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Application of Molecular Diagnostics Technology in the Development of a Companion Diagnostics for Malignant Solid Tumors (악성 고형암의 항암제 동반진단 기술에서 분자진단기술의 적용)

  • Kim, Jin-Hee
    • The Journal of the Korea Contents Association
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    • v.19 no.3
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    • pp.365-374
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    • 2019
  • Unlike benign tumors, malignant tumors are capable of metastasis, easy to relapse, poor survival, and low quality of life. In Korea, here is a tendency to treat the tumors collectively according to the General Principles of Cancer Chemotherapy(GPCC) of the Health Insurance Review & Assessment Service (HIRA). But recently, companion diagnostics(CDx) is recommended rather than unilateral medication because biomarker-based molecular diagnostics is possible to predict the drug response of patients before drug treatment. Not only domestic but also overseas Food and Drug Administratio (FDA) recommends the development of the CDx system at the stage of drug development to ensure the responsiveness and safety of medicines. In this study, I focused on the necessity of CDx development direction as well as CDx development status through literature review. Furthermore I also discussed CDx types according to the molecular diagnostic technology such as immunohistochemistry (IHC), polymerase chain reaction (PCR), in situ hybridization (ISH), and next-generation sequencing (NGS) not only in the approved CDx but also in the developing one by US FDA. And I suggested the technology issue of CDx development process such as a selection of molecular diagnostics at the time of release, a clear understanding of the CDx mechanism, and a convergence of drug with CDx development. The necessity of social insurance system also was proposed for CDx development.

Prognosis of tongue squamous cell carcinoma associated with individual surgical margin and pathological features

  • Cho, Seongji;Sodnom-Ish, Buyanbileg;Eo, Mi Young;Lee, Ju Young;Kwon, Ik Jae;Myoung, Hoon;Yoon, Hye Jung;Kim, Soung Min
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.48 no.5
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    • pp.249-258
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    • 2022
  • The specific muscular structure of the tongue greatly affects margin shrinkage and tumor invasion, making the optimal surgical margin controversial. This study investigated surgical margin correlated prognosis of TSCC (tongue squamous cell carcinoma) according to margin location and its value, and the histopathologic factors which are suggestive of tumor invasion. And we would like to propose defining of the surgical margin for TSCC via prognosis according to location and margin values. We reviewed 45 patients diagnosed with TSCC who visited Seoul National University Dental Hospital (SNUDH) (Seoul, Republic of Korea) from 2010 to 2019, who were managed by a single surgical team. Patient clinical and pathological data of patients were retrospectively reviewed, and in 36 out of 45 patients, the pathologic parameters including the worst pattern of invasion (WPOI) and tumor budding were investigated via diagnostic histopathology slide reading. When standardized with as 0.25 cm anterior margins, as 0.35 cm deep margin, there was no significant difference in disease specific survival (DSS) or loco-regional recurrence-free survival (LRFS). Additionally, there was a non-significant difference in DSS and LRFS at the nearest margin of 0.35 cm (PDSS=0.276, PLRFS=0.162). Aggressive WPOI and high tumor budding showed lower survival and recurrence-free survival, and there were significant differences in close margin and involved margin frequencies. In TSCC, the value and location of the surgical margin did not have a significant relationship with prognosis, but WPOI and tumor budding suggesting the pattern of muscle invasion affected survival and recurrence-free survival. WPOI and tumor budding should be considered when setting an optimal surgical margin.

Reasonable necessity of preoperative laboratory tests in office-based oral and maxillofacial surgery

  • Mi Hyun Seo;Mi Young Eo;Kezia Rachellea Mustakim;Buyanbileg Sodnom-Ish;Hoon Myoung;Soung Min Kim
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.49 no.3
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    • pp.142-147
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    • 2023
  • Objectives: As medical history before surgery is often based on patient reporting, there is the possibility that patients intentionally hide underlying diseases or that dentists cannot recognize abnormal health states. Therefore, more professional and reliable treatment processes are needed under the Korean dental specialist system. The purpose of this study was to elucidate the necessity of a preoperative blood testing routine prior to office-based surgery under local anesthesia. Patients and Methods: Preoperative blood lab data for 5,022 patients from January 2018 to December 2019 were assembled. Study participants were those who underwent extraction or implant surgery under local anesthesia at Seoul National University Dental Hospital. Preoperative blood tests included complete blood count (CBC), blood chemistry, serum electrolyte, serology, and blood coagulation data. Values outside of the normal range were considered an "abnormality," and the percentage of abnormalities among the total number of patients was calculated. Patients were divided into two groups based on the presence of underlying disease. The rates of abnormalities in the blood tests were compared between groups. Chi-square tests were performed to compare data from the two groups, and P<0.05 was considered statistically significant. Results: The percentages of males and females in the study were 48.0% and 52.0%, respectively. Of all patients, 17.0% (Group B) reported known systemic disease, while 83.0% (Group A) reported no specific medical history. There were significant differences between Groups A and B in CBC, coagulation panel, electrolytes, and chemistry panel (P<0.05). In Group A, the results of blood tests that required a change in procedure were identified even though the proportion was very small. Conclusion: Preoperative blood tests for office-based surgery can detect underlying medical conditions that are difficult to identify from patient history alone and can prevent unexpected sequelae. In addition, such tests can result in a more professional treatment process and build patient confidence in the dentist.

Layered structure of sialoliths compared with tonsilloliths and antroliths

  • Buyanbileg Sodnom-Ish;Mi Young Eo;Yun Ju Cho;Mi Hyun Seo;Hyeong-Cheol Yang;Min-Keun Kim;Hoon Myoung;Soung Min Kim
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.50 no.1
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    • pp.13-26
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    • 2024
  • Objectives: The aim of this study was to perform a comparative analysis of the ultrastructural and chemical composition of sialoliths, tonsilloliths, and antroliths and to describe their growth pattern. Materials and Methods: We obtained 19 specimens from 18 patients and classified the specimens into three groups: sialolith (A), tonsillolith (B), and antrolith (C). The peripheral, middle, and core regions of the specimens were examined in detail by histology, micro-computed tomography (micro-CT), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy, and transmission electron microscopy (TEM). Results: In the micro-CT, group A showed alternating radiodense and radiolucent layers, while group B had a homogeneous structure. Group C specimens revealed a compact homogeneous structure. Histopathologically, group A showed a laminated, teardrop-shaped, globular structure. Group B demonstrated degrees of immature calcification of organic and inorganic materials. In group C, the lesion was not encapsulated and showed a homogeneous lamellar bone structure. SEM revealed that group A showed distinct three layers: a peripheral multilayer zone, intermediate compact zone, and the central nidus area; groups B and C did not show these layers. The main elemental components of sialoliths were O, C, Ca, N, Cu, P, Zn, Si, Zr, F, Na, and Mg. In group B, a small amount of Fe was found in the peripheral region. Group C had a shorter component list: Ca, C, O, P, F, N, Si, Na, and Mg. TEM analysis of group A showed globular structures undergoing intra-vesicular calcification. In group B, bacteria were present in the middle layer. In the outer layer of the group C antrolith, an osteoblastic rimming was observed. Conclusion: Sialoliths had distinct three layers: a peripheral multilayer zone, an intermediate compact zone and the central nidus area, while the tonsillolith and antrolith specimens lacked distinct layers and a core.

DEVELOPMENT OF STATEWIDE TRUCK TRAFFIC FORECASTING METHOD BY USING LIMITED O-D SURVEY DATA (한정된 O-D조사자료를 이용한 주 전체의 트럭교통예측방법 개발)

  • 박만배
    • Proceedings of the KOR-KST Conference
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    • 1995.02a
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    • pp.101-113
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    • 1995
  • The objective of this research is to test the feasibility of developing a statewide truck traffic forecasting methodology for Wisconsin by using Origin-Destination surveys, traffic counts, classification counts, and other data that are routinely collected by the Wisconsin Department of Transportation (WisDOT). Development of a feasible model will permit estimation of future truck traffic for every major link in the network. This will provide the basis for improved estimation of future pavement deterioration. Pavement damage rises exponentially as axle weight increases, and trucks are responsible for most of the traffic-induced damage to pavement. Consequently, forecasts of truck traffic are critical to pavement management systems. The pavement Management Decision Supporting System (PMDSS) prepared by WisDOT in May 1990 combines pavement inventory and performance data with a knowledge base consisting of rules for evaluation, problem identification and rehabilitation recommendation. Without a r.easonable truck traffic forecasting methodology, PMDSS is not able to project pavement performance trends in order to make assessment and recommendations in the future years. However, none of WisDOT's existing forecasting methodologies has been designed specifically for predicting truck movements on a statewide highway network. For this research, the Origin-Destination survey data avaiiable from WisDOT, including two stateline areas, one county, and five cities, are analyzed and the zone-to'||'&'||'not;zone truck trip tables are developed. The resulting Origin-Destination Trip Length Frequency (00 TLF) distributions by trip type are applied to the Gravity Model (GM) for comparison with comparable TLFs from the GM. The gravity model is calibrated to obtain friction factor curves for the three trip types, Internal-Internal (I-I), Internal-External (I-E), and External-External (E-E). ~oth "macro-scale" calibration and "micro-scale" calibration are performed. The comparison of the statewide GM TLF with the 00 TLF for the macro-scale calibration does not provide suitable results because the available 00 survey data do not represent an unbiased sample of statewide truck trips. For the "micro-scale" calibration, "partial" GM trip tables that correspond to the 00 survey trip tables are extracted from the full statewide GM trip table. These "partial" GM trip tables are then merged and a partial GM TLF is created. The GM friction factor curves are adjusted until the partial GM TLF matches the 00 TLF. Three friction factor curves, one for each trip type, resulting from the micro-scale calibration produce a reasonable GM truck trip model. A key methodological issue for GM. calibration involves the use of multiple friction factor curves versus a single friction factor curve for each trip type in order to estimate truck trips with reasonable accuracy. A single friction factor curve for each of the three trip types was found to reproduce the 00 TLFs from the calibration data base. Given the very limited trip generation data available for this research, additional refinement of the gravity model using multiple mction factor curves for each trip type was not warranted. In the traditional urban transportation planning studies, the zonal trip productions and attractions and region-wide OD TLFs are available. However, for this research, the information available for the development .of the GM model is limited to Ground Counts (GC) and a limited set ofOD TLFs. The GM is calibrated using the limited OD data, but the OD data are not adequate to obtain good estimates of truck trip productions and attractions .. Consequently, zonal productions and attractions are estimated using zonal population as a first approximation. Then, Selected Link based (SELINK) analyses are used to adjust the productions and attractions and possibly recalibrate the GM. The SELINK adjustment process involves identifying the origins and destinations of all truck trips that are assigned to a specified "selected link" as the result of a standard traffic assignment. A link adjustment factor is computed as the ratio of the actual volume for the link (ground count) to the total assigned volume. This link adjustment factor is then applied to all of the origin and destination zones of the trips using that "selected link". Selected link based analyses are conducted by using both 16 selected links and 32 selected links. The result of SELINK analysis by u~ing 32 selected links provides the least %RMSE in the screenline volume analysis. In addition, the stability of the GM truck estimating model is preserved by using 32 selected links with three SELINK adjustments, that is, the GM remains calibrated despite substantial changes in the input productions and attractions. The coverage of zones provided by 32 selected links is satisfactory. Increasing the number of repetitions beyond four is not reasonable because the stability of GM model in reproducing the OD TLF reaches its limits. The total volume of truck traffic captured by 32 selected links is 107% of total trip productions. But more importantly, ~ELINK adjustment factors for all of the zones can be computed. Evaluation of the travel demand model resulting from the SELINK adjustments is conducted by using screenline volume analysis, functional class and route specific volume analysis, area specific volume analysis, production and attraction analysis, and Vehicle Miles of Travel (VMT) analysis. Screenline volume analysis by using four screenlines with 28 check points are used for evaluation of the adequacy of the overall model. The total trucks crossing the screenlines are compared to the ground count totals. L V/GC ratios of 0.958 by using 32 selected links and 1.001 by using 16 selected links are obtained. The %RM:SE for the four screenlines is inversely proportional to the average ground count totals by screenline .. The magnitude of %RM:SE for the four screenlines resulting from the fourth and last GM run by using 32 and 16 selected links is 22% and 31 % respectively. These results are similar to the overall %RMSE achieved for the 32 and 16 selected links themselves of 19% and 33% respectively. This implies that the SELINICanalysis results are reasonable for all sections of the state.Functional class and route specific volume analysis is possible by using the available 154 classification count check points. The truck traffic crossing the Interstate highways (ISH) with 37 check points, the US highways (USH) with 50 check points, and the State highways (STH) with 67 check points is compared to the actual ground count totals. The magnitude of the overall link volume to ground count ratio by route does not provide any specific pattern of over or underestimate. However, the %R11SE for the ISH shows the least value while that for the STH shows the largest value. This pattern is consistent with the screenline analysis and the overall relationship between %RMSE and ground count volume groups. Area specific volume analysis provides another broad statewide measure of the performance of the overall model. The truck traffic in the North area with 26 check points, the West area with 36 check points, the East area with 29 check points, and the South area with 64 check points are compared to the actual ground count totals. The four areas show similar results. No specific patterns in the L V/GC ratio by area are found. In addition, the %RMSE is computed for each of the four areas. The %RMSEs for the North, West, East, and South areas are 92%, 49%, 27%, and 35% respectively, whereas, the average ground counts are 481, 1383, 1532, and 3154 respectively. As for the screenline and volume range analyses, the %RMSE is inversely related to average link volume. 'The SELINK adjustments of productions and attractions resulted in a very substantial reduction in the total in-state zonal productions and attractions. The initial in-state zonal trip generation model can now be revised with a new trip production's trip rate (total adjusted productions/total population) and a new trip attraction's trip rate. Revised zonal production and attraction adjustment factors can then be developed that only reflect the impact of the SELINK adjustments that cause mcreases or , decreases from the revised zonal estimate of productions and attractions. Analysis of the revised production adjustment factors is conducted by plotting the factors on the state map. The east area of the state including the counties of Brown, Outagamie, Shawano, Wmnebago, Fond du Lac, Marathon shows comparatively large values of the revised adjustment factors. Overall, both small and large values of the revised adjustment factors are scattered around Wisconsin. This suggests that more independent variables beyond just 226; population are needed for the development of the heavy truck trip generation model. More independent variables including zonal employment data (office employees and manufacturing employees) by industry type, zonal private trucks 226; owned and zonal income data which are not available currently should be considered. A plot of frequency distribution of the in-state zones as a function of the revised production and attraction adjustment factors shows the overall " adjustment resulting from the SELINK analysis process. Overall, the revised SELINK adjustments show that the productions for many zones are reduced by, a factor of 0.5 to 0.8 while the productions for ~ relatively few zones are increased by factors from 1.1 to 4 with most of the factors in the 3.0 range. No obvious explanation for the frequency distribution could be found. The revised SELINK adjustments overall appear to be reasonable. The heavy truck VMT analysis is conducted by comparing the 1990 heavy truck VMT that is forecasted by the GM truck forecasting model, 2.975 billions, with the WisDOT computed data. This gives an estimate that is 18.3% less than the WisDOT computation of 3.642 billions of VMT. The WisDOT estimates are based on the sampling the link volumes for USH, 8TH, and CTH. This implies potential error in sampling the average link volume. The WisDOT estimate of heavy truck VMT cannot be tabulated by the three trip types, I-I, I-E ('||'&'||'pound;-I), and E-E. In contrast, the GM forecasting model shows that the proportion ofE-E VMT out of total VMT is 21.24%. In addition, tabulation of heavy truck VMT by route functional class shows that the proportion of truck traffic traversing the freeways and expressways is 76.5%. Only 14.1% of total freeway truck traffic is I-I trips, while 80% of total collector truck traffic is I-I trips. This implies that freeways are traversed mainly by I-E and E-E truck traffic while collectors are used mainly by I-I truck traffic. Other tabulations such as average heavy truck speed by trip type, average travel distance by trip type and the VMT distribution by trip type, route functional class and travel speed are useful information for highway planners to understand the characteristics of statewide heavy truck trip patternS. Heavy truck volumes for the target year 2010 are forecasted by using the GM truck forecasting model. Four scenarios are used. Fo~ better forecasting, ground count- based segment adjustment factors are developed and applied. ISH 90 '||'&'||' 94 and USH 41 are used as example routes. The forecasting results by using the ground count-based segment adjustment factors are satisfactory for long range planning purposes, but additional ground counts would be useful for USH 41. Sensitivity analysis provides estimates of the impacts of the alternative growth rates including information about changes in the trip types using key routes. The network'||'&'||'not;based GMcan easily model scenarios with different rates of growth in rural versus . . urban areas, small versus large cities, and in-state zones versus external stations. cities, and in-state zones versus external stations.

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Detection of Human Papillomavirus and Expression of p53, c-erbB-2 Protein in Inverted Papilloma of the Nasal Cavity and Paranasal Sinuses (비강 및 부비동의 반전성 유두종에서 인유두종바이러스검출과 p53및 c-erbB-2의 발현)

  • Cho Jae-Shik;Baik Joon;Lim Sang-Chul;Cho Yeon;Yoon Je-Hwan;Seo Duk-Jung;Park Chang-Soo
    • Korean Journal of Head & Neck Oncology
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    • v.17 no.2
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    • pp.162-168
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    • 2001
  • Background: Inverted papilloma(IP) of the nasal cavity and paranasal sinuses is a benign neoplastic condition that can be associated with squamous cell carcinoma (SCC). Several studies have indicated an etiologic role for viruses in the development of inverted papilloma. And it is necessary to find out the significance of a biologic markers such as p53, c-erbB-2 to predict the malignant potential. The purposes of this study are to detect HPV in inverted papilloma of the nasal cavity and paranasal sinus, to examine role of HPV as an etiological agent, to examine the relationship between HPV subtype and malignant transformation of inverted papilloma, and to investigate the relation between expression rate of p53, c-erbB-2 and HPV in recurrent or malignant transformation cases. Material and Methods: Thirty two cases of inverted papilloma(IP) in the nasal cavity and paranasal sinuses were reviewed and classified into 3 groups; simple IP, IP with dysplasia group, IP with squamous cell carcinoma group. Paraffin embedded achival tissue was used in this study. The HPV was detected by in situ hybridzation (ISH) using HPV type 6/11, 16/18, 31/33/35 DNA probes. Expression of p53 and c-erbB-2 was examined by immunohistochemical staining. Results: 1) The HPV was detected in 6(19%) out of 32 cases. 2) The HPV 6/11 was dectected in 4 out of 21 cases of simple IP, HPV 16/18 in 1, HPV 31/33/35 in lout of 8 cases of IP with dysplasia respectively. 3) The positive expression of p53 was 13 cases out of 32 cases; 2 out of 21 cases of simple IP, all of 8 cases of IP with dysplasia and 3 cases of IP with squamous cell carcinoma 4) The positive expression of c-erbB-2 was in 24 out of 32 cases; 16 out of 21 cases of simple IP, 6 out of 8 cases of IP with dysplasia, 2 out of 3 cases of IP with squamous cell ca. 5) The recurrence of IP occurred in lout of 6 cases of positive for HPV, in 4 out of 26 cases negative for HPV. 6) The recurrence of IP occurred only in positive cases for p53. 7) The recurrence of IP occurred in 4(17%) out of 24 cases positive for c-erbB-2, in 1(13%) out of 8 cases negative for c-erbB-2. Conclusion: The p53 expression was associated with Inverted papillomas exhibiting evidence of malignant transformation. Also, there was a correlation between the p53 expression and recurrence.

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