Cancer Research and Treatment

Original Articles

Higher Microbial Abundance and Diversity in Bronchus-Associated Lymphoid Tissue Lymphomas Than in Non-cancerous Lung Tissues: Jung Heon Kim, Jae Sik Kim, Noorie Choi, Jiwon Koh, Yoon Kyung Jeon, Ji Hyun Chang, Eung Soo Hwang, Il Han Kim; Received July 24, 2024 Accepted September 29, 2024 Published online September 30, 2024; DOI: https://doi.org/10.4143/crt.2024.689 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
It is well known that the majority of the extranodal marginal zone lymphomas of mucosa-associated lymphoid tissues (MALT lymphomas) are associated with microbiota, e.g., gastric MALT lymphoma with Helicobacter pylori. In general, they are very sensitive to low-dose radiotherapy and chemotherapeutic agents. The microbiota profile is not clearly elucidated in bronchus-associated lymphoid tissue (BALT) lymphoma, a rare type of MALT lymphoma in the lung. Thus, this study aimed to clarify the intratumor microbiome in BALT lymphoma using the third-generation next-generation sequencing (NGS) method.
Materials and Methods
DNAs were extracted from 12 formalin-fixed paraffin-embedded (FFPE) tumor tissues obtained from BALT lymphoma patients diagnosed between 1990 and 2016. 16S rRNA gene was amplified by polymerase chain reaction. Amplicons were sequenced using a Nanopore platform. Next-generation sequencing analysis was performed to assess microbial profiles. For comparison, FFPE specimens from nine non-cancerous lung tissues were also analyzed.
Results
Specific bacterial families including Burkholderiaceae, Bacillaceae, and Microbacteriaceae were associated with BALT lymphoma by a linear discriminant analysis effect size approach. Although the number of specimens was limited, BALT lymphomas exhibited significantly higher microbial abundance and diversity with distinct microbial composition patterns and correlation networks than non-cancerous lung tissues.
Conclusion
This study provides the first insight into intratumor microbiome in BALT lymphoma using the third-generation NGS method. A distinct microbial composition suggests the presence of a unique tumor microenvironment of BALT lymphoma.

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Harnessing Institutionally Developed Clinical Targeted Sequencing to Improve Patient Survival in Breast Cancer: A Seven-Year Experience: Jiwon Koh, Jinyong Kim, Go-Un Woo, Hanbaek Yi, So Yean Kwon, Jeongmin Seo, Jeong Mo Bae, Jung Ho Kim, Jae Kyung Won, Han Suk Ryu, Yoon Kyung Jeon, Dae-Won Lee, Miso Kim, Tae-Yong Kim, Kyung-Hun Lee, Tae-You Kim, Jee-Soo Lee, Moon-Woo Seong, Sheehyun Kim, Sungyoung Lee, Hongseok Yun, Myung Geun Song, Jaeyong Choi, Jong-Il Kim, Seock-Ah Im; Received March 23, 2024 Accepted August 18, 2024 Published online August 21, 2024; DOI: https://doi.org/10.4143/crt.2024.296 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Considering the high disease burden and unique features of Asian patients with breast cancer (BC), it is essential to have a comprehensive view of genetic characteristics in this population. An institutional targeted sequencing platform was developed through the Korea Research-Driven Hospitals project and was incorporated into clinical practice. This study explores the use of targeted next-generation sequencing (NGS) and its outcomes in patients with advanced/metastatic BC in the real world.
Materials and Methods
We reviewed the results of NGS tests administered to BC patients using a customized sequencing platform—FiRST Cancer Panel (FCP)—over 7 years. We systematically described clinical translation of FCP for precise diagnostics, personalized therapeutic strategies, and unraveling disease pathogenesis.
Results
NGS tests were conducted on 548 samples from 522 patients with BC. Ninety-seven point six percentage of tested samples harbored at least one pathogenic alteration. The common alterations included mutations in TP53 (56.2%), PIK3CA (31.2%), GATA3 (13.8%), BRCA2 (10.2%), and amplifications of CCND1 (10.8%), FGF19 (10.0%), and ERBB2 (9.5%). NGS analysis of ERBB2 amplification correlated well with human epidermal growth factor receptor 2 immunohistochemistry and in situ hybridization. RNA panel analyses found potentially actionable and prognostic fusion genes. FCP effectively screened for potentially germline pathogenic/likely pathogenic mutation. Ten point three percent of BC patients received matched therapy guided by NGS, resulting in a significant overall survival advantage (p=0.022), especially for metastatic BCs.
Conclusion
Clinical NGS provided multifaceted benefits, deepening our understanding of the disease, improving diagnostic precision, and paving the way for targeted therapies. The concrete advantages of FCP highlight the importance of multi-gene testing for BC, especially for metastatic conditions.

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Lung and Thoracic cancer

Targeting CD73 to Overcomes Resistance to First-Generation EGFR Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer: Miso Kim, Soyeon Kim, Jeemin Yim, Bhumsuk Keam, Tae Min Kim, Yoon Kyung Jeon, Dong-Wan Kim, Dae Seog Heo; Cancer Res Treat. 2023;55(4):1134-1143. Published online May 23, 2023; DOI: https://doi.org/10.4143/crt.2023.311

Abstract PDF Supplementary Material PubReader ePub

Purpose
In patients with epidermal growth factor receptor (EGFR)-mutant non–small cell lung cancer (NSCLC), EGFR tyrosine kinase inhibitors (TKIs) improve response rate and survival. However, most patients eventually develop resistance. This study aimed to identify the role of CD73 in EGFR-mutant NSCLC and explore whether CD73 inhibition may serve as a therapeutic strategy in NSCLC patients with acquired resistance to EGFR-TKIs.
Materials and Methods
We evaluated the prognostic role of CD73 expression in EGFR-mutant NSCLC using tumor samples from a single institution. We silenced CD73 in EGFR-TKI–resistant cell lines using short hairpin RNA (shRNA) targeting CD73 and also transfected a vector alone as a negative control. Using these cell lines, cell proliferation and viability assays, immunoblot assays, cell cycle analysis, colony-forming assays, flow cytometry, and apoptosis analysis were performed.
Results
High expression of CD73 was associated with shorter survival in patients with metastatic EGFR-mutant NSCLC treated with first-generation EGFR-TKI. CD73 inhibition synergistically inhibited cell viability with first-generation EGFR-TKI treatment compared with the negative control. When CD73 inhibition and EGFR-TKI treatment were combined, G0/G1 cell cycle arrest was induced through the regulation of p21 and cyclin D1. In addition, the apoptosis rate was increased in CD73 shRNA-transfected cells treated with EGFR-TKI.
Conclusion
High expression of CD73 adversely affects the survival of patients with EGFR-mutant NSCLC. The study demonstrated that inhibiting CD73 in EGFR-TKI–resistant cell lines resulted in increased apoptosis and cell cycle arrest, which overcame the acquired resistance to first-generation EGFR-TKIs. Further research is needed to determine whether blocking CD73 plays a therapeutic role in EGFR-TKI–resistant patients with EGFR-mutant NSCLC.

Citations

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Simultaneous blockade of the CD73/EGFR axis inhibits tumor growth
Keivan Ardeshiri, Hadi Hassannia, Ghasem Ghalamfarsa, Hanieh Jafary, Farhad Jadidi
IUBMB Life.2025;[Epub] CrossRef
Comprehensive pan-cancer analysis of CD73: Explore its association with prognosis and tumor immune microenvironment
Chen Chen, Sasa Liu, Yanfen Ma
Heliyon.2024; 10(22): e40329. CrossRef

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Cancer-Specific Sequences in the Diagnosis and Treatment of NUT Carcinoma: Mi-Sook Lee, Sungbin An, Ji-Young Song, Minjung Sung, Kyungsoo Jung, Eun Sol Chang, Juyoung Choi, Doo-Yi Oh, Yoon Kyung Jeon, Hobin Yang, Chaithanya Lakshmi, Sehhoon Park, Joungho Han, Se-Hoon Lee, Yoon-La Choi; Cancer Res Treat. 2023;55(2):452-467. Published online October 14, 2022; DOI: https://doi.org/10.4143/crt.2022.910

Abstract PDF Supplementary Material PubReader ePub

Purpose
NUT carcinoma (NC) is a solid tumor caused by the rearrangement of NUTM1 that usually develops in midline structures, such as the thorax. No standard treatment has been established despite high lethality. Thus, we investigated whether targeting the junction region of NUTM1 fusion breakpoints could serve as a potential treatment option for NC.
Materials and Methods
We designed and evaluated a series of small interfering RNAs (siRNAs) targeting the junction region of BRD4-NUTM1 fusion (B4N), the most common form of NUTM1 fusion. Droplet digital polymerase chain reaction using the blood of patients was also tested to evaluate the treatment responses by the junction sequence of the B4N fusion transcripts.
Results
As expected, the majority of NC fusion types were B4N (12 of 18, 67%). B4N fusion-specific siRNA treatment on NC cells showed specific inhibitory effects on the B4N fusion transcript and fusion protein without affecting the endogenous expression of the parent genes, resulting in decreased relative cell growth and attenuation of tumor size. In addition, the fusion transcript levels in platelet-rich-plasma samples of the NC patients with systemic metastasis showed a negative correlation with therapeutic effect, suggesting its potential as a measure of treatment responsiveness.
Conclusion
This study suggests that tumor-specific sequences could be used to treat patients with fusion genes as part of precision medicine for a rare but deadly disease.

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Indirect targeting of MYC and direct targeting in combination with chemotherapies are more effective than direct mono-targeting in triple negative breast cancer
Negesse Mekonnen, Hobin Yang, Nirmal Rajasekaran, Kyoung Song, Yoon-La Choi, Young Kee Shin
Translational Oncology.2025; 51: 102204. CrossRef
Precision Targeting of BET Proteins - Navigating Disease Pathways, Inhibitor Insights, and Shaping Therapeutic Frontiers: A Comprehensive Review
Rakesh D. Amrutkar, Mehul V. Amesar, Lokesh B. Chavan, Nilesh S. Baviskar, Vaibhav G. Bhamare
Current Drug Targets.2025; 26(3): 147. CrossRef
NUT-midline carcinoma of the lung with rare BRD3-NUTM1 fusion
Prerana Jha, Vaishakhi Trivedi, Nandini Menon, Minit Shah, Irene A George, Rohit Mishra, Trupti Pai, Fuzail Ahmad, Venkataramanan Ramachandran, Vanita Noronha, Kumar Prabhash, Prashant Kumar
Cancer Research, Statistics, and Treatment.2024; 7(1): 110. CrossRef

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General

Interlaboratory Comparison Study (Ring Test) of Next-Generation Sequencing–Based NTRK Fusion Detection in South Korea: Seung Eun Lee, Mi-Sook Lee, Yoon Kyung Jeon, Hyo Sup Shim, Jun Kang, Jihun Kim, Yoon-La Choi; Cancer Res Treat. 2023;55(1):28-40. Published online February 10, 2022; DOI: https://doi.org/10.4143/crt.2021.1572

Abstract PDF Supplementary Material PubReader ePub

Purpose
Tropomyosin receptor kinase (TRK) inhibitors are approved for the treatment of neurotrophic receptor tyrosine kinase (NTRK) fusion-positive tumors. The detection of NTRK fusion using a validated method is required before therapeutic application. An interlaboratory comparison study of next-generation sequencing (NGS)–based NTRK gene fusion detection with validated clinical samples was conducted at six major hospitals in South Korea.
Materials and Methods
A total of 18 samples, including a positive standard reference and eight positive and nine negative clinical samples, were validated using the VENTANA pan-TRK (EPR17341) and TruSight Oncology 500 assays. These samples were then tested using four different NGS panels currently being used at the six participating institutions.
Results
NTRK fusions were not detected in any of the nine negative clinical samples, demonstrating 100% specificity in all six participating institutions. All assays showed 100% analytical sensitivity to identify the NTRK fusion status in formalin-fixed paraffin-embedded (FFPE) samples, although with variable clinical sensitivity. False-negative results were due to low tumor purity, poor RNA quality, and DNA-based sequencing panel. The RNA-based targeted NGS assay showed an overall high success rate of identifying NTRK fusion status in FFPE samples.
Conclusion
This study is the first to test the proficiency of NGS-based NTRK detection in South Korea with the largest participating institutions. RNA-based NGS assays to detect NTRK fusions can accurately characterize fusion transcripts if sufficient RNA of adequate quality is available. The comparative performance data will support the implementation of targeted NGS-based sequencing assays for NTRK fusion detection in routine diagnostics.

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Susana Hernandez, Esther Conde, Aida Molero, Ana Suarez-Gauthier, Rebeca Martinez, Marta Alonso, Carlos Plaza, Carmen Camacho, Debora Chantada, Laura Juaneda-Magdalena, Enrique Garcia-Toro, Patricia Saiz-Lopez, Federico Rojo, Mar Abad, Valentina Boni, Sof
Archives of Pathology & Laboratory Medicine.2024; 148(3): 318. CrossRef
Korean Thyroid Association Guidelines on the Management of Differentiated Thyroid Cancers; Part III. Management of Advanced Differentiated Thyroid Cancers - Chapter 4. Systemic Therapy for Progressive Radioiodine-Refractory Differentiated Thyroid Cancer 2
Dong Yeob Shin, Ho-Cheol Kang, Sun Wook Kim, Dong Gyu Na, Young Joo Park, Young Shin Song, Eun Kyung Lee, Dong-Jun Lim, Yun Jae Chung, Won Gu Kim
International Journal of Thyroidology.2024; 17(1): 168. CrossRef
CANTRK
Tracy L. Stockley, Bryan Lo, Adrian Box, Andrea Gomez Corredor, John DeCoteau, Patrice Desmeules, Harriet Feilotter, Daria Grafodatskaya, Wenda Greer, Cynthia Hawkins, Weei Yuarn Huang, Iyare Izevbaye, Guylaine Lépine, Sebastiao N. Martins Filho, Andreas
The Journal of Molecular Diagnostics.2023; 25(3): 168. CrossRef
NTRK Fusion in a Cohort of BRAF p. V600E Wild-Type Papillary Thyroid Carcinomas
Seung Eun Lee, Mi-Sook Lee, Heejin Bang, Mi Young Kim, Yoon-La Choi, Young Lyun Oh
Modern Pathology.2023; 36(8): 100180. CrossRef
Validation and Clinical Application of ONCOaccuPanel for Targeted Next-Generation Sequencing of Solid Tumors
Moonsik Kim, Changseon Lee, Juyeon Hong, Juhee Kim, Ji Yun Jeong, Nora Jee-Young Park, Ji-Eun Kim, Ji Young Park
Cancer Research and Treatment.2023; 55(2): 429. CrossRef

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Lung and Thoracic cancer

Acquired Resistance Mechanism of EGFR Kinase Domain Duplication to EGFR TKIs in Non–Small Cell Lung Cancer: Chaelin Lee, Miso Kim, Dong-Wan Kim, Tae Min Kim, Soyeon Kim, Sun-Wha Im, Yoon Kyung Jeon, Bhumsuk Keam, Ja-Lok Ku, Dae Seog Heo; Cancer Res Treat. 2022;54(1):140-149. Published online May 3, 2021; DOI: https://doi.org/10.4143/crt.2021.385

Abstract PDF Supplementary Material PubReader ePub

Purpose
Epidermal growth factor receptor kinase domain duplication (EGFR-KDD) is a rare and poorly understood oncogenic mutation in non–small cell lung cancer (NSCLC). We aimed to investigate the acquired resistance mechanism of EGFR-KDD against EGFR-TKIs.
Materials and Methods
We identified EGFR-KDD in tumor tissue obtained from a patient with stage IV lung adenocarcinoma and established the patient-derived cell line SNU-4784. We also established several EGFR-KDD Ba/F3 cell lines: EGFR-KDD wild type (EGFR-KDD^WT), EGFR-KDD domain 1 T790M (EGFR-KDD^D1T), EGFR-KDD domain 2 T790M (EGFR-KDD^D2T), and EGFR-KDD both domain T790M (EGFR-KDD^BDT). We treated the cells with EGFR tyrosine kinase inhibitors (TKIs) and performed cell viability assays, immunoblot assays, and ENU (N-ethyl-N-nitrosourea) mutagenesis screening.
Results
In cell viability assays, SNU-4784 cells and EGFR-KDD^WT Ba/F3 cells were sensitive to 2nd generation and 3rd generation EGFR TKIs. In contrast, the T790M-positive EGFR-KDD Ba/F3 cell lines (EGFR-KDD^T790M) were only sensitive to 3rd generation EGFR TKIs. In ENU mutagenesis screening, we identified the C797S mutation in kinase domain 2 of EGFR-KDD^BDT Ba/F3 cells. Based on this finding, we established an EGFR-KDD domain 1 T790M/domain 2 cis-T790M+C797S (EGFR-KDD^T/T+C) Ba/F3 model, which was resistant to EGFR TKIs and anti-EGFR monoclonal antibody combined with EGFR TKIs.
Conclusion
Our study reveals that the T790M mutation in EGFR-KDD confers resistance to 1st and 2nd generation EGFR TKIs, but is sensitive to 3rd generation EGFR TKIs. In addition, we identified that the C797S mutation in kinase domain 2 of EGFR-KDD^T790M mediates a resistance mechanism against 3rd generation EGFR TKIs.

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Colorectal cancer harboring EGFR kinase domain duplication response to EGFR tyrosine kinase inhibitors
Tomohiro Kondo, Osamu Kikuchi, Yoshihiro Yamamoto, Tomohiko Sunami, Yafeng Wang, Keita Fukuyama, Tomoki Saito, Hideto Nakahara, Sachiko Minamiguchi, Masashi Kanai, Atsushi Sueyoshi, Manabu Muto
The Oncologist.2025;[Epub] CrossRef
A Constitutive EGFR Kinase Dimer to Study Inhibitor Pharmacology
Justin J. Kim, Ilse K. Schaeffner, David E. Heppner, Ciric To, Pasi A. Jänne, Tyler S. Beyett, Michael J. Eck
Molecular Pharmacology.2024; 105(2): 97. CrossRef
Tumor-associated Macrophages Mediate Gefitinib Resistance in Lung Cancer through HGF/c-met Signaling Pathway
Xiali Tang, Yu Chen, Demin Jiao, Xiang Liu, Jun Chen, Yongyang Liu, Chunyan Jiang, Qingyong Chen
Anti-Cancer Agents in Medicinal Chemistry.2024; 24(1): 30. CrossRef
Research progress on the role of bypass activation mechanisms in resistance to tyrosine kinase inhibitors in non-small cell lung cancer
Ziyang Jiang, Zhihan Gu, Xiaomin Yu, Tao Cheng, Bofu Liu
Frontiers in Oncology.2024;[Epub] CrossRef
Molecular Targets and Mechanisms of Casein-Derived Tripeptides Ile-Pro-Pro and Val-Pro-Pro on Hepatic Glucose Metabolism
Chenyang Wang, Lin Zheng, Mouming Zhao
Journal of Agricultural and Food Chemistry.2023; 71(48): 18802. CrossRef
Erlotinib

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Alterations in PD-L1 Expression Associated with Acquisition of Resistance to ALK Inhibitors in ALK-Rearranged Lung Cancer: Su-Jung Kim, Soyeon Kim, Dong-Wan Kim, Miso Kim, Bhumsuk Keam, Tae Min Kim, Yusoo Lee, Jaemoon Koh, Yoon Kyung Jeon, Dae Seog Heo; Cancer Res Treat. 2019;51(3):1231-1240. Published online December 31, 2018; DOI: https://doi.org/10.4143/crt.2018.486

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to evaluate the relationships between the resistance of anaplastic lymphoma kinase (ALK)‒positive non-small cell lung cancer (NSCLC) to ALK inhibitors and the programmed cell death-1/programmed cell death–ligand 1 (PD-L1) pathway, we evaluated alterations in PD-L1 following acquisition of resistance to ALK inhibitors in ALK-positive lung cancer.
Materials and Methods
We established ALK inhibitor-resistant cell lines (H3122CR1, LR1, and CH1) by exposing the parental H3122 ALK-translocated NSCLC cell line to ALK inhibitors. Then, the double-resistant cell lines H3122CR1LR1 and CR1CH1 were developed by exposing the H3122CR1 to other ALK inhibitors. We compared the alterations in PD-L1 expression levels using western blotting, flow cytometry, and quantitative polymerase chain reaction. We also investigated gene expression using RNA sequencing. The expression of PD-L1 in the tumors from 26 ALK-positive metastatic NSCLC patients (11 ALK inhibitor-naïve and 15 ALK inhibitor-resistant patients) was assessed by immunohistochemistry and analyzed.
Results
PD-L1 was expressed at higher levels in ALK inhibitor-resistant cell lines than in the ALK inhibitor-naïve parental cell line at the total protein, surface protein, and mRNA levels. Furthermore, PD-L1 expression in the double-resistant cell lines was much higher than that in the single resistant cell lines. RNA sequencing demonstrated that expression of immune-related genes were largely involved in ALK inhibitor resistance. The mean value of the PD-L1 H-score was 6.5 pre-treatment and 35.0 post-treatment, and the fold difference was 5.42 (p=0.163).
Conclusion
PD-L1 expression increased following acquisition of ALK inhibitor resistance in ALK-positive NSCLC cell lines and tumors.

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Huixian Zhang, Ziheng Zhang, Ningning Yan, Xingya Li
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Co-Occurrence of ALK rearrangement and KRAS G12C mutation in NSCLC: Report of two cases
M Siringo, F Larocca, A Spagnuolo, G Gentile, M Anile, D Diso, D Santini, A Gelibter
Current Problems in Cancer: Case Reports.2024; 14: 100291. CrossRef
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Marco Sposito, Serena Eccher, Luca Pasqualin, Ilaria Mariangela Scaglione, Alice Avancini, Daniela Tregnago, Ilaria Trestini, Jessica Insolda, Adele Bonato, Stefano Ugel, Lisa Derosa, Michele Milella, Sara Pilotto, Lorenzo Belluomini
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Wenchao Xia, Jing Yang, Hongbin Li, Ling Li, Jinfeng Liu
Global Medical Genetics.2024; 11(02): 175. CrossRef
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Shanshan Chen, Jingyi Tang, Fen Liu, Wei Li, Ting Yan, Dangang Shangguan, Nong Yang, Dehua Liao
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High PD-L1 Expression Correlates with an Immunosuppressive Tumour Immune Microenvironment and Worse Prognosis in ALK-Rearranged Non-Small Cell Lung Cancer
Xia Tian, Yalun Li, Qin Huang, Hao Zeng, Qi Wei, Panwen Tian
Biomolecules.2023; 13(6): 991. CrossRef
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Annkristin Heine, Stefanie Andrea Erika Held, Solveig Nora Daecke, Chrystel Flores, Peter Brossart
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Ye Guo, Hanfei Guo, Yongfei Zhang, Jiuwei Cui
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Aaron C. Tan, Johan Chan, Mustafa Khasraw
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Sara Cavallaro, Petra Hååg, Siddharth S. Sahu, Lorenca Berisha, Vitaliy O. Kaminskyy, Simon Ekman, Rolf Lewensohn, Jan Linnros, Kristina Viktorsson, Apurba Dev
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Haifang Wang, Chen Fu, Jun Du, Hongsheng Wang, Rui He, Xiaofeng Yin, Haixia Li, Xin Li, Hongxia Wang, Kui Li, Lei Zheng, Zongcai Liu, Yurong Qiu
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Utility of PD‐L1 immunocytochemistry using body‐fluid cell blocks in patients with non‐small‐cell lung cancer
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Maxim Sorokin, Kirill Ignatev, Elena Poddubskaya, Uliana Vladimirova, Nurshat Gaifullin, Dmitriy Lantsov, Andrew Garazha, Daria Allina, Maria Suntsova, Victoria Barbara, Anton Buzdin
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PLAC8 overexpression correlates with PD-L1 upregulation and acquired resistance to chemotherapies in gallbladder carcinoma
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The efficacy of immune checkpoint inhibitors in anaplastic lymphoma kinase‐positive non‐small cell lung cancer
Ja Yoon Heo, Changhee Park, Bhumsuk Keam, Chan‐Young Ock, Miso Kim, Tae Min Kim, Dong‐Wan Kim, Se Hyun Kim, Yu Jung Kim, Jong Seok Lee, Dae Seog Heo
Thoracic Cancer.2019; 10(11): 2117. CrossRef

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VEGF and Ki-67 Overexpression in Predicting Poor Overall Survival in Adenoid Cystic Carcinoma: Seongyeol Park, Soo Jeong Nam, Bhumsuk Keam, Tae Min Kim, Yoon Kyung Jeon, Se-Hoon Lee, J. Hun Hah, Tack-Kyun Kwon, Dong-Wan Kim, Myung-Whun Sung, Dae Seog Heo, Yung-Jue Bang; Cancer Res Treat. 2016;48(2):518-526. Published online July 14, 2015; DOI: https://doi.org/10.4143/crt.2015.093

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to evaluate potential prognostic factors in patients with adenoid cystic carcinoma (ACC). Materials and Methods A total of 68 patients who underwent curative surgery and had available tissue were enrolled in this study. Their medical records and pathologic slides were reviewed and immunohistochemistry for basic fibroblast growth factor, fibroblast growth factor receptor (FGFR) 2, FGFR3, c-kit, Myb proto-oncogene protein, platelet-derived growth factor receptor beta, vascular endothelial growth factor (VEGF), and Ki-67 was performed. Univariate and multivariate analysis was performed for determination of disease-free survival (DFS) and overall survival (OS).
Results
In univariate analyses, primary site of nasal cavity and paranasal sinus (p=0.022) and Ki-67 expression of more than 7% (p=0.001) were statistically significant factors for poor DFS. Regarding OS, perineural invasion (p=0.032), high expression of VEGF (p=0.033), and high expression of Ki-67 (p=0.007) were poor prognostic factors. In multivariate analyses, primary site of nasal cavity and paranasal sinus (p=0.028) and high expression of Ki-67 (p=0.004) were independent risk factors for poor DFS, and high expression of VEGF (p=0.011) and Ki-67 (p=0.011) showed independent association with poor OS. Conclusion High expression of VEGF and Ki-67 were independent poor prognostic factors for OS in ACC.

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Reduced Dose Intensities of Doxorubicin in Elderly Patients with DLBCL in Rituximab Era: Hyerim Ha, Bhumsuk Keam, Tae Min Kim, Yoon Kyung Jeon, Se-Hoon Lee, Dong-Wan Kim, Chul Woo Kim, Dae Seog Heo; Cancer Res Treat. 2016;48(1):304-311. Published online April 9, 2015; DOI: https://doi.org/10.4143/crt.2014.339

Abstract PDF PubReader ePub

Purpose
The dose intensity of doxorubicin (DID) is important to the survival of diffuse large B cell lymphoma (DLBCL) patients. However, due to expected toxicities, most elderly patients cannot receive full doses of anthracyclines. The purpose of this study was to evaluate the effect of DID on the survival of elderly DLBCL patients (age ≥ 70 years) in the rituximab era.
Materials and Methods
We analyzed 433 DLBCL patients who were treated with R-CHOP between December 2003 and October 2011 at the Seoul National University Hospital. Of these patients, 19.2% were aged ≥ 70 years. We analyzed the survival outcomes according to DID.
Results
Significantly poorer overall survival (OS) was observed for patients aged ≥ 70 years (2-year OS rate: 59.9% vs. 84.2%; p < 0.001). DID ≤ 10 mg/m2/wk had a significant effect on the OS and progression-free survival (PFS) in elderly patients (2-year OS rate: 40.0% in DID ≤ 10 mg/m2/wk vs. 62.6% in DID > 10 mg/m2/wk; p=0.031; 2-year PFS: 35.0% vs. 65.7%; p=0.036). The OS on each 1.7 mg/m2/wk doxorubicin increment above 10 mg/m2/wk in elderly patients was not significant among the groups (2-year OS rate: 75.0% in DID 10.0- 11.7 mg/m2/wk vs. 66.7% in DID 15.0-16.7 mg/m2/wk; p=0.859). Treatment related mortality was not related to DID.
Conclusion
DID can be reduced up to 10 mg/m2/wk in elderly DLBCL patients in the rituximab era. Maintenance of DID > 10 mg/m2/wk and judicious selection of elderly patients who are tolerant to DID is necessary.

Citations

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