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Anti-Tumor Effect of IDF-11774, an Inhibitor of Hypoxia-Inducible Factor-1, on Melanoma

  • Kim, Nan-Hyung;Jeong, Jong Heon;Park, Yu Jeong;Shin, Hui Young;Choi, Woo Kyoung;Lee, Kyeong;Lee, Ai-Young
    • Biomolecules & Therapeutics
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    • v.30 no.5
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    • pp.465-472
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    • 2022
  • Melanoma is one of the most aggressive skin cancers. Hypoxia contributes to the aggressiveness of melanoma by promoting cancer growth and metastasis. Upregulation of cyclin D1 can promote uncontrolled cell proliferation in melanoma, whereas stimulation of cytotoxic T cell activity can inhibit it. Epithelial mesenchymal transition (EMT) plays a critical role in melanoma metastasis. Hypoxia-inducible factor-1α (HIF-1α) is a main transcriptional mediator that regulates many genes related to hypoxia. CoCl2 is one of the most commonly used hypoxia-mimetic chemicals in cell culture. In this study, inhibitory effects of IDF-11774, an inhibitor of HIF-1α, on melanoma growth and metastasis were examined using cultured B16F10 mouse melanoma cells and nude mice transplanted with B16F10 melanoma cells in the presence or absence of CoCl2-induced hypoxia. IDF-11774 reduced HIF-1α upregulation and cell survival, but increased cytotoxicity of cultured melanoma cells under CoCl2-induced hypoxia. IDF-11774 also reduced tumor size and local invasion of B16F10 melanoma in nude mice along with HIF-1α downregulation. Expression levels of cyclin D1 in melanoma were increased by CoCl2 but decreased by IDF-11774. Apoptosis of melanoma cells and infiltration of cytotoxic T cells were increased in melanoma after treatment with IDF-11774. EMT was stimulated by CoCl2, but restored by IDF11774. Overall, IDF-11774 inhibited the growth and metastasis of B16F10 melanoma via HIF-1α downregulation. The growth of B16F10 melanoma was inhibited by cyclin D1 downregulation and cytotoxic T cell stimulation. Metastasis of B16F10 melanoma was inhibited by EMT suppression.

Inhibitory Effects of Methanol Extract of Kaempferia galanga on melanogenesis in B16/F10 Melanoma Cells (B16/F10 흑색종양세포에서 삼내자 메탄올 추출물의 멜라닌 생성에 미치는 억제효과)

  • Yoon, Jung-Won;Han, Jung-Min;Yoon, Hwa-Jung;Ko, Woo-Shin
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.26 no.1
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    • pp.1-18
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    • 2013
  • Objective: Recently the demands for the effective and safe depigmentative and anti-aging agents of the skin have increased due to the medical, pharmaceutical and cosmetic reasons. The purpose of this study is to investigate the MKG(Methanol Extract of Kaempferia galanga) and their dermal bioactivity properties related to cosmeceuticals such as depigmentation. Methods: We assessed inhibitory effects of MKG on melanin production in B16/F10 melanoma cells, on mushroom tyrosinase activity, effects of MKG on the expression tyrosinase, TRP-1, TRP-2, GSK-$3{\beta}$, CREB, MITF in B16/F10 melanoma cells without cytotoxicity range. Cell viability was measured by MTT assay and tyrosinase activity was assessed using by DOPA staining, western-blot analysis. We measured inhibition of melanin synthesis and tyrosinase activity by down-regulation of melanogenic enzyme expressions in ${\alpha}$-MSH induced melanogenesis B16/F10 melanoma cells. Results: MKG inhibited tyrosinase-activity, total melanin contents and dendrite out-growth. MKG inhibited melanogenesis by down-regulation of tyorsinase, TRP-1, TRP-2, CREB, and MITF in B16/F10 cells. The treatment with MKG at the 12.5, $25{\mu}g/ml$ level significantly inhibited the melanin synthesis induced ${\alpha}$-MSH in B16/F10 melanoma cells compared with untreated control. Conclusion: These results suggest that MKG inhibit melanin biosynthesis which is involved in hyper-pigmentation. So MKG is considered to be used as a whitening components reducing cytotoxicity.

Inhibitory Effects of Fractions from Glycine soja Siebold et Zucc. on Melanogenesis in B16F10 Melanoma Cells (B16F10 멜라닌 세포에서 약콩(Glycine soja Siebold et Zucc.) 분획 추출물의 멜라닌 생성 저해 효과)

  • Kim, Bo Ae
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.43 no.3
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    • pp.231-237
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    • 2017
  • This study was performed to cytotoxicity, tyrosinase inhibition activity, intracellular melanin contents to verify the whitening effect of fraction from Glycine soja Siebold et Zucc. (G. soja). Using western blotting, tyrosinase expression in B16F10 melanoma cells and expression levels of tyrosinase related protein-1 (TRP-1) and protein-2 (TRP-2) were examined. As a result, all of the fractions showed a high cell viability over 82% at the concentrations of 0.125, 0.25, 0.5, 2.0 mg/mL. When the whitening effects of fractions from G. soja were tested using B16F10 melanoma cells treated with the ${\alpha}$-melanocyte stimulating hormone (${\alpha}-MSH$), the EtOAc fractions inhibited tyrosinase and melanogenesis effectively. The result of protein expression measurement using western blot showed that TRP-1, TRP-2 and tyrosinase protein expression in B16F10 melanoma cells treated with extracts decreased. Therefore, it is concluded that the fractions from G. soja have whitening effect by inhibiting protein related melanogenesis.

WEKGHTED WEAK TYPE ESTIMATES FOR CERTAIN MAXIMAL OPERATORS IN SPACES OF HOMOGENEOUS TYPE

  • Yoo, Yoon-Jae
    • Bulletin of the Korean Mathematical Society
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    • v.36 no.1
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    • pp.25-31
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    • 1999
  • Let $\nu$ be a positive Borel measure on a space of homogeneous type (X, d, $\mu$), satisfying the doubling property. A condition on a weight $\omega$ for whixh a maximal operator $M\nu f$(x) defined by M$mu$f(x)=supr>0{{{{ { 1} over {ν(B(x,r)) } INT _{ B(x,r)} │f(y)│d mu (y)}}}}, is of weak type (p,p) with respect to (ν, $omega$), is that there exists a constant C such that C $omega$(y) for a.e. y$\in$B(x, r) if p=1, and {{{{( { 1} over { upsilon (B(x,r) } INT _{ B(x,r)}omega(y) ^ (-1/p-1) d mu (y))^(p-1)}}}} C, if 1$infty$.

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A DOUBLE INTEGRAL CHARACTERIZATION OF A BERGMAN TYPE SPACE AND ITS MÖBIUS INVARIANT SUBSPACE

  • Yuan, Cheng;Zeng, Hong-Gang
    • Bulletin of the Korean Mathematical Society
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    • v.56 no.6
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    • pp.1643-1653
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    • 2019
  • This paper shows that if $1<p<{\infty}$, ${\alpha}{\geq}-n-2$, ${\alpha}>-1-{\frac{p}{2}}$ and f is holomorphic on the unit ball ${\mathbb{B}}_n$, then $${\int_{{\mathbb{B}}_n}}{\mid}Rf(z){\mid}^p(1-{\mid}z{\mid}^2)^{p+{\alpha}}dv_{\alpha}(z)<{\infty}$$ if and only if $${\int_{{\mathbb{B}}_n}}{\int_{{\mathbb{B}}_n}}{\frac{{\mid}f(z)-F({\omega}){\mid}^p}{{\mid}1-(z,{\omega}){\mid}^{n+1+s+t-{\alpha}}}}(1-{\mid}{\omega}{\mid}^2)^s(1-{\mid}z{\mid}^2)^tdv(z)dv({\omega})<{\infty}$$ where s, t > -1 with $min(s,t)>{\alpha}$.

NOTES ON THE BERGMAN PROJECTION TYPE OPERATOR IN ℂn

  • Choi, Ki-Seong
    • Communications of the Korean Mathematical Society
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    • v.21 no.1
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    • pp.65-74
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    • 2006
  • In this paper, we will define the Bergman projection type operator Pr and find conditions on which the operator Pr is bound-ed on $L^p$(B, dv). By using the properties of the Bergman projection type operator Pr, we will show that if $f{\in}L_a^p$(B, dv), then $(1-{\parallel}{\omega}{\parallel}^2){\nabla}f(\omega){\cdot}z{\in}L^p(B,dv)$. We will also show that if $(1-{\parallel}{\omega}{\parallel}^2)\; \frac{{\nabla}f(\omega){\cdot}z}{},\;{\in}L^p{B,\;dv),\;then\;f{\in}L_a^p(B,\;dv)$.

SOME RESULTS RELATED WITH POISSON-SZEGÖKERNEL AND BEREZIN TRANSFORM

  • Yang, Gye Tak;Choi, Ki Seong
    • Journal of the Chungcheong Mathematical Society
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    • v.24 no.3
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    • pp.417-426
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    • 2011
  • Let ${\mu}$ be a finite positive Borel measure on the unit ball $B{\subset}{\mathbb{C}}^n$ and ${\nu}$ be the Euclidean volume measure such that ${\nu}(B)=1$. For the unit sphere $S=\{z:{\mid}z{\mid}=1\}$, ${\sigma}$ is the rotation-invariant measure on S such that ${\sigma}(S) =1$. Let ${\mathcal{P}}[f]$ be the Poisson-$Szeg{\ddot{o}}$ integral of f and $\tilde{\mu}$ be the Berezin transform of ${\mu}$. In this paper, we show that if there is a constant M > 0 such that ${\int_B}{\mid}{\mathcal{P}}[f](z){\mid}^pd{\mu}(z){\leq}M{\int_B}{\mid}{\mathcal{P}}[f](z){\mid}^pd{\nu}(z)$ for all $f{\in}L^p(\sigma)$, then ${\parallel}{\tilde{\mu}}{\parallel}_{\infty}{\equiv}{\sup}_{z{\in}B}{\mid}{\tilde{\mu}}(z){\mid}<{\infty}$, and we show that if ${\parallel}{\tilde{\mu}{\parallel}_{\infty}<{\infty}$, then ${\int_B}{\mid}{\mathcal{P}}[f](z){\mid}^pd{\mu}(z){\leq}C{\mid}{\mid}{\tilde{\mu}}{\mid}{\mid}_{\infty}{\int_S}{\mid}f(\zeta){\mid}^pd{\sigma}(\zeta)$ for some constant C.

NOTES ON THE SPACE OF DIRICHLET TYPE AND WEIGHTED BESOV SPACE

  • Choi, Ki Seong
    • Journal of the Chungcheong Mathematical Society
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    • v.26 no.2
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    • pp.393-402
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    • 2013
  • For 0 < $p$ < ${\infty}$, ${\alpha}$ > -1 and 0 < $r$ < 1, we show that if $f$ is in the space of Dirichlet type $\mathfrak{D}^p_{p-1}$, then ${\int}_{1}^{0}M_{p}^{p}(r,f^{\prime})(1-r)^{p-1}rdr$ < ${\infty}$ and ${\int}_{1}^{0}M_{(2+{\alpha})p}^{(2+{\alpha})p}(r,f^{\prime})(1-r)^{(2+{\alpha})p+{\alpha}}rdr$ < ${\infty}$ where $M_p(r,f)=\[\frac{1}{2{\pi}}{\int}_{0}^{2{\pi}}{\mid}f(re^{it}){\mid}^pdt\]^{1/p}$. For 1 < $p$ < $q$ < ${\infty}$ and ${\alpha}+1$ < $p$, we show that if there exists some positive constant $c$ such that ${\parallel}f{\parallel}_{L^{q(d{\mu})}}{\leq}c{\parallel}f{\parallel}_{\mathfrak{D}^p_{\alpha}}$ for all $f{\in}\mathfrak{D}^p_{\alpha}$, then ${\parallel}f{\parallel}_{L^{q(d{\mu})}}{\leq}c{\parallel}f{\parallel}_{\mathcal{B}_p(q)}$ where $\mathcal{B}_p(q)$ is the weighted Besov space. We also find the condition of measure ${\mu}$ such that ${\sup}_{a{\in}D}{\int}_D(k_a(z)(1-{\mid}a{\mid}^2)^{(p-a-1)})^{q/p}d{\mu}(z)$ < ${\infty}$.

RIGIDITY OF PROPER HOLOMORPHIC MAPS FROM Bn+1 TO B3n-1

  • Wang, Sung-Ho
    • Journal of the Korean Mathematical Society
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    • v.46 no.5
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    • pp.895-905
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    • 2009
  • Let $B^{n+1}$ be the unit ball in the complex vector space $\mathbb{C}^{n+1}$ with the standard Hermitian metric. Let ${\Sigma}^n={\partial}B^{n+1}=S^{2n+1}$ be the boundary sphere with the induced CR structure. Let f : ${\Sigma}^n{\hookrightarrow}{\Sigma}^N$ be a local CR immersion. If N < 3n - 1, the asymptotic vectors of the CR second fundamental form of f at each point form a subspace of the CR(horizontal) tangent space of ${\Sigma}^n$ of codimension at most 1. We study the higher order derivatives of this relation, and we show that a linearly full local CR immersion f : ${\Sigma}^n{\hookrightarrow}{\Sigma}^N$, N $\leq$ 3n-2, can only occur when N = n, 2n, or 2n + 1. As a consequence, it gives an extension of the classification of the rational proper holomorphic maps from $B^{n+1}$ to $B^{2n+2}$ by Hamada to the classification of the rational proper holomorphic maps from $B^{n+1}$ to $B^{3n+1}$.

INEQUALITIES FOR THE ANGULAR DERIVATIVES OF CERTAIN CLASSES OF HOLOMORPHIC FUNCTIONS IN THE UNIT DISC

  • Ornek, Bulent Nafi
    • Bulletin of the Korean Mathematical Society
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    • v.53 no.2
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    • pp.325-334
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    • 2016
  • In this paper, a boundary version of the Schwarz lemma is investigated. We take into consideration a function $f(z)=z+c_{p+1}z^{p+1}+c_{p+2}z^{p+2}+{\cdots}$ holomorphic in the unit disc and $\|\frac{f(z)}{{\lambda}f(z)+(1-{\lambda})z}-{\alpha}\|$ < ${\alpha}$ for ${\mid}z{\mid}$ < 1, where $\frac{1}{2}$ < ${\alpha}$ ${\leq}{\frac{1}{1+{\lambda}}}$, $0{\leq}{\lambda}$ < 1. If we know the second and the third coefficient in the expansion of the function $f(z)=z+c_{p+1}z^{p+1}+c_{p+2}z^{p+2}+{\cdots}$, then we can obtain more general results on the angular derivatives of certain holomorphic function on the unit disc at boundary by taking into account $c_{p+1}$, $c_{p+2}$ and zeros of f(z) - z. We obtain a sharp lower bound of ${\mid}f^{\prime}(b){\mid}$ at the point b, where ${\mid}b{\mid}=1$.