• Title/Summary/Keyword: checkpoint

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Advancements of Common Gamma-Chain Family Cytokines in Cancer Immunotherapy

  • Alexandra A. Wolfarth;Swati Dhar;Jack B. Goon;Ugonna I. Ezeanya;Sara Ferrando-Martínez;Byung Ha Lee
    • IMMUNE NETWORK
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    • v.22 no.1
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    • pp.5.1-5.22
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    • 2022
  • The approval of immunotherapies such as checkpoint inhibitors (CPIs), adoptive cell therapies and cancer vaccines has revolutionized the way cancer treatment is approached. While immunotherapies have improved clinical outcome in a variety of tumor types, some cancers have proven harder to combat using single agents, underscoring the need for multi-targeted immunotherapy approaches. Efficacy of CPIs and cancer vaccines requires patients to have a competent immune system with adequate cell numbers while the efficacy of adoptive cellular therapy is limited by the expansion and persistence of cells after infusion. A promising strategy to overcome these challenges is combination treatment with common gamma-chain cytokines. Gamma-chain cytokines play a critical role in the survival, proliferation, differentiation and function of multiple immune cell types, including CD8 T-cells and NK cells, which are at the center of the anti-tumor response. While the short halflife of recombinant cytokines initially limited their application in the clinic, advancements in protein engineering have led to the development of several next-generation drug candidates with dramatically increased half-life and bioactivity. When combining these cytokines with other immunotherapies, strong evidence of synergy has been observed in preclinical and clinical cancer settings. This promising data has led to the initiation of 70 ongoing clinical trials including IL-2, IL-7, IL-15 and IL-21. This review summarizes the recent advancements of common gamma-chain cytokines and their potential as a cancer immunotherapy.

Far Beyond Cancer Immunotherapy: Reversion of Multi-Malignant Phenotypes of Immunotherapeutic-Resistant Cancer by Targeting the NANOG Signaling Axis

  • Se Jin Oh;Jaeyoon Lee;Yukang Kim;Kwon-Ho Song;Eunho Cho;Minsung Kim;Heejae Jung;Tae Woo Kim
    • IMMUNE NETWORK
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    • v.20 no.1
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    • pp.7.1-7.11
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    • 2020
  • Cancer immunotherapy, in the form of vaccination, adoptive cellular transfer, or immune checkpoint inhibitors, has emerged as a promising practice within the field of oncology. However, despite the developing field's potential to revolutionize cancer treatment, the presence of immunotherapeutic-resistant tumor cells in many patients present a challenge and limitation to these immunotherapies. These cells not only indicate immunotherapeutic resistance, but also show multi-modal resistance to conventional therapies, abnormal metabolism, stemness, and metastasis. How can immunotherapeutic-resistant tumor cells render multi-malignant phenotypes? We reasoned that the immune-refractory phenotype could be associated with multi-malignant phenotypes and that these phenotypes are linked together by a factor that acts as the master regulator. In this review, we discussed the role of the embryonic transcription factor NANOG as a crucial master regulator we named "common factor" in multi-malignant phenotypes and presented strategies to overcome multi-malignancy in immunotherapeutic-resistant cancer by restraining the NANOG-mediated multi-malignant signaling axis. Strategies that blunt the NANOG axis could improve the clinical management of therapy-refractory cancer.

Peripheral Blood Immune Cell-based Biomarkers in Anti-PD-1/PD-L1 Therapy

  • Kyung Hwan Kim;Chang Gon Kim;Eui-Cheol Shin
    • IMMUNE NETWORK
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    • v.20 no.1
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    • pp.8.1-8.15
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    • 2020
  • Immune checkpoint blockade targeting PD-1 and PD-L1 has resulted in unprecedented clinical benefit for cancer patients. Anti-PD-1/PD-L1 therapy has become the standard treatment for diverse cancer types as monotherapy or in combination with other anticancer therapies, and its indications are expanding. However, many patients do not benefit from anti-PD-1/PD-L1 therapy due to primary and/or acquired resistance, which is a major obstacle to broadening the clinical applicability of anti-PD-1/PD-L1 therapy. In addition, hyperprogressive disease, an acceleration of tumor growth following anti-PD-1/PD-L1 therapy, has been proposed as a new response pattern associated with deleterious prognosis. Anti-PD-1/PD-L1 therapy can also cause a unique pattern of adverse events termed immune-related adverse events, sometimes leading to treatment discontinuation and fatal outcomes. Investigations have been carried out to predict and monitor treatment outcomes using peripheral blood as an alternative to tissue biopsy. This review summarizes recent studies utilizing peripheral blood immune cells to predict various outcomes in cancer patients treated with anti-PD-1/PD-L1 therapy.

Metabolic reprogramming of the tumor microenvironment to enhance immunotherapy

  • Seon Ah Lim
    • BMB Reports
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    • v.57 no.9
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    • pp.388-399
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    • 2024
  • Immunotherapy represents a promising treatment strategy for targeting various tumor types. However, the overall response rate is low due to the tumor microenvironment (TME). In the TME, numerous distinct factors actively induce immunosuppression, restricting the efficacy of anticancer immune reactions. Recently, metabolic reprogramming of tumors has been recognized for its role in modulating the tumor microenvironment to enhance immune cell responses in the TME. Furthermore, recent elucidations underscore the critical role of metabolic limitations imposed by the tumor microenvironment on the effectiveness of antitumor immune cells, guiding the development of novel immunotherapeutic approaches. Hence, achieving a comprehensive understanding of the metabolic requirements of both cancer and immune cells within the TME is pivotal. This insight not only aids in acknowledging the current limitations of clinical practices but also significantly shapes the trajectory of future research endeavors in the domain of cancer immunotherapy. In addition, therapeutic interventions targeting metabolic limitations have exhibited promising potential as combinatory treatments across diverse cancer types. In this review, we first discuss the metabolic barriers in the TME. Second, we explore how the immune response is regulated by metabolites. Finally, we will review the current strategy for targeting metabolism to not simply inhibit tumor growth but also enhance antitumor immune responses. Thus, we could suggest potent combination therapy for improving immunotherapy with metabolic inhibitors.

A New Function of Skp1 in the Mitotic Exit of Budding Yeast Saccharomyces cerevisiae

  • Kim, Na-Mil;Yoon, Ha-Young;Lee, Eun-Hwa;Song, Ki-Won
    • Journal of Microbiology
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    • v.44 no.6
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    • pp.641-648
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    • 2006
  • We previously reported that Skp1, a component of the Skp1-Cullin-F-box protein (SCF) complex essential for the timely degradation of cell cycle proteins by ubiquitination, physically interacts with Bfa1, which is a key negative regulator of the mitotic exit network (MEN) in response to diverse checkpoint-activating stresses in budding yeast. In this study, we initially investigated whether the interaction of Skp1 and Bfa1 is involved in the regulation of the Bfa1 protein level during the cell cycle, especially by mediating its degradation. However, the profile of the Bfa1 protein did not change during the cell cycle in skp1-11, which is a SKP1 mutant allele in which the function of Skp1 as a part of SCF is completely impaired, thus indicating that Skp1 does not affect the degradation of Bfa1. On the other hand, we found that the skp1-12 mutant allele, previously reported to block G2-M transition, showed defects in mitotic exit and cytokinesis. The skp1-12 mutant allele also revealed a specific genetic interaction with ${\Delta}bfa1$. Bfa1 interacted with Skp1 via its 184 C-terminal residues (Bfa1-D8) that are responsible for its function in mitotic exit. In addition, the interaction between Bfa1 and the Skp1-12 mutant protein was stronger than that of Bfa1 and the wild type Skp1. We suggest a novel function of Skp1 in mitotic exit and cytokinesis, independent of its function as a part of the SCF complex. The interaction of Skp1 and Bfa1 may contribute to the function of Skp1 in the mitotic exit.

Health Monitoring and Efficient Data Management Method for the Robot Software Components (로봇 소프트웨어 컴포넌트의 실행 모니터링/효율적인 데이터 관리방안)

  • Kim, Jong-Young;Yoon, Hee-Byung
    • Journal of Institute of Control, Robotics and Systems
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    • v.17 no.11
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    • pp.1074-1081
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    • 2011
  • As robotics systems are becoming more complex there is the need to promote component based robot development, where systems can be constructed as the composition and integration of reusable building block. One of the most important challenges facing component based robot development is safeguarding against software component failures and malfunctions. The health monitoring of the robot software is most fundamental factors not only to manage system at runtime but also to analysis information of software component in design phase of the robot application. And also as a lot of monitoring events are occurred during the execution of the robot software components, a simple data treatment and efficient memory management method is required. In this paper, we propose an efficient events monitoring and data management method by modeling robot software component and monitoring factors based on robot software framework. The monitoring factors, such as component execution runtime exception, Input/Output data, execution time, checkpoint-rollback are deduced and the detail monitoring events are defined. Furthermore, we define event record and monitor record pool suitable for robot software components and propose a efficient data management method. To verify the effectiveness and usefulness of the proposed approach, a monitoring module and user interface has been implemented using OPRoS robot software framework. The proposed monitoring module can be used as monitoring tool to analysis the software components in robot design phase and plugged into self-healing system to monitor the system health status at runtime in robot systems.

Induction of G2/M Cell Cycle Arrest by Glutamine Deprivation in Human Prostate Carcinoma PC3 Cells (글루타민 결핍에 의한 PC3 인체 전립선 암세포의 G2/M 세포주기 억제 유발)

  • Shin, Dong Yeok;Choi, Sung Hyun;Park, Dong Il;Choi, Yung Hyun
    • Journal of Life Science
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    • v.23 no.6
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    • pp.832-837
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    • 2013
  • In this study, it was investigated the possible mechanisms by which glutamine deprivation exerts its anti-proliferative action in cultured human prostate carcinoma PC3 cells. Glutamine deprivation resulted in inhibition of growth and G2/M arrest of the cell cycle in a time-dependent manner without apoptosis induction, as determined by MTT assay, DAPI staining and flow cytometry analyses. The induction of G2/M arrest by glutamine deprivation was associated with the inhibition of expression of Cdc2, cyclin A and cyclin B1, and up-regulation of the expression of cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1) in both transcriptional and translational levels. Moreover, glutamine deprivation increased the phosphorylation of checkpoint kinase (Chk)1 and Chk2; however, the levels of Cdc25C phosphorylation were decreased in response to glutamine deprivation in a time-dependent manner. Our data provide a first biochemical evidence that glutamine deprivation suppresses cell viability through G2/M phase arrest without induction of apoptosis in PC3 cells.

Process of Digital Elevation Model Using RC Helicopter Surveying System (무선조정 헬리콥터 사진측량시스템을 이용한 수치표고모형 작성)

  • Jang, Ho-Sik
    • Journal of the Korean Society of Surveying, Geodesy, Photogrammetry and Cartography
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    • v.26 no.2
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    • pp.111-116
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    • 2008
  • The study installed non metric camera which was a 10 Mega Pixel camera in RC Helicopter. And the study controlled images hotographed in air on land, considering their overlap. The study could express DEM by abstracting TIN from the acquired images through image registration. Also, the study compared and examined accuracy between reference point and check point observed by Total Station which was a conventional type of survey. As the results, the study could get errors of $-0.194{\sim}0.224\;m$ on X axis, $-0.088{\sim}0.180\;m$ on Y axis and $-0.286{\sim}0.285\;m$ on Z axis. Expressing an error's RMSE in the checkpoint, the study could get of 0.021388 m on X axis, 0.015285 m on Y axis and 0.041872 m on Z axis. It is judged that the above photographing and analyzing technique are better than the existing Total Station to acquire more terrain elevation data.

Page-level Incremental Checkpointing for Efficient Use of Stable Storage (안정 저장장치의 효율적 사용을 위한 페이지 기반 점진적 검사점 기법)

  • Heo, Jun-Young;Yi, Sang-Ho;Gu, Bon-Cheol;Cho, Yoo-Kun;Hong, Ji-Man
    • Journal of KIISE:Computer Systems and Theory
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    • v.34 no.12
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    • pp.610-617
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    • 2007
  • Incremental checkpointing, which is intended to minimize checkpointing overhead, saves only the modified pages of a process. However, the cumulative site of incremental checkpoints increases at a steady rate over time because a number of updated values may be saved for the same page. In this paper, we present a comprehensive overview of Pickpt, a page-level incremental checkpointing facility. Pickpt provides space-efficient techniques aiming to minimizing the use of disk space. For our experiments, the results showed that the use of disk space using Pickpt was significantly reduced, compared with existing incremental checkpointing.

Analysis of Position Accuracy of Topography using LiDAR Data (LiDAR 데이터를 이용한 지형지물의 위치정확도 분석)

  • Kim, Yong-Suk;Kim, Seong-Cheol
    • The Journal of the Korea Contents Association
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    • v.8 no.3
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    • pp.270-278
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    • 2008
  • This study : An analysis of position accuracy of topography according to using LiDAR data, aerial photo and digital map for a study area was conducted. The study area was selected in Hadan area, Sahagu, Busan aerial LiDAR data and aerial photo in the scales of 1:20,000, which are high tech surveying ways were used. The final digital orthoimage according to orientation process for each image and image resampling was producted. Using it, a checkpoint was chosen, information about the checkpoints selected was extracted, a coordinate of Horizontal Position through the screen digitizing was also extracted. Both the coordinates of LiDAR data and aerial photo using digital map in the scales of 1:20,000 announced to the public from NGII(National Geographic Information Institute) were gradually compared and analyzed. Based on the digital map, as a result of being both compared and analyzed, it has shown to us that horizontal position of aerial photo is more accurate than that of aerial LiDAR surveying (RMSE-building x:24cm, y:26cm).