• Journal of Digestive Cancer Reports
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• 제9권1호
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• pp.33-36
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• 2021

• Journal of Life Science
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• 제9권1호
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• pp.58-63
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• 1999

Highly metastatic mouse T-lymphoma CS21 cells can grow in vitro when cocultured with CA12 lymph node stromal cells, but they undergo apoptotic cell death when separated from CA12 stromal cells. It has been found that cysteine and interleukin-7(IL-7) as antiapoptotic soluble factors that produced by CA12 stromal cells. In this study, we report that an ICE family protease is activated in CS21 cells when separated from CA12 stromal cells and cultured alone. Enzyme purification using an avidin affinity column revealed that the involved cysteine protease possessed caspase3-like death protease activity. In addition, when IL-7 was added to CS21 cell culture, the protease activity could not be detected during partial purification of the enzyme. Taken together, these results strongly suggest that the caspase3-like protease activation is suppressed by IL-7 as an antiapoptotic factor that leads to abrogation of apoptosis execution.

• Biomolecules & Therapeutics
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• 제30권5호
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• pp.435-446
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• 2022

The present study evaluated the anti-cancer activity of histone deacetylase (HDAC)-inhibiting CKD-581 in multiple myeloma (MM) and its pharmacological mechanisms. CKD-581 potently inhibited a broad spectrum of HDAC isozymes. It concentration-dependently inhibited proliferation of hematologic cancer cells including MM (MM.1S and RPMI8226) and T cell lymphoma (HH and MJ). It increased the expression of the dishevelled binding antagonist of β-catenin 3 (DACT3) in T cell lymphoma and MM cells, and decreased the expression of c-Myc and β-catenin in MM cells. Additionally, it enhanced phosphorylated p53, p21, cleaved caspase-3 and the subG1 population, and reversely, downregulated cyclin D1, CDK4 and the anti-apoptotic BCL-2 family. Finally, administration of CKD-581 exerted a significant anti-cancer activity in MM.1S-implanted xenografts. Overall, CKD-581 shows anticancer activity via inhibition of the Wnt/β-catenin signaling pathway in hematologic malignancies. This finding is evidence of the therapeutic potential and rationale of CKD-581 for treatment of MM.

• Childhood Kidney Diseases
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• 제21권1호
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• pp.31-34
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• 2017

Tumor lysis syndrome is a serious complication of malignancy, resulting from the massive and rapid release of cellular components into the blood. Generally, it occurs after initiation of chemotherapy. The onset of spontaneous tumor lysis syndrome (STLS) before anti-cancer treatment is rare and occurs mostly in Burkitt lymphoma and non-Hodgkin's lymphoma. There are only a few case reports in children. Here, we report a case of STLS secondary to T-cell acute lymphoblastic leukemia (ALL), which presented with urinary stone and subsequent acute kidney injury with severe hyperuricemia. Occult malignancy should be considered in case of unexplained acute kidney injury with extreme hyperuricemia.

• 한국임상수의학회지
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• 제26권5호
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• pp.419-422
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• 2009

개의 림프종을 분자유전자학적으로 진단하고자 본 연구를 수행하였다. 이를 위하여 12개의 염색 및 고정된 도말 표본으로부터 DNA를 추출한 후, 임파육종에 특이적인 재배열된 항원 수용체 유전자를 중합효소연쇄반응으로 증폭시켰다. 그 결과 6개의 type-B 림프종에서 type-B 세포의 림프종에 특이적인 IgH (immunoglobulin H) 주유전자(major gene)와 type-B 림프종의 부유전자(minor gene)가 증폭되었다. 또한, 3개의 type-T 세포의 림프종의 경우에도 이에 특이적인 $TCR{\gamma}$ 유전자가 증폭되었다. 한편, 에를리키아증에 이환된 표본은 $TCR{\gamma}$ 유전자가 위양성으로 증폭되었지만, 활성화된 림프절 샘플의 경우에는 어떤 유전자의 재배열도 관찰되지 않았다. 따라서 림프종의 진단에 있어서 혈액 또는 조직 도말 표본의 DNA를 이용하여 재배열된 항원 수용체 유전자의 검출을 시도한다면, 특이적이고 객관적으로 림프종을 감별진단 할 수 있을 것이며, 나아가 회고적 분석에도 유용하게 활용될 수 있을 것으로 사료된다.

• 한국환경성돌연변이발암원학회지
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• 제21권1호
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• pp.44-50
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• 2001

To identify nongenotoxic carcinogen determined as negative by ICH guideline-recommended standard genotoxicity test battery; Ames test, chromosome aberration assay, mouse lymphoma $tk^{+/-}$ assay, in vivo micronucleus assay, we picked bisphenol A as a model compound. In this study, we applied in vitro BalB/c 3T3 cell transformation assay and Syrian hamster embryo (SHE) cell transfarmation assay. Bisphenol A was treated upto $769.2 ug/m{\ell}$ in BalB/c 3T3 cells and upto $125 ug/m{\ell}$ in SHE cells. bisphenol A didn't induced morphological transformation both with one stage treatment protocol and with two stage treatment protocol. But, treated far 48 hr, Bisphenol A induced morphological transformation significantly in SHE cells.

• Genomics & Informatics
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• 제14권3호
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• pp.78-84
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• 2016

Extranodal natural killer (NK)/T-cell lymphoma, nasal type (NKTCL), is a malignant disorder of cytotoxic lymphocytes of NK or T cells. It is an aggressive neoplasm with a very poor prognosis. Although extranodal NKTCL reportedly has a strong association with Epstein-Barr virus, the molecular pathogenesis of NKTCL has been unexplored. The recent technological advancements in next-generation sequencing (NGS) have made DNA sequencing cost- and time-effective, with more reliable results. Using the Ion Proton Comprehensive Cancer Panel, we sequenced 409 cancer-related genes to identify somatic mutations in five NKTCL tissue samples. The sequencing analysis detected 25 mutations in 21 genes. Among them, KMT2D, a histone modification-related gene, was the most frequently mutated gene (four of the five cases). This result was consistent with recent NGS studies that have suggested KMT2D as a novel driver gene in NKTCL. Mutations were also found in ARID1A, a chromatin remodeling gene, and TP53, which also recurred in recent NGS studies. We also found mutations in 18 novel candidate genes, with molecular functions that were potentially implicated in cancer development. We suggest that these genes may result in multiple oncogenic events and may be used as potential bio-markers of NKTCL in the future.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6275-6281
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• 2014

Nasal-type extranodal natural killer (NK)/T-cell lymphoma (ENKL) is a highly invasive cancer with a poor prognosis. More effective and safer treatment regimens for ENKL are needed. Pegaspargase (PEG-Asp) has a similar mechanism of action to L-asparaginase (L-Asp), but presents lower antigenicity. The aim of the present research was to evaluate the safety profile and the latent efficacy of a PEG-Asp-based treatment regimen in patients with ENKL. Data collected from 20 patients with histologically confirmed ENKL, admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to August 2013, were included in the study. All patients received $2500IU/m^2$/IM PEG-Asp on day 1 of every 21-day treatment cycle. Patients received combination chemotherapy with CHOP (n=5), EPOCH (n=7), GEMOX (n=7) or CHOP with bleomycin (n=1). After 2-5 treatment cycles (median, 4 cycles) of PEG-Asp-based chemotherapy, five patients (25%) showed a complete response (CR), and the overall response rate (ORR) was 60%. Grade 3/4 neutropenia occurred in fourteen patients (70%). Grade 3 alanine aminotransferase (ALT) elevation was observed in two. Grade 1-2 non-hematological toxicity consisted of activated partial thromboplastin time (APTT) elongation (n=9), hypofibrinogenemia (n=6), hypoproteinemia (n=17), hyperglycemia (n=3), and nausea (n=6). No allergic reactions were detected. No treatment related death was reported. Our results suggested that PEG-Asp-based chemotherapy presented an acceptable tolerance and a potential short-term outcome in patients with nasal-type ENKL.

• Investigative Magnetic Resonance Imaging
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• 제21권1호
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• pp.9-19
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• 2017

Background: Normalized cerebral blood volume (nCBV) can be measured using manual or semiautomatic segmentation method. However, the difference in diagnostic performance on brain tumor differentiation between differently measured nCBV has not been evaluated. Purpose: To compare the diagnostic performance of manually obtained nCBV to that of semiautomatically obtained nCBV on glioblastoma (GBM) and primary central nervous system lymphoma (PCNSL) differentiation. Materials and Methods: Histopathologically confirmed forty GBM and eleven PCNSL patients underwent 3T MR imaging with dynamic susceptibility contrast-enhanced perfusion MR imaging before any treatment or biopsy. Based on the contrast-enhanced T1-weighted imaging, the mean nCBV (mCBV) was measured using the manual method (manual mCBV), random regions of interest (ROIs) placement by the observer, or the semiautomatic segmentation method (semiautomatic mCBV). The volume of enhancing portion of the tumor was also measured during semiautomatic segmentation process. T-test, ROC curve analysis, Fisher's exact test and multivariate regression analysis were performed to compare the value and evaluate the diagnostic performance of each parameter. Results: GBM showed a higher enhancing volume (P = 0.0307), a higher manual mCBV (P = 0.018) and a higher semiautomatic mCBV (P = 0.0111) than that of the PCNSL. Semiautomatic mCBV had the highest value (0.815) for the area under the curve (AUC), however, the AUCs of the three parameters were not significantly different from each other. The semiautomatic mCBV was the best independent predictor for the GBM and PCNSL differential diagnosis according to the stepwise multiple regression analysis. Conclusion: We found that the semiautomatic mCBV could be a better predictor than the manual mCBV for the GBM and PCNSL differentiation. We believe that the semiautomatic segmentation method can contribute to the advancement of perfusion based brain tumor evaluation.

• Korean Journal of Radiology
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• 제25권2호
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• pp.189-198
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• 2024

Objective: To investigate the prognostic utility of radiomics features extracted from ¹⁸F-fluorodeoxyglucose (FDG) PET/CT combined with clinical factors and metabolic parameters in predicting progression-free survival (PFS) and overall survival (OS) in individuals diagnosed with extranodal nasal-type NK/T cell lymphoma (ENKTCL). Materials and Methods: A total of 126 adults with ENKTCL who underwent ¹⁸F-FDG PET/CT examination before treatment were retrospectively included and randomly divided into training (n = 88) and validation cohorts (n = 38) at a ratio of 7:3. Least absolute shrinkage and selection operation Cox regression analysis was used to select the best radiomics features and calculate each patient's radiomics scores (RadPFS and RadOS). Kaplan-Meier curve and Log-rank test were used to compare survival between patient groups risk-stratified by the radiomics scores. Various models to predict PFS and OS were constructed, including clinical, metabolic, clinical + metabolic, and clinical + metabolic + radiomics models. The discriminative ability of each model was evaluated using Harrell's C index. The performance of each model in predicting PFS and OS for 1-, 3-, and 5-years was evaluated using the time-dependent receiver operating characteristic (ROC) curve. Results: Kaplan-Meier curve analysis demonstrated that the radiomics scores effectively identified high- and low-risk patients (all P < 0.05). Multivariable Cox analysis showed that the Ann Arbor stage, maximum standardized uptake value (SUVmax), and RadPFS were independent risk factors associated with PFS. Further, β2-microglobulin, Eastern Cooperative Oncology Group performance status score, SUVmax, and RadOS were independent risk factors for OS. The clinical + metabolic + radiomics model exhibited the greatest discriminative ability for both PFS (Harrell's C-index: 0.805 in the validation cohort) and OS (Harrell's C-index: 0.833 in the validation cohort). The time-dependent ROC analysis indicated that the clinical + metabolic + radiomics model had the best predictive performance. Conclusion: The PET/CT-based clinical + metabolic + radiomics model can enhance prognostication among patients with ENKTCL and may be a non-invasive and efficient risk stratification tool for clinical practice.