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Pediatric cancer
Tandem High-Dose Chemotherapy Increases the Risk of Secondary Malignant Neoplasm in Pediatric Solid Tumors
Hana Lim, Minji Im, Eun Seop Seo, Hee Won Cho, Hee Young Ju, Keon Hee Yoo, Sung Yoon Cho, Jong-Won Kim, Do Hoon Lim, Ki Woong Sung, Ji Won Lee
Cancer Res Treat. 2024;56(2):642-651.   Published online November 24, 2023
DOI: https://doi.org/10.4143/crt.2023.999
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to investigate the incidence and risk factors for secondary malignant neoplasms (SMN) in pediatric solid tumors, focusing on the effects of tandem high-dose chemotherapy (HDCT).
Materials and Methods
Patients (aged < 19 years) diagnosed with or treated for pediatric solid tumors between 1994 and 2014 were retrospectively analyzed. The cumulative incidence of SMN was estimated using competing risk methods by considering death as a competing risk.
Results
A total of 1,435 patients (413 with brain tumors and 1,022 with extracranial solid tumors) were enrolled. Seventy-one patients developed 74 SMNs, with a 10-year and 20-year cumulative incidence of 2.680±0.002% and 10.193±0.024%, respectively. The types of SMN included carcinoma in 28 (37.8%), sarcoma in 24 (32.4%), and hematologic malignancy in 15 (20.3%) cases. Osteosarcoma and thyroid carcinoma were the most frequently diagnosed tumors. Multivariate analysis showed that radiotherapy (RT) > 2, 340 cGy, and tandem HDCT were significant risk factors for SMN development. The SMN types varied according to the primary tumor type; carcinoma was the most frequent SMN in brain tumors and neuroblastoma, whereas hematologic malignancy and sarcomas developed more frequently in patients with sarcoma and retinoblastoma, respectively.
Conclusion
The cumulative incidence of SMN in pediatric patients with solid tumors was considerably high, especially in patients who underwent tandem HDCT or in those who received RT > 2,340 cGy. Therefore, the treatment intensity should be optimized based on individual risk assessment and the long-term follow-up of pediatric cancer survivors.

Citations

Citations to this article as recorded by  
  • Rising Prevalence of Low-Frequency PPM1D Gene Mutations after Second HDCT in Multiple Myeloma
    Katja Seipel, Nuria Z. Veglio, Henning Nilius, Barbara Jeker, Ulrike Bacher, Thomas Pabst
    Current Issues in Molecular Biology.2024; 46(8): 8197.     CrossRef
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  • 139 Download
  • 2 Web of Science
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Effectiveness and Safety of Dabrafenib in the Treatment of 20 Chinese Children with BRAFV600E-Mutated Langerhans Cell Histiocytosis
Ying Yang, Dong Wang, Lei Cui, Hong-Hao Ma, Li Zhang, Hong-Yun Lian, Qing Zhang, Xiao-Xi Zhao, Li-Ping Zhang, Yun-Ze Zhao, Na Li, Tian-You Wang, Zhi-Gang Li, Rui Zhang
Cancer Res Treat. 2021;53(1):261-269.   Published online September 15, 2020
DOI: https://doi.org/10.4143/crt.2020.769
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
We sought to investigate the effectiveness and safety of dabrafenib in children with BRAFV600E-mutated Langerhans cell histiocytosis (LCH).
Materials and Methods
A retrospective analysis was performed on 20 children with BRAFV600E-mutated LCH who were treated with dabrafenib.
Results
The median age at which the patients started taking dabrafenib was 2.3 years old (range, 0.6 to 6.5 years). The ratio of boys to girls was 2.3:1. The median follow-up time was 30.8 months (range, 18.9 to 43.6 months). There were 14 patients (70%) in the risk organ (RO)+ group and six patients (30%) in the RO group. All patients were initially treated with traditional chemotherapy and then shifted to targeted therapy due to poor control of LCH or intolerance to chemotherapy. The overall objective response rate and the overall disease control rate were 65% and 75%, respectively. During treatment, circulating levels of cell-free BRAFV600E (cfBRAFV600E) became negative in 60% of the patients within a median period of 3.0 months (range, 1.0 to 9.0 months). Grade 2 or 3 adverse effects occurred in five patients.
Conclusion
Some children with BRAFV600E-mutated LCH may benefit from monotherapy with dabrafenib, especially high-risk patients with concomitant hemophagocytic lymphohistiocytosis and intolerance to chemotherapy. The safety of dabrafenib is notable. A prospective study with a larger sample size is required to determine the optimal dosage and treatment duration.

Citations

Citations to this article as recorded by  
  • Genetic Landscape and Its Prognostic Impact in Children With Langerhans Cell Histiocytosis
    Chan-Juan Wang, Lei Cui, Shuang-Shuang Li, Hong-Hao Ma, Dong Wang, Hong-Yun Lian, Yun-Ze Zhao, Li-Ping Zhang, Wei-Jing Li, Qing Zhang, Xiao-Xi Zhao, Ying Yang, Xiao-Tong Huang, Wei Liu, Yi-Zhuo Wang, Wan-Shui Wu, Tian-You Wang, Rui Zhang, Zhi-Gang Li
    Archives of Pathology & Laboratory Medicine.2025; 149(2): 175.     CrossRef
  • Targeted therapy and immunotherapy for orbital and periorbital tumors: a major review
    Emmanuel Lee Boniao, Richard C. Allen, Gangadhara Sundar
    Orbit.2024; 43(5): 656.     CrossRef
  • Treatment of children with refractory/relapse high risk langerhans cell histiocytosis with the combination of cytarabine, vindesine and prednisone
    Wenqian Wang, Jian Ge, Honghao Ma, Hongyun Lian, Lei Cui, Yunze Zhao, Zhigang Li, Tianyou Wang, Rui Zhang
    BMC Pediatrics.2024;[Epub]     CrossRef
  • Vemurafenib combined with chemotherapy achieved sustained remission in pediatric LCH: a multi-center observational study
    Jiaying Lei, Wenxia Wang, Danna Lin, Chengguang Zhu, Wenguang Jia, Wenjun Weng, Xiaoshan Liu, Yuhan Ma, Zhixuan Wang, Lihua Yang, Xiangling He, Yunyan He, Yang LI
    Journal of Cancer Research and Clinical Oncology.2024;[Epub]     CrossRef
  • Clinical features and treatment outcomes of liver involvement in paediatric Langerhans cell histiocytosis
    Xinshun Ge, Wenxin Ou, Ang Wei, Hongyun Lian, Honghao Ma, Lei Cui, Dong Wang, Liping Zhang, Xiaoman Wang, Lejian He, Rui Zhang, Tianyou Wang
    BMC Pediatrics.2024;[Epub]     CrossRef
  • Refractory juvenile xanthogranuloma of the mastoid bone responsive to trametinib
    Isaac Hauk, Ignacio Gonzalez‐Gomes, Deepak Chellapandian, Jonathan Metts, Peter H. Shaw
    Pediatric Blood & Cancer.2024;[Epub]     CrossRef
  • Advancements in the understanding and management of histiocytic neoplasms
    Kyung-Nam Koh, Su Hyun Yoon, Sung Han Kang, Hyery Kim, Ho Joon Im
    Blood Research.2024;[Epub]     CrossRef
  • Real-world experience with targeted therapy in patients with histiocytic neoplasms in the Netherlands and in Belgium
    Paul G. Kemps, F. J. Sherida H. Woei-A-Jin, Patrick Schöffski, Thomas Tousseyn, Isabelle Vanden Bempt, Friederike A. G. Meyer-Wentrup, Natasja Dors, Natasha K. A. van Eijkelenburg, Marijn A. Scheijde-Vermeulen, Ingrid M. Jazet, Maarten Limper, Margot Jak,
    Blood Neoplasia.2024; 1(3): 100023.     CrossRef
  • The clinical impact of serum soluble CD25 levels in children with Langerhans cell histiocytosis
    Zi-Jing Zhao, Hong-Yun Lian, Wei-Jing Li, Qing Zhang, Hong-Hao Ma, Dong Wang, Yun-Ze Zhao, Ting Zhu, Hua-Lin Li, Xiao-Tong Huang, Tian-You Wang, Rui Zhang, Lei Cui, Zhi-Gang Li
    Jornal de Pediatria.2024;[Epub]     CrossRef
  • Liver transplantation in a child with sclerosing cholangitis due to Langerhans cell histiocytosis: a case report
    Xue-Lian Wang, Chun-Xiao Fang, Min-Xia Chen, Hua-Mei Yang, Lan-Hui She, Yu Gong, Yi Xu, Wei-Qiang Xiao, Jin-Sheng Tian, Bin Ai, Li Huang, Xu-Fang Li
    Frontiers in Pediatrics.2024;[Epub]     CrossRef
  • BRAF V600E gene mutation is present in primary intraosseous Rosai-Dorfman disease
    Lokman Cevik, Swati Satturwar, Dan Jones, Joel Mayerson, Steve Oghumu, O. Hans Iwenofu
    Human Pathology.2024; 154: 105702.     CrossRef
  • Langerhans cell histiocytosis as a clonal disease of mononuclear phagocyte system
    Evgeniy F. Khynku, Maria K. Monaenkova, Olga B. Tamrazova, Alexey V. Taganov, Мarina А. Gureeva, Gayane E. Bagramova, Anton V. Molochkov
    Almanac of Clinical Medicine.2023; 50(7): 428.     CrossRef
  • Lineage switching of the cellular distribution of BRAF V600E in multisystem Langerhans cell histiocytosis
    Paul Milne, Simon Bomken, Olga Slater, Ashish Kumar, Adam Nelson, Somak Roy, Jessica Velazquez, Kshitij Mankad, James Nicholson, Dan Yeomanson, Richard Grundy, Ahmed Kamal, Anthony Penn, Jane Pears, Gerard Millen, Bruce Morland, James Hayden, Jason Lam, M
    Blood Advances.2023; 7(10): 2171.     CrossRef
  • Treatment of Langerhans Cell Histiocytosis and Histiocytic Disorders: A Focus on MAPK Pathway Inhibitors
    Ashley V. Geerlinks, Oussama Abla
    Pediatric Drugs.2023; 25(4): 399.     CrossRef
  • Dabrafenib, alone or in combination with trametinib, in BRAF V600–mutated pediatric Langerhans cell histiocytosis
    James A. Whitlock, Birgit Geoerger, Ira J. Dunkel, Michael Roughton, Jeea Choi, Lisa Osterloh, Mark Russo, Darren Hargrave
    Blood Advances.2023; 7(15): 3806.     CrossRef
  • Therapiestrategien bei Kindern und Jugendlichen mit Langerhanszell Histiozytosen
    Anke Elisabeth Barnbrock, Caroline Hutter, Konrad Bochennek, Milen Minkov, Thomas Lehrnbecher
    Klinische Pädiatrie.2023; 235(06): 342.     CrossRef
  • Mutant PIK3CA is a targetable driver alteration in histiocytic neoplasms
    Benjamin H. Durham, Oshrat Hershkovitz-Rokah, Omar Abdel-Wahab, Mariko Yabe, Young Rock Chung, Gilad Itchaki, Maayan Ben-Sasson, Vered A. Asher-Guz, David Groshar, Seyram A. Doe-Tetteh, Tina Alano, David B. Solit, Ofer Shpilberg, Eli L. Diamond, Roei D. M
    Blood Advances.2023; 7(23): 7319.     CrossRef
  • Validation of Liquid Chromatography Coupled with Tandem Mass Spectrometry for the Determination of 12 Tyrosine Kinase Inhibitors (TKIs) and Their Application to Therapeutic Drug Monitoring in Adult and Pediatric Populations
    Marie Bellouard, Jean Donadieu, Pauline Thiebot, Etienne Giroux Leprieur, Philippe Saiag, Isabelle Etting, Pamela Dugues, Emuri Abe, Jean-Claude Alvarez, Islam-Amine Larabi
    Pharmaceutics.2023; 16(1): 5.     CrossRef
  • Langerhans cell histiocytosis: promises and caveats of targeted therapies in high-risk and CNS disease
    Oussama Abla
    Hematology.2023; 2023(1): 386.     CrossRef
  • Characteristics and Treatment Outcomes of Pediatric Langerhans Cell Histiocytosis with Thymic Involvement
    Ja-Feng Yao, Dong Wang, Hong-Hao Ma, Hong-Yun Lian, Li Zhang, Tian-You Wang, Zhi-Gang Li, Jin Jiang, Lei Cui, Rui Zhang
    The Journal of Pediatrics.2022; 244: 194.     CrossRef
  • Clinical features and treatment outcomes of pediatric Langerhans cell histiocytosis with macrophage activation syndrome-hemophagocytic lymphohistiocytosis
    Dong Wang, Xi-Hua Chen, Ang Wei, Chun-Ju Zhou, Xue Zhang, Hong-Hao Ma, Hong-Yun Lian, Li Zhang, Qing Zhang, Xiao-Tong Huang, Chan-Juan Wang, Ying Yang, Wei Liu, Tian-You Wang, Zhi-Gang Li, Lei Cui, Rui Zhang
    Orphanet Journal of Rare Diseases.2022;[Epub]     CrossRef
  • Current perspectives on the role of liver transplantation for Langerhans cell histiocytosis: A narrative review
    Jagadeesh Menon, Ashwin Rammohan, Mukul Vij, Naresh Shanmugam, Mohamed Rela
    World Journal of Gastroenterology.2022; 28(30): 4044.     CrossRef
  • Research Progress of BRAF V600E Gene Mutation in Papillary Thyroid Carcinoma
    延泽 刘
    Advances in Clinical Medicine.2022; 12(09): 8499.     CrossRef
  • Recent advances in the understanding of the molecular pathogenesis and targeted therapy options in Langerhans cell histiocytosis
    Jin Kyung Suh, Sunghan Kang, Hyery Kim, Ho Joon Im, Kyung-Nam Koh
    BLOOD RESEARCH.2021; 56(S1): S65.     CrossRef
  • Improvement in Pituitary Imaging After Targeted Therapy in Three Children with BRAF-Mutated Langerhans Cell Histiocytosis with Pituitary Involvement


    Ying Yang, Dong Wang, Na Li, Honghao Ma, Hongyun Lian, Lei Cui, Qing Zhang, Xiaoxi Zhao, Liping Zhang, Yunze Zhao, Chanjuan Wang, Li Zhang, Tianyou Wang, Zhigang Li, Rui Zhang
    OncoTargets and Therapy.2020; Volume 13: 12357.     CrossRef
  • 34,905 View
  • 236 Download
  • 19 Web of Science
  • 25 Crossref
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Long Non-coding RNA CCAT1 Sponges miR-454 to Promote Chemoresistance of Ovarian Cancer Cells to Cisplatin by Regulation of Surviving
De-Ying Wang, Na Li, Yu-Lan Cui
Cancer Res Treat. 2020;52(3):798-814.   Published online March 3, 2020
DOI: https://doi.org/10.4143/crt.2019.498
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Colon cancer-associated transcript 1 (CCAT1) was identified as an oncogenic long non-coding RNA (lncRNA) in a variety of cancers. However, there was a lack of understanding of the mechanism by which CCAT1 conferred cisplatin (also known as DDP) resistance in ovarian cancer cells.
Materials and Methods
Cell viability of A2780, SKOV3, A2780/DDP, and SKOV3/DDP cells upon cisplatin treatment was monitored by MTT assay. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) detected the expression levels of CCAT1 and miR-454. The effect of sh-CCAT1 on cisplatin response was investigated in xenografts study. Bioinformatic analysis, luciferase reporter assay and qRT-PCR were conducted to validate the direct interaction among CCAT1, miR-454, and survivin. Apoptosis was determined by flow cytometry after dual staining of Annexin-V-FITC/propidium iodide, and the expression of apoptosis-related proteins Bcl-2, Bax and survivin were detected by qRT-PCR and Western blotting. Xenograft study was conducted to monitor in vivo tumor formation.
Results
CCAT1 was highly expressed in cisplatin-resistant ovarian cancer cell line A2780/DDP and SKOV3/DDP. Knockdown of CCAT1 restored sensitivity to cisplatin in vitro and in vivo. Our data revealed that silencing of CCAT1 promoted cisplatin-induced apoptosis via modulating the expression of pro- or anti-apoptotic proteins Bax, Bcl-2, and survivin. CCAT1 directly interacted with miR-454, and miR-454 overexpression potentiated cisplatin-induced apoptosis. Survivin was identified as a functional target of miR-454, restoration of survivin attenuated the effect of miR-454 on cisplatin response. In addition, miR-454 inhibitor or overexpression of survivin was found to abolish sh-CCAT1–induced apoptosis upon cisplatin treatment.
Conclusion
CCAT1/miR-454/survivin axis conferred cisplatin resistance in ovarian cancer cells.

Citations

Citations to this article as recorded by  
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    Drug Development Research.2025;[Epub]     CrossRef
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    Cancer Medicine.2024;[Epub]     CrossRef
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    Weijia Li, Xibo Zhao, Rujian Zhang, Jiabin Xie, Guangmei Zhang, Jinghua Pan
    Mediators of Inflammation.2023; 2023: 1.     CrossRef
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    Kaili Cen, Ming Chen, Mengye He, Zhenhao Li, Yinjing Song, Pu Liu, Qi Jiang, Suzhen Xu, Yunlu Jia, Peng Shen
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    Zhong Jiang, Xianjun Zhou, Lulu Han, Fujiang Li, Xiwei Hao, Qian Dong, Xin Chen
    Critical Reviews in Eukaryotic Gene Expression.2022; 32(8): 1.     CrossRef
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    Linjiao Chen, Jie Wang, Qian Liu
    Frontiers in Cell and Developmental Biology.2022;[Epub]     CrossRef
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    Yuwen Han, Jun You, Yun Han, Yinglei Liu, Menghui Huang, Xiaoyan Lu, Jingjing Chen, Yanli Zheng
    OncoTargets and Therapy.2021; Volume 14: 2711.     CrossRef
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  • Back to the Future: Rethinking the Great Potential of lncRNAS for Optimizing Chemotherapeutic Response in Ovarian Cancer
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    Eleonora A. Braga, Marina V. Fridman, Alexey A. Moscovtsev, Elena A. Filippova, Alexey A. Dmitriev, Nikolay E. Kushlinskii
    International Journal of Molecular Sciences.2020; 21(22): 8855.     CrossRef
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  • 237 Download
  • 38 Web of Science
  • 37 Crossref
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