• BMB Reports
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• 제54권8호
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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.

• 생명과학회지
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• 제16권1호
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• pp.12-16
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• 2006

항암유전자 Brca1의 변이는 유방암 및 난소암에 대한 감수성을 증가시키며, Brca1은 DNA손상신호후 세포주기 조절에 필수적인 역할을 한다. 연구결과, Brca1이 세포주기 S기와 G2/M 조절점에서 중요한 역할을 담당함이 밝혀졌다. 그러나, Brca1의 spindle checkpoint 관여여부는 알려져 있지 않다. 본 연구에서는 spindle checkpoint를 활성화시키는 nocodazole를 처리하여 야생형, $p53^{-/-}$ 그리고 $p53^{-/-}\;Brca1^{-/-}$ 세포주의 세포주기 변화를 조사하였다. 야생형과 $p53^{-/-}$ 세포주는 신속한 mitosis기 정지가 나타난 반면, $p53^{-/-}\;Brca1^{-/-}$ 세포주의 경우 모든 세포가 M기에서 정지하지 않았다. Double-thymidine block 기법에 의한 세포주기 동조화후 nocodazole 처리시에도 $p53^{-/-}\;Brca1^{-/-}$ 세포주에서는 일부세포가 M기 조절점을 통과하여 계속 G1기로 진행하였다. 형태학적 분석에서도 nocodazole 함유배지에서 계속 증식하는 세포형태가 관찰되었다. 이와 같은 결과들은 Brca1이 spindle checkpoint가 정상적으로 작동하는데 중요한 역할을 담당한다는 것을 의미하고 있다.

• Molecules and Cells
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• 제25권4호
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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.

• 한국정보처리학회:학술대회논문집
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• 한국정보처리학회 2011년도 춘계학술발표대회
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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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• 제19권2호
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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.

• 전기학회논문지
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• 제57권5호
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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.

• 전기학회논문지
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• 제60권1호
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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.

• 전기학회논문지
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• 제61권1호
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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.

• 한국지능시스템학회논문지
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• 제26권3호
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• pp.202-207
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• 2016

체크포인터를 삽입한 실시간 시스템에서는 고장이 발생하면 고장 직전의 체크포인터로 회귀하여 태스크를 재실행함으로써 과도 고장을 효과적으로 극복할 수 있다. 이번 논문에서는 체크포인터에서 실행되는 데이터 저장과 고장 탐지 과정을 분리한 새로운 체크포인터 방식을 제안한다. 하나의 체크포인터 구간 내에 여러 개의 고장 탐지 과정을 추가하면 고장 발생에서 탐지까지의 지연 시간을 줄일 수 있다. 본 논문에서는 태스크가 데드라인 이내에서 성공적으로 수행될 확률을 최대화하는 고장 탐지 과정의 삽입 방법을 제안한다. 고장 탐지 과정이 분리된 체크포인터 방식을 마코프 체인으로 모델링하고 실시간 태스크의 성공적 수행 확률을 계산하는 모의실험을 수행하여 최적의 해를 구하는 과정을 제시한다.

• Journal of Gynecologic Oncology
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• 제29권6호
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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.