PURPOSE: The microRNA-221/222 (miR-221/222) gene cluster has been reported to be associated with the promotion of epithelial-mesenchymal transition (EMT), downregulation of estrogen receptor-α, and tamoxifen resistance in breast cancer. We studied the expression of miR-222 in human breast cancer samples to analyze its relationship with clinicopathologic features of the tumor, including estrogen receptor status, expression of EMT markers, and clinical outcomes. METHODS: Quantitative real-time polymerase chain reaction was performed to detect the expression of miR-222 in 197 invasive breast cancers. Expression of EMT markers (vimentin, smooth muscle actin, osteonectin, N-cadherin, and E-cadherin) was evaluated using immunohistochemistry. RESULTS: High miR-222 levels were associated with high T stage, high histologic grade, high Ki-67 proliferation index, and HER2 gene amplification. Its expression was significantly higher in the luminal B and human epidermal growth factor receptor 2-positive (HER2+) subtypes than in the luminal A and triple-negative subtypes. In the hormone receptor-positive subgroup, there was a significant negative correlation between miR-222 and estrogen receptor expression, and miR-222 expression was associated with EMT marker expression. In the group as a whole, high miR-222 expression was not associated with clinical outcome. However, subgroup analyses by hormone receptor status revealed that high miR-222 expression was a poor prognostic factor in the hormone receptor-positive subgroup, but not in the hormone receptor-negative subgroup. CONCLUSION: This study showed that miR-222 is associated with down-regulation of the estrogen receptor, EMT, and tumor progression in hormone receptor-positive breast cancer, indicating that miR-222 might be associated with endocrine therapy resistance and poor clinical outcome in hormone receptor-positive breast cancer.
Actins ; Breast Neoplasms* ; Breast* ; Cadherins ; Down-Regulation ; Epithelial-Mesenchymal Transition ; Estrogens ; Genes, erbB-2 ; Humans ; Immunohistochemistry ; Multigene Family ; Muscle, Smooth ; Osteonectin ; Phenobarbital ; Prognosis ; Real-Time Polymerase Chain Reaction ; Receptor, Epidermal Growth Factor ; Tamoxifen

BACKGROUND: The molecular profile of peritumoral non-neoplastic liver parenchyma (PNLP) has recently been suggested as predictive factor of early and late recurrence of hepatocellular carcinoma (HCC). However, there is no definite cut-off point for tumor-free PNLP in terms of either histological or molecular changes. Therefore, our aim is to determine the numerical cut-off point for separating adjacent PNLP and remote PNLP in histopathologic perspective. METHODS: Peritumoral tissues from 20 resected HCC patients were sampled from 0 to 40 mm distance from the tumor border (divided into 5-mm columns). Histopathologic parameters such as necroinflammatory activity, fibrosis, bile ductular reaction, hepatic venulitis, peliosis, and steatosis were compared between each column. RESULTS: The morphologic changes just adjacent to the tumor were notably severe and faded with distance. The parenchyma within 10 mm of the tumor showed significantly severe inflammation, fibrosis, peliosis and hepatic venulitis compared with those from farther areas. The histopathologic changes of the parenchyma became stable beyond 20 mm. CONCLUSIONS: Results of this study revealed that the parenchyma within 10 mm distance from the tumor, or adjacent PNLP, has histopathologic changes that are directly affected by the tumor, and the parenchyma beyond 20 mm as the remote PNLP without tumor effect.
Bile ; Carcinoma, Hepatocellular ; Fibrosis ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Inflammation ; Liver ; Recurrence

BACKGROUND: The recently identified organic anion transporter 3 (rOAT3) was mainly expressed in kidney, liver and brain tissue, and it contributes the movement of endogenous or exogenous substances across the cell membrane. Although the properties of rOAT3 are gradually accumulated, the regulatory mechanism of rOAT3 remains to be elucidated. Caveolin (Cav) also plays a role as a membrane transporter and as a modulating protein for some functional proteins. Therefore, we investigated the protein-protein interaction between rOAT3 and Cav-2 in rat kidney. METHODS: The expressions of rOAT3 and Cav-2 (mRNA and protein) were observed using RT-PCR and Western blot analysis. The localization of rOAT3 and Cav-2 was determined in the caveolae-rich membrane fraction isolated by sucrose gradient ultra-centrifugation. For the direct binding between the rOAT3 and Cav-2 proteins, the immuno-precipitation method and confocal microscopy were employed. In order to perform functional analysis, a Xenopus oocytes expression system with the antisense oligodeoxynucleotides (ODN) technique was used. RESULTS: The expressions of rOAT3 and Cav-2 (mRNA and protein) were detected in the kidney. The caveolae-rich membranous fractions from the kidney contained both rOAT3 and Cav-2 in the same fractions. The immuno-precipitation experiments showed the formation of a complex between the rOAT3 and Cav-2 in the kidney. The confocal microscopic results using primary cultured renal proximal epithelial cells also supported the co-localization of rOAT3 and Cav-2 at the plasma membrane. The uptake function of rOAT3, as tested for by using a Xenopus oocytes expression system was slightly inhibited (with statistical significance) by the Xenopus Cav-2 antisense ODN. CONCLUSION: rOAT3 co-localizes with caveolin-2 in the caveolae, and caveolin-2 plays an important role in regulating the function of rOAT3.
Animals ; Blotting, Western ; Brain ; Caveolae ; Caveolin 2* ; Cell Membrane ; Epithelial Cells ; Kidney* ; Liver ; Membranes ; Microscopy, Confocal ; Oligodeoxyribonucleotides ; Oocytes ; Rats* ; Sucrose ; Xenopus

The mechanism of the loosening after arthroplasty is considered that micromotion makes a gap between implant and bone, the subsidence of implant and osteolysis around the implant. The loosening of femoral component after total knee arthroplasty(TKA) might be related to the improper support of posterior condylar area, the causes of which may be inaccurate osteotomy, improper cementing technique and poor bone quality, etc. The authors found four cases of flexed displacement and osteolysis around the femoral component after TKA. The types of implant were one case of PS type and three cases of High Flex PS type. Revision arthroplasty was done in three patients who had severe clinical symptoms with diffuse bone loss around the distal femur. We evaluated the mechanism of the early loosening by clinical and radiologic assessment of four patients.
Arthroplasty* ; Femur ; Humans ; Knee* ; Osteolysis ; Osteotomy

BACKGROUND/AIMS: Several studies have suggested that surgical resection (SR) can provide a survival benefit over transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) at the intermediate stage according to the Barcelona Clinic Liver Cancer (BCLC) staging system. However, the criteria for SR remain to be determined. This study compared the long-term outcome of intermediate-stage HCC patients treated by either TACE or SR as a primary treatment modality, with the aim of identifying the patient subgroup that gained a survival benefit by either modality. METHODS: In total, 277 BCLC intermediate-stage HCC patients treated by either TACE (N=225) or SR (N=52) were analyzed. RESULTS: The overall median survival time was significantly better for SR than TACE (61 vs. 30 months, P=0.002). Decision-tree analysis divided patients into seven nodes based on tumor size and number, serum alpha-fetoprotein (AFP) level, and Child-Pugh score, and these were then simplified into four subgroups (B1-B4) based on similarities in the overall hazard rate. SR provided a significant survival benefit in subgroup B2, characterized by ‘oligo' (2-4) nodules of intermediate size (5-10 cm) when the AFP levels was <400 ng/ml, or ‘oligo' (2-4) nodules of small to intermediate size (<10 cm) plus a Child-Pugh score of 5 when the AFP level was ≥400 ng/mL (median survival 73 vs. 28 months for SR vs. TACE respectively; P=0.014). The survival rate did not differ significantly between SR and TACE in the other subgroups (B1 and B3). CONCLUSIONS: SR provided a survival benefit over TACE in intermediate-stage HCC, especially for patients meeting certain criteria. Re-establishing the criteria for optimal treatment modalities in this stage of HCC is needed to improve survival rates.
Adult ; Aged ; Carcinoma, Hepatocellular/mortality/pathology/*surgery ; Chemoembolization, Therapeutic ; Female ; Hepatectomy ; Humans ; Liver Neoplasms/mortality/pathology/*surgery ; Male ; Middle Aged ; Neoplasm Staging ; Proportional Hazards Models ; Survival Rate ; Treatment Outcome ; alpha-Fetoproteins/analysis

Immunosuppressive therapy can improve clinical, biochemical and histological features and considerably prolong survival in patients with autoimmune hepatitis. Although ethnicity may affect disease severity and presentation, the long-term outcome of immunosuppression in Korean populations is unknown. This study was aimed to assess the efficacy of immunosuppressive therapy and determine the prognosis of autoimmune hepatitis in Korean populations. We reviewed the medical records of 86 patients diagnosed as having autoimmune hepatitis at the Samsung Medical Center between 1994 and 2008. Seventy-two (83.7%) patients reached remission after a median treatment duration of 3.5 months (range 1 to 44 months). Attempts to withdraw medications were made in 24 cases after the median treatment duration of 36 months (median 6 to 125 months). Thirteen of 24 (54.1%) patients relapsed after treatment withdrawal. Of the 86 patients, 6 (7.2%) experienced disease progression and the overall 5-and 10-yr progression-free survival rates were 91.2% and 85.5%, respectively. In conclusion, immunosuppressive therapy for autoimmune hepatitis results in a favorable rate of remission and excellent progression-free survival, but the relapse rate after treatment withdrawal is high. This suggests that long-term immunosuppressive therapy may be particularly important for treatment of Korean patients.
Adolescent ; Adult ; Aged ; Azathioprine/therapeutic use ; Disease-Free Survival ; Drug Therapy, Combination ; Female ; Hepatitis, Autoimmune/*drug therapy/mortality/pathology ; Humans ; Immunosuppressive Agents/*therapeutic use ; Male ; Middle Aged ; Prednisolone/therapeutic use ; Prognosis ; Recurrence ; Republic of Korea ; Retrospective Studies ; Time Factors ; Treatment Outcome

Purpose: Although surgical resection is usually considered for a single tumor, several reports have suggested that resection can be considered for multiple tumors. The objective of this study was to determine whether resection could provide better long-term outcome for patients with multiple hepatocellular carcinomas (HCCs) within Milan criteria. Methods: A total of 276 patients with multiple HCCs within Milan criteria with liver function preserved who underwent resection, radiofrequency ablation (RFA), or transarterial chemoembolization (TACE) between 2009 and 2013 were analyzed. Propensity-score (PS) matching was conducted. Results: Five-year overall survival (OS) and recurrence-free survival (RFS) were better in the resection group than that in the RFA or TACE group. Patients who underwent resection had more preserved liver function and different tumor characteristics compared to those received RFA or TACE. With similar baseline characteristics generated in the PS model, there was no difference in 5-year OS among 3 groups (79.5% vs. 72.3% or 62.0%, P = 0.232), but the 5-year RFS was better for patients who received resection than those who received RFA or TACE (51.9% vs. 22.0% or 0.0%, P < 0.001). Although the major complication rate was slightly higher than RFA or TACE, there was no significant difference between the 3 groups before and after PS matching. Conclusion Resection was associated with better RFS than RFA or TACE and showed comparable OS in multiple HCC patients within the Milan criteria, but at a cost of slightly increased risk of complication. Resection can be considered as a first-line option if selected appropriately.

Background: To date, there has been no practical guidelines for the prescription of antiepileptic drugs (AEDs) in brain tumor patients in Korea. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for AED usage in brain tumors since 2019. Methods: The Working Group was composed of 27 multidisciplinary medical experts in Korea.References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of the keywords. Results: The core contents are as follows. Prophylactic AED administration is not recommended in newly diagnosed brain tumor patients without previous seizure history. When AEDs are administered during peri/postoperative period, it may be tapered off according to the following recommendations. In seizure-naïve patients with no postoperative seizure, it is recommended to stop or reduce AED 1 week after surgery. In seizure-naïve patients with one early postoperative seizure (<1 week after surgery), it is advisable to maintain AED for at least 3 months before tapering. In seizure-naïve patients with ≥2 postoperative seizures or in patients with preoperative seizure history, it is recommended to maintain AEDs for more than 1 year. The possibility of drug interactions should be considered when selecting AEDs in brain tumor patients. Driving can be allowed in brain tumor patients when proven to be seizure-free for more than 1 year. Conclusion The KSNO suggests prescribing AEDs in patients with brain tumor based on the current guideline. This guideline will contribute to spreading evidence-based prescription of AEDs in brain tumor patients in Korea.

Background: There have been no guidelines for the management of adult patients with diffuse midline glioma (DMG), H3K27M-mutant in Korea since the 2016 revised WHO classification newly defined this disease entity. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for DMG since 2019. Methods: The Working Group was composed of 27 multidisciplinary medical experts in Korea.References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords. As ‘diffuse midline glioma’ was recently defined, and there was no international guideline, trials and guidelines of ‘diffuse intrinsic pontine glioma’ or ‘brain stem glioma’ were thoroughly reviewed first. Results: The core contents are as follows. The DMG can be diagnosed when all of the following three criteria are satisfied: the presence of the H3K27M mutation, midline location, and infiltrating feature. Without identification of H3K27M mutation by diagnostic biopsy, DMG cannot be diagnosed. For the primary treatment, maximal safe resection should be considered for tumors when feasible. Radiotherapy is the primary option for tumors in case the total resection is not possible. A total dose of 54 Gy to 60 Gy with conventional fractionation prescribed at 1-2 cm plus gross tumor volume is recommended. Although no chemotherapy has proven to be effective in DMG, concurrent chemoradiotherapy (± maintenance chemotherapy) with temozolomide following WHO grade IV glioblastoma’s protocol is recommended. Conclusion The detection of H3K27M mutation is the most important diagnostic criteria for DMG. Combination of surgery (if amenable to surgery), radiotherapy, and chemotherapy based on comprehensive multidisciplinary discussion can be considered as the treatment options for DMG.

Background: To date, there has been no practical guidelines for the prescription of antiepileptic drugs (AEDs) in brain tumor patients in Korea. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, had begun preparing guidelines for AED usage in brain tumors since 2019. Methods: The Working Group was composed of 27 multidisciplinary medical experts in Korea.References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of the keywords. Results: The core contents are as follows. Prophylactic AED administration is not recommended in newly diagnosed brain tumor patients without previous seizure history. When AEDs are administered during peri/postoperative period, it may be tapered off according to the following recommendations. In seizure-naïve patients with no postoperative seizure, it is recommended to stop or reduce AED 1 week after surgery. In seizure-naïve patients with one early postoperative seizure (<1 week after surgery), it is advisable to maintain AED for at least 3 months before tapering. In seizure-naïve patients with ≥2 postoperative seizures or in patients with preoperative seizure history, it is recommended to maintain AEDs for more than 1 year. The possibility of drug interactions should be considered when selecting AEDs in brain tumor patients. Driving can be allowed in brain tumor patients when proven to be seizure-free for more than 1 year. Conclusion The KSNO suggests prescribing AEDs in patients with brain tumor based on the current guideline. This guideline will contribute to spreading evidence-based prescription of AEDs in brain tumor patients in Korea.