0.000). RNFL thickness showed significant correlations with spherical equivalent (r = 0.359, r² = 0.129, p = 0.000), axial length (r = -0.262, r² = 0.069, p = 0.000), disc radius (r = 0.359, r² = 0.129, p = 0.000), and radius of the scan circle (r = -0.262, r² = 0.069, p = 0.000). After adjustment for the magnification effect, those relationships were reversed; RNFL thickness showed negative correlation with spherical equivalent and disc radius, and positive correlation with axial length and radius of the scan circle. The distance between the disc margin and the scan circle was closely correlated with RNFL thickness (r = -0.359, r² = 0.129, p = 0.000), which showed a negative correlation with axial length (r = -0.262, r² = 0.069, p = 0.000). CONCLUSIONS: Optic disc radius and RNFL thickness decreased in more severely myopic eyes, but they increased after adjustment for magnification effect. The error due to the magnification effect and optic nerve head size difference might be factors that should be considered when interpreting optical coherence tomography results.

Epidemiologic Aspects of Medical Retirement from the Republic of Korea Army due to Visual Impairment

This study was done to report the epidemiologic characteristics of medical retirement from the Republic of Korea (ROK) Army due to visual impairment and to suggest a practical screening system for the draft. The medical records of 423 eyes of 301 patients who retired from the ROK Army due to visual impairment were reviewed retrospectively between January 2010 and December 2014. The patients were grouped by the presence of trauma, and each group was subdivided by military rank. We analyzed demographic and ophthalmic data, including the etiology of ophthalmologic disease. The etiology was classified into 5 anatomical categories (ocular surface, lens, retina, optic nerve and extraocular visual pathway, and extraocular muscle and orbit), which were then subdivided into the type of disease. The mean age was 24.5 years, and non-traumatic mechanisms accounted for 81.1% (343/423 eyes) of medical retirements. Visual acuity was better in patients without trauma. In enlisted soldiers, disease in the optic nerve and extraocular visual pathway was the most common anatomical category (40.5%), and primary open angle glaucoma (30.8%), retinal dystrophy (18.3%), congenital cataract (14.5%), and retinal detachment (9.7%) were the four most common diseases. Most medical retirements due to visual impairment resulted from non-traumatic mechanisms, even though patients were young. The fundus examination and visual field test would be more useful tools than a conventional vision test for large-scale draft screening for the most common two disease types: primary open angle glaucoma and retinal dystrophy.

Bone Framework Graft through an Intraoral Approach in a Patient with Columellar Scar Contracture

We present our experience with calvarial bone framework insertion through an intraoral approach for a patient who was at risk for columellar necrosis due to a previous open rhinoplasty. A 58-year-old woman exhibited severe columellar contracture, so that the columellar tissue was too fragile to be touched. We could not incise the columella and insert a new nasal implant through the bilateral rim incision. Moreover, the patient had septal cartilage perforation and collapse. The patient needed columellar support as well as nasal dorsum reconstruction. The authors decided to graft an autogenous L-strut bone framework through an intraoral approach. Two pieces of 5-cm × 1-cm sized split calvarial bone were harvested and trimmed to fit the width and length of the nasal dorsum and columella. The right-angle-shaped bone framework was made with an absorbable plate and screws. Through a gingivobuccal incision, the bone framework graft was inserted and the graft was fixed with absorbable screws. The patient did not experience complications such as skin necrosis or inflammation. A bone framework grafted through an intraoral approach can be a good choice for patients who have experienced scar contracture in the columella, septal cartilage perforation, and collapse.

Tuberculous Osteomyelitis of the First Metatarsophalangeal Joint Misdiagnosed as Gouty Arthritis

A-43-year-old man visited our clinic due to pain and swelling of his left first metatarsophalangeal (MTP) joint since 6-months ago. He was diagnosed as gouty arthritis at private clinic and took hypouricemic agent, but he had progressive pain and swelling. There was swelling, erythema and tenderness and ulceration at base of the left first MTP joint. His laboratory results showed elevated C-reactive protein and normal serum uric acid level. The plain radiograph of foot showed bone destruction of left first MTP joint. MRI revealed joint space narrowing, soft tissue swelling and subchondral cyst. He underwent excisional biopsy and histology demonstrated chronic granulomatous inflammation with caseation necrosis. Tissue polymerase chain reaction for mycobacterium tuberculosis was positive. He was diagnosed as tuberculous osteomyelitis. He started on quadruple anti-tuberculous therapy and his symptom was improved. Early diagnosis and anti-tuberculosis therapy could lead to improve outcomes.

Quality of Life According to Location of Integrated Binocular Visual Field Defect in Normal-Tension-Glaucoma Patients

PURPOSE: To investigate the relationship between vision-related quality of life (QOL) and integrated binocular visual field (IVF) defect and the difference in QOL based on the location of visual field defects in Korean normal tension glaucoma (NTG) patients. METHODS: Two hundred monocular visual fields from 100 patients diagnosed with normal tension glaucoma in at least one eye were integrated using the best location method, and the mean deviation (MD) of whole, superior, and inferior IVF was calculated. We analyzed the correlations between subscales of the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) and each calculated MD using Spearman correlation. After adjusting for confounding factors of age, visual acuity of the better eye, number of medications, and education level, the impact of IVF loss on the composite score of the NEI VFQ-25 was evaluated using multivariate linear regression analysis. RESULTS: The MDs of whole and inferior IVF were significantly associated with 7 of 12 NEI VFQ-25 subscales, and the superior IVF was associated with 3 subscales (p < 0.05). After adjusting confounding variables, the composite score of the NEI VFQ-25 showed significant correlation with whole, superior, and inferior IVF. The adjusted R2 and beta coefficient of the regression line were highest in the whole IVF (Adjusted R2 = 0.451, beta = 1.12), followed by the inferior and superior IVF (Adjusted R2 = 0.438, 0.395, beta = 0.95, 0.85). CONCLUSIONS: The IVF of Korean NTG patients can effectively reflect patient QOL, and the inferior IVF was significantly associated with more subscales of NEI VFQ-25 than was the superior IVF. However, overall QOL of patients is thought to be determined by severity of visual field loss rather than its location.

Compared Effectiveness of 10-Session Social Skill Training for Korean Early Elementary School Children in Two Groups Diagnosed as Pure ADHD and ADHD with Comorbidity

OBJECTIVES: Children with attention-deficit hyperactivity disorder (ADHD) have problems in social interactions. We compared the effect of 10-session social skill training (SST) among two groups, children with pure ADHD, and those with ADHD with comorbidity. METHODS: Consecutive 10-session SST was conducted for 34 children from 2006 to 2012. There were 22 children with pure ADHD (male 20, female 2), and 12 children suffering from ADHD with comorbidity (male 11, female 1). All children took medication as prescribed by their doctors before the start of SST. The Child Behavior Checklist (CBCL), the Korean Personality Inventory for Children (K-PIC), the Conner's Rating Scale, the ADHD Rating Scale, and the Home Situation Questionnaire were completed by mothers before and after the SST. All children completed the Child Depression Inventory, the Stat-Trait Anxiety Inventory for Children, the Self-Concept Scale and the ADHD Diagnostic System before and after the SST. RESULTS: Only children with pure ADHD showed improvement in anxiety and self-concept in scales rated by children. In the CBCL rated by parents, the pure ADHD group and the ADHD with comorbidity showed improvement in both externalizing and internalizing subscales. In the K-PIC rated by parents, the pure ADHD group showed improvement in most outcomes and ADHD with comorbidity showed positive change in verbal development. CONCLUSION: These results suggest that SST has significant positive effects on both the pure ADHD and ADHD with comorbidity group. Further research is needed in order to target diverse comorbidity groups with ADHD to improve the effectiveness of the SST.

Acute Transverse Myelitis in a Patient with Rheumatoid Arthritis Treated with Intravenous Immunoglobulin / 대한내과학회지

Acute transverse myelitis (ATM) is a heterogeneous syndrome characterized by acute spinal cord dysfunction resulting in paresis and sensory and autonomic impairment below the level of the lesion. The etiology of ATM includes parainfectious, paraneoplastic, drug-induced, systemic autoimmune disorders, and acquired demyelinating diseases. ATM is very rare in patients with rheumatoid arthritis (RA). A 79-year-old woman with RA, a recurring peptic ulcer, and congestive heart failure presented with acute weakness of both upper and lower extremities. She was diagnosed with ATM based on the results of laboratory and radiological tests. ATM is usually treated with high-dose glucocorticoid. However, we treated her with intravenous immunoglobulin (IVIG) considering the adverse events of high-dose glucocorticoid, and she improved. We report a case of ATM in a patient with RA successfully treated with IVIG.

The Study of Reliability and Validity of the Korean Version of the Trauma Symptom Checklist for Young Children

The present study aimed to evaluate the psychometric properties of the Korean version of the Trauma Symptom Checklist for Young Children (TSCYC) including reliability and validity. The TSCYC is an instrument to identify trauma symptoms in children from age 3 to 12 yr by their caretakers. The Korean version of the TSCYC was administered to the caretakers of a normative group of 299 children (137 boys and 162 girls) aged 3 to 12 yr and a traumatized group of 73 sexually abused children (22 boys and 51 girls) aged 3 to 12 yr and their caretakers rated the TSCYC and the Child Behavior Checklist and the Child Sexual Behavior Inventory. Among normative group, 88 performed a re-test after 4 weeks. The internal consistency, Cronbach's alpha of total scale of the TSCYC was 0.92 (normative group) and 0.96 (traumatized group). For the nine clinical scales in the TSCYC, it ranged between 0.46-0.92 and 0.77-0.96, respectively. Test-retest correlation of the TSCYC was good (Pearson r score ranging 0.52-0.96). Correlations between the TSCYC and other measures of corresponding constructs were satisfactory. Regarding discriminant validity, the mean total score of the TSCYC was significantly higher in the traumatized children than in the normative group. This study demonstrated that Korean version of the TSCYC is a reliable measure with excellent internal consistency and good stability over 4-week test-retest interval. It can be recommended for clinicians to screen for trauma symptoms after child sexual abuse in Korean young children between the ages 3 and 12.

The Korean Version of the Pediatric Symptom Checklist: Psychometric Properties in Korean School-aged Children

Psychosocial problems increase the risk for mental health problems and increase the need for health care services in children and adolescents. Primary care practice is a valuable avenue for identifying the need for more specialized mental health care. We hypothesized that Korean version of the pediatric symptom checklist (PSC) would be a useful tool for early detection of psychosocial problems in children and adolescents in Korea and we aimed to suggest cut-off scores for detecting meaningful psychosocial problems. A total of 397 children with their parents and 97 child patients with their parents were asked to complete the PSC Korean version and the child behavior checklist (CBCL). The internal reliability and test-retest reliability of the PSC as well as the cut-off score of the PSC was determined via receiver operating characteristic analysis of the CBCL score, clinical group scores and non-clinical group scores. The internal consistency of the PSC-Korean version was excellent (Cronbach's alpha = 0.95). The test-retest reliability was r = 0.73 (P or = 60) and presence of clinical diagnosis, the recommended cut-off score of the PSC was 14. Using 494 Korean children aged 7-12 yr, the current study assessed the reliability and validity of a Korean version of the PSC and suggested a cut-off for recommending further clinical assessment. The present results suggest that the Korean version of the PSC has good internal consistency and validity using the standard of CBCL scores.

Combined treatment with silibinin and either sorafenib or gefitinib enhances their growth-inhibiting effects in hepatocellular carcinoma cells

BACKGROUND/AIMS: Silibinin, the main component of silymarin, is used as a hepatoprotectant and exhibits anticancer effects against various cancer cells. This study evaluated the effects of a combination of silibinin with either gefitinib or sorafenib on hepatocellular carcinoma (HCC) cells. METHODS: Several different human HCC cell lines were used to test the growth-inhibiting effects and cell toxicity of silibinin both alone and in combination with either gefitinib or sorafenib. The cell viability and growth inhibition were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, trypan blue staining, and a colony-forming assay. Furthermore, changes in epidermal growth factor receptor (EGFR)-related signals were evaluated by Western blot analysis. RESULTS: Gefitinib, sorafenib, and silibinin individually exhibited dose-dependent antiproliferative effects on HCC cells. Combined treatment with silibinin enhanced the gefitinib-induced growth-inhibiting effects in some HCC cell lines. The combination effect of gefitinib and silibinin was synergistic in the SNU761 cell line, but was only additive in the Huh-BAT cell line. The combination effect may be attributable to inhibition of EGFR-dependent Akt signaling. Enhanced growth-inhibiting effects were also observed in HCC cells treated with a combination of sorafenib and silibinin. CONCLUSIONS: Combined treatment with silibinin enhanced the growth-inhibiting effects of both gefitinib and sorafenib. Therefore, the combination of silibinin with either sorafenib or gefitinib could be a useful treatment approach for HCC in the future.