• Title/Summary/Keyword: checkpoint

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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 Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6.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.

Anti-oxidative and Anti-cancer Activities of Ethanol Extract of Litsea populifolia (인체 폐암 세포주 A549에서 Litsea populifolia 추출물의 항산화 및 항암활성 분석)

  • Jin, Soojung;Oh, You Na;Jeong, Hyun Young;Yun, Hee Jung;Park, Jung-ha;Kwon, Hyun Ju;Kim, Byung Woo
    • Journal of Life Science
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    • v.29 no.6
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    • pp.679-687
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    • 2019
  • Litsea populifolia, a plant species of the Lauraceae family, is widely distributed in the tropical and subtropical areas of Asia. The phylogenetic relationships and botanical characteristics of L. populifolia have been reported; however, its anti-oxidative and anti-cancer activities remain unclear. In this study, we evaluated the anti-oxidative and anti-cancer effects of ethanol extracts of L. populifolia (EELP) together with the molecular mechanism of its anti-cancer activity in human lung adenocarcinoma A549 cells. EELP showed significant anti-oxidative effects with a 50% inhibitory concentration at $11.71{\mu}g/ml$, which was measured by the 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. EELP exhibited cytotoxic activity and induced cell cycle arrest at the G1 phase in A549 cells in a dose-dependent manner, whereas EELP did not have the cytotoxic effect on the normal human lung cell line IMR90. Treatment with EELP also resulted in a decreased expression of G1/S transition-related molecules-including cyclin-dependent kinase (CDK) 2, CDK6, cyclin D1, and cyclin E-both for the transcription and translation levels. EELP-induced G1 arrest was associated with the phosphorylation of checkpoint kinase 2 (CHK2), p53, cell division cycle 25 homolog A (CDC25A), and the reduction of CDC25A expression in A549 cells. Collectively, these results suggest that EELP may exert an anti-cancer effect by cell cycle arrest at the G1 phase through both p53-dependent and p53-independent (ATM/CHK2/CDC25A/CDK2) pathways in A549 cells.

Business Application of Convolutional Neural Networks for Apparel Classification Using Runway Image (합성곱 신경망의 비지니스 응용: 런웨이 이미지를 사용한 의류 분류를 중심으로)

  • Seo, Yian;Shin, Kyung-shik
    • Journal of Intelligence and Information Systems
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    • v.24 no.3
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    • pp.1-19
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    • 2018
  • Large amount of data is now available for research and business sectors to extract knowledge from it. This data can be in the form of unstructured data such as audio, text, and image data and can be analyzed by deep learning methodology. Deep learning is now widely used for various estimation, classification, and prediction problems. Especially, fashion business adopts deep learning techniques for apparel recognition, apparel search and retrieval engine, and automatic product recommendation. The core model of these applications is the image classification using Convolutional Neural Networks (CNN). CNN is made up of neurons which learn parameters such as weights while inputs come through and reach outputs. CNN has layer structure which is best suited for image classification as it is comprised of convolutional layer for generating feature maps, pooling layer for reducing the dimensionality of feature maps, and fully-connected layer for classifying the extracted features. However, most of the classification models have been trained using online product image, which is taken under controlled situation such as apparel image itself or professional model wearing apparel. This image may not be an effective way to train the classification model considering the situation when one might want to classify street fashion image or walking image, which is taken in uncontrolled situation and involves people's movement and unexpected pose. Therefore, we propose to train the model with runway apparel image dataset which captures mobility. This will allow the classification model to be trained with far more variable data and enhance the adaptation with diverse query image. To achieve both convergence and generalization of the model, we apply Transfer Learning on our training network. As Transfer Learning in CNN is composed of pre-training and fine-tuning stages, we divide the training step into two. First, we pre-train our architecture with large-scale dataset, ImageNet dataset, which consists of 1.2 million images with 1000 categories including animals, plants, activities, materials, instrumentations, scenes, and foods. We use GoogLeNet for our main architecture as it has achieved great accuracy with efficiency in ImageNet Large Scale Visual Recognition Challenge (ILSVRC). Second, we fine-tune the network with our own runway image dataset. For the runway image dataset, we could not find any previously and publicly made dataset, so we collect the dataset from Google Image Search attaining 2426 images of 32 major fashion brands including Anna Molinari, Balenciaga, Balmain, Brioni, Burberry, Celine, Chanel, Chloe, Christian Dior, Cividini, Dolce and Gabbana, Emilio Pucci, Ermenegildo, Fendi, Giuliana Teso, Gucci, Issey Miyake, Kenzo, Leonard, Louis Vuitton, Marc Jacobs, Marni, Max Mara, Missoni, Moschino, Ralph Lauren, Roberto Cavalli, Sonia Rykiel, Stella McCartney, Valentino, Versace, and Yve Saint Laurent. We perform 10-folded experiments to consider the random generation of training data, and our proposed model has achieved accuracy of 67.2% on final test. Our research suggests several advantages over previous related studies as to our best knowledge, there haven't been any previous studies which trained the network for apparel image classification based on runway image dataset. We suggest the idea of training model with image capturing all the possible postures, which is denoted as mobility, by using our own runway apparel image dataset. Moreover, by applying Transfer Learning and using checkpoint and parameters provided by Tensorflow Slim, we could save time spent on training the classification model as taking 6 minutes per experiment to train the classifier. This model can be used in many business applications where the query image can be runway image, product image, or street fashion image. To be specific, runway query image can be used for mobile application service during fashion week to facilitate brand search, street style query image can be classified during fashion editorial task to classify and label the brand or style, and website query image can be processed by e-commerce multi-complex service providing item information or recommending similar item.