Genomic Heterogeneity as a Barrier to Precision Medicine in Gastroesophageal Adenocarcinoma

Pectasides, Eirini,Stachler, Matthew D.,Derks, Sarah,Liu, Yang,Maron, Steven,Islam, Mirazul,Alpert, Lindsay,Kwak, Heewon,Kindler, Hedy,Polite, Blase,Sharma, Manish R.,Allen, Kenisha,O'Day, Emily,Lomni American Association for Cancer Research 2018 Cancer discovery Vol.8 No.1

<P>Heterogeneity of actionable genomic alterations among primary and metastatic lesions suggests that biomarker profiling of a single primary tumor site may limit the success of targeted therapy in gastroesophageal adenocarcinoma.</P><P>Gastroesophageal adenocarcinoma (GEA) is a lethal disease where targeted therapies, even when guided by genomic biomarkers, have had limited efficacy. A potential reason for the failure of such therapies is that genomic profiling results could commonly differ between the primary and metastatic tumors. To evaluate genomic heterogeneity, we sequenced paired primary GEA and synchronous metastatic lesions across multiple cohorts, finding extensive differences in genomic alterations, including discrepancies in potentially clinically relevant alterations. Multiregion sequencing showed significant discrepancy within the primary tumor (PT) and between the PT and disseminated disease, with oncogene amplification profiles commonly discordant. In addition, a pilot analysis of cell-free DNA (cfDNA) sequencing demonstrated the feasibility of detecting genomic amplifications not detected in PT sampling. Lastly, we profiled paired primary tumors, metastatic tumors, and cfDNA from patients enrolled in the personalized antibodies for GEA (PANGEA) trial of targeted therapies in GEA and found that genomic biomarkers were recurrently discrepant between the PT and untreated metastases. Divergent primary and metastatic tissue profiling led to treatment reassignment in 32% (9/28) of patients. In discordant primary and metastatic lesions, we found 87.5% concordance for targetable alterations in metastatic tissue and cfDNA, suggesting the potential for cfDNA profiling to enhance selection of therapy.</P><P><B>Significance:</B> We demonstrate frequent baseline heterogeneity in targetable genomic alterations in GEA, indicating that current tissue sampling practices for biomarker testing do not effectively guide precision medicine in this disease and that routine profiling of metastatic lesions and/or cfDNA should be systematically evaluated. <I>Cancer Discov; 8(1); 37–48. ©2017 AACR.</I></P><P><I>See related commentary by Sundar and Tan, p. 14</I>.</P><P><I>See related article by Janjigian et al., p. 49</I>.</P><P><I>This article is highlighted in the In This Issue feature, p. 1</I></P>

남자육상 도약선수에서 고비중 리포단백 콜레스테롤(HDL-c)과 체력, 성호르몬 및 성호르몬 종합단백(SHBG)과의 관련성

유덕수 한국스포츠리서치 2004 한국 스포츠 리서치 Vol.15 No.1

A study was conducted to investigate the contribution of physical fitness evaluated by speed at onset of blood lactate accumulation (OBLA-SP), sex hormones and sex hormone-binding globulin(SHBG) on high-density lipoprotein cholesterol (HDL-c) in 12young male endurance athletes. These athletes has a higher level and wide range of intraindividual variance (44 to 93mg/㎗) for HDL-c. The serum estradiol level was significantly and positively correlated with the level of approtein AI(ApoAI), and serum testosterone level was significantly and positively associated with the levels of both HDL3-C and apoprotein AⅡ(ApoAⅡ). The SHBG level was positively associated with the levels of both HDL-c and HDL2-C. Age, certain anthropometric parameters such as percentage body fat, body mass index, and body fat distribution evaluated by waist to hip ratio, and physical fitness levels were not associated with HDL-c and other lipids and apoproteins. Three results suggest that the HDL-c level in endurance athletes is strongly associated with not only male but also female hormones, and SHBG, being independent of age, body composition and physical fitness level.

육상도약선수의 영양지도 분석

유덕수 한국스포츠리서치 2004 한국 스포츠 리서치 Vol.15 No.1

We also developed food group allowances for the athletes based on their nutrient allowances and current young-aged Korean dietary styles; cereals 400g, potatoes and starches 60g, sugars 20g fats and oils 30g, pulses 120g, meats 150g, fishes and shellfishes 150g, eggs 80g, milks 600g, green and yellow vegetables 300g, the other vegetables 350g, fruits 400g and algae 20g per day. For the experimental period of 45 days, daily diets adjusted to approximate 120% of the dietary allowances were served to the athletes who were free talking snacks and drinks. Dietary guidances for the athletes were assessed by monitors of their dietary intakes, physical constitution and clinical examinations in blood. Means of the dietary intakes of the athletes were 96~99% of the dietary allowances, determined by a nutritional survey with the 24hours recall method. There were less changes in the physical constitution of the athletes before, during and after the experimental period; body weight 57+3㎏ and body fat 8.9+1.8%, Values of the clinical marks in the blood cells 509±4×104 cells/nm3, hemoglobin 15±0.4g/㎗ and hematocrit 46.6±0.7%.

학교체육 경영에서의 프로그램 서비스 유효성에 관한 연구

노덕선,최동제,박주욱 한국스포츠리서치 2004 한국 스포츠 리서치 Vol.15 No.3

The purpose of this study was to consider the effectiveness of a school sport program. For the purpose, it was hypothesized that the results of a sport program were raised the athletes' consciousness for continual sport activities and the recognition of sport. So, it was analyzed from the view point of the motivation and the behavior of athletes by the way of multivariate analysis of variance. The questionnaire was conducted to 427 students in a middle-school attached of Education. The main results were as follows: Athletics(a school sport program) was generally effective for raising the athletes' consciousness for continual sport activities and the recognition of sport with the good managerial conditions, Especially, the results were more positive for the following athlete: 1) The athletes who had the high expectation and performance for their purpose 2) The athletes who had the high expectation and valence for the outcome of athlete 3) The athletes whose desires were satisfied in athletics 4) The athletes who had satisfied the managerial conditions of athletics

넓이뛰기에서의 주관적 강도와 객관적 강도의 대응성 단계분석

유덕수 한국스포츠리서치 2003 한국 스포츠 리서치 Vol.14 No.6

The purpose of this study was to investigate the relationship between subjective intensity (degree of effort) and objective intensity (ratio of running velocity in each trial to the maximum running velocity) in long running, and the changes in running velocity, stride length, stride frequency, and long running motion corresponding to in subjective intensity. Subjects were 37 junior high school boys. Long running motions were recorded with a high speed VTR camera. Stride length, stride frequency, running velocity, angel of the body segment and the angular velocity were obtained through a video motion analysis. The results were summarized as follows: 1) High coefficient of correlation was found between subjective and objective intensities. Junior high school boys graded their output as running velocity. 2) The increase of running velocity with increase in subjective intensity was the result of the increase of stride frequency, which was caused by reduction of support time and nonsupport time. 3) The long running motion at 100% of subjective intensity was characterized by: (1) an increase of knee lifting during forward swing (4) an increase of hip extention speed at recovery phase, and (5) an increase of hip flexion speed at recovery phase. The sprint running at 100% of subjective intensity may need to be instructed for junior high school boys.

중국 육상경기에서의 도약종목의 트레이닝 시스템에 관한 연구

유덕수 한국스포츠리서치 2003 한국 스포츠 리서치 Vol.14 No.6

This study focused on the point how fast the jumping events developed in China and tried to explain it. By comparing the records between Chinese and Japanese jumpers., it was found that the records of China have crossed over that of Japanese after the policy of open door in 1978. The author discussed the reasons from the viewpoints of the training contents of jumping athletes, management of their living environments, and development of sports training system. It showed that the difference is supported by statistical clues and it may come from distinct training systems and may be also the results of reforming the training systems.

육상 높이뛰기 학습에서의 표준설정 방법에 관한 연구

유덕수 한국스포츠리서치 2004 한국 스포츠 리서치 Vol.15 No.2

The purpose of this study is to investigate the method of setting standards for high jump suitable for individual student by making clear from instructive viewpoint the correlation between his record and physical make and strength. The results of the study obtained were as follows. 1. Height and 50m dash-time of individual student proved to be important factors in determining record in all the grades. 2. The method of setting standards(Y cm) high jump, of which height(X1 cm) and 50m dash-time(X2 sec) are the two individual conditions, was obtained. The equation of mulitple regression is as follows. Y-05(X1)-10(X2)+120 Constant(120) is subject to change according to the ability of individual student. 3. Effectiveness of the nomogram made by the equation of multiple regression is demonstrated by applying it to the instruction of the fifth and sixth graders at the elementary school.

林道 切ㆍ盛土面의 崩壞에 關한 硏究 : 七甲山의 林道를 中心으로

吳斗泳,李德鏞 公州大學校 資源科學硏究所 1998 資源科學硏究論文集 Vol.6 No.-

This study make a base on proper gradient and slope length on the forest road execution for methodminimum damage make a survey of erosion and sedimentary amountvariation of slope and inclined plane place in area pass 2-3year after forest road execution. This paper purpose accomplishment surveied sample tree maked erosion and sedimentary amount in chungnam province chilgap mountain east, south, north, in three sample forest road 15 place from 6 month to 8 month 1997 year. The results of the this study gradient, slope area, rain, collaps numerical value research list as follow: 1. The forest road research occured collaps cutting slope 8 place, to banking slope 7 place in A, B, C sample all area. 2. The collaps of gradient occur to banking slope ?? , cutting slope ??, The forest road execution have to banking slope ?? below, cutting slope ??, belowslope execution. 3. The slope length collaps occured to all road uncovered slope previous question. The slope length surveied proper 5m below in cutting slope. Putting the abve resuits together, it is thought that foresr toad execution is the most urgent matter method protection of the slope from cutting slope, banking slope. It is require forest road execution in considerstion of the difficulty ofslope recovery short time for minimum proper slope square and slope place.

검도 미경험 대학생의 습득과정에 관한 연구

육조영,노덕선,김민섭 한국스포츠리서치 2003 한국 스포츠 리서치 Vol.14 No.6

This study has the following two aims : Ⅰ) The first is to clarify the process in which inexperienced students in a physical education class acquire the skill of "ken-tai-icchi no datotsu" (striking with the shinai and body). Ⅱ) The second is to clarify the process of acquiring "basic movement" skills by inexperienced subjects of Kendo in preparation for Kendo Club competitions. In the physical education class, inexperienced students were taught Kendo for about three months (total 21 hours) using the Edo teaching plan. The following results were obtained: 1) "Ken-tai-icchi no datotsu" (striking with the shinai and body) times were shortened by 0.01 seconds. 2) The distance of "fumi-komi" was shortened by 3.7㎝. 3) The time of "datotsu" was shortened by 0.26 seconds. 4) The lateral spreading of legs and right knee joint angle displayed during the "datotsu" movement demonstrated significant changes (p<0.01). However, the shinai angle and the acceleration did not. In the club activity, inexperienced subjects (3 female university students) practiced Kendo about 6 months and were tested on the process of acquiring Kendo skills. The following results were obtained : 1) "Zenshin-koutai suburi" (the action of swing the shinai with forward and backward footwork) increased by 2.7 times. 2) The continuous "kote-men" attack was shortened by 0.9 seconds, while the "shikake-men" attack was shortened by 2.1 seconds. The "shikake-kote" attack was shortened by 1.1 seconds, while the "shikake-do" attack was shortened 1.1 seconds, and the "prediction-attack" was shortened by 1.9 seconds. 3) The distance of "tobi-komi" (including "ayumi-ashi") was shortened by a maximum of 38cm and a minimum of 29㎝.

국제스포츠 정보 시스템의 현황 분석

육조영,윤찬호,김범수,노덕선,이무연,배진희,이승훈 한국스포츠리서치 2004 한국 스포츠 리서치 Vol.15 No.6

Information has become a strategic tool with progress of sports science and sports technology. Demand on sports information is spreading to leisure, recreation, sociology, science of nutrition, psychology, sports medicine, sports therapy, prophylactic medicine, alternative medicine, sports industry and sports nature etc. if on line data base can be manipulated freely then acceleration and quality improvement of the study in this field can be effected and it is possible to gain new insight for receiving latest information But next problem is cost for use. For this reason this author summarized quick and effective on lline search points as follows: 1. Data base should be chosen with clear purpose for its use. Conduct prior investigation on contents and fee system of data base. With the same data base fee system may be differed depending on distributor therefore it is necessary to try different distributors at first as much as possible. 2. Prior to starting on line search prepare search method. If on line is started and then search method is checked than quickly telephone charge will go up. Search method should be prepared in advance by thinking sufficiently of what theme is to be searched. 3. Look for good advisor: lf there is no advisor nearby then the best thing is counselling with the person in charge for the distributor. If the result of search is stored at floppy disk by "downloading" then even after communication line is cut off it will be possible to print out anytime. 4. In this study the author explained about on-line search of lterature data line but recently it is possible to search overseas sports news or information on rate of victory or defeat of prfessional footbali etc. in real time. In Japan it is possible to search feature articles of Nihon Kesai or Asahi (except culture and sports column) by on-line. However in our country there are not many data bases in the field of sports and physical education which can be on-line searched. Our country belongs to up per level in the world in terms of study of sports science and technology and we are attracting attention from countries in Asia and from different parts of the world and the task facing us now is developing independent and unique data base for our country.