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Risk stratification for disease progression in pT3 prostate cancer after robot-assisted radical prostatectomy

Asian Journal of Andrology 2017年第6期19卷 700-706页

作者： Jeong Hee Hong Young Suk Kwon isaac Yi kim Section of Urologic Oncology Rutgers Cancer Institute of New Jersey Division of Urology Rutgers Robert Wood Johnson Medical School Rutgers The State University of New Jersey New Brunswick NJ 08903 USA Department of Urology Dankook University College of Medicine Cheonan 31116 South Korea.

The aim of this study is to identify optimal patients for adjuvant radiation therapy （ART） in pT3 prostate cancer. The role of ART for patients with adverse pathologic features after radical prostatectomy （RP） has been demonstrated, but over- or under-treatment remains a significant concern. Two-hundred and five patients with pT3NOMO who underwent robot-assisted RP without ART were analyzed. Multivariate Cox proportional regression analyses were used to identify predictors of biochemical recurrence （BCR） and clinical progression （CP）. The estimated 5-year BCR-free survival （BCRFS） and CP-free survival （CPFS） were 52.8% and 85.6%, respectively. Preoperative prostate-specifc antigen （PSA）：〉10 ng m1-1 （hazard ratio [HR]： 3.288-6.027; P = 0.003）, pathologic Gleason score （pGS）：〉8 （HR： 4.146; P = 0.014）, and lymphovascular invasion （LVI）（HR： 2.167; P = 0.026） were associated with BCR. Based on these factors, a risk stratification tool was developed. Patients with no risk factors （PSA 〈10 ng m1-1, pGS 6, and absent LVI） showed excellent BCRFS and CPFS at 5 years （91.9% and 100.0%, respectively）, but those with two or more risk factors （PSA ：〉10 ng ml-1, pGS ≥8, or present LVI） had poor BCRFS and CPFS （12.1% and 54.6%, respectively）. In addition, the multivariate analysis revealed that pathologic stage pT3b （HR： 5.393; P = 0.025） was the only predictor of CP. Our study demonstrated the heterogeneity of oncologic outcomes in patients with pT3 prostate cancer. The proposed risk stratification can be used to identify patients who are at risk for disease progression and may aid in identifying the best patients for ART.

关键词： prostatectomy prostate-specific antigen recurrence survival

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Refining the American Urological Association and American Society for Radiation Oncology guideline for adjuvant radiotherapy after radical prostatectomy using the pathologic Gleason score

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Asian Journal of Andrology 2017年第1期19卷 20-25页

作者： Wan Song Young Suk Kwon Seong Soo Jeon isaac Yi kim Section of Urologic Oncology Rutgers Cancer Institute of New Jersey Rutgers The State University of New Jersey New Brunswick NJ 08903 USA Department of Urology Samsung Medical Center Sungkyunkwan University School of Medicine Seoul South Korea.

Recently, it has been suggested that the guideline for adjuvant radiotherapy （ART） following radical prostatectomy （RP） sponsored by the American Urological Association and American Society for Radiation Oncology （AUA/ASTRO） may result in a significant overtreatment. Thus, the objective of the present study was to refine the AUA/ASTRO guideline for ART in patients at risk for biochemical recurrence （BCR） after RP. To this end, we reviewed our prospectively maintained database and selected 193 patients who met the AUA/ASTRO ART criteria. With a median follow-up of 24.0 months, BCR rate was 17.6% （34/193）. When stratified by the Gleason score, BCR rate in men with Gleason score 6 was 6.8%. There was no significant association between BCR-free survival and surgical margin （P= 0.690） and pathologic stage （P= 0.353） in patients with the Gleason score 6. However, in patients with positive surgical margins （PSMs）/pathologic stage ≥T3, there was a significant difference in BCR-free survival according to Gleason score （≤7 vs8-10, P= 0.047）. Multivariate Cox regression analysis demonstrated that pathologic stage ≥T3 （HR = 2.106; P = 0.018）, PSMs （HR = 2.411; P = 0.003）, and pathologic Gleason score 8-10 （HR = 4.715; P 〈 0.001） were independent predictors of BCR after RP. Therefore, in addition to pathologic stage 〉T3 and PSMs, Gleason score 8-10 predicts 8CR after RP. In patients with Gleason score 6, observation rather than ART may be more appropriate regardless of stage and surgical margin status.

关键词： adjuvant radiotherapy biochemical recurrence radical prostatectomy

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Pathological findings following radical prostatectomy in patients who are candidates for active surveillance： impact of varying PSA levels

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Asian Journal of Andrology 2011年第6期13卷 838-841页

作者： Dong Il Kang Thomas L. Jang Jeongyun Jeong Eun Young Choi Kelly Johnson Dong Hyeon Lee Wun-Jae kim isaac Yi kim Section of Urologic Oncology and Dean and Betty Gallo Prostate Cancer The Cancer Institute of New Jersey Robert Wood Johnson Medical School New Brunswick NJ 08903 USA Department of Urology Inje University Medical School Busan 614-735 Korea Department of Urology Ewha Womans University Seoul 158-710 Korea Department of Urology Chungbuk National University College of Medicine Cheongju 361-711 Korea

Active surveillance is an acceptable treatment option in men with a low-risk prostate cancer. In the present study, we have retrospectively reviewed the outcomes of 509 men who fit the criteria for active surveillance but selected radical prostatectomy. Then, the impact of varying prostate-specific antigen （PSA） levels on the risk of upstaging and upgrading in these patients was assessed. Pathological characteristics of patients who fulfilled the inclusion criteria under three active surveillance criteria--those of the University of California-San Francisco, the National Cancer Institute and the European Association of Urology--were examined. The proportion of men who were deemed candidates for active surveillance but were subsequently upstaged or upgraded was determined. Of 509 patients, 186 （36.5%）, 132 （25.9%） and 88 （17.3%） men fulfilled the active surveillance criteria, respectively. Upgrading （Gleason scores 7-10） ranged from 32.8% to 38.6%, while upstaging （≥ pT3） ranged from 10.2% to 12.5%, depending on the three active surveillance criteria. After a median follow-up of 24 months, three patients developed a biochemical recurrence. When the impact of varying PSA levels was examined using a test for trend analysis in the context of PSA for each protocol, rates of upstaging were lower in men with PSA 〈4 ng m1-1. However, there was no impact of varying PSA levels on upgrading. In conclusion, commonly used active surveillance protocols carry the risks of upgrading and upstaging. More reliable and accurate markers are needed to better stratify the risks of men who are appropriate candidates for active surveillance.

关键词： prostatectomy prostate-specific antigen prostatic neoplasm risk

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Risk of complications and urinary incontinence following cytoreductive prostatectomy： a multi-institutional study

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Asian Journal of Andrology 2018年第1期20卷 9-14页

作者： Dae Keun kim Jaspreet Singh Parihar Young Suk Kwon Sinae kim Brian Shinder Nara Lee Nicholas Farber Thomas Ahlering Douglas Skarecky Bertram Yuh Nora Ruel Wun-lae kim Koon Ho Rha isaac Yi kim Department of Urology CHA Seoul Station Medical Center CHA University CHA Medical School Seou104637 Korea Department of Urology School of Medicine Graduate School Hanyang University Seou104763 Korea Section of Urologic Oncology Rutgers Cancer Institute of New Jersey and Division of Urology Rutgers Robert Wood Johnson Medical School Rutgers The State University of New Jersey New Brunswick 08901 USA Department of Biostatistics Rutgers School of Public Health The State University of New Jersey New Brunswick NJ Piscataway 08854 USA Department of Internal Medicine Rutgers Robert Wood Johnson Medical School Rutgers The State University of New Jersey New Brunswick 08901 USA Department of Urology University of California Irvine School of Medicine Orange 92687 USA Division of Urology and UroLogic Oncology City of Hope National Medical Center Duarte 91010 USA Department of Urology Chungbuk National University College of Medicine Cheongju 28644 Korea Department of Urology and Urological Science Institute College of Medicine Yonsei University Seou103722. Korea

Emerging evidence has suggested that cytoreductive prostatectomy （CRP） allows superior oncologic control when compared to current standard of care androgen deprivation therapy alone. However, the safety and benefit of cytoreduction in metastatic prostate cancer （mPCa） has not been proven. Therefore, we evaluated the incidence of complications following CRP in men newly diagnosed with mPCa. A total of 68 patients who underwent CRP from 2006 to 2014 at four tertiary surgical centers were compared to 598 men who underwent radical prostatectomy for clinically localized prostate cancer （PCa）. Urinary incontinence was defined as the use of any pad. CRP had longer operative times （200 min vs 140 min, P 〈 0.0001） and higher estimated blood loss （250 ml vs 125 ml, P 〈 0.0001） compared to the control group. However, both overall （8.82% vs 5.85%） and major complication rates （4.41% vs 2.17%） were comparable between the two groups. Importantly, urinary incontinence rate at 1-year after surgery was significantly higher in the CRP group （57.4% vs 90.8%, P 〈 0.0001）. Univariate logistic analysis showed that the estimated blood loss was the only independent predictor of perioperative complications both in the unadjusted model （OR： 1.18; 95% Ch 1.02-1.37; P= 0.025） and surgery type-adjusted model （OR： 1.17; 95% Ch 1.01-1.36; P= 0.034）. In conclusion, CRP is more challenging than radical prostatectomy and associated with a notably higher incidence of urinary incontinence. Nevertheless, CRP is a technically feasible and safe surgery for selecting PCa patients who present with node-positive or bony metastasis when performed by experienced surgeons. A prospective, multi-institutional clinical trial is currently underway to verify this concept.

关键词： cytoreductive surgical procedures metastatic prostate cancer outcome radical prostatectomy

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A Predictive Model for Pathologic Complete Response in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy Using Machine Learning

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Advances in Breast Cancer Research 2021年第4期10卷 141-155页

作者： isaac kim Kwanbum Lee Seung Ah Lee Yeon Hee Park Seung Ki kim Department of Surgery Bundang CHA Medical Center CHA University School of Medicine Yatap-ro Gyeonggi-do Republic of Korea Division of Hematology-Oncology Department of Internal Medicine Samsung Medical Center Sungkyunkwan University School of Medicine Irwon-ro Gangnam-gu Seoul Republic of Korea

Background: In patients with breast cancer after Neoadjuvant Chemotherapy (NAC), pathological Complete Response (pCR) was associated with better long-term outcomes. We here attempted to predict pCR using machine learning. Patients and Methods: From 2008 to 2017, 1308 breast cancer patients underwent NAC before surgery, of whom 377 patients underwent Cancer SCANTM for gene data. Of 377, 238 were analyzed here, with 139 excluded due to incomplete medical data. Results: The pCR (-) vs. (+) group had 200 vs. 38 patients. In our predictive model with gene data, the Area Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) curve was 0.909 and accuracy was 0.875. In another model without gene data, the AUC of ROC curve was 0.743 and accuracy was 0.800. We also conducted internal validation with 72 patients undergoing NAC and Cancer SCANTM during July 2017 and April 2018. When we applied a 0

关键词： Breast Neoplasm Neoadjuvant Therapy Chemotherapy Response Prediction

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Systematic Radio Telescope Alignment Using Portable Fringe Projection Profilometry

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Nanomanufacturing and Metrology 2024年第1期7卷 75-85页

作者： Joel Berkson Justin Hyatt Nathan Julicher Byeongjoon Jeong isaac Pimienta Rachel Ball Wyatt Ellis Jason Voris Diego Torres‑Barajas Daewook kim James C.Wyant College of Optical Sciences University of Arizona1630 E.University Blvd.TucsonAZ 85721USA Department of Astronomy at Steward Observatory University of Arizona933 N Cherry Ave.TucsonAZ 85721USA

In 2019,the Event Horizon Telescope(EHT)released the first-ever image of a black hole event *** are now aiming for higher angular resolutions of distant targets,like black holes,to understand more about the fundamental laws of gravity that govern our *** achieve this higher resolution and increased sensitivity,larger radio telescopes are needed to operate at higher frequencies and in larger *** like the next-generation Very Large Array(ngVLA)and the Square-Kilometer Array(SKA)require building hundreds of telescopes with diameters greater than 10 ms over the next *** has a twofold *** telescope surfaces need to be more accurate to operate at higher frequencies,and the logistics involved in maintaining a radio telescope need to be simplified to support them properly in large *** of these problems can be solved with improved methods for surface metrology that are faster and more accurate with a higher *** leads to faster and more accurate panel alignment and,therefore,a more productive *** this paper,we present the use of binocular fringe projection profilometry as a solution to this problem and demonstrate it by aligning two panels on a 3-m radio telescope *** measurement takes only 10 min and directly delivers feedback on the tip,tilt,and piston of each panel to create the ideal reflector shape.

关键词： Metrology Fringe projection profilometry Off-axis alignment Radio astronomy Radio antenna

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Revolutionizing Non-Invasive Biomarker Discoveries: The Power of Methylation Screening Analysis in Cell-Free DNA Liquid Biopsy

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Open Journal of Genetics 2023年第1期13卷 48-74页

作者： Min Seob Lee Na Young Min Hyuk Jung Kwon Yonjung kim isaac Kise Lee Eone Diagnomics Genome Center (EDGC) Incheon South Korea NGENI Foundation California USA Incheon National University (INU) Incheon South Korea

Epigenetic changes of DNA, including methylation, have long been recognized as key indicators of various diseases, including aging, cancer, and neurological disorders. Biomarker discoveries based on distinct methylation patterns for both hypermethylation and hypomethylation lead the way in discovery of novel diagnosis and treatment targets. Many different approaches are present to detect the level of methylation in whole genome (whole genome bisulfite sequencing, microarray) as well as at specific loci (methylation specific PCR). Cell-free DNA (cf-DNA) found in body fluids like blood provides information about DNA methylation and serves as a less invasive approach for genetic screening. Cell-free DNA and methylation screening technologies, when combined, have the potential to transform the way we approach genetic screening and personalized therapy. These technologies can help enhance disease diagnostic accuracy and inform the development of targeted therapeutics by providing a non-invasive way for acquiring genomic information and identifying disease-associated methylation patterns. We highlight the clinical benefits of using cell-free DNA (cf-DNA) liquid biopsy analysis and available methylation screening technologies that have been crucial in identifying biomarkers for disease from patients using a non-invasive way. Powering such biomarker discoveries are various methods of cf-DNA methylation analysis such as Bisulfite Sequencing and most recently, Methylation-Specific Restriction Enzyme (MSRE-seq) Analysis, paving the way for novel epigenetic biomarker discoveries for more robust diagnosis such as early disease detection, prognosis, monitoring of disease progression and treatment response as well as discovery of novel drug targets.

关键词： Epigenetics Biomarkers Cell-Free DNA (cf-DNA) Methylation Liquid Biopsy Drug Target Methylation-Specific Restriction Enzyme (MSRE) Cancer Epigenetic Drugs Hypermethylation Hypomethylation

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Epigenetic Signatures of Aging: A Comprehensive Study of Biomarker Discovery

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Advances in Aging Research 2023年第2期12卷 11-38页

作者： Min Seob Lee Hyuk Jung Kwon Yonjung kim Na Young Min So Young Lee isaac Kise Lee Eone Diagnomics Genome Center (EDGC) Incheon South Korea Incheon National University (INU) Incheon South Korea

Background: Aging is a complex biological process that is associated with a decline in physiological functions and an increased risk of age-related diseases. Despite advances in molecular biology and genetics, the underlying mechanisms of aging remain largely unknown. Study: The identification of biomarkers of aging would provide a powerful tool for monitoring the effects of aging and for developing interventions to improve healthspan. Aging is associated with alterations in genetics, epigenetic marks, telomere shortening, cell senescence, and changes in the expression of genes involved in metabolism, inflammation, and DNA damage repair. Epigenetic changes, including modifications to DNA methylation and histone acetylation patterns, play a critical role in the aging process. As we age, these changes can lead to altered gene expression and contribute to the development of age-related diseases such as cancer, Alzheimer’s disease (AD) and cardiovascular disease (CVD). Conclusion: The discovery of aging biomarkers that are sensitive to these epigenetic changes has the potential to revolutionize our understanding of the aging process and inform the development of interventions to improve healthspan and extend lifespan.

关键词： Aging Biomarkers Epigenetics Methylation Geriatric Disease

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condLSTM-Q: A novel deep learning model for predicting COVID-19 mortality in fine geographical scale

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Quantitative Biology 2022年第2期10卷 125-138页

作者： HyeongChan Jo Juhyun kim Tzu-Chen Huang Yu-Li Ni Division of Biology and Biological Engineering CaltechPasadena CA 91125USA The Division of Physics Mathematics and AstronomyCaltechPasadena CA 91125USA Walter Burke Institute for Theoretical Physics CaltechPasadena CA 91125USA

Background: Modern machine learning-based models have not been harnessed to their total capacity for disease trend predictions prior to the COVID-19 pandemic. This work is the first use of the conditional RNN model in predicting disease trends that we know of during development that complemented classical epidemiological ***: We developed the long short-term memory networks with quantile output (condLSTM-Q) model for making quantile predictions on COVID-19 death ***: We verified that the condLSTM-Q was accurately predicting fine-scale, county-level daily deaths with a two-week window. The model’s performance was robust and comparable to, if not slightly better than well-known, publicly available models. This provides unique opportunities for investigating trends within the states and interactions between counties along state borders. In addition, by analyzing the importance of the categorical data, one could learn which features are risk factors that affect the death trend and provide handles for officials to ameliorate the ***: The condLSTM-Q model performed robustly, provided fine-scale, county-level predictions of daily deaths with a two-week window. Given the scalability and generalizability of neural network models, this model could incorporate additional data sources with ease and could be further developed to generate other valuable predictions such as new cases or hospitalizations intuitively.

关键词： COVID-19 machine learning deep learning epidemiology time series forecast

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Positional functionalizations of metal–organic frameworks through invasive ligand exchange and additory MOF-on-MOF strategies:A review

Smart Molecules

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Smart Molecules 2024年第2期2卷 63-84页

作者： Daeyeon Lee Sangho Lee isaac Choi Min kim Department of Chemistry Chungbuk National UniversityCheongjuRepublic of Korea

Metal–organic frameworks(MOFs)represent a unique class of porous materialswith tremendous potential for diverse applications.A key factor contributing totheir versatility is their ability to precisely introduce functional groups at specificpositions within pores and *** review explores two prominent strategiesfor achieving the positional functionalization of MOFs:post-synthetic ligand exchange(PSE)and *** PSE,the existing ligands within solid-stateMOFs can be selectively replaced by the desired functional groups in solutionthrough ligand *** invasive functionalization provides a flexibleapproach to fine-tuning the surface of the MOFs with the target ***,MOF-on-MOF strategies are additive methodologies involving thecontrolled growth of one MOF layer onto *** functionality of the core andshell(or surface)can be independently *** review critically examinesthe examples,strengths,limitations,and applications of these strategies,emphasizingtheir significance in advancing the field of MOF functionalization andpaving the way for tailored multifunctional materials with precise and specificproperties.

关键词： metal–organic frameworks(MOFs) MOF-on-MOF multifunctional materials porous coordination polymers(PCPs) post-synthetic exchanges(PSEs)

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