• BMB Reports
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• v.54 no.8
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• pp.403-412
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• 2021

In the tumor microenvironment, immune checkpoint ligands (ICLs) must be expressed in order to trigger the inhibitory signal via immune checkpoint receptors (ICRs). Although ICL expression frequently occurs in a manner intrinsic to tumor cells, extrinsic factors derived from the tumor microenvironment can fine-tune ICL expression by tumor cells or prompt non-tumor cells, including immune cells. Considering the extensive interaction between T cells and other immune cells within the tumor microenvironment, ICL expression on immune cells can be as significant as that of ICLs on tumor cells in promoting antitumor immune responses. Here, we introduce various regulators known to induce or suppress ICL expression in either tumor cells or immune cells, and concise mechanisms relevant to their induction. Finally, we focus on the clinical significance of understanding the mechanisms of ICLs for an optimized immunotherapy for individual cancer patients.

• Journal of Life Science
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• v.16 no.1
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• pp.12-16
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• 2006

Genetic alternation of Brca1 predispose of breast and ovarian cancer. Brca1 plays critical role in cell cycle regulation following DNA damage. Previous studies revealed that Brca1 plays an important role in S phase and G2/M checkpoint regulation. However, whether Brca1 involves in spindle checkpoint is unclear. In this study, the role of Brca1 in cell cycle response following nocodazole, which is a reagent that depolymerizes microtubules and activates the spindle checkpoint, has been examined using wild type $p53^{-/-}\;and\;p53^{-/-}Brca1^{-/-}$ mouse embryonic fibroblasts (MEFs). While wild type and Brca1-proficient MEFs showed an acute mitotic arrest, Brca1-deficient MEFs failed to arrest at mitotic phase in response to nocodazole treatment. In double-thymidine block and nocodazole treatment experiment, a portion of $p53^{-/-}\;Brca1^{-/-}$ MEFs were clearly by-passed nocodazole induced mitotic arrest. Consistent with this, in morphologic analysis, $p53^{-/-}\;Brca1^{-/-}$ MEFs showed growing cell morphology after nocodazole treatment. Taken together, these results suggest that Brca1 protein is an important component for normal induction of spindlecheckpoint and impairment of Brca1 function could induce dysregulation of mitotic cell cycle that ultimately results in genomic instability.

• Molecules and Cells
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• v.25 no.4
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• pp.457-461
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• 2008

DNA damage checkpoint is an important self-defense mechanism for the maintenance of genome stability. Defects in DNA damage signaling and repair lead to various disorders and increase tumor incidence in humans. In the past 10 years, we have identified many components involved in the DNA damage-signaling pathway, including the product of breast cancer susceptibility gene 1 (BRCA1). Mutations in BRCA1 are associated with increased risk of breast and ovarian cancers, highlighting the importance of this DNA damage-signaling pathway in tumor suppression. While it becomes clear that BRCA1 plays a crucial role in the DNA damage responsive pathway, exactly how BRCA1 receives DNA damage signals and exerts its checkpoint function has not been fully addressed. A series of recent studies reported the discovery of many novel components involved in DNA damage-signaling pathway. These newly identified checkpoint proteins, including RNF8, RAP80 and CCDC98, work in concern in recruiting BRCA1 to DNA damage sites and thus regulate BRCA1 function in G2/M checkpoint control. This review will summarize these recent findings and provide an updated view of the regulation of BRCA1 in response to DNA damage.

• Proceedings of the Korea Information Processing Society Conference
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• 2011.04a
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• pp.156-157
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• 2011

In this work, we study the checkpoint/restart problem for message-passing parallel applications running on cloud computing environment. This is a new direction which arises from the trend of enabling the applications to run on the cloud computing environment. The main objective is to propose an efficient checkpoint algorithm for message-passing parallel applications considering communications with external systems. We further implement the novel algorithm by modifying gSOAP and OpenMPI (the open source libraries) which support service calls and checkpoint message-passing parallel programs, especially. The simulation showed that additional costs to the executing and checkpointing application of the algorithm are negligible. Ultimately, the algorithm supports efficiently the checkpoint/restart service for message-passing parallel applications, that send requests to external services.

• Molecules and Cells
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• v.19 no.2
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• pp.167-179
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• 2005

The cells of metazoans respond to DNA damage by either arresting their cell cycle in order to repair the DNA, or by undergoing apoptosis. This response is highly conserved across species, and many of the genes involved in this DNA damage response have been shown to be inactivated in human cancers. This suggests the importance of DNA damage response with regard to the prevention of cancer. The DNA damage checkpoint responses vary greatly depending on the developmental context, cell type, gene expression profile, and the degree and nature of the DNA lesions. More valuable information can be obtained from studies utilizing whole organisms in which the molecular basis of development has been well established, such as Drosophila. Since the discovery of the Drosophila p53 orthologue, various aspects of DNA damage responses have been studied in Drosophila. In this review, I will summarize the current knowledge on the DNA damage checkpoint response in Drosophila. With the ease of genetic, cellular, and cytological approaches, Drosophila will become an increasingly valuable model organism for the study of mechanisms inherent to cancer formation associated with defects in the DNA damage pathway.

• The Transactions of The Korean Institute of Electrical Engineers
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• v.57 no.5
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• pp.875-880
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• 2008

In this paper, a novel method to determine the optimal checkpoint interval for real-time control task is proposed considering its performance degradation according to tasks's execution time. The control task in this paper has a specific sampling period shorter than its deadline. Control performance is degraded as the control task execution time is prolonged across the sampling period and eventually zero when reached to the deadline. A new performance index is defined to represent the performance variation due to the extension of task execution time accompanying rollback fault recovery. The procedure to find the optimal checkpoint interval is addressed and several simulation examples are presented.

• The Transactions of The Korean Institute of Electrical Engineers
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• v.60 no.1
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• pp.193-200
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• 2011

This paper presents an optimal checkpoint strategy for fault-tolerance in real-time systems. In our environment, multiple real-time tasks with arbitrary periods are scheduled in the system by Rate Monotonic (RM) algorithm, and checkpoints are inserted at a constant interval in each task while the width of interval is different with respect to the task. We propose a method to determine the optimal checkpoint interval for each task so that the probability of completing all the tasks is maximized. Whenever a fault occurs to a checkpoint interval of a task, the execution time of the task would be prolonged by rollback and re-execution of checkpoints. Our scheme includes the schedulability test to examine whether a task can be completed with an extended execution time. A numerical experiment is conducted to demonstrate the applicability of the proposed scheme.

• The Transactions of The Korean Institute of Electrical Engineers
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• v.61 no.1
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• pp.148-154
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• 2012

For a successful checkpointing strategy, we should place checkpoints so as to optimize fault-tolerance capability of real-time systems. This paper presents a novel scheme of checkpoint placement for real-time systems with periodic multi-tasks. Under the influence of transient faults, multi-tasks are scheduled by the Rate Monotonic (RM) algorithm. The optimal checkpoint intervals are derived to maximize the probability of task completion. In particular, this paper is concerned about the general case that the deadline of a task is longer than the period. Compared with the special condition that the deadline is equal to or less than the period, this general case causes a more complicate test procedure for schedulability of the RM algorithm with respect to a given set of checkpoint re-execution vectors. The probability of task completion is also derived in a more complex form. A case study is given to show the applicability of the proposed scheme.

• Journal of the Korean Institute of Intelligent Systems
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• v.26 no.3
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• pp.202-207
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• 2016

Checkpoint placement is an effective fault tolerance technique against transient faults in which the task is re-executed from the latest checkpoint when a fault is detected. In this paper, we propose a new checkpoint placement strategy separating data saving and fault detection processes that are performed together in conventional checkpoints. Several fault detection processes are performed in one checkpoint interval in order to decrease the latency between the occurrence and detection of faults. We address the placement method of fault detection processes to maximize the probability of successful execution of a task within the given deadline. We develop the Markov chain model for a real-time task having the proposed checkpoints, and derive the optimal fault detection and checkpoint interval.

• Journal of Gynecologic Oncology
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• v.29 no.6
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• pp.93.1-93.11
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• 2018

The introduction of checkpoint inhibitors revolutionized immuno-oncology. The efficacy of traditional immunotherapeutics, like vaccines and immunostimulants was very limited due to persistent immune-escape strategies of cancer cells. Checkpoint inhibitors target these escape mechanisms and re-direct the immune system to anti-tumor toxicity. Phenomenal results have been reported in entities like melanoma, where no other therapy was able to demonstrate survival benefit, before the introduction of immunotherapeutics. The first experience in ovarian cancer (OC) was reported for nivolumab, a fully human anti-programmed cell death protein 1 (PD1) antibody, in 2015. While the data are extraordinary for a mono-immunotherapeutic agent and very promising, they do not match up to the revolutionary results in entities like melanoma. The key to exceptional treatment response in OC, could be the identification of the most immunogenic patients. We hypothyse that BRCA mutation could be a predictor of improved response in OC. The underlying DNA-repair-deficiancy should result in increased immunogenicity because of higher mutational load and more neoantigen presentation. This hypothesis was not tested to date and should be subject to future trials. The present article gives an overview of the immunologic background of checkpoint inhibition (CI). It presents current data on nivolumab and other checkpoint-inhibitors in solid tumors and OC specifically and depicts important topics in the management of this novel substance group, such as side effect control, diagnostic PD-1/programmed cell death-ligand 1 (PD-L1) expression assessment and management of pseudoprogression.