1.Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP
Miso KIM ; Hyo Sup SHIM ; Sheehyun KIM ; In Hee LEE ; Jihun KIM ; Shinkyo YOON ; Hyung-Don KIM ; Inkeun PARK ; Jae Ho JEONG ; Changhoon YOO ; Jaekyung CHEON ; In-Ho KIM ; Jieun LEE ; Sook Hee HONG ; Sehhoon PARK ; Hyun Ae JUNG ; Jin Won KIM ; Han Jo KIM ; Yongjun CHA ; Sun Min LIM ; Han Sang KIM ; Choong-kun LEE ; Jee Hung KIM ; Sang Hoon CHUN ; Jina YUN ; So Yeon PARK ; Hye Seung LEE ; Yong Mee CHO ; Soo Jeong NAM ; Kiyong NA ; Sun Och YOON ; Ahwon LEE ; Kee-Taek JANG ; Hongseok YUN ; Sungyoung LEE ; Jee Hyun KIM ; Wan-Seop KIM
Cancer Research and Treatment 2024;56(3):721-742
In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.
2.Clinical practice recommendations for the use of next-generation sequencing in patients with solid cancer: a joint report from KSMO and KSP
Miso KIM ; Hyo Sup SHIM ; Sheehyun KIM ; In Hee LEE ; Jihun KIM ; Shinkyo YOON ; Hyung-Don KIM ; Inkeun PARK ; Jae Ho JEONG ; Changhoon YOO ; Jaekyung CHEON ; In-Ho KIM ; Jieun LEE ; Sook Hee HONG ; Sehhoon PARK ; Hyun Ae JUNG ; Jin Won KIM ; Han Jo KIM ; Yongjun CHA ; Sun Min LIM ; Han Sang KIM ; Choong-Kun LEE ; Jee Hung KIM ; Sang Hoon CHUN ; Jina YUN ; So Yeon PARK ; Hye Seung LEE ; Yong Mee CHO ; Soo Jeong NAM ; Kiyong NA ; Sun Och YOON ; Ahwon LEE ; Kee-Taek JANG ; Hongseok YUN ; Sungyoung LEE ; Jee Hyun KIM ; Wan-Seop KIM
Journal of Pathology and Translational Medicine 2024;58(4):147-164
In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.
3.Impact of Coronavirus Disease 2019 on Gastric Cancer Diagnosis and Stage:A Single-Institute Study in South Korea
Moonki HONG ; Mingee CHOI ; JiHyun LEE ; Kyoo Hyun KIM ; Hyunwook KIM ; Choong-Kun LEE ; Hyo Song KIM ; Sun Young RHA ; Gyu Young PIH ; Yoon Jin CHOI ; Da Hyun JUNG ; Jun Chul PARK ; Sung Kwan SHIN ; Sang Kil LEE ; Yong Chan LEE ; Minah CHO ; Yoo Min KIM ; Hyoung-Il KIM ; Jae-Ho CHEONG ; Woo Jin HYUNG ; Jaeyong SHIN ; Minkyu JUNG
Journal of Gastric Cancer 2023;23(4):574-583
Purpose:
Gastric cancer (GC) is among the most prevalent and fatal cancers worldwide.National cancer screening programs in countries with high incidences of this disease provide medical aid beneficiaries with free-of-charge screening involving upper endoscopy to detect early-stage GC. However, the coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions to routine healthcare access. Thus, this study aimed to assess the impact of COVID-19 on the diagnosis, overall incidence, and stage distribution of GC.
Materials and Methods:
We identified patients in our hospital cancer registry who were diagnosed with GC between January 2018 and December 2021 and compared the cancer stage at diagnosis before and during the COVID-19 pandemic. Subgroup analyses were conducted according to age and sex. The years 2018 and 2019 were defined as the “before COVID” period, and the years 2020 and 2021 as the “during COVID” period.
Results:
Overall, 10,875 patients were evaluated; 6,535 and 4,340 patients were diagnosed before and during the COVID-19 period, respectively. The number of diagnoses was lower during the COVID-19 pandemic (189 patients/month vs. 264 patients/month) than before it.Notably, the proportion of patients with stages 3 or 4 GC in 2021 was higher among men and patients aged ≥40 years.
Conclusions
During the COVID-19 pandemic, the overall number of GC diagnoses decreased significantly in a single institute. Moreover, GCs were in more advanced stages at the time of diagnosis. Further studies are required to elucidate the relationship between the COVID-19 pandemic and the delay in the detection of GC worldwide.
4.Response to growth hormone according to provocation test results in idiopathic short stature and idiopathic growth hormone deficiency
Ju Young YOON ; Chong Kun CHEON ; Jung Hyun LEE ; Min Jung KWAK ; Hyun-Ji KIM ; Ye Jin KIM ; Jeong Eun LEE ; Woo Yeong CHUNG ; Jeongyun KIM ; Jae-Ho YOO
Annals of Pediatric Endocrinology & Metabolism 2022;27(1):37-43
Purpose:
To investigate growth response in children with either idiopathic short stature (ISS) or growth hormone (GH) deficiency (GHD).
Methods:
The data of prepubertal GHD or ISS children treated using recombinant human GH were obtained from the LG Growth Study database. GHD children were further divided into partial and complete GHD groups. Growth response and factors predicting growth response after 1 and 2 years of GH treatment were investigated.
Results:
This study included 692 children (98 with ISS, 443 partial GHD, and 151 complete GHD). After 1 year, changes in height standard deviation score (ΔHt-SDS) were 0.78, 0.83, and 0.96 in ISS, partial GHD, and complete GHD, respectively. Height velocity (HV) was 8.72, 9.04, and 9.52 cm/yr in ISS, partial GHD, and complete GHD, respectively. ΔHt-SDS and HV did not differ among the 3 groups. Higher initial body mass index standard deviation score (BMI-SDS) and midparental height standard deviation score (MPH-SDS) were predictors for better growth response after 1 year in ISS and the partial GHD group, respectively. In the complete GHD group, higher Ht-SDS and BMI-SDS predicted better growth response after 1 year. After 2 years of GH treatment, higher BMI-SDS and MPH-SDS predicted a better growth outcome in the partial GHD group, and higher MPH-SDS was a predictor of good growth response in complete GHD.
Conclusion
Clinical characteristics and growth response did not differ among groups. Predictors of growth response differed among the 3 groups, and even in the same group, a higher GH dose would be required when poor response is predicted.
5.Generation of a recombinant rabies virus expressing green fluorescent protein for a virus neutralization antibody assay
Dong-Kun YANG ; Ha-Hyun KIM ; Yu-Ri PARK ; Jae Young YOO ; Yeseul PARK ; Jungwon PARK ; Bang-Hun HYUN
Journal of Veterinary Science 2021;22(4):e56-
Background:
Fluorescent antibody virus neutralization (FAVN) test is a standard assay for quantifying rabies virus-neutralizing antibody (VNA) in serum. However, a safer rabies virus (RABV) should be used in the FAVN assay. There is a need for a new method that is economical and time-saving by eliminating the immunostaining step.
Objectives:
We aimed to improve the traditional FAVN method by rescuing and characterizing a new recombinant RABV expressing green fluorescent protein (GFP).
Methods:
A new recombinant RABV expressing GFP designated as ERAGS-GFP was rescued using a reverse genetic system. Immuno-fluorescence assay, peroxidase-linked assay, electron microscopy and reverse transcription polymerase chain reaction were performed to confirm the recombinant ERAGS-GFP virus as a RABV expressing the GFP gene. The safety of ERAGS-GFP was evaluated in 4-week-old mice. The rabies VNA titers were measured and compared with conventional FAVN and FAVN-GFP tests using VERO cells.
Results:
The virus propagated in VERO cells was confirmed as RABV expressing GFP.The ERAGS-GFP showed the highest titer (108.0TCID50/mL) in VERO cells at 5 days postinoculation, and GFP expression persisted until passage 30. The body weight of 4-week-old mice inoculated intracranially with ERAGS-GFP continued to increase and the survival rate was 100%. In 62 dog sera, the FAVN-GFP result was significantly correlated with that of conventional FAVN (r = 0.95).
Conclusions
We constructed ERAGS-GFP, which could replace the challenge virus standard-11 strain used in FAVN test.
6.Expression of the VP2 protein of feline panleukopenia virus in insect cells and use thereof in a hemagglutination inhibition assay
Dong-Kun YANG ; Yeseul PARK ; Yu-Ri PARK ; Jae Young YOO ; Sungjun AN ; Jungwon PARK ; Bang-Hun HYUN
Korean Journal of Veterinary Research 2021;61(2):e19-
Feline panleukopenia virus (FPV) causes leukopenia and severe hemorrhagic diarrhea, killing 50% of naturally infected cats. Although intact FPV can serve as an antigen in the hemagglutination inhibition (HI) test, accidental laboratory-mediated infection a concern. A non-infectious diagnostic reagent is required for the HI test. Here, we expressed the viral protein 2 (VP2) gene of the FPV strain currently prevalent in South Korea in a baculovirus expression system; VP2 protein was identified by an indirect immunofluorescence assay, electron microscopy (EM), Western blotting (WB), and a hemagglutination assay (HA). EM showed that the recombinant VP2 protein self-assembled to form virus-like particles. WB revealed that the recombinant VP2 was 65 kDa in size. The HA activity of the recombinant VP2 protein was very high at 1:215. A total of 143 cat serum samples were tested using FPV (HI-FPV test) and the recombinant VP2 protein (HI-VP2 test) as HI antigens. The sensitivity, specificity, and accuracy of the HI-VP2 test were 99.3%, 88.9%, and 99.3%, respectively, compared to the HI-FPV test. The HI-VP2 and HI-FPV results correlated significantly (r = 0.978). Thus, recombinant VP2 can substitute for intact FPV as the serological diagnostic reagent of the HI test for FPV.
7.Isolation and identification of mammalian orthoreovirus type 3 from a Korean roe deer (Capreolus pygargus)
Dong-Kun YANG ; Sungjun AN ; Yeseul PARK ; Jae Young YOO ; Yu-Ri PARK ; Jungwon PARK ; Jong-Taek KIM ; Sangjin AHN ; Bang-Hun HYUN
Korean Journal of Veterinary Research 2021;61(2):e13-
Mammalian reovirus (MRV) causes respiratory and intestinal disease in mammals. Although MRV isolates have been reported to circulate in several animals, there are no reports on Korean MRV isolates from wildlife. We investigated the biological and molecular characteristics of Korean MRV isolates based on the nucleotide sequence of the segment 1 gene. In total, 144 swabs from wild animals were prepared for virus isolation. Based on virus isolation with specific cytopathic effects, indirect fluorescence assays, electron microscopy, and reverse transcription-polymerase chain reaction, one isolate was confirmed to be MRV. The isolate exhibited a hemagglutination activity level of 16 units with pig erythrocytes and had a maximum viral titer of 105.7 50% tissue culture infectious dose (TCID50)/mL in Vero cells at 5 days after inoculation. The nucleotide and amino-acid sequences of the partial segment S1 of the MReo2045 isolate were determined and compared with those of other MRV strains. The MReo2045 isolate had nucleotide sequences similar to MRV-3 and was most similar (96.1%) to the T3/Bat/Germany/342/08 strain, which was isolated in Germany in 2008. The MReo2045 isolate will be useful as an antigen for sero-epidemiological studies and developing diagnostic tools.
8.Immunogenicity of an inactivated rabies vaccine for animals derived from the recombinant ERAGS strain
Dong-Kun YANG ; Ha-Hyun KIM ; Yu-Ri PARK ; Jae Young YOO ; Yeseul PARK ; Sungjun AN ; Bang-Hun HYUN
Clinical and Experimental Vaccine Research 2021;10(2):141-147
Purpose:
The aims of the present study were to evaluate the immunogenicity of an inactivated rabies vaccine based on the ERAGS strain
Materials and Methods:
The ERAGS virus propagated in Vero cells was inactivated with 3 mM binary ethylenimine for 8 hours. Three types of inactivated rabies vaccines were prepared to determine the minimum vaccine virus titers. Four further types of inactivated rabies vaccines were prepared by blending inactivated ERAGS with four different adjuvants; each vaccine was injected into mice, guinea pigs, and dogs to identify the optimal adjuvant. The immunogenicity of a Montanide (IMS) gel-adjuvanted vaccine was evaluated in cats, dogs, and cattle. Humoral immune responses were measured via a fluorescent antibody virus neutralization method and a blocking enzyme-linked immunosorbent assay.
Results:
The minimum virus titer of the inactivated rabies vaccine was over 107.0 50% tissue culture infectious doses (TCID50 values)/mL. Of the four kinds of adjuvants, the IMS gel-adjuvanted vaccine induced the highest mean viral neutralizing antibody (VNA) titers of 6.24 and 2.36 IU/mL in guinea pigs and dogs, respectively, and was thus selected as the vaccine for the target animals. Cats, dogs, and cattle inoculated with the IMS gel-adjuvanted vaccine developed protective VNA titers ranging from 3.5 to 1.2 IU/mL at 4 weeks post-inoculation (WPI).
Conclusion
Our data indicate that cats, dogs, and cattle inoculated with an inactivated rabies vaccine derived from the ERAGS strain developed protective immune responses that were maintained to 12 WPI.
9.Generation of a recombinant rabies virus expressing green fluorescent protein for a virus neutralization antibody assay
Dong-Kun YANG ; Ha-Hyun KIM ; Yu-Ri PARK ; Jae Young YOO ; Yeseul PARK ; Jungwon PARK ; Bang-Hun HYUN
Journal of Veterinary Science 2021;22(4):e56-
Background:
Fluorescent antibody virus neutralization (FAVN) test is a standard assay for quantifying rabies virus-neutralizing antibody (VNA) in serum. However, a safer rabies virus (RABV) should be used in the FAVN assay. There is a need for a new method that is economical and time-saving by eliminating the immunostaining step.
Objectives:
We aimed to improve the traditional FAVN method by rescuing and characterizing a new recombinant RABV expressing green fluorescent protein (GFP).
Methods:
A new recombinant RABV expressing GFP designated as ERAGS-GFP was rescued using a reverse genetic system. Immuno-fluorescence assay, peroxidase-linked assay, electron microscopy and reverse transcription polymerase chain reaction were performed to confirm the recombinant ERAGS-GFP virus as a RABV expressing the GFP gene. The safety of ERAGS-GFP was evaluated in 4-week-old mice. The rabies VNA titers were measured and compared with conventional FAVN and FAVN-GFP tests using VERO cells.
Results:
The virus propagated in VERO cells was confirmed as RABV expressing GFP.The ERAGS-GFP showed the highest titer (108.0TCID50/mL) in VERO cells at 5 days postinoculation, and GFP expression persisted until passage 30. The body weight of 4-week-old mice inoculated intracranially with ERAGS-GFP continued to increase and the survival rate was 100%. In 62 dog sera, the FAVN-GFP result was significantly correlated with that of conventional FAVN (r = 0.95).
Conclusions
We constructed ERAGS-GFP, which could replace the challenge virus standard-11 strain used in FAVN test.
10.Expression of the VP2 protein of feline panleukopenia virus in insect cells and use thereof in a hemagglutination inhibition assay
Dong-Kun YANG ; Yeseul PARK ; Yu-Ri PARK ; Jae Young YOO ; Sungjun AN ; Jungwon PARK ; Bang-Hun HYUN
Korean Journal of Veterinary Research 2021;61(2):e19-
Feline panleukopenia virus (FPV) causes leukopenia and severe hemorrhagic diarrhea, killing 50% of naturally infected cats. Although intact FPV can serve as an antigen in the hemagglutination inhibition (HI) test, accidental laboratory-mediated infection a concern. A non-infectious diagnostic reagent is required for the HI test. Here, we expressed the viral protein 2 (VP2) gene of the FPV strain currently prevalent in South Korea in a baculovirus expression system; VP2 protein was identified by an indirect immunofluorescence assay, electron microscopy (EM), Western blotting (WB), and a hemagglutination assay (HA). EM showed that the recombinant VP2 protein self-assembled to form virus-like particles. WB revealed that the recombinant VP2 was 65 kDa in size. The HA activity of the recombinant VP2 protein was very high at 1:215. A total of 143 cat serum samples were tested using FPV (HI-FPV test) and the recombinant VP2 protein (HI-VP2 test) as HI antigens. The sensitivity, specificity, and accuracy of the HI-VP2 test were 99.3%, 88.9%, and 99.3%, respectively, compared to the HI-FPV test. The HI-VP2 and HI-FPV results correlated significantly (r = 0.978). Thus, recombinant VP2 can substitute for intact FPV as the serological diagnostic reagent of the HI test for FPV.

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