1.A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer
Keun-Wook LEE ; Sae-Won HAN ; Tae Won KIM ; Joong Bae AHN ; Ji Yeon BAEK ; Sang Hee CHO ; Howard LEE ; Jin Won KIM ; Ji-Won KIM ; Tae-You KIM ; Yong Sang HONG ; Seung-Hoon BEOM ; Yongjun CHA ; Yoonjung CHOI ; Seonhui KIM ; Yung-Jue BANG
Cancer Research and Treatment 2024;56(2):590-601
Purpose:
GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a).
Materials and Methods:
Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study.
Results:
RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0).
Conclusion
GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.
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
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.
3.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.
4.Short- and long-term outcomes of subtotal/total colectomy in the management of obstructive left colon cancer
Jung Tak SON ; Yong Bog KIM ; Hyung Ook KIM ; Chungki MIN ; Yongjun PARK ; Sung Ryol LEE ; Kyung Uk JUNG ; Hungdai KIM
Annals of Coloproctology 2023;39(3):260-266
Purpose:
Surgical management of obstructive left colon cancer (OLCC) is still a matter of debate. The classic Hartmann procedure (HP) has a disadvantage that requires a second major operation. Subtotal colectomy/total abdominal colectomy (STC/TC) with ileosigmoid or ileorectal anastomosis is proposed as an alternative procedure to avoid stoma and anastomotic leakage. However, doubts about morbidity and functional outcome and lack of long-term outcomes have made surgeons hesitate to perform this procedure. Therefore, this trial was designed to provide data for morbidity, functional outcomes, and long-term outcomes of STC/TC.
Methods:
This study retrospectively analyzed consecutive cases of OLCC that were treated by STC/TC between January 2000 and November 2020 at a single tertiary referral center. Perioperative outcomes and long-term outcomes of STC/TC were analyzed.
Results:
Twenty-five descending colon cancer (45.5%) and 30 sigmoid colon cancer cases (54.5%) were enrolled in this study. Postoperative complications occurred in 12 patients. The majority complication was postoperative ileus (10 of 12). Anastomotic leakage and perioperative mortality were not observed. At 6 to 12 weeks after the surgery, the median frequency of defecation was twice per day (interquartile range, 1–3 times per day). Eight patients (14.5%) required medication during this period, but only 3 of 8 patients required medication after 1 year. The 3-year disease-free survival was 72.7% and 3-year overall survival was 86.7%.
Conclusion
The risk of anastomotic leakage is low after STC/TC. Functional and long-term outcomes are also acceptable. Therefore, STC/TC for OLCC is a safe, 1-stage procedure that does not require diverting stoma.
5.ERRATUM: Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group
Shinkyo YOON ; Miso KIM ; Yong Sang HONG ; Han Sang KIM ; Seung Tae KIM ; Jihun KIM ; Hongseok YUN ; Changhoon YOO ; Hee Kyung AHN ; Hyo Song KIM ; In Hee LEE ; In-Ho KIM ; Inkeun PARK ; Jae Ho JEONG ; Jaekyung CHEON ; Jin Won KIM ; Jina YUN ; Sun Min LIM ; Yongjun CHA ; Se Jin JANG ; Dae Young ZANG ; Tae Won KIM ; Jin Hyoung KANG ; Jee Hyun KIM
Cancer Research and Treatment 2023;55(3):1061-1061
6.Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group
Shinkyo YOON ; Miso KIM ; Yong Sang HONG ; Han Sang KIM ; Seung Tae KIM ; Jihun KIM ; Hongseok YUN ; Changhoon YOO ; Hee Kyung AHN ; Hyo Song KIM ; In Hee LEE ; In-Ho KIM ; Inkeun PARK ; Jae Ho JEONG ; Jaekyung CHEON ; Jin Won KIM ; Jina YUN ; Sun Min LIM ; Yongjun CHA ; Se Jin JANG ; Dae Young ZANG ; Tae Won KIM ; Jin Hyoung KANG ; Jee Hyun KIM
Cancer Research and Treatment 2022;54(1):1-9
Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea’s public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.
7.Comparison of blowhole colostomy and loop ostomy for palliation of acute malignant colonic obstruction
Yongjun PARK ; Dong Uk CHOI ; Hyung Ook KIM ; Yong Bog KIM ; Chungki MIN ; Jung Tack SON ; Sung Ryol LEE ; Kyung Uk JUNG ; Hungdai KIM
Annals of Coloproctology 2022;38(4):319-326
Purpose:
Surgery to create a stoma for decompression might be required for unresectable stage IV cancer patients with complete colonic obstruction. The aim of this study was to compare the results of blowhole colostomy with those of loop ostomy.
Methods:
Palliative ileostomy or colostomy procedures performed at a single center between January 2011 and October 2020, were analyzed retrospectively. Fifty-nine patients were identified during this period. The demographic characteristics and outcomes between the blowhole colostomy group (n=24) and the loop ostomy group (n=35) were compared.
Results:
The median operative time tended to be shorter in the blowhole colostomy group (52.5 minutes; interquartile range [IQR], 43–65) than in the loop ostomy group (60 minutes; IQR, 40–107), but the difference did not reach statistical significance (P=0.162). The median length of hospital stay was significantly shorter with blowhole colostomy (blowhole, 13 days [IQR, 9–23]; loop, 21 days [IQR, 14–37]; P=0.013). Mean cecum diameter was significantly larger in the blowhole group than in the loop group (8.83±1.91 cm vs. 6.78±2.36 cm, P=0.001), and the emergency operation rate was higher in the blowhole group than in the loop group (22 of 24 [91.7%] vs. 23 of 35 [65.7%], P=0.021).
Conclusion
In surgical emergencies, diverting a blowhole colostomy can be safe and effective for palliative management of colonic obstruction in patients with end-stage cancer and might reduce the operative time in emergent situations.
8.Draft Genome Sequence of the White-Rot Fungus Schizophyllum commune IUM1114-SS01
Da-Woon KIM ; Junhyeok NAM ; Ha Thi KIM NGUYEN ; Jiwon LEE ; Yongjun CHOI ; Jaehyuk CHOI
Mycobiology 2021;49(1):86-88
The monokaryotic strain, Schizophyllum commune strain IUM1114-SS01, was generated from a basidiospore of dikaryotic parental strain IUM1114. It even showed the decolorizing activities for several textile dyes much better than its parental strain. Based on the results of a single-molecule real-time sequencing technology, we present the draft genome of S. commune IUM1114-SS01, comprising 41.1 Mb with GC contents of the genome were 57.44%.Among 13,380 protein-coding genes, 534 genes are carbon hydrate-active enzyme coding genes.
9.Identification of African swine fever virus genomic DNAs in wild boar habitats within outbreak regions in South Korea
Kyung-Lak LEE ; Yongjun CHOI ; Jongchan YOO ; Jusun HWANG ; Hyun-Gi JEONG ; Weon-Hwa JHEONG ; Seon-Hee KIM
Journal of Veterinary Science 2021;22(2):e28-
An African swine fever (ASF) outbreak in wild boars was first reported on October 2, 2019, in South Korea. Since then, additional cases were reported in South Korea's border areas. We here report the identification of ASF virus (ASFV) DNAs from two out of eight environmental abiotic matter samples collected from areas where ASF-positive wild boar carcasses were found. Comparative genomic investigations suggested that the contaminating ASFV DNAs originated from the wild boar whose carcass had been found near the positive sample sites.This is the first report on the identification of ASF viral material in wild boar habitats.
10.6-O-Galloylsalidroside, an Active Ingredient from Acer tegmentosum, Ameliorates Alcoholic Steatosis and Liver Injury in a Mouse Model of Chronic Ethanol Consumption
Young Han KIM ; Dong-Cheol WOO ; Moonjin RA ; Sangmi JUNG ; Ki Hyun KIM ; Yongjun LEE
Natural Product Sciences 2021;27(3):201-207
We have previously reported that Acer tegmentosum extract, which is traditionally used in Korea to reduce alcohol-related liver injury, suppresses liver inflammation caused by excessive alcohol consumption and might improve metabolism. The active ingredient, 6-O-galloylsalidroside (GAL), was isolated from A.tegmentosum, and we hypothesized that GAL could provide desirable pharmacological benefits by ameliorating physiological conditions caused by alcohol abuse. Therefore, this study focused on whether GAL could ameliorate alcoholic fat accumulation and repair liver injury in mice. During chronic alcohol consumption plus binge feeding in mice, GAL was administered orally once per day for 11 days. Intrahepatic lipid accumulation was measured in vivo using a noninvasive method, 1H magnetic resonance imaging, and confirmed by staining with hematoxylin and eosin and Oil Red O. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using a Konelab system, and the triglyceride content was measured in liver homogenates using an enzymatic peroxide assay. The results suggested that GAL alleviated alcohol-induced steatosis,e as indicated by decreased hepatic and serum triglyceride levels in ethanol-fed mice. GAL treatment also correlated with a decrease in the Cd36 mRNA expression, thus potentially inhibiting the development of alcoholic steatosis via the hepatic de novo lipogenesis pathway. Furthermore, treatment with GAL inhibited the expression of cytochrome P450 2E1 and attenuated hepatocellular damage, as reflected by a reduction in ALT and AST levels. These findings suggest that GAL extracted from A.tegmentosum has the potential to serve as a bioactive agent for the treatment of alcoholic fatty liver and liver damage.

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