Background: Breast cancer is a common malignant tumor which affects health of women and multidrug resistance (MDR) is one of the main factors leading to failure of chemotherapy. This study was conducted to establish paclitaxel-resistant breast cancer cell line and nude mice models to explore underlying mechanisms of MDR. Methods: The breast cancer drug-sensitive cell line MCF-7 (MCF-7/S) was exposed in stepwise escalating paclitaxel (TAX) to induce a resistant cell line MCF-7/TAX. Cell sensitivity to drugs and growth curves were measured by MTT assay. Changes of cell morphology and ultrastructure were examined by optical and electron microscopy. The cell cycle distribution was determined by flow cytometry. Furthermore, expression of proteins related to breast cancer occurrence and MDR was tested by immunocytochemistry. In Vivo, nude mice were injected with MCF-7/S and MCF-7/TAX cells and weights and tumor sizes were observed after paclitaxel treatment. In addition, proteins involved breast cancer and MDR were detected by immunohistochemistry. Results: Compared to MCF-7/S, MCF-7/TAX cells had a higher resistance to paclitaxel, cross-resistance and prolonged doubling time. Moreover, MCF-7/TAX showed obvious alterations of ultrastructure. Estrogen receptor (ER) expression was low in drug resistant cells and tumors while expression of human epidermal growth factor receptor 2 (HER2) and Ki-67 was up-regulated. P-glycoprotein (P-gp), lung resistance-related protein (LRP) and glutathione-S-transferase-${\pi}$ (GST-${\pi}$) involved in the MDR phenotype of resistant cells and tumors were all overexpressed. Conclusion: The underlying MDR mechanism of breast cancer may involve increased expression of P-gp, LRP and GST-${\pi}$.
Objectives: To establish a taxol-resistant cell line of human ovarian carcinoma (A2780/Taxol) and investigate its biological features. Methods: The drug-resistant cell line (A2780/Taxol) was established by continuous stepwise selection with increasing concentrations of Taxol. Cell morphology was assessed by microscopy and growth curves were generated with in vitro and in vivo tumor xenograft models. With rhodamine123 (Rh123) assays, cell cycle distribution and the apoptotic rate were analyzed by flow cytometry (FCM). Drug resistance-related and signal associated proteins, including P-gp, MRPs, caveolin-1, PKC-${\alpha}$, Akt, ERK1/2, were detected by Western blotting. Results: A2780/Taxol cells were established with stable resistance to taxol. The drug resistance index (RI) was 430.7. Cross-resistance to other drugs was also shown, but there was no significant change to radioresistance. Compared with parental cells, A2780/Taxol cells were significantly heteromorphous, with a significant delay in population doubling time and reduced uptake of Rh123 (p<0.01). In vivo, tumor take by A2780 cells was 80%, and tumor volume increased gradually. In contrast, with A2780/Taxol cells in xenograft models there was no tumor development. FCM analysis revealed that A2780/Taxol cells had a higher percentage of G0/G1 and lower S phase, but no changes of G2 phase and the apoptosis rate. Expression of P-gp, MRP1, MRP2, BCRP, LRP, caveolin-1, PKC-${\alpha}$, Phospho-ERK1/2 and Phospho-JNK protein was significantly up-regulated, while Akt and p38 MARK protein expression was not changed in A2780/Taxol cells. Conclusion: The A2780/Taxol cell line is an ideal model to investigate the mechanism of muti-drug resistance related to overexpression of drug-resistance associated proteins and activation of the PKC-${\alpha}/ERK$ (JNK) signaling pathway.
Fruitful findings have been produced from five out of sixty cells which were obtained from each 63 individual Aplisia caught at the Jeju coast. Spiking patterns of three out of five cells, such as relaxation oscillator, bursting within a short time of the inter-burst interval, chaotic bursting, period doubling sequences, bursting with long trains of action potentials separated by short silent periods, regular repeated beating or elliptic bursting, and silent states had been changed in order as the temperature was lowered to $10^{\circ}C\;from\;32^{\circ}C$. In the intervals of every about 40 minutes repeated ups and downs of temperature produced similar firing patterns at the allowable temperature ranges. The other two cells showed difference from these. The amplitudes of the action potentials of the two cells will not be highly decreased in 24 hours. Average spike frequencies, the inter-burst interval, peak to peak spike amplitude of action potentials, minimum potential values are compared and analyzed by using the computer programme. The spike frequencies according to temperature show the distribution of bell type, with maximal spike frequencies at intermediate temperatures and minimal ones at either end. The most common pattern consist of high spike frequency during failing and low one during rising temperatures.
The chemotherapy using macromolecules, i.e., monoclonal antibodies loaded with anticancer agents hasn't been successful in delivering therapeutic amount of the conjugates. The comprehensive evaluation of mass transfer factors in tumor is prerequisite for the development of the effective chemotherapy. Characterization of neuroblastoma implanted in immunosuppressed athymic nude rats was performed. Its growth kinetics, glucose metabolic rate (GMR) were measured along with the interstitial fluid pressure (IFP), blood perfusion rate (BPR) and pH distribution throughtout the tumor radius. Volume doubling time and GMR were 8.1 days(SD 0.44 day), 23.53 mg/min/100 g(SD 3.54 mg/min/100 g), respectively. The IFP in tumor center was increased with tumor volume, and approached to 3 mmHg (SD 2.6 mmHg) when the tumor was 3 cm high. The radial distribution of IFP, BPR and pH in 2 cm high tumors showed that BPR and pH were decreased, while IFP was increased as the ~ensors moved toward the tumor center. The elevated IFP, decreased BPR and pH in tumor center suggested that the delivery of conjugates might be increased by properly manipulating mass transfer factors.
The East Asian (China, Korea and Japan) summer monsoon precipitation and its variability are examined from the outputs of the 22 coupled climate models performing coordinated experiments leading to the Intergovernmental Panel on Climate Change Fourth Assessment Report (IPCC AR4) following the multi-model ensemble (MME) technique. Results are based on averages of all the available models. The shape of the annual cycle with maximum during the summer monsoon period is simulated by the coupled climate models. However, models fail to simulate the minimum peak in July which is associated with northward shifts of the Meiyu-Changma-Baiu precipitation band. The MME precipitation pattern is able to capture the spatial distribution of rainfall associated with the location of the north Pacific subtropical high and the Meiyu-Changma-Baiu frontal zone. However precipitation over the east coast of China, Korea-Japan peninsular and the adjoining oceanic regions is underestimated. Future projections to the radiative forcing of doubled $CO_2$ scenario are examined. The MME reveals an increase in precipitation varying from 5 to 10 %, with an average of 7.8 % over the East Asian region at the time of $CO_2$ doubling. However the increases are statistically significant only over the Korea-Japan peninsula and the adjoining north China region. The increase in precipitation may be attributed to the projected intensification of the subtropical high, and thus the associated influx of moist air from the Pacific to inland. The projected changes in the amount of precipitation are directly proportional to the changes in the strength of the subtropical high. Further a possible increase in the length of the summer monsoon precipitation period from late spring through early autumn is suggested.
Scuticociliates Miamiensis avidus (syn. Philasterides dicentrarchi) causes high mortality and bad growth in olive flounder Paralichthys olivaceus. Temperature is an important factor not only for growth of pathogens but also for host immune system in poikilothermal animal. In this study, temperature affecting ciliate growth and pathogenicity against olive flounder were examined. Doubling time for the ciliate growth was 61.82 hours at $5{^{\circ}C}$, 26.32 hours at $10{^{\circ}C}$, 21.14 hours at $15{^{\circ}C}$, 16.86 hours $20{^{\circ}C}$ and 16.21 hours at $25{^{\circ}C}$. Maximum ciliate numbers were similar at $10-20{^{\circ}C}$ at the range of $1.54-1.75{\times}10^{5}$/ ml. Duplicated intraperitoneal injections were conducted with the ciliates by the concentrations of $1{\times}10^{2}$, $1{\times}10^{6}$, $1{\times}10^{4}$and $1{\times}10^{5}$/ fish (average 8.34 cm, 4.33 g) then kept at $10{^{\circ}C}$, $15{^{\circ}C}$ and $20{^{\circ}C}$. Cumulative mortality was low at $10{^{\circ}C}$ and the mortality was increasing at higher water temperatures. In addition, cumulative mortality was higher at higher dose of infections. In conclusion, Scuticocilite M. avidus grew well at higher temperature (at $5{^{\circ}C}$, $10{^{\circ}C}$, $15{^{\circ}C}$ and $25{^{\circ}C}$) in vitro, and olive flounder mortality due to M. avidus was highly water temperature and dose dependent. The results of this study suggest that water temperature control may one of the essential factor to reduce mortality due to M. avidus infection.
In this study, integrated hybrid system (IHS) composed of two alternatively-operating UV/photocatalytic reactor (AOPR) process and biofilter processes of a biofilter system having two units (i.e., Rup and Rdn) with an improved design (R reactor) and a conventional biofilter (L reactor) was constructed, and its transient behavior was observed to perform the successful treatment of waste air containing ethanol and hydrogen sulfide (H2S). At the IHS-operating stages of HA1, HA2 and HA3T of reversed feed direction, the AOPR process showed not only ethanol-removal efficiencies of 55, 50 and 45%, respectively, but also H2S-removal efficiencies of 70, 60 and 37%, respectively. In particular, a drastic decrease of H2S-removal efficiency at the stage of HA3T was observed due to a doubling of H2S-inlet concentration fed to AOPR from 10 ppmv to 20 ppmv at the stage of HA3T. The order of ethanol-breakthroughs and the order of the magnitude of ethanol-removal efficiencies at the sampling ports of each unit of R reactor at the stages of HA1, HB1, HA2, HB2, and the first half of HA3T, were reversed, respectively, at the stages of the second half of HA3T and HB3T. In case of H2S, R reactor did not show H2S-breakthrough as prominent as the ethanol-breakthrough, but showed the trend similar to the ethanol-breakthrough.
The present study assessed the cytotoxic effects on cell growth and senescence in human cancer (A-549, AGS, HCT-116, MDA-MB-231, and U 87-MG) and normal (MRC-5 and mesenchymal stem cells) cell lines treated with efavirenz (EFA), an inhibitor of non-nucleoside reverse transcriptase (RTase). Following EFA treatment, the half-maximal inhibitory concentration (IC50) values were approximately 15 µM, and the IC50 value was significantly (p<0.05) lower in the cancer cell lines, compared to normal cell lines. After determining the IC50 values against EFA, each cell line was treated with 15 µM EFA for up to one week. Significant (p<0.05) decreases in endogenous RTase and telomerase activity were observed in the cancer cell lines. RTase and telomerase activity were absent or detected at very low levels in both EFA-untreated and treated MRC-5 and MSC normal cells. The cell doubling time (CDT) was also significantly (p<0.05) prolonged by the decreased cell growth rate in the EFA-treated cancer cell lines compared to the untreated cell lines. Furthermore, EFA-treated cancer cells displayed a high number of cells with a high intensity of senescence-associated ß-galactosidase activity (SA-ß-gal activity), compared to the untreated cells. The present study showed that inhibition of RTase activity induces cellular senescence and arrests cell growth in human cancer cell lines; however, normal cell lines showed greater tolerance against EFA. RTase treatment could offer optional chemotherapy for cancer treatment in human cancer cell lines with high RTase activity.
Kim, Chae-Kyun;Jeong, Jae-Min;Lee, Myung-Chul;Koh, Chang-Soon;Chung, June-Key
The Korean Journal of Nuclear Medicine
/
v.31
no.3
/
pp.381-387
/
1997
Cancer tissues are characterized by increased glucose uptake. $^{18}F$-fluorodeoxyglucose(FDG), a glucose analogue is used for the diagnosis of cancer in PET studies. This study was aimed to compare the glucose uptake and glucose transporter 1(GLUT1) expression in various human colon cancer cells. We measured FDG uptake by cell retention study and expression of GLUT1 using Western blotting. Human colon cancer cells, SNU-C2A, SNU-C4 and SNU-C5, were used. The cells were incubated with $1{\mu}Ci/ml$ of FDG in HEPES-buffered saline for one hour. The FDG uptake of SNU-C2A, SNU-C4 and SNU-C5 were $16.8{\pm}1.36,\;12.3{\pm}5.55$ and $61.0{\pm}2.17cpm/{\mu}g$ of protein, respectively. Dose-response and time-course studies represent that FDG uptake of cancer cells were dose dependent and time dependent. The rate of FDG uptake of SNU-C2A, SNU-C4 and SNU-C5 were $0.29{\pm}0.03,\;0.21{\pm}0.09$ and $1.07{\pm}0.07cpm/min/{\mu}g$ of protein, respectively. Western blot analysis showed that the GLUT1 expression of SNU-C5 was significantly higher than those of SNU-C2A and SNU-C4. These results represent that FDG uptake into human colon cancer cells are different from each other. In addition, FDG uptake and expression of GLUT1 are closely related in human colon cancer cells.
Jeon, Sung-Wook;Kim, Kang-Hyeok;Lee, Sang Guei;Lee, Yong Hwan;Park, Se Keun;Kang, Wee Soo;Park, Bueyong;Kim, Kwang-Ho
Korean Journal of Environmental Biology
/
v.37
no.4
/
pp.568-578
/
2019
The nymphal development of the potato aphid, Macrosiphum euphorbiae (Thomas), was studied at seven constant temperatures (12.5, 15.0, 17.5, 20.0, 22.5, 25.0, and 27.5±1℃), 65±5% relative humidity (RH), and 16:8 h light/dark photoperiods. The developmental investigation of M. euphorbiae was separated into two steps, the 1st through 2nd and the 3rd through 4th stages. The mortality was under 10% at six temperatures. However, it was 53.0% at 27.5℃. The developmental time of the entire nymph stage was 15.5 days at 15.0℃, 6.7 days at 25.0℃, and 9.7 days at 27.5℃. In the immature stage, the lower threshold temperature of the larvae was 2.6℃ and the thermal constant was 144.5 DD. In our analysis of the temperature-development experiment, the Logan-6 model equation was most appropriate for the non-linear regression models (r2=0.99). When the distribution completion model of each development stage of M. euphorbiae larvae was applied to the 2-parameter and 3-parameter Weibull functions, each of the model's goodness of fit was very similar (r2=0.92 and 0.93, respectively). The adult longevity decreased as the temperature increased but the total fecundity of the females at each temperature was highest at 20℃. The life table parameters were calculated using the whole lifespan periods of M. euphorbiae at the above six temperatures. The net reproduction rate (R0) was highest at 20.0℃(63.2). The intrinsic rate of increase (rm) was highest at 25℃(1.393). The finite rate of doubling time (Dt) was the shortest at 25.0℃(2.091). The finite rate of increase (λ) was also the highest at 25.0℃(1.393). The mean generation time(T) was the shortest at 25.0℃(9.929).
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