• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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• pp.4797-4800
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• 2015

Background: This analysis was conducted to evaluate the efficacy and safety of crizotinib based regimens in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer. Materials and Methods: Clinical studies evaluating the efficacy and safety of crizotinib based regimens on response and safety for Chinese patients with EML4-ALK positive non-small-cell lung cancer were identified by using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: In crizotinib based regimens, 3 clinical studies which including 128 Chinese patients with EML4-ALK positive non-small-cell lung cancer and treated with crizotinib based regimen were considered eligible for inclusion. Pooled analysis suggested that, in all patients, the pooled RR was 59.3% (76/128) in crizotinib based regimens. ALT/AST mild visual disturbances, nausea, and vomiting were the main side effects. No treatment related death occurred in these crizotinib based treatments. Conclusions: This pooled analysis suggests that crizotinib based regimens are associated with good response rate and accepted toxicities in treating Chinese patients with EML4-ALK positive non-small-cell lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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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.

• IMMUNE NETWORK
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• 제11권4호
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• pp.196-202
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• 2011

Background: B cell-activating factor belonging to the TNF family (BAFF) is primarily expressed by macrophages and dendritic cells, and stimulates B cell proliferation, differentiation, survival, and Ig production. In the present study, we explored the effect of activin A on BAFF expression by APCs. Methods: To investigate the effect of activin A on BAFF expression by mouse APCs, we measured the level of BAFF expression at the transcriptional and protein levels using RT-PCR and ELISA. Results: Activin A markedly enhanced BAFF expression in mouse macrophages and dendritic cells at both the transcriptional and protein levels. SB431542, an activin receptor-like kinase 4 (ALK4) inhibitor, completely abrogated activin A-induced BAFF transcription. Furthermore, overexpression of DN-Smad3 abolished activin-induced BAFF expression at the transcriptional and protein levels. Conclusion: These results demonstrate that activin A can enhance BAFF expression through ALK4-Smad3 pathway.

• 사물인터넷융복합논문지
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• 제4권2호
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• pp.21-28
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• 2018

본 연구에서는 ALK receptor tyrosine kinase (ALK) 유전자의 단일염기다형성이 뇌출혈의 발병에 관여하는 지를 연구하였다. 156명의 뇌출혈 환자와 425명의 정상인를 모집하였으며 네 개의 단일염기다형성에 대하여 상관성을 살펴보았다. 통계분석에서는 SNPstats, SPSS22.0, Haploview 프로그램을 활용하였다. Odd ratio, 95% 신뢰구간에서는 genotype 모델 및 allele 모델에서 계산하였다. 통계분석결과, rs1881421, rs1881420, rs3795850, rs2246745 의 단일염기다형성이 뇌출혈과 관련하여 유의성을 보였다. (rs1881421, OR=2.02, 95% CI=1.54-2.64, p<0.001; rs1881420, OR=0.53, 95% CI=1.16-2.01, p=0.003; rs3795850, OR=1.54, 95% CI=1.17-2.02, p=0.002; rs2246745, OR=1.95, 95% CI=1.46-2.60, p<0.001 in each allele analysis). CC, GT, and GC haplotypes 빈도 역시 유의성을 보였다. 네 개의 단일염기다형성의 minor allele 가 뇌출혈의 발병을 증가시키는데 기여하였다. 이러한 연구 결과는 ALK 유전자가 뇌출혈의 위험성과 관련 있음을 시사한다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권7호
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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.

• 한국동물학회지
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• 제12권3호
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• pp.77-84
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• 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.

• The Korean Journal of Physiology and Pharmacology
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• 제1권4호
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• pp.345-353
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• 1997

The effects of crude saponin (SAP) and alkaloid (ALK) fractions of Panax ginseng C.A. Meyer on the detrimental effects of electroconvulsive shock (ECS) and scopolamine on passive avoidance response (PAR) were studied in male Sprague-Dawley rats, referring their effects on the neuronal injury and plasticity of hippocampus in response to electrolytic lesion of left entorhinal cortex (ECL). The detrimental ECS effect on PAR was attenuated by pre- and post-treatments with SAP and ALK, respectively, or by pretreatment with aminoguanidine (AG), an inhibitor of diamine oxidase and NO synthase. And the detrimental scopolamine effect on PAR was also inhibited by pre-treatment with ALK or AG, and by post- treatment with SAP or ALK, respectively. On the 7th day after ECL, the brain sections stained by cresyl violet and by acetylcholinesterase (AChE) histochemistry, respectively, showed the chromatolysis and numeral decrease of neurons and the reduction of AChE reactivity in the hippocampus CA1 area and to a lesser extent, in the dentate gyrus. The neuronal cell death of the CA1 area was significantly reduced by SAP, ALK, or AG, and the reduction of AChE reactivity was significantly attenuated by SAP or ALK and to a lesser extent by AG. These results suggests that the protective effect of ginseng SAP and ALK fractions on ECS- or scopolamine-induced impairment of PAR may be ascribed in part to preservation of hippocampal neurons, particularly cholinergic neurons.

• Applied Biological Chemistry
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• 제34권4호
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• pp.318-326
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• 1991

사염화탄소(carbon tetrachloride, 이하 $CCl_4$라함)에 의한 간 중독시 flavonoids가 미치는 영향을 보기 위하여 $CCl_4$를 투여한 뒤 rutin, hesperidin을 주사하여 경시적으로 간 microsome과 혈청중 total cholesterol, transaminase(GOT, GPT) 및 alkaline phosphatase(Alk. P) 활성도를 측정 비교하여 다음과 같은 결론을 얻었다. (1) 간장중 total cholesterol 함량은 rutin과 hesperidin 1회 투여후 1일에 대조군과 비교할 때 감소하다가 2일에 45%까지 증가되었으나 4일 후에는 정상으로 완전히 회복 되었다. 이와 같은 현상은 혈청중 cholesterol 함량에도 직접적으로 영향을 주어 시간이 경과함에 따라 어느정도 저하됨을 알 수 있었지만 혈청중에서 positive한 결과를 얻기는 어려웠다. (2) 간의 microsome 분획의 Alk. P 활성도는 대조군의 활성치에 비하여 2일에 급격히 증가를 보인 후 4일만에 대조군보다 낮은 활성을 보이다가 6일까지 완만하게 증가하였다. 그러나 본 연구에서 Alk. P 활성도는 $CCl_4$ 투여군과 비교할 때 flavonoids 투여후 별다른 변동은 없었다. 그러나 혈청중 Alk. P 활성도는 hesperidin 투여로 인하여 저하 효과를 나타냈다. (3) GPT 활성도를 측정한 결과 간의 microsome 분획에서는 hesperidin 2회 투여에서, 그리고 혈청중 GPT 활성은 rutin과 hesperidin 두군 모두에서 아주 낮은 활성을 보여 flavonoids가 $CCl_4$ 투여로 인한 간독성을 해독하는 작용이 있음을 보여 주었다. (4) $CCl_4$독성을 일으킨 흰쥐의 간 microsome내 GOT 활성은 rutin 투여로 인하여 불규칙한 변동을 보여 rutin이 GOT활성에 별다른 영향을 미치지 않는 것으로 나타났다. 또한 hesperidin 투여군에서는 증감의 변동없이 대조군치와 거의 비슷한 수준을 유지하였지만 $CCl_4$ 투여군과 비교할 때 낮은 활성을 보였다. 혈청중에서 GOT 활성은 flavonoids 1회 투여군에서는 4일만에, 2회 투여군에서는 6일만에 서서히 영향을 미침을 알 수 있었다. 이상과 같이 $CCl_4$에 의하여 상승되는 total cholesterol, GPT, GOT, Alk. P의 활성도는 flavonoids중 rutin과 hesperidin 성분이 감소시키는 작용이 있는 것으로 보이며, 특히 hesperidin 성분은 $CCl_4$ 중독을 억제 또는 방어하고 치료에 효과가 있는 것으로 본다.

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

• Mycobiology
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• 제44권4호
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• pp.260-268
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• 2016

Regulation of alkaline-resistant laccase from Perenniporia tephropora KU-Alk4 was proved to be controlled by several factors. One important factor was the initial pH, which drove the fungus to produce different kinds of ligninolytic enzymes. P. tephropora KU-Alk4 could grow at pH 4.5, 7.0, and 8.0. The fungus produced laccase and MnP at pH 7.0, but only laccase at pH 8.0. The specific activity of laccase in the pH 8.0 culture was higher than that in the pH 7.0 culture. At pH 8.0, glucose was the best carbon source for laccase production but growth was better with lactose. Low concentrations of glucose at 0.1% to 1.0% enhanced laccase production, while concentrations over 1% gave contradictory results. Veratryl alcohol induced the production of laccase. A trace concentration of copper ions was required for laccase production. Biomass increased with an increasing rate of aeration of shaking flasks from 100 to 140 rpm; however, shaking at over 120 rpm decreased laccase quantity. Highest amount of laccase produced by KU-Alk4, 360 U/mL, was at pH 8.0 with 1% glucose and 0.2 mM copper sulfate, unshaken for the first 3 days, followed by addition of 0.85 mM veratryl alcohol and shaking at 120 rpm. The crude enzyme was significantly stable in alkaline pH 8.0~10.0 for 24 hr. After treating the pulp mill effluent with the KU-Alk4 system for 3 days, pH decreased from 9.6 to 6.8, with reduction of color and chemical oxygen demand at 83.2% and 81%, respectively. Laccase was detectable during the biotreatment process.