• Title/Summary/Keyword: pRB

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Effects of an Extract from the Roots of Platycodon Grandiflorum on the Levels of p53 and pRB in NCI-H460 Human Lung Carcinoma Cells (길경 수용액 추출물에 의한 NCI-H460 인체 폐암세포의 p53 및 pRB의 발현에 미치는 영향)

  • Park, Bong-Kyu;Gam, Chul-Woo;Heo, Tae-Yool;Park, Dong-Il
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1530-1537
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    • 2006
  • Platycodi Radix, the root of Platycodon grandiflorum A. DC (Campanulaceae), commonly known as Doraji in Korea (Chinese name, 'Jiegeng', and Japanese name, 'Kikyo') has been used as an expectorant in traditional Oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health benefits. In Korea, Platycodi Radix is also used as a food and employed as a folk remedy for adult diseases, such as bronchitis, asthma and pulmonary tuberculosis, hyperlipidemia, diabetes, and inflammatory diseases, and as a sedative. Several studies on its chemical and immunopharmacological effects including immunostimulation and antitumor activity have been performed. However, the relevant molecular mechanisms are poorly understood. Platycodi Radix, the root of Platycodon grandiflorum A. DC (Campanulaceae), commonly known as Doraji in Korea (Chinese name, 'Jiegeng', and Japanese name, 'Kikyo') has been used as an expectorant in traditional Oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health bensfits. In Korea, Platycodi Radix is also used as a food and employed as a folk remedy for adult diseases, such as bronchitis, asthma and pulmonary tuberculosis, hyperlipidemia, diabetes, and inflammatory diseases, and as a sedative. Several studies on its chemical and immunopharmacological effects including immunostimulation and antitumor activity have been performed. However, the relevant molecular mechanisms are poorly understood. In the present study, we investigated the effects of an aqueous extract from the roots of P. grandiflorum AEPG) on the cell growth of human lung adenocarcinoma NCI-H460 cells in order to understand its anti-proliferative mechanism. AEPG treatment down-regulated the cyclin D1 expression in both transcriptional and translational levels without alteration of cyclin E. In AEPG-treated cells, the levels of cyclin-dependent kinase (C아) 6 mRNA and protein were significantly inhibited, but the levels of Cdk2 and Cdk4 were slightly inhibited by treatment of AEPG. AEPG treatment induced a marked accumulation of Cdk inhibitors, p16 and p27. However, AEPG treatment did not affect not only retinoblastoma protein (pRB) but also tumor suppressor p53 protein expression. The present results indicated that AEPG-induced inhibition of lung cancer cell proliferation is associated with the blockage of G1 phase progression through induction of Cdk inhibitors such as p16 and p27, and inhibition of cyclin D1 and Cdk6. AEPG exposure, as offered by this study, provides cluse for the mechanism of AEPG action. Taken together, these findings suggest that P. grandiflorum has strong potential for development as an agent for prevention and treatiment against human lung cancer.

Combined chemotherapy and intra-arterial chemotherapy of retinoblastoma

  • Choi, Saerom;Han, Jung Woo;Kim, Hyosun;Kim, Beom Sik;Kim, Dong Joon;Lee, Sung Chul;Lyu, Chuhl Joo
    • Clinical and Experimental Pediatrics
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    • v.56 no.6
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    • pp.254-259
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    • 2013
  • Purpose: Retinoblastoma (RB) is the most common primary malignant intraocular tumor in children. Although systemic chemotherapy has been the primary treatment, intra-arterial chemotherapy (IAC) represents a new treatment option. Here, we performed alternate systemic chemotherapy and IAC and retrospectively reviewed the efficacy and safety of this approach. Methods: Patients diagnosed with intraocular RB between January 2000 and December 2011 at Severance Children's Hospital, Yonsei University, were reviewed. Before February 2010, the primary treatment for RB was chemotherapy (non-IAC/CTX). Since February 2010, the primary treatment for RB has been IAC (IAC/CTX). External beam radiotherapy or high-dose chemotherapy were used as "last resort" treatments just prior to enucleation at the time of progression or recurrence during primary treatment. Enucleation-free survival (EFS) and progression-free survival were assessed. Results: We examined 19 patients (median age, 11.9 months; range, 1.4 to 75.6 months) with a sum of 25 eyes, of which, 60.0% were at advanced Reese Ellsworth (RE) stages. The enucleation rate was 33.3% at early RE stages and 81.8% at advanced RE stages (P=0.028). At 36 months, EFS was significantly higher in the IAC/CTX group than in the non-IAC/CTX group (100% vs. 40.0%, P=0.016). All 5 patients treated with IAC achieved eye preservation, although most patients were at advanced RE stages (IV-V). Conclusion: Despite the limitation of a small sample size, our work shows that an alternative combined approach using IAC and CTX may be safe and effective for eye preservation in advanced RB.

The Effects of Breath-Counting Meditation and Deep Breathing on Heart Rate Variability

  • Kim, Ji-Hwan;Bae, Hyo-Sang;Park, Seong-Sik
    • The Journal of Korean Medicine
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    • v.37 no.2
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    • pp.36-44
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    • 2016
  • Objectives: This study aimed to evaluate the effects of breath-counting meditation (BCM) and deep breathing (DB) on heart rate variability (HRV). These breathing techniques have the characteristics of non-paced and self-controlled breathings, resulting in less increase of HRV. We also compared BCM and DB with usual breathing (UB) or relaxing breathing (RB) which can reveal the characteristics of those. Methods: 83 healthy volunteers sitting in chairs performed non-paced breathing; UB, RB, BCM, and DB each for 5 minutes. One minute of relaxation was permitted between breathings. Participants surfed the internet sitting in front of a computer during UB, while for RB, they remained steady with eyes closed. For BCM, they breathed inwardly counting from 1 to 10 repetitively, while they took a deep breath during DB. Physiological indices were simultaneously recorded with a biofeedback system. Results: Respiration rate, thoracic amplitude, and mean heart rate decreased in RB compared with UB, but there was no change in HRV. Respiration rate in BCM and DB was lower than that in UB or RB, and the amplitude of thorax or abdomen, and HRV all increased (p<0.05). However, mean heart rate and skin conductance decreased in BCM compared with UB (p<0.05), whereas those were no different between DB and UB. Conclusion: BCM, just concentrating mentally on breathing with counting each breath, can increase HRV with less sympathetic activation, while DB, actively moving thorax and abdomen for achieving the deepest respiration rate, can greatly raise HRV with the maintenance of mean vagal or sympathetic tone.

Enzymatic Biotransformation of Ginsenoside Rb1 and Gypenoside XVII into Ginsenosides Rd and F2 by Recombinant β-glucosidase from Flavobacterium johnsoniae

  • Hong, Hao;Cui, Chang-Hao;Kim, Jin-Kwang;Jin, Feng-Xie;Kim, Sun-Chang;Im, Wan-Taek
    • Journal of Ginseng Research
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    • v.36 no.4
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    • pp.418-424
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    • 2012
  • This study focused on the enzymatic biotransformation of the major ginsenoside Rb1 into Rd for the mass production of minor ginsenosides using a novel recombinant ${\beta}$-glucosidase from Flavobacterium johnsoniae. The gene (bglF3) consisting of 2,235 bp (744 amino acid residues) was cloned and the recombinant enzyme overexpressed in Escherichia coli BL21(DE3) was characterized. This enzyme could transform ginsenoside Rb1 and gypenoside XVII to the ginsenosides Rd and F2, respectively. The glutathione S-transferase (GST) fused BglF3 was purified with GST-bind agarose resin and characterized. The kinetic parameters for ${\beta}$-glucosidase had apparent $K_m$ values of $0.91{\pm}0.02$ and $2.84{\pm}0.05$ mM and $V_{max}$ values of $5.75{\pm}0.12$ and $0.71{\pm}0.01{\mu}mol{\cdot}min^{-1}{\cdot}mg$ of $protein^{-1}$ against p-nitrophenyl-${\beta}$-D-glucopyranoside and Rb1, respectively. At optimal conditions of pH 6.0 and $37^{\circ}C$, BglF3 could only hydrolyze the outer glucose moiety of ginsenoside Rb1 and gypenoside XVII at the C-20 position of aglycon into ginsenosides Rd and F2, respectively. These results indicate that the recombinant BglF3 could be useful for the mass production of ginsenosides Rd and F2 in the pharmaceutical or cosmetic industry.

Coupling Intensity Effects in Ladder-type Electromagnetically Induced Transparency of Rb atoms (결합광 세기에 따른 Rb 원자의 사다리형 전자기 유도 투과)

  • Moon, H.S.;Lee, L.;Kim, J.B.
    • Korean Journal of Optics and Photonics
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    • v.16 no.1
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    • pp.1-6
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    • 2005
  • We have studied the polarization effects and the coupling intensity effects of electromagnetically induced transparency(EIT) in the 5S$_{1}$2-/5P$_{3}$2-/5D$_{5}$2/ ladder system of Rb. We obtained the EIT spectrum with the hyperfine structure of 5D$_{5}$2/ transitions and the minimal width of the measured EIT spectrum was 6.5 MHz. We observed the change of the relative magnitudes of the hyperfine structure of EIT according to not only the polarizations of lasers but also the intensity of the coupling laser. The cause of the coupling intensity effects is that the EIT signal nonlinearly increases to the coupling intensity.

Association of Dexamethasone-induced Apoptosis and $G_l-Arrest$ of Human Leukemic CEM Cells with Polyamine Deficit

  • Choi, Sang-Hyun;Lee, Jung-Ae;Chae, Yang-Seok;Min, Bon-Hong;Chun, Yeon-Sook;Chun, Boe-Gwun
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.4
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    • pp.457-466
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    • 1997
  • The effects of DFMO or/and putrescine on the dexamethasone-induced apoptosis of CEM cells were studied to investigate the role of polyamines in anti-leukemic glucocorticoid action. Dexamethasone- induced apoptosis was preceded by significant decreases of cellular polyamine contents and putrescine uptake activity. But DFMO produced decreases of putrescine and spermidine contents and marked increase of putrescine uptake activity, but did not induce apoptosis. However, dexamethasone and DFMO, respectively, induced $G_1-arrest$ in cell cycle and hypophosphorylation of pRb, resulting in the increase of $G_1$ to S ratio and decrease of CEM cell count. DFMO enhanced the dexamethasone-induced apoptosis and $G_1-arrest$. On the other hand, putrescine little affected the apoptotic and $G_1-arresting$ activities of dexamethasone, but almost suppress the effects of DFMO and also the DFMO-dependent enhancement of dexamethasone effects. These results suggested that the dexamethasone-induced apoptosis to be associated with pRb hypophosphorylation and $G_1-arrest$ in CEM cells might be ascribed to the concomitant decreases of cellular polyamine contents and putrescine uptake activity.

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Effect of Rice Bran Dietary Fiber Level on Serum Lipid Concentration, Bowel Function, and Mineral Absorption in Rats (미강 식이섬유 첨가량이 흰쥐의 혈청지질농도, 장 기능 및 무기질 흡수율에 미치는 영향)

  • Jin, Hyun-Jung;Lee, Sang-Sun
    • The Korean Journal of Food And Nutrition
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    • v.24 no.4
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    • pp.622-629
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    • 2011
  • This study was performed to investigate the effect of rice bran dietary fiber powder on serum lipid levels, bowel function, and mineral absorption in rats. Four weeks old male Sprague Dawley rats(SD rat) were divided into four groups : control group fed 5% cellulose as a fiber source, RB10 fed 5% of cellulose and 10% of rice bran dietary fiber powder, RB20 and RB30. The animals were fed the experimental diets for 4 weeks. Serum lipid levels were not significantly different among the groups. But, fecal total cholesterol(TC), triglycerides(TG), and high density lipoprotein cholesterol(HDL-c) excretion increased in the RB30 group. Fecal weight and fecal water content were higher in the rice bran added groups than those in the control group. Transit time was significantly shorter in the rice bran fiber-added groups than that in the control. Weight of the stomach and large intestine in the RB20 and RB30 groups were significantly greater than those in the other groups. Absorption rates of Ca, Mg, P, and Zn decreased significantly in the RB30 group compared to those in the other groups. A high amount of rice bran increased fecal lipids, including TC, TG and HDL-c. Rice bran increased fecal weight and fecal water content and shortened gastrointestinal transit time. However, a high level of rice bran diet decreased mineral absorption rates.

Development of a Screening System for Drugs Against Human Papillomavirus-Associated Cervical Cancer: Based On E7-Rb Binding

  • Cho, Young-Sik;Cho, Cheong-Weon;Kang, Jeong-Woo;Cho, Min-Chul;Lee, Kyung-Ae;Shim, Jung-Hyun;Kwon, Our-Han;Choe, Yong-Kyung;Park, Sue-Nie;Yoon, Do-Young
    • BMB Reports
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    • v.34 no.1
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    • pp.80-84
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    • 2001
  • The human papillomavirus E7 protein can form a specific complex with a retinoblastoma tumor suppressor gene product (p105-Rb) that results in the release of the E2F transcription factor, which is critical for the growth-deregulation and transforming properties of the viral E7 oncoprotein. In an attempt to apply interaction between the E7 oncoprotein and a target cellular protein Rb for an in vitro screening system for drugs against human papillomavirus infection, we primarily investigated the E7Rb binding through a pull down assay and enzyme-linked immunosorbent assay. The pull down assay showed that both glutathione S-transferase-tagged E7 and His-tagged E7 immobilized on resins specifically produced complexes with bacterially expressed Rb in a dose-dependent manner, as determined by immunoblot analyses. This result coincided with that of an enzyme-linked immunosorbent assay, which is a useful system for the mass screening of potential drugs. Taken together, this screening system (based on the interaction between E7 and Rb) can be a promising system in the development of drugs against cervical cancers caused by human papillomavirus infection.

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Synthesis, Sytructure, and Magnetic Properties of One-Dimensional Thiophoshates, $Al_2NiP_2S_6$ (A=Rb, Cs) (1차원 구조를 갖는 Thiophoshates, $Al_2NiP_2S_6$ (A=Rb, Cs)의 합성, 구조 및 자기적 성질)

  • Dong, Yong Kwan;Lee, Kun Soo;Yun, Ho Seop;Hur, Nam Hwi
    • Journal of the Korean Chemical Society
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    • v.45 no.3
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    • pp.242-246
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    • 2001
  • The quaternary thiophosphates, $A_2NiP_2S_6$ (A=Rb, Cs), have been synthesized with halide fluxes and structurally characterized by single-crystal X-ray diffraction technique. These compounds crystallize in the space group $C_{2h}^5-P2_1/n$ of the monoclinic system with two formula units in a cell of dimensions a=5.960(2), b=12.323(4), $c=7.491(3)\AA$, $\beta=97.05(3)^{\circ}$, and $V=546.0(3)\AA^3$ for Rb2NiP2S6 and a=5.957(4), b=12.696(7), $c=7.679(4)\AA$, $b=93.60(5)^{\circ}$, and $V=579.7(5)\AA^3$ for $Cs_2NiP_2S_6.$ These compounds are isostructural. The structure of $Cs_2NiP_2S_6$ is made up of one-dimensional $_\infty^1[NiP_2S_6^{2-}]$ chains along the a axis and these chains are isolated by $Cs^+$ ions. The Ni atom is octahedrally coordinated by six S atoms. These Ni$S_6$ octahedral units are linked by sharing three m-S atoms of the $[P_2S_6^{4-}]$ anions to form the infinite one-dimensional $_\infty^1[NiP_2S_6^{2-}]$ chain. For $Cs_2NiP_2S_6$, the magnetic susceptibility reveals an antiferromagnetic exchange interaction below 8K,which corresponds to the Neel temperature ($T_N$). Above $T_N$, this compound obeys Curie-Weiss law. The magnetic moment, C, and ${\theta}forCs_2NiP_2S_6$ are 2.77 B.M., 0.9593 K, and -19.02 K, respectively. The effective magnetic moment obtained from the magnetic data is agreed with the spin-only value of $Ni^{2+}d^8$(2.83 B.M.) system.

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The Geochemistry of Yuksipryeong Two-Mica Leucogranite, Yeongnam Massif, Korea (영남육괴내 육십령 복운모화강암에 대한 지화학적 연구)

  • Koh, Jeong-Seon;Yun, Sung-Hyo
    • The Journal of the Petrological Society of Korea
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    • v.12 no.3
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    • pp.119-134
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    • 2003
  • Yuksipryeong two-mica granite presents strongly peraluminous characteristics in both mineralogy and geochemistry. It has high aluminum saturation index with 1.15∼l.20 and high corundum with 2.20∼2.98 wt% CIPW norm. As the color index is <16% and FeO$\^$T/+ MgO + TiO$_2$is average 1.9 wt%, it corresponds to leucogranite. Yuksipryeong two-mica leucogranite shows negative linear trend for TiO$_2$, Al$_2$O$_3$, FeO, Fe$_2$O$_3$, MgO, CaO, K$_2$O, P$_2$O$\_$5/, Rb, Ba, and Sr as SiO$_2$increases, and the positive relation of Zr and Th, which result from feldspar, biotite, apatite and zircon fractionation. Pegmatitic dike has higher SiO$_2$and P$_2$O$\_$5/, but lower another major elements. Yuksipryeong two-mica leucogranite has lower Rb, but higher Ba and Sr than Manaslu, Hercynian two-mica leucogranites, and S-type granites in Lachlan Fold Belt. Pegmatitic dike has higher Rb and Nb but lower Ba, Sr, Zr, Th, and Pb contents than Yuksipryeong two-mica leucogranite, resulting in removing or mobilizing for some trace elements from the granitic melt. Yuksipryeong two-mica leucogranite has total REEs with 95.7∼l23.3 ppm, and chondrite-normalized REE pattern is very steep ((La/Yb)$\_$N/ = 6.9∼24.8), light REEs (LREEs)-enriched End heavy REEs (HREEs)- depleted pattern with low to moderate Eu anomalies (Eu/Eu*= 0.7∼0.9). While pegmatitic dike has low total REEs with 7.0 ppm, and chondrite-normalized REE pattern is flat-pattern ((La/Yb)$\_$N/ = 2.1) with strong negative Eu anomalies (Eu/Eu*= 0.2). The melt compositions having formed two-mica leucogranites depend on not only the source rock but also the amounts of the residual remaining after melting of source rocks. The CaO/Na$_2$O and Rb/Sr-Rb/Ba ratios depend mainly on the composition of source rocks in the strongly peraluminous granite, that is, plagioclase/clay ratio of the source rocks. Yuksipryeong two-mica leucogranite has higher CaO/Na$_2$O and lower Rb/Sr-Rb/Ba ratios than Manaslu and Hercynian two-mica leucogranites (Millevaches and Gueret) derived from clay-rich, plagioclase-poor (polite), which suggest that the probable source rocks for Yuksipryeong two-mica leucogranite is clay-poor, plagioclase-rich quartzofeldspathic rocks. As the concentrations of Al$_2$O$_3$remain nearly constant but those of TiO$_2$increases as increasing temperature in the strong peraluminous melt, the Al$_2$O$_3$/TiO$_2$ratio may reflect relative temperature at which the melts have formed. Comparing the polite-derived Manaslu and Hercynian two- mica leucogranites, Manaslu two-mica leucogranite has higher Al$_2$O$_3$/TiO$_2$ratio than latter, and its melt have formed at relatively lower temperature ($\leq$ 875$^{\circ}C$) than Hercynian two-mica leucogranites. Likewise, comparing the quartzofeldspathic rock-derived granites, Yuksipryeong two-mica granite has higher Al$_2$O$_3$/TiO$_2$, ratio than S-type granites in Lachlan Fold Belt (>875$^{\circ}C$). The melt formed Yuksipryeong two-mica leucogranite are considered to have been formed at temperature at below the maximum 875$^{\circ}C$C$.