• Title/Summary/Keyword: checkpoint

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Role of Iridin Isolated from Iris koreana Nakai on Doxorubicin-induced Necrosis in HK-2 Cells, and Effect on Cancer Cells (노랑붓꽃에서 분리된 Iridin의 독소루비신 유도 HK-2 세포 괴사에 대한 역할 및 암세포에 대한 작용)

  • Nho, Jong Hyun;Lee, Ki Ho;Jung, Ho Kyung;Lee, Mu Jin;Jang, Ji Hun;Sim, Mi Ok;Jung, Ja Kyun;Jung, Da Eun;Cho, Hyun Woo
    • Korean Journal of Plant Resources
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    • v.31 no.2
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    • pp.95-101
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    • 2018
  • Doxorubicin is a anti-cancer drugs that interferes with the growth and spread of cancer cells in human body. Doxorubicin is used to treat different types of cancers that affect the ovary, thyoid and lungs, but induced side effect such as nephrotoxicity and cardiotoxicity. Thus, we investigated that the effect of iridin on doxorubicin-induced necrosis in HK-2 cells, a human proximal tubule cell. To confirm effect of iridin on doxorubicin-induced necrosis, HK-2 cells are treated with $10{\mu}M$ doxorubicin and $80{\mu}M$ iridin. $80{\mu}M$ iridin reduced $10{\mu}M$ doxorubicin-induced necrosis, the mitochondrial over activation and caspase-3 activation. However, iridin reduces anti-cancer effect of doxorubicin such as PARP1 and caspase-3 activation, checkpoint proteins (CDK4 and CDK6) in NCI-H1129 cells (Human non-small cell lung cancer cell). In HCT-116 cells (Human colorectan cancer cell), iridin do not increased protein expression of CDK4 and CDK6 decreased by doxorubicin. Results indicate that treatment of iridin was diminished doxorubicin-induced necrosis in HK-2 cells. However, iridin was decreased anti-cancer effect of doxorubicin on NCI-H1229, but not HCT-116. Thus, further experiment are required to iridin treatment on various cancer cells and animal models because effect of iridin different cell type.

Phenotypic Suppression of Rad53 Mutation by CYC8 (CYC8에 의한 rad53 돌연변이의 표현형 억제에 대한 연구)

  • Park, Kyoung-Jun;Choi, Do-Hee;Kwon, Sung-Hun;Kim, Joon-Ho;Bae, Sung-Ho
    • Korean Journal of Microbiology
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    • v.46 no.2
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    • pp.122-126
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    • 2010
  • RAD53 functions as an effector kinase of checkpoint pathways in Saccharomyces cerevisiae, which plays a central role to regulate many downstream cellular processes in response to DNA damage. It also involves in transcriptional activation of various genes including RNR genes which encode the key enzyme required for dNTP synthesis. In this study, we identified CYC8 as a suppressor for the hydroxyurea sensitivity of $rad53{\Delta}$ mutation. $Rad53{\Delta}$ mutant transformed with a multi-copy plasmid containing CYC8 showed increased hydroxyurea resistance. In contrast, TUP1 which forms a complex with CYC8 did not function as a suppressor. In the case of mutations, both $cyc8{\Delta}$ and $tup1{\Delta}$ suppressed hydroxyurea sensitivity of $rad53{\Delta}$. Since CYC8 can propagate as a prion in yeast, overexpression of CYC8 induced misfolding of the normal CYC8 proteins, resulting in dominant cyc8-phenotype. Therefore, it is suggested that CYC8 can act as a multi-copy suppressor due to its prion property. It was observed that the levels of RNR transcription were increased in the yeast strains containing either multi-copies of CYC8 gene or $cyc8{\Delta}$ mutation, suggesting that the increased level of RNR will elevate the intracellular pools of dNTPs, which, in turn, suppress the phenotype of $rad53{\Delta}$ mutation.

CDC6 mRNA Expression Is Associated with the Aggressiveness of Prostate Cancer

  • Kim, Ye-Hwan;Byun, Young Joon;Kim, Won Tae;Jeong, Pildu;Yan, Chunri;Kang, Ho Won;Kim, Yong-June;Lee, Sang-Cheol;Moon, Sung-Kwon;Choi, Yung-Hyun;Yun, Seok Joong;Kim, Wun-Jae
    • Journal of Korean Medical Science
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    • v.33 no.47
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    • pp.303.1-303.10
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    • 2018
  • Background: Cell division cycle 6 (CDC6) is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle. CDC6 has been associated with oncogenic activities in human cancers; however, the clinical significance of CDC6 in prostate cancer (PCa) remains unclear. Therefore, we investigated whether the CDC6 mRNA expression level is a diagnostic and prognostic marker in PCa. Methods: The study subjects included 121 PCa patients and 66 age-matched benign prostatic hyperplasia (BPH) patients. CDC6 expression was evaluated using real-time polymerase chain reaction and immunohistochemical (IH) staining, and then compared according to the clinicopathological characteristics of PCa. Results: CDC6 mRNA expression was significantly higher in PCa tissues than in BPH control tissues (P = 0.005). In addition, CDC6 expression was significantly higher in patients with elevated prostate-specific antigen (PSA) levels (> 20 ng/mL), a high Gleason score, and advanced stage than in those with low PSA levels, a low Gleason score, and earlier stage, respectively. Multivariate logistic regression analysis showed that high expression of CDC6 was significantly associated with advanced stage (${\geq}T3b$) (odds ratio [OR], 3.005; confidence interval [CI], 1.212-7.450; P = 0.018) and metastasis (OR, 4.192; CI, 1.079-16.286; P = 0.038). Intense IH staining for CDC6 was significantly associated with a high Gleason score and advanced tumor stage including lymph node metastasis stage (linear-by-linear association, P = 0.044 and P = 0.003, respectively). Conclusion: CDC6 expression is associated with aggressive clinicopathological characteristics in PCa. CDC6 may be a potential diagnostic and prognostic marker in PCa patients.

T-Cell Immunoglobulin Mucin 3 Expression on Tumor Infiltrating Lymphocytes as a Positive Prognosticator in Triple-Negative Breast Cancer

  • Byun, Kyung Do;Hwang, Hyo Jun;Park, Ki Jae;Kim, Min Chan;Cho, Se Heon;Ju, Mi Ha;Lee, Jin Hwa;Jeong, Jin Sook
    • Journal of Breast Cancer
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    • v.21 no.4
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    • pp.406-414
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    • 2018
  • Purpose: T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is an emerging immune response molecule related to T-cell anergy. There has been tremendous interest in breast cancer targeting immune checkpoint molecules, especially in the triple-negative breast cancer (TNBC). This study was designed to investigate TIM-3 expression on tumor infiltrating lymphocytes (TILs), its relationships with clinicopathological parameters and expression of programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1), and its prognostic role. Methods: Immunohistochemistry on tissue microarray blocks produced from 109 samples of invasive ductal carcinoma type TNBC was performed with antibodies toward TIM-3, PD-1, PD-L1 and breast cancer-related molecular markers. Associations between their expression and clinicopathological parameters as well as survival analyses were performed. Results: TIM-3 was expressed in TILs from all 109 TNBCs, consisting of 17 cases (<5%), 31 cases (6%-25%), 48 cases (26%-50%), and 13 cases (>51%). High TIM-3 was significantly correlated with younger patients (p=0.0101), high TILs (p=0.0029), high tumor stage (p=0.0018), high PD-1 (p=0.0001) and high PD-L1 (p=0.0019), and tended to be associated with higher histologic grade, absence of extensive in situ components and microcalcification. High TIM-3 expression was significantly associated with a combinational immunophenotype group of high PD-L1 and high PD-1 (p<0.0001). High TIM-3 demonstrated a significantly better disease-free survival (DFS) (p<0.0001) and longer overall survival (OS) (p=0.0001), together with high TILs and high PD-1. In univariate survival analysis, high TIM-3 showed reduced relapse risk (p<0.0001) and longer OS (p=0.0003), together with high PD-1 expression. In multivariate analysis, high TIM-3 was statistically significant in predicting prognosis, showing better DFS (hazard ratio [HR], 0.0994; 95% confidence interval [CI], 0.0296-0.3337; p=0.0002) and longer OS (HR, 0.1109; 95% CI, 0.0314-0.3912; p=0.0006). Conclusion: In this study, we demonstrate that TIM-3 expression is an independent positive prognostic factor in TNBC, despite its association with poor clinical and pathologic features.

Traditional Korean Medicine for Non-Small Cell Lung Cancer Patient Undergoing Pembrolizumab Immunotherapy: A Case Report (Pembrolizumab 면역치료를 시행 중인 비소세포성 폐암환자의 한방치료 증례보고)

  • Shim, So-hyun;Seo, Hee-jeong;Seo, Hyung-bum;Cho, Im-hak;Lee, Chan;Kim, So-yeon;Han, Chang-woo;Park, Seong-ha;Yun, Young-ju;Lee, In;Kwon, Jung-nam;Hong, Jin-woo;Choi, Jun-yong
    • The Journal of Internal Korean Medicine
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    • v.40 no.4
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    • pp.709-722
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    • 2019
  • Objective: The purpose of this study was to report the effect of traditional Korean medicine (TKM) in alleviating the side effects of lung cancer patient undergoing immunotherapy. Method: A 43-year-old man, who was diagnosed with non-small cell lung cancer, received pembrolizumab treatments. The patient was treated with acupuncture and herbal medicine (Geoeoyangpye-tang) to control various uncomfortable symptoms. The degree of pain was measured by the numeric rating scale (NRS). The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) and the EORTC 13-item lung cancer-specific module (EORTC LC-13 questionnaire) were used to assess the change in the quality of life. Results: After the TKM treatment, the flank pain and arthralgia based on the NRS were significantly improved. Various uncomfortable symptoms such as fatigue, dyspnea, insomnia, and loss of appetite were also significantly improved, based on the EORTC QLQ-C30 and EORTC QLQ-LC13. The size of the primary tumor was decreased during treatment. The disease status was stable radiologically after two months from discharge.

Effects of an Anti-cancer Drug, Tubastatin A, on the Growth and Development of Immature Oocytes in Mice (항암제 tubastatin A에 의한 생쥐 미성숙 난모세포의 성장과 발달에 미치는 효과)

  • Choi, Yun-Jung;Min, Gyesik
    • Journal of Life Science
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    • v.29 no.1
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    • pp.105-111
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    • 2019
  • In recent years, progress has been made in the search for the development of new anti-cancer agents by employing specific inhibitors of histone deacetylase (HDAC)-6 to block signal transduction pathways in cancer cells. This study examined the effects of tubastatin A (TubA), an HDAC-6 inhibitor, on the growth and development of immature oocytes in murine ovaries using RNA sequencing analysis. The results from a gene set enrichment analysis (GSEA) indicated that the expression of most of the gene sets involved in the cell cycle and control and progression of meiosis decreased in the TubA-treated group as compared with that in germinal vesicle (GV) stage oocytes. In addition, an ingenuity pathway analysis (IPA) suggested that TubA not only caused increased expression of p53 and pRB and decreased expression of CDK4/6 and cyclin D but also caused elevated expression of genes involved in the control of the DNA check point in G2/M stage oocytes. These results suggest that TubA may induce cell cycle arrest and apoptosis through the induction of changes in the expression of genes involved in signal transduction pathways associated with DNA damage and the cell cycle of immature oocytes in the ovary.

A Study on the Development Site of an Open-pit Mine Using Unmanned Aerial Vehicle (무인항공기를 이용한 노천광산 개발지 조사에 관한 연구)

  • Kim, Sung-Bo;Kim, Doo-Pyo;Back, Ki-Suk
    • Journal of Convergence for Information Technology
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    • v.11 no.1
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    • pp.136-142
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    • 2021
  • Open-pit mine development requires continuous management because of topographical changes and there is a risk of accidents if the current status survey is performed directly in the process of calculating the earthwork. In this study, the application of UAV photogrammetry, which can acquire spatial information without direct human access, was applied to open-pit mines development area and analyzed the accuracy, earthwork, and mountain restoration plan to determine its applicability. As a result of accuracy analysis at checkpoint using ortho image and Digital Surface Model(DSM) by UAV photogrammetry, Root Mean Square Error(RMSE) is 0.120 m in horizontal and 0.150 m in vertical coordinates. This satisfied the tolerance range of 1:1,000 digital map. As a result of the comparison of the earthwork, UAV photogrammetry yielded 11.7% more earthwork than the conventional survey method. It is because UAV photogrammetry shows more detailed topography. And result of monitoring mountain restoration showed possible to determine existence of rockfall prevention nets and vegetation. If the terrain changes are monitored by acquiring images periodically, the utility of UAV photogrammetry will be further useful to open-pit mine development.

A Study on the Accuracy Evaluation of UAV Photogrammetry using Oblique and Vertical Images (연직사진과 경사사진을 함께 이용한 UAV 사진측량의 정확도 평가 연구)

  • Cho, Jungmin;Lee, Jongseok;Lee, Byoungkil
    • Journal of the Korean Society of Surveying, Geodesy, Photogrammetry and Cartography
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    • v.39 no.1
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    • pp.41-46
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    • 2021
  • As data acquisition using unmanned aerial vehicles is widely used, as one of the ways to increase the accuracy of photogrammetry using unmanned aerial vehicles, a method of inputting both vertical and oblique images in bundle adjustment of aerial triangulation has been proposed. In this study, in order to find a suitable method for increasing the accuracy of photogrammetry, the accuracy of the case of adjusting the oblique images taken at different shooting angles and the case of adjusting the oblique images with different shooting angles at the same time with the vertical images were compared. As a result of the study, it was found that the error of the checkpoint decreases as the angle of the input oblique images increases. In particular, when the vertical images and oblique images are used together, the height error decreases significantly as the angle of the oblique images increases. The current 『Aerial Photogrammetry Work Regulation』 requires RMSE (Root Mean Square Error), which is the same as GSD (Ground Spatial Distance) of a vertical image. When using an oblique images with a shooting angle of 50°, a result close to this standard is obtained. If the vertical images and the 50° oblique images were adjusted at the same time, the work regulations could be satisfied. Using the results of this study, it is expected that photogrammetry using low-cost cameras mounted on unmanned aerial vehicles will become more active.

Relationship between DNA mismatch repair and CRISPR/Cas9-mediated knock-in in the bovine β-casein gene locus

  • Kim, Seung-Yeon;Kim, Ga-Yeon;You, Hyeong-Ju;Kang, Man-Jong
    • Animal Bioscience
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    • v.35 no.1
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    • pp.126-137
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    • 2022
  • Objective: Efficient gene editing technology is critical for successful knock-in in domestic animals. RAD51 recombinase (RAD51) gene plays an important role in strand invasion during homologous recombination (HR) in mammals, and is regulated by checkpoint kinase 1 (CHK1) and CHK2 genes, which are upstream elements of RAD51 recombinase (RAD51). In addition, mismatch repair (MMR) system is inextricably linked to HR-related pathways and regulates HR via heteroduplex rejection. Thus, the aim of this study was to investigate whether clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9)-mediated knock-in efficiency of human lactoferrin (hLF) knock-in vector in the bovine β-casein gene locus can be increased by suppressing DNA MMR-related genes (MSH2, MSH3, MSH6, MLH1, and PMS2) and overexpressing DNA double-strand break (DSB) repair-related genes (RAD51, CHK1, CHK2). Methods: Bovine mammary epithelial (MAC-T) cells were transfected with a knock-in vector, RAD51, CHK1, or CHK2 overexpression vector and CRISPR/sgRNA expression vector to target the bovine β-casein gene locus, followed by treatment of the cells with CdCl2 for 24 hours. After 3 days of CdCl2 treatment, the knock-in efficiency was confirmed by polymerase chain reaction (PCR). The mRNA expression levels of DNA MMR-related and DNA DSB repair-related genes were assessed by quantitative real-time PCR (RT-qPCR). Results: Treatment with CdCl2 decreased the mRNA expression of RAD51 and MMRrelated genes but did not increase the knock-in efficiency in MAC-T cells. Also, the overexpression of DNA DSB repair-related genes in MAC-T cells did not significantly affect the mRNA expression of MMR-related genes and failed to increase the knock-in efficiency. Conclusion: Treatment with CdCl2 inhibited the mRNA levels of RAD51 and DNA MMR-related genes in MAC-T cells. However, the function of MMR pathway in relation to HR may differ in various cell types or species.

A Case of Palliative Chemotherapy of Advanced Gastric Cancer with Multiple Hepatic Metastasis (다발성 간 전이가 동반된 진행성 위암의 고식적 항암치료 1례)

  • Hae Jin Shin;Hyun Yong Jeong;Hee Seok Moon;Jae Kyu Sung;Sun Hyung Kang
    • Journal of Digestive Cancer Research
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    • v.3 no.1
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    • pp.30-34
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    • 2015
  • We report a case of a 55-year-old man who diagnosed with advanced gastric cancer (AGC), with A review of the literature. A 55-year old man was transferred to our hospital for further evaluation and treatment after being diagnosed with adenocarcinoma through endoscopic biopsy during a regular health examination. An abdominal computed tomography (CT) showed AGC, stage IIA (T3N3M0), while an endoscopic examination showed AGC, Borrmann type 2. The patient is currently under observation after undergoing radical subtotal gastrectomy with gastroduodenostomy and subsequent administration of oral chemotherapeutic agents. As an abdominal CT response assessment performed after surgery revealed new metastasis to the liver, the patient received palliative chemotherapy as progressive disease was suspected. After receiving chemotherapy in the order of FOLFOX (5-fluorouracil (5-FU)) + Leucovorin + Oxaliplatin), FOLFIRI (5-FU + Leucovorin + Irinotecan), EAP-II (Etoposide + Doxorubicin + Cisplatin), ELF (Etoposide + Leucovorin + 5-FU), TS-1 (Tegafur + Gimeracil) + Cisplatin, an abdominal CT response assessment showed progressive disease for which the regimen was altered to PFL (Paclitaxel + 5-FU + Leucovorin). The patient has currently completed his second cycle of chemotherapy and after an abdominal CT response assessment, further course of therapy will be decided.

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