• Biomolecules & Therapeutics
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• 제31권3호
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• pp.340-349
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• 2023

Mad2B (Mad2L2), the human homolog of the yeast Rev7 protein, is a regulatory subunit of DNA polymerase ζ that shares sequence similarity with the mitotic checkpoint protein Mad2A. Previous studies on Mad2B have concluded that it is a mitotic checkpoint protein that functions by inhibiting the anaphase-promoting complex/cyclosome (APC/C). Here, we demonstrate that Mad2B is activated in response to cisplatin-induced DNA damage. Mad2B co-localizes at nuclear foci with DNA damage markers, such as proliferating cell nuclear antigen and gamma histone H2AX (γ-H2AX), following cisplatin-induced DNA damage. However, unlike Mad2A, the binding of Mad2B to Cdc20 does not inhibit the activity of APC/C in vitro. In contrast to Mad2A, Mad2B does not localize to kinetochores or binds to Cdc20 in spindle assembly checkpoint-activated cells. Loss of the Mad2B protein leads to damaged nuclei following cisplatin-induced DNA damage. Mad2B/Rev7 depletion causes the accumulation of damaged nuclei, thereby accelerating apoptosis in human cancer cells in response to cisplatin-induced DNA damage. Therefore, our results suggest that Mad2B may be a critical modulator of DNA damage response.

• Nutrition Research and Practice
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• 제10권2호
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• pp.139-147
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• 2016

BACKGROUND/OBJECFTIVES: The present study was conducted to examine the inhibitory effect of loquat leaves on MDA-MB-231 cell proliferation and invasion. MATERIALS/METHODS: Female athymic nude mice were given a subcutaneous (s.c.) inoculation of MDA-MB-231 cells and randomly grouped to receive a s.c. injection of either 500 mg/kg ethanol, water extract or vehicle five times a week. Tumor growth, mitotic rate and necrosis were examined. MDA-MB-231 cells were cultured with DMSO or with various concentrations of loquat water or ethanol extract. Proliferation, adhesion, migration, invasion and matrix metalloproteinase (MMP) activity were examined. RESULTS: Tumor growth of xenograft nude mouse was significantly reduced by loquat extracts. The results of mitotic examination revealed that loquat extracts reduced tumor cell division. Both ethanol and water extracts significantly inhibited MDA-MB-231 cell proliferation. The protein expression of ErbB3 was significantly down-regulated by loquat leaf extracts. Loquat leaf extracts increased apoptosis of MDA-MB-231 cells following 24 hour incubation and the ethanol extract was more potent in inducing apoptosis than the water extract. Furthermore, loquat extracts inhibited adhesion, migration and invasion of MDA-MB-231 cells. MMP activity was significantly inhibited by loquat extracts. CONCLUSION: Our results show that extracts of loquat inhibit the growth of tumor in MDA-MB-231 xenograft nude mice and the invasion of human breast cancer cells, indicating the inhibition of tumor cell proliferation and invasion.

• Asian Pacific Journal of Cancer Prevention
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• 제13권8호
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• pp.4129-4131
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• 2012

Background: An association between the ABO blood group and the risk of certain malignancies, including pancreatic and gastric cancer, has been reported previously. However, it is unclear whether this association is valid for gastrointestinal stromal tumors (GIST). In this study, ABO blood groups and the Rh factor were investigated in a series of GIST cases. Material and Methods: In 162 patients with GIST, blood group and Rh factor were examined and compared with a control group of 3,022,883 healthy volunteer blood donors of the Turkish Red Crescent between 2004 and 2011. The relationship of blood groups with tumor size, mitotic activity, and age were also evaluated. Results: Overall, the ABO blood group and Rh factor distributions of the 162 patients with GIST were similar to those of the general population. There were no significant differences between both ABO blood types and Rh factor in terms of tumor size, mitotic activity, and age. Conclusion: This is the first study reported on this issue. In our study, we didn't find any relationship between GIST and ABO blood group and Rh factor. However further studies with larger number of patients are needed to establish the role of blood groups in this population.

• Asian-Australasian Journal of Animal Sciences
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• 제23권6호
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• pp.777-785
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• 2010

The effect of two doses of different sources of zinc, inorganic (zinc oxide) or chelated (zinc glutamate chelate), on morphology and turn-over of the small intestine was assessed in early-weaned pigs orally challenged with enterotoxigenic E. coli K88 (ETEC). Sixty pigs weaned at 21 days were assigned to one of the following 5 diets: control (C); C+Zinc oxide (ZnO), either a 200 or a 2,500 mg Zn/kg dose; or C+zinc chelate with glutamic acid (Glu-Zn), either a 200 or a 2,500 mg Zn/kg dose. On d 2, the pigs were orally inoculated with 1.5 ml of a $10^{10}$ CFU/ml E. coli K88ac O148 suspension. Zinc supplements did not improve the performance of the pigs, but on d 5 faecal excretion of ETEC was reduced, and this was mainly due to high zinc doses (p<0.05). The villous height in the duodenum was improved by the zinc supplements (p<0.01) whatever the source and the level, whereas no effect was seen in the other two tracts of small intestine. The diet did not affect apoptosis and mitosis counts, while ETEC-susceptible pigs had more mitotic cells in the villi than non-susceptible pigs, particularly in the jejunum (p<0.01). The duodenum had fewer mitotic cells in the villi (p<0.05) and in the crypts (p<0.01) and more apoptotic cells in the villi. High dietary doses of ZnO or Zn-Glutamate improve villous height of the duodenum, but not of the jejunum and the ileum, and do not affect the epithelial proliferative activity and apoptotic index of intestinal mucosa of early-weaned pigs orally challenged with ETEC.

• Clinical and Experimental Otorhinolaryngology
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• 제11권4호
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• pp.224-232
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• 2018

Objectives. Spiral ganglion neurons (SGNs) include potential endogenous progenitor populations for the regeneration of the peripheral auditory system. However, whether these populations are present in adult mice is largely unknown. We examined the presence and characteristics of SGN-neural stem cells (NSCs) in mice as a function of age. Methods. The expression of Nestin and Ki67 was examined in sequentially dissected cochlear modiolar tissues from mice of different ages (from postnatal day to 24 weeks) and the sphere-forming populations from the SGNs were isolated and differentiated into different cell types. Results. There were significant decreases in Nestin and Ki67 double-positive mitotic progenitor cells in vivo with increasing mouse age. The SGNs formed spheres exhibiting self-renewing activity and multipotent capacity, which were seen in NSCs and were capable of differentiating into neuron and glial cell types. The SGN spheres derived from mice at an early age (postnatal day or 2 weeks) contained more mitotic stem cells than those from mice at a late age. Conclusion. Our findings showed the presence of self-renewing and proliferative subtypes of SGN-NSCs which might serve as a promising source for the regeneration of auditory neurons even in adult mice.

• Reproductive and Developmental Biology
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• 제35권4호
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• pp.499-502
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• 2011

Aurora A kinase is a mitotic serine/threonine kinase whose proposed functions include the maturation of centrosomes, G2/M transition, alignment of chromosomes at metaphase, and cytokinesis. In this study, we investigated the effect of MLN8237, an aurora A kinase inhibitor, on the postovulatory aging of oocytes based on the frequency of oocyte fragmentation, cdk1 kinase activity, and cyclin B degradation. The fragmentation of ovulated oocytes during prolonged culture was inhibited by treatment with MLN8237 in a concentration-dependent manner. The frequency of fragmented oocytes was significantly lower in oocytes treated with 2 ${\mu}M$ MLN8237 (13%) than in control oocytes (64%) after two days of culture. Most of the control (non-fragmented) oocytes (91%) were activated after two days of culture. In comparison, only 22% of the MLN8237-treated oocytes were activated; the rest of the oocytes (78%) were still in metaphase with an abnormal spindle and dispersed chromosomes. Next, cdk1 activity and the level of cyclin B were examined. The level of cyclin B and cdk1 activity in MLN8237-treated oocytes were nearly equal to those in control oocytes. Our results indicate that MLN8237 inhibited the fragmentation of ovulated oocytes during prolonged culture, although it blocked the spontaneous decrease in activity of cdk1 and degradation of cyclin B. This mechanism of inhibition is different from that in oocytes treated with nocodazole, which have high levels of cdk1 activity and cyclin B.

• Radiation Oncology Journal
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• 제14권4호
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• pp.255-264
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• 1996

목적 : Paclitaxel(Taxol)은 미소관의 집합을 촉진시키고 분해를 방지하여 세포주기 중 유사분열을 정지시킴으로써 방사선조사와 병용할 경우 방사선감작제로서의 가능성이 있다. 정상세포 중 횐쥐의 소장에서 paclitaxel이 방사선의 독성을 증가시키는지 알기 위하여 실험을 시도하였다. 대상 및 방법 : Paclitaxel군은 paclitaxel 10mg/kg을 복강내 1회 주입하였다. 방사선조사군은 8 Gy를 전복부에 단일조사하였다. Paclitaxel과 방사선병용군은 paclitaxel(10mg/kg)을 복강내 주입 후 24시간에 방사선조사군과 동일한 방법으로 조사하였다. 실험완료 후 소장점막에서 유사분열수, apoptosis와 기타 점막의 변화를 시간별로(6시간 -5일) 관찰하였다. 결과 : Paclitaxel은 소장점막의 소낭선세포에서 유사분열을 정지시키며 약간의 apoptosis을 유발하였으며 유사분열정지는 6시간에서 최대치를 보였고 24시간에 정상으로 회복되었다. 방사선조사는 apoptosis를 유발하였으며 6시간에 최대치를 보이고 24시간에 정상으로 회복되었다. Paclitaxel과 방사선병용군에서 유사분열정지는 6시간에서 3일까지 나타났으며 apoptosis는 6시간과 24시간에 약간 보였으며 3일에 정상으로 회복되었다. 병용군에서 apoptosis의 빈도는 정상군보다 높았으나 방사선단독군에 비하여 현저하게 감소되어 방사선보호작용이 있었다.

• 대한의생명과학회지
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• 제29권3호
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• pp.178-183
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• 2023

Natural killer (NK) cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. Regulation of the cytotoxic activity of NK cells relies on integrated interactions between inhibitory receptors and numerous activating receptors that act in tandem to eliminate tumor cells efficiently. Conventional chemotherapy is designed to produce an anti-proliferative or cytotoxic effect on early tumor cell division. Therapies designed to kill cancer cells and simultaneously maintain host anti-tumor immunity are attractive strategies for controlling tumor growth. Depending on the drug and dose used, several chemotherapeutic agents cause DNA damage and cancer cell death through apoptosis, immunogenic cell death, or other forms of non-killing (i.e., mitotic catastrophe, senescence, autophagy). Among stress-induced immunostimulatory proteins, changes in the expression levels of NK cell activating and inhibitory ligands and tumor cell death receptors play an important role in the detection and elimination by innate immune effectors including NK cells. Therefore, we will address how these cytotoxic lymphocytes sense and respond to high and low concentrations of drug-induced stress to the drug cisplatin, among the various types of drugs that contribute to their anticancer activity.

• Radiation Oncology Journal
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• 제21권4호
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• pp.306-314
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• 2003

목적: K562 세포의 방사선에 의한 세포 사망은 mitotic catastrophe 현상이 위주로 나타나지만 herbimycin A (HMA)에 의하여 apoptosis 반응이 촉진되는 반면 genisteln에 의하여 두 가지 형태의 세포사망이 모두 억제된다. 본 연구에서는 HMA와 genistein에 의한 K562세포의 방사선 유도 세포주기 조절 변화와 세포 사망 양상의 연관성을 조사하였다. 대상 및 방법: 지수증식기의 KS62 세포에 6 MV 선형가속기(Clinac 1,m C, Varian)를 이용하여 200~300 cGy/min의 선량률로 10 Gy를 균일하게 조사하였다. HMA와 genistein은 각각 250 nM와 25$\mu$M농도로 방사선 조사 후 즉시 투여하였다. 실험에서는 세포주기, 오절인자의 발현 및 활성, 노화 및 분화정도 등에 있어서의 시간에 따른 변화를 조사하였다. 결과: 방사선 단독조사에서 KS62세포는 G2기의 정체를 보였으나 정상적인 053을 가지는 세포와는 달리 지속적인 세포주기의 정체를 보이지 않았다. G2정체가 유지되는 동안 cyclin Bl의 점진적인 증가를 관찰할 수 있었으며, 이는 염색체의 복제가 완료되지 않은 상태에서 M기로 진행하여 미성숙한 염색체 응축과 mitotic catastrophe 현상이 나타나는 것과 일치한다. 방사선 조사와 함께 HMA를 투여한 경우에는 G2정체가 빠르게 해소되었으며 동시에 Gl기에서 세포가 정체되는 양상을 보였다. 세포주기 조절인자 cdc2 kinase 활성 증가와 cyclln I와 A 발현 및 CDK2 활성의 감소 등의 현상으로 설명되며, 이는 apoptosis의 증가와 연관성을 갖는다. 반면 genistein의 경우에는 cyclin Bl과 떨cfsc 발현 및 cdc2활성이 모두 감소하는 등 G2정체를 계속 유지하였다. 이와 함께 방사선에 의한 노화와 megakaryocyte로의 분화도 지속되는 것을 관찰할 수 있었다. 결론: HMA와 genistein에 의한 KS62세포의 방사선 유도 세포사망의 변화는 세포주기 조절과 밀접하게 연관되어 있음을 확인하였다. 이는 다양한 방사선 유도 세포사망의 기전을 이해하는 데 독창적인 모델을 제공하며, 방사선을 이용한 암 치료법의 개발에 새로운 표적을 제공할 수 있을 것이다.

• Journal of Microbiology and Biotechnology
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• 제27권2호
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• pp.405-411
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• 2017

Homologous recombination occurs between homologous chromosomes and is significantly involved in programmed double-strand break (DSB) repair. Activation of two recombinases, Rad51 and Dmc1, is essential for an interhomolog bias during meiosis. Rad51 participates in both mitotic and meiotic recombination, and its strand exchange activity is regulated by an inhibitory factor during meiosis. Thus, activities of Rad51 and Dmc1 are coordinated to promote homolog bias. It has been reported that Hed1, a meiosis-specific protein in budding yeast, regulates Rad51-dependent recombination activity. Here, we investigated the role of Hed1 in meiotic recombination by ectopic expression of the protein after pre-meiotic replication in Saccharomyces cerevisiae. DNA physical analysis revealed that the overexpression of Hed1 delays the DSB-to-joint molecule (JM) transition and promotes interhomolog JM formation. The study indicates a possible role of Hed1 in controlling the strand exchange activity of Rad51 and, eventually, meiotic crossover formation.