• Title/Summary/Keyword: checkpoint

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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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Proof-of-concept study of the caninized anti-canine programmed death 1 antibody in dogs with advanced non-oral malignant melanoma solid tumors

  • Masaya Igase;Sakuya Inanaga;Shoma Nishibori;Kazuhito Itamoto;Hiroshi Sunahara;Yuki Nemoto;Kenji Tani;Hiro Horikirizono;Munekazu Nakaichi;Kenji Baba;Satoshi Kambayashi;Masaru Okuda;Yusuke Sakai;Masashi Sakurai;Masahiro Kato;Toshihiro Tsukui;Takuya Mizuno
    • Journal of Veterinary Science
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    • v.25 no.1
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    • pp.15.1-15.15
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    • 2024
  • Background: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%). Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. Conclusions: The present study demonstrated that ca-4F12-E6 was well-tolerated in non-OMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.

Induction of G2/M Arrest and Apoptosis by the Methanol Extract of Typha orientalis in Human Colon Adenocarcinoma HT29 Cells (포황 메탄올 추출물에 의한 인체 대장암 세포주 HT29의 G2/M Arrest 및 Apoptosis 유발)

  • Jin, Soojung;Yun, Seung-Geun;Oh, You Na;Lee, Ji-Young;Park, Hyun-Jin;Jin, Kyong-Suk;Kwon, Hyun Ju;Kim, Byung Woo
    • Microbiology and Biotechnology Letters
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    • v.41 no.4
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    • pp.425-432
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    • 2013
  • Typha orientalis, also known as bulrush or cattail, is a perennial herbaceous plant found in freshwater wetlands and has been widely used in constructed wetlands for wastewater treatment. Recent data has revealed that SH21B, a mixture composed of seven herbs including T. orientalis, exhibited an anti-adipogenic activity by the inhibition of the expression of adipogenic regulators. However, the anti-cancer effect of T. orientalis and its molecular mechanisms remain unclear. In this study, we evaluated the anti-cancer effect and its mechanism in the methanol extract of T. orientalis (METO) on human colon carcinoma HT29 cells. It was found that METO treatment showed cytotoxic activity in a dose-dependent manner, and induced G2/M cell cycle arrest and apoptosis in HT29 cells. The induction of G2/M arrest by METO was associated with the up-regulation of phospho-Cdc2 (Tyr15), an inactive form of Cdc2 and the down-regulation of Cdc25c phosphatase. METO also induced tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) expression. In addition, METO-induced apoptosis was characterized by the proteolytic activation of caspase-3, degradation of poly ADP ribose polymerase (PARP), and up-regulation of death receptor FAS and pro-apoptotic Bax expression. Collectively, these results indicate that the cell cycle inhibition and apoptosis induction of METO in HT29 cells allows for the possibility of its use in anti-cancer therapies.

Regulatory Mechanism of Radiation-induced Cancer Cell Death by the Change of Cell Cycle (세포주기 변화에 타른 방사선 유도 암세포 사망의 조절기전)

  • Jeong Soo-Jin;Jeong Min-Ho;Jang Ji-Yeon;Jo Wol-Soon;Nam Byung-Hyouk;Jeong Min-Za;Lim Young-Jin;Jang Byung Gon;Youn Seon-Min;Lee Hyung Sik;Hur Won Joo;Yang Kwang Mo
    • Radiation Oncology Journal
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    • v.21 no.4
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    • pp.306-314
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    • 2003
  • Purpose : In our Previous study, we have shown the main cel1 death pattern Induced by irradiation or protein tyrosine kinase (PTK) inhibitors in K562 human myeiogenous leukemic cell line. Death of the cells treated with irradiation alone was characterized by mitotic catastrophe and typical radiation-induced apoptosis was accelerated by herblmycin A (HMA). Both types of cell death were inhibited by genistein. In this study, we investigated the effects of HMA and genistein on cell cycle regulation and its correlation with the alterations of radiation-induced cell death. Materials and Methods: K562 cells In exponential growth phase were used for this study. The cells were Irradiated with 10 Gy using 6 MeV Linac (200-300 cGy/min). Immediately after irradiation, cells were treated with 250 nM of HMA or 25 $\mu$N of genistein. The distributions of cell cycle, the expressions of cell cycle-related protein, the activities of cyclin-dependent kinase, and the yield of senescence and differentiation were analyzed. Results: X-irradiated cells were arrested In the G2 phase of the cell cycle but unlike the p53-positive cells, they were not able to sustain the cell cycle arrest. An accumulation of cells in G2 phase of first ceil-cycle post-treatment and an increase of cyclin Bl were correlated with spontaneous, premature, chromosome condensation and mitotic catastrophe. HMA induced rapid G2 checkpoint abrogation and concomitant p53-independent Gl accumulation. HMA-induced cell cycle modifications correlated with the increase of CDK2 kinase activity, the decrease of the expressions of cyclins I and A and of CDK2 kinase activity, and the enhancement of radiation-induced apoptosis. Genistein maintained cells that were arrested in the G2-phase, decreased the expressions of cyclin Bl and cdc25c and cdc25C kinase activity, increased the expression of pl6, and sustained senescence and megakaryocytic differentiation. Conclusion: The effects of HMA and genistein on the radiation-induced cell death of KS62 cells were closely related to the cell cycle regulatory activities. In this study, we present a unique and reproducible model in which for investigating the mechanisms of various, radiation-induced, cancer cell death patterns. Further evaluation by using this model will provide a potent target for a new strategy of radiotherapy.

Analysis of Geolocation Accuracy of Precision Image Processing System developed for CAS-500 (국토관측위성용 정밀영상생성시스템의 위치정확도 분석)

  • Lee, Yoojin;Park, Hyeongjun;Kim, Hye-Sung;Kim, Taejung
    • Korean Journal of Remote Sensing
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    • v.36 no.5_2
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    • pp.893-906
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    • 2020
  • This paper reports on the analysis of the location accuracy of a precision image generation system manufactured for CAS 500. The planned launch date of the CAS 500 is 2021, and since it has not yet been launched, the analysis was performed using KOMPSAT-3A satellite images having similar specifications to the CAS 500. In this paper, we have checked the geolocation accuracy of initial sensor model, the model point geolocation accuracy of the precise sensor model, the geolocation accuracy of the precise sensor model using the check point, and the geolocation accuracy of the precise orthoimage using 30 images of the Korean Peninsula. In this study, the target geolocation accuracy is to have an RMSE within 2 pixels when an accurate ground control point is secured. As a result, it was confirmed that the geolocation accuracy of the precision sensor model using the checkpoint was about 1.85 pixels in South Korea and about 2.04 pixels in North Korea, and the geolocation accuracy of the precise orthoimage was about 1.15 m in South Korea and about 3.23 m in North Korea. Overall, it was confirmed that the accuracy of North Korea was low compared to that of South Korea, and this was confirmed to have affected the measured accuracy because the GCP (Ground Control Point) quality of the North Korea images was poor compared to that of South Korea. In addition, it was confirmed that the accuracy of the precision orthoimage was slightly lower than that of precision sensor medel, especially in North Korea. It was judged that this occurred from the error of the DTM (Digital Terrain Model) used for orthogonal correction. In addition to the causes suggested by this paper, additional studies should be conducted on factors that may affect the position accuracy.