Cancer Research and Treatment

Original Articles

Genitourinary cancer

Next-generation Proteomics-Based Discovery, Verification, and Validation of Urine Biomarkers for Bladder Cancer Diagnosis: Jungyo Suh, Dohyun Han, Ja Hyeon Ku, Hyeon Hoe Kim, Cheol Kwak, Chang Wook Jeong; Cancer Res Treat. 2022;54(3):882-893. Published online October 9, 2021; DOI: https://doi.org/10.4143/crt.2021.642

Abstract PDF Supplementary Material PubReader ePub

Purpose
We aimed to identify, verify, and validate a multiplex urinary biomarker-based prediction model for diagnosis and surveillance of urothelial carcinoma of bladder, using high-throughput proteomics methods.
Materials and Methods
Label-free quantification of data-dependent and data-independent acquisition of 12 and 24 individuals was performed in each of the discovery and verification phases using mass spectrometry, simultaneously using urinary exosome and proteins. Based on five scoring system based on proteomics data and statistical methods, we selected eight proteins. Enzyme-linked immunosorbent assay on urine from 120 patients with bladder mass lesions used for validation. Using multivariable logistic regression, we selected final candidate models for predicting bladder cancer.
Results
Comparing the discovery and verification cohorts, 38% (50/132 exosomal differentially expressed proteins [DEPs]) and 44% (109/248 urinary DEPs) are consistent at statistically significance, respectively. The 20 out of 50 exosome proteins and 27 out of 109 urinary proteins were upregulated in cancer patients. From eight selected proteins, we developed two diagnostic models for bladder cancer. The area under the receiver operating characteristic curve (AUROC) of two models were 0.845 and 0.842, which outperformed AUROC of urine cytology.
Conclusion
The results showed that the two diagnostic models developed here were more accurate than urine cytology. We successfully developed and validated a multiplex urinary protein-based prediction, which will have wide applications for the rapid diagnosis of urothelial carcinoma of the bladder. External validation for this biomarker panel in large population is required.

Citations

Citations to this article as recorded by

A novel machine learning algorithm selects proteome signature to specifically identify cancer exosomes
Bingrui Li, Fernanda G Kugeratski, Raghu Kalluri
eLife.2024;[Epub] CrossRef
A novel machine learning algorithm selects proteome signature to specifically identify cancer exosomes
Bingrui Li, Fernanda G Kugeratski, Raghu Kalluri
eLife.2024;[Epub] CrossRef
Comprehensive Urinary Proteome Profiling Analysis Identifies Diagnosis and Relapse Surveillance Biomarkers for Bladder Cancer
Qi Chang, Yongqiang Chen, Jianjian Yin, Tao Wang, Yuanheng Dai, Zixin Wu, Yufeng Guo, Lingang Wang, Yufen Zhao, Hang Yuan, Dongkui Song, Lirong Zhang
Journal of Proteome Research.2024; 23(6): 2241. CrossRef
Construction of noninvasive prognostic model of bladder cancer patients based on urine proteomics and screening of natural compounds
Shun Wan, Jinlong Cao, Siyu Chen, Jianwei Yang, Huabin Wang, Chenyang Wang, Kunpeng Li, Li Yang
Journal of Cancer Research and Clinical Oncology.2023; 149(1): 281. CrossRef
Extracellular Vesicles as Potential Bladder Cancer Biomarkers: Take It or Leave It?
Ana Teixeira-Marques, Catarina Lourenço, Miguel Carlos Oliveira, Rui Henrique, Carmen Jerónimo
International Journal of Molecular Sciences.2023; 24(7): 6757. CrossRef
Advances in the application of label‐free quantitative proteomics techniques in malignancy research
Xiao Meng, Dong Liu, Yan Guan
Biomedical Chromatography.2023;[Epub] CrossRef
Off the fog to find the optimal choice: Research advances in biomarkers for early diagnosis and recurrence monitoring of bladder cancer
Jiaxin Zhao, Jinming Li, Rui Zhang
Biochimica et Biophysica Acta (BBA) - Reviews on Cancer.2023; 1878(4): 188926. CrossRef
An overview of metabolomic and proteomic profiling in bipolar disorder and its clinical value
Henrique Caracho Ribeiro, Flávia da Silva Zandonadi, Alessandra Sussulini
Expert Review of Proteomics.2023; 20(11): 267. CrossRef
Proteome and immune responses of extracellular vesicles derived from macrophages infected with the periodontal pathogen Tannerella forsythia
Younggap Lim, Hyun Young Kim, Dohyun Han, Bong‐Kyu Choi
Journal of Extracellular Vesicles.2023;[Epub] CrossRef
A Liquid Biopsy in Bladder Cancer—The Current Landscape in Urinary Biomarkers
Milena Matuszczak, Adam Kiljańczyk, Maciej Salagierski
International Journal of Molecular Sciences.2022; 23(15): 8597. CrossRef
Next-generation proteomics of serum extracellular vesicles combined with single-cell RNA sequencing identifies MACROH2A1 associated with refractory COVID-19
Takahiro Kawasaki, Yoshito Takeda, Ryuya Edahiro, Yuya Shirai, Mari Nogami-Itoh, Takanori Matsuki, Hiroshi Kida, Takatoshi Enomoto, Reina Hara, Yoshimi Noda, Yuichi Adachi, Takayuki Niitsu, Saori Amiya, Yuta Yamaguchi, Teruaki Murakami, Yasuhiro Kato, Tak
Inflammation and Regeneration.2022;[Epub] CrossRef

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10 Web of Science
11 Crossref

Gynecologic Cancer

Performance and Diagnostic Accuracy of Human Papillomavirus Testing on Self-Collected Urine and Vaginal Samples in a Referral Population: Hyun-Woong Cho, Jin Hwa Hong, Kyung Jin Min, Yung-Taek Ouh, Seok Ju Seong, Jun Hye Moon, Seong Hwan Cho, Jae Kwan Lee; Cancer Res Treat. 2021;53(3):829-836. Published online December 24, 2020; DOI: https://doi.org/10.4143/crt.2020.1165

Abstract PDF PubReader ePub

Purpose
The study aimed to evaluate the diagnostic accuracy of polymerase chain reaction ‒based high-risk human papillomavirus (HPV) assays on self-collected vaginal and urine samples for detection of precancerous cervical lesions in referral population.
Materials and Methods
Women referred for colposcopy following abnormal cytology, were included this study. A total of 314 matched urine, vaginal, and cervical samples were collected. All samples were tested for HPV DNA using the RealTime HR-S HPV and Anyplex II HPV 28 assays. Primary endpoints were sensitivity for cervical intraepithelial neoplasia (CIN) 2+/CIN3+ and specificity for Result
The sensitivity of Realtime HR-S and Anyplex HPV assay was 93.13% (95% confidence interval [CI], 87.36 to 96.81) and 90.08% (95% CI, 83.63 to 94.61) for CIN2+ (n=130); specificity for Conclusion
The detection performance for hrHPV and CIN2+ on self-collected vaginal samples was comparable to that of clinician-collected cervical samples. On the other hand, HPV tests using urine were inferior to those using clinician-collected cervical samples in terms of detecting hrHPV and CIN2+.

Citations

Citations to this article as recorded by

Variables that impact HPV test accuracy during vaginal self collection workflow for cervical cancer screening
Laurence Vaughan, Devin Gary, Millie Shah, Lyndsay Lewellen, Laura Galbraith, Valentin Parvu
Gynecologic Oncology Reports.2024; 54: 101421. CrossRef
Clinical performance of a newly developed domestic urine‐based HPV test for cervical cancer screening in China
Hui‐Fang Xu, Xue‐Lian Zhao, Shuang Zhao, Shang‐Ying Hu, Xun Zhang, Fang‐Hui Zhao, You‐Lin Qiao
Journal of Medical Virology.2023;[Epub] CrossRef
Can HPV Test on Random Urine Replace Self-HPV Test on Vaginal Self-Samples or Clinician-Collected Cervical Samples?
Yu-Hsiang Shih, Lou Sun, Shih-Tien Hsu, Ming-Jer Chen, Chien-Hsing Lu
International Journal of Women's Health.2023; Volume 15: 1421. CrossRef
Preliminary Results of Feasibility and Acceptability of Self-Collection for Cervical Screening in Italian Women
Illari Sechi, Narcisa Muresu, Mariangela V. Puci, Laura Saderi, Arcadia Del Rio, Andrea Cossu, Maria R. Muroni, Santina Castriciano, Marianna Martinelli, Clementina E. Cocuzza, Giovanni Sotgiu, Andrea Piana
Pathogens.2023; 12(9): 1169. CrossRef
Human papillomavirus testing using HPV APTIMA® assay and an external cellularity control in self‐collected samples
Christophe Pasquier, Stéphanie Raymond, Delphine Duchanois, Karine Sauné, Kevin Oliveira‐Mendes, Christophe Vayssiere, Jacques Izopet
Journal of Medical Virology.2023;[Epub] CrossRef
Comparison of Different Self-Sampling Devices for Molecular Detection of Human Papillomavirus (HPV) and Other Sexually Transmitted Infections (STIs): A Pilot Study
Illari Sechi, Clementina Cocuzza, Marianna Martinelli, Narcisa Muresu, Santina Castriciano, Giovanni Sotgiu, Andrea Piana
Healthcare.2022; 10(3): 459. CrossRef
The Potential of Urine for Human papillomavirus-related Cervical Cancer Prevention
Maryame Lamsisi, Guorong Li, Celine Chauleur, Moulay Mustapha Ennaji, Thomas Bourlet
Future Virology.2022; 17(7): 495. CrossRef
Evaluation of BD Onclarity™ HPV Assay on Self-Collected Vaginal and First-Void Urine Samples as Compared to Clinician-Collected Cervical Samples: A Pilot Study
Marianna Martinelli, Chiara Giubbi, Illari Sechi, Fabio Bottari, Anna Daniela Iacobone, Rosario Musumeci, Federica Perdoni, Narcisa Muresu, Andrea Piana, Robert Fruscio, Fabio Landoni, Clementina Elvezia Cocuzza
Diagnostics.2022; 12(12): 3075. CrossRef
Urine HPV in the Context of Genital and Cervical Cancer Screening—An Update of Current Literature
Alexandros Daponte, George Michail, Athina-Ioanna Daponte, Nikoletta Daponte, George Valasoulis
Cancers.2021; 13(7): 1640. CrossRef
Diagnostic Test Accuracy of First-Void Urine Human Papillomaviruses for Presence Cervical HPV in Women: Systematic Review and Meta-Analysis
Peter Bober, Peter Firment, Ján Sabo
International Journal of Environmental Research and Public Health.2021; 18(24): 13314. CrossRef

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NUDT15 Variants Cause Hematopoietic Toxicity with Low 6-TGN Levels in Children with Acute Lymphoblastic Leukemia: Eun Sang Yi, Young Bae Choi, Rihwa Choi, Na Hee Lee, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Soo-Youn Lee, Hong Hoe Koo; Cancer Res Treat. 2018;50(3):872-882. Published online September 13, 2017; DOI: https://doi.org/10.4143/crt.2017.283

Abstract PDF PubReader ePub

Purpose
We aimed to identify the impact of NUDT15 variants on thiopurine intolerance and 6-thioguanine nucleotide (6-TGN) levels in Korean children with acute lymphoblastic leukemia (ALL).
Materials and Methods
Genotyping of NUDT15 was tested in 258 patients with ALL registered at Samsung Medical Center. Patients were classified into normal-activity (wild-type), intermediate-activity (heterozygous variant), and low-activity groups (homozygous or compound heterozygous variant). Clinical and laboratory features during the first year of maintenance therapy were investigated.
Results
A total of 182 patients were included in the final analysis. There were five (2.7%), 46 (25.3%), and 131 (72.0%) patients in low-, intermediate-, and normal-activity groups, respectively. The lowest 6-mercaptopurine (6-MP) dose (mg/m2/day) was administered to the low-activity group (low-activity group 7.5 vs. intermediate-activity group 24.4 vs. normalactivity group 31.1, p < 0.01) from three months to a year after beginning maintenance therapy. The low-activity group experienced the longest duration of therapy interruption during the first year (low-activity group 169 days vs. intermediate-activity group 30 days vs. normal-activity group 16 days, p < 0.01). They also showed the lowest blood cell counts and had a longer duration of leukopenia (low-activity group 131 days vs. intermediate-activity group 92 days vs. normal-activity group 59 days, p < 0.01). 6-TGN level and its ratio to 6-MP dose were lowest in the low-activity group.
Conclusion
NUDT15 variants cause hematopoietic toxicity with low 6-TGN levels. NUDT15 genotyping should be conducted before administering thiopurine, and dose adjustments require caution regardless of 6-TGN levels.

Citations

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The frequency of NUDT15 rs116855232 and its impact on mercaptopurine-induced toxicity in Syrian children with acute lymphoblastic leukemia
Muhammad Muhammad, Maher Saifo, Majd Aljamali, Mousa Alali, Khaled M. Ghanem
Frontiers in Oncology.2024;[Epub] CrossRef
Editorial Response to the Letter Relating to our Article “Predicting Adverse Events to Thiopurines in IBD: Are We a Step Closer?”
Mohmmed Tauseef Sharip, Miles Parkes, Sreedhar Subramanian
Inflammatory Bowel Diseases.2024;[Epub] CrossRef
Mercaptopurine induced myelosuppression in a child with a NUDT15 rs116855232 homozygous variant
Navya Gupta, Latha Sneha Magatha, Dhaarani Jayaraman, Julius Xavier Scott, Sharon Benita Antony, Teena Koshy
Journal of Oncology Pharmacy Practice.2023; 29(4): 999. CrossRef
Density functional study of transition metal (Fe,Co,Ni)‐doped C60 fullerenes as 6‐thioguanine delivery system
ShiQuan Wu, Li Li, QiQi Liang, HuaXu Gao, DeYuan Hu, TianYu Tang, Yanlin Tang
Applied Organometallic Chemistry.2023;[Epub] CrossRef
The influence of NUDT15 variants on 6-mercaptopurine-induced neutropenia in Vietnamese pediatric acute lymphoblastic leukemia
Mai-Lan Nguyen, Anh Vu Hoang, Bich Tram Duong, Nguyen The Nguyen Phung
Human Genetics and Genomics Advances.2023; 4(2): 100183. CrossRef
NUDT15 genetic testing-guided 6-mercaptopurine dosing in children with ALL likely to be cost-saving in China
XiaoXia Wei, Jing Zhuang, Na Li, Bin Zheng, Hong Sun, JiaQin Cai, Xuhui Huang, Guifeng Zhang, Jie Zhuang
International Journal of Hematology.2022; 115(2): 278. CrossRef
NUDT15 is a key genetic factor for prediction of hematotoxicity in pediatric patients who received a standard low dosage regimen of 6-mercaptopurine
Kanyarat Khaeso, Patcharee Komvilaisak, Su-on Chainansamit, Nontaya Nakkam, Kunanya Suwannaying, Pitchayanan Kuwatjanakul, Keiko Hikino, Areerat Dornsena, Sirimas Kanjanawart, Napat Laoaroon, Suda Vannaprasaht, Takeshi Taketani, Wichittra Tassaneeyakul
Drug Metabolism and Pharmacokinetics.2022; 43: 100436. CrossRef
NUDT15 Genetic Variants in Chinese Han, Uighur, Kirghiz, and Dai Nationalities
Fang Zhang, Gulbanur Amat, Yanjing Tang, Ru Chen, Xin Tian, Wenting Hu, Changcheng Chen, Shuhong Shen, Yangyang Xie
Frontiers in Pediatrics.2022;[Epub] CrossRef
A direct sequencing assay for pharmacogenetic testing of thiopurine-intolerant NUDT15 alleles in an Asian population
Kok-Siong Poon, Izz Irfan B. Imran, Silvester Kheng-Han Chew, Patrice Tan, Karen Mei-Ling Tan
BMC Research Notes.2022;[Epub] CrossRef
NUDT15Genotyping in Thiopurine Drug Therapy
Jong Kwon Lee, Rihwa Choi, Soo-Youn Lee
Laboratory Medicine Online.2022; 12(4): 217. CrossRef
The Effect of NUDT15, TPMT, APEX1, and ITPA Genetic Variations on Mercaptopurine Treatment of Pediatric Acute Lymphoblastic Leukemia
Jae Min Lee, Ye Jee Shim, Do-Hoon Kim, Nani Jung, Jung-Sook Ha
Children.2021; 8(3): 224. CrossRef
Pharmacogenomics in Pediatric Oncology: Mitigating Adverse Drug Reactions While Preserving Efficacy
Abdelbaset A. Elzagallaai, Bruce C. Carleton, Michael J. Rieder
Annual Review of Pharmacology and Toxicology.2021; 61(1): 679. CrossRef
DNA-thioguanine nucleotide as a treatment marker in acute lymphoblastic leukemia patients with NUDT15 variant genotypes
Hee Young Ju, Ji Won Lee, Hee Won Cho, Ju Kyung Hyun, Youngeun Ma, Eun Sang Yi, Keon Hee Yoo, Ki Woong Sung, Rihwa Choi, Hong Hoe Koo, Soo-Youn Lee, A. M. Abd El-Aty
PLOS ONE.2021; 16(1): e0245667. CrossRef
NUDT15: A bench to bedside success story
Ann M. Moyer
Clinical Biochemistry.2021; 92: 1. CrossRef
Association Between Genetic Polymorphisms of Metabolic Enzymes and Azathioprine-Induced Myelosuppression in 1,419 Chinese Patients: A Retrospective Study
Zhao-Yang Chen, Yang-Hui Zhu, Ling-Yan Zhou, Wei-Qiao Shi, Zhou Qin, Bin Wu, Yu Yan, Yu-Wen Pei, Ning-Ning Chao, Rui Zhang, Mi-Ye Wang, Ze-Hao Su, Xiao-Jun Lu, Zhi-Yao He, Ting Xu
Frontiers in Pharmacology.2021;[Epub] CrossRef
NUDT15 polymorphism in healthy children with Bai nationality in Yunnan of China
Gangling Pu, Yali Wang, Shaoqin Duan, Jingpei Chen, Chunhui Yang, Tingting Cui, Chunlian Fang, Yan Zhou, Han Zhang, Xin Tian
Pediatrics International.2021; 63(7): 790. CrossRef
Significance of TPMT and NUDT15 variants in 6-mercaptopurine metabolism in acute lymphoblastic leukaemia/lymphoma patients
E. S. Kotova, O. A. Gavrilina, A. B. Sudarikov
Russian journal of hematology and transfusiology.2021; 66(2): 253. CrossRef
NUDT15 c.415C>T Polymorphism Predicts 6-MP Induced Early Myelotoxicity in Patients with Acute Lymphoblastic Leukemia Undergoing Maintenance Therapy
Aswin Anand Pai, Ajith Mohan, Esther Sathya Bama Benjamin, Raveen Stephen Stallon Illangeswaran, Infencia Xavier Raj, Nancy Beryl Janet, Arun Kumar Arunachalam, ML Kavitha, Uday Kulkarni, Anup J Devasia, NA Fouzia, Aby Abraham, Alok Srivastava, Biju Georg
Pharmacogenomics and Personalized Medicine.2021; Volume 14: 1303. CrossRef
Reducing risk in thiopurine therapy
Anthony M. Marinaki, Monica Arenas-Hernandez
Xenobiotica.2020; 50(1): 101. CrossRef
Precision therapy of 6‐mercaptopurine in Chinese children with acute lymphoblastic leukaemia
Yue Zhou, Li Wang, Xiao‐Ying Zhai, Li Wen, Fang Tang, Fan Yang, Xi‐Ting Liu, Lei Dong, Li‐Juan Zhi, Hai‐Yan Shi, Guo‐Xiang Hao, Yi Zheng, Evelyne Jacqz‐Aigrain, Tian‐You Wang, Wei Zhao
British Journal of Clinical Pharmacology.2020; 86(8): 1519. CrossRef
NUDT15 Genetic Variants are Related to Thiopurine-Induced Neutropenia in Thai Children with Acute Lymphoblastic Leukemia
Apichaya Puangpetch, Rawiporn Tiyasirichokchai, Samart Pakakasama, Supaporn Wiwattanakul, Usanarat Anurathapan, Suradej Hongeng, Chonlaphat Sukasem
Pharmacogenomics.2020; 21(6): 403. CrossRef
Association of NUDT15 c.415C>T and FPGS 2572C>T Variants with the Risk of Early Hematologic Toxicity During 6-MP and Low-Dose Methotrexate-Based Maintenance Therapy in Indian Patients with Acute Lymphoblastic Leukemia
Sunitha Kodidela, Patchava Dorababu, Dimpal N. Thakkar, Biswajit Dubashi, Rajan Sundaram, Niveditha Muralidharan, Ravi Prasad Nidanapu, Anil Aribandi, Suresh Chandra Pradhan, Chakradhara Rao Satyanarayana Uppugunduri
Genes.2020; 11(6): 594. CrossRef
Classification and regression tree-based prediction of 6-mercaptopurine-induced leucopenia grades in children with acute lymphoblastic leukemia
Shaik Mohammad Naushad, Patchava Dorababu, Yedluri Rupasree, Addepalli Pavani, Digumarti Raghunadharao, Tajamul Hussain, Salman A. Alrokayan, Vijay Kumar Kutala
Cancer Chemotherapy and Pharmacology.2019; 83(5): 875. CrossRef
Pathway genes and metabolites in thiopurine therapy in Korean children with acute lymphoblastic leukaemia
Rihwa Choi, Insuk Sohn, Min‐Ji Kim, Hye In Woo, Ji Won Lee, Youngeun Ma, Eun Sang Yi, Hong Hoe Koo, Soo‐Youn Lee
British Journal of Clinical Pharmacology.2019; 85(7): 1585. CrossRef
Nucleoside diphosphate-linked moiety X-type motif 15 R139C genotypes impact 6-thioguanine nucleotide cut-off levels to predict thiopurine-induced leukopenia in Crohn’s disease patients
Xia Zhu, Kang Chao, Miao Li, Wen Xie, Hong Zheng, Jin-Xin Zhang, Pin-Jin Hu, Min Huang, Xiang Gao, Xue-Ding Wang
World Journal of Gastroenterology.2019; 25(38): 5850. CrossRef
Homozygous mutation in NUDT15 in childhood acute lymphoblastic leukemia with increased susceptibility to mercaptopurine toxicity: A case report
Juan Cheng, Hao Zhang, Hai‑Zhen Ma, Juan Li
Experimental and Therapeutic Medicine.2019;[Epub] CrossRef
Pharmacogenetics of thiopurines for inflammatory bowel disease in East Asia: prospects for clinical application of NUDT15 genotyping
Yoichi Kakuta, Yoshitaka Kinouchi, Tooru Shimosegawa
Journal of Gastroenterology.2018; 53(2): 172. CrossRef

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APEX1 Polymorphism and Mercaptopurine-Related Early Onset Neutropenia in Pediatric Acute Lymphoblastic Leukemia: Hyery Kim, Heewon Seo, Yoomi Park, Byung-Joo Min, Myung-Eui Seo, Kyung Duk Park, Hee Young Shin, Ju Han Kim, Hyoung Jin Kang; Cancer Res Treat. 2018;50(3):823-834. Published online September 4, 2017; DOI: https://doi.org/10.4143/crt.2017.351

Abstract PDF Supplementary Material PubReader ePub

Purpose
Mercaptopurine (MP) is one of the main chemotherapeutics for acute lymphoblastic leukemia (ALL). To improve treatment outcomes, constant MP dose titration is essential to maintain steady drug exposure, while minimizing myelosuppression. We performed two-stage analyses to identify genetic determinants of MP-related neutropenia in Korean pediatric ALL patients.
Materials and Methods
Targeted sequencing of 40 patients who exhibited definite MP intolerance was conducted using a novel panel of 211 pharmacogenetic-related genes, and subsequent analysis was performed with 185 patients.
Results
Using bioinformatics tools and genetic data, four functionally interesting variants were selected (ABCC4, APEX1, CYP1A1, and CYP4F2). Including four variants, 23 variants in 12 genes potentially linked to MP adverse reactions were selected as final candidates for subsequent analysis in 185 patients. Ultimately, a variant allele in APEX1 rs2307486was found to be strongly associated with MP-induced neutropenia that occurred within 28 days of initiating MP (odds ratio, 3.44; p=0.02). Moreover, the cumulative incidence of MP-related neutropenia was significantly higher in patients with APEX1 rs2307486 variants, as GG genotypes were associated with the highest cumulative incidence (p < 0.01). NUDT15 rs116855232 variants were strongly associated with a higher cumulative incidence of neutropenia (p < 0.01), and a lower median dose of tolerated MP throughout maintenance treatment (p < 0.01).
Conclusion
We have identified that APEX1 rs2307486 variants conferred an increased risk of MP-related early onset neutropenia. APEX1 and NUDT15 both contribute to cell protection from DNA damage or misincorporation, so alleles that impair the function of either gene may affect MP sensitivities, thereby inducing MP-related neutropenia.

Citations

Citations to this article as recorded by

Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response
Ashwin Kamath, Suresh Kumar Srinivasamurthy, Mukta N. Chowta, Sheetal D. Ullal, Youssef Daali, Uppugunduri S. Chakradhara Rao
Pharmaceuticals.2022; 15(8): 990. CrossRef
The Effect of NUDT15, TPMT, APEX1, and ITPA Genetic Variations on Mercaptopurine Treatment of Pediatric Acute Lymphoblastic Leukemia
Jae Min Lee, Ye Jee Shim, Do-Hoon Kim, Nani Jung, Jung-Sook Ha
Children.2021; 8(3): 224. CrossRef
Interplay between IL6 and CRIM1 in thiopurine intolerance due to hematological toxicity in leukemic patients with wild-type NUDT15 and TPMT
Hyery Kim, Seungwon You, Yoomi Park, Jung Yoon Choi, Youngeun Ma, Kyung Tak Hong, Kyung-Nam Koh, Sunmin Yun, Kye Hwa Lee, Hee Young Shin, Suehyun Lee, Keon Hee Yoo, Ho Joon Im, Hyoung Jin Kang, Ju Han Kim
Scientific Reports.2021;[Epub] CrossRef
NUDT15 polymorphism in healthy children with Bai nationality in Yunnan of China
Gangling Pu, Yali Wang, Shaoqin Duan, Jingpei Chen, Chunhui Yang, Tingting Cui, Chunlian Fang, Yan Zhou, Han Zhang, Xin Tian
Pediatrics International.2021; 63(7): 790. CrossRef
A Dual Face of APE1 in the Maintenance of Genetic Stability in Monocytes: An Overview of the Current Status and Future Perspectives
Gabriela Betlej, Ewelina Bator, Antoni Pyrkosz, Aleksandra Kwiatkowska
Genes.2020; 11(6): 643. CrossRef
Homozygote CRIM1 variant is associated with thiopurine-induced neutropenia in leukemic patients with both wildtype NUDT15 and TPMT
Yoomi Park, Hyery Kim, Heewon Seo, Jung Yoon Choi, Youngeun Ma, Sunmin Yun, Byung-Joo Min, Myung-Eui Seo, Keon Hee Yoo, Hyoung Jin Kang, Ho Joon Im, Ju Han Kim
Journal of Translational Medicine.2020;[Epub] CrossRef
Pharmacogenomics as a Tool to Limit Acute and Long-Term Adverse Effects of Chemotherapeutics: An Update in Pediatric Oncology
Emma C. Bernsen, Melanie M. Hagleitner, Theodorus W. Kouwenberg, Lidwien M. Hanff
Frontiers in Pharmacology.2020;[Epub] CrossRef
Long-term treatment outcomes of children and adolescents with lymphoblastic lymphoma treated with various regimens: a single-center analysis
Ho Jung Choi, Juhee Shin, Sunghan Kang, Jin Kyung Suh, Hyery Kim, Kyung-Nam Koh, Ho Joon Im
BLOOD RESEARCH.2020; 55(4): 262. CrossRef
NUDT15 Variants Cause Hematopoietic Toxicity with Low 6-TGN Levels in Children with Acute Lymphoblastic Leukemia
Eun Sang Yi, Young Bae Choi, Rihwa Choi, Na Hee Lee, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Soo-Youn Lee, Hong Hoe Koo
Cancer Research and Treatment.2018; 50(3): 872. CrossRef

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Expression of MDM-2 and p53 Proteins in Gastric Adendegrees Carcinoma and Its Relationship with Clinicopathologic Factors: Ji Woong Yang, Hyoung Joong Kim, Tae Jin Lee, Eon Sub Park, Jae Hyoung Yoo; J Korean Cancer Assoc. 2000;32(3):476-486.

Abstract PDF: PURPOSE
MDM-2 is an oncoprotein that inhibits p53 tumor-suppressor protein. These abnor malities have a role in tumorigenesis through inactivation of p53 function. To determine the clini copathological and prognostic value of MDM2 abnormalities in gastric adendegrees Carcinoma, MDM-2& p53 protein expression were analysed in surgically resected materials of gastric adendegrees Carcinoma.
MATERIALS AND METHODS
Fifty cases which had got follow-up after surgical resection were immunohistdegrees Chemically studied with p53 and MDM-2 antibodies. We defined variable clinico pathologic factors for expression of p53 and MDM-2 protein and analysed their relationships.
RESULTS
Immunohistdegrees Chemical stain revealed expression of MDM-2 protein as a 52.0% (26/50) and p53 protein 20.0% (10/50), respectively. But their expressions were not assdegrees Ciated with clinicopathological factors such as T-factor, N-factor, stage, histology and differentiation. Overall, p53-negative patients seemed to have a better prognosis regardless of MDM-2 protein status (P= 0.057). MDM-2 protein status was considered to have no play as a prognostic factor.
CONCLUSION
In the gastric adendegrees Carcinoma, p53 protein expression seemed to have a inverse relationship with clinical outcomes but MDM-2 protein expression, which was observed more frequently than those of p53, seemed not to be prognostic indicator.

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Nitric Oxide Synthesis in Murine Skin Cancers: Chang Yeol Yim, Chang Hwan Lee, Soo Mi Choi, Wan Hee Yoo, Sung Joong Lee, Seong Hee Lim, Myung Hee Sohn; J Korean Cancer Assoc. 1995;27(1):101-111.

Abstract PDF: Nitric oxide(NO) is a major cytotoxic effector molecule of activated macrophages. Although the antitumor activity of NO produced by activated macrophages was demonstrated in in vitro experiments, the in vivo role of tumor infiltrating macropheges in tumor growth is currently uncertain. It is also unknown that tumor infiltrating macrophages produce NO, and thereby contribute either a host antitumor immune defense mechanism or a promoting mechanism of in vivo tumor growth by suppressing immune function. The purpose of the current study was to evaluate whether the NO synthesizing pathway is activated in in vivo growing tumor tissue, and thereby the produced NO inhibits tumor growth using various murine skin tumor models. Further experiments were designed to test whether tumor infiltrating macrophages are the major source of NO produced by the in vivo growing tumor tissue. Freshly diesociated murine skin tumors were found to have much higher levels of nitric axide secretion into culture medi- um than long-term cultured tumor. Immunomagnetic depletion of macrophages from freshly dissociated tumor cells using anti-Mac-1 antibody decreased NO production(17.5+-1.5 vs 5.0+-1.1 uM nitrite). Addition of the nitric oxide synthase inhibitor N-monomethyl-L-arginine(MLA) resulted in a dose-dependent decrease in nitric oxide synthesis in freshly dissociated tumor. There was a reciprocal relationship of NO synthesis with tritiated thymidine incorporation in these cultures. Strong iron-dithiol-dinitrosyl and heme-nitrosyl electron paramagnetic resonance signals were observed in freshly dissociated, but not long-term cultured tumor cells. Inhibition of NO synthesis using in vivo MLA administration resulted in a trend of increased growth rate of RD-995 murine skin cancer. This study demonstrates the role of macrophage NO synthesis as a host defense against tumor in vivo.

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