• Title, Summary, Keyword: RET

Search Result 61, Processing Time 0.041 seconds

EGF Induced RET Inhibitor Resistance in CCDC6-RET Lung Cancer Cells

  • Chang, Hyun;Sung, Ji Hea;Moon, Sung Ung;Kim, Han-Soo;Kim, Jin Won;Lee, Jong Seok
    • Yonsei Medical Journal
    • /
    • v.58 no.1
    • /
    • pp.9-18
    • /
    • 2017
  • Purpose: Rearrangement of the proto-oncogene rearranged during transfection (RET) has been newly identified potential driver mutation in lung adenocarcinoma. Clinically available tyrosine kinase inhibitors (TKIs) target RET kinase activity, which suggests that patients with RET fusion genes may be treatable with a kinase inhibitor. Nevertheless, the mechanisms of resistance to these agents remain largely unknown. Thus, the present study aimed to determine whether epidermal growth factor (EGF) and hepatocyte growth factor (HGF) trigger RET inhibitor resistance in LC-2/ad cells with CCDC6-RET fusion genes. Materials and Methods: The effects of EGF and HGF on the susceptibility of a CCDC6-RET lung cancer cell line to RET inhibitors (sunitinib, E7080, vandetanib, and sorafenib) were examined. Results: CCDC6-RET lung cancer cells were highly sensitive to RET inhibitors. EGF activated epidermal growth factor receptor (EGFR) and triggered resistance to sunitinib, E7080, vandetanib, and sorafenib by transducing bypass survival signaling through ERK and AKT. Reversible EGFR-TKI (gefitinib) resensitized cancer cells to RET inhibitors, even in the presence of EGF. Endothelial cells, which are known to produce EGF, decreased the sensitivity of CCDC6-RET lung cancer cells to RET inhibitors, an effect that was inhibited by EGFR small interfering RNA (siRNA), anti-EGFR antibody (cetuximab), and EGFR-TKI (Iressa). HGF had relatively little effect on the sensitivity to RET inhibitors. Conclusion: EGF could trigger resistance to RET inhibition in CCDC6-RET lung cancer cells, and endothelial cells may confer resistance to RET inhibitors by EGF. E7080 and other RET inhibitors may provide therapeutic benefits in the treatment of RET-positive lung cancer patients.

Effect of diets with different energy and lipase levels on performance, digestibility and carcass trait in broilers

  • Hu, Y.D.;Lan, D.;Zhu, Y.;Pang, H.Z.;Mu, X.P.;Hu, X.F.
    • Asian-Australasian Journal of Animal Sciences
    • /
    • v.31 no.8
    • /
    • pp.1275-1284
    • /
    • 2018
  • Objective: A 28-d trial was conducted to evaluate the effect of diets with different energy and lipase levels on performance, nutrient digestibility, serum profiles, gut health, and carcass quality in broilers. Methods: A total of 720 one-day-old male Ross 308 broilers ($45.4{\pm}0.5g$) were randomly assigned to one of the following four treatments: i) RET, reduced energy treatment (metabolizable energy = 2,950 and 3,100 kcal/kg for starter and finisher diet), ii) BDT, basal diet treatment (metabolizable energy = 3,050 and 3,200 kcal/kg for starter and finisher diet, iii) RET015, RET+0.15 g/kg lipase, and iv) RET03, RET+0.3 g/kg lipase. There were 10 replications (cages) per treatment with 18 birds per cage. Results: During d 1 to 14, broilers fed BDT, RET015, and RET03 diets had higher (p<0.05) body weight gain than those fed RET diet. During d 1 to 14, 15 to 28 and the overall experiment, feed conversion ratio in RET03 treatment was lower (p<0.05) compared with RET treatment. On d 14, the apparent total tract digestibility (ATTD) of dry matter (DM), ether extract (EE), and gross energy in RET03 treatment was higher (p<0.05) than those in RET treatment, while the ATTD of N was increased (p<0.05) by RET03 treatment. On d 28, broilers fed RET03 diet had higher (p<0.05) ATTD of DM than those fed RET and RET015 diets, while the ATTD of EE in BDT and RET03 treatments was increased (p<0.05) compared with RET and RET015 treatments. Broilers fed RET03 diet had higher villus height (VH) and VH:crypt depth (CD) ratio than those fed RET and BDT diets. The activity of pancreatic lipase in BDT and RET03 treatments was higher (p<0.05) than that in RET treatment. Conclusion: Taken together, lipase supplementation (3,000 U/kg feed) increased growth performance, nutrient digestibility, VH, VH:CD ratio and lipase activity, but decreased triglyceride, low-density lipoprotein cholesterol and the abdominal fat percentage in broilers fed reduced energy diet.

RET Modelling through the Phase Function Measurement at 12.5 GHz (12.5 GHz 대역 위상 함수 특성 측정을 통한 RET 모델링)

  • Han, Il-Tak;Bae, Seok-Hee;Jung, Myoung-Won;Pack, Jung-Ki
    • The Journal of Korean Institute of Electromagnetic Engineering and Science
    • /
    • v.18 no.3
    • /
    • pp.334-340
    • /
    • 2007
  • The prediction for vegetation attenuation using the RET model recommended in the ITU-R requires six RET input parameters. Among these, 4 parameters are related to the scattering characteristics of vegetation. To extract these parameters, two methods can be used. One is to extract the parameters by curve fitting of the measured vegetation-attenuation curve with the RET prediction model, and the other is to use the additional phase function measurement data. In the former method, fitting is quite complex and it does not result in the unique results in some cases. In addition, the extracted parameters lack the physical meaning as well. Thus, in this paper, the measurement method of phase function, and the method of extracting the RET model parameters which lead to more accurate and physically more meaningful results are presented. The extracted RET model parameters are also presented. The RET modeling method, measurement data, and the extracted RET model parameters presented in this paper were submitted to the ITU-R meeting in 2006, and adapted for ITU-R report and recommendation P.833.

RET Proto-Oncogene Mutation in Medullary Thyroid Carcinoma (갑상선 수질암 조직에서 RET 원암유전자의 돌연변이 양상)

  • Chung Woong-Youn;Song Hyeun-Jung;Cho Nam-Hoon;Park Cheong-Soo
    • Korean Journal of Head & Neck Oncology
    • /
    • v.18 no.1
    • /
    • pp.3-10
    • /
    • 2002
  • Background: The molecular pathogenesis of hereditary medullary thyroid carcinoma is well known to be associated with germ-line mutation in the RET proto-oncogene and sporadic medullary thyroid carcinoma has been shown to carry somatic RET mutation especially in exon 13 and 16. The aim of this study is to evaluate the genetic background in the pathogenesis of the sporadic medullary thyroid carcinoma which shows extremely high incidence in Korea. Materials and Methods: Direct DNA sequencing for RET exon 13 and 16, as well as immunohistochemistrical assay for a monoclonal RET antibody were performed from 20 cases of archival tissues of medullary thyroid carcinoma. Results: Monoclonal RET antibody with C-terminal epitope showed comparatively stronger expression in tumor cells than in normal tissues and immunoreactive area in the tumor was $66.0{\pm}40.1%$. Direct sequencing of RET exon 13 revealed 4 cases of mis-sense mutations in Codon 778, Codon 767, and both in Codon 768 and 778. One case showed a silent mutation (ACG-ACT) in RET exon 16 (Codon 926). Conclusions: The strong RET immunoreactivity of medullary thyroid carcinoma may suggest that there could be a genetic alteration in oncoprotein level. RET proto-oncogene mutation may be involved in the evolutional process of medullary thyroid carcinoma in the aspect of molecular basis.

Exploring Professional Development of Science Teachers through the Research Experience for Teachers Program (연구 참여 경험을 통한 과학 교사의 전문성 발달 과정 탐색)

  • Baik, In-Young;Kim, Heui-Baik
    • Journal of The Korean Association For Science Education
    • /
    • v.31 no.5
    • /
    • pp.663-679
    • /
    • 2011
  • This case study focused on three science teachers who participated in the Research Experience for Teachers (RET) program conducted by the Center for Bridging Advanced Science and Education (CBASE). The RET program provides opportunities for participants to experience experimentations in a science laboratory for six months, enabling teachers develop teaching materials based on their experience from the RET program. The purpose of this study was to explore how the teachers had developed their professionalism through participation in the program and which factors promoted the professional development of science teachers. In this research, we defined pedagogical content knowledge (PCK) as the required knowledge for teachers to develop for their professional development. As a result of the RET program, all three participants showed integration of PCK elements: orientation to teaching science, knowledge of science, knowledge of students, knowledge of teaching, and knowledge of sources. The PCK elements which had been developed by the RET program were applied in school context and the teachers' belief became clear and strong. The teachers were able to understand the process of authentic science as they learned it from 'legitimate peripheral participation' in the authentic research context. They also showed dynamic integration between newly established elements of PCK by reflecting on the school context while developing the teaching materials. The professional development of each teacher was different depending on the purpose and PCK, which participants had already possess. This study will provide meaningful implication for the development of professional development program for science teachers based on research experience.

Evaluation of Meteorological Elements Used for Reference Evapotranspiration Calculation of FAO Penman-Monteith Model (FAO Penman-Monteith 모형의 증발산량 산정에 이용되는 기상요소의 평가)

  • Hur, Seung-Oh;Jung, Kang-Ho;Ha, Sang-Keun;Kim, Jeong-Gyu
    • Korean Journal of Soil Science and Fertilizer
    • /
    • v.39 no.5
    • /
    • pp.274-279
    • /
    • 2006
  • The exact estimation of crop evapotranspiration containing reference or potential evapotranspiration is necessary for decision of crop water requirements. This study was carried out for the evaluation and application of various meteorological elements used for the calculation of reference evapotranspiration (RET) by FAO Penman-Monteith (PM) model. Meteorological elements including temperature, net radiation, soil heat flux, albedo, relative humidity, wind speed measured by meteorological instruments are required for RET calculation by FAO PM model. The average of albedo measured for crop growing period was 0.20, ranging from 0.12 to 0.23, and was slightly lower than 0.23. Determinant coefficients by measured albedo and green grass albedo were 0.97, 0.95 and standard errors were 0.74, 0.80 respectively. Usefulness of deductive regression models was admitted. To assess an influence of soil heat flux (G) on FAO PM, RET with G=0 was compared with RETs using G at 5cm soil depth ($G_{5cm}$) and G at surface ($G_{0cm}$). As the results, RET estimated by G=0 was well agreed with RET calculated by measured G. Therefore, estimated net radiation, G=0 and albedo of green grass could be used for RET calculation by FAO PM.

Comparison of reference evapotranspiration estimation methods with limited data in South Korea

  • Jeon, Min-Gi;Nam, Won-Ho;Hong, Eun-Mi;Hwang, Seonah;Ok, Junghun;Cho, Heerae;Han, Kyung-Hwa;Jung, Kang-Ho;Zhang, Yong-Seon;Hong, Suk-Young
    • Korean Journal of Agricultural Science
    • /
    • v.46 no.1
    • /
    • pp.137-149
    • /
    • 2019
  • Accurate estimation of reference evapotranspiration (RET) is important to quantify crop evapotranspiration for sustainable water resource management in hydrological, agricultural, and environmental fields. It is estimated by different methods from direct measurements with lysimeters, or by many empirical equations suggested by numerous modeling using local climatic variables. The potential to use some such equations depends on the availability of the necessary meteorological parameters for calculating the RET in specific climatic conditions. The objective of this study was to determine the proper RET equations using limited climatic data and to analyze the temporal and spatial trends of the RET in South Korea. We evaluated the FAO-56 Penman-Monteith equation (FAO-56 PM) by comparing several simple RET equations and observed small fan evaporation. In this study, the modified Penman equation, Hargreaves equation, and FAO Penman-Monteith equation with missing solar radiation (PM-Rs) data were tested to estimate the RET. Nine weather stations were considered with limited climatic data across South Korea from 1973 - 2017, and the RET equations were calculated for each weather station as well as the analysis of the mean error (ME), mean absolute error (MAE), and root mean square error (RMSE). The FAO-56 PM recommended by the Food Agriculture Organization (FAO) showed good performance even though missing solar radiation, relative humidity, and wind speed data and could still be adapted to the limited data conditions. As a result, the RET was increased, and the evapotranspiration rate was increased more in coastal areas than inland.

RET Proto Oncogene Mutation Detection and Medullary Thyroid Carcinoma Prevention

  • Yeganeh, Marjan Zarif;Sheikholeslami, Sara;Hedayati, Mehdi
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.16 no.6
    • /
    • pp.2107-2117
    • /
    • 2015
  • Thyroid cancer is the most common endocrine neoplasia. The medullary thyroid carcinoma (MTC) is one of the most aggressive forms of thyroid malignancy,accounting for up to 10% of all types of this disease. The mode of inheritance of MTC is autosomal dominantly and gain of function mutations in the RET proto-oncogene are well known to contribute to its development. MTC occurs as hereditary (25%) and sporadic (75%) forms. Hereditary MTC has syndromic (multiple endocrine neoplasia type 2A, B; MEN2A, MEN2B) and non-syndromic (Familial MTC, FMTC) types. Over the last two decades, elucidation of the genetic basis of tumorigenesis has provided useful screening tools for affected families. Advances in genetic screening of the RET have enabled early detection of hereditary MTCs and prophylactic thyroidectomy for relatives who may not show any symptom sof the disease. In this review we emphasize the main RET mutations in syndromic and non syndromic forms of MTC, and focus on the importance of RET genetic screening for early diagnosis and management of MTC patients, based on American Thyroid Association guidelines and genotype-phenotype correlation.

Analysis for the Regional Characteristic of Climatic Aridity Condition in May (5월 기후 건조현상의 지역별 특성 분석)

  • Rim, Chang-Soo;Kim, Seong-Yeop
    • Journal of Korea Water Resources Association
    • /
    • v.46 no.6
    • /
    • pp.613-627
    • /
    • 2013
  • In this study, to understand the May aridity condition of each region for the year of the worst drought on record in each duration (1-, 3-, 6-, 12-, 24 months), monthly climate data recorded from 1973 to 2006 at 53 climatological stations in South Korea were used to estimate the FAO Penman-Monteith reference potential evapotranspiration (RET). Monthly precipitation and RET were used to estimate P/RET as aridity index and variation index (VI) of P/RET, and these indexes are compared with SPI (Standard Precipitation Index). Fifty three climatological stations were grouped into 20 regions, so that May aridity conditions of 20 regions were studied. Furthermore, regional trend of May aridity index was studied by applying Mann-Kendall trend analysis, Spearman rank test, and Sen's slope estimator. The study results show that variation index (VI) of P/RET and SPI have close correlation. Throughout the country, as the duration is shorter, May aridity was more severe. In case of 3-month and 6-month duration, most of region show significant or non-significant decreasing trend of aridity index. However, no region show significant decreasing trend of aridity index in case of 12-month and 24-month duration.

The role of Lactobacillus reuteri DSM 17938 for the absorption of iron preparations in children with iron deficiency anemia

  • Manoppo, Jeanette;Tasiringan, Hilda;Wahani, Audrey;Umboh, Adrian;Mantik, Max
    • Korean Journal of Pediatrics
    • /
    • v.62 no.5
    • /
    • pp.173-178
    • /
    • 2019
  • Purpose: To determine whether Lactobacillus reuteri DSM 17938 plays a role in absorption of iron preparations given to children with iron deficiency anemia (IDA). Methods: We performed a quasi-experimental study involving pre- and postintervention tests using a control group in North Sulawesi province, Indonesia, between July and September 2017. We conducted a single-blind controlled trial that included primary school children who were diagnosed with IDA based on reticulocyte hemoglobin equivalent (Ret-He) levels <27.8 pg/L. Results: A total of 66 children were randomized into 2 groups. Thirty-four children received iron preparations with the addition of L. reuteri DSM 17938 (group 1), whereas the other 32 received iron preparations alone (group 2). The baseline Ret-He levels before intervention were similar in both groups. After 14 days of intervention, mean Ret-He level in group 1 changed from $24.43{\pm}1.64$ to $28.21{\pm}1.72pg/L$ (P=0.000). Mean Ret-He level in group 2 changed from $24.31{\pm}1.42$ to $27.03{\pm}2.14pg/L$ (P=0.000). Statistical analysis showed a significant increase in Ret-He levels in both groups; Ret-He levels were significantly higher in the experimental group than in the control group (P<0.05). Conclusion: Children with IDA receiving iron preparations with L. reuteri DSM 17938 for 14 days show higher Ret-He levels than those receiving iron preparations alone.