Cancer Research and Treatment

Original Articles

CNS cancer

Hypo-trimethylation of Histone H3 Lysine 4 and Hyper-tri/dimethylation of Histone H3 Lysine 27 as Epigenetic Markers of Poor Prognosis in Patients with Primary Central Nervous System Lymphoma: Hoon Gi Kim, Minseok S. Kim, Young Sam Lee, Eun Hee Lee, Dae Cheol Kim, Sung-Hun Lee, Young Zoon Kim; Cancer Res Treat. 2022;54(3):690-708. Published online November 17, 2021; DOI: https://doi.org/10.4143/crt.2021.1121

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Purpose
This study aimed to investigate the methylation status of major histone modification sites in primary central nervous system lymphoma (PCNSL) samples and examine their prognostic roles in patients with PCNSL.
Materials and Method
Between 2007 and 2020, 87 patients were histopathologically diagnosed with PCNSL. We performed immunohistochemical staining of the formalin-fixed paraffin-embedded samples of PCNSL for major histone modification sites, such as H3K4, H3K9, H3K27, H3K14, and H3K36. After detection of meaningful methylation sites, we examined histone modification enzymes that induce methylation or demethylation at each site using immunohistochemical staining. The meaningful immunoreactivity was validated by western blotting using fresh tissue of PCNSL.
Results
More frequent recurrences were found in hypomethylation of H3K4me3 (p=0.004) and hypermethylation of H3K27me2 (p<0.001) and H3K27me3 (p=0.002). These factors were also statistically related to short PFS and overall survival in the univariate and multivariate analyses. Next, histone modification enzymes inducing the demethylation of H3K4 (lysine-specific demethylase-1/2 and Jumonji AT-rich interactive domain [JARID] 1A-D]) and methylation of H3K27 (enhancer of zeste homolog [EZH]-1/2) were immu- nohistochemically stained. Among them, the immunoreactivity of JARID1A inversely associated with the methylation status of H3K4me3 (R²=-1.431), and immunoreactivity of EZH2 was directly associated with the methylation status of H3K27me2 (R²=0.667) and H3K27me3 (R²=0.604). These results were validated by western blotting in fresh PCNSL samples.
Conclusion
Our study suggests that hypomethylation of H3K4me3 and hypermethylation of H3K27me2 and H3K27me3 could be associated with poor outcomes in patients with PCNSL and that these relationships are modified by JARID1A and EZH2.

Citations

Citations to this article as recorded by

Updates of primary central nervous system lymphoma
Jiaying Wu, Delian Zhou, Xiaojian Zhu, Yicheng Zhang, Yi Xiao
Therapeutic Advances in Hematology.2024;[Epub] CrossRef
3-deazaneplanocin A, a histone methyltransferase inhibitor, improved the chemoresistance induced under hypoxia in melanoma cells
Mika Hosokawa, Sekai Tetsumoto, Mirano Yasui, Yusuke Kono, Ken-ichi Ogawara
Biochemical and Biophysical Research Communications.2023; 677: 26. CrossRef
Extranodal lymphoma: pathogenesis, diagnosis and treatment
Hua Yang, Yang Xun, Chao Ke, Kensuke Tateishi, Hua You
Molecular Biomedicine.2023;[Epub] CrossRef
Diagnostic and Therapeutic Perspectives Associated to Cobalamin-Dependent Metabolism and Transcobalamins’ Synthesis in Solid Cancers
Valentin Lacombe, Guy Lenaers, Geoffrey Urbanski
Nutrients.2022; 14(10): 2058. CrossRef
Primary central nervous system lymphoma: advances in its pathogenesis, molecular markers and targeted therapies
Isaias Hernández-Verdin, Andrea Morales-Martínez, Khê Hoang-Xuan, Agustí Alentorn
Current Opinion in Neurology.2022; 35(6): 779. CrossRef

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Clinical Analysis for Brain Tumor-Related Epilepsy during Chemotherapy for Systemic Cancer with Single Brain Metastasis: Young Zoon Kim, Eun Hee Lee, Kyoung Soo Lee; Cancer Res Treat. 2011;43(3):160-169. Published online September 30, 2011; DOI: https://doi.org/10.4143/crt.2011.43.3.160

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PURPOSE
The purpose of this prospective observational study was to determine the incidence, patterns, and predisposing factors for brain tumor-related epilepsy (BTRE) during chemotherapy for systemic cancer with single brain metastasis (BM).
MATERIALS AND METHODS
Between February 2006 and June 2010, 103 patients who underwent chemotherapy for systemic cancer with single BM were enrolled. We compared the clinical factors of patients and BM between patients with and without BTRE. We determined the number of patients with BTRE attacks, and seizure-free survival according to the following comparative groups: presence vs. absence of a history of BTRE; high-risk vs. low-risk groups; and presence vs. absence of disease-progression of BM.
RESULTS
Ninety-three of 103 patients (90.3%) remained seizure-free during chemotherapy. The seizure-free rates were 88.9% and 91.0% among patients with or without a history of BTRE, respectively (p=0.694), 87.8% and 92.6% among high- and low-risk patients (p=0.427), respectively, and 62.5% and 98.7% among patients with or without disease-progression of BM (p=0.001), retrospectively. Based on multivariate analysis, the significance of abnormal findings on electroencephalogram (EEG) (p=0.017), and the absence of disease-progression of BM (p=0.001) had an association with seizure-free survival.
CONCLUSION
The significance of abnormal findings on EEG, and disease-progression of BM play important roles in the development of BTRE during chemotherapy for systemic cancer with BM.

Citations

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Seizure outcomes in patients with brain metastases and epilepsy: a systematic review on the efficacy of antitumor treatment and antiseizure medication
Josien C C Scheepens, Pim B van der Meer, Linda Dirven, Maaike J Vos, Martin J B Taphoorn, Johan A F Koekkoek
Neuro-Oncology Practice.2025; 12(3): 376. CrossRef
Analysis of prognostic factors and the role of epilepsy in neurosurgical patients with brain metastases
Matteo Maria Ottaviani, Maria Rossella Fasinella, Alessandro Di Rienzo, Maurizio Gladi, Lucia Giovanna Maria di Somma, Maurizio Iacoangeli, Mauro Dobran
Surgical Neurology International.2024; 15: 79. CrossRef
Tumor-associated epilepsy in patients with brain metastases: necrosis-to-tumor ratio forecasts postoperative seizure freedom
Majd Bahna, Muriel Heimann, Christian Bode, Valeri Borger, Lars Eichhorn, Erdem Güresir, Motaz Hamed, Ulrich Herrlinger, Yon-Dschun Ko, Felix Lehmann, Anna-Laura Potthoff, Alexander Radbruch, Christina Schaub, Rainer Surges, Johannes Weller, Hartmut Vatte
Neurosurgical Review.2022; 45(1): 545. CrossRef
Brain tumor–related epilepsy and risk factors for metastatic brain tumors: analysis of 601 consecutive cases providing real-world data
Kenichiro Asano, Seiko Hasegawa, Masashi Matsuzaka, Hiroki Ohkuma
Journal of Neurosurgery.2022; 136(1): 76. CrossRef

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Intrapleural Chemotherapy with Cisplatin and Cytarabine in the Management of Malignant Pleural Effusion: Kee Won Kim, Suk Young Park, Myung Sook Kim, Seok Chan Kim, Eun Hee Lee, So Young Shin, Jong Ho Lee, Jong Bum Kweon, Kuhn Park; Cancer Res Treat. 2004;36(1):68-71. Published online February 29, 2004; DOI: https://doi.org/10.4143/crt.2004.36.1.68

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Purpose

The purpose of this study was to evaluate the efficacy of intrapleural chemotherapy (IPC) with cisplatin and cytarabine in the management of malignant pleural effusion (MPE) from non-small-cell lung cancer (NSCLC).

Materials and Methods

A prospective analysis was carried out on 40 patients with pathologically proven MPE from NSCLC who had received IPC. A single dose of cisplatin 100 mg/m² plus cytarabine 1200 mg/m² in 250 ml normal saline was instilled into the pleural space via a chest tube and drained 4 hours later. Patients were evaluated for toxicities and responses at 1, 2, & 3 weeks and then at monthly intervals if possible. Systemic chemotherapy was administered, if the patient agreed to receive it, after achieving complete control (CC) of MPE.

Results

The median duration of chest tube insertion for drainage was 7 (3~32) days. Among the assessable 37 patients, CC and partial control (PC) were 32 (86.5%) and 4 (10.8%) patients, respectively (overall response rate 97.3%). The median duration of response was 12 months (2~23) and there were only two relapses of IPC after achieving CC. Among the 35 patients who were assessable until they died, 28 patients (80.0%) maintained CC until the last follow-up. There was only one toxic death and the toxicities of IPC, versus the results obtained, were deemed acceptable.

Conclusion

The procedures were tolerable to the patients and chemotherapy-induced complications were at an acceptable level. The outcome of this trial indicates that IPC has a superior and long lasting treatment response in the management of patients with MPE from NSCLC.

Citations

Citations to this article as recorded by

Efficacy of hyperthermic intrathoracic chemotherapy for initially diagnosed lung cancer with symptomatic malignant pleural effusion
Zihui Li, Jie Deng, Fei Yan, Li Liu, Yanling Ma, Jianhai Sun
Scientific Reports.2023;[Epub] CrossRef
Survival Benefits for Pulmonary Adenocarcinoma With Malignant Pleural Effusion After Thoracoscopic Surgical Treatment: A Real-World Study
Xin Li, Mingbiao Li, Jinshuang Lv, Jinghao Liu, Ming Dong, Chunqiu Xia, Honglin Zhao, Song Xu, Sen Wei, Zuoqing Song, Gang Chen, Hongyu Liu, Jun Chen
Frontiers in Oncology.2022;[Epub] CrossRef
Modified indwelling pleural catheter versus silver nitrate pleurodesis for the management of malignant pleural effusion
Mohammed F. Abdelghany, Khaled Essmat, Atef Farouk El-Karn, Sahar Farghly Youssif
The Egyptian Journal of Chest Diseases and Tuberculosis.2022; 71(2): 248. CrossRef
Chinese herbal injections versus intrapleural cisplatin for lung cancer patients with malignant pleural effusion: A Bayesian network meta-analysis of randomized controlled trials
Yi-Fang Xu, Yun-Ru Chen, Fan-Long Bu, Yu-Bei Huang, Yu-Xin Sun, Cheng-Yin Li, Jodi Sellick, Jian-Ping Liu, Dan-Mei Qin, Zhao-Lan Liu
Frontiers in Oncology.2022;[Epub] CrossRef
Making cold malignant pleural effusions hot: driving novel immunotherapies
Pranav Murthy, Chigozirim N. Ekeke, Kira L. Russell, Samuel C. Butler, Yue Wang, James D. Luketich, Adam C. Soloff, Rajeev Dhupar, Michael T. Lotze
OncoImmunology.2019;[Epub] CrossRef
Efficacy and safety of intrapleural cisplatin versus silver nitrate in treatment of malignant pleural effusion
Mohammad K. El Badrawy, Raed El-Metwally Ali, Asem A. Hewidy, Mohamed A. El-Layeh, Fatma M. F. Akl, Abdelhadi Shebl
Egyptian Journal of Bronchology.2018; 12(1): 98. CrossRef
Biodegradable drug-eluting pellets provide steady and sustainable cisplatin release in the intrapleural cavity: In vivo and in vitro studies
Yin-Kai Chao, Yu-Wen Wen, Kuo-Sheng Liu, Yi-Chuan Wang, Chih-Wei Wang, Shih-Jung Liu
International Journal of Pharmaceutics.2015; 484(1-2): 38. CrossRef

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Expression of P53, Bcl-2, Bax, and P-glycoprotein in Relation to Chemotherapeutic Response in Patients with Advanced Non-Small-Cell Lung Cance: Suk Young Park, Eun Hee Lee, Kee Won Kim, Chul Seung Kay, Seok Chan Kim, Ji Won Suhr, Kyung Shick Lee; J Korean Cancer Assoc. 2001;33(2):158-162.

Abstract PDF: PURPOSE
To evaluate the relationship between the expressions of p53, bcl-2, bax, and p-glycoprotein and the chemotherapeutic response seen in patients with advanced NSCLC.
MATERIALS AND METHODS
Forty-four patients pathologically proven as NSCLC were reviewed. They had undergone at least two cycles of the same chemotherapeutic agents (cisplatin 60 mg/m2 day 1+ vinorelbine 25 mg/m2 day 1, 8, 21-day cycle) and the clinical response was evaluated by WHO criteria. The expressions of p53, bcl-2, bax, and p-glycoprotein were determined by immunohistochemistry.
RESULTS
Patients recorded as CR (2/44) and PR (20/44) were classified as the responder group (22/44) and stable (17/44) and progression (5/44) as the non-responder group (22/44). Positive expression of p53, bcl-2, bax, and p-glycoprotein were 84.1%, 65.9%, 88.6%, and 61.4% respectively. The expression score of p53 was significantly higher in the non-responder group than that seen in the responder group (8.59+/-1.89 vs 5.32+/-2.15, p<0.05). However, the expression scores of bcl-2, bax, and p-glycoprotein were not significantly correlated with the clinical response.
CONCLUSION
This study suggests that p53 gene mutation plays an important role in the clinical response to chemotherapy including cisplatin and vinorelbine. In future investigations, the correlation with the survival time will be studied.

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Combination Chemotherapy with Cisplatin and Vinorelbine in Patients with Non-Small-Cell Lung Cancer: Kee Won Kim, Suk Young Park, Ji Won Suhr, Seung Joon Kim, Dong Hoen Yang, Eun Hee Lee, Kyung Shick Lee; J Korean Cancer Assoc. 2000;32(5):911-917.

Abstract PDF: PURPOSE
To determine the therapeutic effect and toxicities of cisplatin and vinorelbine combination chemotherapy in patients with inoperable non-small-cell lung cancer.
MATERIALS AND METHODS
Between Jan 1998 and Dec 1999, 28 patients with inoperable non- small-cell lung cancer were treated with cisplatin and vinorelbine combination chemotherapy as induction treatment. A combination of vinorelbine 25 mg/m2 day 1,8 and cisplatin 60 mg/m2 day 1 were given and repeated every 3 weeks. Then we assessed response and toxicity according to WHO grades.
RESULTS
According to response criteria, there were 1 complete response, 12 partial response (42.9%), 12 stable disease (42.9%), and 3 progression (10.7%). The median survival was 12 months. According to toxicity grades, 24 grade 3 myelosuppression (24.7%), 12 grade 4 myelo suppression (10.7%), 6 grade 3 and 4 constipation (6.1%), and mild 7 (7.2%) thrombophlebitis were experienced in evaluable 97 cycles. There was no other clinically severe toxicity.
CONCLUSION
These results suggest that combination chemotherapy with cisplatin and vinorelbine in patients with inoperable non-small-cell lung cancer was effective and safe.

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