• Asian Pacific Journal of Cancer Prevention
• /
• 제15권7호
• /
• pp.3057-3063
• /
• 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
• /
• 제77권6호
• /
• pp.258-261
• /
• 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
• /
• 제15권9호
• /
• pp.3927-3932
• /
• 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.

• 한국동물학회지
• /
• 제12권3호
• /
• pp.77-84
• /
• 1969

著者는 白色레그혼의 種卵을 孵化시켜 얻은 鷄胎中 賢과 後賢에 있어서의 alk. p., PAS-陽性物質 및 燐脂質의 消長과 局在位置의 變異를 組織化學的 方法으로 追究하여 다음과 같은 結果를 얻었다. 1. 分泌尿細管의 器官形成에 앞서 未分化 間葉組織內에 强한 alk. p. 活性이 出現하였으며 同活性은 分泌尿細管의 分化와 함께 消失하였다. 2. 中賢 및 後賢 分泌尿細管의 分化와 함께 alk. p. 및 PAS-陽性物質은 分泌尿細管의 刷子綠에 强陽性反應을 보였다. 3. 中賢 및 後賢 分泌尿細管의 細胞質과 刷子綠은 强한 燐脂質 陽性反應을 띠었다. 4. 造賢組織의 分化中 未分化 間葉組織에 alk. p. 活性이 出現하였다가 組織의 分化와 함께 消失된 事實에서 보아 alk. p. 는 組織分化에 關與하는 것으로 생각된다. 5. 中賢 및 後賢 分泌尿細管의 刷子　 에 있어서 alk. p. 와 PAS-陽性物質 및 燐脂質의 變異와 分布狀態가 一致한 것으로 보아 alk. p. 는 炭水化物의 再吸收 및 燐脂質代謝에 關與하는 것으로 思料된다.

• Molecules and Cells
• /
• 제37권3호
• /
• pp.270-274
• /
• 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
• /
• 제18권5호
• /
• pp.488-495
• /
• 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.

• 한국식품영양과학회지
• /
• 제12권2호
• /
• pp.176-187
• /
• 1983

마늘 flavor의 발현과 flavor에 영향을 미치는 요인들에 대하여 살펴보았다. 마늘 flavor는 alk(en)yl-$\small{L}$-cysteine sulfoxide에 alliinase가 작용하여 생성된 alk(en)yl thiosulfinate에 의한 것으로 alk(en)yl기는 주로 allyl기이다. 마늘의 flavor세기는 성숙도 부위, 배양조건, 저장조건, 가공처리법에 따라 달라진다. 마늘의 flavor를 증진시키기 위해서는, 마늘 재배시 토양내 유황의 함량이 많을수록 flavor 전구체의 생성량이 증가하여 flavor 세기가 커졌으므로, 충분한 양의 유황을 공급하되 alliin함량이 최대로 되기 위한 다른 무기질과의 조성비율 중 현재까지 연구된 2종류의 무기질 조성(NS : ${NO_3}^{-2}$, 40%, ${SO_4}^{-2}$, 60%, NP : ${NO_3}^{-2}$, 62%, ${PO_4}^{-3}$, 38%)을 고려하여야 할 것이며, 너무 습하지 않은 토양에서 재배하는것이 바람직하다. 마늘은 성숙함에 따라 인편내 alliin함량도 증가되므로 완전히 성숙한 후에 수확하는 것이 바람직하다. 또한 마늘의 flavor를 유지하기 위해서는 수확후 저장하는 동안에 일어나는 flavor 손실을 최소로 하여야 할 것이다. 자연조건에 저장하는 동안에 일어나는 flavor 손실은 주로 호흡, 발아, 부패에 의한 것이므로 이를 억제하기 위한 저장방법으로 저온 저습저장, 예건처리, gas치환, 발아억제 처리등의 방법이 있으나 현재까지 경제, 실용성등을 고려하여 가장 많이 사용하는 방법은 예건처리후 저온저습조건에 저장하는 방법이다. 가공처리된 마늘은 생마늘에 비하여 flavor가 상당히 많이 감소되는데 건조시켜 분말로 만들 경우, 건조방법에 따라 flavor 감소정도는 크지만 flavor 감소율이 적은 방법 (진공건조, 동결건조)이라도 그 손실률은 거의 50%에 달한다. 그외의 마늘 가공처리품들인 oil이나 extract등도 제조시 기질과 효소가 접촉하는 과정을 거칠 때 flavor의 손실이 크므로 되도록 이면 flavor 손실이 크지 않은 방법으로 제조하는 것이 바람직하다. 마늘 flavor를 합성하는 방법으로는 thiosulfinate 합성에 의한 방법과 alk(en)yl-$\small{L}$-cysteine sulfo-xide-alliinase 분해물에 의한 방법, 그리고 $\small{L}$-5-alk(en)yl thiomethylhydantoin${\pm}$S-oxides에 의한 방법이 있으며 이들 방법에 의해 생마늘과 유사한 flavor를 얻을 수 있어 앞으로 식품첨가물로서 기대되는 바이다.

• Asian-Australasian Journal of Animal Sciences
• /
• 제25권3호
• /
• pp.304-310
• /
• 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.

• 한국해양환경ㆍ에너지학회지
• /
• 제18권1호
• /
• pp.1-8
• /
• 2015

본 연구에서 새롭게 도출된 총알칼리도($Alk_T$)와 총이산화탄소($TCO_2$) 분석방법의 정밀도와 정확도를 확인하기 위해 스크립스 해양 연구소에서 제조된 이산화탄소 표준물질(Batch 132; $Alk_T=2229.24{\pm}0.39{\mu}mol/kg$, $TCO_2=2032.65{\pm}0.45{\mu}mol/kg$)을 분석하였다. 분석 결과, 총알칼리도와 총이산화탄소의 평균 농도는 각각 $2354.09{\mu}mol/kg$과 $2089.60{\mu}mol/kg$으로 제시된 농도 값과 총알칼리도는 약 5.6%, 총이산화탄소는 약 2.3%의 차이를 보였다. 기존의 알칼리도 측정방법(Gran Titration)과 본 연구 분석 방법을 중탄산나트륨($NaHCO_3$) 0.340 g($Alk_T$ $2023.33{\mu}mol/kg$) 용액에 적용하여 비교 실험을 진행한 결과, 기존의 방법으로 측정된 중탄산나트륨의 평균 알칼리도 농도는 $2193.39{\mu}mol/kg$(sd=57.15, n=7)이었고, 본 연구방법의 경우 $2017.02{\mu}mol/kg$(sd=10.98, n=7)의 알칼리도 평균 농도를 보였다. 또한, 초순수와 해수에 중탄산 나트륨을 첨가해 총알칼리도의 수득률(recovery yield)을 측정한 실험에서 초순수에 대한 첨가실험은 다양한 농도 변화 범위($0{\sim}4952.39{\mu}mol/kg$) 내에서 평균 약 100.8%($R^2$=0.999), 해수에 대한 첨가실험은 다양한 농도 변화 범위($0{\sim}2041.32{\mu}mol/kg$)내에서 평균 약 102.3%($R^2$=0.999)로 나타났다. 해수의 이산화탄소 분압($pCO^2$)을 측정하는 Pro Oceanus사의 PSI-Pro$^{TM}$을 사용하여 측정된 이산화탄소 분압과 본 연구를 통해 측정된 $H_2CO_3^*$ 농도와의 비교 실험을 시행한 결과, 약 2주간의 경시변화 실험을 통하여 측정된 이산화탄소 분압은 $427{\sim}705{\mu}atm$의 변화를 보였고, 본 연구방법으로 측정된 $H_2CO_3^*$의 농도는 $9.15{\sim}15.24{\mu}mol/kg$의 변화를 보였다. 측정된 분압과 계산된 $H_2CO_3^*$ 농도의 결정계수($R^2$)는 0.977로 나타났다. 본 연구방법을 적용해 동해 강릉 사천항의 표층 해수 중의 총알칼리도와 총이산화탄소의 일 변화 측정실험 결과, 두 항목의 농도는 일몰 이후 증가하고 일출 이후부터는 감소하는 경향을 보였다. 총이산화탄소와 용존산소의 농도는 상반되는 경향을 나타냈는데 이는 식물플랑크톤의 광합성과 호흡의 영향으로 생각된다. 현장 선상에서 시행된 북동태평양의 클라리온-클리퍼톤 균열대(Clarion-Clipperton Fracture Zone)에서 총알칼리도와 총이산화탄소의 측정실험 결과, 표층(0~60 m)과 저층(200~2000 m)에서 총알칼리도의 평균 농도는 각각 $2422.38{\mu}mol/kg$(sd=78.73, n=20)과 $2465.87{\mu}mol/kg$(sd=57.68, n=103)로 측정되었고, 표층과 저층저층의 총이산화탄소 평균 농도는 각각 $2134.47{\mu}mol/kg$(sd=65.40, n=20)과 $2431.87{\mu}mol/kg$(sd=65.02, n=103)으로 측정되었다. 총알칼리도와 총이산화탄소의 수직 분포는 수심이 증가할수록 점차 농도가 증가하는 경향을 확인할 수 있었으며, 측정된 농도 결과는 부근해역에서의 기존 연구결과보다 약간 높은 경향을 보였다.

• 한국대기환경학회지
• /
• 제27권5호
• /
• pp.580-602
• /
• 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.