• Biomolecules & Therapeutics
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• v.23 no.4
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• pp.320-326
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• 2015

The clinical benefits of oncogenic BRAF inhibitor therapies are limited by the emergence of drug resistance. In this study, we investigated the role of a negative regulator of the MAPK pathway, Spry2, in acquired resistance using BRAF inhibitor-resistant derivatives of the BRAF-V600E melanoma (A375P/Mdr). Real-time RT-PCR analysis indicated that the expression of Spry2 was higher in A375P cells harboring the BRAF V600E mutation compared with wild-type BRAF-bearing cells (SK-MEL-2) that are resistant to BRAF inhibitors. This result suggests the ability of BRAF V600E to evade feedback suppression in cell lines with BRAF V600E mutations despite high Spry2 expression. Most interestingly, Spry2 exhibited strongly reduced expression in A375P/Mdr cells with acquired resistance to BRAF inhibitors. Furthermore, the overexpression of Spry2 partially restored sensitivity to the BRAF inhibitor PLX4720 in two BRAF inhibitor-resistant cells, indicating a positive role for Spry2 in the growth inhibition induced by BRAF inhibitors. On the other hand, long-term treatment with PLX4720 induced pERK reactivation following BRAF inhibition in A375P cells, indicating that negative feedback including Spry2 may be bypassed in BRAF mutant melanoma cells. In addition, the siRNA-mediated knockdown of Raf-1 attenuated the rebound activation of ERK stimulated by PLX4720 in A375P cells, strongly suggesting the positive role of Raf-1 kinase in ERK activation in response to BRAF inhibition. Taken together, these data suggest that RAF signaling may be released from negative feedback inhibition through interacting with Spry2, leading to ERK rebound and, consequently, the induction of acquired resistance to BRAF inhibitors.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4329-4333
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• 2015

Background: To investigate the change of frequency and immuno-inhibitory function of myeloid-derived suppressor cells (MDSCs) after treatment of cisplatin (DDP) in A375 human melanoma model. Materials and Methods: BALB/c nude mice were inoculated with A375 cells to establish the human melanoma model and randomly divided into control group given normal saline (NS) and experimental group treated with DDP (5 mg/kg). The percentages of MDSCs in the tumor tissue and peripheral blood after DDP treatment were detected by flow cytometry. The proliferation and interferon-${\gamma}$ (IFN-${\gamma}$) secretion of T cells co-cultured with MDSCs were analyzed through carboxyfluorescein succinimidyl ester (CFSE) labeling assay and enzyme-linked immunospot (ELISPOT) assay, respectively. Results: In A375 human melanoma model, DDP treatment could significantly decrease the percentage of MDSCs in the tumor tissue, but exerted no effect on the level of MDSCs in peripheral blood. Moreover, DDP treatment could attenuate the immuno-inhibitory function of MDSCs. T cells co-cultured with DDP-treated MDSCs could dramatically elevate the proliferation and production of INF-${\gamma}$. Conclusions: DDP can decrease the frequency and attenuate immuno-inhibitory function of MDSCs in A375 melanoma model, suggesting a potential strategy to augment the efficacy of combined immunotherapy.

• Bulletin of the Korean Chemical Society
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• v.33 no.9
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• pp.2991-2998
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• 2012

A series of new diarylureas and diarylamides possessing 1,3,4-triarylpyrazole scaffold was synthesized and their in vitro antiproliferative activities against A375P human melanoma cell line and NCI-60 cell line panel were tested. Compounds 9, 11, 12, 14, and 17-21 showed superior potency against A375P to Sorafenib. Over the NCI-60 cancer cell line panel, compound 14 possessing a methoxy group, amide linker, and 4-chloro-3-(trifluoromethyl)phenyl terminal ring showed the highest potency and broad-spectrum anticancer activity. Compound 13 showed high selectivity towards leukemia subpanel over other cancer types.

• Bulletin of the Korean Chemical Society
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• v.33 no.11
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• pp.3635-3639
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• 2012

A series of new diarylureas possessing aminoisoquinoline scaffold was synthesized, and their in vitro antiproliferative activity against A375P human melanoma cell line was tested. Compounds 1d, 1l, 1n, 1p, 1q, and 1t showed superior potency against A375P to Sorafenib. The highest potency was shown by compound 1p possessing 3,5-bis(trifluoromethyl)phenyl terminal ring with $IC_{50}$ value of $0.41{\mu}M$.

• Asian-Australasian Journal of Animal Sciences
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• v.9 no.4
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• pp.359-362
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• 1996

A study was conducted to assess the influence of copper on the total sulphur amino acid requirements of broiler chickens reared under two growing periods. The TSAA levels used were 0.73, 0.83, 0.93% with copper levels of 0, 125, 250 and 375 mg/kg for the starter period and the TSAA levels of 0.72, 0.79 and 0.86% with copper levels of 0, 125, 250 and 375 mg/kg for the grower period. Total feed consumption, body weight gain and feed L gain ratio were used as the parameters for the assessment. The results showed that adding copper at 250 mg/kg to the diets improved feed : gain ratio of the starter broilers and resulted in small improvement of body weight gain and feed : gain ratio of the grower broilers. Growth was depressed in relation to the reduction of feed intake on the chicks fed diet containing 375 mg/kg copper. There was a significant interaction between dietary TSAA and copper levels for feed intake, hence, indicating that the supplementation of copper at the level of 375 mg/kg increased the TSAA requirement of the starter broilers, although no interference with the requirement of grower broilers.

• Honam Mathematical Journal
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• v.32 no.3
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• pp.375-387
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• 2010

The paper studies an existence problem of a (generalized) universal covering space over a digital wedge with a compatible adjacency. In algebraic topology it is well-known that a connected, locally path connected, semilocally simply connected space has a universal covering space. Unlike this property, in digital covering theory we need to investigate its digital version which remains open.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.26 no.3
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• pp.273-277
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• 1981

This study was carried out in 1979 to establish the proper mulching culture method for an aromatic tobacco, ST 375-4. Three different methods of mulching were employed: Improved mulching (I. M.), General mulching (G. M.) and Non-mulching (N. M.). The number of seedlings per hole was 5 for I. M., and one for G. M. and N. M. In comparison with N. M., I. M. had shortened final date of leaf harvest by 14 days, enabling curing leaves before the rainy season. It also reduced transplanting labour hours by 44.9%. Yield and price value increased with improved mulching culture. There was little difference in relative light intensity at leaves between N. M. and I. M.

• Bulletin of the Korean Mathematical Society
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• v.50 no.2
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• pp.375-388
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• 2013

In this paper, we introduce an iterative sequence for finding solution of a system of mixed equilibrium problems and the set of fixed points of a nonexpansive mapping in Hilbert spaces. Then, the weak and strong convergence theorems are proved under some parameters controlling conditions. Moreover, we apply our result to fixed point problems, system of equilibrium problems, general system of variational inequalities, mixed equilibrium problem, equilibrium problem and variational inequality.

• Communications of the Korean Mathematical Society
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• v.21 no.2
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• pp.375-384
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• 2006

We consider a class of bilinear models with periodic regime switching and find easy-to-check sufficient conditions that ensures the existence of a stationary process obtained from given difference equation. Existence of a higher order moments is examined.

• Honam Mathematical Journal
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• v.34 no.3
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• pp.375-379
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• 2012

We find a general solution $f:G{\rightarrow}G$ of the symmetric functional equation $$x+f(y+f(x))=y+f(x+f(y)),\;f(0)=0$$ where G is a 2-divisible abelian group. We also prove that there exists no measurable solution $f:\mathbb{R}{\rightarrow}\mathbb{R}$ of the equation. We also find the continuous solutions $f:\mathbb{C}{\rightarrow}\mathbb{C}$ of the equation.