• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6327-6332
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• 2012

Esophageal cancer is a common malignant tumor occurring in human esophageal epithelial tissue. The primary purpose of this paper was to define the effects of ${\beta}$-carotene and 1,25-dihydroxyvitamin $D_3$, alone and in combination, on cell proliferation, cell cycle and apoptosis of human esophageal cancer EC9706 cells. Treatment with different concentrations of ${\beta}$-carotene and/or 1,25-dihydroxyvitamin $D_3$. MTT assay showed that ${\beta}$-carotene and 1,25-dihydroxyvitamin $D_3$ significantly inhibited proliferation of EC9706 cells in a dose- and time-dependent manner. Further studies also demonstrated that ${\beta}$-carotene alone or 1,25-dihydroxyvitamin $D_3$ alone caused a marked increase on the induction of apoptosis in EC9706 cells. The percentage of G0/G1-phase cells significantly increased on addition of 1,25-dihydroxyvitamin $D_3$ alone, but there were no significant changes with ${\beta}$-carotene alone. These two agents in combination synergistically inhibited cell growth and induced apoptosis. Therefore, our results indicate that ${\beta}$-carotene and 1,25-dihydroxyvitamin $D_3$ in combination may provide a novel strategy for preventing and treating esophageal cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6139-6144
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• 2012

Aims: Mammalian target of rapamycin (mTOR) is master regulator of the PI3K/Akt/mTOR pathway and plays an important role in NSCLCs. Here we characterized mRNA and protein expression levels of mTOR and its functional associated molecules including PTEN, IGF-1R and 4EBP1 in surgically resected NSCLCs. Methods: Fifty-four patients with NSCLCs who underwent pulmonary resection were included in current study. mRNA levels of mTOR, PTEN, IGF-1R, and 4EBP1 were evaluated by RT-PCR and protein expression of mTOR, PTEN, and IGF-1R by immunohistochemistry (IHC). Association of expression of the relevant molecules with clinical characteristics, as well as correlations between mTOR and PTEN, 4EBP1 and IGF-1R were also assessed. Results: The results of RT-PCR showed that in NSCLCs, the expression level of mTOR increased, while PTEN, 4EBP1 and IGF-1R decreased. Statistical analysis indicated high IGF-1R expression was correlated with advanced clinical stage (stage III) and PTEN expression was reversely associated with tumor size (P=0.16). The results of IHC showed mTOR positive staining in 51.8% of cases, while IGF-1R positive staining was found in 83.3% and loss of PTEN in 46.3%. Protein expression of mTOR was correlated with its regulators, PTEN and IGF-1R, to some extent. Conclusions: Abnormal activation of mTOR signaling, high expression of IGF-1R, and loss of PTEN were observed in resected NSCLC specimens. The poor expression agreement of mTOR with its regulators, PTEN, and IGF-1R, implied that combination strategy of mTOR inhibitors with other targets hold significant potential for NSCLC treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7337-7341
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• 2014

Background: The physiological role of vitamin D extends beyond bone health and calcium-phosphate homeostasis to effects on cancer risk, mainly for colorectal cancer. Vitamin D may have an anticancer effect in colorectal cancer mediated by binding of the active form $1,25(OH)_2D$ to the vitamin D receptor (VDR). The Taq1 VDR gene polymorphism, a C-to-T base substitution (rs731236) in exon 9 may influence its expression and function. The aim of this study wass to determine the 25(OH)D vitamin D level and to investigate the association between circulating vitamin D level and Taq1VDR gene polymorphism among Jordanian colorectal cancer patients. Materials and Methods: This case control study enrolled ninety-three patients and one hundred and two healthy Jordanian volunteers from AL-Basheer Hospital/Amman (2012-2013). Ethical approval and signed consent forms were obtained from all participants before sample collection. 25(OH)D levels were determined by competitive immunoassay Elecsys (Roche Diagnostic, France). DNA was extracted (Promega, USA) and amplified by PCR followed by VDR Taq1 restriction enzyme digestion. The genotype distribution was evaluated by paired t-test and chi-square. Comparison between vitamin D levels among CRC and control were assessed by odds ratio with 95% confidence interval. Results: The vitamin D serum level was significantly lower among colorectal cancer patients (8.34 ng/ml) compared to the healthy control group (21.02ng/ml). Patients deficient in vitamin D (less than 10.0 ng/ml) had increased colorectal cancer risk 19.2 fold compared to control. Only 2.2% of CRC patients had optimal vitamin D compared to 23.5% among healthy control. TT, Tt and tt Taq1 genotype frequencies among CRC cases was 35.5%, 50.5% and 14% compared to 43.1%, 41.2% and 15.7% among healthy control; respectively. CRC patients had lower mean vitamin D level among TT ($8.91{\pm}4.31$) and Tt ($9.15{\pm}5.25$) genotypes compared to control ($21.3{\pm}8.31$) and ($19.3{\pm}7.68$); respectively. Conclusions: There is significant association between low 25(OH)D serum level and colorectal cancer risk. The VDRTaq1 polymorphism was associated with increased colorectal cancer risk among patient with VDRTaq1 TT and Tt genotypes. Understanding the functional mechanism of VDRTaq1 TT and Tt may provide a strategy for colorectal cancer prevention and treatment.

• 한국작물학회:학술대회논문집
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• 한국작물학회 2017년도 9th Asian Crop Science Association conference
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• pp.338-338
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• 2017

One of the problems in increasing rice production is getting lines or varieties that have high adaptability so that able to produce maximum production in a variety of environmental conditions. One strategy that can be done to get adaptive varieties is through the improvement of native varieties. This research was conducted in rain fed paddy field, Aceh province, Indonesia from June to September 2014. The texture of the soil was clay-loam with the soil pH ranged from 6.5-6.7. Five potential progenies of rice from crossing between native Indonesian rice with introduced rice varieties consist of C3, C4, S3, S5, S6 were used in this study. Besides that, one national rice variety Ciherang also used as a comparison. The plants were growth in the plot with the size of $2m{\times}1.4m$ with plant distance was $20cm{\times}20cm$. The fertilizers used in this study were Urea, NPK, and KCl. Randomized block design with 6 rice progenies/variety and 3 replications were used in this study. There were 18 experimental units and each experimental unit had 10 samples for the sources of data. The variables that were observed in this study including plant height at harvesting time, number of productive tiller, the percentage of empty grains and filled grain per panicle, weight of filled grains per hill, weight of filled grain per plot and yield potential per hectare. Analyzed were also conducted for the depth of root penetration, dry-root weight, dry-shoot weight, shoot-root weight ratio and its correlation with the weight of filled grain per hill. The research results show that there was significant difference on plant height at harvesting time, number of productive tillers, the percentage of empty grains and filled grain per panicle, weight of filled grains per hill, weight of filled grain per plot and yield potential per ha (p>0.01) among the treatments. In addition, depth root penetration, dry-root weight, dry-shoot weight, shoot-root weight ratio also had significant difference (p>0.01) among the treatment. The highest plant at harvesting time was found in S6, reaching 129.8 cm and the shortest plants was found in C3 reaching 107.5 cm. The largest number of productive tillers and the highest percentage of filled grains per panicle were found in Ciherang reaching 10.5 tillers and 80.7% respectively. Ciherang also had the heaviest weight of filled grains per hill and per plot reaching 21.1 g and 2.18 kg respectively. Whereas, S6 had the lowest number of tillers and the lowest percentage of filled grain per panicle.. The highest yield potential per ha was found in Ciherang reaching 7.79 tons. Among the progenies, S5 had the highest yield potential reaching 5 tons/Ha. The result also showed significant relationship between shoot-root weight ratio with weight of filled grains per hill. The highest value of shoot-root weight ratio (1.57) in Ciherang is thought had closed relationship with its yield potential.

• 환경생물
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• 제34권2호
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• pp.107-115
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• 2016

전 세계적으로 원자력 발전소는 442기가 가동 중이며, 62기가 충원될 예정이다. 원자력 발전소의 증가에 따라 방사성 폐기물 유출에 대한 위험성도 증가하였다. 이러한 이유 때문에, 방사성 폐기물의 처리는 인간, 동물, 식물을 포함하는 자연 생태계를 보전하는 관점에서 중요하다. 또한, 방사성 폐기물 유출은 그 지역뿐만 아니라 전 세계적으로 심각한 문제를 야기한다. 본 연구는 입체 배양세포에 방사성 핵종원소(세슘, 스트론튬, 코발트)를 처리하였고 이에 대한 영향력을 확인하였다. 입체 배양 구조체는 아가로오스 하이드로겔을 이용하여 제작했으며 암세포 및 정상세포 (HeLa, HepG2, COS-7)를 사용하여 입체 배양을 실시 하였다. 입체 형태로 세포를 배양한 후 세슘, 스트론튬, 코발트 농도 변화에 따라 세포 생존능력을 분석하였다. 이때 입체 배양세포에서 생존능력이 단층 배양세포 보다 최대 42% 우수한 것을 확인하였다. 입체 배양구조체는 세포가 형태 및 생리학적으로 in vivo환경인 조직과 비슷하게 배양을 가능하게 하였다. 따라서, 입체 배양구조체는 기존의 단층 배양 한계점인 in vivo 환경에 적용시킬 수 없다는 한계를 극복하였다. 본 입체 배양 기술이 중금속 독성평가 및 단시간 내에 다수의 물질 분석을 수행하는 고속 대량 스크리닝 기술에 활용될 것으로 기대한다.

• 한국해양학회지:바다
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• 제16권1호
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• pp.39-51
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• 2011

본 연구는 해수담수화 부산물인 고염해수에 대한 어류의 단기적인 영향을 평가하기 위하여 해양생태독성평가용 표준시험종인 송사리(Oryzias latipes)를 이용하여 급성독성평가 및 행동패턴의 변화를 관찰하였다. 30.0 psu 해수에 순치된 송사리를 7일 동안 고염수에 노출하여 급성독성평가를 수행한 결과, 40.0~80.0 psu에 노출된 송사리의 사망률은 농도-반응의 선형관계가 뚜렷하였다. 반면 40.0 psu 이하의 염분에서는 송사리의 독성반응이 관찰되지 않았으나 50.0 psu 보다 높은 농도에서는 뚜렷한 독성 반응이 나타났다(7-day $LC_{50}$=514 psu). 송사리의 행동 변화 분석은 카메라를 통해 투시된 실시간 배정 영상을 추출하여 현재의 프레임과 차영상을 추출하는 기법을 이용하였다. 고염수 노출에 따른 송사리의 행동변화를 분석한 결과, 40.0 psu와 50.0 psu에 노출되고, 각각 3.1시간과 4.6시간 동안 초기 염분 스트레스를 받은 후에는 안정된 활동패턴을 보였다. 그러나 60.0 psu 보다 높은 농도에 노출된 송사리의 활동량은 염분노출 초기에 급격히 증가하였으며, 50% 가량 사망하였다. 70.0 psu 보다 높은 농도에서 실험생물의 활동량은 노출 후 급격히 증가하였으며, 행동패턴은 심각하게 교란되었고, 12시간 이내에 모든 개체가 사망하였다. 본 연구 결과, 고염해수에 대한 급성독성평가와 행동변화 모니터링 결과는 유의한 연관성이 나타났으며, 따라서 해수담수화에 따른 고염해수의 해양배출은 확산후 최종농도가 50.0 psu 이하로 배출될 수 있도록 조절하여야한다. 또한 카메라 관찰을 통한 영상 분석 기법은 시험생물의 행동변화에 따른 영향을 실시간으로 모니터링할 수 있으므로 조기 경보시스템으로 활용 가지가 높은 것으로 판단된다.

• Biomolecules & Therapeutics
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• 제18권1호
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• pp.39-47
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• 2010

Brain-derived neurotrophic factor (BDNF) is a neurotrophic factor involved in neuronal differentiation, plasticity, survival and regeneration. BDNF draws massive attention mainly due to the potential as a therapeutic target in neurological diseases such as depression and Alzheimer's disease. In a primary screening for the natural compounds enhancing BDNF release from cultured rat primary cortical neuron, we found that compounds such as baicalein, tanshinone IIa, cinnamic acid, epiberberine, genistein and wogonin among many others increased BDNF release. All the compounds at $0.1{\mu}M$ of concentration barely showed stimulatory effect on BDNF induction, however, their combination (mixture 1; baicalein, tanshinone IIa and cinnamic acid, mixture 2; epiberberine, genistein and wogonin) showed synergistic increase in BDNF release as well as mRNA and protein expression. The level of BDNF expression was comparable to the maximum BDNF stimulation attainable by a positive control oroxylin A ($20{\mu}M$) without cell toxicity as determined by MTT analysis. Both mixtures synergistically increased the phosphorylation of extracellular signal-regulated kinase (ERK) as well as cAMP response element binding protein (CREB), an immediate and essential regulator of BDNF expression. Similar to these results, mixture of these compounds synergistically inhibited the up-regulation of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide treatments in rat primary astrocytes. These results suggest that the combinatorial treatment of natural compounds in lower concentration might be a useful strategy to obtain sufficient BDNF stimulation in neurological disease condition such as depression, while minimizing potential side effects and toxicity of higher concentration of a single compound.

• Journal of Gastric Cancer
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• 제3권4호
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• pp.191-194
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• 2003

Purpose: Neuroendocrine carcinomas of the stomach account for only about $0.3\%$ of all gastric tumors. The prognosis of this disease is very poor compared with the common type of gastric adenocarcinoma. The purpose of this retrospective study was to review the clinicopathologic features of 18 cases of this unusual gastric tumor and to establish a treatment strategy for this tumor. Materials and Methods: Excluding 2 cases of non-curative resection and 1 case of operative mortality, 18 cases of typical neuroendocrine carcinoma who had curative resection from January 1991 to December 2000 at Asan Medical Center were analyzed; 6841 gastric cancer patient were treated surgically during the same period. Results: The mean age at the time of diagnosis was 58.6 years (range: $35\∼75$ yr). Sixteen patients were male, and two were female. Eleven tumors ($61.1\%$) developed in the lower part of the stomach, three ($16.7\%$) in the middle part, and three ($16.7\%$) in the upper part. One tumor involved the entire stomach. Eight cases ($44.4\%$) were Borrmann type 2, and six case ($33.3\%$) were Borrmann type 3. The mean tumor size was 6.94 cm (range: $0.6\∼15$ cm). Nine cases ($50\%$) showed recurrence of the disease, and eight of them died within 20 months. Of the nine recurred cases, 7 cases ($77.8\%$) showed liver metastasis. The mean disease-free interval was 6.8 months (range: $2.5\∼11$ months) after surgical resection, and the mean survival was 17.9 months (range: $8\∼40$ months) for recurrence cases. One patient with liver metastasis was treated with a liver-wedge resection just after diagnosis and was still alive for 37.5 months postoperatively. There were 9 deaths after the median follow- up period of 40 months (range: $8\∼72$ months). Conclusion: Gastric neuroendocrine carcinomas frequently recur at the liver, even in early stage cancer, and have a poor prognosis. We experienced a case of successful control of hepatic metastasis by surgical resection and a case of a small cell carcinoma which was successfully controlled with systemic chemotherapy.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3223-3228
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• 2012

HMGN5 is a typical member of the HMGN (high mobility group nucleosome-binding protein) family which may function as a nucleosomal binding and transcriptional activating protein. Overexpression of HMGN5 has been observed in several human tumors but its role in tumorigenesis has not been fully clarified. To investigate its significance for human lung cancer progression, we successfully constructed a shRNA expression lentiviral vector in which sense and antisense sequences targeting the human HMGN5 were linked with a 9-nucleotide loop. Inhibitory effects of siRNA on endogenous HMGN5 gene expression and protein synthesis were demonstrated via real-time RT-PCR and western blotting. We found HMGN5 silencing to significantly inhibit A549 and H1299 cell proliferation assessed by MTT, BrdU incorporation and colony formation assays. Furthermore, flow cytometry analysis showed that specific knockdown of HMGN5 slowed down the cell cycle at the G0/G1 phase and decreased the populations of A549 and H1299 cells at the S and G2/M phases. Taken together, these results suggest that HMGN5 is directly involved in regulation cell proliferation in A549 and H1299 cells by influencing signaling pathways involved in cell cycle progression. Thus, our finding suggests that targeting HMGN5 may be an effective strategy for human lung cancer treatment.

• Asian-Australasian Journal of Animal Sciences
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• 제17권5호
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• pp.670-677
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• 2004

Sixteen multiparous Holstein-Friesian crossbred cows in mid-lactation were blocked according to days in milk (DIM) and previous lactation and randomly assigned according to a Randomized Complete Block (RCB) design with four replications to receive four dietary treatments. The dietary treatments consisted of T1: No cassava hay (CH) or stylo 184 hay (SH) supplementation, supplementation of concentrate to milk yield at 1:2 (control), T2: Supplementation of 1 kg of CH/hd/d, supplementation of concentrate to milk yield at 1:2, T3: Supplementation of 1 kg of CH+SH/hd/d, supplementation of concentrate to milk yield at 1:2, T4: Supplementation of 2 kg of CH+SH/hd/d, supplementation of concentrate to milk yield at 1:3. All animals received Ruzi grass from a cut-and-carry system as roughage source. The feeding trial lasted for 9 weeks. The results revealed that DMI of concentrate of supplemented treatments were significantly lower (p<0.05) than those in the control, but there was no significant difference between T2 and T3. There was no significant difference in forage DM intake between the control and supplemented treatments. CP and NDF digestibility of supplemented treatments were significantly (p<0.05) greater than the control and there were no significant differences among supplemented treatments. Milk yield and 3.5% FCM (14.3, 14.5, 14.7 and 14.8; 13.9, 14.3, 14.3 and 14.6 kg/hd/d, respectively) were not significantly different among treatments. Milk protein percentage of supplemented treatments was significantly (p<0.05) higher than the control, but there were no significant differences among supplemented treatments. There was no significant difference in milk fat percentage between the control and supplemented treatments. However, milk fat percentage tended to be higher for supplemented animals as compared to the control group. There were also no significant differences in lactose, solids-not-fat and total solids percentages among treatments. Cows in supplemented treatments gave incomes over supplement cost (IOSC) of 2.72, 2.74 and 2.93 US$/hd/d, respectively which were greater than for cows on control treatment. Furthermore, IOSC were greatest for cows in T4 as compared to other treatments. Based on this study it was concluded that, feeding cassava hay solely or in combination with stylo 184 hay as a supplemental protein source could be a potential valuable strategy in small-holder dairy farming systems in the tropics. This strategic supplementation significantly reduced concentrate use, which resulted in improved milk yields and milk quality for the supplemented cows. Moreover, it resulted in higher economical returns through increased productivity and lower ratios of concentrate to milk yield, from 1:2 to 1:3.