• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.493-501
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• 1998

The most significant direct role of estrogen in vivo is its ability to elicit receptor-mediated cellular proliferation in mammalian target tissues. However, the mechanism by which exogenously added estrogen causes the neoplastic transformation of renal cortical cells is yet to be uncovered. The present study was designed to evaluate interaction of $17{\beta}-estradiol\;(E_2)$ with epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I) on proliferation and $P_i$ uptake in primary cultured rabbit renal proximal tubular cells in phenol red-free, hormonally defined-medium. $[^3H]-thymidine$ incorporation increased markedly by about 133% and 141% more in the presence of $10^{-9}\;and\;10^{-6}\;M\;E_2$, respectively, than that of control. Cell count was 162% and 143% greater in the presence of $10^{-9}\;and\;10^{-6}\;M\;E_2$ , respectively, compared with control. Among all time points examined, there was an increase in $[^3H]-thymidine$ incorporation in the presence of $10^{-9}\;M\;E_2$ at day 9 or 13, respectively. However, $E_2$ ($10^{-9}\;M$) significantly drove up cell count to 160% of that of control at day 13, while it had a slight but statistically insignificant effect at day 9. $E_2-induced$ stimulation of $[^3H]-thymidine$ incorporation was completely reversed by $E_2$ antagonists (progesterone or tamoxifen). $E_2$ ($10^{-9}\;M$) or EGF ($10^{-8}\;M$) significantly stimulated $[^3H]-thymidine$ incorporation by 144% and 154% of control. $E_2$ plus EGF was synergistic on $[^3H]-thymidine$ incorporation (204% of control), while $E_2$ plus IGF-I showed a slight but no significant synergistic effect. Cell number also displayed similar pattern. $E_2$ ($10^{-9}\;M$) significantly stimulated $P_i$ uptake to 134% of control. $E_2$-induced stimulation of $P_i$ uptake was partially reversed by $E_2$ antagonists. EGF or IGF-I ($10^{-8}\;M$) significantly also increased $P_i$ uptake to 132% or 129% of control. $E_2$ plus EGF had synergistic effect on $P_i$ uptake, while $E_2$ plus IGF-I did not. In conclusion, $E_2$ may act not only directly interaction with its receptors but also indirectly as a modulator of EGF in proliferation and $P_i$ uptake of primary cultured rabbit renal proximal tubular cells.

• The Korean Journal of Physiology and Pharmacology
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• 제3권1호
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• pp.83-91
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• 1999

Angiotensin II (ANG II) has a biphasic effect on $Na^+$ transport in proximal tubule: low doses of ANG II increase the $Na^+$ transport, whereas high doses of ANG II inhibit it. However, the mechanisms of high dose ANG II-induced inhibition on $Na^+$ uptake are poorly understood. Thus the aim of the present study was to investigate signal transduction pathways involved in the ANG II-induced inhibition of $Na^+$ uptake in the primary cultured rabbit renal proximal tubule cells (PTCs) in hormonally defined serum-free medium. ANG II $(10^{-9}\;M)-induced$ inhibition of $Na^+$ uptake was blocked by losartan $(10^{-8}\;M,\;AT_1\;antagonist),$ but not by PD123319 $(10^{-8}\;M,\;AT_2\;antagonist)$ (P<0.05). ANG II-induced inhibition of $Na^+$ uptake was also completely abolished by neomycin $(10^{-4}\;M,$ PLC inhibitor), W-7 $(10^{-4}\;M,$ calmodulin antagonist), and $AACOCF_3\;(10^{-6}\;M,\;PLA_2\;inhibitor)$ (P<0.05). ANG II significantly increased $[^3H]arachidonic$ acid (AA) release compared to control. The ANG II-induced $[^3H]AA$ release was blocked by losartan, $AACOCF_3,$ neomycin, and W-7, but not by PD123319. ANG II-induced $[^3H]AA$ release in the presence of extracellular $Ca^{2+}$ was greater than in $Ca^{2+}-free$ medium, and it was partially blocked by TMB-8 $(10^{-4}\;M,$ intracelluar $Ca^{2+}$ mobilization blocker). However, in the absence of extracellular $Ca^{2+},$ it was completely blocked by TMB-8. In addition, econazole $(10^{-6}\;M,$ cytochrome P-450 monooxygenase inhibitor) and indomethacin $(10^{-6}\;M,$ cyclooxygenase inhibitor) blocked ANG II-induced inhibition of $Na^+$ uptake, but NGDA $(10^{-6}\;M,$ lipoxygenase inhibitor) did not affect it. In conclusion, $PLA_2-mediated$ AA release is involved in ANG II-induced inhibition of $Na^+$ uptake and is modulated by $[Ca^{2+}]_i$ in the PTCs.

• 핵의학기술
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• 제20권1호
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• pp.47-51
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• 2016

FDG를 이용한 PET/CT 검사에서 FDG의 대부분이 비뇨기계를 통해 배설된다. FDG가 신장에 저류될 경우 판독 성능이 저하된다. PET-CT 검사에서 FDG의 신장 저류로 인해 추가 검사가 필요한 경우 이뇨제 사용 없이 쉬운 방법인 수분 섭취를 이용해 배설을 촉진할 수 있는 방법을 선택하는 데 도움을 주고자 한다. 11개월간 세브란스병원에서 PET-CT 검사를 시행한 환자 중 신장에 질환이 없고 기능이 정상인 환자 총 80명을 대상으로 하였다. 두 집단으로 구분하였고, 각 40명씩 구성하였다. (1) Torso 검사가 끝난 후 수분 섭취 없이 30분 동안 휴식만 취한 집단, (2) 30분 전 물 500 cc를 한 번에 섭취한 후 휴식을 취한 집단으로 나눴다. 영상분석은 SUV 측정과 Blind test, 두 가지로 하였다. SUV 측정은 양쪽 신장의 SUVmax와 근육과 지방의 SUVmax을 VOI 를 설정하여 측정하였고 간의 SUVmean을 ROI를 설정하여 측정하였다. 검증 후에 p < 0.05 인 경우를 통계적으로 유의하다고 판단하였다. Blind test는 Torso 검사와 추가 검사의 영상을 비교하여 신장 방사능 배설정도를 4등급으로 점수를 나타내어 분류 및 기록하였다. SUV 측정 결과 수분 미섭취 군의 신장 SUV 값은 6.8% 증가하였고, 수분 섭취 군의 SUV의 값은 49.7% 감소하였다(p < 0.001). Blind test에서 수분 미섭취 군의 평균은 17.25점이었고, 수분섭취 군의 평균은 34.75점으로 더 높은 점수를 나타냈다.

• Nuclear Medicine and Molecular Imaging
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• 제43권4호
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• pp.309-316
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• 2009

목적: $^{18}$F-FDG PET/CT는 다양한 장관내 악성 종양을 발견하는데 높은 민감도를 보이고 있다. 하지만 $^{18}$F-FDG가 다양한 형태로 장관 내 생리적, 병리적 섭취증가를 보이기 때문에 그 특이도는 낮다. 이 연구는 장관 내 국소적인 $^{18}$F-FDG 섭취증가를 보일 때 생리적 섭취와 병리적 섭취를 감별하는 데 있어 추가 지연(dual time point) $^{18}$F-FDG PET/CT의 임상적 유용성을 알아보고자 하였다. 대상 및 방법: 2007년 1월부터 2008년 6월까지 장관 내 국소적인 섭취증가를 보여 추가 지연 촬영 $^{18}$F-FDG PET/CT를 실시한 132명(남:여=77:55, 나이 62.8$\pm$11.6세)을 대상으로 하였다. $^{18}$F-FDG 정맥 주사 후 50-60분 후에 조기 영상을 촬영하였고, 정맥 주사 후 4-5시간에 국소 섭취 증가 부위를 포함하고 있는 복부 부위에 대해 추가 지연 촬영을 실시하였다. 초기 영상에서 보였던 국소적 섭취가 지연 영상에서 보이지 않거나 이동하였을 경우에는 생리적 섭취증가로 간주하였고, 지연 영상에서 지속적으로 관찰되는 섭취증가에 대해서는 대장내시경과 병리조직 검사를 실시하였다. 지연 영상에서 지속적으로 관찰되는 장관 내 섭취에 대해서는 각각 Suvmax값과 조기 영상과 지연 영상의 Syvmax값의 차이($\Delta$%Suvmax)를 계산하였다. 결과: 132명의 환자에서 153개의 국소적 섭취증가병소를 관찰할 수 있었다. 이 중 72개 병소에서는 지연 영상에서 섭취 증가가 사라져 생리적 섭취로 판단할 수 있었다. 조기 영상에서만 보였던 생리적 섭취는 맹장을 포함한 오름 결장에서 가장 많이 관찰되었다. 지연 영상에서도 지속적으로 섭취증가를 보인 81개 병소에서 61개는 악성 종양으로 확진되었고, 14개는 양성 질환으로 확인 되었다. 나머지 6개의 병소는 대장내시경에서 특이소견을 보이지 않아 생리적 섭취로 확인되었다. 악성 종양은 $\Delta$%Suvmax가 20.8%$\pm$18.7%로 통계적으로 유의하게 증가하였고, 반대로 리 악성에서는 3.7%$\pm$24.2%로 감소하였다. 가장 유용한 진단적 가치를 주는 요소는 $\Delta$%Suvmax 임을 확인하였고, 악성과 비악성 질환을 감별하는데 임계수를 -5%로 정하였을 때 가장 좋은 민감도, 특이도, 정확도를 보였다. 결론: $^{18}$F-FDG PET/CT를 이용한 추가 지연 촬영은 생리적 섭취와 병리적 섭취를 감별하는데 있어 검사의 특이도를 높이고 불필요한 검사를 줄일 수 있는 유용한 비침습적 방법으로 생각된다.

• Nuclear Medicine and Molecular Imaging
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• 제41권3호
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• pp.209-217
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• 2007

목적: mdr1유전자를 표적으로 한 short hairpin RNA (shMDR)는 다약재내성을 나타내는 암세포에서 효과적으로 mdr1 유전자의 발현을 억제 할 수 있고 sodium iodide symporter (NIS)는 유전자 치료와 리포터로의 기능을 동시에 나타낼 수 있다. 이 연구에서는 사람 대장암세포(HCT15)에 shMDR과 NIS를 동시에 이입하고 Tc-99m sestamibi와 I-125 섭취를 측정하였고 doxorubicin과 I-131 치료효과도 관찰하였다. 대상 및 방법: 사람 태아 신장 세포주(Human Embryonic Kidney cells; HEK293)에 liposome 시약으로 shMDR을 이입하고 RT-PCR과 western blot으로 분석하였다. shMDR와 NIS 유전자가 발현하는 adenovirus를 만들고 HCT15 세포에 이입 후 48시간에 shMDR에 의한 Pgp의 기능 억제를 확인하기위해 Tc-99m sestamibi 섭취와 doxorubicin 세포독성을 측정하였다. 또한 NIS유전자의 기능을 확인 하기위해 I-125 섭취와 I-131 세포독성도 확인하였다. 결과: shMDR이 이입 된 HEK293 세포에서 mdr1의 mRNA와 Pgp의 발현이 각각 75%, 80% 감소하였다. NIS 유전자가 발현하는 adenovirus를 HCT15 세포에 이입하고 NIS 유전자 발현을 확인 한 결과 대조군에 비해 월등히 높게 발현하였다. Ad-shMDR 300 MOI, Ad-shMDR 300 MOI 와 Ad-NIS 10 MOI를 처리한 경우 Tc-99m sestamibi의 섭취가 대조군보다 1.5배 정도 증가하였다. HCT15 세포에 Ad-NIS 10 MOI를 감염시킨 경우 I-125 섭취가 대조군에 비해 25배 이상 증가였다. 또한 Ad-shMDR와 Ad-NIS를 동시 감염 시켰을 경우 doxorubicin의 세포 독성이 증가하여 나타났고 Ad-NIS 20 MOI를 감염시켰을 때 I-131에 의한 세포독성이 대조군보다 증가하였다. 결론: 세포에 shMDR의 이입으로 mdr1 유전자의 발현이 억제되고 Tc-99m sestamibi의 섭취와 doxorubicin의 세포독성이 증가하였으며 NIS 유전자의 이입으로 I-125의 섭취와 I-131의 세포독성이 증가하였다. 다약제내성세포에 shMDR와 NIS 유전자의 동시 이입은 doxorubicin과 방사성 옥소의 이중치료 효과를 높일 수 있을 것으로 본다.

• The Korean Journal of Physiology
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• 제27권2호
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• pp.227-232
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• 1993

The temperature dependence of $Na^+-dependent$ succinate uptake was studied in brush border (BBMV) and basolateral (BLMV) membrane vesicles isolated from the rabbit kidney cortex. The succinate uptake was markedly altered by temperature in a similar fashion in both membranes. The temperature dependence was characterized by a nonlinear Arrhenius plot with a break point at 22 and $25^{\circ}C$ for BBMV and BLMV, respectively. The activation energy was 3.91 and 17.09 kcal/mole at above and below the break point respectively, far BBMV; 2.65 and 14.05 kcal/mole, respectively, for BLMV. When temperature increased f개m 20 to $35^{\circ}C$, the Vmax of succinate transport increased from $3.49{\pm}0.11\;to\;5.90{\pm}0.86\;nmole/mg/5\;sec$ for BBMV and from $2.86{\pm}0.25\;to\;3.63{\pm}0.32\;nmole/mg/5\;sec$ for BLMV, with no change in Km in both membranes. These results suggest that renal dicarboxylate transport is similarly sensitive to a change in membrane physical state in BBMV and BLMV.

• 약학회지
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• 제43권3호
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• pp.369-377
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• 1999

A new series of highly water soluble platinum(II) complexes {Pt(II)[1,3-bis(phenylthio) propane](trans- -1,2-diaminocyclohexane) (PC-1) and Pt(II)[1,3-bis-(phenythio)propane] cis-1,2-diaminocyclohexane(PC-2)} were synthesized, and characterized by their elemental analysis and by various spectroscopic techniques[infrared(IR), 13C-nuclear magnetic resonance (NMR)]. In vitro antitumor activity of new Pt(II) complexes was tested against P-388 and L-1210 mouse lymphocytic leukemia cell lines, PC-14 / P, PC-14/ADM and PC-14 / CDDP human pulmonary adenocarcinima, DU-145 human prostate carcinoma, HT-1376 human bladder carcinoma, ZR-75-1 human breast carcinoma, MKN-45/P and MKN-45/CDDP human gastric adenocarcinoma cell lines using colorimetric MTT[3-(4,5-dimethyl thiazol-2-yl)-2.5-diphenyltetrazoliumbromide] assay for cell survival and proliferation. PC-1 showed active against L-1210, P-388 leukemia, human lung, stomach, prostate, bladder and breast cancer cell lines, and the antitumor activity of these compounds were comparable or superior to those of PC-2 and displatin. The nephrotoxicities of PC-1 and PC-2 were found quite less than that of cisplatin using MTT and [3H] thymidine uptake in rabbit proximal tubule cells and human kidney cortical cells. Based on these results, this novel platinum (II) complex compound (PC-1) represents a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.

• 대한의생명과학회지
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• 제12권1호
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• pp.23-27
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• 2006

The rate of metallothionein synthesis on cadmium-poisoned rats reflects the level of toxicity, and also it reduces the toxicity which is caused by the uptake of cadmium. Chlorella supplementation in the diets of the cadmium-poisoned rats decreased the concentration of cadmium in blood and urine compared with the control group. Although the liver and kidneys of rats are major target organs of cadmium and coherence of metallothionein and cadmium, no previous study has determined the correlation between the rate of metallothionein synthesis in the liver and kidneys of rats and dietary supplementation of chlorella with cadmium uptake. This study analyzed total metallothionein level on the tissue of the liver and kidneys, the concentration of cadmium bound to the metallothionein, and the total concentration of cadmium on the tissue of the liver and kidneys after dietary supplementation with 1%, 5%, and 10% dried chlorella and 40 ppm of cadmium to 46 male SD rats (mean weight: $150\pm20\;g$) for 4 weeks. According to the data analysis of the total rate of metallothionein synthesis in the liver and kidneys, the group of SD rats on the supplementation with 1% chlorella and 40 ppm of cadmium showed a rate of $93.2\pm8.9\;ng/g$, a significant decrease of 58.8% compared to that of the control group of SD rats on the supplementation with cadmium only, which showed a rate of $227.3\pm32.5 ng/g$ (P=0.0001). In contrast, no significant difference was observed through the changing of chlorella concentrations between 5% and 10% chlorella supplementation with cadmium. The group supplemented with 1% or greater chlorella levels represented a greater decrease in the total cadmium concentration of the kidney and liver tissues, the amount of total metallothionein synthesis, the amount of metallothionein with binding to cadmium, and the concentration of free cadmium without binding to metallothionein. Consequently, the supplementation of 1% and 5% chlorella was effective in reducing the synthesis of metallothionein for cadmium uptake, but increased the rate of binding of cadmium to metallothionein.

• The Korean Journal of Physiology and Pharmacology
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• 제4권2호
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• pp.159-167
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• 2000

We have synthesized a novel platinum(II) coordination complex containing cis-1,2-diaminocyclohexane (DACH) as a carrier ligand and 1,2-dichloroethane (DCE) as a leaving group. In addition, nitrate was added to improve the water-solubility. A new series of [Pt(cis-DACH)(DCE)] $2NO_3(PC)$ was evaluated for its cytotoxic activity on T-24 and J-82 human bladder carcinoma cells and normal primary cultured kidney cells. PC has demonstrated high levels of cytotoxicity against T-24 and J-82 cells. The cytotoxicity of PC against rabbit proximal renal tubular cells, human renal cortical cells and human renal cortical tissues, determined using the MTT assaying technique, the $[^3H]-thymidine$ uptake and glucose consumption tests, was found to be quite less than those of cisplatin. Based on these results, this novel platinum(II) coordination complex appears to be better for improving antitumor activities with low nephrotoxicity and is a valuable lead in the development of new clinically available anticancer chemotherapeutic agents.

• 약학회지
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• 제44권5호
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• pp.399-405
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• 2000

We have synthesized a novel platinum (II) coordination complex containing trans-ι-1,2-diaminocyclohexane (DACH) as a carrier ligand and 1,2-bis (diphenylphosphino)ethane (DPPE) as a leaving group. In addition, nitrate was added to improve the water-solubility. A new series of [Pt (trans-ι-DACH) (DPPE)].2NO$_3$(PC) was evaluated for its cytotoxic activity on MKN-45 human gastric adenocarcinoma cells and normal primary cultured kidney cells. PC has demonstrated high levels of cytotoxicity against MKN-45/S, MKN-45/ADR and MKN-45/CDDP cells. The cytotoxicity of PC against rabbit proximal renal tubular cells, human renal cortical cells, and human renal cortical tissues, determined using the MTT assaying technique, the ($^3$H)-thymidine uptake and the glucose consumption tests, was found to be quite less than those of cisplatin. Based on these results, this novel platinum (II) coordination complex appears to be better for improving antitumor activities with low nephrotoxicity and is a valuable lead in the development of new clinically available anticancer chemotherapeutic agents.