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Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKTCL) is a rare type of lymphoma that accounts for only 5%–18% of all cases of non-Hodgkin lymphoma (NHL). In published series, 60%–90% of NK/T-cell lymphomas are localized to the nasal and upper airway. We describe a 55-year man who presented with cough, sputum, dyspnea on exertion, and a chest computed tomography scan shows diffuse ground glass opacities (GGOs), suggestive of an interstitial lung disease. He was treated with a corticosteroid and his symptoms improved. However, when the corticosteroid was tapered, his symptoms recurred. The patient underwent a surgical lung biopsy and ENKTCL was diagnosed. We present this case because ENKTCL involving only the lung is very rare but very informative. To our knowledge, our patient is the first case that primary pulmonary ENKTCL is presented with GGOs., Graphical Abstract

A better understanding of tumor biology is important in the identification of molecules that are downregulated in malignancy and in determining their role in tumor suppression. B-cell translocation gene 1 (BTG1) has been shown to act as a tumor suppressor in several types of human malignancy. In this study, we analyzed BTG1 expression in ovarian carcinoma cell lines, and we investigated the mechanism underlying the observed alterations. The methylation status of the BTG1 promoter region was determined by methylation-specific polymerase chain reaction, and the effect of demethylation on BTG1 expression was analyzed. BTG1 protein expression in ovarian high-grade serous carcinoma tissue samples was evaluated using immunohistochemistry. BTG1 mRNA and protein expression were reduced in ovarian carcinoma cells. In BTG1-silenced ovarian cancer cells, the BTG1 promoter was highly methylated. Treatment with 5-aza-deoxycytidine significantly elevated BTG1 mRNA and protein expression. Immunostaining demonstrated that BTG1 expression was significantly lower in ovarian carcinoma tissue samples than nonpathological ovaries and fallopian tubes. We demonstrated that BTG1 silencing in ovarian carcinoma occurs through epigenetic repression and is involved in the ovarian carcinogenesis. Our data suggest that BTG1 is a potential therapeutic target for patients with ovarian carcinoma.

The aim of the study described here was to compare ultrasound features, pathologic characteristics and prognoses of the follicular variant of papillary thyroid carcinoma (FVPTC) according to cytology results. Eighty-seven FVPTCs were classified according to the first cytology results as the surgery group (n = 66, follicular neoplasm/Hurthle cell neoplasm, suspicious for malignancy and malignancy) and the indeterminate group (n = 21, non-diagnostic and benign), for whom the management was follow-up. The indeterminate group had a longer mean interval to surgery (p = 0.020) and larger tumor size (p = 0.018). More tumors were assessed as probably benign in the indeterminate group than in the surgery group (p

// Gun Yoon 1, * , Chang Won Koh 2, * , Nara Yoon 3 , Ji-Ye Kim 4 , Hyun-Soo Kim 4 1 Shinsegae Women’s Hospital, Daegu, Republic of Korea 2 Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea 3 Department of Pathology, The Catholic University of Korea Incheon St. Mary’s Hospital, Incheon, Republic of Korea 4 Department of Pathology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea * These authors have contributed equally to this work Correspondence to: Hyun-Soo Kim, email: hyunsookim@yuhs.ac Keywords: p16, endometrium, peritumoral stroma, endometrioid carcinoma, serous carcinoma Received: October 07, 2016 Accepted: November 16, 2016 Published: November 25, 2016 ABSTRACT p16 is a negative regulator of cell proliferation and is considered a tumor suppressor protein. Alterations in p16 protein expression are associated with tumor development and progression. However, the p16 expression status in the peritumoral stroma has not been investigated in the endometrium. Therefore, we evaluated stromal p16 expression in different types of endometrial lesions using immunohistochemistry. Differences in the p16 expression status according to the degree of malignancy and histological type were analyzed. This study included 62, 26, and 36 cases of benign, precancerous, and malignant endometrial lesions, respectively. Most benign lesions showed negative or weak expression, whereas precancerous lesions showed a variable degree of staining proportion and intensity. Atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) and serous endometrial intraepithelial carcinoma (SEIC) had significantly higher stromal p16 expression levels than benign lesions. Endometrioid carcinoma (EC), serous carcinoma (SC), and carcinosarcoma showed significantly elevated stromal p16 expression levels compared with benign and precancerous lesions. In addition, there were significant differences in stromal p16 expression between AH/EIN and SEIC and between EC and SC. In contrast, differences in stromal p16 expression among nonpathological endometrium, atrophic endometrium, endometrial polyp, and hyperplasia without atypia were not statistically significant. Our observations suggest that stromal p16 expression is involved in the development and progression of endometrial carcinoma, and raise the possibility that p16 overexpression in the peritumoral stroma is associated with aggressive oncogenic behavior of endometrial SC.

We performed a retrospective analysis of the clinical features and patient outcomes for advanced-stage glassy cell carcinoma of the uterine cervix. The study was restricted to cases in which the glassy cell features constituted at least 95% of the biopsied specimen. During the study period, 675 patients were diagnosed with primary cervical carcinoma. Five (0.7%) of the 675 patients had cervical glassy cell carcinoma; of these, three were premenopausal, and two were postmenopausal. Abnormal vaginal bleeding was the most frequent presenting symptom. Glassy cell carcinoma presented as a fungating, exophytic, or infiltrative mass. The greatest tumor dimension ranged from 3 to 9 cm. All patients had parametrial extension. Four patients had stage IIB tumors, and one had a stage IIIB tumor. All patients received concurrent chemoradiation therapy. The patient with a stage IIIB tumor died of hypovolemic shock caused by upper gastrointestinal bleeding during radiation therapy. Three patients with stage IIB tumors survived for more than 8 years without tumor recurrence or metastasis. One of these three patients died of pelvic recurrence 10 years after the initial diagnosis. Cervical glassy cell carcinoma has traditionally been considered an aggressive, highly malignant tumor with poor prognosis, but our data suggest that patient survival is not significantly decreased compared with other histological types of cervical carcinoma. It will be necessary to analyze patient outcomes using a larger number of cervical glassy cell carcinoma cases to confirm our findings.

Mild mitochondrial stress in POMC neurons promotes thermogenesis in inguinal white adipose tissues and prevents diet-induced obesity. Normal mitochondrial dynamics and functions in hypothalamic neurons are pivotal in the maintenance of systemic energy homeostasis. CRIF1 has been identified as a mito-ribosomal protein which critically mediates incorporation of mitochondrial DNA (mtDNA)-encoded oxidative phosphorylation (OXPHOS) polypeptides into the inner mitochondrial membrane. Complete loss of CRIF1 in neurons causes severe OXPHOS dysfunction and leads to a neuronal death. To study the impact of mitochondrial stress in hypothalamic proopiomelanocortin (POMC) neurons, we generated a mice model lacking CRIF1 expression specifically in the POMC neurons using cre-lox system. Both male and female POMC-cre; CRIF1f/f mice developed obesity since the 10-15 weeks of age due to a gradual loss of POMC neurons. Unexpectedly, energy expenditure and thermogenesis were enhanced in POMC-cre; CRIF1+/f mice compared to their wild littermates. Moreover, they were resistance to diet-induced obesity when exposed to a high fat diet (HFD) before the 10 weeks of age. For the mechanism of enhanced thermogenesis, we found increased UCP1 expression and brown adipocyte-like cells in the inguinal subcutaneous white adipose tissue (ingWAT), so called "browning of subcutaneous fat depot." More strikingly, the expression of mitochondrial unfolded protein response (UPRmt) markers was significantly increased in the ingWAT of POMC-cre; CRIF1+/f mice. These findings strongly suggest that mild mitochondrial stress in POMC neurons causes mitochondrial stress response in the remote organ (ingWAT) via unidentified cell-non-autonomous mechanisms, leading to increased thermogenic activity in this fat depot. Disclosure S. Kim: None. S. Min: None. G. Kang: None. J. Kim: None. J. Choi: None. M. Kim: None. Funding National Research Foundation of Korea (NRF-2013M3C7A1056024)

Constitutive Proopiomelanocortin (POMC)-expressing cells are mainly found in the hypothalamic arcuate nucleus, brainstem solitary tract nucleus, and pituitary gland. The cAMP-dependent protein kinase A (PKA) critically transduces signaling pathways of many important hormones and neurotransmitters including glucagon, GLP-1, α-MSH, dopamine and catecholamine. We generated the mice deleting PKA regulatory subunit R1A (Prkar1a) in POMC-expressing cells to induce constitutive activation of PKA signaling in POMC cells. These mice exhibited interesting phenotypes similar to human Cushing's syndrome; thin skin, hair loss, increased fat mass but reduced muscle and bone mass, female infertility, retarded linear growth, hump and insulin resistance. Moreover, they had increased corticosterone levels both in urine and plasma along with adrenal cortical hypertrophy. Interestingly, despite severe insulin resistance and obesity, plasma glucose concentrations were significantly lower in both fasting and post-glucose loading conditions. These mice showed enhanced insulin-independent glucose disposal. FDG-PET scanning and 2DG uptake tests revealed increased glucose uptake in the brain and the kidney. Normalization of corticosteroid levels by bilateral adrenalectomy and corticosteroid replacement could not normalize blood glucose. Collectively, our hypothesis is that abnormal activation of PKA signaling in pituitary POMC cells causes human Cushing’s syndrome-like phenotype whereas unusual activation of PKA signaling in hypothalamic POMC neurons enhances glucose disposal in the brain and the kidney. Disclosure J. Choi: None. S. Min: None. G. Kang: None. J. Kim: None. M. Kim: None. Funding National Research Foundation of Korea

Research on the relationship between the Child Behavior Checklist (CBCL) and Diagnostic and Statistical Manual for Mental Disorder diagnoses for preschool children is scarce. Cluster analysis can be useful for investigating characteristics of a clinical group by using CBCL subscales and classifying subtypes of a Diagnostic and Statistical Manual for Mental Disorder diagnosis group. This study conducted a cluster analysis of the CBCL 1.5–5 for preschool children diagnosed with a mental disorder. Participants were 333 children (255 males and 78 females) aged 1.5 to 5 years who were diagnosed with a mental disorder. The CBCL 1.5–5 and Bayley Scales of Infant Development II were used as assessment instruments. Three clusters were extracted and then compared with CBCL 1.5–5 profiles of each Diagnostic and Statistical Manual for Mental Disorder-5 subject group to determine their clusters. Cluster 1 was named “intellectual disorder cluster.” Cluster 2 was referred to as “other mental disorders cluster,” and Cluster 3 was called “autism spectrum disorder cluster.” When differences in profiles of behavior problems distinguished by CBCL 1.5–5 scales were examined among different clusters, discriminant validity was found to be high.

Purpose: To evaluate the long-term cure and complication rates of the canal transobturator tape (TOT) procedure for stress urinary incontinence (SUI) in females and assess how to reduce mesh erosion in TOT surgery. Materials and Methods: The canal TOT procedure was developed in 2009 and was effective in mitigating the complications of the original TOT procedure in the short-term follow-up. This study was designed for a long-term follow-up. Between October 2006 and December 2010, 232 consecutive women with stress and mixed urinary incontinence underwent the canal TOT procedure. All patients were followed up by urological examination and self-assessment questionnaires. We performed urodynamic studies in patients with pure SUI symptoms and pelvic examination for all patients 5 years post-surgery. Results: A minimum 5 years follow-up data were available for 144 patients. Complications were evaluated according to the Clavien-Dindo classification. Vaginal mesh erosion was reported in 2 patients (1.4%), and the mesh was surgically removed. No bladder or urethral mesh erosion were observed. The subjective and objective cure rates at 5 years were 77.8 and 94.5% respectively. Conclusions: Canal TOT procedure is an effective minimally invasive procedure with satisfactory results for female SUI in the long term. Compared to the rate of mesh erosion after the original TOT procedure, this technique might be useful in preventing mesh erosion because the mesh is always anatomically well positioned.

This study investigated the distribution of HPV types in Korean women and evaluated the carcinogenic risk of individual HPV types and the potential effects of HPV vaccines. A total of 4,081 HPV-positive samples between 2014 and 2017 were included. The most prevalent genotypes were HPV 16, 58, 68, and 56. Among them, HPV 16 was significantly higher in high-grade squamous intraepithelial neoplasia or worse (HSIL+ ) group. In cytologically evaluating the risk for HSIL+ by individual HPV types, HPV 16 was associated with the highest risk of HSIL+ (OR = 10.82; 95% CI: 7.93–14.77), followed by HPV 33, 31, 52, 18, 58, 51, and 35, in descending order (OR = 3.50 [type 33] to 2.62 [type 35]). Among those types, HPV 16, 18, 31, 33, and 58 were also significantly associated with HSIL+ on histologic evaluation. The analysis of the HPV subgroups covered by the different vaccines revealed that the HPV types covered by the 9-valent vaccine had a high association with HSIL+ (OR = 4.09; 95% CI: 3.02–5.54). Our findings highlight the different carcinogenic risks posed by the high risk HPV genotypes and the positive potential effects of the 9-valent HPV vaccine in reducing HPV-associated cervical cancer in Korea.

Background/aim Previous studies have documented that osteoprotegerin (OPG) is involved in the development and progression of several human malignancies. However, OPG has also been shown to act as a tumor suppressor. The aim of this study was to examine the expression status of OPG in ovarian carcinoma cells and investigate the underlying mechanism responsible for alterations in OPG expression. Materials and methods The expression levels of OPG mRNA and protein were assessed in human ovarian carcinoma cell lines. The methylation status of the OPG promoter region was determined using the bisulfite pyrosequencing technique. The effects of demethylation on OPG expression were also analyzed. Results The human ovarian carcinoma cell lines, SW 626, OVCAR-3, ES-2, TOV-112D, and TOV-21G, expressed significantly lower levels of OPG mRNA and protein than the normal human ovarian epithelial cell line, HS823.Tc. Moreover, three CpG sites in the OPG promoter region were highly methylated in the SW 626, OVCAR-3, ES-2, and TOV-112D ovarian carcinoma cell lines compared to normal control cells. Furthermore, in all the examined ovarian carcinoma cell lines, treatment with the demethylating agent, 5-aza-2-deoxycytidine, resulted in significantly increased expression levels of OPG mRNA and protein compared to the respective pre-treatment levels. Conclusion OPG expression was down-regulated in the studied ovarian carcinoma cells compared to the normal control cells, while demethylation significantly restored OPG expression in the OPG-down-regulated cell lines. Our results suggest that OPG down-regulation in ovarian carcinoma occurs, at least partly, through epigenetic repression, suggesting its involvement in ovarian carcinogenesis.

Purpose The aim of the present study was to develop a serodiagnostic test for differentiation infected from vaccinated animal (DIVA) strategy accompanying the marker vaccine lacking an immunodominant epitope (IDE) of nucleoprotein of Newcastle disease virus (NDV). Materials and methods Recombinant epitope-repeat protein (rERP) gene encoding eight repeats of the IDE sequence (ETQFLDLMRAVANSMR) by tetra-glycine linker was synthesized. Recombinant baculovirus carrying the rERP gene was generated to express the rERP in insect cells. Specificity and sensitivity of an indirect enzyme-linked immunosorbent assay (ELISA) employing the rERP was evaluated. Results The rERP with molecular weight of 20 kDa was successfully expressed by the recombinant baculovirus in an insect-baculovirus system. The rERP was antigenically functional as demonstrated by Western blotting. An indirect ELISA employing the rERP was developed and its specificity and sensitivity was determined. The ELISA test allowed discrimination of NDV infected sera from epitope deletion virus vaccinated sera. Conclusion The preliminary results represent rERP ELISA as a promising DIVA diagnostic tool.

Low-grade mitochondrial stress can promote health and longevity, a phenomenon termed mitohormesis. Here, we demonstrate the opposing metabolic effects of low-level and high-level mitochondrial ribosomal (mitoribosomal) stress in hypothalamic proopiomelanocortin (POMC) neurons. POMC neuron-specific severe mitoribosomal stress due to Crif1 homodeficiency causes obesity in mice. By contrast, mild mitoribosomal stress caused by Crif1 heterodeficiency in POMC neurons leads to high-turnover metabolism and resistance to obesity. These metabolic benefits are mediated by enhanced thermogenesis and mitochondrial unfolded protein responses (UPR(mt)) in distal adipose tissues. In POMC neurons, partial Crif1 deficiency increases the expression of β-endorphin (β-END) and mitochondrial DNA-encoded peptide MOTS-c. Central administration of MOTS-c or β-END recapitulates the adipose phenotype of Crif1 heterodeficient mice, suggesting these factors as potential mediators. Consistently, regular running exercise at moderate intensity stimulates hypothalamic MOTS-c/β-END expression and induces adipose tissue UPR(mt) and thermogenesis. Our findings indicate that POMC neuronal mitohormesis may underlie exercise-induced high-turnover metabolism.

The treatment of gynecomastia depends on multiple factors, and the best modality is controversial. In this study, we aimed to determine the best management approach by comparing outcomes of two groups of patients with gynecomastia who received subcutaneous mastectomy combined with liposuction and liposuction only. We conducted a retrospective analysis of 64 patients who underwent surgery for gynecomastia. We divided the patients into two groups: group A, patients who underwent liposuction only; and group B, patients who underwent liposuction and subcutaneous mastectomy. The serial photographs of all patients were clinically evaluated with respect to size, shape, scarring, and overall outcome by three plastic surgeons, and patient satisfaction was surveyed with regard to palpable lumps, size, shape, scarring, and overall outcome. Of the 64 subjects, 16 received liposuction only, and 48 received the combination procedure. A total of 125 breasts were involved. The doctors’ scores for size and overall outcome were significantly better in the combination group, whereas scarring was better in the liposuction-only group. Similarly, patient satisfaction regarding size was significantly higher in the combination group, and satisfaction regarding scarring was significantly higher in the liposuction-only group. The scores for scarring in the combination treatment group were acceptable. Our study shows that combination treatment with liposuction and subcutaneous mastectomy results in satisfactory outcomes, including the extent of scarring. We conclude that this combination treatment should be recommended as the standard surgical treatment for gynecomastia and can provide excellent results in cases where glandular tissue needs to be removed. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, was first described by Rosai and Dorfman in 1969 [1]. A subtype of this disease shows overlapping features with IgG4-related disease [2]. Soft tissue involvement of RDD is very rare, and there has been no report of RDD associated with acute myeloid leukemia to date. Here, we describe a case of soft tissue RDD (STRDD) with features of IgG4-related disease in a patient with a history of acute myeloid leukemia.

Adult pancreatic hemangioma is a rare disease. We presented a case of a woman with pancreatic tail mass mimicking a distant metastasis from the kidney. A 68-year-old woman was found with a left kidney mass on medical checkup. Computed tomography scan showed a 4.3 cm-sized mass in the left kidney, suggesting renal cell carcinoma (RCC), and a strongly enhancing tiny nodule in the pancreatic tail. We could not rule the possibility of RCC metastasis, hence, surgical resection of the pancreatic mass simultaneously with radical nephrectomy for RCC was conducted. Gross pathologic examination revealed hemangioma. Immunohistochemistry revealed that the tumor was positive for CD34, CD31 and factor VIII-related antigen. There were no significant postoperative events, and the patient was discharged on postoperative day 7 without any complications. Treatment strategies for pancreatic hemangioma have not been established. To our knowledge, this was the first case report of asymptomatic pancreatic hemangioma. In previous literature, treatment differed on a case-by-case basis, ranging from observation to surgical resection. The most important factor in deciding whether to perform surgery is possibly risk-benefit effectiveness; however, tumor location, patient symptoms, and other factors are also important.

Domestic ducks are considered a potential reservoir of Newcastle disease virus. In the study, a Newcastle disease virus (NDV) isolated from a domestic duck during surveillance in South Korea was characterized. The complete genome of the NDV isolate was sequenced, and the phylogenetic relationship to reference strains was studied. Phylogenetic analysis revealed that the strain clustered in genotype I of Class II ND viruses, has highly phylogenetic similarity to NDV strains isolated from waterfowl in China, but was distant from the viruses isolated in chickens and vaccine strains used in South Korea. Pathogenicity experiment in chickens revealed it to be a lentogenic virus. The deduced amino acid sequence of the cleavage site of the fusion (F) protein confirmed that the isolate contained the avirulent motif (112)GKQGRL(117) at the cleavage site and caused no apparent disease in chickens and ducks. With phylogeographic analysis based on fusion gene, we estimate the origin of an ancestral virus of the isolate and its sister strain located in China around 1998. It highlights the need of continuous surveillance to enhance current understanding of the molecular epidemiology and evolution of the pathogenic strains.

Our aim is to explore differences in Hector Battifora mesothelial-1 (HBME-1), cytokeratin-19 (CK19), Galectin-3 (Gal-3), and CD56 expression in infiltrative follicular variants of papillary carcinoma (IFVPTC) and encapsulated follicular variants of papillary carcinoma (EFVPTC) and to provide clues for distinguishing the two subtypes preoperatively. Tissue microarrays from 100 EFVPTC (45 non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) and 55 invasive EFVPTCs), 43 IFVPTCs, and 64 follicular neoplasms (FN) were immunostained with HBME-1, CK19, Gal-3, and CD56. Each case was scored 1 point for every positive result. Immunohistochemical expression was not significantly different in invasive EFVPTC and NIFTP, except for that of HBME-1. HBME-1, CK19, Gal-3, and CD56 expression were significantly higher in IFVPTC than in EFVPTC. At the cutoff of 3 points, the score method had special diagnostic value for differentiating IFVPTC from EFVPTC and FN and for predicting lymph node metastasis. Scoring of immunohistochemistry results may be applied to core biopsy or cell blocks to assist ultrasonographic, cytologic and molecular tests in differentiating IFVPTC and EFVPTC preoperatively, possibly appropriately guiding EFVPTC preoperatively for limited operation or active surveillance.

Backgrounds/Aims Hepatocellular carcinoma (HCC) recurrence remains a great concern following hepatic resection and liver transplantation. We investigated the metformin-induced cytotoxic effects on sorafenib in an in vitro study using HCC cell lines. Methods This research was conducted through an in vitro study using one HepG2.2.15 liver tumor and two patient-derived graft HCC cell lines. Results An in vitro study revealed noticeable cytotoxic effects of metformin as well as noticeable synergistic cytotoxic effects of metformin and sorafenib on cell viability. Assays for the mechanisms of action of antitumor effects revealed that alpha-fetoprotein expression was suppressed by both metformin and sorafenib, but no synergistic effect was observed. LC3-I and LC3-II assays revealed the synergistic upregulation of autophagy and assays for IL-1β, IL-6, p53, and TNF-α revealed the synergistic upregulation of cell damage and apoptosis. In contrast, metformin did not affect HBx expression, thus no noticeable synergistic effect was considered to be present. Conclusions Our in vitro study demonstrated cytotoxic effects of metformin and synergistic antitumor effects of sorafenib. These results should be verified in further clinical studies with patients of advanced HCC.

Objective To investigate the prognostic value of the expressions of programmed cell death ligand 1 (PD-L1) and immune checkpoint markers in residual tumors after neoadjuvant chemotherapy (NAC) for advanced high-grade serous ovarian cancer (HGSOC). Methods We collected pre- and post-NAC tumor samples from patients with advanced HGSOC between 2006 and 2017. Post-NAC tumor tissue samples were available for immunostaining from 131 patients. The expressions of PD-L1 and immune checkpoint markers were assessed by immunohistochemical staining and the status of tumor-infiltrating lymphocytes (TILs) was also evaluated. We examined whether there are significant associations between protein expression status and patient outcomes and whether significant changes in protein expression levels occurred in response to NAC. Results PD-L1 expression in the tumor cells was evaluated in 113 patients, 12 (10.6%) of whom had high PD-L1 expression (≥25%) in post-NAC tissues. However, these high levels were not associated with progression-free survival (PFS; P = 0.348) or overall survival (OS; P = 0.699). Similarly, high stromal TILs [≥50%; n = 16 (15.0%)] among the 107 patients evaluated did not show any significant impact on PFS (P = 0.250) or OS (P = 0.800). Moreover, an abundance of TILs (intraepithelial, CD8+, and Foxp3+) and the expression of immune checkpoint markers (PD-1, ICOS, and LAG-3) in residual tumors did not confer any significant survival benefit. The impact of NAC on PD-L1 expression and stromal TILs varied considerably among individual patients. Conclusion Although the expression of PD-L1 and immune checkpoint markers in residual tumors after NAC had no prognostic impact on survival in patients with HGSOC, post-NAC evaluation of these proteins in chemoresistant tumors may help select patients for immunotherapy trials.

In this study, we fabricated an organic scintillator array sensor (OSAS) based the array of organic scintillators. The scintillator array of OSAS for detecting positions of 192 Ir gamma-ray source was fabricated using four types of organic scintillators, which emit the scintillating lights of different wavelength, respectively. To evaluate the performance of the OSAS, 192 Ir gamma-ray source employed in a HDR brachytherapy was used. In this research, the spectra were measured with positions of 192 Ir gamma-ray source which was moved at intervals of 5 mm and 10 mm using the OSAS. The experimental results show that the proposed OSAS can measure and discriminate the wavelength of scintillating lights generated in the OSAS according to the positions of 192 Ir gamma-ray source. It is expected that the OSAS can used to detect positions of 192 Ir gamma-ray source during a HDR brachytherapy. Further studies are planned to fabricate the OSAS with the different intervals of movements and the small size of organic scintillators.

We modified the nondiagnostic/unsatisfactory category of the Bethesda system for reporting thyroid cytopathology to inform cytopathologic adequacy to better stratify the malignancy risk. Malignancy rates from 1,450 cytopathologic specimens not satisfying adequacy criteria from April 2011 to March 2016 were calculated based on sub-classification of the nondiagnostic/unsatisfactory category and sonographic patterns using matched surgical pathology. Rates were compared with those of 1,446 corresponding adequate specimens from July to December 2013. Upon resection, 63.2% of nondiagnostic, 36.7% of unsatisfactory + benign, 72.5% of unsatisfactory + atypia (follicular lesion) of undetermined significance, 98.1% of unsatisfactory + suspicious for malignancy, and 100.0% of unsatisfactory + malignant cases were confirmed to be malignant on surgical pathology. In nodules with inadequate specimens, those with high suspicion sonographic patterns had a malignancy rate (93.2%) higher than the others (45.5%) (p p = 0.020). For atypia (follicular lesion) of undetermined significance, the malignancy rate of inadequate specimens (72.5%) was higher than that of adequate specimens (51.3%) (p = 0.027). Sparse cellular samples with a few groups of benign follicular cells should not represent a benign lesion. There might be value in qualifying atypia (follicular lesion) of undetermined significance cases less than optimal.

BACKGROUND B-cell translocation gene 1 (BTG1) acts as a tumour suppressor in human malignancies. However, the precise mechanism of BTG1 down-regulation in colorectal carcinoma (CRC) remains unclear. We analyzed BTG1 expression in CRC cell lines and tissues and investigated the mechanism underlying the observed alterations. MATERIALS AND METHODS Real-time polymerase chain reaction (PCR) and western blot analyses were performed to analyze BTG1 expression in CRC cell lines. The methylation status of the BTG1 promoter region in cell lines was determined by methylation-specific PCR, and the effect of demethylation on BTG1 expression was explored with 5-aza-deoxycytidine treatment. BTG1 protein expression in CRC tissue samples was evaluated using immunostaining. RESULTS CRC cell lines and tissue samples expressed lower levels of BTG1 compared to controls, and BTG1 levels were significantly lower in metastatic than primary CRC. In BTG1-down-regulated CRC cell lines, the BTG1 promoter was highly methylated, and 5-aza-deoxycytidine significantly restored BTG1 expression. CONCLUSION BTG1 down-regulation in CRC occurs through epigenetic repression, which is involved in the development and progression of CRC.

368 Copyrightc 2015 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Received: 2014. 10. 15 Revised: 2015. 1. 13 Accepted: 2015. 6. 15

When fabricating a RuO2 electrode, the high electro-catalytic activity in chlorine evolution is considered as one of the most important factors. Thermal decomposition method carried out under various fabrication conditions including the types of solvents, precursors, and calcination times have led to the enhancement electro-catalytic activity of RuO2 electrode in chlorine evolution. Nevertheless, it has not been fully investigated how these parameters directly affect to the chlorine evolution efficiency in the RuO2 electrode. Therefore, the aim of this study was to investigate the effect on the chlorine evolution in RuO2 electrodes, depending upon the preparation parameters including solvents, precursors, and calcination times. As major results, the chlorine evolution efficiency was dominantly affected by these three major preparation parameters. The RuO2 electrode fabricated with ethanol as the solvent showed highest chlorine evolution efficiency. The choice of Ru(AcAc)3 as precursor and the increase of the calcination time up to 3 h are also the good choices for increasing chlorine electrocatalytic activities. The chlorine evolution efficiency was not significantly related to the total voltammetric charge but to the outer voltammetric charge, which is affected by the morphology of the RuO2 electrode surface. The size and number of cracks on the electrode surfaces or the outer voltammetric charges increased with easily evaporated solvents, decomposed precursors, and tensile stress from longer thermal treatments.

We report a case of multiple hemangiomas involving the urinary bladder in a 4-year-old boy who presented with recurrent episodes of gross hematuria. On ultrasonography, compared with the bladder wall, the lesions presented as multiple isoechoic polypoid intraluminal masses with mildly increased vascularity on color Doppler exam. Cavernous hemangioma was confirmed by cold-cup biopsy, and the all lesions were coagulated with a Holmium laser. Despite their rarity, bladder hemangiomas should be included in the differential diagnosis of multiple intravesical masses in children with gross hematuria.

Background All nasal bone fractures have the potential for worsening of olfactory function. However, few studies have studied the olfactory outcomes following reduction of nasal bone fractures. This study evaluates posttraumatic olfactory dysfunction in patients with nasal bone fracture before and after closed reduction. Methods A prospective study was conducted for all patients presenting with nasal bone fracture (n=97). Each patient consenting to the study underwent the Korean version of Sniffin' Sticks test (KVSS II) before operation and at 6 month after closed reduction. The nasal fractures were divided according to the nasal bone fracture classification by Haug and Prather (Types I-IV). The olfactory scores were compared across fracture types and between preoperative and postoperative settings. Results Olfactory dysfunction was frequent after nasal fracture (45/97, 46.4%). Our olfactory assessment using the KVSS II test revealed that fracture reduction was not associated with improvements in the mean test score in Type I or Type II fractures. More specifically, the mean posttraumatic Threshold, discrimination and identification score decreased from 28.8 points prior to operation to 23.1 point at 6 months for Type II fracture with septal fracture. Conclusion Our study has revealed two alarming trends regarding post-nasal fracture olfactory dysfunction. First, our study demonstrated that almost half (46.4%) of nasal fracture patients experience posttraumatic olfactory dysfunction. Second, closed reduction of these fractures does not lead to improvements olfaction at 6 months, which suggest that olfactory dysfunction is probably due to factors other than the fracture itself. The association should be further explored between injuries that lead to nasal fracture and the mechanism behind posttraumatic olfactory dysfunction.

In January 2014, a viral hemagglutinating agent named UPO216 was isolated from fecal droppings of wild birds at the UPO wetland in South Korea during an avian influenza surveillance program. Electron microscopy identified the UPO216 virus as an avian paramyxovirus (APMV). Pathogenicity tests and molecular pathotyping revealed that the virus was avirulent in chickens. The UPO216 virus was assigned to a serological group antigenically distinct from known serotypes of APMV (−1, −2, −3, −4, −6, −7, −8, and −9) by hemagglutination inhibition test, despite showing weak cross-reactivity with APMV-1 and APMV-9. The UPO216 virus RNA genome is 15,180 nucleotides (nts) in length, encodes 3′-N-P(V/W)-M-F-HN-L-5′ in that order, and shows unique genetic characteristics in terms of genomic composition and evolutionary divergence (0.43 or greater from known serotypes of APMV). Phylogenetic analysis revealed that the UPO216 occupies a branch separate from APMV-1, -9, -12, and -13. Serologic surveillance of wild birds (n = 880; 15 species, five Orders) detected UPO216-reactive antibodies in 4% (20/494) of serum samples taken from five species of wild duck belonging to the Order Anseriformes. In particular, UPO216-specific antibodies showing no cross-reaction with other serotypes of APMV were detected in four species: Eurasian teal (1/36), European wigeon (1/73), mallard (4/139), and Spot-Billed duck (1/137). These results indicate that the UPO216 virus has antigenically and genetically unique characteristics distinct from known serotypes of APMV and likely has been circulating widely in wild duck species of the Order Anseriformes. Thus, we propose the UPO216 isolate as a prototype strain of a novel APMV serotype (putative APMV-15).

Metaplastic papillary tumor (MPT) of the fallopian tube is a very uncommon lesion, displaying papillary growth of bland-appearing cells with abundant, eosinophilic cytoplasm and mucinous metaplasia. It is difficult for pathologists to determine whether to categorize this lesion as a metaplastic proliferative lesion or a true neoplasm. We recently experienced a case of tubal MPT and initiated a comprehensive review of previously published cases with thorough analysis of clinicopathological characteristics. MPT is typically related to pregnancy, but we describe the first case of pregnancy-unrelated, incidentally detected tubal MPT in a 51-year-old woman who underwent surgery for endometrial cancer. The MPT consisted of small papillary formations with epithelium consisting of nonciliated, columnar cells with abundant eosinophilic cytoplasm arranged as either a single layer or pseudostratified layer. The stroma had a myxoid appearance. Intraluminal and extracellular mucin and floating papillary tufts were observed. Nuclei of the epithelial lining cells were centrally located, rounded or oval, and displayed intranuclear pseudoinclusions or grooves. The MPT cells were positive for paired box 8, epithelial membrane antigen, and cytokeratin. Interestingly, Wilms tumor 1 (WT1) protein was localized within the cytoplasm of MPT cells. Furthermore, the MPT cells did not express phosphatase and tensin homolog deleted on chromosome 10 (PTEN). In summary, MPT of the fallopian tube is a very unusual, distinctive entity displaying unique histopathological features and immunophenotype. Our observation of cytoplasmic WT1 expression and loss of PTEN expression in tubal MPT suggests its neoplastic nature and raises the possibility of WT1 or PTEN involvement in the development of MPT.

Mitotically-active cellular fibroma (MACF) is a rare form of ovarian fibromatous tumor. Although it is generally acknowledged to have indolent biological behavior, its rarity and overlapping histopathological features with more common and aggressive entities make MACF prone to misdiagnosis and overtreatment. The clinicopathological characteristics of ovarian MACF have not been clearly established. Our 10-year review of cellular fibromatous tumors of the ovary diagnosed at a single institution revealed four cases of cellular fibroma (CF) and three cases of MACF. The mean age of patients with MACF was 46 years (range=20-71 years). Patients presented with symptoms related to pelvic masses, such as abdominal pain and discomfort and flank pain. Serum levels of cancer antigen 125 was increased in two patients with MACF. All cases of MACF were a single unilateral tumor. Magnetic resonance imaging revealed solid or mixed solid and cystic ovarian masses with diameters of 7.3-14.9 cm. The radiological impressions included benign stromal tumor, benign epithelial tumor, and borderline epithelial tumor. Grossly, MACFs exhibited yellow-to-tan fleshy cut surfaces, without necrosis or hemorrhage. Extensive hyaline degeneration, resulting in a fibrotic cut surface, was observed in one case. Histologically, MACF displayed frequent mitotic figures, as well as increased cellularity and mild cytological atypia. The mean mitotic count was 8.7 per 10 high-power fields. MACF is a newly-recognized subtype of ovarian cellular fibromatous tumor. Pathologists and clinicians should be aware of this rare entity to prevent misdiagnosis of MACF as fibrosarcoma or adult granulosa cell tumor and resultant overtreatment.

Clinical Study for the One Case that Diagnosed Polycystic Ovarian DiseaseJi-Ye Kim, So-Young JungInae Korean Medicine ClinicObjectives: The aim of this study is to report the effect of oriental trea tments for polycystic ovarian disease patient with amenorrhoea. Methods: A 27 years old women, who diagnosed polycystic ovarian disease , was enrolled in this study. She received oriental treatment suc h as herbal medicine, acupuncture for 8 months. And we proceeded to checkup female ho rmone regularly, such as Estrogen, LH, FSH, Prolactin. We observed the menstruat ion period and figure out LH/FSH ratio. Results: Polycystic ovarian disease patient restart cyclic menstruation . LH/FSH ratio of polycystic ovarian dise ase patient was decreased to normal level. Conclusions: In polycystic ovarian disease patient with amenorrhoea in this case, oriental herbal medicine and acupuncture treatment make c yclic menstruation and restore LH/FSH ratio to normal level. Key Words: Polycystic Ovarian Disease, LH/FSH Ratio, Herbal Medicine, Acupuncture

Triacylglycerol (TG) is the major form of stored energy in eukaryotic organisms and is synthesized by diacylglycerol acyltransferase (DGAT) in the endoplasmic reticulum (ER). DGAT2, one of the two DGAT enzymes, is barely detectable in cells, even though its mRNA transcripts are maintained at considerable levels. However, little is known about how DGAT2 expression is altered by protein stability. DGAT2 was highly unstable in cells and was rapidly degraded by proteasomes in an ubiquitin-dependent manner. Deletion mutation analysis identified transmembrane domain 1 (TMD1) as a protein degradation signal. TMD1 is also important for ER localization of DGAT2. Moreover, DGAT2 interacted with p97/VCP, a crucial component of the ER-associated degradation (ERAD) pathway, and polyubiquitinated DGAT2 accumulated following treatment with an ERAD inhibitor. Furthermore, gp78, an E3 ligase involved in ERAD, regulates the degradation of DGAT2 through direct interactions and ubiquitination. Consequently, the stabilization of DGAT2 increased the number of lipid droplets in hepatic cells. Therefore, DGAT2 is regulated by gp78-associated ERAD at the post-translational level.

To the Editor: Highly pathogenic avian influenza (HPAI) viruses have caused considerable economic losses to the poultry industry and poses potential threats to animal and human health (www.oie.int/en/ and www.who.int/en/). Since 2003, influenza A(H5N1) viruses with a hemagglutinin (HA) gene derived from A/goose/Guandong/1/96–like viruses have become endemic to 6 countries (Bangladesh, China, Egypt, India, Indonesia, and Vietnam) (1) (www.cdc.gov/). Furthermore, HPAI viruses with an H5 subtype continue to undergo substantial evolution because of extensive genetic divergence and reassortment between other subtypes of influenza viruses. Especially in China, novel subtypes of H5 HPAI virus, such as influenza A(H5N2), influenza A(H5N5), and influenza A(H5N8) viruses, were reported during 2009–2011 (2,3).

This study investigated the relationship between steroid hormone receptor signaling and cellular metabolism in tumorigenesis by examining the expression of metabolic proteins with respect to androgen receptor (AR) and human epidermal growth factor receptor-2 (HER-2) status in estrogen receptor-negative (ER−) breast cancer. ER− breast cancer cases (n = 334) were selected from a microarray analysis, including those that were AR+ and AR− (n = 127 and 207, respectively) and HER-2+ and HER-2− (n = 140 and 194, respectively). The expression of proteins involved in glycolysis, glutaminolysis, and mitochondrial and intermediary (i.e., serine/glycine) metabolism was determined by immunohistochemistry and correlated with AR and HER-2 status. The expression of several proteins involved in glycolysis, glutaminolysis, and serine/glycine metabolism was higher (p

Avian paramyxovirus 2 (APMV-2) infections are associated with respiratory diseases in poultry worldwide. The hemagglutination inhibition (HI) test is a useful tool for surveillance and monitoring of this virus. In this study, full-length hemagglutinin (HN) gene of APMV-2 was chemically synthesized based on its published sequence, cloned and expressed in Spodoptera frugiperda insect cells using recombinant baculoviruses. The biological, antigenic and immunogenic properties of the expressed protein were evaluated to assess its ability to produce diagnostic reagents for HI testing. Recombinant APMV-2 HN protein showed two distinct bands with molecular masses of 64 and 75kDa, which showed hemagglutination (HA) and neuraminidase activities, respectively. The recombinant HN (rHN) protein extracted from infected cells produced high HA titers (2(13) per 25μL). HA activity of the protein was inhibited by APMV-2 antiserum, although there were weak cross reactions with other APMV serotype antisera. The rHN protein induced high titers of APMV-2-specific antibodies in immunized chickens based on the HI test. These results indicated that recombinant APMV-2 HN protein is a useful alternative to the APMV-2 antigen in HI assays.

Objective: The purpose of the current study is to understand the clinicopathological implications of redox proteins in association with androgen receptor (AR) and HER-2 status in estrogen receptor (ER)-negative breast cancers through evaluation of the expression patterns of redox proteins, such as catalase, thioredoxin reductase (TxNR), glutathione S-transferase π (GSTπ), thioredoxin interacting protein (TxNIP), and manganese superoxide dismutase (MnSOD). Methods: Two hundred cases of ER-negative breast cancer samples were collected as a tissue microarray. Immunohistochemical staining was done for redox-related proteins, after which the resulting data set was organized by AR and HER-2 status. Results: The redox proteins that had a significant association with AR and HER-2 status were tumoral catalase (p < 0.001) and stromal GSTπ (p < 0.001). Tumoral catalase was least expressed in the AR-/HER-2- group, while stromal GSTπ was least expressed in both the AR+/HER-2- and the AR-/HER-2- groups. Stromal GSTπ was highly expressed in HER-2 positive groups (p < 0.001). Stromal GSTπ negativity and tumoral MnSOD positivity were associated with a shorter disease-free survival (p = 0.041 and p = 0.007, respectively) in univariate analysis. Conclusion: ER-negative breast cancers showed different expressions of redox-related proteins according to AR and HER-2 status. Catalase expression was high in AR-negative groups, while stromal GSTπ expression was high in HER-2-positive groups.

Background: To evaluate the feasibility of conization without a prior punch biopsy for patients with abnormal cytology. Methods: A retrospective review was performed for 700 patients who underwent conization at a single institution from January 2003 to August 2012. Each of these patients was assigned to one of two groups, either the ‘see-and-treat' group or the ‘three-step' group, depending on whether the patient had undergone a punch biopsy before conization or not. The final histologic results of two groups were compared. Results: The overtreatment risk was higher in the ‘see-and-treat' group in patients with atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (ASCUS/LSIL) cytology (64.7% in the ‘see-and-treat' group vs. 36.5% in the ‘three-step' group; p = 0.001). There was no significant statistical difference in the rate of cervical dysplasia or invasive carcinoma in patients with high-grade squamous intraepithelial lesion (HSIL) cytology between groups (91.8% in the ‘see-and-treat' group vs. 93.5% in the ‘three-step' group; p = 0.793). Conclusion: The patients with HSIL on cytology can be managed by a ‘see-and-treat' strategy with a low risk of overtreatment. On the other hand, the ‘three-step' management is more appropriate in patients with ASCUS/LSIL cytology.

Cancers cells have the ability to develop chemotherapy resistance, which is a persistent problem during cancer treatment. Chemotherapy resistance develops through different molecular mechanisms, which lead to modification of the cancer cells signals needed for cellular proliferation or for stimulating an immune response. The endoplasmic reticulum (ER) is an important organelle involved in protein quality control, by promoting the correct folding of protein and ER-mediated degradation of unfolded or misfolded protein, namely, ER-associated degradation. Disturbances of the normal ER functions causes an accumulation of unfolded or misfolded proteins in the ER lumen, resulting in a condition called “ER stress (ERS).” ERS triggers the unfolded protein response (UPR)—also called the ERS response (ERSR)—to restore homeostasis or activate cell death. Although the ERSR is one emerging potential target for chemotherapeutics to treat cancer, it is also critical for chemotherapeutics resistance, as well. However, the detailed molecular mechanism of the relationship between the ERSR and tumor survival or drug resistance remains to be fully understood. In this review, we aim to describe the most vital molecular mechanism of the relationship between the ERSR and chemotherapy resistance. Moreover, the review also discusses the molecular mechanism of ER stress-mediated apoptosis on cancer treatments.

Newcastle disease virus (NDV) causes significant economic losses to the poultry industry in Southeast Asia. In the present study, 12 field isolates of NDV were recovered from dead village chickens in Vietnam between 2007 and 2012, and were characterized. All the field isolates were classified as velogenic. Based on the sequence analysis of the F variable region, two distinct genetic groups (Vietnam genetic groups G1 and G2) were recognized. Phylogenetic analysis revealed that all the 12 field isolates fell into the class II genotype VII cluster. Ten of the field isolates, classified as Vietnam genetic group G1, were closely related to VIIh viruses that had been isolated from Indonesia, Malaysia, and Cambodia since the mid-2000s, while the other two field isolates, of Vietnam genetic group G2, clustered with VIId viruses, which were predominantly circulating in China and Far East Asia. Our results indicate that genotype VII viruses, especially VIIh viruses, are predominantly responsible for the recent epizootic of the disease in Vietnam.

From the avian influenza virus (AIV) outbreaks and market surveillances in Vietnam during November 2011 and March 2012, a total of 196 AIV were isolated. Although H5N1 highly pathogenic avian influenza (HPAI) was the most prevalent subtype in Vietnam, 57 low pathogenic avian influenza (LPAI) viruses were identified from mainly domestic ducks and some chickens. Of note, various subtypes of LPAI viruses were isolated from domestic ducks in Vietnam: H3 (n = 16), H4 (n = 4), H6 (n = 24), H7 (n = 1), and H9 (n = 10). Geographically, the LPAI viruses were identified in different regions of Vietnam. Phylogenetic analysis of HA and NA genes in LPAIV in Vietnam showed that some H3 (group I) and H4 subtypes AIV clustered with the viruses of several Asian isolates from domestic poultry and wild birds. However, the H6, H9, and some H3 (group II and III) subtypes AIV were closely related to isolates from domestic poultry in Southern China. In addition, whereas the N2 and N6 subtypes AIV belonged to the Eurasian lineage, the N8 subtype AIV was classified to be both of Eurasian and American lineage. These findings revealed that the regional trade and wild birds play a key role transmission of LPAIV in domestic ducks in Vietnam. Further surveillance at the intercountry level is needed to understand the epidemiology of these viruses and to cope with emergence of novel AIV types.

Newcastle disease virus (NDV) isolation was attempted from La Sota-vaccinated or unvaccinated chickens exposed to the virulent NDV variant E347Kmt. Shedding viruses were purified by plaque assay and then were sequenced for HN and F genes. The amino acid sequences of the F gene of all shedding viruses were identical to the sequence of the challenge virus. However, amino acid substitution occurred at four positions (70, 347, 466, and 517) in the HN protein among shedding viruses from vaccinated and challenged chickens but not from unvaccinated and challenged chickens. Amino acid substitution occurred more frequently at position 347 (K to G or V) in the HN protein compared with the other positions. There was minor antigenic variation between some of mutant viruses shed and challenge virus. However, none of mutant viruses had a significantly lower antigenic R value with La Sota virus compared with challenge virus E347Kmt. Our findings indicate that vaccinal immunity might facilitate an evolutional event through antigenic selection, genetic mutation among virulent virus populations shed from vaccinated flocks, or both.

CO 2 separation from N 2 over 3-aminopropyltrimethoxysilane-grafted mesoporous SAPO-34, which had been synthesized using an amphiphilic organosilane additive was investigated. The presence of mesopores with a mean pore diameter of ∼3.3 nm was confirmed by the characteristic small angle X-ray diffraction peak at ca. 1.3°, transmission electron microscopy, and N 2 adsorption isotherm. The CO 2 adsorption isotherms of the SAPO-34 samples were obtained at 273, 298 and 303 K, and the heat of adsorption was estimated using the Clausius–Clapeyron equation. The amine-functionalized mesoporous SAPO-34 showed a significantly improved CO 2 /N 2 selectivity of 177 and a sharp breakthrough in the fixed bed adsorption. CO 2 adsorption–desorption of the sample was stable and reproducible during five cyclic runs.

ObjectivesThis study was designed to determine the prognostic value of multidetector coronary computed tomography angiography (CTA) in relation to exercise electrocardiography (XECG) findings.BackgroundThe prognostic usefulness of coronary CTA findings of coronary artery disease in relation to XECG findings has not been explored systematically.MethodsPatients with suspected coronary artery disease who had undergone both coronary CTA and XECG (