1.Increased Apolipoprotein B/ Apolipoprotein A-I Ratio Is Associated With Decline in Lung Function in Healthy Individuals: The Kangbuk Samsung Health Study
Jonghoo LEE ; Hye Kyeong PARK ; Min-Jung KWON ; Soo-Youn HAM ; Hyun-Il GIL ; Si-Young LIM ; Jae-Uk SONG
Journal of Korean Medical Science 2024;39(6):e51-
Background:
Lung dysfunction and high apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio are both recognized risk factors for cardiovascular disease. However, few studies have examined the association between the apoB/ApoA-I ratio and lung function. Therefore, we investigated whether this ratio is associated with decreased lung function in a large healthy cohort.
Methods:
We performed a cohort study on 68,418 healthy Koreans (34,797 males, mean age:38.1 years) who underwent a health examination in 2019. ApoB/apoA-I ratio was categorized into quartiles. Spirometric values at the fifth percentile in our population were considered the lower limit of normal (LLN), which was used to define lung function impairment. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs), using the lowest quartile as the reference, were estimated to determine lung function impairment.
Results:
Mean apoB/apoA-I ratio was 0.67 ± 0.21. Subjects with the highest quartile of this ratio had the lowest predicted forced expiratory volume in one second (FEV1 %) and forced vital capacity (FVC%) after controlling for covariates (P < 0.001). However, FEV1 /FVC ratio was not significantly different among the four quartiles (P = 0.059). Compared with the lowest quartile (Q1, reference), the aORs (95% CI) for FEV1 % < LLN across increasing quartiles (from Q2 to Q4) were 1.216 (1.094–1.351), 1.293 (1.156–1.448), and 1.481 (1.311– 1.672) (P for trend < 0.001), respectively. Similarly, the aORs for FVC% < LLN compared with the reference were 1.212 (1.090–1.348), 1.283 (1.147–1.436), and 1.502 (1.331–1.695) with increasing quartiles (P for trend < 0.001). However, the aORs for FEV1 /FVC < LLN were not significantly different among groups (P for trend = 0.273).
Conclusion
High apoB/apoA-I ratio was associated with decreased lung function. However, longitudinal follow-up studies are required to validate our findings.
2.In vitro evaluation of the antitumor activity of axitinib in canine mammary gland tumor cell lines
Hye-Gyu LEE ; Ga-Hyun LIM ; Ju-Hyun AN ; Su-Min PARK ; Kyoung-Won SEO ; Hwa-Young YOUN
Journal of Veterinary Science 2024;25(1):e1-
Background:
Axitinib, a potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptor (VEGFR) tyrosine kinase 1,2 and 3, is used in chemotherapy because it inhibits tumor angiogenesis by blocking the VEGF/VEGFR pathway. In veterinary medicine, attempts have been made to apply tyrosine kinase inhibitors with anti-angiogenic effects to tumor patients, but there are no studies on axitinib in canine mammary gland tumors (MGTs).
Objectives:
This study aimed to confirm the antitumor activity of axitinib in canine mammary gland cell lines.
Methods:
We treated canine MGT cell lines (CIPp and CIPm) with axitinib and conducted CCK, wound healing, apoptosis, and cell cycle assays. Additionally, we evaluated the expression levels of angiogenesis-associated factors, including VEGFs, PDGF-A, FGF-2, and TGF-β1, using quantitative real-time polymerase chain reaction. Furthermore, we collected canine peripheral blood mononuclear cells (PBMCs), activated them with concanavalin A (ConA) and lipopolysaccharide (LPS), and then treated them with axitinib to investigate changes in viability.
Results:
When axitinib was administered to CIPp and CIPm, cell viability significantly decreased at 24, 48, and 72 h (p < 0.001), and migration was markedly reduced (6 h, p < 0.05; 12 h, p < 0.005). The apoptosis rate significantly increased (p < 0.01), and the G2/M phase ratio showed a significant increase (p < 0.001). Additionally, there was no significant change in the viability of canine PBMCs treated with LPS and ConA.
Conclusion
In this study, we confirmed the antitumor activity of axitinib against canine MGT cell lines. Accordingly, we suggest that axitinib can be applied as a new treatment for patients with canine MGTs.
3.Korean Practice Guidelines for Gastric Cancer 2022: An Evidence-based, Multidisciplinary Approach
Tae-Han KIM ; In-Ho KIM ; Seung Joo KANG ; Miyoung CHOI ; Baek-Hui KIM ; Bang Wool EOM ; Bum Jun KIM ; Byung-Hoon MIN ; Chang In CHOI ; Cheol Min SHIN ; Chung Hyun TAE ; Chung sik GONG ; Dong Jin KIM ; Arthur Eung-Hyuck CHO ; Eun Jeong GONG ; Geum Jong SONG ; Hyeon-Su IM ; Hye Seong AHN ; Hyun LIM ; Hyung-Don KIM ; Jae-Joon KIM ; Jeong Il YU ; Jeong Won LEE ; Ji Yeon PARK ; Jwa Hoon KIM ; Kyoung Doo SONG ; Minkyu JUNG ; Mi Ran JUNG ; Sang-Yong SON ; Shin-Hoo PARK ; Soo Jin KIM ; Sung Hak LEE ; Tae-Yong KIM ; Woo Kyun BAE ; Woong Sub KOOM ; Yeseob JEE ; Yoo Min KIM ; Yoonjin KWAK ; Young Suk PARK ; Hye Sook HAN ; Su Youn NAM ; Seong-Ho KONG ;
Journal of Gastric Cancer 2023;23(1):3-106
Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.
4.Erratum: Korean Practice Guidelines for Gastric Cancer 2022: An Evidencebased, Multidisciplinary Approach
Tae-Han KIM ; In-Ho KIM ; Seung Joo KANG ; Miyoung CHOI ; Baek-Hui KIM ; Bang Wool EOM ; Bum Jun KIM ; Byung-Hoon MIN ; Chang In CHOI ; Cheol Min SHIN ; Chung Hyun TAE ; Chung sik GONG ; Dong Jin KIM ; Arthur Eung-Hyuck CHO ; Eun Jeong GONG ; Geum Jong SONG ; Hyeon-Su IM ; Hye Seong AHN ; Hyun LIM ; Hyung-Don KIM ; Jae-Joon KIM ; Jeong Il YU ; Jeong Won LEE ; Ji Yeon PARK ; Jwa Hoon KIM ; Kyoung Doo SONG ; Minkyu JUNG ; Mi Ran JUNG ; Sang-Yong SON ; Shin-Hoo PARK ; Soo Jin KIM ; Sung Hak LEE ; Tae-Yong KIM ; Woo Kyun BAE ; Woong Sub KOOM ; Yeseob JEE ; Yoo Min KIM ; Yoonjin KWAK ; Young Suk PARK ; Hye Sook HAN ; Su Youn NAM ; Seong-Ho KONG
Journal of Gastric Cancer 2023;23(2):365-373
5.Fatty acid synthetase expression in triple-negative breast cancer
Jin Hee PARK ; Hye Seung HAN ; So Dug LIM ; Wook Youn KIM ; Kyoung Sik PARK ; Young Bum YOO ; Seung Eun LEE ; Wan-Seop KIM
Journal of Pathology and Translational Medicine 2022;56(2):73-80
Background:
Triple-negative breast cancer (TNBC) has a relatively poor prognosis. Research has identified potential metabolic targets, including fatty acid metabolism, in TNBC. The absence of effective target therapies for TNBC led to exploration of the role of fatty acid synthetase (FASN) as a potential target for TNBC therapy. Here, we analyzed the expression of FASN, a representative lipid metabolism–related protein, and investigated the association between FASN expression and Ki-67 and the programmed death ligand 1 (PD-L1) biomarkers in TNBC.
Methods:
Immunohistochemical expression of FASN was analyzed in 166 patients with TNBC. For analytical purposes, patients with 0–1+ FASN staining were grouped as low-grade FASN and patients with 2–3+ FASN staining as high-grade FASN.
Results:
FASN expression was observed in 47.1% of TNBC patients. Low and high expression of FASN was identified in 75.9% and 24.1%, respectively, and no statistically significant difference was found in T category, N category, American Joint Committee on Cancer stage, or recurrence rate between the low and high-FASN expression groups. Ki-67 proliferation level was significantly different between the low and high-FASN expression groups. FASN expression was significantly related to Ki-67 as the level increased. There was no significant difference in PD-L1 positivity between the low- and high-FASN expression groups.
Conclusions
We identified FASN expression in 166 TNBC patients. The Ki-67 proliferation index was positively correlated with FASN level, indicating higher proliferation activity as FASN increases. However, there was no statistical association with PD-L1 SP142, the currently FDA-approved assay, or FASN expression level.
6.Overexpression of FRAT1 protein is closely related to triple-negative breast cancer
Sang Eun NAM ; Young-Sin KO ; Kyoung Sik PARK ; TongYi JIN ; Young-Bum YOO ; Jung-Hyun YANG ; Wook-Youn KIM ; Hye-Seung HAN ; So-Dug LIM ; Seung Eun LEE ; Wan-Seop KIM
Annals of Surgical Treatment and Research 2022;103(2):63-71
Purpose:
Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis and a lack of targeted therapy. Overexpression of FRAT1 is thought to be associated with this aggressive subtype of cancer. Here, we performed a comprehensive analysis and assessed the association between overexpression of FRAT1 and TNBC.
Methods:
First, using different web-based bioinformatics platforms (TIMER 2.0, UALCAN, and GEPIA 2), the expression of FRAT1 was assessed. Then, the expression of the FRAT1 protein and hormone receptors and HER2 status were assessed by immunohistochemical analysis. For samples of tumors with equivocal immunoreactivity, we performed silver in situ hybridization of the HER2 gene to determine an accurate HER2 status. Next, we used the R package and bc-GenExMiner 4.8 to analyze the relationship between FRAT1 expression and clinicopathological parameters in breast cancer patients.Finally, we determined the relationship between FRAT1 overexpression and prognosis in patients.
Results:
The expression of FRAT1 in breast cancer tissues is significantly higher than in normal tissue. FRAT1 expression was significantly related to worse overall survival (P < 0.05) and was correlated with these clinicopathological features:T stage, N stage, age, high histologic grade, estrogen receptor status, progesterone receptor status, Her-2 status, TNBC status, basal-like status, CK5/6 status, and Ki67 status.
Conclusion
FRAT1 was overexpressed in breast cancer compared to normal tissue, and it may be involved in the progression of breast cancer malignancy. This study provides suggestive evidence of the prognostic role of FRAT1 in breast cancer and the therapeutic target for TNBC.
7.A Case Report of Multiple Capillary Hemangioma in a Chronic Myeloid Leukemia Patient Taking Tyrosine Kinase Inhibitors
Hyun Jeong BYUN ; Donghwi JANG ; Jongeun LEE ; Se Jin OH ; Youngkyoung LIM ; Ji-Hye PARK ; Jong Hee LEE ; Dong-Youn LEE
Annals of Dermatology 2021;33(3):278-280
A capillary hemangioma is a vascular tumor with small capillary sized vascular channel. Multiple capillary hemangioma in relation with drugs have been rarely reported. Here in, we report a case of multiple capillary hemangioma in patient diagnosed with chronic myeloid leukemia who received tyrosine kinase inhibitors (TKIs). Histopathological findings have shown capillary proliferation in the upper dermis, which is consistent with capillary hemangioma. Since TKIs can paradoxically activate the MEK/ERK pathway which is required for angiogenesis, we presumed that the lesions as the cutaneous side effects of TKIs.
8.Phase II Study of Pemetrexed as a Salvage Chemotherapy for Thymidylate Synthase–Low Squamous Cell Lung Cancer
Mihong CHOI ; Heung Tae KIM ; Ji-Youn HAN ; Geon Kook LEE ; Soo-Hyun LEE ; Kun Young LIM ; Jungnam JOO ; Hye Jin WON ; Jin Soo LEE ; Youngjoo LEE
Cancer Research and Treatment 2021;53(1):87-92
Purpose:
Squamous cell carcinomas (SqCC) of the lung often express high levels of thymidylate synthase (TS), which is associated with primary resistance to pemetrexed. We explored the efficacy of pemetrexed in a selected population of patients with lung SqCC with low TS expression.
Materials and Methods:
In this single-arm phase II trial, we enrolled 32 previously-treated patients with advanced lung SqCC exhibiting low immunohistochemical staining for TS (i.e., in 10% or less of tumor cells). The primary endpoint was 12-week progression-free survival (PFS) rate.
Results:
Of 32 patients, eight patients (25%) had an Eastern Cooperative Oncology Group performance status of 2, and seven patients (22%) had previously received three or more lines of chemotherapy. The disease control rate from pemetrexed treatment was 30%, and no objective response was observed. The 12-week PFS rate was 24.5% (95% confidence interval [CI], 13.0 to 46.1). Median PFS was 1.3 months (95% CI, 1.3 to 2.7), and median overall survival was 11.8 months (95% CI, 8.1 to not applicable). Most of adverse events were grade 1 or 2.
Conclusion
Pemetrexed demonstrated modest activity as a salvage chemotherapy in patients with advanced lung SqCC with low TS expression, although its toxicity was generally manageable.
9.Evidence-Based Guidelines for the Treatment of Helicobacter pylori Infection in Korea 2020
Hye-Kyung JUNG ; Seung Joo KANG ; Yong Chan LEE ; Hyo-Joon YANG ; Seon-Young PARK ; Cheol Min SHIN ; Sung Eun KIM ; Hyun Chul LIM ; Jie-Hyun KIM ; Su Youn NAM ; Woon Geon SHIN ; Jae Myung PARK ; Il Ju CHOI ; Jae Gyu KIM ; Miyoung CHOI ; Korean College of Helicobacter and Upper Gastrointestinal Research
Gut and Liver 2021;15(2):168-195
Helicobacter pylori infection is one of the most common infectious diseases worldwide. Although the prevalence of H. pylori is gradually decreasing, approximately half of the world's population still becomes infected with this disease. H. pylori is responsible for substantial gastrointestinal morbidity worldwide, with a high disease burden. It is the most common cause of gastric and duodenal ulcers and gastric cancer. Since the revision of the H. pylori clinical practice guidelines in 2013 in Korea, the eradication rate of H. pylori has gradually decreased with the use of a clarithromycin-based triple therapy for 7 days. According to a nationwide randomized controlled study conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research released in 2018, the intention-to-treat eradication rate was only 63.9%, which was mostly due to increased antimicrobial resistance, especially from clarithromycin. The clinical practice guidelines for the treatment of H. pylori were updated according to evidence-based medicine from a meta-analysis conducted on a target group receiving the latest level of eradication therapy. The draft recommendations developed based on the meta-analysis were finalized after an expert consensus on three recommendations regarding the indication for treatment and eight recommendations for the treatment itself. These guidelines were designed to provide clinical evidence for the treatment (including primary care treatment) of H. pylori infection to patients, nurses, medical school students, policymakers, and clinicians. These may differ from current medical insurance standards and will be revised if more evidence emerges in the future.
10.Complete response in hepatocellular carcinoma with lymph node metastasis by combination therapy of atezolizumab and bevacizumab: a case report
Sang Youn HWANG ; Sun Mi LEE ; Jeong Woo LIM ; Gi Jung JEON ; Hye Won LEE
Journal of Liver Cancer 2021;21(2):177-180
Sorafenib is the oldest first line systemic treatment in patients with advanced hepatocellularcarcinoma (HCC) and has been used exclusively for nearly 10 years. The superiority ofadministering a combination of atezolizumab plus bevacizumab (AteBeva) compared tosorafenib as first line systemic treatment for unresectable HCC was recently proven duringthe IMbrave150 Phase III randomized trial. While clinicians can expect improved responsesand treatment outcomes due to the good results of the IMbrave 150 trial, they must alsoconsider that atezolizumab can cause various immune-related adverse events (IrAEs). Basedon the above suggestions, we herein present a case of HCC with lymph node metastasiswho achieved complete remission following treatment with AteBeva and developed an IrAE(adrenal insufficiency). Further study of real-life data regarding combination therapy withAteBeva is needed to manage patients with advanced HCC.

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