• 동의생리병리학회지
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• 제22권2호
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• pp.403-409
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• 2008

In Oriental medicine daeseungki-tang is one of the prescription that is used clinically for constipation of paralytics. The objective of the study was to observe the effect of daeseungki-tang on apoptotic neuronal cell death. In the present study, middle cerebral artery occlusion(MCAO) rats were treated with daeseungi-tang for 5 days and the edema percentage of cerebral hemisphere of MCAO rats were investigated primary. Secondary, appearances of Bax, Bcl-2,-factors that is related to apoptotic neuronal cell death - and HSP72 in the brain of MCAO rats were investigated via immunohistochemistry. Daeseungki-tang significantly decreased edema percentage of the cerebral hemisphere of MCAO rats. Daeseungki-tang significantly decreased Bax positive cells, but did not change the apperances of Bcl-2 positive cells in the penumbra of the cerebral cortex and the caudoputamen of MCAO rats. Daeseungki-tang significantly decreased HSP72 positive cells in the penumbra of the cerebral cortex, but not in the caudoputamen of MCAO rats. Based on the present results, it can be suggested that treatment with daeseungki-tang may decrease edema of the cerebral hemisphere and restrain apoptotic neuronal cell death in the penumbra of the cerebral cortex.

• Biomolecules & Therapeutics
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• 제31권5호
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• pp.526-535
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• 2023

Breast cancer is the most common cancer and a frequent cause of cancer-related deaths among women wordlwide. As therapeutic strategies for breast cancer have limitations, novel chemotherapeutic reagents and treatment strategies are needed. In this study, we investigated the anti-cancer effect of synthetic homoisoflavane derivatives of cremastranone on breast cancer cells. Homoisoflavane derivatives, SH-17059 and SH-19021, reduced cell proliferation through G2/M cell cycle arrest and induced caspase-independent cell death. These compounds increased heme oxygenase-1 (HO-1) and 5-aminolevulinic acid synthase 1 (ALAS1), suggesting downregulation of heme. They also induced reactive oxygen species (ROS) generation and lipid peroxidation. Furthermore, they reduced expression of glutathione peroxidase 4 (GPX4). Therefore, we suggest that the SH-17059 and SH-19021 induced the caspase-independent cell death through the accumulation of iron from heme degradation, and the ferroptosis might be one of the potential candidates for caspase-independent cell death.

• 응용통계연구
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• 제25권1호
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• pp.115-123
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• 2012

In animal tumorigenicity data, tumor onsets occur at several sites and onset times cannot be exactly observed. Instead, the existence of tumors is examined only at death time or sacrifice time of the animal. Such an incomplete data structure makes it difficult to investigate the effect of treatment on tumor onset times; in addition, such dependence should be considered when censoring due to death is related with tumor onset. A bivariate frailty effect is incorporated to model bivariate tumor onsets and to connect death with tumor. For the inference of parameters, EM algorithm is applied and a real NTP(National Toxicology Program) dataset is analyzed as an illustrative example.

• 약학회지
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• 제46권1호
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• pp.18-23
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• 2002

Ailanthus altissima has been used to settle an upset stomach, to alleviate a fever and as an insecticide. We reported that the water extract of A. altissima induced apoptotic cell death in Jurkat T-acute Iymphoblastic leukemia cells. Here, we showed the dose-dependent inhibitions of cell viability by the extract, as measured by cell morphology. The cell cycle control genes are considered to play important roles in tumorigenesis. The purpose of the present study is also to investigate the effect of A. altissima on cell cycle progression and its molecular mechanism in the cells. The level of p21 protein was increased after treatment of the extract, whereas both Bcl-2 and Bax protein levels were not changed. These results suggest that A. altissima induces apoptotic cell death via p21-dependent signaling pathway in Jurkat cells which delete wild type p53. Gl checkpoint related gene products tested (cyclin D3, cyclin dependent kinase 4, retinoblastoma, E2Fl) were decreased in their protein levels in a dose-dependent manner after treatment of the extract Taken together, these results indicate that the increase of apoptotic cell death by A. altissima may be due to the inhibition of cell cycle in Jurkat cells.

• Biomolecules & Therapeutics
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• 제24권4호
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• pp.426-432
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• 2016

Age-related rotator cuff tendon degeneration is related to tenofibroblast apoptosis. Anthocyanins reduce oxidative stress-induced apoptotic cell death in tenofibroblasts. The current study investigated the presence of cell protective effects in cyanidin and delphinidin, the most common aglycon forms of anthocyanins. We determined whether these anthocyanidins have antiapoptotic and antinecrotic effects in tenofibroblasts exposed to $H_2O_2$, and evaluated their biomolecular mechanisms. Both cyanidin and delphinidin inhibited $H_2O_2$-induced apoptosis in a dose-dependent manner. However, at concentrations of $100{\mu}g/ml$ or greater, delphinidin showed cytotoxicity against tenofibroblasts and a decreased antinecrotic effect. Cyanidin and delphinidin both showed inhibitory effects on the $H_2O_2$-induced increase in intracellular ROS formation and the activation of ERK1/2 and JNK. In conclusion, both cyanidin and delphinidin have cytoprotective effects on cultured tenofibroblasts exposed to $H_2O_2$. These results suggest that cyanidin and delphinidin are both beneficial for the treatment of oxidative stress-mediated tenofibroblast cell death, but their working concentrations are different.

• 한국음향학회지
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• 제36권3호
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• pp.172-178
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• 2017

초음파는 세포사멸을 포함하여 의학 및 생물학분야에 널리 응용되고 있으나 그 정확한 기작에 대해선 논쟁의 여지가 있다. 본 연구에서는 40 kH 초음파 조사시스템을 단세포 효모에 적합하게 개발하고 세포사멸 유도시 40 kH 초음파의 생물학적 현상을 살펴보았다. 아이오딘화 칼륨 선량 측정법을 이용하여 1.5 ml 실험튜브에 40 kH 초음파 조사 시스템의 최적 조건을 맞추어 세포사멸을 시간 의존적 방식으로 연구하였고 초음파 조사과정동안 온열효과와는 별개로 세포 사멸이 관찰되었다. 40 kH 초음파와 과산화수소의 동시 처리는 세포사멸에 상조적인 효과가 관찰되어 활성산소가 40 kH 초음파사멸에 관련이 있었다. 그러나 활성산소 저해제, NAC(N-acetyl-Lcysteine)는 초음파에 의한 세포사멸에 약한 영향만을 미쳤고 다른 세포사멸, 괴사억제제[글리실리진(glycyrrhizin) 또는 zVAD-fmk] 역시도 세포사멸을 완전히 억제하진 못하였다. 본 연구를 통하여 40 kH 초음파에 의한 세포사멸에는 온열효과나 활성산소만으로 사멸이 유도되지는 않는 것으로 보인다.

• Journal of Chest Surgery
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• 제42권6호
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• pp.725-731
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• 2009

배경: Ia 병기의 비소세포성폐암에서 폐엽 절제술과 종격동 림프절 청소술은 표준 치료로 받아들여지고 있으나 약 15~40%의 환자의 재발 또는 사망 등의 치료 실패를 경험하게 된다. 저자들은 Ia 비소포성폐암에서의 치료 실패 유형을 분석하고 각각에 따른 위험 인자를 분석하고자 하였다. 대상 및 방법: 1992년 1월부터 2005년 8월까지 비소세포성폐암으로 완전(R0)절제술을 시행받은 156명의 환자를 대상으로 후향적인 연구를 시행하였다. 치료 실패의 원인을 폐암연관 사망 및 폐암무관 사망으로 분류하고 각각의 위험인자를 분석하였다. 결과: 전체 156명의 환자중 남자가 93명, 여자는 63명이었으며, 평균 연령은 61.31세였다. 중앙 추적관찰 기간은 33.8개월이었다. 5년 생존율은 87.6%였고 10년 생존율은 78.3%였다. 미세 림프관-혈관 침윤이 있었던 환자는 10명이었다. 추적기간 중 19예의 폐암재발이 진단되었으며, 12예의 폐암연관 사망이 발생하였다. 폐암무관 사망은 16예에서 발생하였다. 폐암 재발과 폐암연관 사망의 위험인자는 미세 림프관-혈관 침윤(HR=6.81, p=0.007, HR=7.81, p<0.001)이었으며, 폐암무관 위험인자는 전폐절제술(HR=25.92, p=0.001)과 수술 후 심혈관계 또는 호흡기계통의 합병증 발생여부(HR=29.67, p=0.002)인 것으로 나타났다. 결론: Ia 비소세포성폐암의 완전절제술 후 사망 원인은 재발과 이로 인한 폐암연관 사망뿐만 아니라 폐암무관 사망 또한 많은 비율을 차지한다. 재발 및 폐암연관 사망의 위험인자인 미세 림프관-혈관 침윤이 있는 환자들 대상으로 수술 후 보조 항암요법을 선택적으로 시행하는 것이 도움이 될 수 있을 것으로 판단되며, 전폐절제술을 받은 환자나 심혈관계 또는 호흡기계 합병증이 발생했던 환자들에 있어서는 병발증으로 인한 사망을 줄이기 위해 세심한 관리가 필요할 것으로 판단된다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9291-9293
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• 2014

Background: Patients with refractory or relapsed multiple myeloma are considered to have a very poor prognosis, and new regimens are needed to improve the outcome. Gemcitabine, a nucleoside antimetabolite, is an analog of deoxycytidine which mainly inhibits DNA synthesis through interfering with DNA chain elongation and depleting deoxynucleotide stores, resulting in gemcitabine-induced cell death. Here we performed a systemic analysis to evaluate gemcitabine based chemotherapy as salvage treatment for patients with refractory and relapsed multiple myeloma. Methods: Clinical studies evaluating the impact of gemcitabine based regimens on response and safety for patients with refractory and relapsed multiple myeloma were identified by using a predefined search strategy. Pooled response rate (RR) of treatment were calculated. Results: In gemcitabine based regimens, 3 clinical studies which including 57 patients with refractory and relapsed multiple myeloma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 15.7% (9/57) in gemcitabine based regimens. Major adverse effects were hematologic toxicity, including grade 3 or 4 anemia, leucopenia and thrombocytopenia i. No treatment related death occurred with gemcitabine based treatment. Conclusion: This systemic analysis suggests that gemcitabine based regimens are associated with mild activity with good tolerability in treating patients with refractory or relapsed multiple myeloma.

• Journal of Acupuncture Research
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• 제20권2호
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• pp.98-111
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• 2003

Objective : This study was designed to analyze the effects of bee venom and melittin on cell death in neuroblastoma cell line. Methods : MTT assay, morphologic method, DNA fragmentation, flow cytometry, immunocytochemistry analysis, RT-PCR and Western blot were performed. Results : The obtained results are summarized as follows: 1. The MTT assay demonstrated that neuroblastoma cell viability was significantly inhibitted dose-dependently by treatment with bee venom and melittin in comparison with control. 2. Cell culture demonstrated that control group proliferated highestly at he 5th day in comparison with the 4th day in bee venom and melittin group. And in bee venom and melitti group cell proliferation decreased 2.5 times than control group. 3. The morphologic study demonstrated that neuroblastoma cell showed apoptosis after treatment with bee venom and melittin for 6 hours using microscope. 4. The Flow cytometry demonstrated that apoptosis of neuroblastoma cell treated with bee venom and melittin was related with stop of cell cycle in stage of $G_0/G_1$. 5 .DNA fragmenation demonstrated that neuroblastoma cell treated with bee venom and melittin showed DNA ladder below 1 Kbp. 6. Immunocytochemistry assay demonstrated that Fos and MAPK which are related with cancer were down-regulated by treatment with bee venom and melittin. 7. RT-PCR analysis demonstrated that Fos and MAPK mRNA were transcripted. Fos was down-regulated form treatment with $5{\mu}g/ml$ bee venom and MAPK was down-regulated form $1{\mu}g/ml$ bee venom. 8. Western blot demonstrated that Fos was down-regulated from $1{\mu}g/ml$ bee venom whereas MAPK was expressed by $1{\mu}g/ml$ bee venom but down-regulated by $10{\mu}g/ml$ bee venom. Conclusions : We found that some cancer related genes ware down-regulated by treatment with bee venom and melittin. Further study is needed for investigating the anti-cancer effect of bee venom and melittin.

• 생명과학회지
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• 제21권11호
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• pp.1641-1651
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• 2011

TNF ligand 군에 속하는 Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L)은 death receptor를 통한 세포사멸을 유도하는 것으로 알려졌다. TRAIL은 정상세포에서는 세포사를 일으키지 않고 암세포에서만 특이적으로 세포사멸을 유도함으로써 잠재력 있는 항암제로 주목을 받고 있다. 그러나, 최근 연구에 의하면 악성 신장암과 간암과 같은 일부 암에서는 TRAIL에 의한 세포사에 저항성을 가지는 것으로 알려져 있다. 그러므로, TRAIL 만으로는 다양한 악성종양을 위한 치료법으로 적절하지 않다. TRAIL에 대한 저항성을 가지는 분자적 기전을 이해하고, TRAIL 저항성을 극복할 수 있는 증감제를 밝혀내는 것이 보다 효율적인 TRAIL을 이용한 암세포 치료 전략에 필요하다. 화학치료제들이 TRAIL 수용체인 death receptor의 발현을 증가시키고, 세포 내의 TRAIL에 의한 신호전달 체계를 활성화 시키는 것으로 알려져 있고, 이러한 기전을 통하여 다양한 화학치료제들이 TRAIL에 의한 세포사멸을 증가시키는 것을 확인하였다. 이 논문에서, 우리는 TRAIL에 의한 세포 사멸을 증가시키기 위한 생물학적 약물을 정리하고, 그 분자적 기전을 고찰한다.