1.Immune deficiency phenotypes of Il2rg, Rag2 or Il2rg/Rag2 double knockout rats;establishment of human leukemia xenograft models
Joo‑Il KIM ; Hyun‑Jin LIM ; Euna KWON ; Tomoji MASHIMO ; Byeong‑Cheol KANG
Laboratory Animal Research 2024;40(4):487-497
Background:
Genetically immunodeficient mice lacking Il2rg and Rag2 genes have been widely utilized in the field of biomedical research. However, immunodeficient rats, which offer the advantage of larger size, have not been as extensively used to date. Recently, Severe Combined Immunodeficiency (SCID) rats were generated using CRISPR/ Cas9 system, targeting Il2rg and Rag2 in National BioResource Project in Japan. We imported and investigated more detailed phenotypes of wild-type (WT) Il2rg knockout (KO), Rag2 KO and Il2rg/Rag2 KO rats for 20 weeks.
Results:
During experiments, Il2rg KO, Rag2 KO and Il2rg/Rag2 KO rats showed decreased white blood cells and sys‑ temic lymphopenia, with reduced CD4+, CD8+ T cells and CD161+ NK cells. Additionally, all KO strains exhibited reduced relative spleen weights, hypoplasia of the germinal center in the white pulp, and atrophy with the disap‑ pearance of the boundary between the cortex and medulla in the thymus, compared to WT rats. Furthermore, we established human acute lymphoblastic leukemia xenograft rat model by intravenously injecting 5.0 × 106 cells/kg of NALM6 cells into Il2rg/Rag2 KO rats.
Conclusions
These findings indicate that Il2rg KO, Rag2 KO, and Il2rg/Rag2 KO rats exhibited SCID phenotypes, sug‑ gesting their potential application as immunodeficient animal models for tumor xenograft studies.
2.Antigenicity evaluation of lac color and exploratory study for identifying potential biomarkers of anaphylaxis
Hyun‑Jin LIM ; Kang Min HAN ; Seung‑Hyun KIM ; Soo‑Kyung RYU ; Ji‑Ran YOU ; Jung‑Hee YOON ; Euna KWON ; Ji‑Eun KIM ; Byeong‑Cheol KANG
Laboratory Animal Research 2024;40(4):461-475
Background:
Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensi‑ tization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups.
Results:
In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p < 0.05).
Conclusions
Our study concludes that lac color, at the tested concentrations, does not induce antigenicity in the guinea pig model, providing valuable safety data. Furthermore, the biomarkers identified in this study offer a supportive approach to evaluating the immunogenicity of substances in future research.
3.Practice guidelines for managing extrahepatic biliary tract cancers
Hyung Sun KIM ; Mee Joo KANG ; Jingu KANG ; Kyubo KIM ; Bohyun KIM ; Seong-Hun KIM ; Soo Jin KIM ; Yong-Il KIM ; Joo Young KIM ; Jin Sil KIM ; Haeryoung KIM ; Hyo Jung KIM ; Ji Hae NAHM ; Won Suk PARK ; Eunkyu PARK ; Joo Kyung PARK ; Jin Myung PARK ; Byeong Jun SONG ; Yong Chan SHIN ; Keun Soo AHN ; Sang Myung WOO ; Jeong Il YU ; Changhoon YOO ; Kyoungbun LEE ; Dong Ho LEE ; Myung Ah LEE ; Seung Eun LEE ; Ik Jae LEE ; Huisong LEE ; Jung Ho IM ; Kee-Taek JANG ; Hye Young JANG ; Sun-Young JUN ; Hong Jae CHON ; Min Kyu JUNG ; Yong Eun CHUNG ; Jae Uk CHONG ; Eunae CHO ; Eui Kyu CHIE ; Sae Byeol CHOI ; Seo-Yeon CHOI ; Seong Ji CHOI ; Joon Young CHOI ; Hye-Jeong CHOI ; Seung-Mo HONG ; Ji Hyung HONG ; Tae Ho HONG ; Shin Hye HWANG ; In Gyu HWANG ; Joon Seong PARK
Annals of Hepato-Biliary-Pancreatic Surgery 2024;28(2):161-202
Background:
s/Aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021.
Methods:
Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop.
Results:
In November 2021, the finalized draft was presented for public scrutiny during a formal hearing.
Conclusions
The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.
4.Pharmacological properties of Technekitty injection (Tc-99m) in diagnosing feline hyperthyroidism
Jae Cheong LIM ; So-Young LEE ; Eun Ha CHO ; Yu Mi JUNG ; Ki Hwan PARK ; Young Uk PARK ; Sung Soo NAM ; Tae Hoon LEE ; Jae Won LEE ; Jisu SUN ; Hye Kyung CHUNG ; Yong Jin LEE ; Yeon CHAE ; Byeong-Teck KANG
Journal of Biomedical and Translational Research 2024;25(4):185-199
Thyroid scanning using technetium-99m ( 99mTc) is the gold standard for diagnosing feline hyperthyroidism. In cats with an overactive thyroid, a thyroid scan is the most appropriate imaging technique to detect and localize any hyperfunctional adenomatous thyroid tissue. In this study, the pharmacological properties of the Technekitty injection (Tc-99m), developed as a diagnostic agent for feline hyperthyroidism using 99mTc as an active ingredient, were tested in FRTL-5 thyroid follicular cell line and ICR mice. The percentage of cell uptake of the Tc-99m in FRTL-5 thyroid cells was 0.182 ± 0.018%, which was about 6 times higher compared to Clone 9 hepatocytes. This uptake decreased by 38.2% due to competitive inhibition by iodine (sodium iodide). In tissue distribution tests by using ICR mice, the highest distribution was observed in the liver, kidneys, spleen, lungs, and femur at 0.083 hours after administration, and this distribution decreased as the compound was excreted through the kidneys, the pri-mary excretory organ. Maximum distribution was confirmed at 1 hour in the small intestine, 6hours in the large intestine, and 2 hours in the thyroid gland. Additionally, the total amount excreted through urine and feces over 48 hours (2 days) was 78.80% of the injected dose, with 37.70% (47.84% of the total excretion) excreted through urine and 41.10% (52.16% of the total excretion) through feces. In conclusion, the Tc-99m has the same mechanism of action, potency, absorption, distribution, metabolism, and excretion characteristics as 99mTc used for feline hyperthyroidism in the United States, Europe, and other countries, because the Technekitty injection (Tc-99m) contains 99mTc as its sole active ingredient. Based on these results, the Technekitty injection (Tc-99m) is expected to be safely used in the clinical diagnosis of feline hyperthyroidism.
5.Clinical Application of Artificial Intelligence-Based Computed Tomography Analysis of Myosteatosis in Localized Renal Cell Carcinoma
Byeong Jin KANG ; Kyung Hwan KIM ; Seung Baek HONG ; Nam Kyung LEE ; Suk KIM ; Sihwan KIM ; Hong Koo HA
Journal of Urologic Oncology 2024;22(3):237-245
Purpose:
Myosteatosis, defined as fat infiltration in muscle tissue, has been linked to poor outcomes in various cancers. However, the prognostic impact of myosteatosis on renal cell carcinoma (RCC) remains poorly understood. This study evaluated the predictive value of myosteatosis based on an artificial intelligence (AI)-driven computed tomography (CT) analysis in patients with localized RCC who underwent partial nephrectomy.
Materials and Methods:
This retrospective study included 170 patients with localized RCC who underwent partial nephrectomy at a single institution between 2011 and 2017. Myosteatosis was assessed on CT scans using an AI-based tool. The patients were categorized into 2 groups according to the presence or absence of myosteatosis. The clinical outcomes, including disease-free survival (DFS), were compared to determine the prognostic significance of myosteatosis.
Results:
Of 170 patients, 36 (21.2%) were diagnosed with myosteatosis. These patients were older and had a higher body mass index. The myosteatosis group had a higher proportion of females than the no myosteatosis group. Lymphovascular invasion and tumor necrosis were prevalent pathological features in patients with myosteatosis. Kaplan-Meier analysis demonstrated that myosteatosis was associated with significantly shorter DFS (p<0.05). Multivariate analysis confirmed that myosteatosis independently predicted adverse outcomes in patients with localized RCC.
Conclusion
AI-based CT analysis of myosteatosis is a reliable method for improving the risk stratification of patients with localized RCC. Patients with myosteatosis demonstrate poor pathological features and shorter DFS. These findings highlight the potential of AI-driven body composition analysis to refine prognostic models and personalized treatment strategies.
6.Immune deficiency phenotypes of Il2rg, Rag2 or Il2rg/Rag2 double knockout rats;establishment of human leukemia xenograft models
Joo‑Il KIM ; Hyun‑Jin LIM ; Euna KWON ; Tomoji MASHIMO ; Byeong‑Cheol KANG
Laboratory Animal Research 2024;40(4):487-497
Background:
Genetically immunodeficient mice lacking Il2rg and Rag2 genes have been widely utilized in the field of biomedical research. However, immunodeficient rats, which offer the advantage of larger size, have not been as extensively used to date. Recently, Severe Combined Immunodeficiency (SCID) rats were generated using CRISPR/ Cas9 system, targeting Il2rg and Rag2 in National BioResource Project in Japan. We imported and investigated more detailed phenotypes of wild-type (WT) Il2rg knockout (KO), Rag2 KO and Il2rg/Rag2 KO rats for 20 weeks.
Results:
During experiments, Il2rg KO, Rag2 KO and Il2rg/Rag2 KO rats showed decreased white blood cells and sys‑ temic lymphopenia, with reduced CD4+, CD8+ T cells and CD161+ NK cells. Additionally, all KO strains exhibited reduced relative spleen weights, hypoplasia of the germinal center in the white pulp, and atrophy with the disap‑ pearance of the boundary between the cortex and medulla in the thymus, compared to WT rats. Furthermore, we established human acute lymphoblastic leukemia xenograft rat model by intravenously injecting 5.0 × 106 cells/kg of NALM6 cells into Il2rg/Rag2 KO rats.
Conclusions
These findings indicate that Il2rg KO, Rag2 KO, and Il2rg/Rag2 KO rats exhibited SCID phenotypes, sug‑ gesting their potential application as immunodeficient animal models for tumor xenograft studies.
7.Antigenicity evaluation of lac color and exploratory study for identifying potential biomarkers of anaphylaxis
Hyun‑Jin LIM ; Kang Min HAN ; Seung‑Hyun KIM ; Soo‑Kyung RYU ; Ji‑Ran YOU ; Jung‑Hee YOON ; Euna KWON ; Ji‑Eun KIM ; Byeong‑Cheol KANG
Laboratory Animal Research 2024;40(4):461-475
Background:
Lac color, a natural red dye derived from the larvae of laccifer lacca kerr, is one of the most commonly used substances in food. To date, no studies have reported on the antigenicity of lac color and the other biomarkers that can determine anaphylactic reactions. To address this, we evaluated the antigenicity of lac color through active systemic anaphylaxis (ASA) in addition to identifying potential biomarkers performing exploratory studies. For ASA test, Guinea pigs (n = 5) were sensitized with 0(negative control), 4 mg/kg of lac color, 4 mg/kg of lac color + FCA, and 5 mg/kg of ovalbumin + FCA (positive control) 3 times a week for three weeks. Fourteen days after the last sensi‑ tization, animals were challenged intravenously weekly for two weeks. Hematological and histopathological analyses were performed and compared to control groups.
Results:
In the ASA test, all lac color groups showed mild symptoms such as nose rubbing, urination, and evacuation, which are insufficient indicators of anaphylaxis. Exploratory studies identified several biomarkers: decreased platelet count, and increased basophil count; distention in the lung, and redness on the inner wall of trachea; mononuclear inflammatory cell infiltration (MICI) in the ear, and heart hemorrhage. When these biomarkers were applied to the ASA test of lac color, in comparison to the negative control group, the positive control group (ovalbumin + FCA) showed a significant over 60-fold reduction in platelet count and nearly threefold higher basophil count compared to other groups. Furthermore, only positive control group exhibited full lung distention and severe redness on the inner wall of the trachea. Mononuclear inflammatory cell infiltration (MICI) in the ear was about three times higher, and heart hemorrhage was only present in the positive control group compared to others. None of the lac color groups were different from the negative control group (p > 0.05), whereas the positive control group was significantly different (p < 0.05).
Conclusions
Our study concludes that lac color, at the tested concentrations, does not induce antigenicity in the guinea pig model, providing valuable safety data. Furthermore, the biomarkers identified in this study offer a supportive approach to evaluating the immunogenicity of substances in future research.
8.Diagnosis and Treatment of Perihilar Cholangiocarcinoma:A National Survey from the Korean Pancreatobiliary Association
Eunae CHO ; Seong-Hun KIM ; Seong Ji CHOI ; Min Kyu JUNG ; Byeong Jun SONG ; Jin Myung PARK ; Jingu KANG ; Won Suk PARK ; Joo Kyung PARK ; Sang Myung WOO ; Hyo Jung KIM ;
Gut and Liver 2024;18(1):174-183
Background/Aims:
Based on their anatomy, cholangiocarcinomas (CCAs) are classified into intrahepatic, hilar, and distal CCAs. Although the diagnosis and treatment of each type of CCA are thought to be different, real-world data studies on the current practice are limited. Therefore, this study was designed to capture the current practice of diagnosing and treating perihilar CCA in Korea.
Methods:
We conducted a survey using an online platform. The questionnaire consisted of 18 questions designed to evaluate the current practice of diagnosing and treating perihilar CCA in Korea. The targets of this survey were biliary endoscopists who are members of the Korean Pancreatobiliary Association.
Results:
In total, 119 biliary endoscopists completed the survey. Of the respondents, 89.9% thought that the use of the International Classification of Diseases, 11th Revision (ICD-11) system is necessary to classify CCA. Approximately half of the respondents would recommend surgery or chemotherapy until patients were 80 years of age. For the pathological diagnosis of CCA, endoscopic retrograde cholangiopancreatography with biopsy was the most preferred modality. Routine preoperative biliary drainage was performed by 44.5% of the respondents. For operable CCAs, 64.7% of the respondents preferred endoscopic biliary drainage using plastic stents. For palliative biliary drainage, 69.7% of the respondents used plastic stents. For palliative endoscopic biliary drainage using metal stents, 63% of the respondents preferred the stent-in-stent method.
Conclusions
A new coding system using the ICD-11 is needed for classifying CCAs. Guidelines for diagnosing and treating CCA based on the clinical situation in Korea are needed.
9.Neglected Osteoporotic Vertebral Compression Fracture Treated with Postural Reduction and Minimally Invasive Transpedicular Fixation with Weekly Teriparatide
Woo Jin SHIN ; Seung-Pyo SUH ; Byung Jun KANG ; Tae Byeong KANG
The Journal of the Korean Orthopaedic Association 2024;59(1):61-66
Osteoporotic vertebral compression fractures (OVCFs) are the most common osteoporotic fractures in postmenopausal women. One the other hand, they may be misdiagnosed if the deformity is not severe at the time of occurrence. In general, it is treated through absolute bed rest and braces. Vertebroplasty or kyphoplasty is sometimes performed when there is a severe decrease in the height of the vertebral body. In addition, transpedi cular fixation can be performed when there is an accompanying injury to the posterior complex or neurologic symptoms. In this case, the authors performed minimally invasive transpedicular fixation after achieving vertebral body height recovery through postural reduction in OVCF patient who were neglected for one month after the injury. After securing initial stability through screw fixation, complete bony union was achieved more quickly and stably through weekly teriparatide administration. The authors report this case with a review of the relevant literature.
10.Surgical management of giant adrenal myelolipoma using a modified Makuuchi incision: a case report
Byeong Jin KANG ; Seung Hyeon KIM ; Kyoungha JANG ; Kyung Hwan KIM ; Hong Koo HA
Kosin Medical Journal 2024;39(1):75-79
Giant adrenal myelolipomas are rare, benign, and hormonally inactive tumors. We present the case of a 53-year-old man with a 19-cm retroperitoneal mass, initially suspected to be a retroperitoneal liposarcoma, angiomyolipoma, or adrenal myelolipoma. After conducting endocrine assessments, which were within normal ranges, we decided to perform surgical excision using a modified Makuuchi incision. The tumor was successfully removed, and the final pathological examination confirmed the diagnosis of adrenal myelolipoma. The patient was discharged with no complications and remained without disease recurrence or distant metastasis as of 1 year postoperatively. In conclusion, giant myelolipomas are rare and cause symptoms owing to their large size. Surgical removal is recommended for large or symptomatic myelolipomas. The modified Makuuchi incision allows efficient and safe tumor removal in open surgery for giant myelolipomas.

Result Analysis
Print
Save
E-mail