National Research Foundation Research Articles

Effects of Ozanimod on Cognitive Processing Speed: Findings From the Phase 3 SUNBEAM and DAYBREAK Extension Trials (P6-3.001)

Effects of Ozanimod on Cognitive Processing Speed: Findings From the Phase 3 SUNBEAM and DAYBREAK Extension Trials (P6-3.001)

Five-Year Safety of Ofatumumab in People Living With Relapsing Multiple Sclerosis (P8-3.004)

Five-Year Safety of Ofatumumab in People Living With Relapsing Multiple Sclerosis (P8-3.004)

Longitudinal Clinical and MRI Outcomes in Relapsing Multiple Sclerosis (RMS) Patients After Short-term Ponesimod Treatment Interruption and Re-initiation (P6-3.007)

Longitudinal Clinical and MRI Outcomes in Relapsing Multiple Sclerosis (RMS) Patients After Short-term Ponesimod Treatment Interruption and Re-initiation (P6-3.007)

Neurofilament Light Chain Levels and Disease Activity During Long-Term Treatment of Relapsing Multiple Sclerosis with the Bruton’s Tyrosine Kinase Inhibitor Evobrutinib (P1-3.011)

Neurofilament Light Chain Levels and Disease Activity During Long-Term Treatment of Relapsing Multiple Sclerosis with the Bruton’s Tyrosine Kinase Inhibitor Evobrutinib (P1-3.011)

NfL as a Predictor of GdE Lesions in Patients With Relapsing Multiple Sclerosis Treated With Ozanimod in the Phase 2 RADIANCE Trial (P1-3.012)

NfL as a Predictor of GdE Lesions in Patients With Relapsing Multiple Sclerosis Treated With Ozanimod in the Phase 2 RADIANCE Trial (P1-3.012)

Delayed Signs of Early Disability Progression After 8.5 Years of Ocrelizumab Treatment in Patients With Relapsing Multiple Sclerosis (S46.003)

Delayed Signs of Early Disability Progression After 8.5 Years of Ocrelizumab Treatment in Patients With Relapsing Multiple Sclerosis (S46.003)

Effect of Longer-term Ofatumumab Treatment on Disability Progression and Brain Volume Change (S16.009)

Effect of Longer-term Ofatumumab Treatment on Disability Progression and Brain Volume Change (S16.009)

Serum Glial Fibrillary Acidic Protein compared with Neurofilament Light Chain as Biomarker for Multiple Sclerosis Disease Progression (P5-3.016)

Serum Glial Fibrillary Acidic Protein compared with Neurofilament Light Chain as Biomarker for Multiple Sclerosis Disease Progression (P5-3.016)

DETERMINATION OF HINGE POSITIONS ON THE TIBIAL WEDGE IN BIPLANE OPEN-WEDGE HIGH TIBIAL OSTEOTOMY AS VARUS DEFORMITY ANGLE

It is still difficult to determine an appropriate hinge position to prevent fracture in the lateral cortex of tibia in the process of making an open wedge during biplane open wedge high tibial osteotomy. The objective of this study was to present a biomechanical basis for determining the hinge position as varus deformity.T Three-dimensional lower extremity models were constructed using Mimics. The tibial wedge started at 40 mm distal to the medial tibial plateau, and osteotomy for three hinge positions was performed toward the head of the fibula, 5 mm proximal from the head of the fibula, and 5 mm distal from the head of the fibula. The three tibial models were made with varus deformity of 5, 10, 15 degrees with heterogeneous material properties. These properties were set to heterogeneous material properties which converted from Hounsfield's unit to Young's modulus by applying empirical equation in existing studies. For a loading condition, displacement at the posterior cut plane was applied referring to Hernigou's table considering varus deformity angle. All computational analyses were performed to calculate von-mises stresses on the tibial wedges.The maximum stress increased to an average of 213±9% when the varus angle was 10 degrees compared to 5 degrees and increased to an average of 154±8.9% when the varus angle was 15 degrees compared to 10 degrees. In addition, the maximum stress of the distal position was 19 times higher than that of the mid position and 5 times higher than that of the proximal position on average.Conclusion:For varus deformity angles, the maximum stress of the tibial wedge tended to increase as the varus deformity angle increased. For hinge position of tibial wedge, maximum stress was the lowest in the mid position, while the highest in the distal position.*This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (NRF-2022R1A2C1009995)

Abstract 6697: Deep learning algorithm for cancer detection using multimodal characteristics of whole methylome sequencing of cf-DNA

Abstract Background Various cell-free DNA (cfDNA) features including methylation and genomic profiles have been investigated for their potential use in early cancer detection. We developed deep learning models based the data generated by the enzymatic conversion based whole methylome sequencing of cfDNA. Methods Cell-free whole genome Enzymatic Methyl sequencing(cfWEMseq) data were generated from 198 cancer patients (stage I: 11%, II: 17%, III: 22%, IV: 20%, unknown: 31%) and 69 healthy controls. The cancer types were consisted of breast (n=31), liver (n=24), esophageal (n=38), pancreatic (n=30), colon (n=34), ovarian (n=18), and lung (n=23). Sequence data was produced on average of 200 million reads using Novaseq 6000 (Illumina). For model training and evaluation, data partitioning was stratified by cancer type, and 5-fold cross validation was used. Coverage and methylation beta values ​​were calculated by binning at fixed size of 100K, 1M, and 5M base and variable size from Topologically Associated Domains (TAD). Genome Coverage (GC), Genome Methylation Beta values ​​(GMB), and Mutation Signature (MS) features were trained using a one-dimensional convolutional neural network (1D-CNN). The performance of the model was evaluated by measuring the average value of the results measured in each test set of 5 fold. Results We tested the cancer detection performance of various feature combinations using all data from cfWEMseq (n=267). Regardless of the bin size, the GMB single model achieved higher performance than the GC single model. The best-performing model is the ensemble model of GMB (100k bin) and MS. The cancer detection performance of this ensemble model reached an accuracy 96% (CI: 93.6% to 98.1%), AUC 0.99 (CI: 0.97 to 1.0) and sensitivity 98.0% (CI: 92.4% to 99.5%) with a specificity of 90%. Conclusions These results provide an opportunity for higher accuracies by integrating methylation information and genomic data using cfWEMseq. This research was supported through the National Research Foundation (NRF) funded by the Ministry of Science and ICT (2020M2D9A3094213). Citation Format: Juntae Park, Minjung Kim, Sook Ryun Park, Ki-Byung Song, Eunsung Jun, Dongryul Oh, Jeong-Won Lee, Young Sik Park, Ki-Won Song, Jeong-Sik Byeon, Bo Hyun Kim, Chang-Seok Ki, Eunhae Cho. Deep learning algorithm for cancer detection using multimodal characteristics of whole methylome sequencing of cf-DNA. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6697.

Abstract 161: Patient-derived organoids (PDOs) hub of National Cancer Center, Korea: pre-clinical model for drug screening

Abstract Purpose Cancer is one of the leading causes of death worldwide. Patient-derived tumor cells can serve as a powerful resource for studying pathophysiologic mechanisms and developing robust strategies for precision medicine. To address this problem, we launched the patient-derived organoids (PDOs) Hub to establish a comprehensive model of various tumor organoids from pancreatic, biliary tract, liver, colorectal, breast, gastric, ovarian, and oral cancers, with matching clinical data and molecular characteristics. Methods All specimens were collected from histologically confirmed cancer patients at the National Cancer Center. Samples obtained from surgery, biopsy, or body fluid (malignant ascites or pleural effusion) were collected for ex vivo culture of tumor cells. PDOs were managed according to our standard operating procedure (SOP), which included specimen delivery process, separation of cells from tissues, criteria for subculture, quality control (QC), production of genomic and histologic data, and the 384-well-based drug response evaluation system. Organoids were considered to be successfully cultured when they were maintained for five or more passages. Results A total of 263 PDOs were established from various cancer types, including oral cancer (N = 89), pancreatic cancer (N = 48), ovarian cancer (N = 32), breast cancer (N = 30), biliary tract cancer (N = 29), hepatocellular carcinoma (N = 17), gallbladder cancer (N = 8), gastric cancer (N = 7) and colorectal cancer (N = 3). PDOs broadly recapitulated the histologic and genetic characteristics of the patient’s tumor. These organoids available for long-term culture were cryopreserved, and a total of 2986 stocks have been accumulated. Drug screening tests were performed with 60 PDOs (pancreatic cancer, N = 36; breast cancer, N = 15; ovarian cancer, N = 6; gastric cancer, N = 3) using selected agents among the 47 drugs for each type of cancer. Profiles of cytotoxic agents were well correlated with the patient’s clinical responses to the matched drugs and tested investigational agents also showed promising antitumor activity. Conclusions We have established a model of several human cancer organoids. This will serve as the platform that can recapitulate the physiology and drug response profiles of human cancer and pave the way for screening innovative drugs, identifying novel targets, and stratifying patients for pertinent therapeutic options. (This work was supported by National Research Foundation of Korea grant, funded by the Korean government (MSIT) (No. 2020M3A9A5036362)) Citation Format: Yebeen Yu, Mi Rim Lee, Wonyoung Choi, Sumin Kang, Jeong Eun Gong, Soobeen Heo, Hye Ju Park, Sang Myung Woo, So-Youn Jung, Sung Weon Choi, Jong-Ho Lee, Myong Cheol Lim, Ji Yeon Baek, Bo Hyun Kim, Ji Hoon Kim, Yuri Cho, Sang-Jae Park, Yun-Hee Kim, Sun-Young Kong. Patient-derived organoids (PDOs) hub of National Cancer Center, Korea: pre-clinical model for drug screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 161.

Abstract 6555: Integrated bioinformatics analysis identified ASNS and DDIT3 as the therapeutic target in castration resistance prostate cancer

Abstract Background: Many studies have demonstrated the mechanisms of progression to castration-resistant prostate cancer (CRPC) and novel strategies for the treatment of CRPC. Despite these advances, the molecular mechanism underlying the progression to CRPC remain unclear, and no effective treatments for CRPC are currently available. Here, we characterized the pathways and key genes involved in the progression to CRPC to gain insight into the mechanisms and potential therapeutic targets of CRPC. Methods: Bicalutamide-resistant prostate cancer cells derived from LNCaP was generated and named Bical R. RNA sequencing was used to identify differentially expressed genes (DEGs) between LNCaP and Bical R. DAVID and Clue GO were used to perform functional enrichment analysis, and the Cytohubba plug-in Cytoscape was used to identify hub genes associated with progression to CRPC. To validate the expression of hub genes, we performed qRT-PCR and western blot analyses. Further validation was performed using GEO microarray (GSE 32269 and GSE28403). To elucidate the clinical usefulness of these genes, we assessed the disease-free survival of patients with prostate cancer from The Cancer Genome Atlas (TCGA) database. Results: In total, 631 DEGs (302 upregulated genes and 329 downregulated genes) were identified, and Kyoto Encyclopedia of Genes and Genomes pathways were analyzed based on DAVID and Clue GO. We found that the PI3K-Akt and MAPK signaling pathways are of great significance for investigating the mechanism of CRPC progression. Hub genes from protein-protein interaction network of upregulated DEGs (AGT, ASNS, ATF3, ATF4, DDIT3, EFNA5, and VEGFA) were identified. Among the hub genes, ASNS and DDIT3 were markedly up-regulated in CRPC cell lines and CRPC tissues, respectively. Additionally, patients with high expression of ASNS and DDIT3 showed worse disease-free survival in TCGA database. Conclusion: Our study revealed that the PI3K-Akt and MAPK signaling pathways may be important in the mechanism of CRPC progression, and ASNS and DDIT3 may be associated with progression to CRPC. These results may contribute to the development of potential therapeutic targets and mechanisms underlying the progression to CRPC to improve clinical efficacy for CRPC treatment. Acknowledgements: This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (No. 2022R1A2C2003513). Citation Format: Ae Ryang Jung, Sun Shin, U-Syn Ha, Mee Young Kim, Sung-Hoo Hong, Ji Youl Lee, Sae Woong Kim, Yeun-Jun Chung, Yong Hyun Park. Integrated bioinformatics analysis identified ASNS and DDIT3 as the therapeutic target in castration resistance prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6555.

Abstract 194: Ovarian cancer patient-derived organoids and tumor xenografts as preclinical models for precision medicine

Abstract Background: Patient-derived organoids (PDO) and patient-derived xenografts (PDX) has been investigated as preclinical models for drug development and precision medicine. In this study, we established ovarian cancer PDOs and PDX models from Aug 2020 to Nov 2022, and developed protocols. Methods: We obtained tumor tissue from several sites (ovary, omentum, diaphragm, and peritoneum) or ascites from surgery of ovarian cancer patients. The tissue samples were dissociated for single cells and ascitic samples were centrifuged and washed to concentrate the tumor cells. Then, it is embedded in matrigel or basement membrane extract (BME) and seeded on a 24-well plate supplemented with culture medium containing modified growth factors. The association with clinical characteristics with success of model establishment were evaluated. Drug screening for organoids were designed on the 384-well plate using Celltiter-Glo 3D cell viability assay (Promega). The list of drugs consists of alkylating agent, monoclonal antibody, taxane, tyrosine kinase inhibitor (TKI), and poly(ADP-ribose) polymerase inhibitor (PARPi). For increase of success rate for xenograft, we compared intrabursa and subcutaneous injection xenograft models using ES-2 cell line then patient tumors in NOG mouse. Results: A total of 397 organoids passed first passage, however 32 (8%) organoids were continuously cultured over 5 passages. The associated clinical factors for establishment of organoids were stage (p=0.020, low stage 20% of success vs. high stage 2.4% of success) and pathologic types (p=0.035, low grade serous cancer (LGSC) 30% and clear cell 16.7% of success vs. high grade serous cancer (HGSC) 5.6% of success). Thirteen drugs were evaluated and AUC represented various range according to patient from 0.0004 to 1.3876. Three sites (ovary, omentum and ascites) established organoids from one patient represented difference in drug sensitivity which suggest role of cancer microenvironment. The growth upto 100mm3 of intrabursa injection (12.33 ± 0.6667) was faster than that of subcutaneous injection model (15.00 ± 1.000, p-value = 0.09) using ES-2 cell. Then comparison of patients tumor (N=10) into intrabursa vs. subcutaneous are undergoing with one completed case showing fast intrabursa growing. Conclusions: During relative short period we developed many PDOs and PDXs for future study including drug development. Moreover, we focused to develop better model for PDXs and it will give a new approach for successful model establishment. (This work was supported by National Research Foundation of Korea grant, founded by the Korea government (MSIT) [No.2020R1A2C2010566]) Citation Format: Yebeen Yu, Hye Ju Park, Cha Yeon Kang, Myong Cheol Lim, Sang Yoon Park, Yo Han Woo, Yun-Hee Kim, Sun-Young Kong. Ovarian cancer patient-derived organoids and tumor xenografts as preclinical models for precision medicine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 194.

Abstract 6468: Association of food groups and dietary pattern with breast cancer risk: A systematic review and meta-analysis

Abstract We conducted a systematic review and meta-analysis of current evidence for the association between food groups, dietary patterns, and breast cancer risk among the Asian population. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. We performed a systematic literature search up to November 2022 in English in the PubMed, Web of Science, Embase, and Cochrane databases. Risk ratios (RRs) with 95% confidence intervals (CIs) were extracted as effect sizes. Publication bias was estimated by the funnel plot method. We collected the data from 15 cohort studies and 30 case-control studies meeting the search criteria. The meta-analysis found that fruit and vegetable consumption was associated with a 27% and 35% lower risk of breast cancer, respectively [RR = 0.73 (0.56, 0.96); RR = 0.65 (0.47, 0.90)]. By contrast, no significance was found between meat, soy food, and green tea consumption and breast cancer risk (P > 0.05). However, soy protein and isoflavone intake could lower breast cancer risk by 35% and 32%, respectively [RR = 0.65 (0.51, 0.83); RR = 0.68 (0.55, 0.82)]. As for dietary pattern, higher adherence to a healthy dietary pattern and healthy eating index was associated with a 38% and 62% reduction in breast cancer risk, respectively [RR = 0.62 (0.44, 0.88; RR = 0.38 (0.22, 0.67)], while high adherence to an unhealthy dietary pattern was associated with a 44% increased risk [RR = 1.44 (1.06, 1.96)]. Considering alcohol consumption, a 75% increased risk of breast cancer was found [RR= 1.75 (1.33, 2.30)]. The present meta-analysis found that high intakes of fruit, vegetable, soy protein, and soy isoflavone significantly reduced the risk of breast cancer, while high intake of alcohol had a significantly increased risk. Meat, soy food, and green tea consumption were not significantly associated with breast cancer risk. Considering dietary patterns, higher adherence to a healthy eating index and a healthy dietary pattern may reduce breast cancer risk. Conversely, adherence to unhealthy dietary patterns may increase breast cancer risk. However, further studies are needed to confirm the associations between dietary patterns and breast cancer in the Asian population. This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No.2022R1F1A1074279). MSIT: Ministry of Science and ICT. Citation Format: Jialei Fu, Woo-Kyoung Shin, Dan Huang, Sukhong Min, Li-Juan Tan, Hyein Jung, Khongorzul Ganbat, Jiwon Jeong, Seok-Jae Oh, Bayarmaa Nasan Ulzii, Daehee Kang, Sangah Shin. Association of food groups and dietary pattern with breast cancer risk: A systematic review and meta-analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6468.

Abstract 1327: Mechanism of tumor microenvironment remodeling and progression based on FAM20C-mediated extracellular kinome network in oral squamous cell carcinoma

Abstract Tumorigenesis and tumor growth are accomplished through the crosstalk between intra- and extracellular molecules, which is often mediated by phosphorylation, and research on intracellular signal transduction has made great progress. Despite the significance of the tumor microenvironment (TME) for tumor progression, relatively few kinome studies have been conducted on phosphorylation cascade in the TME of oral squamous cell carcinoma (OSCC). OSCC is an aggressive cancer with a high recurrence rate of 40-60%, but there are uncertain molecular classification and no identifiable driver mutation genes to be a druggable target. As the presence of extranodal extension (ENE) is currently the most significant risk factor for locoregional recurrence or distant metastasis, differences in molecular profiles between patients with and without ENE may provide insight into regulatory mechanisms that are critical for the recurrence and progression of OSCC. Using LC-MS-based secretome analysis, we examined total and phosphoproteins from ten patients' plasma with or without ENE. Global proteome analysis revealed that the ENE group had higher levels of protein phosphorylation, the ERK 1/2 cascade, signal transduction, phagocytosis, and the integrin-mediated signaling pathway than the without ENE group. Furthermore, 319 phosphosites originating from 165 proteins were discovered, with the majority of phosphorylated proteins having lipid binding, complement system, extracellular matrix, and calcium binding. Interestingly, we discovered 82 proteins with Ser-x-Glu/pSer sites among the phosphorylated proteins, indicating that they could be substrates of the unique extracellular secreted serine kinase, family with sequence similarity 20C (FAM20C). Proteins associated to tumor metastasis, such as insulin-like growth factor-binding proteins (IGFBPs), osteopontin (OPN), and serine protease inhibitors (Serpins), are known as substrates for the FAM20C. In accordance with the proteome results in plasma, gene ontology (GO) term analysis using the NanoString oncology panel revealed that extracellular structure organization-related genes were up-regulated and enzyme inhibitor, kinase regulator, and protein tyrosine kinase activity-related genes were down-regulated in human OSCC cell line, Cal-27, with knockout of FAM20C. Furthermore, we functionally demonstrated that FAM20C depletion inhibited invasion by lowering protein production of Vimentin, TGF-β, and ERK phosphorylation. Collectively, we discovered that the secreted kinase FAM20C controls metastasis by cross-talking with proteins in the TME and propose that this may be the evidence for OSCC prognosis. (This research was supported by National Cancer Center, Korea (No. 2210980) and National Research Foundation of Korea grant funded by the Korea government (No. 2020M3A9A5036362)). Citation Format: Mi Rim Lee, Yu-Sun Lee, Sumin Kang, Hye Won Shon, Jeong Eun Gong, Hye Joo Park, Jung-Ah Hwang, Kyung-Hee Kim, Sung Weon Choi, Yun-Hee Kim. Mechanism of tumor microenvironment remodeling and progression based on FAM20C-mediated extracellular kinome network in oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1327.

Abstract 2787: Targeting Nrf2 signaling pathway by Keap1-mediated degradation in acquired gemcitabine resistant pancreatic cancer cells

Abstract Redox status is a main indicator of cancer cell adaptation to chemotherapy. Nuclear factor erythroid 2-related factor 2 (Nrf2) is one of the crucial regulators of redox condition and can affected to drug resistance through redox imbalance. The incidence and mortality of pancreatic cancer (PC) have been gradually increasing globally. Although the first line treatment with anticancer agents improves the disease status, acquired drug resistance is major huddles in the treatment failure. Targeting Nrf2 has been suggested as a promising therapeutic approach for the overcoming drug resistance. In the present study, Nrf2 was found to be upregulated in tumor tissues and gemcitabine-resistant PC cells. In addition, Nrf2 knockdown exhibited to recover gemcitabine sensitivity in the gemcitabine-resistant PC cells. To further validate the role of Nrf2 in gemcitabine-resistant cells, the effects of Nrf2 inhibitor, periplocin, were employed. Periplocin exerted the antiproliferative activities by regulating Nrf2 suppression which leads to the increase of reactive oxygen species generation. Furthermore, the downregulation of Nrf2 by periplocin was correlated to Keap1-mediated protein degradation. Docking simulation also confirmed the binding interaction of Nrf2 and Keap1 by periplocin. These findings suggest that targeting the Nrf2 might be a therapeutic strategy for overcoming acquired gemcitabine PC. Keywords: Pancreatic cancer cell, Gemcitabine resistance, Nuclear factor erythroid-2-related factor 2 (Nrf2), Kelch Like ECH Associated Protein 1 (Keap1), protein degradation Acknowledgements: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2022R1I1A1A01063346). Citation Format: Sang Kook Lee, Eun Seo Bae, Woong Sub Byun, Chae Won Ock, Won Kyung Kim, Hyen Joo Park. Targeting Nrf2 signaling pathway by Keap1-mediated degradation in acquired gemcitabine resistant pancreatic cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2787.

Abstract 743: Association between physical activity and lipid profile among breast cancer survivors

Abstract Backgrounds/Aims: Unfavorable lipid profiles may be associated with prognosis among breast cancer survivors. We aimed to examine the association between physical activity levels and subclasses of lipoprotein among breast cancer survivors. Methods: We included a total of 378 women diagnosed with primary breast cancer and survived for ≥6 months since the surgery. Physical activity levels were presented as the metabolic equivalent of task (MET) hours/week from a structured questionnaire. High-throughput proton nuclear magnetic resonance (NMR) metabolomics platform was used to quantify plasma levels of specific lipid biomarkers and particle sizes. The multivariable adjusted least-square means (LS-means) and 95% confidence intervals (CIs) of lipid profile markers across physical activity (quartile) were estimated by using generalized linear models. Results: We observed inverse associations of physical activity levels with circulating levels of total triglycerides (TG), TG in very low-density lipoprotein (VLDL), and TG in high-density lipoprotein (HDL) among breast cancer survivors. LS-means (95% CIs) for 1st and 4th quartiles of physical activity were 1.07 (0.99-1.17) and 0.96 (0.88-1.04; p for trend=0.048) for total TG (nmol/L), 0.68 (0.62-0.74) and 0.60 (0.54-0.66; p for trend=0.045) for TG in VLDL (nmol/L), and 0.14 (0.13-0.15) and 0.12 (0.11-0.13; p for trend=0.045) for TG in HDL (nmol/L). These associations were limited to breast cancer survivors with stage II or III. We also found a smaller VLDL size with high physical activity among those with stage II or III. Among participants with a BMI of ≥25 kg/m2, we found that high physical activity was associated with decreased levels of TG in VLDL and small VLDL size; according to subsequent quartiles of physical activity, LS-means (95% CIs) were 0.73 (0.62-0.87), 0.88 (0.72-1.08), 0.74 (0.61-0.89), and 0.56 (0.44-0.71) for TG in VLDL (nmol/L), respectively (p for trend=0.047); and 38.67 (38.34-39.00), 38.75 (38.36-39.15), 38.65 (38.28-39.01), and 37.98 (37.52-38.45) for VLDL size (nm), respectively (p for trend=0.024). Conclusions: We found that high physical activity was associated with lower circulating levels of subclasses of TG and smaller VLDL size among breast cancer survivors with stage II or III or those with a BMI of ≥25 kg/m2. Further prospective or randomized controlled studies are warranted to confirm the significance of physical activity associated with favorable lipid profiles among breast cancer survivors. Funding Information: This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT, MSIT) (No. 2014R1A2A2A01007794, 2019R1F1A1061017, and 2021R1F1A1062476) and K-BIO KIURI Center program (NRF2020M3H1A107330413). Citation Format: Hyun Jeong Cho, Minji Kang, Zisun Kim, Hyun Jo Youn, Jihyoung Cho, Jun Won Min, Yoo Seok Kim, Jung Eun Lee. Association between physical activity and lipid profile among breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 743.

MP68-01 PATTERN ANALYSIS OF LASER FIBER DEGRADATION ACCORDING TO THE LASER SETTING: IN VITRO STUDY OF THE DOUBLE-FIRING PHENOMENON

You have accessJournal of UrologyCME1 Apr 2023MP68-01 PATTERN ANALYSIS OF LASER FIBER DEGRADATION ACCORDING TO THE LASER SETTING: IN VITRO STUDY OF THE DOUBLE-FIRING PHENOMENON Sang Won So, Gyoohwan Jung, Hyeji Park, and Sung Yong Cho Sang Won SoSang Won So More articles by this author , Gyoohwan JungGyoohwan Jung More articles by this author , Hyeji ParkHyeji Park More articles by this author , and Sung Yong ChoSung Yong Cho More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003331.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: It is essential to understand the mechanism of the various causes of laser fiber damage and an ideal method of reducing endoscope damage induced by laser emission in multiple sites. This study classified the different patterns of laser fiber degradation according to laser settings and analyzed the role of cavitation bubbles to find a desirable way of minimizing endoscope damage. METHODS: A total of 118 laser fibers were analyzed after 1-,3-, and 5-min laser emission to artificial stones under the settings of 1J-10Hz, 1J-20Hz, 1J-30Hz, and 2J-10Hz. Every 3cm from the fiber tip was marked and examined with a digital microscope and a high-speed camera. The images of the fibers and the movement of cavitation bubbles were taken with a distance of 1 to 5 mm from the gel. RESULTS: Seven types of fiber damage (charring, limited and extensive peeled-off, bumpy, whitish plaque, crack, and break-off) coincided during laser emission. Damages rapidly increased with emission time>3 min regardless of the laser settings. The damaged lengths covered 5 mm on average, and the fibers at 5-min emission were significantly shorter than others. The fiber durability of 1J-10Hz setting was better than other settings after 3-min laser emission. Backward movement of the cavitation bubbles was found at the 1-mm distance from the gel, and the damaged lengths were longer than the diameters of the cavitation bubbles because of their proximal movement. CONCLUSIONS: The damage patterns of the laser fiber tips were classified into seven types. The heat damage around the surface of the laser fiber can be increased according to the high-energy or high-frequency laser setting, a short distance to the stone, a short distance from the tips of flexible ureteroscopes, no cutting laser fiber procedures, and the inappropriate use of irrigation fluid or laser fiber jacket. Source of Funding: This work was supported by a grant No. 2019R1C1C1008339 mainly and another one No. 2017R1A2B3007907 in part of the National Research Foundation (NRF) grant funded by the Korean government (MSIT) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e952 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sang Won So More articles by this author Gyoohwan Jung More articles by this author Hyeji Park More articles by this author Sung Yong Cho More articles by this author Expand All Advertisement PDF downloadLoading ...

MP77-06 THE PROJECTED SHORT AND LONG-TERM ANTICIPATION OF THE PROSTATE CANCER POPULATION IN KOREA BASED ON PSA TESTING AND SOCIAL-AGING TREND DURING THE LAST DECADES

You have accessJournal of UrologyCME1 Apr 2023MP77-06 THE PROJECTED SHORT AND LONG-TERM ANTICIPATION OF THE PROSTATE CANCER POPULATION IN KOREA BASED ON PSA TESTING AND SOCIAL-AGING TREND DURING THE LAST DECADES Young Hwii Ko, Ki Hak Moon, Hee Chang Jung, Phil Hyun Song, Jae Young Choi, Yeong Uk Kim, Jae Youn Jang, and Jong Gyun Ha Young Hwii KoYoung Hwii Ko More articles by this author , Ki Hak MoonKi Hak Moon More articles by this author , Hee Chang JungHee Chang Jung More articles by this author , Phil Hyun SongPhil Hyun Song More articles by this author , Jae Young ChoiJae Young Choi More articles by this author , Yeong Uk KimYeong Uk Kim More articles by this author , Jae Youn JangJae Youn Jang More articles by this author , and Jong Gyun HaJong Gyun Ha More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003351.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The current serum prostate-specific antigen testing incidence in males aged over 40 years in Korea was only 7.26% national-widely (2016), and most of the detected prostate cancer (PCa) were driven by the elderly (aged over 60 years occupies over 90% of PCa in 2019) or the super-elderly (over aged over 75 years occupied 1/3 of cases) population. Based on these trends, we anticipated the short and long-term PCa incidence national-widely. METHODS: A regression equation model for the estimated incidence of PCa was extracted based on two key pieces of information; 1) the expected age distribution available from the national statistics, projected with the reported incidence of PCa divided by ’50s, ’60s, ’70s, and over 80’s from the last two decades (2006-2018), 2) the reported increasing incidence of PSA across the nation for the last decades (2006-2016) in each age subgroup. RESULTS: The incidence of PCa increased about threefold (4,425 in 2006 to 15,043 in 2016). PCa incidences increased with age (p<0.001). The average exposure rate for the PSA has increased by 1.08% by each year. Based on the officially reported expected life expectancy, 28,822 new PCa cases in 2030 (when PSA incidence was expected to be 14.4%) and 40,478 cases in 2040 were extracted from the current equation projected (when PSA incidence was expected to be 26.4%). If public PSA screening has been routinely performed only in the ‘60s and ‘70s in 2030, the number of cases would be 37,503 in 2030 (PSA incidence was expected to be 23.06%) and 43,719 in 2040 (Figure 1). CONCLUSIONS: With the accelerating trend of social aging, the incidence of PCa was anticipated to be increased almost two-fold by 2030. With the aid of a national-wide screening program only for the limited age subgroups, significantly enhanced detection could be expected. Source of Funding: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT). (No. 2022R1A2C1009074) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1103 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Young Hwii Ko More articles by this author Ki Hak Moon More articles by this author Hee Chang Jung More articles by this author Phil Hyun Song More articles by this author Jae Young Choi More articles by this author Yeong Uk Kim More articles by this author Jae Youn Jang More articles by this author Jong Gyun Ha More articles by this author Expand All Advertisement PDF downloadLoading ...

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*Department of Ophthalmology, Myongji Hospital, Hanyang University College of Medicine, Goyang, South Korea; †Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea; ‡Integrated Major in Innovative Medical Science, Seoul National University College of Medicine, Seoul, South Korea; and §Department of Ophthalmology, Seoul National University Hospital, Seoul, South Korea. This work was supported by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT) (2020R1F1A1072264). None of the authors has any financial/conflicting interests to disclose.