Cancer Research and Treatment

Original Articles

Chemotherapy-Free Salvage Therapy with Rituximab, Lenalidomide, and Poseltinib in Relapsed or Refractory Primary Central Nervous System Lymphoma: A Multi-center, Phase II Study: Dong Hyun Kim, Sanyeowool An, Hongyul Ahn, Han Song, Ka-Won Kang, Sang Eun Yoon, Seok Jin Kim, Hyo Jung Kim, Youngil Koh, Deok-Hwan Yang, Consortium for Improving Survival of Lymphoma (CISL); Received September 6, 2025 Accepted November 11, 2025 Published online November 12, 2025; DOI: https://doi.org/10.4143/crt.2025.977 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Relapsed or refractory (R/R) primary central nervous system lymphoma (PCNSL) is an aggressive malignancy for which salvage chemotherapy has limited efficacy. We conducted an investigator-initiated, single-arm, multicenter phase II trial to evaluate the efficacy and safety of a chemotherapy-free salvage regimen comprising rituximab, lenalidomide, and poseltinib (R2P) in patients with R/R PCNSL.
Materials and Methods
The R2P regimen consisted of two phases: six cycles of induction with rituximab, lenalidomide, and poseltinib, followed by three cycles of consolidation with lenalidomide and poseltinib. The primary endpoints were complete response rate (CRR) and overall response rate (ORR). Secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS).
Results
A total of 10 patients were enrolled (one withdrew before cycle 1; nine were evaluable for efficacy). The median age was 70 years (range, 53 to 75 years), and all had received methotrexate-based first-line chemotherapy. The ORR was 55.6%, and the CRR was 33.3%. The median PFS was 5.6 months, and the median OS was not reached. Next-generation sequencing was performed in four patients (three responders and one non-responder). CD79B missense mutations were identified in all three responders. A total of 11 adverse events (AEs) were observed in six patients. The most common AE was neutropenia (30.0%). The only grade ≥ 3 AE was a single case of grade 3 neutropenia. No dose modifications were required due to toxicity.
Conclusion
Poseltinib in combination with lenalidomide and rituximab showed activity in patients with R/R PCNSL, warranting further investigation in larger studies.

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The Efficacy and Safety of Platinum/Vinorelbine as More Than Second-Line Chemotherapy for Advanced Non-small Cell Lung Cancer: Ik-Chan Song, Hyo-Jin Lee, Young-Jun Yang, Yoon-Seok Choi, Hye-Won Ryu, Myung-Won Lee, Ji Young Moon, Deog-Yeon Jo, Samyong Kim, Hwan-Jung Yun; Cancer Res Treat. 2015;47(4):638-644. Published online March 2, 2015; DOI: https://doi.org/10.4143/crt.2014.316

Abstract PDF PubReader ePub: Purpose
There is no regimen that is strongly recommended for more than second-line treatment. We investigated the efficacy and safety of platinum/vinorelbine as more than second-line treatment. Materials and Methods We selected patients with advanced non-small cell lung cancer (NSCLC) who received treatment with platinum/vinorelbine at Chungnam National University Hospital from August 2001 to December 2013. The primary end point was the response rate, and secondary end points were progression-free survival (PFS), overall survival (OS), and toxicity.
Results
Thirty-five patients were enrolled. Response rate was 22.9% (complete response, 0 patients [0%]; partial response, eight patients [22.9%]; stable disease, 10 patients [28.6%]; progressive disease, 14 patients [40.0%]). A significantly higher response rate was observed for patients who had responded to previous chemotherapy than for those who did not (34.8% [8/23] vs. 0% [0/12], p=0.020). The median PFS was 4 months (range, 1 to 21 months). Patients with adenocarcinoma and non-smokers had a significantly longer PFS than patients with non-adenocarcinoma and smokers (5 months vs. 2 months, p=0.007; 4.5 months vs. 2 months, p=0.046, respectively). The median OS was 10 months (range, 1 to 41 months). Patients with good performance status and non-smokers had a significantly longer OS than patients with poor performance status and smokers (14 months vs. 4 months, p=0.02; 18.5 months vs. 6 months, p=0.049, respectively). The main serious adverse event (grade 3 or 4) was neutropenia (15 events, 13.3%) in a total of 113 cycles. Conclusion Platinum/vinorelbine was effective as more than second-line chemotherapy, and the toxicity was tolerable, in patients with advanced NSCLC.

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Diagnostic and Prognostic Implications of Spine Magnetic Resonance Imaging at Diagnosis in Patients with Multiple Myeloma: Ik-Chan Song, Ji-Na Kim, Yoon-Seok Choi, Haewon Ryu, Myung-Won Lee, Hyo-Jin Lee, Hwan-Jung Yun, Samyong Kim, Soon Tae Kwon, Deog-Yeon Jo; Cancer Res Treat. 2015;47(3):465-472. Published online November 3, 2014; DOI: https://doi.org/10.4143/crt.2014.010

Abstract PDF PubReader ePub

Purpose
The aim of this study is to determine the diagnostic and prognostic role of baseline spinal magnetic resonance imaging (MRI) in patients with multiple myeloma.
Materials and Methods
We enrolled patients newly diagnosed with multiple myeloma from 2004-2011 at a single center. Abnormal MRI findings that were not detected in radiographs have been analyzed and categorized as malignant compression fractures or extramedullary plasmacytoma. The bone marrow (BM) infiltration patterns on MRI have been classified into five categories.
Results
A total of 113 patients with a median age of 65 years (range, 40 to 89 years) were enrolled in the study. Malignant compression fractures not detected in the bone survey were found in 26 patients (23.0%), including three patients (2.6%) with no related symptoms or signs. Extramedullary plasmacytoma was detected in 22 patients (19.5%), including 15 (13.3%) with epidural extension of the tumor. Of these 22 patients, 11 (50.0%) had no relevant symptoms or signs. The presence of malignant compression fractures did not influence overall survival; whereas non-epidural extramedullary plasmacytoma was associated with poor overall survival in the multivariate analysis (hazard ratio, 3.205; 95% confidence interval [CI], 1.430 to 9.845; p=0.042). During the follow-up for a median of 21 months (range, 1 to 91 months), overall survival with the mixed BM infiltrative pattern (median, 24.0 months; 95% CI, 22.9 to 25.1 months) was shorter than those with other patterns (median 56 months; 95% CI, 48.9 to 63.1 months; p=0.030).
Conclusion
These results indicate that spine MRI at the time of diagnosis is useful for detecting skeletal lesions and predicting the prognosis in patients with multiple myeloma.

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Prognostic significance of extramedullary disease (EMD) detected on pre-transplant 18F-FDG PET/CT in patients with multiple myeloma: Results of PIPET-M trial
Uday Yanamandra, Arun Kumar Reddy Gorla, Kanhaiyalal Agrawal, Bhagwant Rai Mittal, Gaurav Prakash, Alka Rani Khadwal, Neelam Varma, Subhash Varma, Pankaj Malhotra
Medical Journal Armed Forces India.2023; 79(6): 672. CrossRef
Clinical impact of spine magnetic resonance imaging as a valuable prognostic tool for patients with multiple myeloma: a retrospective study
Jung Min Lee, Hee Jeong Cho, Joon-Ho Moon, Sang Kyun Sohn, Byunggeon Park, Dong Won Baek
Journal of Yeungnam Medical Science.2022; 39(4): 300. CrossRef
Diagnostic value of whole-body ultra-low dose computed tomography in comparison with spinal magnetic resonance imaging in the assessment of disease in multiple myeloma
Davide Ippolito, Cammillo Talei Franzesi, Sara Spiga, Valeria Besostri, Sara Pezzati, Fausto Rossini, Sandro Sironi
British Journal of Haematology.2017; 177(3): 395. CrossRef
Automated “Bone Subtraction” Image Analysis Software Package for Improved and Faster CT Monitoring of Longitudinal Spine Involvement in Patients with Multiple Myeloma
Marius Horger, Hendrick Ditt, Shu Liao, Katja Weisel, Jan Fritz, Wolfgang M. Thaiss, Sascha Kaufmann, Konstantin Nikolaou, Christopher Kloth
Academic Radiology.2017; 24(5): 623. CrossRef
Multimodality imaging of osseous involvement In haematological malignancies
Abhishek R Keraliya, Katherine M Krajewski, Jyothi P Jagannathan, Atul B Shinagare, Marta Braschi-Amirfarzan, Sree H Tirumani, Nikhil H Ramaiya
The British Journal of Radiology.2016; 89(1059): 20150980. CrossRef
Risk Stratification in Multiple Myeloma
Melissa Gaik-Ming Ooi, Sanjay de Mel, Wee Joo Chng
Current Hematologic Malignancy Reports.2016; 11(2): 137. CrossRef
Temporomandibular joint involvement in patients with multiple myeloma—a retrospective study
W. Abboud, R. Yahalom, M. Leiba, G. Greenberg, N. Yarom
International Journal of Oral and Maxillofacial Surgery.2016; 45(12): 1545. CrossRef

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Five-Year Follow-up Study of Monoclonal Gammopathy of Undetermined Significance in a Korean Elderly Urban Cohort: Yun-Gyoo Lee, Soo-Mee Bang, Jeong-Ok Lee, Jin Won Kim, Keun-Wook Lee, Jee Hyun Kim, Jung Han Song, Tae-Hee Kim, Ki Woong Kim, Jong-Seok Lee; Cancer Res Treat. 2015;47(2):215-220. Published online August 29, 2014; DOI: https://doi.org/10.4143/crt.2013.262

Abstract PDF PubReader ePub

Purpose
We previously reported the prevalence of monoclonal gammopathy of undetermined significance (MGUS) to be 3.3% among an elderly Korean urban cohort recruited during 2005-2006. Here, we report a 5-year follow-up study of the previously identified MGUS cohort.
Materials and Methods
The 680 participants from the initial cohort were followed-up for a median of 5 years. Sera were collected between 2010 and 2011. Two-step screening was performed with standard serum electrophoresis followed by immunofixation and determination of the serum concentration of monoclonal-protein (M-protein).
Results
Of the 680 participants (21 with MGUS), 348 (51%) agreed to participate in the follow-up study and 10 were found to have MGUS. Among the 21 MGUS patients initially identified, nine were followed-up, six had persistent M-protein, and one patient had progressed to multiple myeloma (progression rate, 1.0%/yr). The M-protein disappeared in the remaining two individuals. Among the 339 participants without MGUS who were followed-up, four developed an M-protein. There was no significant difference in survival with respect to the presence of MGUS (p=0.66).
Conclusion
The 5-year follow-up data show that the natural clinical course of MGUS in Korea is similar to that in Western countries. MGUS was not associated with an increased risk of death over the 5-year study period.

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Prevalence of monoclonal gammopathy of undetermined significance in Shenzhen, China
Anping Xu, Tong Guo, Shuping Zhang, Houlong Luo, Mengxue Shen, Yinghui Ye, Ling Ji
Hematology.2024;[Epub] CrossRef
Isatuximab plus carfilzomib and dexamethasone in East Asian patients with relapsed multiple myeloma: IKEMA subgroup analysis
Kihyun Kim, Chang-Ki Min, Youngil Koh, Kenichi Ishizawa, Sung-Hyun Kim, Shigeki Ito, Junji Tanaka, Michihiro Uchiyama, Yawara Kawano, Jin Seok Kim, Philippe Moreau, Thomas Martin, Yvonne Dong, Marie-Laure Risse, Kenshi Suzuki
International Journal of Hematology.2022; 116(4): 553. CrossRef
Screening Tests for Early Diagnosis of Multiple Myeloma and Related Plasma Cell Disorders
Jin Seok Kim, Sung-Soo Yoon, Chang-Ki Min, Je-Jung Lee, Dok Hyun Yoon, Kihyun Kim
The Korean Journal of Medicine.2021; 96(5): 371. CrossRef
Prevalence of monoclonal gammopathy of undetermined significance in a large population with annual medical check-ups in China
Jian-hua Han, Ji-nuo Wang, Yue-lun Zhang, Xin-xin Cao, Dao-bin Zhou, Teng-da Xu, Wei Su, Jian Li
Blood Cancer Journal.2020;[Epub] CrossRef
Monoclonal gammopathy of undetermined significance in Chinese population: A prospective epidemiological study
Ling Ma, Shuang Xu, Jianhua Qu, Jian Hou, Yang Wang, Lei Wen, Yang Liu, Ying Kang, Ming Jiang, Weijun Fu, Juan Du, Lin Zhou, Xiaojun Huang, Zhaoxia Zhang, Jin Lu
Hematological Oncology.2019; 37(1): 75. CrossRef
The clinical features and prognosis of the monoclonal gammopathy undetermined significance: A single center study
Ling Ma, Shuang Xu, Lei Wen, Yang Liu, Ying Kang, Xiaojun Huang, Jin Lu
Blood Cells, Molecules, and Diseases.2018; 73: 9. CrossRef
Recent advances in multiple myeloma: a Korean perspective
Junshik Hong, Jae Hoon Lee
The Korean Journal of Internal Medicine.2016; 31(5): 820. CrossRef

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Cytoplasmic Trapping of CXCR4 in Hepatocellular Carcinoma Cell Lines: Seong-Woo Kim, Ha-Yon Kim, Ik-Chan Song, Seon-Ah Jin, Hyo-Jin Lee, Hwan-Jung Yun, Samyong Kim, Deog-Yeon Jo; Cancer Res Treat. 2008;40(2):53-61. Published online June 30, 2008; DOI: https://doi.org/10.4143/crt.2008.40.2.53

Abstract PDF PubReader ePub

Purpose

The chemokine receptor CXCR4 plays a role in the metastasis and progression of a broad range of malignant tumors; however, its influence on hepatocellular carcinoma (HCC) is not well defined. Thus, we analyzed the expression of CXCR4 and its functions in HCC cell lines in vitro.

Materials and Methods

Five HCC cell lines (HepG2, Hep3B, SK-HEP-1, NCI-H630 and PLC/PRF5) were investigated. The CXCR4 expression was analyzed by RT-PCR, Western blotting, flow cytometry and immunofluorescence staining. In addition, the effects of stromal cell-derived factor-1 (SDF-1) on the migration, proliferation and survival of the cells were investigated, as well as the SDF-1-induced phosphorylation of signaling molecules.

Results

All five cell lines had abundant CXCR4 in their cytoplasm, whereas a cell surface CXCR4 expression was only detected in a very small population of PLC/PRF5 cells. In contrast, SDF-1 bound to all the cells. SDF-1 induced the phosphorylation of AKT and ERK1/2 in the PLC/PRF5 cells and the phosphorylation of Stat3, AKT and ERK1/2 in the Hep3B cells. Nonetheless, SDF-1 did not induce migration or proliferation in any of the cells, nor did it rescue the cells from serum deprivation-induced apoptosis. Recruitment of CXCR4 from the cytoplasm to the cell surface was not elicited by dexamethasone, proinflammatory cytokines or VEGF. Hypoxia increased both the cytoplasmic and cell surface expressions of CXCR4 in only the PLC/PRF5 cells.

Conclusions

CXCR4 is trapped in the cytoplasm and it is not recruited to the cell surface by standard extrinsic stimuli in the majority of HCC cell lines, and the result of this is a negligible response to SDF-1.

Citations

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CXCR4, regulated by HIF1A, promotes endometrial breakdown via CD45+ leukocyte recruitment in a mouse model of menstruation
Shufang Wang, Xihua Chen, Shige Guo, Fang Zhou, Xin Zhang, Cong Lu, Xuqing Yang, Qianxing Wang, Bin He, Jiedong Wang, Hanbi Wang, Xiangbo Xu
Reproductive Biology.2023; 23(3): 100785. CrossRef
Interaction of immune checkpoint PD-1 and chemokine receptor 4 (CXCR4) promotes a malignant phenotype in pancreatic cancer cells
Megan M. Harper, Miranda Lin, Michael J. Cavnar, Prakash K. Pandalai, Reema A. Patel, Mei Gao, Joseph Kim, Ming Tan
PLOS ONE.2022; 17(7): e0270832. CrossRef
The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors—A Review of Literature
Jan Korbecki, Klaudyna Kojder, Patrycja Kapczuk, Patrycja Kupnicka, Barbara Gawrońska-Szklarz, Izabela Gutowska, Dariusz Chlubek, Irena Baranowska-Bosiacka
International Journal of Molecular Sciences.2021; 22(2): 843. CrossRef
Somatostatin and CXCR4 chemokine receptor expression in hepatocellular and cholangiocellular carcinomas: tumor capillaries as promising targets
Daniel Kaemmerer, Robin Schindler, Franziska Mußbach, Uta Dahmen, Annelore Altendorf-Hofmann, Olaf Dirsch, Jörg Sänger, Stefan Schulz, Amelie Lupp
BMC Cancer.2017;[Epub] CrossRef
Role of C-X-C chemokine ligand 12/C-X-C chemokine receptor 4 in the progression of hepatocellular carcinoma
Kuo-Shyang Jeng, Chi-Juei Jeng, Wen-Juei Jeng, Chiung-Fang Chang, I-Shyan Sheen
Oncology Letters.2017; 14(2): 1905. CrossRef
An Ultra‐High Fluorescence Enhancement and High Throughput Assay for Revealing Expression and Internalization of Chemokine Receptor CXCR4
Hua He, Xiaojuan Wang, Tiantian Cheng, Yongqing Xia, Jun Lao, Baosheng Ge, Hao Ren, Naseer Ullah Khan, Fang Huang
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CXCR4 expression affects overall survival of HCC patients whereas CXCR7 expression does not
Maria Neve Polimeno, Caterina Ierano, Crescenzo D'Alterio, Nunzia Simona Losito, Maria Napolitano, Luigi Portella, Giosuè Scognamiglio, Fabiana Tatangelo, Anna Maria Trotta, Steven Curley, Susan Costantini, Raffaele Liuzzi, Francesco Izzo, Stefania Scala
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Mechanisms regulating cell membrane localization of the chemokine receptor CXCR4 in human hepatocarcinoma cells
Edgar B. Cepeda, Tatjana Dediulia, Joan Fernando, Esther Bertran, Gustavo Egea, Estanislao Navarro, Isabel Fabregat
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Immunohistochemical Expression of CXCR4 on Breast Cancer and Its Clinical Significance
Marina Okuyama Kishima, Carlos Eduardo Coral de Oliveira, Bruna Karina Banin-Hirata, Roberta Losi-Guembarovski, Karen Brajão de Oliveira, Marla Karine Amarante, Maria Angelica Ehara Watanabe
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Intracellular coexpression of CXC- and CC– chemokine receptors and their ligands in human melanoma cell lines and dynamic variations after xenotransplantation
Sandra Pinto, Alicia Martínez-Romero, José-Enrique O’Connor, Rosario Gil-Benso, Teresa San-Miguel, Liria Terrádez, Carlos Monteagudo, Robert C Callaghan
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Intracellular trafficking and endocytosis of CXCR4 in fetal mesenchymal stem/stromal cells
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Downregulation of the proangiogenic prostaglandin E receptor EP3 and reduced angiogenesis in a mouse model of diabetes mellitus
Kazuhito Oba, Kanako Hosono, Hideki Amano, Shin-ichiro Okizaki, Yoshiya Ito, Masayoshi Shichiri, Masataka Majima
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Tacrolimus promotes hepatocellular carcinoma and enhances CXCR4/SDF-1α expression in vivo
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Histone deacetylase inhibitors induce CXCR4 mRNA but antagonize CXCR4 migration
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bcl-2 and p53 Gene Expression in Colonic Adenoma and Carcinoma: Chang Young Lim, Jeong Won Kim, Il Han Song, Young Joo Jin, Im Whan Rho, Dong Kook Park, Jeong Hee Cho, Sung Bae Choi; J Korean Cancer Assoc. 1998;30(1):89-99.

Abstract PDF: PURPOSE
Recently, it is suggested that the inhibitian of apoptosis is associated with tumorigenesis of colon. Bcl-2 gene is an important inhibitory regulator of apoptosis, and bcl-2 acts antagonistly with the wild type p53 gene, one of the tumor suppressor genes, in apoptosis. To detnmine the role of bcl-2 and p53 gene in colonic tumorigenesis, we performed the study.
MATERIALS AND METHODS
We tested the tissue obtained by polypectomy and surgical resection by immunohistochemical staining for Bcl-2 and p53.
RESULTS
We found that in normal colonic tissue, the Bcl-2 was sparcely expressed, and the p53 was expressed sporadically. The rate of positivity of staining was below 5%. However, in colonic adenoma and colon cancer tissue, Bcl-2 and p53 were expressed more than in nonnal colonic tissue(p<0.05). (Scoring in Colonic adenoma: Bcl-2 6.2+/-1.1, p53 5.7+/-1.0; Scoring in Colonic carcinoma: Bcl-2 4.7+/-1.0, p53 8.3+/-0.9) CONCLUSION: Our results suggested that the bcl-2 and p53 play an important role in colonic tumorigenesis.

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