• BMB Reports
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• v.46 no.2
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• pp.113-118
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• 2013

TTRAP is a multi-functional protein that is involved in multiple aspects of cellular functions including cell proliferation, apoptosis and the repair of DNA damage. Here, we demonstrated that the lentivirus-mediated overexpression of TTRAP significantly inhibited cell growth and induced apoptosis in osteosarcoma cells. The ectopic TTRAP suppressed the growth and colony formation capacity of two osteosarcoma cell lines, U2OS and Saos-2. Cell apoptosis was induced in U2OS cells and the cell cycle was arrested at G2/M phase in Saos-2 cells. Exogenous expression of TTRAP in serum-starved U2OS and Saos-2 cells induced an increase in caspase-3/-7 activity and a decrease in cyclin B1 expression. In comparison with wild-type TTRAP, mutations in the 5'-tyrosyl-DNA phosphodiesterase activity of TTRAP, in particular $TTRAP^{E152A}$, showed decreased inhibitory activity on cell growth. These results may aid in clarifying the physiological functions of TTRAP, especially its roles in the regulation of cell growth and tumorigenesis.

• Biotechnology and Bioprocess Engineering:BBE
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• v.5 no.5
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• pp.382-385
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• 2000

A mathematical model was developed, based on the time dependent changes of the specific growth rate, for prediction of the typical microbial cell growth in batch cultures. This model could predict both the lag growth phase and the stationary growth phase of batch cultures, and it was tested with the batch growth of Trichoderma reesei and Lactobacillus delbrueckii.

• Biomolecules & Therapeutics
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• v.24 no.2
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• pp.147-155
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• 2016

Chaetominine is a quinazoline alkaloid originating from the endophytic fungus Aspergillus fumigatus CY018. In this study, we showed evidence that chaetominine has cytotoxic and apoptotic effects on human leukemia K562 cells and investigated the pathway involved in chaetominine-induced apoptosis in detail. Chaetominine inhibited K562 cell growth, with an $IC_{50}$ value of 35 nM, but showed little inhibitory effect on the growth of human peripheral blood mononuclear cells. The high apoptosis rates, morphological apoptotic features, and DNA fragmentation caused by chaetominine indicated that the cytotoxicity was partially caused by its pro-apoptotic effect. Under chaetominine treatment, the Bax/Bcl-2 ratio was upregulated (from 0.3 to 8), which was followed by a decrease in mitochondrial membrane potential, release of cytochrome c from mitochondria into the cytosol, and stimulation of Apaf-1. Furthermore, activation of caspase-9 and caspase-3, which are the main executers of the apoptotic process, was observed. These results demonstrated that chaetominine induced cell apoptosis via the mitochondrial pathway. Chaetominine inhibited K562 cell growth and induced apoptotic cell death through the intrinsic pathway, which suggests that chaetominine might be a promising therapeutic for leukemia.

• Radiation Oncology Journal
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• v.17 no.3
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• pp.223-229
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• 1999

Purpose : The expression pattern of c-jun by ionizing radiation according to cell growth state (exponential growth vs. stationary phase) and its relationship with cell cycle redistribution were investigated. Materials and Methods : The exponential growth phase (day 4) and stationary phase (day 9) cells were determined from cell growth curve according to the elapse of days in CaSki. The cells were irradiated using 6 MV X-ray with a dose of 2 Gy at a fixed dose rate of 3 Gy/min. Northern blot analysis was peformed with total cellular RNA and cell cycle distribution was analyzed using flow cytometry according to time-course after irradiation. Results : The maximum expression of c-jun occurred 1 hour after irradiation in both exponential growth and stationary phase cells. After then c-jun expression was elevated upto 6 hours in exponential growth phase cells, but the level decreased in stationary phase cells. Movements of cells from G0-G1 to S, G2-M phase after irradiation were higher in exponential growth phase than stationary phase. Conclusion : c-jun may be involved in the regulation of cellular proliferation according to the growth states after irradiation.

• Journal of Microbiology and Biotechnology
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• v.8 no.1
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• pp.8-13
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• 1998

Animal cells in culture typically convert most of the glucose they consume into lactate. The accumulation of lactate, however, is commonly cited as one of the factors that inhibit cell growth and limit the maximum cell concentration that can be achieved in culture. The specific production of lactate and the amount of glucose converted to lactate can be reduced when cells are grown in a fed-batch culture in which the residual glucose concentration is maintained at low levels. Such a fed-batch culture was used to grow and adapt hybridoma cells into a low-lactate-producing state before changing into continuous culture. The cells reached and maintained a high viable cell concentration at steady state. In a similar manner, cells that were initially grown in batch culture and a glucose-rich environment reached a steady state with a cell concentration that is much lower. The feed composition and dilution rates for both cultures were similar, suggesting steady state multiplicity. From a processing perspective the desired steady state among those is the one with the least metabolite production. At such seady state nutrient concentration in the feed can be further increased to increase cell and product concentrations without causing the metabolite inhibitory effect typically seen in a cell culture. Controlling cell metabolism in a continuous culture to reduce or eliminate waste metabolite production may significantly improve the productivity of mammalian cell culture processes.

• BMB Reports
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• v.36 no.1
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• pp.49-59
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• 2003

Platelet-derived growth factor (PDGF) is a critical regulator of mesenchymal cell migration and proliferation. The vital functions of PDGFs for angiogenesis, as well as development of kidney, brain, cardiovascular system and pulmonary alveoli during embryogenesis, have been well demonstrated by gene knock-out approaches. Clinical studies reveal that aberrant expression of PDGF and its receptor is often associated with a variety of disorders including atherosclerosis, fibroproliferative diseases of lungs, kidneys and joints, and neoplasia. PDGF contributes to cancer development and progression by both autocrine and paracrine signaling mechanisms. In this review article, important features of the PDGF isoforms and their cell surface receptor subunits are discussed, with regards to signal transduction, PDGF-isoform specific cellular response, and involvement in angiogenesis, and tumorstromal interactions.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3233-3238
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• 2012

Esophageal carcinoma (EC) is one of the most aggressive cancers with a poor prognosis. Understanding the molecular mechanisms underlying esophageal cancer progression is a high priority for improved EC diagnosis and prognosis. Recently, MSP58 was shown to behave as an oncogene in colorectal carcinomas and gliomas. However, little is known about its function in esophageal carcinomas. We therefore examined the effects of MSP58 knockdown on the growth of esophageal squamous cell carcinoma (ESCC) cells in vitro and in vivo in order to gain a better understanding of its potential as a tumor therapeutic target. We employed lentiviral-mediated small hairpin RNA (shRNA) to knock down the expression of MSP58 in the ESCC cell lines Eca-109 and EC9706 and demonstrated inhibition of ESCC cell proliferation and colony formation in vitro. Furthermore, flow cytometry and western blot analyses revealed that MSP58 depletion induced cell cycle arrest by regulating the expression of P21, CDK4 and cyclin D1. Notably, the downregulation of MSP58 significantly inhibited the growth of ESCC xenografts in nude mice. Our results suggest that MSP58 may play an important role in ESCC progression.

• Journal of Microbiology and Biotechnology
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• v.23 no.11
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• pp.1586-1597
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• 2013

Energy-efficient metabolic responses were often noted in high-productive cultures. To better understand these metabolic responses, an investigation into the relationship between metabolic responses and energy regulation was conducted via a comparative analysis among cultures with different energy source supplies. Both glycolysis and glutaminolysis were studied through the kinetic analyses of major extracellular metabolites concerning the fast and slow cell growth stages, respectively, as well as the time-course profiles of intracellular metabolites. In three cultures showing distinct antibody productivities, the amino acid metabolism and energy state were further examined. Both the transition of lactate from production to consumption and steady intracellular pools of pyruvate and lactate were observed to be correlated with efficient energy regulation. In addition, an efficient utilization of amino acids as the replenishment for the TCA cycle was also found in the cultures with upregulated energy metabolism. It was further revealed that the inefficient energy regulation would cause low cell productivity based on the comparative analysis of cell growth and productivity in cultures having distinct energy regulation.

• BMB Reports
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• v.48 no.8
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• pp.473-478
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• 2015

The NEK6 (NIMA-related kinases 6) is reported to play po-tential roles in tumorigenesis. Although it is suggested to function in several cellular pathways, the underlying mechanism in tumorigenesis is still largely unknown. In the present study, we discovered interaction of NEK6 with Smad4, a key member of transforming growth factor beta (TGFβ) pathway. Over-expression of NEK6 in hepatocellular carcinoma (HCC) cell lines suppresses TGFβ-mediated transcription activity in a kinase activity-dependent manner. In addition, NEK6 suppresses the cell growth arrest induced by TGFβ. Mechanically, NEK6 blocks nuclear translocation of Smad4, which is essential for TGFβ function. Moreover, we identified that NEK6 could be regulated by TGFβ and hypoxia. Our study sheds new light on the roles of NEK6 in canonical TGFβ/Smad pathway and tum-origenesis. [BMB Reports 2015; 48(8): 473-478]

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.9
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• pp.1364-1370
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• 2002

The objective of this study was to examine the effect of compensatory growth nutritional regimen on mammary gland growth and lactation. One hundred twenty-two Sprague Dawley female rats (35 days of age) were randomly assigned to either a control or a stair-step compensatory nutrition (SSCN) feeding regimen or an alternating 2-2-3-3-week schedule beginning with 40% energy restriction for 2 weeks followed by re-alimentation (control diet) for 2 weeks. Pup weight gain and milk yield were improved 8% and 8 to 15%, respectively, by the SSCN regimen. The gene expression of $\beta$-casein was 2.3-fold greater in the SSCN group than in the control group during early lactation, but they were greater at all stages of the second lactation. The gene expression of insulin-like growth factor-I was 40% lower in the SSCN group than in the control group during early lactation of the second lactation, but during late lactation it was 80% greater than in the control group. The concentration of serum corticosterone tended to be higher in the SSCN group during the late stage of the first lactation. These results suggest that the stair-step compensatory nutrition regimen improves lactation performance and persistency by modulation of cell differentiation and apoptotic cell death.