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The spectrum of vascular tumors ranges from hemangioma (HEM), to epithelioid hemangioendothelioma (EHE) and to angiosarcoma (AS). To the best of our knowledge, the usefulness of F‑18 fluorodeoxyglucose positron emission tomography (FDG‑PET) for vascular tumors has never been comprehensively studied. The present study investigated the usefulness of FDG‑PET for pathologically diagnosed vascular tumors. The present study included 26 patients with vascular tumor (male:female, 17:9; age, 60.9±14.4 years; 7 HEM, 6 EHE and 13 AS) who underwent FDG‑PET between January 2007 and May 2014 at the Seoul National University Bundang Hospital (Seongnam, Korea) and Konkuk University Medical Center, (Seoul, Korea). Representative FDG uptake was measured as the maximum standardized uptake value (SUVmax) over the lesion with the highest FDG uptake. Disease progression was clinically defined as the aggravation of known lesions or novel lesion development during follow‑up on computed tomography, magnetic resonance imaging, or FDG‑PET. FDG‑PET revealed multi‑organ involvement only in AS (6/13 [46.2%]), whereas HEM and EHE involved a single organ. Tumor SUVmax was significantly greater in AS (6.32±4.84) compared with EHE (3.10±2.68) and HEM (2.33±0.76) (P=0.0284). There was no difference in tumor SUVmax between HEM and EHE (P>0.05). Disease progression was primarily noticed in AS (9/13 [69.2%]). Only 1 patient with EHE (1/6=16.7%) and no patients with HEM (0/7=0%) experienced disease progression. Mortality was reported only in patients with AS (4/13 [30.8%]). Using the cutoff SUVmax of 3.0, the two‑year progression‑free survival rate of 14 patients with tumor SUVmax <3.0 (75.0%) was significantly higher compared with that of 12 patients with tumor SUVmax ≥3.0 (0%) (P=0.0053). In conclusion, FDG‑PET is useful for the differential diagnosis and prognosis prediction of vascular tumors. [ABSTRACT FROM AUTHOR]

The stability of baselines produced by Cheongyang (CYG) observatory from the period of 2014 to 2016 is analysed. Step heights of higher than 5 nT were found in H and Z components in 2014 and 2015 due to magnetic noise in the absolute-measurement hut. In addition, a periodic modulation behaviour observed in the H and Z baseline curves was related to annual temperature variation of about 20 °C in the fluxgate magnetometer hut. Improvement in data quality was evidenced by a small dispersion between successive measurements from June 2015 to the end of 2016. Moreover, the baseline was also improved by correcting the discontinuity in the H and Z baselines. [ABSTRACT FROM AUTHOR]

Tumor angiogenesis is one of the major hallmarks of tumor progression. Nobiletin is a natural flavonoid isolated from citrus peel that has anti-angiogenic activity. Steroid receptor coactivator (Src) is an intracellular tyrosine kinase so that focal adhesion kinase (FAK) binds to Src to play a role in tumor angiogenesis. Signal transducer and activator of transcription 3 (STAT3) is a marker for tumor angiogenesis which interacts with Src. Paxillin (PXN) acts as a downstream target for both FAK and STAT3. The main goal of this study was to assess inhibition of tumor angiogenesis by nobiletin in estrogen receptor positive (ER+) breast cancer cells via Src, FAK, and STAT3-mediated signaling through PXN. Treatment with nobiletin in MCF-7 and T47D breast cancer cells inhibited angiogenesis markers, based on western blotting and RT-PCR. Validation of in vitro angiogenesis in the human umbilical vein endothelial cells (HUVEC) endothelial cell line proved the anti-angiogenic activity of nobiletin. Electrophoretic mobility shift assay and the ChIP assay showed that nobiletin inhibits STAT3/DNA binding activity and STAT3 binding to a novel binding site of the PXN gene promoter. We also investigated the migration and invasive ability of nobiletin in ER+ cells. Nobiletin inhibited tumor angiogenesis by regulating Src, FAK, and STAT3 signaling through PXN in ER+ breast cancer cells. [ABSTRACT FROM AUTHOR]

Molecular markers are helpful diagnostic tools, particularly for cytologically indeterminate thyroid nodules. Preoperative RET/PTC1 rearrangement analysis in BRAF and RAS wild-type indeterminate thyroid nodules would permit the formulation of an unambiguous surgical plan. Cycle threshold values according to the cell count for detection of the RET/PTC1 rearrangement by real-time reverse transcription-polymerase chain reaction (RT-PCR) using fresh and routine air-dried TPC1 cells were evaluated. The correlation of RET/PTC1 rearrangement between fine-needle aspiration (FNA) and paired formalin-fixed paraffin-embedded (FFPE) specimens was analyzed. RET/PTC1 rearrangements of 76 resected BRAF and RAS wild-type classical PTCs were also analyzed. Results of RT-PCR and the Nanostring were compared. When 100 fresh and air-dried TPC1 cells were used, expression of RET/PTC1 rearrangement was detectable after 35 and 33 PCR cycles, respectively. The results of RET/PTC1 rearrangement in 10 FNA and paired FFPE papillary thyroid carcinoma (PTC) specimens showed complete correlation. Twenty-nine (38.2%) of 76 BRAF and RAS wild-type classical PTCs had RET/PTC1 rearrangement. Comparison of RET/PTC1 rearrangement analysis between RT-PCR and the Nanostring showed moderate agreement with a κ value of 0.56 (p = 0.002). The RET/PTC1 rearrangement analysis by RT-PCR using routine air-dried FNA specimen was confirmed to be technically applicable. A significant proportion (38.2%) of the BRAF and RAS wild-type PTCs harbored RET/PTC1 rearrangements. [ABSTRACT FROM AUTHOR]

A subpopulation of breast cancer cells with cluster of differentiation (CD)44-positive and CD24-negative expression has been reported to have stem cell properties and to have a higher tumorigenic capacity than other cells. However, the clinicopathological characteristics of this subpopulation are not fully understood. In this study, we aimed to identify the correlations between the expression of CD44 and CD24 and clinicopathological parameters and overall survival. We studied specimens from 262 patients with invasive breast cancer. Immunohistochemical staining for CD44 and CD24 was performed using tissue microarrays. The clinicopathological factors were evaluated from the patients' medical records. In correlation analysis, CD44 expression was significantly associated with human epidermal growth factor receptor 2 (HER2)-negative status (P<0.001). Conversely, CD24 expression was significantly associated with HER2-positive status (P<0.001). CD44 and CD24 expression did not demonstrate any correlation with the age, tumor size, axillary lymph node metastasis status, tumor stage, histological grade, estrogen receptor status and progesterone receptor status of patients. Upon survival analysis, there was no statistical difference in overall survival according to the expression of CD44 and CD24. The results from this study suggest that CD44 and CD24 are clinically significant markers associated with breast tumorigenesis, but not sufficient factors in determining the prognosis of invasive breast cancer. [ABSTRACT FROM AUTHOR]

Pediatric mesenteric panniculitis is an extremely rare disease of unknown etiology characterized by chronic inflammation, fat necrosis, and fibrosis in the mesenteric adipose tissue. A previously healthy 13-year-old boy was admitted because of right upper abdominal pain. An abdominal computed tomography scan revealed increased attenuation and enhancement in the left upper abdominal omental fat and anterior peritoneal wall thickening. A laparoscopic biopsy showed mesenteric panniculitis with chronic inflammation, adiponecrosis, and septal fibrosis. Serological tests for autoimmune diseases, nested polymerase chain reaction for Mycobacterium tuberculosis, and special immunohistochemical stains for malignancy were all negative. Symptomatic improvement and improved abnormal findings were achieved after an 8-month treatment with prednisolone according to a follow-up abdominal computed tomography scan. Here, we report a case of pediatric mesenteric panniculitis treated with prednisolone. [ABSTRACT FROM AUTHOR]

Background: The importance of sensitive methods for the detection of epidermal growth factor receptor (EGFR) mutation is emphasized. The aim of this study is to perform comparative and concordance analyses of direct sequencing, pyrosequencing and peptide nucleic acid (PNA) clamping for detecting EGFR gene mutations using archived tissue and cytology specimens. Methods: Samples from a total of 112 cases, which were diagnosed with adenocarcinoma of the lung at nine hospitals in Korea were collected. Using the above three methods, the concordance rates of EGFR mutations in exons 18, 19, 20 and 21 were analysed and validated in comparative tissue and cytology specimens. Results: Comparison of EGFR mutation detection between the tissue and cytology had a high concordance rate. The diagnostic performance of pyrosequencing and PNA clamping in tissue was higher than that of direct sequencing as well as cytology. Additionally, among some of the patients who had EGFR wild type by single method, EGFR mutations were detected by other methods. Cytology specimens had a diagnostic performance for the detection of EGFR mutations. Conclusions: Cytology specimens had a diagnostic performance for the detection of EGFR mutations that was comparable to that of tissues. For detecting EGFR mutations, pyrosequencing or PNA clamping was more sensitive than direct sequencing. In EGFR mutation negative patients who are difficult to obtain tissue, repeating test using pyrosequencing or PNA clamping is recommended to improve the detection rate of EGFR mutation than only one, especially in cytology. [ABSTRACT FROM AUTHOR]

Background: Combination therapy, which reduces the dosage intensity of the individual drugs while increasing their efficacy, is not a novel approach for the treatment of cancer. Methylsulfonylmethane (MSM) is an organic sulfur compound shown to act against tumor cells. Tamoxifen is a commercially available therapeutic agent for breast malignancies. Methods: In the current study, we analyzed the combinatorial effect of MSM and tamoxifen on the suppression of ER-positive breast cancer xenograft growth and metastasis. Additionally, we also validated the molecular targets by which the drug combination regulated tumor growth and metastasis. Results: We observed that the combination of MSM and tamoxifen regulated cell viability and migration in vitro. The intragastric administration of MSM and subcutaneous implantation of tamoxifen tablets led to tumor growth suppression and inhibition of the Janus kinase 2 (Jak2)/signal transducer and activator of transcription 5b (STAT5b) pathway. Our study also assessed the regulation of signaling molecules implicated in the growth, progression, differentiation, and migration of cancer cells, such as Jak2, STAT5b, insulin-like growth factor-1Rß, and their phosphorylation status. Conclusions: Study results indicated that this combination therapy inhibited tumor growth and metastasis. Therefore, this drug combination may have a synergistic and powerful anticancer effect against breast cancer. [ABSTRACT FROM AUTHOR]

Background: Combination therapy, which reduces the dosage intensity of the individual drugs while increasing their efficacy, is not a novel approach for the treatment of cancer. Methylsulfonylmethane (MSM) is an organic sulfur compound shown to act against tumor cells. Tamoxifen is a commercially available therapeutic agent for breast malignancies. Methods: In the current study, we analyzed the combinatorial effect of MSM and tamoxifen on the suppression of ER-positive breast cancer xenograft growth and metastasis. Additionally, we also validated the molecular targets by which the drug combination regulated tumor growth and metastasis. Results: We observed that the combination of MSM and tamoxifen regulated cell viability and migration in vitro. The intragastric administration of MSM and subcutaneous implantation of tamoxifen tablets led to tumor growth suppression and inhibition of the Janus kinase 2 (Jak2)/signal transducer and activator of transcription 5b (STAT5b) pathway. Our study also assessed the regulation of signaling molecules implicated in the growth, progression, differentiation, and migration of cancer cells, such as Jak2, STAT5b, insulin-like growth factor-1Rβ, and their phosphorylation status. Conclusions: Study results indicated that this combination therapy inhibited tumor growth and metastasis. Therefore, this drug combination may have a synergistic and powerful anticancer effect against breast cancer. [ABSTRACT FROM AUTHOR]

We report on a case of malignant pleural effusion as initial metastatic presentation of occult gastric cardia cancer in a young woman. To the best of our knowledge, this is the first report of gastric adenocarcinoma metastasized to pleura as an initial presentation. Location of cardia and signet ring cell histology may contribute to the manifestation. Utilization of positron emission tomography-computed tomography was helpful for proper diagnosis. For patients with such distinct clinical presentations, it would be appropriate to consider gastric cancer as one of the possible primary sites. [ABSTRACT FROM AUTHOR]

Background: Previously, cutaneous lymphomas were classified according to either the European Organization for the Research and Treatment of Cancer (EORTC) or the World Health Organization (WHO) classification paradigms. The aim of this study was to determine the relative frequency of Korean cutaneous lymphoma according to the new WHO-EORTC classification system. Methods: A total of 517 patients were recruited during a recent 5 year-period (2006-2010) from 21 institutes and classified according to the WHO-EORTC criteria. Results: The patients included 298 males and 219 females, and the mean age at diagnosis was 49 years. The lesions preferentially affected the trunk area (40.2%). The most frequent subtypes in order of decreasing prevalence were mycosis fungoides (22.2%), peripheral T-cell lymphoma (17.2%), CD30+ T-cell lymphoproliferative disorder (13.7%), and extranodal natural killer/T (NK/T) cell lymphoma, nasal type (12.0%). Diffuse large B-cell lymphoma accounted for 11.2% of cases, half of which were secondary cutaneous involvement; other types of B-cell lymphoma accounted for less than 1% of cases. Conclusions: In comparison with data from Western countries, this study revealed relatively lower rates of mycosis fungoides and B-cell lymphoma in Korean patients, as well as higher rates of subcutaneous panniculitis-like T-cell lymphoma and NK/T cell lymphoma. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 56-year-old female showing neuroendocrine dysplasia combined in a tubular adenoma in the rectum with no history of inflammatory bowel disease. Her colonoscopic examination shows a large circumferential mass at the rectum and that her gross examination identified a slightly elevated circumferential mass in the rectum extending to the submucosa. The article discusses the importance of recognizing neuroendocrine dysplasia in the large intestine.

Rhabdoid colorectal carcinomas are very rare and only 10 cases have been previously reported. We report two cases of rhabdoid colorectal carcinoma, one arising in the sigmoid colon of a 62-year-old man and another in the rectum of an 83-year-old woman. In both cases, the patients had advanced tumors with lymph node metastases. The tumors mostly showed a diffuse arrangement with rhabdoid features and small glandular regions were combined. Transitional areas from the adenocarcinomas to the rhabdoid tumors were also noted. Adenocarcinoma cells were positive for mixed cytokeratin (CK), CK20 and epithelial membranous antigen (EMA), but focal positive for vimentin. The rhabdoid tumor cells were positive for mixed CK, but focal positive or negative for CK20 and EMA. In addition, they were diffusely positive for vimentin, but negative for desmin. The histological and immunohistologial findings of these two cases suggest that the rhabodid tumor cells originated from dedifferentiated adenocarcinomas. [ABSTRACT FROM AUTHOR]

Background: ERG, a member of the ETS family of transcription factors, is a highly specific endothelial marker. We investigated whether the use of ERG immunostaining can help pathologists detect lymphovascular invasion (LVI) and decrease interobserver variability in LVI diagnosis. Methods: Fifteen cases of surgically resected colorectal cancers with hepatic metastasis were selected and the most representative sections for LVI detection were immunostained with ERG, CD31, and D2-40. Eight pathologists independently evaluated LVI status on hematoxylin and eosin (H&E) and the corresponding immunostained sections and then convened for a consensus meeting. The results were analyzed by kappa (κ) statistics. Results: The average rate of LVI positivity was observed in 43% with H&E only, 10% with CD31, 29% with D2-40, and 16% with ERG. Agreement among pathologists was fair for H&E only (κ=0.27), D2-40 (κ=0.21), ERG (κ=0.23), and was moderate for CD31 (κ=0.55). Consensus revealed that ERG nuclear immunoreactivity showed better visual contrast of LVI detection than the other staining, with improved agreement and LVI detection rate (κ=0.65, LVI positivity rate 80%). Conclusions: The present study demonstrated a superiority with ERG immunostaining and indicated that ERG is a promising panendothelial marker that might help pathologists increase LVI detection and decrease interobserver variability in LVI diagnosis. [ABSTRACT FROM AUTHOR]

Multifocal papillary thyroid carcinoma (mPTC) comprises about 20-30% of PTC. In mPTC, individual tumor foci can be identical or frequently composed of different histological types including follicular, solid, tall-cell or conventional patterns. We report a case of mPTC consisting of one encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) and three conventional PTCs in a 44-year-old woman. This case genetically demonstrates unique features including the simultaneous presence of the BRAF V600E (T1799A) mutation and the BRAF K601E (A1801G) mutation in conventional PTC and FVPTC, respectively. [ABSTRACT FROM AUTHOR]

Background: Simian virus 40 (SV40), a polyomavirus, was discovered as a contaminant of a human polio vaccine in the 1960s. It is known that malignant mesothelioma (MM) is associated with SV40, and that the virus works as a cofactor to the carcinogenetic effects of asbestos. However, the reports about the correlation between SV40 and MM have not been consistent. The purpose of this study is to identify SV40 in MM tissue in Korea through detection of SV40 protein and DNA. Methods: We analyzed 62 cases of available paraffin-blocks enrolled through the Korean Malignant Mesothelioma Surveillance System and performed immunohistochemistry for SV40 protein and real-time polymerase chain reaction (PCR) for SV40 DNA. Results: Of 62 total cases, 40 had disease involving the pleura (64.5%), and 29 (46.8%) were found to be of the epithelioid subtype. Immunostaining demonstrated that all examined tissues were negative for SV40 protein. Sufficient DNA was extracted for real-time PCR analysis from 36 cases. Quantitative PCR of these samples showed no increase in SV40 transcript compared to the negative controls. Conclusions: SV40 is not associated with the development of MM in Korea. [ABSTRACT FROM AUTHOR]

Mutations of the epidermal growth factor receptor (EGFR) are the strongest predictive factor for response to EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. EGFR TKIs are approved in Korea as a first-line treatment for lung cancer patients with mutated EGFR. Rapid and accurate EGFR mutation testing is essential for patient selection and establishing targeted therapies with EGFR TKIs. Thus, a standard set of guideline recommendations for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of guideline recommendations for EGFR mutation testing that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists. [ABSTRACT FROM AUTHOR]

DNA extraction from microdissected cells has become essential for handling clinical specimens with advances in molecular pathology. Conventional methods have limitations for extracting amplifiable DNA from specimens containing a small number of cells. We developed an ammonium sulfate DNA extraction method (A) and compared it with two other methods (B and C). DNA quality and quantity, β-globin amplification, and detectability of two cancer associated gene mutations were evaluated. Method A showed the best DNA yield, particularly when the cell number was very low. Amplification of the β-globin gene using DNA from the SNU 790 cell line and papillary thyroid carcinoma (PTC) cells extracted with Method A demonstrated the strongest band. BRAFV600E mutation analysis using ethanol-fixed PTC cells from a patient demonstrated both a "T" peak increase and an adjacent "A" peak decrease when 25 and 50 cells were extracted, whereas mutant peaks were too low to be analyzed using the other two methods. EGFR mutation analysis using formalin-fixed paraffin-embedded lung cancer tissues demonstrated a mutant peak with Method A, whereas the mutant peak was undetectable with Methods B or C. Method A yielded the best DNA quantity and quality with outstanding efficiency, particularly when paucicellular specimens were used. [ABSTRACT FROM AUTHOR]

Purpose: Given the emerging evidence for differential responses to new targeted therapies and the identification of molecular differences between specific subtypes of non-small cell lung carcinoma (NSCLC), there is an increased need for greater accuracy in subtyping NSCLC. In a substantial proportion of cases, standard morphology cannot specifically subtype the tumor, resulting in a final diagnosis of NSCLC-not otherwise specified. In this study, we added newly proposed markers (napsin A, desmocollin-3) to conventional markers (p63, thyroid transcription factor-1 [TTF-1], cytokeratin 5/6 [CK5/6], high molecular weight cytokeratin [HMWCK], cytokeratin 7 [CK7]) and evaluated for the minimal panel of immunohistochemical markers required for subtyping poorly differentiated (PD) NSCLC. Materials and Methods: Resection specimens of 110 adenocarcinomas (ADCs) and 171 squamous cell carcinomas (SCCs) were collected and tissue microarrays were constructed to simulate small biopsy conditions. All specimens were stained with TTF-1, napsin A, CK7, p63, CK5/6, HMWCK, desmocollin-3 and mucicarmine. Results: For 32 PD ADC, a combination of TTF-1 and napsin A increased sensitivity (81%). With regard to the 29 PD SCC, a combination of desmocollin-3 and p63 did not substantially increase diagnostic performance. Logistic regression analysis identified napsin A, p63 and TTF-1 as the optimal panel to separate PD ADC and PD SCC. Mucin stains for PD NSCLC increased accuracy rate (88%) for diagnosis of PD ADC. Conclusion: We recommend a minimal panel of immunohistochemical and histochemical markers to include TTF-1, p63, napsin A and one of mucin stains for tumor subtyping of PD NSCLC in a small biopsy sample. (J Lung Cancer 2012;11(1):21-- 32) [ABSTRACT FROM AUTHOR]

We report the synthesis of the antiferromagnetic (AFM) FePt3nanoparticles (NPs) from a bimetallic precursor [(CO)3Fe(µ-dppm)(µ-CO)PtCl2] and the study of their magnetic behaviors with annealing temperature. As-synthesized FePt3NPs having a sharp edge shape with an average side length of 2.7 nm adopt a cubic L12cell with a= 3.898 (space group: Pm-3m) and are chemically ordered, undergoing AFM transition near 200 K. Magnetization data for the NPs annealed at 600 °C indicate evolution of the ferromagnetic (FM) phase within the AFM matrix. When the sample is annealed at 900 °C, FM impurity is almost completely suppressed and AFM order develops near 127 K, which is in good agreement with that of the bulk FePt3alloys. [ABSTRACT FROM AUTHOR]

A perfusion system is described for the production of a human monoclonal antibody in non-secreting murine myeloma (NS0) cells that was previously shown to be difficult to produce at high levels using fed-batch culture. The perfusion system was based on the use of a commercially available cell settler as the separation device to separate the cells from the culture. Separation efficiency of the cell settler was above 98%. Based on the growth and glucose consumption rates, fresh media was added to the culture and the turnover rate for the bioreactor was set at a maximum of 1.5 times the bioreactor volume per day. The perfusion process resulted in twice the maximum viable cell densities and up to three times the total protein production in a 53-day run period when compared to the fed-batch process. In addition, charge heterogeneity of the antibody as measured by ion exchange chromatography was lower for material purified from the perfusion runs compared to fed-batch. Perfusion mode of culture using a commercially available gravity settler is therefore a viable alternative to fed-batch mode for high-level production of this monoclonal antibody in NS0 cells. [ABSTRACT FROM AUTHOR]

The carbon and nitrogen source requirements of Aspergillus fumigatus NRRL 2436 for growth and production of the angiogenesis inhibitor fumagillin were studied in chemically defined media. Both carbon and nitrogen sources strongly influenced fumagillin formation. Two out of 29 carbon sources tested interfered with fumagillin biosynthesis. The best combination of two carbon sources was 30 g L-1 xylan and 50 g L-1 mannose. Of fifteen nitrogen sources tested, three ammonium salts (chloride, sulfate, and dibasic phosphate) failed to support fumagillin formation, presumably due to the low pH which developed. The dosage-response study of the best nitrogen source, L-glutamic acid, revealed that 9 g L-1 was optimal. Volumetric production of fumagillin was increased by 15-fold over that in the starting (Peterson-Goldstein) medium as a result of these findings. Correspondence to: A.L. Demain; email: ademain@drew.edu --> [ABSTRACT FROM AUTHOR]

This paper describes a 2-terminal-pair impedance bridge, measuring the capacitance ratio in the high frequency range up to 1 MHz. The bridge was configured with two voltage sources and a phase control unit which enabled the bridge balance by synchronizing the voltage sources with an enhanced phase resolution. Without employing the transformers such as inductive voltage divider, injection and detection transformers, etc, the bridge system is quite simple to set up, and the balance procedure is quick and easy. Using this dual-source coaxial bridge, the 1:1 and 10:1 capacitance ratios were measured with 1 pF–1 nF capacitors in the frequency range from 1 kHz to 1 MHz. The measurement values obtained by the dual-source bridge were then compared with reference values measured using a commercial precision capacitance bridge of AH2700A, the Z-matrix method developed by ourselves, and the 4-terminal-pair coaxial bridge by the Czech Metrological Institute. All the measurements agreed within the reference uncertainty range of an order of 10−6–10−5, proving the bridge ability as a trustworthy tool for measuring the capacitance ratio in the high frequency range. [ABSTRACT FROM AUTHOR]