Cancer Research and Treatment

Original Articles

Hematologic malignancy

Long-term Psychiatric and Endocrine Complications Following Hematopoietic Stem Cell Transplantation in Hematologic Disease in Korea: A Nation-Wide Cohort Study: Min Ji Jeon, Eunjin Noh, Seok Joo Moon, Eun Sang Yu, Chul Won Choi, Dae Sik Kim, Eun Joo Kang; Cancer Res Treat. 2024;56(4):1262-1269. Published online May 9, 2024; DOI: https://doi.org/10.4143/crt.2024.047

Abstract PDF PubReader ePub: Purpose
Numerous patients experience long-term complications after hematopoietic stem cell transplantation (HSCT). This study aimed to identify the frequency and risk factors for psychiatric and endocrine complications following HSCT through big data analyses.
Materials and Methods
We established a cohort of patients with hematologic disease who underwent HSCT in Korea between 2010 and 2012 using the Health Insurance Review & Assessment Service data. A total of 3,636 patients were identified, and insurance claims were tracked using psychiatric and endocrine diagnostic International Classification of Diseases, 10th Revision codes for the ensuing decade. We identified the incidence rates of long-term complications based on the baseline disease and HSCT type. Prognostic factors for each complication were scrutinized using logistic regression analysis.
Results
A total of 1,879 patients underwent allogeneic HSCT and 1,757 patients received autologous HSCT. Post-HSCT, 506 patients were diagnosed with depression, 465 with anxiety disorders, and 659 with diabetes. The highest incidence of long-term complications occurred within the first year post-HSCT (12.2%), subsequently decreasing over time. Risk factors for depressive disorders after allogeneic HSCT included female sex, a total body irradiation–based conditioning regimen, and cyclosporine. Identified risk factors for diabetes mellitus comprised old age, total body irradiation–based conditioning regimen, and non-antithymocyte globulin protocol. Regarding autologous HSCT, only female sex was identified as a risk factor for depressive disorders, whereas elderly patients and those with multiple myeloma were identified as poor prognostic factors for diabetes mellitus.
Conclusion
The incidence of long-term psychiatric and endocrine complications post-HSCT remains high, and patients with risk factors for these complications require vigilant follow-up.

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Association of Single Nucleotide Polymorphisms in PIM-1 Gene with the Risk of Korean Lung Cancer: Dae Sik Kim, Jae Sook Sung, Eun Soon Shin, Jeong-Seon Ryu, In Keun Choi, Kyong Hwa Park, Yong Park, Eui Bae Kim, Seh Jong Park, Yeul Hong Kim; Cancer Res Treat. 2008;40(4):190-196. Published online December 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.4.190

Abstract PDF PubReader ePub

Purpose

The expression of the PIM-1 gene, which is a proto-oncogene that encodes a serine/threonine kinase, is associated with multiple cellular functions such as proliferation, differentiation, apoptosis and tumorigenesis. In particular, several studies have reported that the PIM-1 gene is associated with the development of lymphoma, leukemia and prostate cancer. Therefore, this study was conducted to evaluate the association between the single nucleotide polymorphisms in the PIM-1 gene and the risk of lung cancer occurrence in the Korean population.

Materials and Methods

To evaluate the role of the PIM-1 gene in the development of lung cancer, the genotypes of the PIM-1 gene were determined in 408 lung cancer patients and 410 normal subjects.

Results

We found that the T-C-T-C haplotypes of the PIM-1 gene (-1196 T>C, IVS4 +55 T>C, IVS4 +1416 T>A and +3684 C>A) were associated with an increased risk of lung cancer [adjusted odds ratio (aOR): 3.98; 95% CI: 1.24~12.75, p-value: 0.020]. In particular, these haplotypes showed an increased risk of lung cancer in males (aOR: 5.67; 95% CI: 1.32~24.30, p-value: 0.019) and smokers (aOR: 7.82; 95% CI: 1.75~34.98, p-value: 0.007).

Conclusions

The present results suggest that the T-C-T-C haplotype of the PIM-1 gene could influence the risk of developing smoking-related lung cancer in the Korean population. Additional functional studies with an larger sample sized analysis are warranted to reconfirm our findings.

Citations

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A review on structure-function mechanism and signaling pathway of serine/threonine protein PIM kinases as a therapeutic target
Ajaya Kumar Rout, Budheswar Dehury, Satya Narayan Parida, Sushree Swati Rout, Rajkumar Jena, Neha Kaushik, Nagendra Kumar Kaushik, Sukanta Kumar Pradhan, Chita Ranjan Sahoo, Ashok Kumar Singh, Meenakshi Arya, Bijay Kumar Behera
International Journal of Biological Macromolecules.2024; 270: 132030. CrossRef
Impact of Pim1 mutations on the survival outcomes of patients with breast cancer: Insights from a clinical study
Syed Sultan Beevi, Kavitha Anbrasu, Vinod Kumar Verma, Nagesh Kishan Panchal, Krishna Kiran Kannepalli, Raghu Ram Pillarisetti, Sailaja Madigubba, Jyotsana Dwivedi, Neha Damodar, Radhika Chowdary Darapuneni
Human Gene.2024; 40: 201295. CrossRef
HCG11 inhibits salivary adenoid cystic carcinoma by upregulating EphA2 via binding to miR-1297
Shujuan Yan, Meng Wang
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology.2023; 135(2): 257. CrossRef
Therapeutic targeting of PIM KINASE signaling in cancer therapy: Structural and clinical prospects
Aanchal Rathi, Dhiraj Kumar, Gulam Mustafa Hasan, Mohammad Mahfuzul Haque, Md Imtaiyaz Hassan
Biochimica et Biophysica Acta (BBA) - General Subjects.2021; 1865(11): 129995. CrossRef
Loss of PIM1 correlates with progression and prognosis of salivary adenoid cystic carcinoma (SACC)
Jiajie Xu, Xin Zhu, Qingling Li, Chao Chen, Zhenying Guo, Zhuo Tan, Chuanming Zheng, Minghua Ge
Cancer Cell International.2018;[Epub] CrossRef
PIM Kinase as an Executional Target in Cancer
Xinning Zhang, Mengqiu Song, Joydeb Kumar Kundu, Mee-Hyun Lee, Zhen-Zhen Liu
Journal of Cancer Prevention.2018; 23(3): 109. CrossRef
HistoneH3 demethylase JMJD2A promotes growth of liver cancer cells through up-regulating miR372
Jiahui An, Jie Xu, Jiao Li, Song Jia, Xiaonan Li, Yanan Lu, Yuxin Yang, Zhuojia Lin, Xiaoru Xin, Mengying Wu, Qidi Zheng, Hu Pu, Xin Gui, Tianming Li, Dongdong Lu
Oncotarget.2017; 8(30): 49093. CrossRef
Expressions of osteopontin (OPN), ανβ3 and Pim-1 associated with poor prognosis in non-small cell lung cancer (NSCLC)
Yi Jin, Da-yue Tong, Lu-ying Tang, Jian-ning Chen, Jing Zhou, Zhi-ying Feng, Chun-kui Shao
Chinese Journal of Cancer Research.2012; 24(2): 103. CrossRef
Overexpression of Osteopontin, αvβ3 and Pim-1 Associated with Prognostically Important Clinicopathologic Variables in Non-Small Cell Lung Cancer
Yi Jin, Da-yue Tong, Jian-ning Chen, Zhi-ying Feng, Jian-yong Yang, Chun-kui Shao, Jia-ping Li, Rossella Rota
PLoS ONE.2012; 7(10): e48575. CrossRef
No Association between PIK3CA Polymorphism and Lung Cancer Risk in the Korean Population
Jae-Sook Sung, Kyong-Hwa Park, Seung-Tae Kim, Jae-Hong Seo, Sang-Won Shin, Jun-Suk Kim, Yeul-Hong Kim
Genomics & Informatics.2010; 8(4): 194. CrossRef

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Clinical Factors Related to Suspected Second Primary Lung Cancer Development in Patients with Head and Neck Cancer: Eui Bae Kim, Yong Park, Seh Jong Park, Dae Sik Kim, Jee Won Kim, Hee Yun Seo, Hwa Jung Sung, In Keun Choi, Kyong Hwa Park, Sang Cheul Oh, Chul Won Choi, Byung Soo Kim, Yeul Hong Kim, Jun Suk Kim, Sang Won Shin, Chul Yong Kim, Kwang-Yoon Jung; Cancer Res Treat. 2008;40(4):178-183. Published online December 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.4.178

Abstract PDF PubReader ePub

Purpose

The rate of second primary lung cancer development for patients with head and neck cancer (HNC) has been noted. The aim of our study was to evaluate the incidence and clinical features of suspected second primary lung cancer that developed in patients with primary HNC.

Materials and Methods

We conducted a retrospective study of 469 patients who were newly diagnosed with HNC at the Korea University Medical Center between January 2000 and December 2006.

Results

A total of 469 patients were included (389 men and 80 women). Eighteen patients (3.8%) had suspected second primary lung cancers. Statistically significant clinical variables for lung cancer development included the origin site for the primary HNC (oro-hypopharynx and larynx) (p=0.048), abnormal chest x-ray findings (p=0.027) and the histological HNC type (squamous cell carcinoma) (p=0.032). When the second primary lung cancers were combined with HNCs, the adjusted overall survival of patients with a second primary lung cancer was 16 months (p<0.001).

Conclusions

Considering the relative risk factors for a second primary lung cancer developing in patients with HNC, advanced diagnostic tools, such as chest CT or PET CT scan, should be applied for the early detection of a second primary lung cancer.

Citations

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Long-Term Survival in Metachronous Primary Malignancies: Stage III Nasopharyngeal Cancer and Stage IV Non-Small-Cell Lung Cancer
Gabriela Rahnea-Nita, Alexandru Nechifor, Mihai-Teodor Georgescu, Dorel Firescu, Adrian-Cornel Maier, Radu-Valeriu Toma, Valentin Titus Grigorean, Liliana-Florina Andronache, Roxana-Andreea Rahnea-Nita, Ionut Simion Coman, Laura-Florentina Rebegea
Journal of Clinical Medicine.2025; 14(10): 3299. CrossRef
African American race as a risk factor associated with a second primary lung cancer after initial primary head and neck cancer
Yusra F. Shao, Seongho Kim, John D. Cramer, Dina Farhat, Jeffrey Hotaling, Syed Naweed Raza, George Yoo, Ho‐sheng Lin, Harold Kim, Ammar Sukari, Misako Nagasaka
Head & Neck.2022; 44(10): 2069. CrossRef
Should fluorodeoxyglucose positron emission tomography/computed tomography be the first-line imaging investigation for restaging the laryngeal carcinoma patients?
Tarun Jain, Guman Singh, Sumit Goyal, Ajay Yadav, Dinesh Yadav, Nitin Khunteta, Hemant Malhotra
World Journal of Nuclear Medicine.2021; 20(02): 164. CrossRef
Modern Radiology in the Management of Head and Neck Cancer
G.J.C. Burkill, R.M. Evans, V.V. Raman, S.E.J. Connor
Clinical Oncology.2016; 28(7): 440. CrossRef
Synchronous Squamous Cell Carcinoma and Chronic Lymphocytic Leukemia of the Palate
Pablo Rosado, Soledad Fernández, Luis Junquera, Juan Carlos De Vicente
Journal of Craniofacial Surgery.2011; 22(1): 348. CrossRef

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The Bone Morphogenesis Protein-2 (BMP-2) is Associated with Progression to Metastatic Disease in Gastric Cancer: Yong Park, Jee Won Kim, Dae Sik Kim, Eui Bae Kim, Se Jong Park, Jin Yong Park, Woo Suk Choi, Jong Gyu Song, Hee Yun Seo, Sang Cheul Oh, Byung Soo Kim, Jong Jae Park, Yeul Hong Kim, Jun Suk Kim; Cancer Res Treat. 2008;40(3):127-132. Published online September 30, 2008; DOI: https://doi.org/10.4143/crt.2008.40.3.127

Abstract PDF PubReader ePub

Purpose

Bone Morphogenetic Proteins (BMPs) are members of the TGF-β superfamily and it has been demonstrated that BMPs enhance migration, invasion and metastasis. The purpose of this study was to identify the association between the serum BMP-2 level and the progression status of gastric cancer.

Materials and Methods

Fifty-five patients with metastatic gastric cancer (metastatic disease group), six patients with early gastric cancer without lymph node metastasis (the EGC group), and ten healthy control subjects were enrolled in this study. The serum BMP-2 level was quantified by use of a commercially available ELISA kit. In EGC group patients and patients with metastatic disease, whole blood was obtained before endoscopic mucosal resection and before the commencement of a scheduled cycle of systemic chemotherapy, respectively.

Results

No significant difference in the mean serum BMP-2 levels was observed between the control subjects and the EGC group patients (87.95 pg/ml for the control subjects and 84.50 pg/ml for the EGC group, p=1.0). However, the metastatic disease group patients had a significantly higher level of serum BMP (179.61 pg/ml) than the control subjects and EGC group patients (87.95 pg/ml for the control subjects and 84.50 pg/ml for the EGC group, p<0.0001). Moreover, the mean serum BMP-2 level from patients with a bone metastasis was significantly higher than the mean serum BMP-2 level from patients without a bone metastasis (204.73 pg/ml versus 173.33 pg/ml, p=0.021).

Conclusions

BMP-2 seems to have a role in progression to metastatic disease in gastric cancer, especially in the late stage of tumorigenesis, including invasion and metastasis. BMP-2 may facilitate bone metastasis in gastric cancer. To confirm these findings, further studies are required with tissue specimens and the use of a cancer cell line.

Citations

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Jalil Nourisa, Berit Zeller-Plumhoff, Heike Helmholz, Bérengère Luthringer-Feyerabend, Vladimir Ivannikov, Regine Willumeit-Römer
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BMP Signaling in Development, Stem Cells, and Diseases of the Gastrointestinal Tract
Yongchun Zhang, Jianwen Que
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Sahitya Injamuri, Mohamed N. Rahaman, Youqu Shen, Yue‐Wern Huang
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Annatto-Derived Tocotrienol Promotes Mineralization of MC3T3-E1 Cells by Enhancing BMP-2 Protein Expression via Inhibiting RhoA Activation and HMG-CoA Reductase Gene Expression

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Case Report

Hepatitis B Virus Reactivation in a Surface Antigen-negative and Antibody-positive Patient after Rituximab Plus CHOP Chemotherapy: Eui Bae Kim, Dae Sik Kim, Seh Jong Park, Yong Park, Kyoung Ho Rho, Seok Jin Kim; Cancer Res Treat. 2008;40(1):36-38. Published online March 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.1.36

Abstract PDF PubReader ePub

Rituximab is a monoclonal antibody that targets B-lymphocytes, and it is widely used to treat non-Hodgkin's lymphoma. However, its use has been implicated in HBV reactivation that's related with the immunosuppressive effects of rituximab. Although the majority of reactivations occur in hepatitis B carriers, a few cases of reactivation have been reported in HBsAg negative patients. However, reactivation in an HBsAg negative/HBsAb positive patient after rituximab treatment has never been reported in Korea. We present here an HBsAg-negative/HBsAb-positive 66-year-old female who displayed reactivation following rituximab plus CHOP chemotherapy for diffuse large B-cell lymphoma. While she was negative for HBsAg at diagnosis, her viral status was changed at the time of relapse as follows: HBsAg positive, HBsAb negative, HBeAg positive, HBeAb negative and an HBV DNA level of 1165 pg/ml. Our observation suggests that we should monitor for HBV reactivation during rituximab treatment when prior HBV infection or occult infection is suspected, and even in the HBsAg negative/HBsAb positive cases.

Citations

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Recurrence and influencing factors of hepatitis B surface antigen seroclearance induced by peginterferon alpha-based regimens
Rui Lu, Meng Zhang, Zi-Han Liu, Miao Hao, Yan Tian, Mei Li, Feng-Ping Wu, Wen-Jun Wang, Juan-Juan Shi, Xin Zhang, Xiao-Li Jia, Zi-Cheng Jiang, Xue-Mei Li, Guang-Hua Xu, Ya-Ping Li, Shuang-Suo Dang
World Journal of Gastroenterology.2024; 30(44): 4725. CrossRef
Very late-onset hepatitis B reactivation following chemoimmunotherapy
Edward R. Scheffer Cliff, Joe Sasadeusz, Kumar Visvanathan, Andrew Grigg
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Development and validation of a nomogram for steroid-resistance prediction in immune thrombocytopenia patients
Jieni Yu, Zhiqiang Xu, Yuanyuan Zhuo, Huahua Wei, Yinhai Ye, Qinhong Xu, Youli Li, Lihong Yu, Weiying Feng, Pan Hong, Kejie Zhang
Hematology.2021; 26(1): 956. CrossRef
Hepatitis B virus reactivation with corticosteroid therapy in patients with adrenal insufficiency
Masako Hatano, Toshihide Mimura, Akira Shimada, Mitsuhiko Noda, Shigehiro Katayama
Endocrinology, Diabetes & Metabolism.2019;[Epub] CrossRef
Late reactivation of occult hepatitis B virus infection in a patient with chronic lymphocytic leukemia after rituximab and fludarabine-based regimen
Nuria Dominguez, Maria Luisa Manzano, Raquel Muñoz, Ana Martin, Inmaculada Fernandez, Gregorio Castellano
Leukemia & Lymphoma.2015; 56(4): 1160. CrossRef
Giving rituximab in patients with occult or resolved hepatitis B virus infection: are the current guidelines good enough?
Jesse Civan, Hie Won Hann
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Mauro Viganò, Giampaolo Mangia, Pietro Lampertico
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Tae Won Lim, Hee Taek Oh, Seung Un Song, Hae Won Lee, Ji Yeon Kim, Seon Ja Park
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Occult Hepatitis B Virus Infection: Transmission and Reactivation
Sang Hee Song, Seong Gyu Hwang
The Korean Journal of Gastroenterology.2013; 62(3): 148. CrossRef
Reactivation of Hepatitis B Virus Following Systemic Chemotherapy for Malignant Lymphoma
Seung Jun Jang, Young Kul Jung, Hae Lim Baek, Hyun Hwa Yoon, Seung Kak Shin, Jun Shik Hong, Jin Ny Park, Oh Sang Kwon, Yun Soo Kim, Duck Joo Choi, Jae Hoon Lee, Ju Hyun Kim
Korean Journal of Medicine.2013; 85(6): 598. CrossRef
Occult Hepatitis B: Clinical Viewpoint and Management
Mehdi Zobeiri
Hepatitis Research and Treatment.2013; 2013: 1. CrossRef
Highly Sensitive Detection of Hepatitis B Virus Surface Antigen by Use of a Semiautomated Immune Complex Transfer Chemiluminescence Enzyme Immunoassay
Kazuhiko Takeda, Mari Maruki, Takahiro Yamagaito, Machiko Muramatsu, Yasuhiro Sakai, Hiroaki Tobimatsu, Hironori Kobayashi, Yoshiteru Mizuno, Yukio Hamaguchi
Journal of Clinical Microbiology.2013; 51(7): 2238. CrossRef
Reactivation of hepatitis B virus following rituximab-plus-steroid combination chemotherapy
Shigeru Kusumoto, Yasuhito Tanaka, Ryuzo Ueda, Masashi Mizokami
Journal of Gastroenterology.2011; 46(1): 9. CrossRef
Fulminant Hepatic Failure with Hepatitis B Virus Reactivation after Rituximab Treatment in a Patient with Resolved Hepatitis B
Seong Min Chung, Joo Hyun Sohn, Tae Yeob Kim, Ki Deok Yoo, Yong Woo Ahn, Joong Ho Bae, Yong Cheol Jeon, Jung Hye Choi
The Korean Journal of Gastroenterology.2010; 55(4): 266. CrossRef
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Alessandro Allegra, Giuseppa Penna, Andrea Alonci, Angela Granata, Arianna D’Angelo, Caterina Musolino
Medical Oncology.2010; 27(3): 912. CrossRef

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Original Articles

Glucose Transporter-1 Expression in Squamous Cell Carcinoma of the Tongue: Yoon Seok Choi, Seok Jin Kim, Dae Sik Kim, Seh Jong Park, Yong Park, Hye Jin Shin, Kwang-Yoon Jung, Seung-Kuk Baek, Bong Kyung Shin, Jung Woo Choi, Byung Soo Kim, Sang Won Shin, Yeul Hong Kim, Jun Suk Kim; Cancer Res Treat. 2007;39(3):109-115. Published online September 30, 2007; DOI: https://doi.org/10.4143/crt.2007.39.3.109

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Purpose

Tumor cells are known to express hypoxia-related proteins such as glucose transporter-1 (Glut-1). These hypoxia-induced changes may allow tumor cells to survive under sustained hypoxic microenvironments, and the surviving tumor cell under hypoxia may develop a more aggressive phenotype and so result in a poor prognosis.

Materials and Methods

The Glut-1 expression was analyzed by immunohistochemistry, and its association with the prognosis was assessed in 60 patients with squamous cell carcinoma of the tongue.

Results

The Glut-1 expression was diffuse with a membranous pattern, and the median percentage of Glut-1 positive tumor cells was 60% (range: 0.0~90.0%). A high Glut-1 expression (the percentage of positive tumor cells ≥ the median value, 60%) was associated with the location of primary lesion, lymph node metastasis status and disease stage (p<0.05). The expression of Glut-1 was correlated with the Ki-67 expression (r=0.406, p=0.001). Microvessel density, as represented by CD31 staining, was also correlated with the Glut-1 expression although its significance is weak (r=0.267, p=0.039). On the univariate analysis, the group with a high Glut-1 expression showed poorer overall survival than the group with a low Glut-1 expression (p<0.05). However, the Glut-1 expression failed to show any independent prognostic significance on the multivariate analysis.

Conclusion

The expression of Glut-1 may be useful for predicting the prognosis and determining the treatment strategy for the management of squamous cell carcinoma of the tongue.

Citations

Citations to this article as recorded by

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