• The Korean Journal of Physiology and Pharmacology
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• v.2 no.4
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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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• v.3 no.1
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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.

• The Korean Journal of Nuclear Medicine Technology
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• v.20 no.1
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• pp.47-51
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• 2016

Purpose By ingestion of 18F-FDG of kidney of PET/CT during the inspection, if additional examination is required, depending on whether you want to water intake, we want to confirm a change in the rate of decrease of F-18 FDG of the kidney. Materials and Methods The 80 patients without kidney disease were performed PET/CT examination. Device was analyzed after setting the kidney to a three-dimensional region of interest. In patients require additional examination, and inspection after 30 minutes, a PET/CT torso examination after the water of the 500 cc ingested at a time. After the addition of both water intake group and no hydration group of kidney of SUV, it was compared with PET/CT torso scan. Results High and low of the kidney SUV did not show a significant difference in the rate of decrease. Reduction rates of background (BKG) of additional examination was 2.8% and reduction rates of SUV was 49.7% (Hydration) : -6.8% (No hydration), so did show a significant difference. In the image blind test, the average point score of hydration and no hydration was 34.25 : 17.25. Conclusion An undercurrent of 18F-FDG in the kidney at the time of torso examination, it was confirmed that the reduction rate after the addition of water intake is high. It is considered that can be expected to improve the quality of an image due to a decrease in elongation through the kidneys examination with additional fluid intake as needed intake.

• Nuclear Medicine and Molecular Imaging
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• v.43 no.4
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• pp.309-316
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• 2009

Purpose: F-18 FDG can be accumulated in the liver, bowel, kidney, urinary tract, and muscles physiologically. The aim of this study was to evaluate the clinical value of dual time point 18F-FDG PET /8 imaging for the differentiation of the colonic focal uptake lesions. Materials and Methods: One hundred thirty two patients (M:F = 77:55, Age 62.8$\pm$11.6 years) underwent $^{18}$F-FDG PET/CT at two time points, prospectively: early image at 50-60 min and delayed image at 4-4.5 hours after the intravenous injection of $^{18}$F-FDG. Focally increased uptake lesions on early images but disappeared or shifted on delayed images defined a physiological uptake. For the differential evaluation of persistent focal uptake lesions on delayed images, colonoscopy and histopathologic examination were performed. SUVmax changes between early and delayed images were also compared. Results: Among the 132 patients, 153 lesions of focal colonic uptake were detected on early images of $^{18}$F-FDG PET/CT. Of these, 72 (47.1%) lesions were able to judge with physiological uptake because the focal increased uptake disappeared from delayed image. Among 81 lesions which was showed persistent increased uptake in delayed image, 61 (75.3%) lesions were confirmed as the malignant tumor and 14 (17.3%) lesions were confirmed as the benign lesions including adenoma and inflammatory disease. Remaining 6 (7.4%) lesions were confirmed as the physiological uptake because there was no particular lesion in the colonoscopy. In the malignant lesions, the calculated dual time point change for SUVmax ($\Delta$%SUVmax) was 20.8$\pm$18.7%, indicating a significant increase in SUVmax between the two point (p<0.01). In contrast, the change in SUVmax for the non-malignant lesions including benign lesions and physiological uptake was -13.7%$\pm$24.2%. For the differentiation of the malignant and non-malignant focal colonic uptake lesions, $\Delta$%SUVmax was the most effective parameter, and the cut-off value using -5% provided the best sensitivity, specificity, and accuracy. Conclusion: The dual time point $^{18}$F-FDG PET/CT imaging with SUVmax change evaluation could be an important noninvasive method for the differentiation of malignant and benign focal colonic uptake lesions including physiologic uptake.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.3
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• pp.209-217
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• 2007

Purpose: Multidrug resistance (MDR) of the cancer cells related to mdr1 gene expression can be effectively treated by selective short hairpin RNA for mdr1 gene (shMDR). Sodium/iodide symporter (NIS) gene is well known to have both reporter and therapeutic gene characteristics. We have co-transfected both shMDR and NIS gene into colon cancer cells (HCT15 cell) expressing MDR and Tc-99m sestamibi and I-125 uptake were measured. In addition, cytotoxic effects of doxorubicin and I-131 therapy were also assessed after transfection. Material and Methods: At first, shMDR was transfected with liposome reagent into human embryonic kidney cells (HEK293) and HCT cells. shMDR transfection was confirmed by RT-PCR and western blot analysis. Adenovirus expressing NIS (Ad-NIS) gene and shMDR (Ad-shMDR) were co-transfected with Ad-NIS into HCT15 cells. Forty-eight hours after infection, inhibition of P-gycoprotein (Pgp) function by shMDR was analyzed by a change of Tc-99m sestamibi uptake and doxorubicin cytotoxicity, and functional activity of induced NIS gene expression was assessed with I-125 uptake assay. Results: In HEK293 cells transfected with shMDR, mdr1 mRNA and Pgp protein expressions were down regulated. HCT15 cells infected with 20 MOI of Ad-NIS was higher NIS protein expression than control cells. After transfection of 300 MOI of Ad-shMDR either with or without 10 MOI of Ad-NIS, uptake of Tc-99m sestamibi increased up to 1.5-fold than control cells. HCT15 cells infected with 10 MOI of Ad-NIS showed approximately 25-fold higher I-125 uptake than control cells. Cotransfection of Ad-shMDR and Ad-NIS resulted in enhanced cytotoxic by doxorubicin in HCT15 cells. I-131 treatment on HCT15 cells infected with 20 MOI of Ad-NIS revealed increased cytotoxic effect. Conclusion: Suppression of mdr1 gene expression, retention of Tc-99m sestamibi, enhanced doxorubicin cytotoxicity and increases in I-125 uptake were achieved in MDR expressing cancer cell by co-transfection of shMDR and NIS gene. Dual therapy with doxorubicin and radioiodine after cotransfection shMDR and NIS gene can be used to overcome MDR.

• The Korean Journal of Physiology
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• v.27 no.2
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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.

• YAKHAK HOEJI
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• v.43 no.3
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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.

• Biomedical Science Letters
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• v.12 no.1
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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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• v.4 no.2
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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.

• YAKHAK HOEJI
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• v.44 no.5
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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.