• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3057-3063
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• 2014

Background: Anaplastic lymphoma kinase (ALK) gene rearrangement in non-small cell lung cancer (NSCLC) has been intensively studied. The gold standard for ALK detection is FISH, but this is not routinely conducted in clinical practice, so that the IHC method has a role. The aim of this study was to identify the incidence of ALK rearrangement and risk or prognostic factors for ALK positivity using both of IHC and FISH methods. Materials and Methods: From January 2008 to December 2012, 267 completely resected NSCLC patients in Chiang Mai University Hospital were enrolled in this study. Clinical and pathological variables and outcomes of treatment were retrospectively reviewed. IHC and FISH were used to evaluate ALK rearrangement. Sensitivity and specificity of IHC were analyzed. Multivariable analysis was used to identify clinico-pathological correlations with positive results of IHC and clinical outcomes. Results: Twenty-two (8.2%) of 267 specimens were IHC-positive for ALK with intense cytoplasmic staining, whereas only 10 (3.8%) were FISH-positive. Sensitivity, specificity and the positive likelihood ratio with IHC were 80.0%, 94.9%, and 15.8 respectively. Age less than 55 years (RR 4.4, 95%CI 1.78-10.73, p value=0.001) and presence of visceral pleural invasion (VPI) (RR 2.9, 95%CI 1.21-6.78, p value =0.017) were identified as risk factors for ALK rearrangement with FISH. There were no statistically significant differences in other clinical and pathological variables. ALK rearrangement was not a prognostic factor for tumor recurrence or overall survival. Conclusions: The incidences of ALK positivity in completely resected NSCLCs in northern Thailand were 8.2% by IHC and 3.8% by FISH. IHC with mouse monoclonal, Ventana D5F3 antibody can be used as a screening tool before FISH method because of high specificity and high positive likelihood ratio. Age less than 55 years and VPI are risk factors for ALK positivity.

• Tuberculosis and Respiratory Diseases
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• v.77 no.6
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• pp.258-261
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• 2014

Anaplastic lymphoma kinase (ALK) rearrangement, is a kind of driver mutation, accounts for 3%-5% of non-small cell lung cancer (NSCLC). NSCLC patients harboring ALK fusion genes have distinct clinical features and good response to ALK inhibitors. Metastasis from lung cancer to the ovary has rarely been known. We report a case of a 54-year-old woman with bilateral ovarian metastases from ALK rearranged NSCLC. She underwent bilateral salpingo-oophorectomy for ovary masses, which were progressed after cytotoxic chemotherapy although primary lung mass was decreased. Histopathological examination of the ovary tumor showed characteristic adenocarcinoma patterns of the lung and ALK rearrangement.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.3927-3932
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• 2014

Background: Epidermal growth factor receptor (EGFR) mutations and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) define specific molecular subsets of lung adenocarcinomas with distinct clinical features. Our purpose was to analyze clinical features and prognostic value of EGFR gene mutations and the EML4-ALK fusion gene in lung adenocarcinoma. Patients and Methods: EGFR gene mutations and the EML4-ALK fusion gene were detected in 92 lung adenocarcinoma patients in China. Tumor marker levels before first treatment were measured by electrochemiluminescence immunoassay. Results: EGFR mutations were found in 40.2% (37/92) of lung adenocarcinoma patients, being identified at high frequencies in never-smokers (48.3% vs. 26.5% in smokers; P=0.040) and in patients with abnormal serum carcinoembryonic antigen (CEA) levels before the initial treatment (58.3% vs. 28.6%, P=0.004). Multivariate analysis revealed that a higher serum CEA level before the initial treatment was independently associated with EGFR gene mutations (95%CI: 1.476~11.343, P=0.007). We also identified 8 patients who harbored the EML4-ALK fusion gene (8.7%, 8/92). In concordance with previous reports, younger age was a clinical feature for these (P=0.008). Seven of the positive cases were never smokers, and no coexistence with EGFR mutation was discovered. In addition, the frequency of the EML4-ALK fusion gene among patients with a serum CEA concentration below 5ng/ml seemed to be higher than patients with a concentration over 5ng/ml (P=0.021). No significant difference was observed for time to progression and overall survival between EML4-ALK-positive group and EML4-ALK-negative group or between patients with and without an EGFR mutation. Conclusions: The serum CEA level before the initial treatment may be helpful in screening population for EGFR mutations or EML4-ALK fusion gene presence in lung adenocarcinoma patients.

• The Korean Journal of Zoology
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• v.12 no.3
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• pp.77-84
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• 1969

For the purpose of making clear the activity of the alkaline phosphatase to the morphogenesis and function of the various structures of the developing chick kidney in relation to PAS-positive materials and phospholipid, the author observed histochemically the aforementioned enzyme and other substances. The mesonephros and metanephros of 4-20 day white leghorn embryos were used, obtaining the following results. 1. Before definite appearance of the secretory tubules the alkaline phosphatase activity showed strongly in the undifferentiated mesenchymal tissue. As the tubules grew differentiated, the alkaline phosphatase activity was found to have disappeared in the mesenchymal tissue surrounding the tubules. The above mentioned fact indicates that the alkaline phosphatase may be concerned with morphogenesis of the developing chick kindney. 2. The fact that the strong alkaline phosphatase activity and the occurrence of the PAS-positive materials were observed at the luminal borders of differentiated secretory tubules of mesonephros and metanephros, indicates that alkaline phosphatase may be concerned with reabsorption of carbohydrate at the borders. 3. A strong positive reaction of phospholipid was found in the cytoplasm and brush borders of the mesonephric and metanephric tubules. The fact that vicissitude of alkaline phosphatase was found to coincide with that of phospholipid suggests that the enzyme may have influence on the metabolism of the phospholipid.

• Molecules and Cells
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• v.37 no.3
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• pp.270-274
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• 2014

Lymphatic vessels are essential to regulate interstitial fluid homeostasis and diverse immune responses. A number of crucial factors, such as VEGFC, SOX18, PROX1, FOX2C, and GJC2, have been implicated in differentiation and/or maintenance of lymphatic endothelial cells (LECs). In humans, dysregulation of these genes is known to cause lymphedema, a debilitating condition which adversely impacts the quality of life of affected individuals. However, there are no currently available pharmacological treatments for lymphedema, necessitating identification of additional factors modulating lymphatic development and function which can be targeted for therapy. In this report, we investigate the function of genes associated with Bone Morphogenetic Protein (BMP) signaling in lymphatic development using zebrafish embryos. The knock-down of BMP type II receptors, Bmpr2a and Bmpr2b, and type I receptors, Alk3 and Alk3b, as well as SMAD5, an essential cellular mediator of BMP signaling, led to distinct lymphatic defects in developing zebrafish. Therefore, it appears that each constituent of the BMP signaling pathway may have a unique function during lymphatic development. Taken together, our data demonstrate that BMP signaling is essential for normal lymphatic vessel development in zebrafish.

• Bulletin of the Korean Chemical Society
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• v.18 no.5
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• pp.488-495
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• 1997

The stability of bridgehead olefins containing 8 and 10 membered rings has been investigated by the MMX molecular mechanics calculation together with the GMMX conformational searching program. A number of 'hyperstable' bridgehead olefins, which have negative olefin strain values, have been found from the calculated values of strain energy and olefin strain for the series of in- and out-bicyclo[n.3.3]alk-1-ene and in- and out-bicyclo[n.4.4]alk-1-ene (n=1 to 8). For the bridgehead olefins with 'out' topology, hyperstable olefins were found in the systems having cyclononene or larger rings. For the bridgehead olefins with 'in' topology, hyperstable olefins were found in the systems having cyclodecene or larger rings.

• Journal of the Korean Society of Food Science and Nutrition
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• v.12 no.2
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• pp.176-187
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• 1983

Volatile flavor components of garlic and factors which influence on its flavors were reviewed. Growth, storage and processing conditions influence on the flavor intensity of garlic. To intensify garlic flavors, it is desirable that sufficient sulfate nutrition be supplied to the soil of growing garlic and that the suggested proportions of mineral composition and water content be considered. And to maintain the flavor intensity of post harvested garlic, flavor losses taken place during over inter storage mainly due to respiration, sprout and decay, have to be minimized. Among the various storage methods, combination method of post harvest hot-air drying and low temperature ($0^{\circ}C$), low humidity (RH 70-75%) is useful. The flavor of processed garlic is very much decreased as compared with that of fresh, and the decreasing rate of flavors depends on processing method. The synthetic garlic flavors were obtained by three types based on intermediate thiosulfinate, S-alk(en) yl-$\small{L}$-cyteine sulfoxlde-alliinase fission products and $\small{L}$-5-alk (en)yl thiomethylhydantoin ${\pm}$ S-oxides. These synthetic garlic flavors may be promised to be applied to food additives.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.3
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• pp.304-310
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• 2012

The present study showed that Transforming growth factor beta 1 (TGF-${\beta}_1$) can induce apoptosis of bovine mammary epithelial cells. This apoptosis was also observed with phosphorylation of Smad2/3 within 0.5-2 h. Afterwards the signal transferred into the nucleus. Moreover, intracellular free $Ca^{2+}$ concentration was significantly elevated as well as Caspase-3 activated and DNA lysised, thereby inducing the programmed cell death. This signaling pathway of TGF-${\beta}_1$ was blocked by SB-431542 ($10^{-2}{\mu}M$) via inhibiting ALK-5 kinase activity, which thus reversed the anti-proliferation and apoptosis effect of TGF-${\beta}_1$ in mammary epithelial cells. These results indicated that TGF-${\beta}_1$ induced apoptosis of bovine mammary epithelial cells through the ALK-5-Smad2/3 pathway, which plays an important role in inhibiting survival of mammary epithelial cells. Moreover, intracellular $Ca^{2+}$ also played a critical role in TGF-${\beta}_1$-induced cell apoptosis.

• Journal of the Korean Society for Marine Environment & Energy
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• v.18 no.1
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• pp.1-8
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• 2015

To evaluate accuracy and precision of determination of total alkalinity ($Alk_T$) and carbon dioxide ($TCO_2$) derived from present study, experiment was applied with $CO_2$ CRM (Batch 132, Scripps Institution of Oceanography; $Alk_T=2229.24{\pm}0.39{\mu}mol/kg$, $TCO_2=2032.65{\pm}0.45{\mu}mol/kg$). As the result, average concentration of $Alk_T$ and $TCO_2$ was $2354.09{\mu}mol/kg$ (~5.6% difference with $CO_2$ CRM) and $2089.60{\mu}mol/kg$ (~2.3% difference with $CO_2$ CRM), respectively. For previous method (Gran Titration) by addition $NaHCO_3$ to deionized water($Alk_T$ $2023.33{\mu}mol/kg$), average concentration was $2193.39{\mu}mol/kg$ (sd=57.15, n=7). Whereas, average concentration was $2017.02{\mu}mol/kg$ (sd=10.98, n=7) for the present study. Recovery yield experiments of total alkalinity in deionized water and seawater were implemented by addition of $NaHCO_3$. The recovery yield of deionized water in the range 0 to $4952.39{\mu}mol/kg$ was 100.8% ($R^2$=0.999), and seawater in the range 0 to $2041.32{\mu}mol/kg$ was 102.3% ($R^2$=0.999). Comparison of $pCO_2$ sensor (PSI $CO_2-Pro^{TM}$) with present method showed very meaningful correlation coefficient ($R^2$=0.977) in the range of 427 to $705{\mu}atm$ and 9.16 to $15.24{\mu}mol/kg$ throught elapsed time for two weeks. Field experiment of diurnal variation of total carbon dioxide was accomplished at Sachon harbor in the coastal waters of East Sea of Korea. Concentration of $Alk_T$ and $TCO_2$ was increased during night, and decreased during daylight hours. The results showed mirror type between $TCO_2$ and dissolved oxygen, which was attributable to photosynthesis and respiration of phytoplankton. Also, open ocean field study was performed to obtain vertical profile of $Alk_T$ and $TCO_2$ in C-C zone (Clarion-Clipperton Fracture Zone), Northeastern Pacific. Average concentrations of $Alk_T$ in the surface mixed layer (0~60 m) and deeper layer below 200 m were $2422.38{\mu}mol/kg$ (sd=78.73, n=20) and $2465.87{\mu}mol/kg$ (sd=57.68, n=103), respectively. And average concentrations of $TCO_2$ were $2134.47{\mu}mol/kg$ (sd=65.4, n=20) and $2431.87{\mu}mol/kg$ (sd=65.02, n=103) in the same depth ranges such as $Alk_T$. Vertical distributions of $Alk_T$ and $TCO_2$ concentrations tended to increase with depth, and analyzed concentrations showed slightly higher than those of previous studies in this area.

• Journal of Korean Society for Atmospheric Environment
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• v.27 no.5
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• pp.580-602
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• 2011

Volatile organic compound (VOC) emissions in the 2007 CAPSS (Clean Air Protection Supporting System) emissions inventory are chemically speciated for the SAPRC99 (Statewide Air Pollution Research Center 99) mechanism, following the Source Classification Code (SCC) matching method to borrow the U.S.EPA's chemical speciation profiles. CMAQ simulations with High-order Direct Decoupled Method (HDDM) are in turn applied to evaluate uncertainty in the method by comparing the simulated model VOC species to the observations in the Seoul Metropolitan Area (SMA) for a 2007 June episode. Simulations under-predicted ALK1 to ALK4 in SAPRC99 by a factor of 2 to 5 and over-predicted ALK5 by a factor of 7.5 while ARO1, ARO2, OLE1, and ethylene (ETH) are comparable to the observations, showing relative difference by 10 to 30%. OLE2 emissions are roughly 4 times overestimated. Emission rates for individual VOC model species are revised referring to the ratio of simulated to observed concentrations. Impact of the VOC emission changes on the overall ozone prediction was insignificant for the days of which 1-hr maximum ozone are lower than 100 ppb. However, simulations showed ozone difference by 5 to 10 ppb when high ozone above 120 ppb was observed in the vicinity of Seoul. This result suggests that evaluations on individual model VOC emissions be necessary to lead ozone control plans to the right direction. Moreover, the simulated ratios of ARO1 and ARO2 to $NO_x$ are roughly 50% lower than the observed ones, which imply that adjustment in $NO_x$ and VOC emission rates may be required to mimic the real VOC/$NO_x$ condition over the area.