• Title/Summary/Keyword: B lymphoma

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Cordycepin Enhanced Therapeutic Potential of Gemcitabine against Cholangiocarcinoma via Downregulating Cancer Stem-Like Properties

  • Hong Kyu Lee;Yun-Jung Na;Su-Min Seong;Dohee Ahn;Kyung-Chul Choi
    • Biomolecules & Therapeutics
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    • v.32 no.3
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    • pp.368-378
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    • 2024
  • Cordycepin, a valuable bioactive component isolated from Cordyceps militaris, has been reported to possess anti-cancer potential and the property to enhance the effects of chemotherapeutic agents in various types of cancers. However, the ability of cordycepin to chemosensitize cholangiocarcinoma (CCA) cells to gemcitabine has not yet been evaluated. The current study was performed to evaluate the above, and the mechanisms associated with it. The study analyzed the effects of cordycepin in combination with gemcitabine on the cancer stem-like properties of the CCA SNU478 cell line, including its anti-apoptotic, migratory, and antioxidant effects. In addition, the combination of cordycepin and gemcitabine was evaluated in the CCA xenograft model. The cordycepin treatment significantly decreased SNU478 cell viability and, in combination with gemcitabine, additively reduced cell viability. The cordycepin and gemcitabine co-treatment significantly increased the Annexin V+ population and downregulated B-cell lymphoma 2 (Bcl-2) expression, suggesting that the decreased cell viability in the cordycepin+gemcitabine group may result from an increase in apoptotic death. In addition, the cordycepin and gemcitabine co-treatment significantly reduced the migratory ability of SNU478 cells in the wound healing and trans-well migration assays. It was observed that the cordycepin and gemcitabine cotreatment reduced the CD44highCD133high population in SNU478 cells and the expression level of sex determining region Y-box 2 (Sox-2), indicating the downregulation of the cancer stem-like population. Cordycepin also enhanced oxidative damage mediated by gemcitabine in MitoSOX staining associated with the upregulated Kelch like ECH Associated Protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) expression ratio. In the SNU478 xenograft model, co-administration of cordycepin and gemcitabine additively delayed tumor growth. These results indicate that cordycepin potentiates the chemotherapeutic property of gemcitabine against CCA, which results from the downregulation of its cancer-stem-like properties. Hence, the combination therapy of cordycepin and gemcitabine may be a promising therapeutic strategy in the treatment of CCA.

Diagnostic Performance of 18F-Fluorodeoxyglucose Positron Emission Tomography/CT for Chronic Empyema-Associated Malignancy

  • Miju Cheon;Jang Yoo;Seung Hyup Hyun;Kyung Soo Lee;Hojoong Kim;Jhingook Kim;Jae Il Zo;Young Mog Shim;Joon Young Choi
    • Korean Journal of Radiology
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    • v.20 no.8
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    • pp.1293-1299
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    • 2019
  • Objective: The purpose of this study was to evaluate the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for chronic empyema-associated malignancy (CEAM). Materials and Methods: We retrospectively reviewed the 18F-FDG PET/CT images of 33 patients with chronic empyema, and analyzed the following findings: 1) shape of the empyema cavity, 2) presence of fistula, 3) maximum standardized uptake value (SUV) of the empyema cavity, 4) uptake pattern of the empyema cavity, 5) presence of a protruding soft tissue mass within the empyema cavity, and 6) involvement of adjacent structures. Final diagnosis was determined based on histopathology or clinical follow-up for at least 6 months. The abovementioned findings were compared between the 18F-FDG PET/CT images of CEAM and chronic empyema. A receiver operating characteristic (ROC) analysis was also performed. Results: Six lesions were histopathologically proven as malignant; there were three cases of diffuse large B-cell lymphoma, two of squamous cell carcinoma, and one of poorly differentiated carcinoma. Maximum SUV within the empyema cavity (p < 0.001) presence of a protruding soft tissue mass (p = 0.002), and involvement of the adjacent structures (p < 0.001) were significantly different between the CEAM and chronic empyema images. The maximum SUV exhibited the highest diagnostic performance, with the highest specificity (96.3%, 26/27), positive predictive value (85.7%, 6/7), and accuracy (97.0%, 32/33) among all criteria. On ROC analysis, the area under the curve of maximum SUV was 0.994. Conclusion: 18F-FDG PET/CT can be useful for diagnosing CEAM in patients with chronic empyema. The maximum SUV within the empyema cavity is the most accurate 18F-FDG PET/CT diagnostic criterion for CEAM.

Leukoencephalopathy after CNS Prophylactic Therapy in Pediatric Hematologic Malignancy (소아 혈액종양 환자에서 중추신경계 예방적 치료 후 발생한 백질뇌병증)

  • Lee, Jun Hwa;Lee, Sun Min;Choi, Eun Jin;Lee, Kun Soo
    • Clinical and Experimental Pediatrics
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    • v.46 no.6
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    • pp.566-571
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    • 2003
  • Purpose : Leukoencephalopathy(LE) is one of the most serious complications in children with hematologic malignancies during the course of treatment. Early recognition is important to reduce the impact and sequelae from LE. We therefore investigated the clinical features of LE following central nervous system(CNS) prophylaxis in children with hematologic malignancies and evaluated the significance of regular check-ups of brain MRI. Methods : We retrospectively reviewed children with hematologic malignancies who had CNS prophylaxis including intrathecal(IT) methotrexate(MTX) and/or cranial irradiation at the Department of Pediatrics, Kyungpook National University Hospital from Oct. 1995 to May 2002. Fifteen cases of acute leukemia and one case of lymphoma who experienced LE following CNS prophylaxis were included in the study. Clinical data were analyzed from the medical records and brain MRIs were reviewed by neuroradiologists. Results : The ages ranged from 1 to 13 years(median age=5.2 years), and the male to female ratio was 3 : 1. The time interval from the beginning of chemotherapy to the time of diagnosis of LE ranged from 2 to 17 months. They all had IT MTX two to 15 times and ten underwent cranial irradiation(1,800 rads). At the time of diagnosis, ten of them had neuropsychiatric symptoms including seizures, personality changes, headache, etc. After the change of treatment modality, four cases showed significant improvement on follow-up MRIs, six cases had no significant changes and two had worsening of LE. Four patients died of infection and bone marrow relapse. Conclusion : CNS prophylaxis with IT therapy and cranial irradiation may cause leukoencephalopathy during the course of treatment. As a result, regular brain MRI check-up is recommended for the early detection and reducing the incidence of LE, along with changes in the treatment modality.

Nodal Status of the Head and Neck Cancer Patients (두경부 암 환자의 경부 림프절 전이 분석)

  • Yang, Dae-Sik;Choi, Myung-Sun;Choi, Jong-Ouck
    • Radiation Oncology Journal
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    • v.15 no.4
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    • pp.321-329
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    • 1997
  • Purpose : It is well known that the risk of lymph nodes metastases to head and neck cancers are influenced by the location and size of the Primary tumor. as well as the degree and types of histological differentiation. However, data on the statistical analyses of lymph node metastases from the head and neck cancers among Korean Population are not available at present. In order to obtain current status of such data, we have analyzed cancer patients at the department of radiation oncology, korea universityhospital for radiation treatment. Materials and Methods : We have evaluated nine-hundred and ninetyseven (997) head and neck cancer Patients who visited to the Department of radiation oncology, between November 1981 to December 1995. After careful physical examinations and CAT scan, Patients were divided into two groups, those with positive lymph node metastases and with negative lymph node metastases. The nodal status were classified according to the TNM system of American Joint Committee on Cancer (AJCC) Besults : Four-hundred and sixteen Patients out of the 997 patients were lymph node positive $(42\%)$ and 581 patients were lymph node negative $(58\%)$ when they were first presented at the department of radiation oncelogy. According to the AJCC classification, the distribution of positive lymph node is as follow: Nl:106 $(25.5\%),\;N2a:100\;(24\%),\;N2b:68\;(16.4\%),\;N2c:69\;(16.6\%),\;3:73\;(15\%).$ respectively. The frequency of lymph node metastases according to the primary sites is as follow : larynx 283 $(28.5\%)$, paranasal sinuses: 182 $(18\%),\;oropharynx:144\;(14.5\%)\;nasopharynx:122(12\%),\;oral\;cavity\;92\;(9\%),\;hypopharynx:71\;(7\%),\;falivary\;gland:58\;(6\%)$ unknown primary:31 $(3\%),\;skin:\;14(2\%)$,. The most frequent Primary site for the positive Iymph node metastases was nasopharynx $(71\%)$ followed by hypopharynx $(69\%),\;oropharynx\;(64\%),\;oral\;cavity\;(39\%)$ The most common histologic type was squamous cell carcinoma (652/997: $65.4\%$). followed by malignant lymphoma $(109/997:11\%)$. Conclusion : Statistical results of lymph node metastases from head and neck cancer at our department were very similar to those obtained from other countries. It is concluded that the location of Primary cancer influences sites of metastases on head and neck, and stage of the primary cancer also influences the development of metastatic lesions. Since the present study is limited on the data collected from one institute. further statistical analyses on Korean cancer Patients are warrented.

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Protective effect of lycopene against cytokine-induced β-cell apoptosis in INS-1 cells (라이코펜이 사이토카인에 의해 유도된 베타세포 사멸에 미치는 효과 및 기전 연구)

  • Kim, Kyong;Jang, Se-Eun;Bae, Gong Deuk;Jun, Hee-Sook;Oh, Yoon Sin
    • Journal of Nutrition and Health
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    • v.51 no.6
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    • pp.498-506
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    • 2018
  • Purpose: Lycopene, a carotenoid with anti-oxidant properties, occurs naturally in tomatoes and pink grapefruit. Although the beneficial effects of lycopene on various disorders have been established, little attention has been paid to the possible anti-diabetic effects of lycopene focusing on ${\beta}$-cells. Therefore, this study investigated the potential of lycopene to protect ${\beta}$-cells against apoptosis induced by a cytokine mixture. Methods: For toxicity experiments, the cells were treated with 0.1 ~ 10 nM of lycopene, and the cell viability in INS-1 cells (a rat ${\beta}$-cell line) was measured using a MTT assay. To induce cytokine toxicity, the cells were treated with a cytokine mixture (20 ng/mL of $TNF{\alpha}$ + 20 ng/mL of IL-$1{\beta}$) for 24 h, and the effects of lycopene (0.1 nM) on the cytokine toxicity were measured using the MTT assay. The expression levels of the apoptotic proteins were analyzed by Western blotting, and the level of intracellular reactive oxidative stress (ROS) was monitored using a DCFDA fluorescent probe. The intracellular ATP levels were determined using a luminescence kit, and mRNA expression of the genes coding for anti-oxidative stress response and mitochondrial function were analyzed by quantitative reverse-transcriptase PCR. Results: Exposure of INS-1 cells to 0.1 nM of lycopene increased the cell viability significantly, and protected the cells from cytokine-induced death. Lycopene upregulated the mRNA and protein expression of B-cell lymphoma-2 (Bcl-2) and reduced the expression of the Bcl-2 associated X (Bax) protein. Lycopene inhibited apoptotic signaling via a reduction of the ROS, and this effect correlated with the upregulation of anti-oxidative stress response genes, such as GCLC, NQO1, and HO-1. Lycopene increased the mRNA expression of mitochondrial function-related genes and increased the cellular ATP level. Conclusion: These results suggest that lycopene reduces the level of oxidative stress and improves the mitochondrial function, contributing to the prevention of cytokine-induced ${\beta}$-cell apoptosis. Therefore, lycopene could potentially serve as a preventive and therapeutic agent for the treatment of type 2 diabetes.