• Title/Summary/Keyword: cancer progression

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Diagnosis of Chronic Kidney Disease using Sonography (초음파 영상을 이용한 만성 콩팥병의 진단)

  • Ahn, Yu-Ji;Ye, Soo-Young
    • Journal of the Korean Society of Radiology
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    • v.11 no.3
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    • pp.153-159
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    • 2017
  • Chronic kidney disease can be treated if it is detected early, but as the disease progresses, it becomes impossible to recover. Finally, renal replacement therapy such as transplantation or dialysis should be used. Ultrasonography is used to diagnose kidney cancer, inflammatory disease, nodular disease, and chronic kidney disease. It is used to identify information about degree of inflammation using information such as kidney size, internal echo characteristics. Currently, the degree of disease in the clinic uses the value of glomerular filtration rate. However, even in ultrasound, changes in the degree of inflammation and disease can be observed. In this study, we used ultrasound images to quantify the changes in brightness, size, cortex, and subclinical changes of the kidney with progression of the disease, and compared them with the glomerular filtration rate used in clinical practice. In 105 cases, we performed 35 cases of normal kidney, 35 cases of early kidney disease, and 35 cases of terminal kidney. The brightness of the cortex of the image was obtained and the difference in brightness between the cortex and the proximal portion was obtained by the slope. The graph of the portion which was not smooth due to the ultrasonic characteristics was used as the function regrass. The size reduction was obtained from the original data. The results were as follows: It was proportional to the glomerular filtration rate. It is considered that the algorithm can be applied to the disease if the algorithm study continues.

Expression of p53 and Ki-67 in Cervical Dysplasia with Human Papilloma Virus Infection or Non-infection (인유두종 바이러스의 감염 또는 감염되지 않은 자궁 경부 이형성증에서 p53 및 Ki-67의 발현)

  • Choi, Sook-Kyung;Kim, Tai Jeon;Hong, Seung Bok;Lee, Hun Taeck
    • Korean Journal of Clinical Laboratory Science
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    • v.36 no.2
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    • pp.178-184
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    • 2004
  • This research focuses on the overall evaluation of tumor protein (p53) and cell growth marker (Ki-67) in their functions as carcinogenic factors in both a HPV-infected group and in a HPV-noninfected group with the precancerous dysplasia of uterine cervix. Histological grades were determined by the H&E staining and the expression level of p53 and Ki-67 were tested by the immunohistochemistry method. The results were as follows. Among the total of 66 cases, p53 (+) was observed in 19 cases (29.0%) from the mild grade group, 22 cases (33.0%) from the moderate grade group, and 19 cases (29.0%) from the severe grade group. The values correlate with the increase of dysplasia intensity in HPV-noninfected group and showed significant correlation (p<0.05), but there were no significant difference from the HPV-infected group. Among a total of 66 cases, the mitotic index of Ki-67 (+) were observed in 19 cases (29.0%) from the mild grade group, 22 cases (33.0%) from the moderate grade group, and 19 cases (29.0%) from the severe grade group. The values were significantly different against dysplasia intensity (p<0.05), but showed no significant difference from HPV infection. After cross comparing the statistical parameters of p53 and ki-67 in their significance, p53 was shown to be statistically significant with Ki-67 while there was no statistically significant difference with Ki-67 (p<0.05). Taken together, tumor protein (p53) and an index of Ki-67 observed in cervical dysplasia and in HPV related dysplasia of cervix uterine did not have any notable significance with HPV infection. The incidence rate of p53, however, had some significant correlation with dysplasia while Ki-67 had no particular statistical significance. As a result, p53 and Ki-67 can be considered as effective diagnostic markers in predicting the disease progression of dysplasia to cervical cancer.

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The Relationship between the Polymorphism of CYP1A1, GSTM1, GSTT1, GSTP1 and p53 Overexpression in Head and Neck Squamous Cell Carcinoma (두경부 편평세포암종에서 CYP1A1, GSTM1, GSTT1, GSTP1 유전자 다형성 및 p53 과발현)

  • Tae Kyung;Park Hye-Kyung;Lee Seung-Hwan;Kim Kyung-Rae;Lee Hyung-Seok
    • Korean Journal of Head & Neck Oncology
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    • v.19 no.2
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    • pp.148-157
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    • 2003
  • Background and Objectives: Individual genetic susceptibilities to chemical carcinogens have been recognized as a major important host factors in human cancers. The cytochrome P450 family (CYPs) and glutathione S-transferase(GST) have been reported to be associated with risks to the smoking-related human cancers. Inactivation of tumor suppressor genes like p53 playa key role in tumor progression. The purpose of this study is to demonstrate an association between p53 overexpression and the prevalence of the genetic polymorphisms of CYP1A1 and GSTs in Korean head and neck squamous cell carcinoma (HNSCC). Materials and Methods: The polymorphisms of CYPIA1 and GSTs were analyzed by PCR and PCR-RFLP in 98 Korean head and neck squamous cell carcinoma patients. The expression of p53 was analyzed by immunohistochemistry with anti-p53 Ab (DO7). Results: Overexpression of p53 detected in 45.9% of HNSCC. The odds ratio for p53 overexpression in GSTM1(-), GSTT1(-), GSTP1(val/val) and CYP1A1(val/val) were 1.53, 1.83, 1.17 and 1.47, respectively. Among the combined genotypes, the odds ratio of the CYP1A1 val/val, GSTM1 (-), CYP1A1 val/val, GSTT1(-), and CYP1A1 val/val, GSTT1(-) were 2.0, 2.34 and 4.68, respectively. Conclusion: Based on our results, it might be suggested that p53 overexpression is slightly increased in GSTM1(-), GSTT1(-), GSTP1 val/val, CYP1A1 val/val genotypes. The further study is needed to evaluate the relationship and mechanism between the p53 overexpression and the specific CYP1A1 and GSTs genotypes.

Comparison of Exercise Pulmonary Function Test Using by Treadmill and Bicycle Ergometer in Patients with Respiratory Diseases (호흡기 질환 환자에서 자전거 타기와 답차를 이용한 운동 부하 폐기능 검사의 비교)

  • Park, Ji-Hyun;Lee, Heung-Bum;Lee, Yong-Chul;Rhee, Yang-Kuen
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.3
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    • pp.386-393
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    • 1999
  • Objective : Cardiopulmonary exercise testing in patients with heart and lung problems is used to assess functional capacity, evaluate responses to medical treatment, plan for exercise therapy, assess progression of disease process, and determine prognosis. Particularly in the patients with lung cancer, the exercise pulmonary function test gives significant physiologic assessment of the lung resection candidate. Common exercise modalities are running and cycling. Until now, the comparison of two tests mainly has been done in normal person and patients with cardiac diseases. This study is designed to compare the treadmill and bicycle exercise pulmonary function test in patients with respiratory diseases. Methods : Twenty one patients underwent a progressively incremental exercise test to the symptom-limited stage with the treadmill (Vmax29 Sensor Medics, USA) and the bicycle(model No. 2,900 Sensor Medics, USA) with 7 days apart between the two tests. Measurements were made of the metabolic, cardiorespiratory parameters, blood gases, and symptoms. Results : The results of the treadmill exercise showed significant elevation in the $VO_2$max, VEmax, and anaerobic threshold compared to those of bicycle exercise. In contrast, the results of the breathing and heart rate reserve showed the reverse. Conclusion : These results suggest that the type of exercise should be taken into consideration when interpreting exercise test in patients with respiratory diseases.

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G1 Arrest of U937 Human Monocytic Leukemia Cells by Sodium Butyrate, an HDAC Inhibitor, Via Induction of Cdk Inhibitors and Down-regulation of pRB Phosphorylation (Cdk inhibitors의 발현 증가 및 pRB 인산화 저해에 의한 HDAC inhibitor인 sodium butyrate에 의한 인체백혈병세포의 G1 arrest유발)

  • Choi, Yung-Hyun
    • Journal of Life Science
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    • v.19 no.7
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    • pp.871-877
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    • 2009
  • We investigated the effects of sodium butyrate, a histone deacetylase inhibitor, on the cell cycle progression in human monocytic leukemia U937 cells. Exposure of U937 cells to sodium butyrate resulted in growth inhibition, G1 arrest of the cell cycle and induction of apoptosis in a dose-dependent manner as measured by MTT assay and flow cytometry analysis. The increase in G1 arrest was associated with the down-regulation in cyclin D1, E, A, cyclin-dependent kinase (Cdk) 4 and 6 expression, and up-regulation of Cdk inhibitors such as p21 and p27. Sodium butyrate treatment also inhibited the phosphorylation of retinoblastoma protein (pRB) and p130, however, the levels of transcription factors E2F-1 and E2F-4 were not markedly modulated. Furthermore, the down-regulation of phosphorylation of pRB and p130 by this compound was associated with enhanced binding of pRB and E2F-1, as well as p130 and E2F-4, respectively. Overall, the present results demonstrate a combined mechanism involving the inhibition of pRBjp130 phosphorylation and induction of Cdk inhibitors as targets for sodium butyrate that may explain some of its anti-cancer effects in U937 cells.

Prognostic value of nodal SUVmax of 18F-FDG PET/CT in nasopharyngeal carcinoma treated with intensity-modulated radiotherapy

  • Lee, So Jung;Kay, Chul-Seoung;Kim, Yeon-Sil;Son, Seok Hyun;Kim, Myungsoo;Lee, Sea-Won;Kang, Hye Jin
    • Radiation Oncology Journal
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    • v.35 no.4
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    • pp.306-316
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    • 2017
  • Purpose: To investigate the predictive role of maximum standardized uptake value ($SUV_{max}$) of 2-[$^{18}F$]fluoro-2-deoxy-D-glucose($^{18}F-FDG$) positron emission tomography/computed tomography (PET/CT) in nasopharyngeal cancer patients treated with intensity-modulated radiotherapy (IMRT). Materials and Methods: Between October 2006 and April 2016, 53 patients were treated with IMRT in two institutions and their PET/CT at the time of diagnosis was reviewed. The $SUV_{max}$ of their nasopharyngeal lesions and metastatic lymph nodes (LN) was recorded. IMRT was delivered using helical tomotherapy. All patients except for one were treated with concurrent chemoradiation therapy (CCRT). Correlations between $SUV_{max}$ and patients' survival and recurrence were analyzed. Results: At a median follow-up time of 31.5 months (range, 3.4 to 98.7 months), the 3-year overall survival (OS) and disease-free survival (DFS) rates were 83.2% and 77.5%, respectively. In univariate analysis, patients with a higher nodal pre-treatment $SUV_{max}$ (${\geq}13.4$) demonstrated significantly lower 3-year OS (93.1% vs. 55.5%; p = 0.003), DFS (92.7% vs. 38.5%; p < 0.001), locoregional recurrence-free survival (100% vs. 50.5%; p < 0.001), and distant metastasis-free survival (100% vs. 69.2%; p = 0.004), respectively. In multivariate analysis, high pre-treatment nodal $SUV_{max}$ (${\geq}13.4$) was a negative prognostic factor for OS (hazard ratio [HR], 7.799; 95% confidence interval [CI], 1.506-40.397; p = 0.014) and DFS (HR, 9.392; 95% CI, 1.989-44.339; p = 0.005). Conclusions: High pre-treatment nodal $SUV_{max}$ was an independent prognosticator of survival and disease progression in nasopharyngeal carcinoma patients treated with IMRT in our cohort. Therefore, nodal $SUV_{max}$ may provide important information for identifying patients who require more aggressive treatment.

Effect of Ailanthi Cortex on the Apoptosis and Cell Cycle of HL-60 Leukemia Cell Line (HL-60 백혈병 세포의 세포고사에 미치는 저근백피의 효과)

  • Jeong Young Mok;Park Sin Ki;Lee Jun;Kim Young Mok;Yun Yong Gab;Kim Won Sin;Han Dong Min;An Won Gun;Yoon Yoo Sik;Jeon Byung Hun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.4
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    • pp.914-922
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    • 2003
  • Ailanthus altissima has been used to settle an upset stomach, to alleviate a fever, and as an insecticide. We reported that the water extract of A. altissima induced apoptotic cell death in HL-60 human leukemia cell line. Here, we showed the dose-dependent inhibitions of cell viability by the extract, as measured by cell morphology. The cell cycle control genes are considered to play important roles in tumorigenesis. The purpose of the present study is also to investigate the effect of A. altissima on cell cycle progression and its molecular mechanism in the cells. The level of p21 protein was increased after treatment of the extract, whereas both Bcl-2 and Bax protein levels were not changed. These results suggest that A. altissima induces apoptotic cell death via p21-dependent signaling pathway in HL-60 human leukemia cell line which delete wild type p53. G1 checkpoin related gene products tested (cyclin D3, cyclin dependent kinase 4, retinoblastoma, E2F1) were decreased in their protein levels in a dose-dependent manner after treatment of the extract. Taken together, these results indicate that the increase of apoptotic cell death by A. altissima may be due to the inhibition of cell cycle in HL-60 human leukemia cell line

Pathophysiological Functions of Deubiquitinating Enzymes in Obesity and Related Metabolic Diseases (탈유비퀴틴화 효소 DUBs의 비만 및 대사 관련 질환에서 병태생리학적 기능)

  • Lee, Seul Gi;Kwon, Taeg Kyu
    • Journal of Life Science
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    • v.32 no.6
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    • pp.476-481
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    • 2022
  • Ubiquitin signaling regulates virtually all aspects of eukaryotic biology and dynamic processes in which protein substrates are modified by ubiquitin. To regulate these processes, deubiquitinating enzymes (DUBs) cleave ubiquitin or ubiquitin-like proteins from these substrates. DUBs have been implicated in the pathogenesis of cancer, leading to the development of increasing numbers of small-molecule DUB inhibitors. On the other hand, recent studies have focused on the function of DUBs in metabolic diseases such as obesity, diabetes, and fatty liver diseases. DUBs play a positive or negative role in the progression and development of metabolic diseases. Their involvement in cell pathology and regulation of major transcription factors in metabolic syndrome has been examined in vitro and in animal and human biopsies. UCH, USP7, and USP19 were linked to adipocyte differentiation, body weight gain, and insulin resistance in genetic or diet-induced obesity. CYLD, USP4, and USP18 were found to be closely associated with fatty liver diseases. In addition, these liver diseases were accompanied by body weight change in certain cases. Collectively, in this review, we discuss the current understanding of DUBs in metabolic diseases with a particular focus on obesity. We also provide basic knowledge and regulatory mechanisms of DUBs and suggest these enzymes as therapeutic targets for metabolic diseases.

SKP2 Contributes to AKT Activation by Ubiquitination Degradation of PHLPP1, Impedes Autophagy, and Facilitates the Survival of Thyroid Carcinoma

  • Yuan Shao;Wanli Ren;Hao Dai;Fangli Yang;Xiang Li;Shaoqiang Zhang;Junsong Liu;Xiaobao Yao;Qian Zhao;Xin Sun;Zhiwei Zheng;Chongwen Xu
    • Molecules and Cells
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    • v.46 no.6
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    • pp.360-373
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    • 2023
  • Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid carcinoma. Despite a good prognosis, approximately a quarter of PTC patients are likely to relapse. Previous reports suggest an association between S-phase kinase-associated protein 2 (SKP2) and the prognosis of thyroid cancer. SKP1 is related to apoptosis of PTC cells; however, its role in PTC remains largely elusive. This study aimed to understand the expression and molecular mechanism of SKP2 in PTC. SKP2 expression was upregulated in PTC tissues and closely associated with clinical diagnosis. In vitro and in vivo knockdown of SKP2 expression in PTC cells suppressed cell growth and proliferation and induced apoptosis. SKP2 depletion promoted cell autophagy under glucose deprivation. SKP2 interacted with PH domain leucine-rich repeat protein phosphatase-1 (PHLPP1), triggering its degradation by ubiquitination. Furthermore, SKP2 activates the AKT-related pathways via PHLPP1, which leads to the cytoplasmic translocation of SKP2, indicating a reciprocal regulation between SKP2 and AKT. In conclusion, the upregulation of SKP2 leads to PTC proliferation and survival, and the regulatory network among SKP2, PHLPP1, and AKT provides novel insight into the molecular basis of SKP2 in tumor progression.

Imaging-Based Versus Pathologic Survival Stratifications of Diffuse Glioma According to the 2021 WHO Classification System

  • So Jeong Lee;Ji Eun Park;Seo Young Park;Young-Hoon Kim;Chang Ki Hong;Jeong Hoon Kim;Ho Sung Kim
    • Korean Journal of Radiology
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    • v.24 no.8
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    • pp.772-783
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    • 2023
  • Objective: Imaging-based survival stratification of patients with gliomas is important for their management, and the 2021 WHO classification system must be clinically tested. The aim of this study was to compare integrative imaging- and pathology-based methods for survival stratification of patients with diffuse glioma. Materials and Methods: This study included diffuse glioma cases from The Cancer Genome Atlas (training set: 141 patients) and Asan Medical Center (validation set: 131 patients). Two neuroradiologists analyzed presurgical CT and MRI to assign gliomas to five imaging-based risk subgroups (1 to 5) according to well-known imaging phenotypes (e.g., T2/FLAIR mismatch) and recategorized them into three imaging-based risk groups, according to the 2021 WHO classification: group 1 (corresponding to risk subgroup 1, indicating oligodendroglioma, isocitrate dehydrogenase [IDH]-mutant, and 1p19q-codeleted), group 2 (risk subgroups 2 and 3, indicating astrocytoma, IDH-mutant), and group 3 (risk subgroups 4 and 5, indicating glioblastoma, IDHwt). The progression-free survival (PFS) and overall survival (OS) were estimated for each imaging risk group, subgroup, and pathological diagnosis. Time-dependent area-under-the receiver operating characteristic analysis (AUC) was used to compare the performance between imaging-based and pathology-based survival model. Results: Both OS and PFS were stratified according to the five imaging-based risk subgroups (P < 0.001) and three imaging-based risk groups (P < 0.001). The three imaging-based groups showed high performance in predicting PFS at one-year (AUC, 0.787) and five-years (AUC, 0.823), which was similar to that of the pathology-based prediction of PFS (AUC of 0.785 and 0.837). Combined with clinical predictors, the performance of the imaging-based survival model for 1- and 3-year PFS (AUC 0.813 and 0.921) was similar to that of the pathology-based survival model (AUC 0.839 and 0.889). Conclusion: Imaging-based survival stratification according to the 2021 WHO classification demonstrated a performance similar to that of pathology-based survival stratification, especially in predicting PFS.